Assistant/Associate Professor in Exercise Physiology job with UNITED ARAB EMIRATES UNIVERSITY | 206355 – Times Higher Education (THE)

Job Description

The United Arab Emirates University invites applications for a faculty position. Qualified candidates at all levels will be considered at a rank commensurate with academic accomplishments. Candidates are expected to have a strong commitment to teaching excellence and student advising at the undergraduate and graduate levels, a demonstrable research capability that will enable the candidate to develop and sustain an internally and/or externally funded research program in his/her area of expertise, publish his/her research findings in refereed journals, and actively engage in promoting the growth of the UAE University. The application package should include a cover letter, a detailed resume, a brief description of current/future research activities, teaching philosophy, and courses taught. English is the language of instruction and communication. Screening of applications will continue until the position is filled. The responsibilities of an exercise physiologist who will work in the Physical Education Department include: Conduct stress tests, using electrocardiograph (EKG) machines. Demonstrate correct use of exercise equipment or performance of exercise routines. Develop exercise programs to improve participant strength, flexibility, endurance, or circulatory functioning, in accordance with exercise science standards, regulatory requirements, and credentialing requirements. Explain exercise program or physiological testing procedures to participants. Interpret exercise program participant data to evaluate progress or identify needed program changes. Measure amount of body fat, using such equipment as hydrostatic scale, skinfold calipers, or tape measures. Measure oxygen consumption or lung functioning, using spirometers. Perform routine laboratory tests of blood samples for cholesterol level or glucose tolerance. Prescribe individualized exercise programs, specifying equipment such as treadmill, exercise bicycle, ergometers, or perceptual goggles. Provide clinical oversight of exercise for participants at all risk levels. Recommend methods to increase lifestyle physical activity. Teach courses or seminars related to exercise or diet for patients, athletes, or community groups. Assess physical performance requirements to aid in the development of individualized recovery or rehabilitation exercise programs. Calibrate exercise or testing equipment. Educate athletes or coaches on techniques to improve athletic performance, such as heart rate monitoring, recovery techniques, hydration strategies, or training limits. Evaluate staff performance in leading group exercise or conducting diagnostic tests. Interview participants to obtain medical history or assess participant goals. Mentor or train staff to lead group exercise. Order or recommend diagnostic procedures, such as stress tests, drug screenings, or urinary tests. Plan or conduct exercise physiology research projects. Present exercise knowledge, program information, or research study findings at professional meetings or conferences. Provide emergency or other appropriate medical care to participants with symptoms or signs of physical distress. Supervise maintenance of exercise or exercise testing equipment. Teach behavior modification classes related to topics such as stress management or weight control. Teach group exercise for low, medium, or high-risk clients to improve participant strength, flexibility, endurance, or circulatory functioning.

Minimum Qualification

Applicants must have an earned doctorate in the applicable field. The ability to teach undergraduate courses is a must. Industrial and professional experience is a plus.

Preferred Qualification

Ph.D. in exercise physiology

Expected Skills/Rank/Experience

Assistant or Associate Professor in Exercise Physiology

Special Instructions to Applicant

Division College of Education - (CEDU)

Department Foundations of Education - (CEDU)

Job Close Date open until filled

Job Category Academic - Faculty

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Assistant/Associate Professor in Exercise Physiology job with UNITED ARAB EMIRATES UNIVERSITY | 206355 - Times Higher Education (THE)

Scientists generate millions of nave human pluripotent stem cells, far more than have ever been produced – UB News Center

BUFFALO, N.Y. For decades, the enormous disease-curing potential of human stem cells has been thwarted by the inability to produce sufficient quantities of mature human cells in vivo in a living organism.

Now, a team led by University at Buffalo scientists has developed a method that dramatically ramps up production of mature human cells in mouse embryos. Producing human cells in vivo is critical because cells made in a petri dish often do not behave the same way that cells do in the body.

The research was published on May 13 in Science Advances.

This is fundamental research that allows us to use the mouse embryo to help us better understand human development, said Jian Feng, PhD, corresponding author and professor of physiology and biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB.

Further development of our technology could enable the generation of even larger quantities of specific types of mature human cells to allow us to create more effective mouse models to study diseases that gravely affect humans, such as malaria or COVID-19, said Feng.

And because this method produces so many mature human cells, it could potentially generate materials to treat chronic diseases, such as diabetes or kidney failure, by replacing a patients damaged cells with healthy human cells or tissues.

Infectious disease applications

Feng explained that it might be possible to create a much better mouse model of the human immune system or components of the human respiratory system in order to study COVID-19, a disease that wreaks havoc in humans, but barely affects mice.

It could also be possible to use the new method to produce mice with even more mature human red blood cells. Such mice would be very effective in the study of malaria, a disease which affects only humans by destroying our red blood cells.

We have a lot of questions to answer before the technology can be useful, but this is the first time that anyone has generated so many mature human cells in a mouse embryo, said Feng.

Millions of mature human cells in 17 days

Previous efforts to produce human cells in mouse embryos have generated small amounts of immature cells that are hard to quantify. In contrast, the UB method resulted in millions of mature human cells in a mouse embryo in 17 days.

In this study, the researchers injected 10-12 nave human stem cells into a mouse blastocyst when it was 3.5 days old. The mouse embryo then generated millions of mature human cells, including red blood cells, eye cells and liver cells, as it developed.

We know that up to four percent of the total number of cells in the mouse embryo were human cells, Feng. This is a low estimate because we cannot quantify the large amount of human red blood cells generated in the mouse embryo.

He said that because these mature human red blood cells do not have a nucleus, they are not counted by the method that the scientists use to quantify the total number of cells.

The teams technique involved overcoming an important challenge: Converting human pluripotent stem cells, which can differentiate into all types of cells in the body, into a form that is compatible with the inner cell mass inside a mouse blastocyst a three-day old mouse embryo. The human stem cells are in a primed state, whereas the inner cell mass inside the mouse blastocyst is in a nave state.

When the primed human cells are put into the mouse blastocyst, they fail to develop, said Feng, noting that the mismatch between the cells different developmental stages seems to be responsible.

We wanted to see if it was possible for the human primed cells to go back to the nave state, just like the pluripotent stem cells inside a mouse blastocyst, said Feng. This is what we have done.

Our method is to transiently inhibit the mTOR kinase for three hours to shock the human primed cells to the nave state, said Feng. Blocking the mTOR kinase triggers a series of events that rewire gene expression and cellular metabolism so that the primed cells become nave.

Converting the later stage human primed stem cells back to an earlier, less developed nave state allowed the human stem cells to co-develop with the inner cell mass in a mouse blastocyst.

The injected human stem cells now develop at the much more rapid pace of the mouse embryo, supporting the generation of millions of mature human cells in 17 days, said Feng.

In addition to Feng, UB co-authors are Zhixing Hu, Hanqin Li, Houbo Jiang, Yong Ren, and Boyang Zhang of the Department of Physiology and Biophysics, and Xinyang Yu and Michael J. Buck of the Department of Biochemistry, all of the Jacobs School. Other co-authors are Jingxin Qiu and Aimee B. Stablewski of the Roswell Park Comprehensive Cancer Center.

Funding for this research was provided by NYSTEM and the Buffalo Blue Sky Initiative.

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Scientists generate millions of nave human pluripotent stem cells, far more than have ever been produced - UB News Center

Staying hydrated is important in sickness and in health – stopthefud

Whether sick or healthy, the body needs water to function properly.

BY DARCY DiBIASE

Your body relies on water to work properly, and its your responsibility to make sure it has the hydration it needs to work its best.

Up to 60% of your body is water. Your skin, organs, muscles and even your bones have water in them. Water regulates your internal body temperature, dissolves and transports nutrients in the bloodstream, assists in flushing out waste and lubricates your joints.

How much water you need in a day is determined by your activity level, the weather and your physiology. You might be at higher risk of dehydration if you exercise at a high intensity, have medical conditions (such as kidney stones or diabetes), are sick with a fever or diarrhea, are pregnant or are breastfeeding.

You may be dehydrated if you are thirsty, have a dry mouth, feel sleepy or are light-headed.

The best way to tell if you are well hydrated is by checking your urine. It should be colorless or light yellow. If your urine is dark yellow or amber, up your fluids. If it persists more than a few days even with increased fluids, call your primary care physician, says Susan Levinsohn, MD, of Upstate Family Medicine and Preventative Care.

Another indicator of dehydration can be a mild headache. Before you reach for the pain reliever, drink a large glass of water and wait 20 minutes, Levinsohn says.

Dehydration is most threatening to the young, the elderly and the sick. These are the groups of people who may not be in tune with whether they are getting enough fluids.

Living in Upstate New York, were lucky to have, for the most part, excellent tap water. You can be a good steward of the environment and leave the bottled water on the store shelves and out of the landfills, Levinsohn said. If your tap water isnt to your liking, you can try using a filtration pitcher to improve the taste and odor of your water.

Invest in a good-quality refillable water bottle made of BPA-free plastic, glass or stainless steel. Carrying it with you throughout the day makes it even easier to get in enough water. You can also experiment with making your water more flavorful by adding fresh fruit, cucumbers or herbs to a large pitcher and letting it steep overnight.

Water is the best source of hydration for the human body, but remember hydration can come from many places including other types of beverages, fruits, vegetables and even soup, Levinsohn says.

While you can hydrate with many beverages, pay attention to added artificial colors, sweeteners, salt, caffeine and fat in packaged drinks. Some drinks can be filled with empty calories that can throw off your daily nutrition balance.

Sugary sports drinks are not necessary to hydrate, even if you arent well, Levinsohn says. Artificial sweeteners can also make you crave more sweets, which isnt necessarily good for your health.

Bottom line: Staying hydrated is part of staying healthy and adding more water to your daily routine is an easy way to achieve that.

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New Online BME Courses Offered in Summer 2020 – IIT Today

The Department of Biomedical Engineering is offering the following new online courses in Summer 2020 Session B (June 1-July 25).

Check with your faculty academic advisor for how you can apply this to your degree, and view the course schedule in MyIIT to register.

BME402/502Introduction to Regulatory Science for Engineers

Instructor: Diana M. Easton, Ph.D.

Engineers must be equipped to answer the growing demands for new medical technologies.Introduction to Regulatory Science for Engineers teaches engineers how the regulated environment impacts the design, testing, and delivery of medical devices.It will equip students with the essential skills and tools critical to the practice of engineering in the medical device industry.In this course, students will be exposed to the core concepts, processes, and tools surrounding the global medical device regulatory framework, and will gain foundational knowledge for the practical application of regulations throughout the product development lifecycle. From knowledge gained in the class, students will be expected to work in teams and use critical thinking, data analysis, and interpretation skills to research, evaluate, and present a scientific, technical, and legally justifiable approach for the global introduction of a new medical device.

BME427Extracellular Matrix Structure and Function

Instructor: Rama S. Madhurapantula, Ph.D.

Extracellular Matrix (ECM) is a highly complex system in mammalian biology responsible for structural support and functional (biochemical) signals for physiology. Specific amino acid sequences on the various ECM elements are responsible to trigger intra- and extracellular cascades leading to cell division, proliferation, tissue regeneration, wound healing, and inflammation.This course will focus on the following key concepts:(a) Gene expression, structure and function of various ECM proteins and complexes and the physiological processes; (b) Etiology and the molecular progression of diseases caused by abnormalities to ECM proteins; (c) Mechanobiology of various ECM proteins; (d) Structure function and mechanical function of ECM interfaces with other tissues (muscle, bone, skin, etc.); and (e) Implications for tissue engineering and the development of novel biomimetic and biological ECM implants.

BME 437/537Intro to Molecular Imaging

Instructor: Ken Tichauer, Ph.D.

This course provides an overview of molecular imaging, a subcategory of medical imaging that focuses on noninvasively imaging molecular pathways in living organisms. Topics include imaging systems, contrast agents, reporter genes and proteins, tracer kinetic modeling. Preclinical and clinical applications will also be discussed with an emphasis on cancer and the central nervous system. (Prerequisite: Math 252 or equivalent)

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New Online BME Courses Offered in Summer 2020 - IIT Today

Children Can Catch Their Mothers Stress Particularly If She Tries To Hide It – The British Psychological Society

ByEmily Reynolds

The way parents feel and behave often rubs off on their children. Kids own life paths can be influenced by the strength of their parents romantic relationship, for example, or how often their parents lie to them.

We may also pick things up as our parents try to hide them, as new research published in the Journal of Family Psychology suggests. Even when parents try to hide their stress, the team finds, they can still pass on those feelings to their children anyway.

To examine how stress is passed on from parent to child, Sara Waters from Washington State University Vancouver and colleagues looked at the physiological responses that occur when parents suppressed their anxiety. A total of 107 parents and their children aged between 7 and 11 were first fitted with ECG sensors to measure the hearts pre-ejection period (PEP), a measure of sympathetic nervous system activation, before spending five minutes listening to soothing music through headphones.

Parents were then separated from their children and completed a stress test, in which they were asked to give a five minute speech about themselves and then answer five minutes of questions in front of two evaluators. During the test, evaluators provided negative, non-verbal feedback, shaking their heads, crossing their arms and frowning.

The stressed-out parents were then assigned to either a suppression or control condition, before being reunited with their children. Those in the suppression condition were asked to mask their emotion, behaving in such a way that their child would not be able to know they were feeling anything at all, while those in the control condition were told to act naturally, as they would at home. Parent and child were then asked to engage in a six minute conversation about a source of conflict in their relationship, a six minute cooperation task in which they built with blocks, and six minutes of free play.

Trained observers who rated these interactions found that parents and children were less warm and engaged with each other in the suppression condition. There was also a significant link between a mothers physiological stress and that of her child: mothers PEP reactivity at one time point was related to childrens reactivity shortly thereafter. In the control group, however, stress was not transmitted from mother to child.

Interestingly enough, stress wasnt transmitted from fathers to their children, which the team believes is down to how men deal with stress outside of laboratory conditions. Because men are more likely to say theyre fine when theyre not, while women are more likely to show how theyre feeling, the team argues that children were more used to emotional suppression in their male caretakers and were therefore less affected. However, fathers in the suppression condition did become linked to their childrens physiology in the opposite direction: they picked up stress from their children, not the other way around.

As the study focused purely on pairings between a single child and parent, future research could focus on emotional suppression and stress in larger groups or family systems, exploring how a second parent, sibling or other family member affects this physiological link, for instance. Researchers could also examine the techniques that parents use in the control condition: their warm and engaging interactions may stem from specific, positive emotion regulation strategies rather than simply being the result of not suppressing their emotions.

Hiding stress from your children is entirely understandable you may wish to protect them from negative feelings and see emotional suppression as the best way to do that. But, as Waters says, it may be more comforting for children to have their feelings honoured listening to them honestly, rather than brushing over them altogether.

Keep It to Yourself? Parent Emotion Suppression Influences Physiological Linkage and Interaction Behavior

Emily Reynoldsis a staff writer atBPS Research Digest

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UI research entity distributes antibodies to those studying COVID-19 – UI The Daily Iowan

The Developmental Studies Hybridoma Bank housed at the University of Iowa distributes and stores antibodies for biological research.

The Developmental Studies Hybridoma Bank, housed at the University of Iowa, stores and distributes antibodies that now are being distributed to help researchers study the novel coronavirus.

Originally created by the National Institutes of Health 34 years ago, the Developmental Studies Hybridoma Bank is a self-funded entity that keeps antibodies, proteins produced by the immune system to fight viruses and diseases, for companies worldwide for basic research.

David Soll, the banks director, brought the entity to the UI from Johns Hopkins University. The entity sends about 60,000 samples a year worldwide for biological and cancer research, he said.

The bank sells its antibodies to researchers for $40, Soll said. None of the antibodies can be used for commercial purposes, however, as the bank doesnt own the antibodies, it just stores them for researchers, he said.

Although it did not have antibodies specifically for COVID-19, the bank did have a large number of antibodies that react similarly to the coronavirus and could allow researchers to study the interaction between the virus and human cells, Soll said.

The antibodies the bank has can help researchers study the cytokines proteins that are important to cell signaling which sometimes cause the body to react violently to a virus, he said.

We have a very large footprint inside the research community, and the way we do it is we dont own any of the antibodies, people from all over the world bank their antibodies with us, Soll said.

The bank also makes antibodies, Soll said. Its currently producing plasmids and then inserting a piece of DNA into them that codes them for targeted viruses, he added.

The plasmids are injected into mice, Soll said, and then the mouse will make the proteins of the virus and then make antibodies against it.

RELATED: University of Iowa molecular genetics researcher studying COVID-19 testing methods to alleviate test shortages

Diane Slusarski, UI biology department head, is a member of the Developmental Studies Hybridoma Banks advisory board, which meets with Soll to discuss the entitys inventory and work.

The bank provides antibodies for biomedical research and basic research at a good price, Slusarski said. This allows basic research to move forward, she said, because often the budgets arent very large.

The bank has accumulated a lot of antibodies over its years of operations, which makes it so they have the immune response for viruses as well as the antibodies, she said.

The immune responses can be used to understand how the body reacts to other viruses even though the bank doesnt have coronavirus specific antibodies, Slusarski said.

Because the bank is housed at the UI, the biology department is able to give graduate students an opportunity to learn what it takes to make an antibody, Slusarski said.

Now youre going to have people interested in these immune [antibodies] that they have, Slusarski said. So theyre very strategic in looking at how we can help.

Kevin Campbell, UI professor of molecular physiology and biophysics, keeps some of the antibodies his lab has created in the bank.

When he first started teaching at the UI, Campbell said his lab made proteins to study muscles and have been helpful in the productivity of his work, which focuses on muscle physiology and muscular dystrophy.

Campbell said the bank functions as a storage facility to prevent researchers from losing their antibodies if a freezer fails them, and the bank grows the supply of the antibody.

The biggest [benefit] is that now you can make [the antibodies] available to everybody in the world doing research, he said. So that really frees you up from having to send the antibodies out to laboratories.

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UI research entity distributes antibodies to those studying COVID-19 - UI The Daily Iowan

The Myth of Precambrian Sponges – Discovery Institute

Sponges are sessile marine invertebrates that are considered to be the most basal and most primitive branch of the multicellular animals (Metazoa). Therefore, evolutionists would expect to find such sponges as the earliest animals in the fossil record. Also, immunological evidence (Wilkinson 1984) and especially molecular clock data placed the origin of sponges long before the Cambrian and even before the Ediacaran era (Peterson et al. 2004,Sperling et al. 2007,Sperling et al. 2010,Erwin et al. 2011,Cunningham et al. 2017a). Consequently, the alleged discovery of sponge-like fossils from layers prior to the Cambrian explosion, which gave rise to all the more complex animal phyla, was welcomed by evolutionary biologists as clear confirmation of Darwins theory. When the branching order of reconstructed phylogenetic relationships agrees well with the stratigraphic order of appearance in the fossil record, evolutionary biologists speak of so-called stratigraphic fit. The existence of Precambrian fossil sponges was accepted as established fact in many textbooks and academic articles (e.g.,Debrenne & Reitner 2001,Reitner 2005,Budd 2008,Mller et al. 2009). A perfect example isCarrera & Botting (2008), who confidently stated that it is fairly clear that sponges possess a long record back to the Proterozoic, represented in the Ediacara fauna. The evidence seemed convincing enough that even most critics of Darwinian evolution acknowledged the existence of sponges prior to the Cambrian explosion (e.g.,Meyer 2013,Evolution News2016).

I will show that this concession was premature and much too generous. Lets see how good or rather how embarrassingly bad the case for Precambrian sponges really is and have an exhaustive look at all the potential candidates in alphabetical order.

Ausia fenestratais known from a few specimens from the Ediacaran of Namibia and Russia. These about 5 cm small fossils look like a triangular bag with numerous ovate depressions or openings in it. It has been considered to be a cnidarian sea pen by its original describers (Hahn & Plug 1985), or a halkieriid stem mollusk (Dzik 2011), or a chordate tunicate (ascidian) (Fedonkin et al. 2007, 2008,2012), or a sponge-like animal related to the Cambrian Archaeocyatha or even as a true sponge (Fedonkin 1996, McMenamin 1998: 38-39). This shows that the preserved characters are totally insufficient for any definite placement. Unsurprisingly,Antcliffe et al. (2014)consideredAusiaas failing to meet the diagnostic criteria of sponges, andMuscente (2015)commented that such interpretations of aspiculate organisms are inherently subjective, and the affinities of the fossils remain disputed. Interestingly, another genus and species that has been attributed to the same family Ausiidae,Burykhia huntifrom the Ediacaran of Russia, was considered by its describers (Fedonkin et al. 2012) as a possible tunicate, but no possible relation to sponges was even mentioned.

Coronacollina aculais a very strange Ediacaran organism described byClites et al. (2012)from Australia. The fossil is a triradial cone-like mound with four 37 cm long radial spicules, which has been considered as resembling the Cambrian demosponge genusChoia.Coronacollinahas been called the oldest organism with a skeleton and in this way considered as a precursor to the Cambrian explosion (UC Riverside 2012). Serezhnikova (2014) accepted the similarity withChoiaand stated that records of Coronacollina supported the Precambrian origin of sponges and their ability for biomineralization in the Late Proterozoic. In their revision of Ediacaran tri-radial body plans,Hall et al. (2018)excludedCoronacollinafrom the otherwise monophyletic group Trilobozoa or Triradialomorpha, but did not propose any other relationships.Muscente et al. (2015)refuted any structural similarity of the spicules with those of sponges.Cunningham et al. (2017a)observed that there is not even a definite association with the putative spicules and concluded: As such, neither Palaeophragmodictya nor Coronacollina are considered to reflect poriferans, or even metazoans, on the basis of current evidence. None of the recent exhaustive revisions of putative Precambrian sponges still consideredCoronacollinaworthy of discussion (Antcliffe et al. 2014,Botting & Muir 2017).

Cucullus fraudulentusis a bag-like or tube-like fossil and represents the most abundant and largest organism from the Neoproterozoic Miaohe biota of the Doushatuo Formation in China. It was described by Steiner (1994: 125) as a putative cyanobacterial colony or mega-alga of uncertain affinity. Chen et al. (1994) suggested that their new species,Sinospongia hubeiensis, later been synonymized withCucullus fraudulentus, is a poriferan. Therefore, Li et al. (1996) and Hu (1997) attributedCucullusto demosponges, whileSteiner & Reitner (2001)still considered them as microbial colonies. Due to poor preservation, its morphology and affinities remained unclear. ThusXiao et al. (2002)still could not decide if it was a sponge or a siphonous green alga. Finks et al. (2004) rejected an affinity ofCuculluswith sponges in their revised edition of the prestigiousTreatise on Invertebrate Paleontology.Xiao & Dong (2006)consideredCucullusto be a protoarenicolid, which these authors do not identify as an animal but as dasycladacean algae. When new and better preserved material became available from the Doushantuo Formation in China,Wang & Wang (2011)resurrected an affinity to demosponges based on the observation of assumed organic walls formed by non-mineralized spongin fibers.Antcliffe et al. (2014)disagreed and concluded:

There is however, no unequivocal morphological evidence to support assignment to the Porifera. Furthermore, no spicules have been described in association with Cucullus. We conclude that assignment to the Porifera is highly speculative and that Cucullus fails the diagnosis test as the possibility that the specimens are microbialites seems to us much more likely.

Lets repeat this in plain English:Cucullusis not a sponge but rather of microbial origin.Serezhnikova (2014)also found that the interpretation ofCucullusandSinospongiaas sponges and their comparison withVaveliksiaare difficult to support.Muscente (2015)basically agreed with that skeptical position.

Eocyathispongiaqianiawas described byYin et al. (2015)after a single specimen from the Early Ediacaran Doushantuo Formation in China, as a sponge grade fossil with cellular resolution. Of course, it was immediately celebrated in the popular media as the discovery of the oldest sponge (Yirka 2015).Cunningham et al. (2017a)remarked:

It represents the most plausible report of a sponge from the Precambrian. However, more analyses and specimens are needed to test this hypothesis. In particular, high-resolution tomographic analysis of the walls of the specimen could reveal whether pores are present, and therefore whether Eocyathispongia could have functioned as a sponge.

Cunningham et al. (2017b)commented, Eocyathispongiais considered to be one of the strongest candidates for a Precambrian sponge. However, although it could be a sponge, it has no convincing sponge apomorphies such as pores or spicules, just a generalized sponge gestalt.Bottjer et al. (2019)rather suggested that although it contains no characters that are exclusive to crown group sponges , if not a stem group sponge it could be an extinct organism between the last common ancestor of metazoans and the last common ancestor of living sponges. However,Botting & Muir (2018)in their review of early sponge evolution mention a severe problem for the sponge hypothesis:

Eocyathispongia is an extremely interesting fossil, but several features are not easily compatible with sponge biology. The morphology is problematic for a sponge, especially a very small one, as it appears to actively minimise the available surface area for incurrent pores, on which it would depend for feeding.

In my view this tiny fossil, which is only about a single millimeter in size, represents just another vase-shaped encysting protist from the Doushantuo layers (Li et al. 2008).

Namapoikiarietoogensisis a calcified reef-building organism of up to one meter size, discovered in the Ediacaran Nama group of southern Namibia. In the original description its affinities have been considered to be with either cnidarians or sponges (Wood et al. 2002).Zhuralev et al. (2012)agreed thatNamapoikiais only of a cnidarian or poriferan grade of organisationAntcliffe et al. (2014)clarified in their large revision of alleged Precambrian sponges that diagnostic poriferan morphological characteristics are lacking and that such a structure could arrive from the calcification of microbial colonies.Wood & Curtis (2015)still considered it to be of uncertain affinity, though resembling chaetetid sponges or simple colonial cnidarians.Cunningham et al. (2017a)said thatNamapoikiapossesses no characters diagnostic of any particular eukaryotic group.Wood & Penny (2018)finally placed its probable affinity within total-group poriferans, mainly based on similarities in growth pattern and (inferred!) biomineralization. They concluded that such an interpretation confirms the presence of poriferans, with calcareous skeletons, in the terminal Ediacaran. However,Tang et al. (2019)remained unconvinced and offered the qualification that Namapoikiahas been interpreted as an encrusting poriferan, but more work is needed to confirm that it is a calcified encrusting sponge rather than a microbial structure, which strongly suggests thatNamapoikiastill fails to meet the diagnostic criteria required byAntcliffe et al. (2014).

Curiously,Wikipediaclaims thatZhuralev et al. (2015)instead proposed an affinity with lophophorate bilaterian animals or their stem group. However, this is total nonsense and factually incorrect as this paper does not even remotely make such a claim. This example shows how utterly unreliableWikipediais as source for scientifically accurate information.

Otavia antiquais an irregular spheroid microfossil found in 760-550 million year old layers in Namibia, of which some predate the Ediacaran and even the assumed neoproterozoic snowball earth period called Cryogenian. It was described as a sponge-like fossil byBrain et al. (2012), and again celebrated by the press as Namibia sponge fossils are worlds first animals (AFP 2012,Gess 2012).Antcliffe et al. (2014)rejected its identification as a sponge and remarked that alternative hypotheses have not been sufficiently explored and/or have been rejected without sufficient reason. They even raised severe doubts thatOtaviais a genuine fossil of biogenic origin at all, or maybe of microbial origin rather than an animal. Antcliffe et al. concluded that no features are presented that are diagnostic of sponges. We interpret these objects as calciphosphate grains that have been pitted by sediment reworking. This sounds much less spectacular and thus did not hit the news headlines. Even the more recent textbook byJain (2016: page 7),Fundamentals of Invertebrate Palaeontology,ignored the refutation and still teaches gullible students the obsolete story thatOtaviais a calcareous sponge and the oldest animal.

The type speciesPalaeophragmodictya reticulatawas described byGehling & Rigby (1996)as long expected sponges from the Neoproterozoic Ediacara fauna of South Australia. The very title of their work shows how eagerly Darwinists longed for an empirical confirmation of their theoretical expectations. The sponge affinity was accepted by most other authors (e.g.,Seilacher 1999, Finks et al. 2004,McCall 2006). About ten years later a second speciesP. spinosawas discovered bySerezhnikova (2007)in the White Sea region of Russia and demolished these expectations again. She did not identifyPalaeophragmodictyaas sponge at all, but recognized that it is just a holdfast of an unknown sessile organism (again affirmed bySerezhnikova 2014) that might have been a cnidarian. Nevertheless, the story was apparently too nice to be spoiled by stupid facts, so that the sponge interpretation was retained in many recent articles (e.g.,Maloof et al. 2010,Brain et al. 2012,Dohrmann et al. 2013,Stearley 2013). But the truth could not be ignored forever. Antcliffe et al. (2014)

agree with Serezhnikova (2007a) that some of the material is likely to represent the holdfast of other Ediacaran-age organisms, we question whether these specimens represent sponges of any kind. No compelling arguments are presented that Palaeophragmodictya should be considered separately from other disc-like structures of Ediacaran age.

Furthermore, Antcliffe et al. present extensive evidence and arguments that these fossils indeed represent holdfasts of the typical Ediacaran frond-like organisms.Cunningham et al. (2017a)acknowledged thatPalaeophragmodictyais perhaps the most widely recognized candidate for a sponge within the Ediacaran macrobiota but the taxon may be more readily interpreted as decayed attachment discs from an organism of uncertain affinity.Likewise,Botting & Muir (2018)remarked that this fossil taxon was a misidentified holdfast of an Ediacaran frond and bears little resemblance to extant or early fossil sponges. Finally, the only potential sponge character inPalaeophragmodictyaand some other alleged Precambrian sponges, the presence of apparent skeletal nets, has been discredited by a new study byLuzhnaya & Ivantsov (2019), who documented such structures in the characteristic Ediacaran fronds, which were never considered as sponges and certainly are not because they have no openings for water circulation.

Rugoconites enigmaticusis another circular organism from the Ediacaran biota of Australia described byGlaessner & Wade (1966).Gehling & Rigby (1996)mentioned thatRugoconiteshas some characters in common withPalaeophragmodictya, but recognized that the lack of evidence of a spicular framework prevents a clear assignment of Rugoconites to the poriferans. Some authors considered them to be jellyfish (Cloud & Gessner 1982,Sepkoski 2002), while others considered them as possible sponges (Darroch et al. 2018). Nevertheless, the consensus among specialists today generally tends to classifyRugoconitesas member of the Ediacaran monophylum Trilobozoa or Triradialomorpha with a tri-radial body plan (Ivantsov & Fedonkin 2002,Xiao & Laflamme 2009,Hall et al. 2018).

The genusSinospongiais known from two species,S. typicaandS. chenjunyuani, from the Miaohe biota of the Doushantuo Formation in China (a third speciesSinospongia hubeiensiswas synonymized withCucullus fraudulentus, see above). It was considered as mega-algae by Steiner (1994), as microbial colonies bySteiner & Reitner (2001), and as Protoarenicolidae byXiao & Dong (2006), which these authors do not identify as animals but as dasycladacean algae with holdfasts.Xiao et al. (2002)suggested three possible interpretations: sponge, cnidarian, or siphonous green alga, because no convincing sponge spicules have been found in association with these fossils, and alternative algal interpretations are possible and alternative interpretations, such as a cnidarian-grade organism or a siphonous green alga (especially of the order Dasycladales), should be entertained. As already mentioned above,Serezhnikova (2014)concluded, Therefore, the interpretation of Cucullus and Sinospongia as sponges and their comparison with Vaveliksia are difficult to support. The more recent revisions of alleged Precambrian sponges byAntcliffe et al. (2014),Muscente et al. (2015), andBotting & Muir (2018)did not even bother to further discussSinospongiaas a putative sponge.

Thectardis avalonensisis a conical organism of about 9 cm length and 3 cm diameter, known from numerous specimens from the Ediacaran Mistaken Point locality in Newfoundland (Clapham et al. 2004). It is believed to have been attached with its pointed end to the bacterial mat sea floor as a suspension feeding mat sticker, but it lacks any visible holdfast structures. In the original description no affinity to sponges or any other group was suggested.Sperling et al. (2011)proposed a most likely attribution to sponges, only based on the habitat beneath the photic zone (which precludes photosynthesis) and because its body plan would be consistent with the hydrodynamics of the sponge water-canal system. This is a very weak level of argumentation for the far-reaching conclusion that the recognition of sponges in the Mistaken Point biota provides some of the earliest body fossil evidence for this group, which must have ranged through the Ediacaran based on biomarkers, molecular clocks, and their position on the metazoan tree of life, in spite of their sparse macroscopic fossil record. Consequently,Antcliffe et al. (2014)correctly pointed out that such poor indirect criteria could at best exclude certain affinities, but not confirm any. They concluded that the interpetation ofThectardis avalonensisas a fossil sponge is therefore highly problematic. They even elaborated that the fossil might rather be just the misinterpreted remains of the decay process of an unknown larger organism.Muscente et al. (2015)concluded Thectardisfrom Newfoundland have been interpreted as sponges based on inferences regarding soft tissue anatomy, biomechanics, and taphonomy. However, such interpretations of aspiculate organisms are inherently subjective, and the affinities of the fossils remain disputed. Christian paleontologist RalphStearley (2013)still affirmed that the conical fossilThectardisfrom the Avalon assemblage is also probably a sponge, but this was just in a book review.Serezhnikova (2014)agreed that the general body plan ofThectardisis similar to the sponge-like archaeocyaths, but offered the qualification that the affinity of the Precambrian taxa to Porifera is limited by a lack of data on their possible filtering structures.Liu & Conliffe (2015)remarked that until more informative specimens are found, this taxon will likely remain of uncertain biological affinity.Botting & Muir (2018)remarked that although it is theoretically possible that some alleged Ediacaran Biota sponges (e.g., the featureless triangle-shaped objectThectardisClapham et al., 2004; Sperling et al., 2011) are in fact genuine, there is no evidence to that effect. Let that sink in: NO EVIDENCE! There seems to be a pattern here: desperate attempts to fulfill Darwinian expectations in the absence of any convincing evidence.

A 3-10 cm large sac-shaped organism of radial symmetry with a perforated body wall and an attachment disc, the type speciesVaveliksia velikanoviwas described by Fedonkin (1983) from the Ediacaran of Ukraine. A second species,Vaveliksia vana,was described from the Vendian of the White Sea region in Russia byIvantsov et al. (2004). They concluded: From the above observations and assumptions, one may propose thatVaveliksiahas the same level of organization as archaeocyaths or sponges.McCall (2006)suggested possible coelenterate and hydrozoa affinities instead.Serezhnikova (2014), who co-described the second species ofVaveliksia, listed it as problematic lower metazoans with a levelof organization of parazoa (?).Antcliffe et al. (2014)mentioned the possibility thatVaveliksiacould rather be an agglutinated amoebozoan, thus a colonial protist, and concluded that Vaveliksia vanalacks any definitive poriferan characteristics and fails the characters and diagnosis criteria.

Malloof et al. (2010)reported unnamed ellipsoidal fossils as sponge-grade metazoans from the Neoproterozoic of Australia. Paleontologist ChrisNedin (2010)was not convinced and commented on his respected Ediacaran blog that Proterozoic Sponges Claim Doesnt Hold Water. Well, blogs dont count in science, butAntcliffe et al. (2014)came to the same conclusion and remarked that

no characteristics that are distinctive for sponges are presented by the authors. These fossils have no morphology that is diagnostic of sponges and should in our view be more readily ascribed to the calcimicrobes that abound at these localities.

Finally,Wallace et al. (2014)described unnamed chambered structures from Cryogenian reefs, for which they pose the question of whether they could be the oldest sponge-grade organisms. However, they concluded:

The closest morphological analogues for the structures are: a) some types of reef-dwelling sponges; and b) some complex microbialites from Archean and Paleoproterozoic carbonates. The structures lack spicules and ostia found in sponges, ruling out a true Poriferan origin. However, it is plausible that they are proto-sponges, sponge-grade organisms, or complex microbial precursors to sponge-grade organisms. Whatever their affinity, we suggest these structures record a significant evolutionary event on the path towards organic complexity.

It is very clear from their conclusions that these fossils also fail all three criteria ofAntecliffe et al. (2014)for an identification as sponges and thus have to be considered as problematic fossils of uncertain affinity, but more likely of microbial origin.

That was the last candidate. But what about more indirect evidence from alleged sponge embryos, sponge needles, and sponge biomarkers? Here comes the story of their demise.

Phosphatized microfossils from the 609-million-year old Doushantuo Formation in China, which were originally interpreted as colonial green algae, were later re-interpreted as alleged animals (Xiao et al. 1998) and especially sponge embryos and sponge larvae (Li et al. 1998a,1998b, Chen et al. 1999,Chen et al. 2000,Xiao & Knoll 2000,Xiao et al. 2000, Chien et al. 2001,Chen 2012). This interpretation was immediately disputed by other Chinese researchers (Zhang et al. 1998, Xue et al. 1999), who alternatively identified these fossils as collapsed acritarch protists, thus not sponges at all but unicellular organisms. Even thoughCao & Zhu (2001)disagreed with this, they acknowledged that whether or not they are larvae of sponges, it is not determined as yet.Hagadorn et al. (2006)showed that the absence of epithelialization is consistent only with a stem-metazoan affinity for Doushantuo embryos, thus rejecting any sponge affinities.

Bailey et al. (2007)suggested that the alleged embryos are giant actually vacuolate sulphur bacteria close to the recent genusThiomargarita. However, this was convincingly rejected byDonoghue (2007),Xiao et al. (2007),Yin et al. (2007),Cunningham et al. (2012), andIgisu et al. (2014), even though these authors did not all agree on the embryo nature of the fossils.

After careful synchrotron-tomographic studies, which included a team of the most eminent paleontologists like Philip Donoghue and Stefan Bengtson,Huldtgren et al. (2011)concluded that the alleged embryos are neither metazoans nor embryos but just encysting eukaryotic protists (also seeButterfield 2011, who commented that wherever the Doushantuo fossils eventually end up, it will clearly not be within crown-group Metazoa, andKaplan 2011, whose comments are titled, Enigmatic fossils are neither animals nor bacteria).Xiao et al. (2012)readily disagreed in a response to this article, but were again refuted byHuldtgren et al. (2012). But then, in a study byChen et al. (2014), co-authored by Shuhai Xiao, the authors came to the same result that the available evidence also indicates that the Doushantuo fossils are unlikely crown-group animals.

Even the alleged and much celebrated oldest bilaterian animalVernanimalculafrom the Doushantuo Formation was debunked byBengtson et al. (2012)in an article titled A merciful death for the earliest bilaterian, in which the authors came to the scathing conclusion that there is no evidential basis for interpretingVernanimalculaas an animal.

Yin et al. (2016)presented new evidence in the form of meroblastic cleavage patterns for the identification of Doushantuo fossils as metazoan embryos, but acknowledged that their phylogenetic affinity cannot be established. Just recently,Yin et al. (2019)described gastrulation-like cell division in the fossilCaveasphaerafrom this locality, which they said foreshadows animal-like embryology. However, it was not considered as a sponge or even a metazoan by these authors. CarlZimmer (2019)commented in theNew York Timesthat these balls of cells may be the oldest animal embryos or something else entirely.

Cunningham et al. (2017b)reviewed all the published evidence from the Wenan biota of the Doushantuo Formation and concluded that although the Wengan Biota includes forms that could be animals, none can currently be assigned to this group with confidence. If there are not even definite animals, there can be no sponge embryos either.

Independent of the doubtful nature of the Doushantuo embryos, recently a multicellular organism was described as a microfossil from the Ediacaran Nyborg Formation in Norway (Agi et al. 2019). It was namedCyathinema digermulenseand the authors considered it as sharing characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Even though sponge affinities are not ruled out, they have not been demonstrated either.

Even if all the body fossils discussed above fail to establish the presence of sponges prior to the Cambrian era, maybe we could at least find their most durable parts as microfossils: sclerotized needles, so-called spicules, that form the skeleton of sponges and are made of silica or calcite.

Indeed, several works described alleged sponge spicules from Precambrian deposits, mainly in China (Dunn 1964, Tang et al. 1978, Ding et al. 1985, Zhao et al. 1988,Allison & Awramik 1989,Brasier 1992,Steiner et al. 1993,Gehling & Rigby 1996,Brasier et al. 1997,Li et al. 1998a,Tiwari et al. 2000,Xiao et al. 2000,Du & Wang 2012, andDu et al. 2015). Even elaborate scenarios for the presumed evolution of sponge skeletons in the Proterozoic have been proposed based on this evidence (Mller et al. 2007).

Steiner et al. (1993)questioned the Doushantuo spicules andGehling & Rigby (1996)mentioned that of the many reported spicules from Proterozoic sediments most have proven to be volcanic shards or other inorganic crystals (Pickett, 1983).

Zhou et al. (1998) considered the spicule-like structures from the Doushantuo Formation described byLi et al. (1998)as nothing but pseudo-fossils, whileZhang et al. (1998)considered them as detached spines of collapsed acritarch protists.Cao & Zhu (2001)disagreed and remarked that based on the observation of extant specimens they tend to the interpretation of the sponges as monaxial spicules.

Yin et al. (2001)showed that the alleged sponge spicules from the Doushantuo Formation in China are indistinguishable from coexistent diagenetic crystals, thus inorganic artefacts rather than fossil remains. They found that the evidence for a sponge spicule interpretation of the Doushantuo spicular structures are at best ambiguous at present, but strangely added the inconsistent disclaimer (likely for political reasons) that despite our initial questioning the proposed interpretation of Doushantuo spicular structures as demosponge microscleres, we do not deny that sponges spicules do exist in Doushantuo cherts.

Antcliffe et al. (2014)reviewed all the published evidence for alleged sponge spicules from the Precambrian and dismissed all of them, mostly as abiogenic artifacts (e.g., the once oldest, widely accepted hexactinellid spicules from Mongolia, which were shown to be cruciform arsenopyrite crystals by EDX analysis). They found that the earliest reliable sponge fossils are hexact spicules from Iran dated to c. 535 Ma.

Muscente et al. (2015)used the most modern analytical techniques like scanning electron microscopy and synchrotron nanotomography to decisively assess the veracity of assumed Precambrian sponge needles, especially from the Doushantuo Formation. They found that their new data invalidate the oldest and only Precambrian demosponges with mineralized spicules. Thehighlightssection in their article says it all:

Finally,Botting & Muir (2018)agreed in the most recent review of early sponge evolution that there are no definite records of Precambrian sponges: isolated hexactine-like spicules may instead be derived from radiolarians. AndTang et al. (2019)likewise stated that the oldest spicules are Cambrian in age, but hypothesized based on a new Cambrian fossil that potential Ediacaran sponges might have lacked biomineralized spicules (also seeTang 2019). So, when alleged Precambrian spicules were found they were naturally considered as evidence for Darwinian evolution, and now since they are consistently lacking, Darwinian evolution is invoked to explain their absence. Whatever the evidence says, Darwinists always claim victory.

The latest claim was made recently byChang et al. (2019), who reported alleged sponge spicules from the Ediacaran-Cambrian boundary of the Yanjiahe Formation in China. However, in the actual article they only say that monaxon spicules and spicule-like structures in the lower Yanjiahe Formation might putatively be interpreted as demosponge remains, thus acknowledging a high degree of uncertainty. They also acknowledged that their interpretation of the monaxon spicules would be incongruent with the evolutionary scenario ofBotting & Muir (2018), who suggested a hexactine-based ground plan. In the Yanjiahe Formation non-monaxon spicules only appear just beneath the Lower CambrianProtohertzina anabariteszone (see their Figure 6).

The fact is this: Despite the multiple premature claims of success, genuine sponge needles from the Precambrian era thus not only have proved to be elusive like the proverbial needles in a haystack but indeed seem to be non-existent.

Based on chemical analyses of sediments it has been suggested that fossil steroids (24-isopropylcholestane and 26-methylstigmastane) are lipid biomarkers that provide indirect evidence for the existence of demosponges in the Precambrian (McCaffrey et al. 1994, Moldowan et al. 1994,Love et al. 2009,Sperling et al. 2010).Antcliffe (2013)questioned the evidence for sponge biomarkers because 24isopropylcholestane is also produced by marine algae or their diagenetic alteration, and claimed that it seems more likely that these compounds represent algal biochemical evolution at a time when algal burial occurred in great quantity with well-known coeval algal fossils but no sponge fossils. This was reasonably rejected byLove & Summons (2015), and even very recent studies byGold et al. (2016a),Gold et al. (2016b),Brocks et al. (2017),Sperling & Stockey (2018), andZumberge et al. (2018)still considered this so-called sponge biomarker hypothesis to be validated by the most up-to-date evidence. The popular science media reported Sponges on ancient ocean floors 100 million years before Cambrian period (UC Riverside 2018). However,Nettersheim et al. (2019)found these putative typical sponge biomarkers to be common among unicellular organisms (Rhizaria) and concluded that negating these hydrocarbons as sponge biomarkers, our study places the oldest evidence for animals closer to the Cambrian Explosion. Ooops!

In a thorough revision of all twenty potential Precambrian sponge fossils, including most of the taxa discussed above (exceptEocyathispongia) as well as all the other unnamed candidates for sponge-grade metazoans,Antcliffe et al. (2014)came to the conclusion that that no Precambrian fossil candidate yet satisfies all three of these criteria to be a reliable sponge fossil. The authors suggested that molecular clocks should be recalibrated accordingly to a Lower Cambrian age of sponges and metazoans (such a recalibration is just a euphemism for using a fudge factor to get the desired outcome).Muscente et al. (2015)confirmed this result that no unequivocal sponge fossils occur below the EdiacaranCambrian boundary. Another recent study about the early history of sponges (Botting & Muir 2018) also found that there are no definite records of Precambrian sponges. Just a year later,Nettersheim et al. (2019)refuted the only remaining biomarker evidence (see above), so that all the empirical evidence for Precambrian sponges had finally evaporated. Maybe new fossil finds will come up with something better, but considering the track record so far, we probably dont have to hold our breath.

We can safely conclude that, contrary to common misconception, there exists zero compelling evidence for the existence of any genuine Precambrian fossil sponges. Unambiguous sponges only appear in the Cambrian explosion together with the other animal phyla. The oldest reliable fossil record for sponges is represented by siliceous spicules from the basal Cambrian of Iran (Antcliffe et al. 2014) and China (Chang et al. 2017,Chang et al. 2019) (the latter are slightly older, just below theProtohertzina anabariteszone). With an age of about 535 million years these are even two million years younger than the oldest trace fossil evidence for crown-group arthropods like trilobites recently dated to 537 million years ago (Daley et al. 2018). The first complete body fossils of sponges only appear even somewhat later in the Lowermost Cambrian (Steiner et al. 1993,Yuan et al. 2002.Flgel & Singh 2003). Only after 525 million years ago sponges became more common (Antcliffe et al. 2014), and crown group demosponges do not appear before 515 million years (Botting et al. 2015).

Having sponges appear after arthropods is not only a very bad stratigraphic fit, but indeed rather a temporal paradox like in many other cases (e.g., the oldest tetrapods and birds). If a good stratigraphic fit is considered to be confirmation for Darwins theory, then a poor stratigraphic fit (as well as a mismatch between molecular clocks and fossil record) has to count as conflicting evidence, even if evolutionists can fudge boldad hocexplanations (like 200-million-year-long ghost lineages,Sperling et al. 2010) to accommodate and explain away such unwelcome data.

Interestingly, the most comprehensive revision of the early fossil record of sponges, byAntcliffe et al. (2014), came to a conclusion very similar to that of intelligent design proponent Stephen C. Meyer in his seminal bookDarwins Doubt. Here is what they said in their conclusion: The Cambrian explosion was an evolutionary event of great magnitude and closely connected to the origin of animals. Science deniers like Jerry Coyne, Donald Prothero, and Nick Matzke, who downplayed the Cambrian explosion in their polemical reviews of Meyers book, should read the actual specialists to learn about the significance and abruptness of the origin of animal body plans in the Cambrian explosion, including the body plan of the most primitive animals, sponges.

Photo: Living Guantanamo sponge, by Timothy W. Brown / Public domain.

More:
The Myth of Precambrian Sponges - Discovery Institute

Study provides genetic explanation behind the sex bias observed in certain diseases – News-Medical.Net

Some diseases exhibit a clear sex bias, occurring more often, hitting harder or eliciting different symptoms in men or women.

For instance, the autoimmune conditions lupus and Sjgren's syndrome affect nine times more women than men, while schizophrenia affects more men and tends to cause more severe symptoms in men than in women.

Likewise, early reports suggest that despite similar rates of infection, men are dying from COVID-19 more often than women, as happened during previous outbreaks of the related diseases SARS and MERS.

For decades, scientists have tried to pinpoint why some diseases have an unexpected sex bias. Behavior can play a role, but that explains only a piece of the puzzle. Hormones are commonly invoked, but how exactly they contribute to the disparity is unclear. As for genes, few, if any, answers have been found on the X and Y sex chromosomes for most diseases.

Now, work led by researchers in the Blavatnik Institute at Harvard Medical School and at the Broad Institute of MIT and Harvard provides a clear genetic explanation behind the sex bias observed in some of these diseases.

The team's findings, reported May 11 in Nature, suggest that greater abundance of an immune-related protein in men protects against lupus and Sjgren's but heightens vulnerability to schizophrenia.

The protein, called complement component 4 (C4) and produced by the C4 gene, tags cellular debris for prompt removal by immune cells.

The team's key findings:

"Sex acts as a lens that magnifies the effects of genetic variation," said the study's first author, Nolan Kamitaki, research associate in genetics in the lab of Steven McCarroll at HMS and the Broad.

We all know about illnesses that either women or men get a lot more, but we've had no idea why. This work is exciting because it gives us one of our first handles on the biology."

Steven McCarroll, Dorothy and Milton Flier Professor of Biomedical Science and Genetics, HMS

McCarroll is the director of genomic neurobiology at the Stanley Center for Psychiatric Research at the Broad. McCarroll is also the co-senior author of the study with Timothy Vyse of King's College London.

Although C4 variation appears to contribute powerfully to disease risk, it is only one among many genetic and environmental factors that influence disease development.

The study's results are informing the ongoing development of drugs that modulate the complement system, the authors said.

"For example, researchers will need to make sure that drugs that tone down the complement system do not unintentionally increase risk for autoimmune disease," said McCarroll. "Scientists will also need to consider the possibility that such drugs may be differentially helpful in male and female patients."

On a broader level, the work offers a more solid foundation for understanding sex variation in disease than has been available before.

"It's helpful to be able to think about sex-biased disease biology in terms of specific molecules, beyond vague references to 'hormones,'" McCarroll said. "We now realize that the complement system shapes vulnerability for a wide variety of illnesses."

In 2016, researchers led by Aswin Sekar, a former McCarroll lab member who is a co-author of the new study, made international headlines when they revealed that specific C4 gene variants underlie the largest common genetic risk factor for developing schizophrenia.

The new work suggests that C4 genes confer both an advantage and disadvantage to carriers, much as the gene variant that causes sickle cell disease also protects people against malaria.

"C4 gene variants come with this yin and yang of heightened and reduced vulnerability in different organ systems," said McCarroll.

The findings, when combined with insights from earlier work, offer insights into what may be happening at the molecular level.

When cells are injured, whether from a sunburn or infection, they leak their contents into the surrounding tissue. Cells from the adaptive immune system, which specialize in recognizing unfamiliar molecules around distressed cells, spot debris from the cell nuclei.

If these immune cells mistake the flotsam for an invading pathogen, they may instigate an attack against material that isn't foreign at all--the essence of autoimmunity.

Researchers believe that complement proteins help tag these leaked molecules as trash so they're quickly removed by other cells, before the adaptive immune system pays too much attention to them.

In people with lower levels of complement proteins, however, the uncollected debris lingers longer, and adaptive immune cells may become confused into acting as if the debris is itself the cause of problem.

As part of the new study, Kamitaki and colleagues measured complement protein levels in the cerebrospinal fluid of 589 people and blood plasma of 1,844 people. They found that samples from women aged 20 through 50 had significantly fewer complement proteins--including not only C4 but also C3, which activates C4--than samples from men of the same age.

That's the same age range in which lupus, Sjgren's and schizophrenia vulnerabilities differ by sex, Kamitaki said.

The results align with previous observations by other groups that severe early-onset lupus is sometimes associated with a complete lack of complement proteins, that lupus flare-ups can be linked to drops in complement protein levels and that a common gene variant associated with lupus affects the C3 receptor.

"There were all these medical hints," said McCarroll. "Human genetics helps put those hints together."

The bulk of the findings arose from analyses of whole genomes from 1,265 people along with single nucleotide polymorphism (SNP) data from 6,700 people with lupus and 11,500 controls.

C4 genes and proteins come in two types, C4A and C4B. The researchers found that having more copies of the C4A gene and higher levels of C4A proteins was associated with greater protection against lupus and Sjgren's, while C4B genes had a significant but more modest effect. On the other hand, C4A was linked with increased risk of schizophrenia, while C4B had no effect on that illness.

In men, common combinations of C4A and C4B produced a 14-fold range of risk for lupus and 31-fold range of risk for Sjgren's, compared to only 6-fold and 15-fold ranges in women, respectively.

The researchers didn't expect the genes' effects to be so strong.

Large genetic effects tend to come from rare variants, while common gene variants generally have small effects. The C4 gene variants are common, yet they are very impactful in lupus and Sjgren's."

Steven McCarroll, Dorothy and Milton Flier Professor of Biomedical Science and Genetics, HMS

Still, complement genes don't tell the full story of lupus, Sjgren's or schizophrenia risk, none of which are caused entirely by genetics.

"The complement system contributes to the sex bias, but it's only one of probably many genetic and environmental contributors," said Kamitaki.

Complement genes and another family of immune-related genes, called human leukocyte antigen or HLA genes, are interspersed throughout the same complex stretch of the human genome. HLA variants have been shown to raise risk of developing other autoimmune diseases, including type 1 diabetes, celiac disease and rheumatoid arthritis, and researchers had long believed that something similar was happening with lupus and Sjgren's.

The culprit, however, remained stubbornly hard to pin down, because specific variants in HLA genes and C4 genes always seemed to appear together in the same people.

Kamitaki and colleagues overcame this hurdle by analyzing DNA from a cohort of several thousand African American research participants. The participants' DNA contained many more recombinations between complement and HLA genes, allowing the researchers to finally tease apart the genes' contributions.

"It became quite clear which gene was responsible," said McCarroll. "That was a real gift to science from African American research participants. The question had been unsolved for decades."

The discovery provides further proof that the field of genetics would benefit from diversifying the populations it studies, McCarroll said.

"It will really help for genetics to expand more strongly beyond European ancestries and learn from genetic variation and ancestries all over the world," he said.

C4 variation could contribute to sex-based vulnerabilities in other diseases not yet analyzed, the authors said. It's not yet clear whether C4 pertains to the sex bias seen in COVID-19.

"We don't know the mechanism yet for why men seem to get sicker from COVID-19," said McCarroll. "Complement molecules are potentially important in any immune or inflammatory condition, and in COVID-19, it seems the immune response can be part of a downward spiral in some patients. But we don't know the key details yet."

It also remains to be seen how the differing effects of complement genes apply to people with intersex traits, also known as disorders or differences of sex development, who don't always fit textbook genetic or biological definitions of male and female.

"That is important to understand," said McCarroll.

Source:

Journal reference:

Kamitaki, N., et al. (2020) Complement genes contribute sex-biased vulnerability in diverse disorders. Nature. doi.org/10.1038/s41586-020-2277-x.

See original here:
Study provides genetic explanation behind the sex bias observed in certain diseases - News-Medical.Net

Seattle Genetics Announces the Approval of TUKYSA (tucatinib) in Switzerland for the Treatment of Patients with Metastatic HER2-Positive Breast Cancer…

BOTHELL, Wash.--(BUSINESS WIRE)-- Seattle Genetics, Inc., Inc. (Nasdaq:SGEN) today announced that the Swiss Agency for Therapeutic Products (Swissmedic) has granted approval for TUKYSA (tucatinib) tablets in combination with trastuzumab and capecitabine, for the treatment of patients with metastatic HER2-positive breast cancer, who have previously received two or more anti-HER2 regimens in any setting, including trastuzumab, pertuzumab and trastuzumab-emtansine (TDM1).

The application for TUKYSA approval was reviewed by Swissmedic as part of Project Orbis, an initiative of the U.S. Food and Drug Administration (FDA) Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international regulatory agencies in Canada, Australia and Singapore. On April 17, the FDA approved TUKYSA in the U.S. under the FDAs Real-Time Oncology Review (RTOR) pilot program, four months prior to its action date, and represented the first new drug approved under Project Orbis.

Were grateful to Swissmedic for their collaboration through FDAs Project Orbis in approving this important new medicine in Switzerland, said Jennifer Stephens, Vice President of Regulatory Affairs at Seattle Genetics. We're committed to bringing new targeted therapies to patients, and we are excited about this important first step toward making TUKYSA available to patients in Switzerland.

TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.i,ii

The approval is based on results from the pivotal trial HER2CLIMB, a randomized (2:1), double-blind, placebo-controlled trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). The study results were published in The New England Journal of Medicine in December 2019.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In 2018, more than two million new cases of breast cancer were diagnosed worldwide, including 522,513 in Europe. iii Between 15 and 20 percent of breast cancer cases are HER2-positive.iv Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.v,vi,vii Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.viii,ix,x

About TUKYSA (tucatinib)

TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.xi In the U.S., TUKYSA is approved in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Important U.S. Safety Information

Warnings and Precautions

If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.

Adverse Reactions

Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in 2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in 1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in 2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade 3 laboratory abnormalities reported in 5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

Drug Interactions

Use in Specific Populations

For more information, please see the full Prescribing Information for TUKYSA here.

About Seattle Genetics

Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in peoples lives. ADCETRIS (brentuximab vedotin) and PADCEVTM (enfortumab vedotin-ejfv) use the companys industry-leading antibody-drug conjugate (ADC) technology. ADCETRIS is approved in certain CD30-expressing lymphomas, and PADCEV is approved in certain metastatic urothelial cancers. TUKYSATM (tucatinib), a small molecule tyrosine kinase inhibitor, is approved in certain HER2-positive metastatic breast cancers. The company is headquartered in Bothell, Washington, with locations in California, Switzerland and the European Union. For more information on our robust pipeline, visit http://www.seattlegenetics.com and follow @SeattleGenetics on Twitter.

Forward Looking Statements

Certain statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of TUKYSA including its efficacy, safety and therapeutic uses including the potential use of TUKYSA in combination with trastuzumab and capecitabine for the treatment of patients with metastatic HER2-positive breast cancer, who have previously received two or more anti-HER2 regimens in any setting, including trastuzumab, pertuzumab and trastuzumab-emtansine (TDM1) and the potential to bring TUKYSA to patients in Switzerland. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include reimbursement processes, the extent of reimbursement, the possibility that adverse events or safety signals may occur, the possibility that the ultimate utilization and adoption of TUKYSA by prescribing physicians may be limited, including due to impacts related to the COVID-19 pandemic, the possibility of difficulties in supplying and commercializing a new therapeutic agent, and the possibility of adverse regulatory actions. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption Risk Factors included in the companys Quarterly Report on Form 10-Q for the quarter ended March 31, 2020 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

i TUKYSA [package insert]. Bothell, WA: Seattle Genetics, Inc.ii Anita Kulukian, Patrice Lee, Janelle Taylor, et al. Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor ModelsMol Cancer Ther 2020;19:976-987.iii Breast. Globocan 2018. World Health Organization. 2019. https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf iv Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177-82.v Loibli S, Gianni L. HER2-positive breast cancer. Lancet. 2017; 389(10087): 2415-29.vi Slamon D, Clark G, Wong S, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177-82.vii Breast Cancer HER2 Status. American Cancer Society website. http://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed March 9, 2020.viii Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2019;37:1081-1089.ix Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22:525-531.x Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer. 2003;97:2972-2977.xi TUKYSA [package insert]. Bothell, WA: Seattle Genetics, Inc.

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Seattle Genetics Announces the Approval of TUKYSA (tucatinib) in Switzerland for the Treatment of Patients with Metastatic HER2-Positive Breast Cancer...

Ironshore to Present Posters at the 2020 Neuroscience Education Institute Virtual Scientific Poster Session – Business Wire

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Ironshore Pharmaceuticals Inc. (Ironshore), a wholly owned subsidiary of Highland Therapeutics Inc. and a leader in the commercialization of novel treatments for Attention-Deficit/Hyperactivity Disorder (ADHD), today announced it is presenting two posters featuring new analyses of its novel delayed-release and extended-release methylphenidate formulation. These analyses demonstrate that the uniphasic drug delivery system and site of absorption produce a gradual absorption and protracted elimination phase resulting in attenuated peak drug concentration levels across the dosing range and may lead to a dose-dependent duration of effect. The posters are available for download at the Virtual Scientific Poster Session of the Neuroscience Education Institute (NEI). This initiative was coordinated in response to the COVID-19 pandemic and is designed to fill the void in the presentation and dissemination of emerging science historically presented during live meetings. The posters will be accessible to NEIs 65,700 members and subscribers at http://nei.global/vsp.

The two poster presentations are:

Model-Based Approach to Establish Predicted Clinical Response of Delayed-Release and Extended-Release Methylphenidate (DR/ER-MPH) for ADHD TreatmentRoberto Gomeni, PhD, Marina Komolova, PhD; Bev Incledon, PhD; Stephen V. Faraone, PhDhttps://www.neiglobal.com/VSP/NEIVSPDetail/tabid/562/args/7/Default.aspx

Site-Specific Colonic Absorption for an Optimized Pharmacokinetic Profile of DR/ER-MPH for the Treatment of ADHDFeng Zhang, PhD; Norberto J. DeSousa, MA; F. Randy Sallee, MD, PhD; David Lickrish; Bev Incledon, PhDhttps://www.neiglobal.com/VSP/NEIVSPDetail/tabid/562/args/6/Default.aspx

The posters will enable NEIs stakeholders to learn more about JORNAY PM (methylphenidate HCl) extended-release capsules CII, which was approved in August 2018 by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD in patients 6 years and older.

Ironshore is proud to participate in NEIs innovative new forum to present data that are relevant to psychiatrists, psychiatric nurse practitioners, and other mental health care professionals, said Dr. Randy Sallee, Ironshores Chief Medical Officer. We look forward to sharing new data related to the unique absorption profile of JORNAY PM facilitated by the DELEXIS delayed-release, extended-release, drug delivery technology as well as an evaluation of the medicines pharmacokinetic profile, after single 20mg and 100mg doses, in relation to that of other FDA-approved stimulant medications.

Dr. Bev Incledon, EVP, Research & Development for Ironshore Pharmaceuticals & Development, Inc. added, Head-to-head studies assessing safety and efficacy of Jornay PM and other stimulants have not been conducted and Jornay PM is not substitutable with other methylphenidate products on a milligram per milligram basis. In this analysis, a 100-mg dose of JORNAY PM produces a maximum serum methylphenidate concentration that is either equal to or lower than that of 54mg and 60mg of other methylphenidate products. While this may surprise some healthcare professionals, this result is directly attributable to the site of absorption for Jornay PM, the colon, which has vastly different absorption qualities relative to the stomach and upper intestine. Although the Cmax was proportionately lower than expected, the absorption window was significantly longer. Together, this resulted in 74% bioavailability relative to a Ritalin IR comparator.

JORNAY PM is the first and only stimulant medication that is dosed in the evening and has demonstrated improved ADHD symptom control in the early morning, throughout the day and during the evening time period in two pivotal Phase 3 trials.

WARNING: ABUSE AND DEPENDENCE

See full prescribing information for complete boxed warning.

See additional important safety information below.

JORNAY PM is the first product to leverage the novel DELEXIS delayed-release and extended-release drug delivery technology that contains two functional film coatings. The first layer delays the initial release of drug for up to 10 hours while the second layer helps to control the rate of release of the active pharmaceutical ingredient from the time the patient awakens the next morning, throughout the day and into the evening.

About ADHDADHD is among the most common childhood psychiatric conditions with behavioral symptoms fluctuating throughout the day. It is usually first diagnosed in childhood and often lasts into adulthood. Children with ADHD may have trouble paying attention, controlling impulsive behaviors, or be overly active. Many home-based difficulties for children and adolescents with ADHD occur during the early morning routine (i.e., before the school day begins).

About JORNAY PMDeveloped by Ironshore Pharmaceuticals & Development, Inc., JORNAY PM is a central nervous system (CNS) stimulant prescription medicine used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in people six years of age and older. JORNAY PM may help increase attention and decrease impulsiveness and hyperactivity in people six years of age and older with ADHD. It is not known if JORNAY PM is safe and effective in children under six years of age.

JORNAY PM is dosed once daily in the evening and should be initiated at 8:00 p.m. Timing of administration of JORNAY PM may be adjusted between 6:30 p.m. and 9:30 p.m. to optimize the tolerability and the efficacy the next morning and throughout the day. The recommended starting dose for patients 6 years and older is 20 mg once daily in the evening. Dosage may be titrated weekly in increments of 20 mg per day up to maximum daily dose of 100 mg. The mean optimized dose required to improve symptoms from the time the patient wakes up, throughout the day and into the evening in children 6-12 years old was 67 mg in Study 1 and 68.1 mg in Study 2. The relative bioavailability of JORNAY PM (given once a day) compared to the same daily dose of a methylphenidate immediate-release oral product (given 3 times a day) in adults is approximately 74%. JORNAY PM is primarily absorbed in the colon which may contribute to the reduced bioavailability of the drug. JORNAY PM is not interchangeable on a milligram-per-milligram basis with other methylphenidate formulations.

Please see additional dosing information in the full prescribing information for JORNAY PM at http://ironshorepharma.com/labeling.pdf.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE AND DEPENDENCECNS stimulants, including JORNAY PM, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

PREGNANCY AND LACTATION

Please visit http://ironshorepharma.com/labeling.pdf for additional important safety information and the Full Prescribing Information, including Boxed Warning, for JORNAY PM.

About Ironshore Pharmaceuticals Inc.Ironshore Pharmaceuticals Inc. commercializes innovative, patient-centric treatment options to improve the lives of patients and caregivers. Based in North Carolina, Ironshore Pharmaceuticals Inc. is responsible for the sales, marketing and distribution of pharmaceutical products within the US. Ironshore Pharmaceuticals Inc. is a wholly owned subsidiary of Highland Therapeutics Inc. based in Toronto, Canada.

About Ironshore Pharmaceuticals & Development, Inc.Ironshore Pharmaceuticals & Development, Inc., based in Grand Cayman, develops novel therapeutics by leveraging its proprietary drug-delivery technology, DELEXIS. Ironshore Pharmaceuticals & Development, Inc. is a wholly owned subsidiary of Highland Therapeutics Inc. based in Toronto, Canada.

Forward-Looking StatementsThis press release contains forward-looking information, which reflects Ironshores current expectations regarding future events. Forward-looking information is based on a number of assumptions and is subject to a number of risks and uncertainties, many of which are beyond Ironshores control that could cause actual results and events to differ materially from those that are disclosed in or implied by such forward-looking information. These forward-looking statements are made as of the date of this press release and, except as expressly required by applicable law, Ironshore assumes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

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Ironshore to Present Posters at the 2020 Neuroscience Education Institute Virtual Scientific Poster Session - Business Wire