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Cell Biology

Anti-CRISPR proteins decrease off-target side effects of CRISPR-Cas9 – UC Berkeley

CRISPR-Cas9 gene editing is based on a tactic bacteria developed to protect themselves from viruses.

The Cas9 protein gloms onto a targeted piece of DNA (purple) before cutting it. Bacteria developed Cas9 as aweapon to kill viruses by snipping their DNA, but some viruses came up witha defense, called anti-CRISPR, that inactivates Cas9. The guide RNA (orange)directs Cas9 to its target. (Fuguo Jiang image)

Research now shows that the countermeasure viruses came up with inhibitory proteins referred to as anti-CRISPRs can be used to improve CRISPR-Cas9 as a gene-therapy tool, decreasing off-target gene editing that could cause unwanted side effects.

In a study reported online this week in the journal Science Advances, researchers from UC Berkeley and UC San Francisco show that recently discovered anti-CRISPR proteins decrease off-target effects by as much as a factor of four, acting like a kill switch to disable CRISPR-Cas9 after its done its job.

The study demonstrated that one particular anti-CRISPR protein called AcrIIA4 reduced by four-fold the off-target effects of a CRISPR-Cas9 molecule that uses a guide RNA to find, snip and replace the mutated hemoglobin gene responsible for sickle cell disease. It does this without significantly reducing the desired on-target gene-editing.

Unexpected mutations can arise as a result of off-target gene editing, but our paper like many others shows that off-target effects can be modulated and it is not as serious as people might think, said UC Berkeley postdoctoral fellow Jiyung Jenny Shin, from the lab of Jacob Corn at the Innovative Genomics Institute and one of three first authors of the paper.

In her experiments on human cells in culture, Shin found that delivering CRISPR-Cas9 and then, several hours later, the anti-CRISPR protein, was the most effective way to reduce off-target effects. The protein mimics DNA, glomming onto Cas9, the enzyme that actually cuts the double-stranded DNA, and preventing further cutting.

Even after six hours of effective CRISPR, inserting anti-CRISPR decreases off-target effects by more than two-fold compared to on-target effects, Shin said. Therapeutically, you could treat a patient with CRISPR first, and then treat with anti-CRISPR at a later time and decrease off-target effects.

The researcher who discovered AcrIIA4, Joseph Bondy-Denomy of UC San Francisco, foresees these anti-CRISPR proteins becoming a standard part of CRISPR gene therapy, given along with CRISPR-Cas9 to disable gene editing after a fixed period of time to prevent random off-target cutting.

This Cas9 inhibitor could be encoded on the same piece of DNA as Cas9, for example, precisely timed to turn Cas9 off after the gene editing is done, instead of letting Cas9 linger in the cell and risk off-target effects, said Bondy-Denomy, who is also a co-author of the paper.

Anti-CRISPR bindingThe team included researchers in the lab of Jennifer Doudna, one of the inventors of CRISPR-Cas9 gene editing, who determined how the anti-CRISPR protein binds to the CRISPR-Cas9 complex. Using cryo-electron microscopy, they found that anti-CRISPR essentially mimics DNA, tricking CRISPR-Cas9 into binding with it, and then never letting go.

The anti-CRISPR protein (red on right) mimics DNA, binding in the site where the cutting enzyme Cas9 typically grips the target DNA (left) before it cuts. But the anti-CRISPR protein doesnt let go, essentially killing Cas9s gene editing ability. (Fuguo Jiang image?

The CRISPR inhibitor targets a spot on the Cas9 protein that is so essential for Cas9s function that it cannot operate to cut DNA when its bound by the anti-CRISPR.

Last year, Bondy-Denomy reported finding four anti-CRISPR proteins used by attacking viruses to inactivate the version of the Cas9 protein found in the bacterium Listeria monocytogenes. Two of these also inhibited the Cas9 protein most commonly used by researchers, which is adapted from the bacterium Streptococcus pyogenes and is referred to as SpyCas9. Another team found three other anti-CRISPR proteins that work against a different but promising Cas9 protein adapted from the bacterium Neisseria meningitidis.

The current study looked at the effect of one of the proteins from Listeria, AcrIIA4, on SpyCas9 loaded with a guide RNA that homes in on complementary DNA to bind and cut.

Research at UC Berkeley and elsewhere suggests that CRISPR-Cas9 constantly feints with the cells DNA repair system: as the enzyme cuts at its target site, the cell repairs the DNA, and CRISPR-Cas9 cuts again, repeating this vicious cycle until a mutation arises in the DNA that prevents enzyme binding, at which point the CRISPR-Cas9 molecule moves on to find another binding site.

The current work from the Corn and Doudna labs now suggests that adding an anti-CRISPR after Cas9 has successfully edited a target gene would prevent unintended damage to other portions of a genome.

The ability to turn Cas9 gene editing off is just as important as the ability to turn it on, said Corn, scientific director for biomedicine of the IGI and a UC Berkeley assistant adjunct professor of molecular and cell biology. Imagine if you had an electric razor with no off-switch! For eventual therapeutic applications, it is critical to be able to precisely control when and where gene editing is active. The anti-CRISPR proteins offer opportunities to completely turn off Cas9 as well as fine-tune its activity.Jennys data suggests that there is an ideal time window for letting Cas9 do its job and then turning it off after that amount of time has passed, Bondy-Denomy said. We can actually use the anti-CRISPR proteins as tools to figure out what that time window is, that is, for any one cell type with any one guide RNA sequence, how long we want Cas9 to be active in the cell.

Shin and postdoctoral fellows Fuguo Jiang and Jun-Jie Liu are the three first authors of the paper, which was also co-authored by Benjamin Rauch of UCSF and postdoc Nicolas Bray, researcher Seung Hyun Baik and professor Eva Nogales, in addition to Corn and Doudna, of IGI and UC Berkeleys Department of Molecular and Cell Biology. Doudna and Nogales are Howard Hughes Medical Institute investigators.

The work was supported in part by HHMI, the Li Ka Shing Foundation, the Heritage Medical Research Institute and the National Institute on Aging.

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Anti-CRISPR proteins decrease off-target side effects of CRISPR-Cas9 - UC Berkeley

Cell Biology

Iowa State University plant scientists explore the balance between plant growth and drought response – KMAland

(Ames)--Dry weather forces plants to save energy by reducing their growth rate, but its not as if a plant can consult a rain gauge or weather report. So how do they know when to ease up on growth?

Yanhai Yin, a professor of genetics, development and cell biology and a Plant Sciences Institute Faculty Scholar, has spent years charting the genetic mechanisms that govern plant stress response and growth to answer that question.

Yin and his colleagues recently published an article in the peer-reviewed academic journal The Plant Cell focusing on WRKYs (pronounced workies), a family of proteins named for the several critical amino acids of which theyre composed. The new paper shows how WRKYs govern both stress response and growth in plants, making the proteins of particular interest to plant breeders and crop growers eager for varieties that will withstand dry conditions.

They are important regulators for the balance of drought response and growth, Yin said. They are very promising targets for plant breeding.

The paper describes how researchers in Yins lab managed to cross Arabidopsis plants in such a manner as to eliminate, or knock out, three different WRKYs genes. The resulting plants showed dramatically less growth than normal but were more drought tolerant. Arabidopsis is a small flowering plant often used as a model in experiments.

Jianai Chen and Trevor Nolan, graduate assistants in Yins lab, contributed to the paper, as well as Mingcai Zhang and Zhaohu Li of China Agricultural University, who are long-time collaborators with Yin.

Much of Yins research has centered on a plant protein known as BES1, an important switch in plant genomes regulated by a plant steroid called brassinosteroid that influences thousands of other genes. Yin said WRKYs and BES1 work together to promote plant growth under normal conditions.

Previous studies have shown that WRKYs also help to govern bacterial response in plants as well. Yin said his future studies will tease out how growth, drought tolerance and bacterial response interact with one another. Such efforts could lead to crops with genetics better suited to withstand many of the most pressing challenges producers face.

As the paper hints, harnessing the versatility of WRKYs to breed more resilient crops would make rain gauges look primitive by comparison.

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Iowa State University plant scientists explore the balance between plant growth and drought response - KMAland

Genetics

IT’S ALL ABOUT THE GENES: High school students participate in genetics camp – Stanly News & Press

For one week this summer, students from local high schools came together to study genetics in Project GENES, and even take a look at their own genes.

The project, supported by the Burroughs Wellcome Fund, involves students from Gray Stone Day School, Independence High School and Phillip O. Berry Academy of Technology in hands-on activities, labs and field trips involving DNA.

These students recently met for a residential camp at Pfeiffer University, where biology professors Dane Fisher and Laura Reichenberg guided them through genetics investigations.

Our goal is to do STEM [science, technology, engineering, and math] outreach to high school students, with a focus on students underrepresented in science, Reichenberg said. We collaborate with their high school science teachers and the teachers recruit students each year.

The students recruited take part in Project GENES for one year. Fisher and Reichenberg visit their high schools for DNA modules that increase in complexity, then the students come together for the summer camp, where they put in practice what they have learned.

Theyre basically isolating their own DNA. They get to amplify one of their own genes, Reichenberg said.

Students run tests on their PTC gene, a gene that determines a persons ability or inability to taste a specific flavor. Students then get the chance to try to taste the flavor, comparing those results with their lab work.

This year, students attending the camp took a field trip to the North Carolina Research Campus in Kannapolis, where they looked at samples under microscopes and tested them for antimicrobial properties.

According to Reichenberg, several students who attended the Project GENES camps in previous years have since graduated and gone on to STEM careers.

The former Oakboro Elementary is scheduled to open in August as Oakboro Choice STEMSchool for kindergarten through eighth grade.

Marina Shankle is a freelance contributor for The Stanly News &Press.

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IT'S ALL ABOUT THE GENES: High school students participate in genetics camp - Stanly News & Press

Genetics

Kailos Genetics Receives Investment From In-Q-Tel – GenomeWeb

NEW YORK (GenomeWeb) Kailos Genetics said today that it has received a strategic investment from In-Q-Tel, a nonprofit that invests in technologies to support the mission of the US intelligence community.

Terms and financial details of the deal were not disclosed.

Kailos said it plans to use the investment in a partnership with In-Q-Tell to develop its next-generation sequencing laboratory and software for the benefit of the intelligence community.

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Kailos Genetics Receives Investment From In-Q-Tel - GenomeWeb

Neuroscience

Applying neuroscience to Cannes-winning work: Nike What Girls Are Made Of – AdNews

AdNews has partnered with Neuro-Insight to bring an analysis of some of this year's winning Cannes work to understand what made them successful through a neuroscience lens. We look at Nikes What Girls Are Made Of campaign.

AdNews has partnered with Neuro-Insight to bring an analysis of some of this year's winning Cannes work to understand what it is that made them successful through a neuroscience lens.

NikeWomen is continuing to ask charged, rhetorical questions to audiences in this Russian spot. It followed NikeWomens viral Arab ad, which garnered over one million views in just a few days,and featuresa young female choir singer become empowered by the presence of female athletes. Now, the analysts and Neuro-Insight find out what the public thinks of the campaign.

Nike - What Girls Are Made Of

Nike are well known for their campaigns that question common perceptions and dare people to be the greatest version of themselves. Not to be outdone, this years What Girls Are Made Of campaign challenged female stereotypes, its powerful execution landing a Gold Lion award for film at the 2017 Cannes Lion festival.

The ad opens on a young girl performing a Russian childrens song in front of a large crowd. In her classical voice, she sings about girls being made of flowers and of rings, of gossips and marmalade. But a female athlete soon breaks through the performance, a scene after which the girl starts changing the lyrics of the tune, much to the surprise of the very conventional audience attending. The song becomes about girls strength, perseverance and freedom from other peoples opinions, with impressive performances of female athletes surrounding the young singer. The ad ends with the little girl now on the football field, looking straight at the camera, resolute to make a goal; the final message Youre made of what you do. Believe in more appears on screen, followed by the brand logo.

The narrative of this ad is powerful, but what are people truly taking out of it, and what is the emotional impact of this less cliched depiction of women? Neuro-Insight has looked at its second-by-second impact on the brain to determine the likely effectiveness of the ad.

How we did it

Neuro-Insight measured brain activity to see how 50 females and 50 males responded to the ad. The specific technology used by Neuro-Insight is founded in work originally developed for academic and neuroscience research, and has been used to analyse the effectiveness of Cannes award winners for over five years. The technology allows us to simultaneously record viewers second-by-second changes in approach (like)/withdraw (dislike), emotional intensity, engagement and memory whilst watching advertisements. The measure Neuro-Insight predominantly focusses on is Long-term Memory Encoding, based on its strong and highly researched link to actual consumer behaviour.This measure reveals, on a second-by-second basis, what the brain is storing (or encoding) into conscious and unconscious long-term memory and is plotted in the form of a time series graph. The higher the lines on the graph, the more strongly that moment in the ad is stored in memory and the more likely it is to influence consumer behaviour.

Time Series

Looking at memory encoding response allows to see how well viewers follow the key message of the ad. The times series videos that are below contrast male and female viewers response to the Nike commercial. The red trace reflects memory encoding from the left hemisphere, which is primarily responsible for the encoding of the detail in experiences, such as text, dialogue or brand messages. In contrast the right hemisphere, which is represented by the blue line, is concerned with the storing of global features, such as soundtracks, scenery and facial expressions, as well as the emotional underpinnings of a particular experience.

Long term memory encoding for Female Viewers

Long term memory encoding for Male Viewers

The above time series graphs reveal key differences in response between male and female viewers, which are indicative of what both genders are taking on board.

Amongst the female audience, the highest levels of left brain response are for scenes where there is a key development in the little girls story: when she starts changing the lyrics of the song, when the rest of the choir appears behind her, and when we see her move from the performance space to the football field. The strong left-brain response indicates that, along with these moments, the non-stereotypical portrayals of women delivered by the lyrics are also being encoded. The high levels of left brain response carry through until end branding, making it likely that women will link the ads story to the Nike brand.

Figure 1: Women focus on the young singer and the detailed message of the song

In contrast, right brain response is overall stronger than left brain response amongst male viewers. Whilst the detailed message delivered by the young singer is a key driver of response for women, men are particularly engaged with scenes featuring athletes: right brain memory response peaks for every appearance of an athlete, suggesting the overall feel of the athletic performances dominates over the underlying message. Branding is associated with falling responses and low levels of left brain memory encoding, suggesting it isnt coming across strongly.

Figure 2: Men are responding to the overall feel of the scenes featuring athletes

Looking at emotional responses (not shown here), it is evident that the ad triggers a much more positive emotion amongst women: levels of approach response are more than 3 times higher for female viewers. The difference is particularly marked during the second part of the ad, where the message changes from a stereotypical to a more empowering depiction of women: the portrayal of women as made of iron, of striving, of self-dedication, made of bravery and will that is harder than stone is associated with strong approach amongst women, indicating the ads message is very well liked. These lines are however associated with a fair bit of withdrawal amongst men: clearly, a narrative about women empowerment is most powerfully motivating for a female audience.

In summary, and perhaps unsurprisingly, the commercial is more effective with a female audience than it is with a male audience. Although male viewers engage with the sports scenes, the underlying message is neither a strong take out nor a motivating force for them, and the brand itself isnt that well encoded. However, amongst a target audience of women, the challenging stance Nike took paid off: it associated the brand with a motivating message that had strong cut through, resulting in an ad that is likely to build strong brand equity and have in-market impact.

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Applying neuroscience to Cannes-winning work: Nike What Girls Are Made Of - AdNews

Physiology

How your risk of heart disease stems back to your time in the womb – Medical Xpress

July 11, 2017 Credit: Ryan Melaugh

Smoking, lack of exercise, bad diet and our genes are all well-known risk factors for heart disease, cancer and diabetes. But, as researchers are beginning to understand, the environment in the womb as we first begin to grow may also determine our future.

The history of science is littered with self-experimenters so passionate about their work that they used themselves as human guinea pigs, however ill-advisedly.

Sir Joseph Barcroft (18721947) was one such character. Professor of Physiology at Cambridge, he was best known for his studies of the oxygenation of blood. He also led mountain expeditions where he analysed the oxygen content of his blood and that of other expedition members.

In the middle of his career, Barcroft built an airtight glass chamber in his laboratory in Cambridge. There, he could live and exercise at oxygen levels equivalent to 16,000 feet. Like many self-experimentation stories, things did not always go to plan: in one experiment, he had to be rescued by colleagues after spending six days in the chamber and reportedly turning blue.

Despite his occasional misguided venture, Barcroft's scientific legacy was significant and so, in his honour, the University of Cambridge has recently opened a new state-of-the-art facility in his name. Research at the Barcroft Centre focuses on farm animals mainly sheep and chickens, but also pigs to model important aspects of human physiology.

The Centre's work spans several areas including Professor Jenny Morton's studies on understanding fatal neurodegenerative diseases such as Huntington's disease and a similar childhood disease, Batten disease, and Dr Frances Henson's work on bone diseases such as osteoarthritis.

However, a significant amount of its work focuses on how we develop in the womb and how this programmes us for increased risk of heart disease in later life. This seems fitting as, in later years, Barcroft became interested in fetal development, and in particular the effects of low levels of oxygen on the unborn baby in the womb.

Carrying on this legacy are Professor Dino Giussani and his postdocs Dr Kim Botting and Dr Youguo Niu. All are also members of the Centre for Trophoblast Research (CTR), which this year celebrates its tenth anniversary and focuses on the interactions between the pregnant mother and the fetus, as mediated by the placenta.

Low levels of oxygen or hypoxia can occur in high-altitude pregnancies. But, as Giussani explains, there are far more common causes. "Smoking, pre-eclampsia, even maternal obesity these all increase the risk of hypoxia for the mother's baby, as do inherited genetic variants," he says.

Housed in the Barcroft Centre is a suite of hypoxia chambers superficially similar, perhaps, to that in which Barcroft placed himself, but nowadays far more sophisticated (and much safer). These are not intended for humans, but rather for animals, each of which is very closely monitored, often remotely using technology developed by the team.

The smallest of these chambers doubles as an incubator for fertilised hens' eggs. Scientists can watch the development of the fetus directly. They can see how the heart grows, for example, how it is affected by hypoxia, and what effect potential drugs have in ameliorating possible complications.

Of course, we grow in a womb, with a placenta connecting us to our mother and controlling our nutritional intake. Mice and rats are the most commonly used mammals in research, but to model mammalian development in longer-living species with similar rates of development to humans, it is necessary to turn to larger animals. Sheep make a good model. Not only is their gestation and postnatal life more comparable to a human's than to a rat's, but a newborn lamb's physiology is also similar in a crucial way to a newborn baby's: its heart is mature at birth. By comparison, a newborn rat's heart is still very immature.

For part of gestation, the sheep are placed in hypoxia chambers, which contain finely controlled, lower-than-normal levels of oxygen. "This reduces the amount of oxygen in the blood of the pregnant sheep and thereby in her fetus," explains Botting. "This mimics conditions where the placenta is not working appropriately, as in pregnancy complicated by pre-eclampsia or maternal obesity."

The pregnant ewes deliver outside the chambers in normal ambient air. Once born, most of the lambs are put out to pasture in the paddocks adjacent to the Centre, where they grow to adulthood.

"The lambs which were hypoxic in the womb are not noticeably different," says Giussani. "The sheep will effectively live a normal life. That is the very point, because underneath, a silent killer is brewing; we want to investigate what happens as they grow because there is a theory that a complicated pregnancy may increase the risk of heart disease in the offspring later in life."

Professor Abby Fowden, Head of the School of the Biological Sciences, and another CTR member and user of the Barcroft Centre, says that the facilities are unique. "It's probably the only centre in the UK that has the capacity the surgical and care facilities to do these kinds of long-term developmental and neurodegenerative studies," she explains.

Like Giussani, Fowden and her collaborator Dr Alison Forhead are interested in how the early environment in the womb programmes us for disease in later life. They are particularly interested in the role of hormones in both the mother and the fetus and how they affect growth and development.

There are some conditions, such as hypothyroidism whereby the body produces insufficient thyroid hormones and maternal stress, that probably affect normal fetal development, but about which surprisingly little is understood. To model these conditions, Fowden and Forhead again turn to a range of mammals including sheep and pigs.

As Forhead explains, normal development of the fetus is crucial for health in later life. "In the case of many organs, you're born with a certain number of functional units, and in postnatal life you don't have the capacity to change that number. So the number you're born with has long-lasting consequences."

Take nephrons, for example. These are functional units of our kidneys that filter the blood and are responsible for how much salt and water is excreted into the urine. "If you're born with fewer nephrons, this has consequences for how much salt you retain, setting you up in later life to be at greater risk of developing high blood pressure."

What is apparent from this work is just how much of disease in later life is programmed in the womb. While our lifestyle our diet, how much we exercise after birth plays an important role in whether we develop heart disease or type 2 diabetes, for example, much of the risk is present before we are even born, programmed during pregnancy into how our DNA and tissues function.

And these effects don't necessarily stop at the next generation, as Giussani is discovering in his parallel work with rodents, which allows two or more generations to be studied in a comparably short time.

"If we look at the 'grandchildren' of pregnant rats that had a hypoxic pregnancy, we see this disease risk being passed on again, but in a really interesting way," he says. "A male 'child' passes on the cardiovascular risk to the 'grandchild', but female offspring confer protection. This is really exciting as inheritable protection against a future risk of heart disease has never been demonstrated in mammals."

In other words, while we must still recognise our own contribution to our risk of developing certain diseases, some of this risk was programmed into us before we were born: in fact, even before our parents were born. Work at the Barcroft Centre in monitoring animals for not just one generation but several will be vital for understanding the consequences of pregnancy not only for our children but also for their children and even their children's children.

Explore further: Study suggests that aging begins in the womb

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How your risk of heart disease stems back to your time in the womb - Medical Xpress

Physiology

Clover Connection: Extension research center celebrating 50 years – Athens Daily Review

In addition to having county extension offices that serve the citizens of Texas, AgriLife Extension also has 12 Research and Extension Centers. The center that serves us here in Henderson County is located in Overton. It will be celebrating its 50th birthday on Wednesday, July 12.

For half a century, Texas A&M AgriLife Research has conducted trials and developed new innovations to help East Texas and Texas producers optimize their operations and to provide quality goods, including flowers, fruits and vegetables, and beef to consumers.

Overton center staff will welcome public, state and area officials and Texas A&M University System officials to the facility at 1:15 p.m., July 12, for presentations on its history and contributions to Texans.

Presentations by staff will be followed by a keynote address from John Sharp, Texas A&M System chancellor, and comments by Dr. Craig Nessler, AgriLife Research director, Dr. Doug Steele, Texas A&M AgriLife Extension Service director, and Dr. Mark Hussey, vice chancellor and dean for College of Agriculture and Life Sciences at Texas A&M University, all from College Station. A reception will follow the ceremony.

Nessler said the 50-year milestone for the Overton center, and the future of AgriLife Research around the state should be celebrated by all Texans.

AgriLife Research scientists in Overton have made amazing contributions to the daily lives of Texans in the past 50 years, he said. Much of what we do as researchers is done behind the scenes, and without a desire for attention and accolades. But if you enjoy ornamental flowers or great lawn turf, produce or consume beef, or grow fruits and vegetables, theres a good chance youve benefited from AgriLife Research efforts in Overton.

AgriLife Research at the Overton center focuses on the problems and potential successes for residents and producers in East Texas, Long said. Developing new technology and techniques for producers and consumers is the mission of AgriLife Researchs statewide system.

Scientists at the center cover a wide range of disciplines, including horticulture, soil and crop science, animal science and related fields. The research trials performed by scientists at the center are provided to producers and consumers through coordinated efforts with AgriLife Extension specialists, and agents around the state who represent the educational arm of the system.

Dr. Charles Long, the centers director for the past 35 years, said research conducted at the center has made lasting impacts for Texas farmers and ranchers, various agricultural industries, the states economy and the residents who enjoy the end product.

Research activities at the center fit the highest regional agricultural priority, as available financial, facility and personnel resources allow, Long said.

The plan is to conduct research in areas of the highest need, while ensuring programs are sufficiently supported to provide a reasonably high probability of success, Long said.

Scientists at the Overton center conduct research in five disciplines soil science, pasture utilization, forage plant breeding, animal physiology and horticulture.

Over the past 50 years, AgriLife Researchers have developed and conducted trials on thousands of varieties of ornamental flowers, fruits and vegetables, and forages.

For example, Dr. Lloyd Nelson, AgriLife Research small grains breeder, developed Panterra and Axcella 2, turf-type annual ryegrasses bred specifically for winter overseeding of warm-season grasses on athletic fields and home lawns. The varieties have been used in the Olympics and World Cup and on Professional Golfers Association courses.

Nelson also developed forages. He is responsible for TAM 90, a ryegrass that combined cold and rust tolerance from other popular ryegrass varieties to create the winter forage. Since its creation in 1990, 85 million pounds of TAM 90 have been sold, enough to overseed 2.8 million acres.

Scientists also conduct research to identify physiological and temperamental traits in beef cattle that can optimize production for producers.

Dr. Ron Randel, an internationally known AgriLife Research physiologist, oversees several projects at the center focused on the reproductive physiology of tropically adapted cattle, the nutrition-reproduction interaction and most recently the temperament and stress responsiveness of beef cattle. He has researched the physiology and endocrinology of ovarian and pituitary functions in Brahman cattle for more than four decades.

Those two scientists are just a couple of examples of what AgriLife Research has been doing over the past five decades, Long said. There are success stories after success stories that continue to impact the lives of people all over the world, and they were written right here in Overton.

Kate Pittack is the Henderson County Extension Agent 4-H & Youth Development for Texas A&M AgriLife Extension Service. Contact her at: kate.pittack@ag.tamu.edu & visit our webpage at http://henderson.agrilife.org

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Clover Connection: Extension research center celebrating 50 years - Athens Daily Review

Embryology

Treatment for Infertility Does Not Appear to Raise Risk of Divorce – Doctors Lounge

Category: Endocrinology | Family Medicine | Gynecology | Nursing | Psychiatry | Urology | Conference News

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Study finds couples who seek in vitro fertilization are not at added risk of divorce

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MONDAY, July 10, 2017 (HealthDay News) -- Couples who undergo assisted reproduction treatment (ART) do not have a higher likelihood of divorce, according to research presented at the annual meeting of the European Society of Human Reproduction and Embryology, held from July 2 to 5 in Geneva.

The study included 42,845 women in Denmark who had ART between 1994 and 2009.

The researchers found no link between ART and separation or divorce. They added that 20 percent of women who underwent ART separated or divorced within 16 years, compared to 22 percent of women who were not treated.

"Findings on the security of relationships and parenthood can be particularly helpful in supporting patients' commitment to treatment," Mariana Martins, Ph.D., a psychology faculty member at the University of Porto in Portugal, said in a news release from the European Society of Human Reproduction and Embryology. "We have previously found that subjects who divorce, re-partner, and come back to treatment are the ones that five years before had the most stress. We also know that despite all the strain that this infertility can bring, going through ART can actually bring benefit to a couple's relationship, because it forces them to improve communication and coping strategies."

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Treatment for Infertility Does Not Appear to Raise Risk of Divorce - Doctors Lounge

Anatomy

Milwaukee Brewers: The Anatomy Of An All-Star Selection – Reviewing the Brew

MILWAUKEE, WI - JUNE 21: Corey Knebel

Milwaukee Brewers: This Is More Than Just A Ride by Steven Ohlrogge

Milwaukee Brewers: How They Stole The Cubs Soul by Matthew Dewoskin

With the season Knebel is putting together, there is little doubt he is the right guy for the job. He has saved 13 games since taking over for Neftali Feliz. He also adds a 1.76 ERA and 72 strikeouts to the mix in 2017.

Knebel came into to Brewers system in 2015 through a trade with the Texas Rangers. In order to get their All-Star closer, Milwaukee sent Yovani Gallardo to Texas. This deal ended with the Brewers gettinginfielder Luis Sardinas and pitcher Marcos Diplan as well.

Diplan currently sits as the number eleven prospect in the organization according to MLB Pipeline. Sardinas was eventually flipped later that year to get Ramon Flores from Seattle. Flores ended up hitting .205 for Milwaukee Brewers through 104 games in 2016.

While Diplan still has the potential to be a star, Knebel is the most beneficial part of the trade so far. His journey started after getting drafted 39th overall by the Detroit Tigers in 2013. He was a part of the deal that sent Soria from the Rangers to the Tigers. It ultimately ended with his selection to the All-Star team as a member of the Milwaukee Brewers.

Based purely on numbers Knebel has put together a great year. He has faced a total of 168 batters and has allowed only eight earned runs. It has been a display of dominance throughout the year. What is even more impressive is that opposing batters are hitting .168 off of him, and those who are getting hits are not stringing them together. He has left 91.5 percent of runners on base.

According to Fargraphs Knebelis able to pull this off with a very impressive fastball that averages 97 MPH. He compliments that with a curveball he throws just under 30 percent of the time. It may seem low, but for a player who generally only throws an inning every time he goes out there it is enough to keep hitters off balance.

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With the Milwaukee Brewers currently pacing the division, it is surprising they only have one All-Star this year. Players like Eric Thames or Jimmy Nelson have proven their worth of a bid this year, but were snubbed. In the end the honor would have been nice, but the team is after the ring at the end of October.

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Milwaukee Brewers: The Anatomy Of An All-Star Selection - Reviewing the Brew

Anatomy

Mkhwebane: Anatomy of a serious stuff up – Rand Daily Mail (registration)

Mkhwebane has made a number of questionable moves and statements since she took over from her revered predecessor Thuli Madonsela.

Her worst decision in her short tenure has got to be her instruction to parliament to change the constitution in order to tinker with the mandate and the independence of the SA Reserve Bank.

Lets recap.

A few weeks ago Mkhwebane found against Absa/Bankorp in a case involving the banks liability for the repayment of the R1.1 billion lifeboat the Reserve Bank extended to it between the late 1980s and the early 1990s.

The facts around whether or not Absa should repay the lifeboat in full are still in dispute. However what was bizarre about Mkhwebanes report was her instruction that parliament should change the wording of Section 224 (1&2) of the constitution.

She even gaves MPs the exact words they should substitute for the ones used by the crafters of our supreme law something that would have taken away the independence of the central bank.

She has united the Reserve Bank the national Treasury and parliament against her findings.

The rest is here:
Mkhwebane: Anatomy of a serious stuff up - Rand Daily Mail (registration)