Monthly Archives: January 2020

Biochemistry

Protein Structure Associated with Inherited Retinal Diseases is Solved – Technology Networks

Researchers at the University of New Hampshire have reported the first structural model for a key enzyme, and its activating protein, that can play a role in some genetically inherited eye diseases like retinitis pigmentosa and night blindness.

There has been substantial research on the biochemical pathway involving this enzyme, known as PDE6, but defining atomic-level models is important for locating PDE6 mutations in order to understand why they cause disease and how we can develop new therapeutic interventions to manage retinal diseases, said Rick Cote, director of Center of Integrated Biomedical and Bioengineering Research and principal investigator on the study.

Vision starts in the photoreceptor cells of the retina which contains rods, responsible for low light vision, and cones, which are active in brighter light and capable of color vision. When light is absorbed by the rods and cones, it triggers a pathway which activates the enzyme phosphodiesterase 6, or PDE6. This generates a nerve impulse to the brain that ultimately results in visual perception. Some genetically inherited eye diseases are caused by mutations to PDE6, or its activating protein, transducin, that can lead to disruptions of normal vision or even total blindness.

In the study, researchers reported how they were able to use chemical cross-linking combined with mass spectrometric analysis to resolve the structure of PDE6 in its nonactivated and transducin-activated states. This approach permitted visualization of flexible regions of individual PDE6 catalytic and inhibitory subunits that were poorly resolved in previous work as well as the overall molecular architecture of the activated protein complex.

Determining the structure of these visual signaling proteins has always been a challenge because of their complexity, said Michael Irwin, doctoral student in biochemistry and lead author. Having detailed structural information about how PDE6 is activated by transducin will help us understand the molecular causes of visual disorders and blinding diseases resulting from mutations in these proteins.

Current medical treatment for such genetically inherited retinal diseases may include gene therapy or drugs meant to inhibit the disease process. However, they are not always successful in restoring the balance of PDE6 and preventing blindness. Scientists believe that knowing the molecular structures of these visual signaling proteins and how they interact with each other can offer clues for the development of new drugs to both restore vision and prevent blindness.

Reference

Irwin et al. (2019) The molecular architecture of photoreceptor phosphodiesterase 6 (PDE6) with activated G protein elucidates the mechanism of visual excitation. Journal of Biological Chemistry. DOI: https://doi.org/10.1074/jbc.RA119.011002

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Protein Structure Associated with Inherited Retinal Diseases is Solved - Technology Networks

Biochemistry

Impeachment: What you need to know, students react – The State News

On Dec. 18, 2019, the House of Representatives voted to approve articles of impeachment against President Donald Trump.

Trump was impeached on the grounds of abuse of power and obstruction of Congress.

The abuse of power article stems from a whistleblower complaint that accused Trump of asking Ukrainian President Volodymyr Zelensky to investigate 2020 Democratic presidential candidate Joe Bidens son in exchange for previously authorized military aid Trump had cut. The whistleblowers memo and a summarized transcript of the phone call between Trump and Zelensky have since been released.

The obstruction of Congress article was brought due to Trumps refusal to comply with congressional subpoenas, according to NBC.

Trump is the third president in U.S. history to be impeached, joining Andrew Johnson and Bill Clinton.

Impeachment was a controversial decision, with the vote decided almost entirely along party lines, with just two Democrats, Collin Peterson and Jeff Van Drew, voting against both articles of impeachment and another, Jared Golden, voting against obstruction of Congress, according to The New York Times. No Republicans voted in favor of impeachment.

Up next is a vote in the Senate to decide whether or not to remove Trump from office. Senate majority leader Mitch McConnell has said there will be a trial before the vote.

Speaker of the House Nancy Pelosi is withholding the articles until Democrats can reach an agreement with McConnell on how a Senate trial should proceed. Democrats want four Trump officials to testify, while McConnell has said hell only allow the evidence from the House trial to be used, according to CNN.

The Senate will vote on trial parameters. If the Democrat and Independent vote is united, theyll need four Republicans to join them, according to the Senates website.

For Trump to be removed, two-thirds of the senate will have to vote in favor of removal. The Senate has a Republican majority. Given the close party lines the House vote followed, removal is unlikely unless new evidence comes out.

Ahead of the Senate vote, The State News gathered student opinions on Trumps impeachment.

Psychology and neuroscience sophomore Kate Frieden said she believes Trumps impeachment is a defining moment in his presidency.

Its such a monumental moment in history, Frieden said. When Im an adult and I have my own kids, my kids are going to be like, What was it like living in Trumps America? ... I have very, very little hope that anything will be done, but I hope that a fair trial is given.

Pre-veterinary sophomore Jacobo Bacariza said Trumps willingness to exercise his power as president is something Congress isnt used to.

Hes definitely using it unlike our previous presidents, Bacariza said. America spoke a few years back, and we wanted Trump as our president. ... (Trumps) someone that you cant really beat right now, and you just have to wait until he serves his two terms.

Bacariza said Democrats impeached Trump because they cant win in the 2020 election.

Lindsay Guare, a junior triple majoring in computer science, biochemistry and genetics, said shes glad hes being held accountable.

(Impeachment is necessary) in order to show that we uphold people to a certain standard. Guare said.

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Impeachment: What you need to know, students react - The State News

Biochemistry

Interview: Dr Andrew Morgan on the microbiome – fundamental to both health and disease – All about feed

Some 30 years ago Dr Andrew Morgan got involved in studying the microbiome and he has played an important role in the development of DuPonts microbiome platform. Even as a schoolboy he was inspired by the emerging field of modern biology when he read the book What is life? by Erwin Schrdinger.

When I first became involved in working with enzymes for animal nutrition back in the late 1980s, there was hardly any understanding of the interaction between nutrition, the microbiome, and the gut and immune function of neither animals nor humans. In fact, the term 'microbiome' wasnt used at the time. The discipline of nutribiosis, as we call it now, was still in its infancy. Since then, we have come a long way and we have been amazed by the interactions between the microbes that live in the gut and the host physiology that maintains a healthy or homeostatic state, says Dr Andrew Morgan.

Dr Andrew Morgan is a DuPont Fellow at DuPont Nutrition & Biosciences and was Chief Scientist for the DuPont Nutrition & Health and legacy Danisco businesses for over a decade. He is involved in both the human and animal nutrition sides of the business. Dr Morgan has an impressive career, starting at BP Research, BP Nutrition (= Nutreco today), Finnfeeds and then moving on to Danisco and now DuPont. Dr Morgan has a First Class Honours Degree in Biochemistry and is a Doctor of Philosophy in Microbial Biochemistry & Genetics (University of Sussex).

He gave a presentation during the recent first conference of World Rising Nutritionists 2019 in Lisbon, providing deep knowledge into the science around the 3 pillars of nutribiosis, namely:

The gut is the main reservoir of microbes in the body, with about 30% of metabolites in the bloodstream originating from the gut microbes and so it should not be too surprising that gut microbes have a strong relationship with health. Dr Morgan continues: Microbes make us what we are: ultimately all living organisms evolved from microbes and have learned to co-exist with them. In humans tens of trillions of microbes populate our bodies, both inside and out. The composition and behaviour of bacteria in the gut is critically important for human and animal health.

At the start of my involvement in the then nascent field of the way enzymes affect animal nutrition in 1989, I started by reading the scientific literature available to get a better understanding of animal nutrition and the potential role that enzymes could play in animal nutrition and health. At the time, there were 3 theories of how enzymes might affect animal nutrition. One was based on a correlation between viscosity in the gut and performance; another suggested that enzymes degrade the cell walls of feed materials and release additional nutrients and the third my own theory was that enzymes had an influence on the composition of the gut microflora. Thats when we started to work on testing these hypotheses and today we know that they were all correct.

Dr Andrew Morgan, a DuPont Fellow at DuPont Nutrition & Biosciences. Some 30 years ago he got involved in studying the microbiome and he has played an important role in the development of DuPonts microbiome platform. Photo: Dupont

From that time onwards knowledge and developments really shifted into top gear. In the early 1990s we focused on enzymes that degrade NSP for animal nutrition and over time we built the tools needed to study the different mechanisms of action including DNA-based methods for monitoring shifts in the gut microflora (microbiota) composition. By the mid-1990s we were able to clearly demonstrate that NSP-hydrolysing enzymes depolymerise high molecular weight arabinoxylan and betaglucan substrates, thus generating small polymers and oligosaccharides; the result was a favourable shift in the microflora/microbiota composition. By the early 2000s we had built a health and nutrition toolbox (Enteromix), including GI tract simulation and cell line models that supported our research and development for both human and animal applications. We have added substantially to these in recent years, including models from metagenomics, metabolomics and bioinformatics. That knowledge platform really showed its value when we started to work on probiotics in the mid 2000s. With our health & nutrition platform, as well as leading manufacturing and formulation capabilities, we were able to develop state-of-the-art probiotic science and technology which supports the development of a substantial portfolio of products and that is what brought us to where we are today. DuPont has a very strong position in enzymes, fibres, prebiotics and probiotics.

Giving good bacteria the upper hand over the bad is the reason why we launched our microbiome venture in 2017." - Dr Morgan.

Dr Morgan continues: And were not done; were focusing on the future. Our platform is now designed to produce next-generation probiotics and other kinds of microbiome modulator. We have established a Microbiome Venture to develop new human microbiome solutions, but that knowledge is also readily transferable to the animal side of the business. A lot of research is being done on next-generation probiotics and on molecules that modulate the microbiome. We are especially building on our strengths in Lactobacillus and Bifidobacterium probiotics, where today we have an industry leading portfolio of scientifically documented strains. In humans, we are tailoring solutions to certain health conditions and age criteria, including solutions for early life when the microbiome is just getting established in the infant. In fact, we already have probiotic offerings for early life that build on over a decade of research and recently we launched a human milk oligosaccharide (HMO) product; HMOs present in breast milk play an important role in shaping the infant microbiome.

Giving good bacteria the upper hand over the bad is the reason why we launched our microbiome venture in 2017 to shape a whole new range of solutions. We know that the diet we eat and our lifestyle is essential to health, but when things go wrong with the microbiome so-called dysbiosis we want to find solutions that help shift the balance back towards homeostasis. This is a long-term endeavour, but we are one of a very few companies with the full range of capabilities needed to succeed. The expectation that we will be able to prevent disease and support health in both humans and animals by influencing the microbiome in a far more targeted way is both promising and exciting.

As a bonus, it will help to solve the rise of antimicrobial resistance as well, because, with greater understanding of the microbiome, alternative more targeted solutions will emerge and the need to use antibiotics will decline. If one looks at it in a holistic way, one can conclude that microbiome science holds the promise of fundamentally new solutions designed to support health and prevent disease that will beneficially impact both animal and human health and nutrition for years to come.

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Biochemistry

With already 2900 people dead from the flu, we need a better vaccine – MSUToday

The CDC estimates that at least 6.4 million people have caught the flu, resulting in 55,000 hospitalizations and 2,900 deaths already this season. Though the flu vaccine can reduce the chances of infection at best, it's only 40% to 60% effective, which is why we need a better vaccine.

Michigan State University researchers are working on this global health problem and have data that show how cellular RNA levels change following infection or vaccination. RNA stands for ribonucleic acid, which is a long, single-stranded chain of cells that processes protein and carries genetic information of many viruses, including influenza. This discovery could help make future flu vaccines work better or even aid in the design of a universal vaccine.

Understanding these differences could help us identify new targets for building better vaccines as well as help us figure out better ways to treat the disease, said George Mias, assistant professor of biochemistry and molecular biology and chief of the Systems Biology Division at the Institute for Quantitative Health Science and Engineering at MSU.

Mias and his co-authors reanalyzed data from 18 previously published studies where scientists had taken blood samples from flu patients and vaccine recipients and studied those samples for gene expression. Gene expression can be measured by looking for the levels of RNA in cells. When a gene is expressed in a cell it means the DNA has been used to produce RNA for this gene. The gene expression in cells can change in response to stimuli, including disease.

The motivation for combining the different datasets is that typically the smaller datasets will be underpowered statistically to detect significant differences, Mias said. By combining multiple studies, were increasing our power and ability to detect gene expression differences between the variables that were interested in.

The researchers found 978 genes with changed expression for flu infection and flu vaccination. Roughly a third of those genes, 334, overlapped while about two-thirds, 644, were unique to either flu infection or flu vaccination.

The distinct genes were involved in different processes in the body. Several genes that were expressed differently in flu infection, for example, are involved in the bodys defensive mechanisms. On the flip side, genes exclusively expressed in vaccination were involved in antigen processing, which stimulates the bodys immune response.

The investigators also found 907 genes related to age and 48 related to sex that affect disease/vaccine gene expression changes. Understanding these differences could help scientists in their quest to develop a universal vaccine.

We especially need to find something that works across ages better, Mias said.

At present, the CDC recommends a high-dose vaccine for people over the age of 65 because their immune systems need more stimulation in order to create the necessary antibodies to protect them from flu viruses.

Mias and his co-authors hope their results will serve as a starting point for future studies by providing gene targets that could be further explored through animal models or human research using newer RNA-sequencing technology.

We found things that are specific to the flu or to the vaccine, so we need to ask, What are the effects of those genes? Mias said. For instance, if the vaccine is activating additional genes and pathways that the disease itself is not activating, we should be asking, Are they relevant and could they be linked to any side effects? Those are questions that deserve to be answered.

The paper was published in the journal Frontiers in Immunology. Co-authors are Gustavo de los Campos, professor of epidemiology and biostatistics at MSU, and Lavida Rogers, former MSU graduate student.

(Note for media: Please include a link to the original paper in online coverage: https://www.frontiersin.org/articles/10.3389/fimmu.2019.02616/full)

Written by Nancy Averett

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With already 2900 people dead from the flu, we need a better vaccine - MSUToday

Biochemistry

NMSU students win awards for research at National Diversity in STEM Conference – New Mexico State University NewsCenter

Date: 01/06/2020Writer: Amanda Adame, 575-646-7953, aadame4@nmsu.edu Facebook Twitter LinkedIn Google+ Pinterest

Four New Mexico State University students in the College of Arts and Sciences were honored at the Society for the Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS) awards at The 2019 National Diversity in STEM Conference in Honolulu in November. The awards recognize the next generation of underrepresented researchers and Science, Technology, Engineering and Math (STEM) leaders while also giving visibility to their research and schools.

The student researchers represented areas of study from sociology to biology and chemistry and biochemistry as well as conservation ecology.

We are proud to see our students presenting their research at the largest multidisciplinary and multicultural STEM event in the country, said Enrico Pontelli, dean of the College of Arts and Sciences. SACNAS has a solid history of serving the purpose of engaging and encouraging underrepresented students in the STEM fields.

Daniel Aguirre, who is conducting research in NMSUs Department of Chemistry and Biochemistry, presented a poster in the chemistry category titled, In-Silico Dual Specificity Protein Phosphatase Differentiation Via Molecular Dynamic Simulations. His presentation included research about Dual Specificity Protein Phosphatases and if they play a role in the development of cancer, obesity and autoimmunity.

Isabella Terrazas, who is studying microbiology, presented about her research Cortical Granule Motility in Response to Hormone Stimulation during Sea Star Meiosis. She is studying how fertilization and proper development is required for sperm to bind. This activation of Rho, G proteins and actin, cell division plays a role in promoting translocation of cortical granules (CGs) to the cell surface.

Valerie Brewer, who is studying conservation ecology, presented her research Effects of Urbanization on Extra-Pair Paternity in the Song Sparrow. She explored how urbanization can affect the behavior of free-living animals. Preliminary results suggested that there are higher rates of extrapair offspring and nests in rural areas compared to urban.

Riva Silver, an unclassified student, presented her sociological research Exploring the Pathway Model Connecting Water and Education in West Texas Colonias Using Quasi-Youth Participatory Action Research; A Mixed Methods Approach. Through youth participatory action research, the study explored the connection between water infrastructure and high school graduation rates in unincorporated communities in rural areas that dont have access to city water and sewer services. The results suggest improved water infrastructure increases quality of life and education, which promotes higher high school graduation rates.

The students were among 82 graduate and undergraduate underrepresented groups in sciences. These awards also help encourage students to continue pursing STEM fields. The organization serves a community of over 20,000 supporters, more than 6,000 members and more than 115 student and professional chapters throughout the United States and Puerto Rico.

The SACNAS National Diversity in STEM Conference partners with institutions by providing a venue where students and professionals are able to enhance their science communication skills. As a multidisciplinary scientific society, the opportunity to present research to a general scientific audience fosters skills needed to not only build public support for science but also ensure that science is accessible to everyone. Through the awards, we recognize and celebrate presenters that make STEM inclusive, said Sonia Zrate, SACNAS President.

To learn more about SACNAS and the presentations by NMSU students visit sacnas.org.

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NMSU students win awards for research at National Diversity in STEM Conference - New Mexico State University NewsCenter

Biochemistry

Researchers study the effects of antidepressants to identify the least harmful drugs – News-Medical.net

About one in ten women in Qubec will suffer from depression during pregnancy. Without treatment, the illness carries risks for both mother and child. Yet antidepressants are not without consequences for fetal development. The team of professor Cathy Vaillancourt at the Institut National de la Recherche Scientifique (INRS) is studying the effects of these drugs in order to identify the least harmful ones.

Professor Vaillancourt, in collaboration with the teams of Professors J. Thomas Sanderson and Nicolas Doucet of the INRS, has just modeled for the first time the interaction of commonly used antidepressants with estrogen, and more specifically with the enzyme that synthesizes the estrogen: aromatase. It is an important contribution, since estrogen production is essential to the development of the fetus and to the mother's physiological adaptation during pregnancy. The results of their study were recently published in The Journal of Steroid Biochemistry and Molecular Biology.

Prescribing antidepressants for pregnant women is controversial. Studies show that, when administered to mothers during pregnancy, some of these treatments are associated with a risk of heart and lung malformations in newborns. Others are thought to result in impaired cognitive development, including autism, in children.

The harmful effects of antidepressants are thought to be due to their interaction with certain key hormones. Most antidepressants prescribed to pregnant women target serotonin, a hormone produced both in the brain and, as shown by Professor Vaillancourt's team in 2017, in the placenta. This is the family of antidepressants called selective serotonin reuptake inhibitors (SSRIs) such as Zoloft, Celexa or Prozac. However, estrogen would also be targeted by these treatments.

We wanted to see how the antidepressants that have been developed to block the serotonin transporter also affect aromatase. Using molecular models, we found that all the antidepressants we analyzed seemed to be able to bind directly to the enzyme and regulate its activity. This remains to be confirmed and the precise mechanism needs to be further investigated."

Cathy Vaillancourt, lead author of the study

Her doctoral student tested the effect of different types of antidepressants on placenta samples collected after delivery. "The antidepressants we chose to test are those most commonly prescribed in pregnant women, namely sertraline (Zoloft), venlafaxine (Effexor), fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa)," says Andre-Anne Hudon Thibeault "By comparing different doses and molecules, we were able to uncover some of their specificities."

By observing the effects of antidepressants on the placenta's hormonal system, the team can determine in advance if there will be a risk for the fetus. "Fetal development is strongly linked to the placenta. Every healthy fetus has a healthy placenta," maintains Vaillancourt.

Not all types of antidepressants have these harmful effects. Not all pharmacological molecules have the same hormonal affinity. "Depending on its form, a molecule may not interact the same way with estrogen and may therefore be less harmful to the developing fetus," asserts Professor Vaillancourt, who specializes in the involvement of maternal exposure to environmental and drugs factors in the endocrinology of the human placenta.

It's more a matter of the pharmacological molecule being administered and the dosage. "By testing several types of antidepressants at varying doses, our work will contribute to better choices regarding the type of antidepressant and the dose prescribed for pregnant women, while minimizing the side effects on the course of pregnancy and on fetal development," says Andre-Anne Hudon Thibeault, primary author and recent PhD graduate of INRS.

Discontinuing medication isn't always advisable. Depression can have serious consequences if left untreated. "Depression is one of the leading risk factors for suicide in pregnant women," says Vaillancourt. "Some studies suggest that depression can also compromise fetal development, due in part to poor lifestyle habits."

At the same time, Professor Vaillancourt is collaborating with a team of researchers in Vancouver who are studying a cohort of pregnant women and following their children over the long term. "This will give us a nice map of the various effects in women and the consequences for children's heart and brain development," says Vaillancourt. "We're still in the early stages of the project, but I'm confident that some antidepressants are safer and others can be developed for use during pregnancy."

Source:

Journal reference:

Thibeault, A-A. H., et al. (2019) Serotonin and serotonin reuptake inhibitors alter placental aromatase. The Journal of Steroid Biochemistry and Molecular Biology. doi.org/10.1016/j.jsbmb.2019.105470.

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Researchers study the effects of antidepressants to identify the least harmful drugs - News-Medical.net

Biochemistry

Agenus Announces the Appointment of Dr. Jennifer Buell to the position of President and COO – Yahoo Finance

LEXINGTON, Mass., Jan. 9, 2020 /PRNewswire/ -- Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents that activate immune response to cancers, is pleased to announce the appointment of Dr. Jennifer Buell to President and COO.

Dr. Jennifer Buell, President & COO of Agenus

"Jen's tenure with Agenus, her exceptional leadership and cultural attributes, and her deep understanding of our science and operations makes her the top candidate for this newly created position," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. He added, "I am very excited to partner with Jen as we set to realize Agenus' vision of defeating cancer in the coming years."

After her tenure at Harvard Clinical Research Institute, Dr. Buell rejoined Agenus in 2013 as the Head of Global R&D operations. She was subsequently appointed as Chief Communications and External Affairs Officer, and then, to the position of Chief Operating Officer.

Dr. Buell brings over 20 years of biopharmaceutical industry experience and knowledge. Her efforts in the rapid advancement of discovery candidates through development has resulted in Agenus' record of advancing 13 I-O candidates to the clinic in the past four years. Her experience also includes extensive communication with internal and external constituencies, regulators, investors, and collaborators. Dr. Buell's previous operational and research experience include her tenures at Bristol-Myers Squibb and Harvard Clinical Research Institute. Dr. Buell obtained her PhD in Cellular, Biochemical, and Molecular Biochemistry with an MS in Biostatistics from Tufts University in Boston.

About AgenusAgenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body's immune system to fight cancer. The Company's vision is to expand the patient populations benefiting from cancer immunotherapy by pursuing combination approaches that leverage a broad repertoire of antibody therapeutics, proprietary cancer vaccine platforms, and adoptive cell therapies (through its AgenTus Therapeutics subsidiary). The Company is equipped with a suite of antibody discovery platforms and a state-of-the-art GMP manufacturing facility with the capacity to support early phase clinical programs. Agenus is headquartered in Lexington, MA. For more information, please visit http://www.agenusbio.com and our twitter handle @agenus_bio. Information that may be important to investors will be routinely posted on our website and twitter.

Forward-Looking StatementsThis press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding Agenus' clinical development plans and timelines, the vision of defeating cancer in the coming years, and the expected contributions of Dr. Buell. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.

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Agenus Announces the Appointment of Dr. Jennifer Buell to the position of President and COO - Yahoo Finance

Biochemistry

Persistent TB infection of macrophages puts the brakes on immune engines, study shows – News-Medical.net

Scientists from Trinity College Dublin have discovered both how TB puts the brakes on our immune engines and how we can kick-start those engines back into gear - providing hope that improved treatment options could soon be on the horizon.

Although ancient, TB is still the world's deadliest infectious disease. While it is rampant in Africa, the growing problem of antibiotic resistance is posing a significant threat worldwide.

Part of TB's success as a pathogen is because of its ability to infect the cells of our immune system, which are normally tasked with responding to the infection. It infects our lung macrophage cells and then manipulates them to its benefit - creating a safe home for it to hide out unperturbed, sometimes for years.

As part of an SFI-funded Starting Investigator Research Grant, Frederick Sheedy, Ussher Assistant Professor in the School of Biochemistry and Immunology at Trinity, mentored by St James' Hospital TB specialist, Professor Joseph Keane, has been examining how these lung macrophage immune cells fuel the fight against infection.

The work has been at the forefront of showing how the simple sugar glucose is used to promote the macrophages anti-bacterial activities.

In surprising results, published this week in leading international journal Cell Reports, Dr Emer Hackett (a PhD candidate in Professor Sheedy's group) found that persistent infection of these macrophages with TB puts the brakes on the glucose-fuelled engine. This essentially shuts down our natural response to infection, which allows the bacteria to hide out unperturbed.

Specifically, Dr Hackett found a small RNA molecule (which comprises tiny pieces of genetic information) which the bacteria promotes and which targets key enzymes that act as pumps in our immune engines to commit glucose to promote the anti-bacterial response.

When the bacteria promotes this small RNA molecule, which is termed microRNA-21, these enzyme pumps are removed from the engine and glucose is not used in the same way. This then allows the bacteria to escape and thrive.

Although this newly identified pathway is corrupted by the bacteria, the study also yielded some hope for the future.

Professor Sheedy explained:

We found that when TB-infected cells are treated with a key 'Interferon gamma protein signal' which is normally produced following vaccination, they will remove this microRNA to effectively relieve the brake and restore our normal immune response.

What is particularly promising from a societal impact perspective is that as well as increasing our knowledge of how TB corrupts our normal immune response to infection, our identification of the microRNA-21 means that scientists should be able to develop improved immunotherapies or vaccine strategies to help in the fight against TB infection."

Source:

Journal reference:

Hackett, E.E., et al. (2020) Mycobacterium tuberculosis Limits Host Glycolysis and IL-1 by Restriction of PFK-M via MicroRNA-21. Cell Reports. doi.org/10.1016/j.celrep.2019.12.015.

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Persistent TB infection of macrophages puts the brakes on immune engines, study shows - News-Medical.net

Embryology

Reproductive Biology Associates Announces Opening of New Location in Cartersville, Georgia – PRNewswire

This 2,000 square-foot, state-of-the-art facility offers a full range of comprehensive diagnostic and treatment services for women and men, including consultations, ultrasounds, bloodwork, as well as semen analysis, saline infusion sonohysterograms and OB checks. This expansion marks the seventh location for RBA, which also has offices in metro Atlanta, Cumming, Fayetteville, Lawrenceville, Marietta and Piedmont.

The new location will be spearheaded by RBA's renowned physicians, who boast more than 200 years of cumulative experience in the diagnosis and treatment of infertility and have achieved in excess of 30,000 babies.Joining the award-winning team of reproductive endocrinologists is Dr. Monica Best, who has spent her career caring for patients in the Atlanta market.

"RBA has a solid reputation as being the area's leader in reproductive healthcare, giving each patient an individualized treatment plan that offers the latest in reproductive technologies," says Andrew A. Toledo, M.D., CEO of RBA. "Our expansion into the Cartersville area allows us to reach more patients who are looking to build their families through compassionate, best-in-class fertility service and care."

In addition to its geographical expansion, RBA also recently launched its R-Baby-Assuranceprogram, a financial guarantee program that gives eligible patients who are seeking in vitro fertilization (IVF) services the opportunity to pay a flat fee with the guarantee that they will take a baby home, or they are provided a full refund.

Since its inception in 1983, RBA has remained steadfast in its commitment to the development of revolutionary technologies and techniques to enhance pregnancy outcomes. RBA's specialized treatment plans combine compassionate patient care with state-of-the-art technology, much of which its physicians pioneered.

The new RBA facility is located at 962 Joe Frank Harris Parkway, Suite 206 in Cartersville, Georgia. A grand opening celebration is scheduled for February 2020.

For more information about RBA, visit https://rbaivf.com/.

About Reproductive Biology AssociatesFounded in 1983 and based in Atlanta, RBA is the oldest continuously operating full-service private fertility treatment center in the United States and is led by reproductive endocrinologistsDaniel B. Shapiro, MD; Andrew A. Toledo, MD;andZsolt Peter Nagy, PhD, who specializes in embryology. Since its establishment, the center's mission has focused on the development, improvement, and application of clinical and applied sciences to improve fertility care, with its RBA team being responsible for several notable firsts in reproductive medicine.

In 2016, RBA joined forces with Lee Equity Partners, serial entrepreneur Martn Varsavsky, and MyEggBank North America to establish Prelude, a comprehensive fertility company that is now the fastest growing network of fertility centers in the United States (Prelude Network). Preludehelps patients achieve their best possible pregnancy outcomes through access to top-tier centers, including RBA, and more than 30 internationally recognized reproductive endocrinologists, placing emphasis on the best clinical protocols and scientific advancements and sharing these best practices across its network.

About InceptionInception was founded in 2015 with an ambitious goal to create a family of organizations intent on improving the way patients experience their fertility journey. The company's mission is to shift the paradigm of the fertility market by raising the standard of care, streamlining fragmented components into an integrated system, and enhancing the overall patient experience. Inception's network of full service fertility centers, The Prelude Network, is now the largest of its kind including some of the country's top-tier fertility practices in 17 markets across the US.www.inceptionllc.com / http://www.aspirefertility.com

MEDIA CONTACT:Amanda SchlusselKrupp Kommunicationsaschlussel@kruppnyc.com

SOURCE The Prelude Network (Prelude)

https://www.inceptionllc.com/

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Reproductive Biology Associates Announces Opening of New Location in Cartersville, Georgia - PRNewswire

Embryology

Cheryl Tweedy is considering sperm donation to have more children but how does it work? – Yahoo News

Cheryl Tweedy has revealed she could look to sperm donation to grow her family [Photo: Getty]

Cheryl Tweedy has revealedplans to have more children by sperm donor.

The pop singer, 36, explained that she wants to provide more than one sibling for two-year-old son Bear, who she shares with ex-boyfriend Liam Payne, 26.

Speaking to The Times Magazine, the star, who is currently single, said that the thought of potential solo fertility treatment makes me very happy.

She continued: If time was on my side and I was in my twenties, yeah, I would wait and consider more options, or wait for somebody I felt was right, but

You could meet somebody and for that year it feels incredible, but there is never a guarantee because there are so many variables that can happen.

Life is a funny old game.

Cheryl, went on to confirm that she is considering having a second and possibly third child with the help of a sperm donor from out of town.

She explained: You can get it from abroad.

Do you imagine some guy from Newcastle saying, Thats my child!?

Theres a lot to choose from and a lot to think about, she added.

READ MORE: What is spurgling and why do experts have concerns about the sperm stealing practice?

Cheryl Tweedy certainly isnt alone in considering fertility treatment without a father.

Latest figures from the Human Fertilisation and Embryology Authority (HFEA) showthe number of women attempting to start a family without a father increased by more than a third (35%) in two years; 1,272 women registered to have fertility treatment without a partner in 2016 up from 942 in 2014.

Likewise, there has been a rise in the use of sperm donation to start or grow a family. In 2016, 4,306 treatment cycles involved a patient using their own eggs and donor sperm, up 15% from 3,749 in 2015.

So why is sperm donation becoming more popular?

Some experts believe women are feeling more empowered to make that choice, while Dr Geetha Venkat director ofHarley Street Fertility Clinic believes the fact that many women are waiting until they are older to have children, and the changing circumstances surrounding starting a family are both contributing to the process becoming a more popular option.

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Of course sperm donation is also considered by some couples where the male partner has sperm abnormalities, poor sperm production or no sperm at all.

Some men carry inherited genetic diseases and are thus seeking donated sperm so as not to transmit the disease to their children, Dr Venkat continues.

Sperm donors can change lives and make families a reality.

READ MORE: Single mum, 39, who used sperm donor, explains choice to her baby boy in moving video

According to Dr Venkat there is a shortage of sperm donors in the UK and many people have to wait to benefit from donated sperm.

Some couples are fortunate enough to have friends and family willing to donate sperm as a known donor, she explains.

However, most are not so fortunate and thus they are likely to be in the queue waiting for around one year on average for sufficient donors to volunteer to donate their sperm.

Dr Venkat says that to meet the demand, over 500 sperm donors are needed every year from all nationalities, religions, ethnicities and cultures.

UK fertility clinics are able to import sperm from overseas, but only under certain conditions, she adds.

Dr Venkat says the person/people who receive a sperm donation will be the childs legal and social parent(s) the donor will not be named on the birth certificate.

The donor has no legal, financial or social obligations to any child created from the donation either now or in 18 years time, she explains.

Donors are asked to complete an HFEA form and this details personal details about them that could be handed to the donor-conceived person when they reach age 18 or older.

This information enables the childs parents to talk to them about their origins as they grow up and helps them build a mental picture of the donor, but they cannot meet them, she adds.

Its worth nothing that if youre having treatment at a licensed fertility clinic in the UK, the donor will have no legal rights or responsibilities to any children born with their sperm.

This is a personal choice, says Dr Venkat. But the most important thing is that donor procedures are carried out and that only healthy, safe sperm is used for your health and that of any child you have.

If you use a donor through a fertility clinic can find out:

height, weight, eye and hair colour

the year and country of birth

their ethnicity

whether they had any children at the time of donation, how many and gender

their marital status and medical history

they may choose to write a message at the time of their donation but you wont be able to find out any information that might reveal who the donor is.

READ MORE:Woman considers divorcing husband who fathered 47 children through sperm donations

When fertility treatment involves directly inserting sperm into a woman's womb, it is called Intrauterineinsemination (IUI).

The donor sperm is prepared in the laboratory to separate fast moving sperm from more sluggish or non-moving sperm, advises Dr Venkat.

The sperm is washed in the laboratory before insemination in order to concentrate the best sperm into a small amount of fluid.

Dr Venkat explains that using a catheter, your doctor will place the concentrated sperm directly into your uterus through your cervix, under ultrasound guidance.

The insemination procedure is relatively painless and is performed in a few minutes, although some women may experience some temporary, menstrual-like, cramping, she says.

IUI treatment can be performed in a natural cycle without fertility medicines or in a stimulated cycle with fertility drugs.

Though the treatment is available on the NHS, the waiting list can be very long in some areas and there are strict rules.

Dr Venkat advises speaking to your GP about your personal situation.

To give you an idea of costings, prices for IUI start at 1,100 per cycle with the HSFC.

Though you can go abroad for sperm donor treatment, like Cheryl Tweedy seems to hint shes considering, Dr Venkat says suggests remaining in the UK for the safest option.

The success rate with IUI treatment depends on your partner fertility status and your age.

Most couples who opt to undergo IUI have a 5 to 20%chance of becoming pregnant with each attempt, Dr Venkat says.

The chances are higher for stimulated IUI cycles in younger women using good quality sperm. However, it is not uncommon for multiple IUI cycles to be attemptedduethe poor success rate with a single cycle.

Link:
Cheryl Tweedy is considering sperm donation to have more children but how does it work? - Yahoo News