Cell Biology

Biology Textbooks May Be Wrong: Newly Discovered Driver of Plant Cell Growth Contradicts Current Theories – SciTechDaily

A new study shows the swelling of tiny pectin filaments within cell walls propels these shape and growth of plant cells.

The shape and growth of plant cells may not rely on increased fluidic pressure, or turgor, inside the cell as previously believed. Rather, a new study shows the swelling of tiny pectin filaments within the cell wall propels these morphological changes.

If true, this discovery could overturn the current textbook model for plant cell expansion, and it suggests similar biochemical processes could underlie cell growth in other organisms as well, including animals. The authors also hope their observations inspire the development of new smart materials mimicking the unique expansion of plant cell walls.

Composed of a network of puzzle-like pieces, called pavement cells, the outermost layer of plants protects the structure and integrity of the specialized cells within. The walls of pavement cells are composed of polysaccharides, proteins and pectins and can shift between different states in response to chemical cues to support cell shape, size and division. But just how cell wall components contribute to the shaping and expansion of the puzzle-like cells is yet unclear.

Kalina Haas and colleagues studied the morphogenesis of pavement cells in Arabidopsis cotyledon (the first leaves to emerge from a germinating seed). They employed data sonification methods to perceptualize the wide variety of pavement cell shapes with sound. Using super-resolution imaging techniques to home in on homogalacturonan (HG) polysaccharides, a kind of pectin in the cell wall, the researchers found that these polysaccharides assemble into discrete nanofilaments rather than a cross-linked network bound to structural proteins.

Though the microscopy methods could not provide a closer look at these structures, Haas et al. postulated that HG are multi-subunit structures that, when demethylated, shift from their crystalline state into a swelling state that leads to wall expansion and growth of lobes on the pavement cells.

They validated their hypothesis in models whereby they simulated lobe development in cotyledon and induced demethylation of pectin components in the cell wall. This altered the plant cell shape despite the absence of hydration and turgor pressure.

Reference: Pectin homogalacturonan nanofilament expansion drives morphogenesis in plant epidermal cells, by K.T. Haas; R. Wightman at University of Cambridge in Cambridge, UK; K.T. Haas at Laboratoire Matire et Systmes Complexes in Paris, France; K.T. Haas at UMR 7057 CNRS in Paris, France; K.T. Haas at Universit Paris Diderot in Paris, France; E.M. Meyerowitz at Howard Hughes Medical Institute in Pasadena, CA; E.M. Meyerowitz at California Institute of Technology in Pasadena, CA; A. Peaucelle at Institut Jean-Pierre Bourgin in Versailles, France; A. Peaucelle at UMR 1318 AgroParisTech in Versailles, France; A. Peaucelle at INRAE in Versailles, France; A. Peaucelle at Universit Paris-Saclay in Versailles, France.DOI: 10.1126/science.aaz5103

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Biology Textbooks May Be Wrong: Newly Discovered Driver of Plant Cell Growth Contradicts Current Theories - SciTechDaily

Cell Biology

A Bold and Controversial Idea for Making Breast Milk – The Atlantic

Biomilq does seem to be onto something though, at least culturally. Since the postwar days of doctors pushing formula as the superior scientific option, the conventional and medical wisdom has swung in the opposite directionto the point where women often feel guilty for being unable to breastfeed. Theres just a feeling of failure: I cant do this for my child. This is really important, said Maryanne Perrin, a breast-milk researcher at the University of North Carolina at Greensboro, who has studied women trying to buy breast milk online for their children. I heard a lot of anxiety in the voices and comments, she added. In other words, there is definitely a demand for human breast milk.

The idea for Biomilq, in fact, came out of Stricklands own struggles to breastfeed as a new mom. Her son had trouble latching after he was born, and she wasnt making enough milk. During those months of life, my whole world revolved around whether or not my body would produce enough of this food, she says. She wished for an option that was not formula. Strickland has a background in cell biology, so she naturally wondered: What about breast cells?

In 2013, she began growing mammary cells in a tiny lab space in North Carolina, and in 2019, she met Egger, a student at Dukes business school and a former food scientist at General Mills, who had worked on products such as Go-Gurt. They officially launched Biomilq late last year to make lab-grown human milkor as they prefer to call it, cultured breastmilk. Another start-up based in Singapore, TurtleTree Labs, recently announced it is trying to re-create cow and human milk with cells as well.

Human milk is currently available for sale, but it is not easy to buy. Officially, parents can go to a milk bank to buy donated breast milk that has been screened and pasteurizedbut this requires a doctors prescription and can go for a hefty $4 or $5 an ounce to cover processing costs. (Milk banks also prioritize donor milk for sick or preterm infants in the hospital, for whom cow-based formula is particularly prone to causing a serious gut disease called necrotizing enterocolitis.) Unofficially, parents can go on Facebook or Craigslist or another online marketplace where women share or sell extra breast milk. These markets are cheaper and more convenient, but theyre also unregulated. Donors largely follow the honor system for disclosing medications and other health information. Meanwhile, formula is cheap, safe, and widely available in grocery stores. Biomilq promises to combine the nutrition of breastmilk with the practicality of formula.

Its hard to say, at this nascent stage, exactly how still-hypothetical breast milk made by cells in a bioreactor would compare with formula. The cultured human-milk proteins could be more suitable in a babys gut than dairy proteins, and sugars specific to human milk could help feed a babys new gut microbes.

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A Bold and Controversial Idea for Making Breast Milk - The Atlantic

Cell Biology

Researchers Forge a New Weapon to Fight Parasites and Other Infections | Newsroom – UC Merced University News

Breakthrough collaborative science by an interdisciplinary team of researchers brought together by computational biology Professor David Ardell promises a new approach for treating all types of infections.

Infections have become more dangerous in recent years because bacteria and parasites rapidly evolve resistance to the medicines.

But Ardells lab and a team of researchers from two other universities used a novel genomics- and systems-biology-based approach to find chemical compounds extracted from bacteria harvested from the ocean that could inhibit enzymes from a broad spectrum of related parasites without affecting human versions of those enzymes.

The team also describes a strategy for administering new drugs to be developed from their technology that should make it harder for parasites to evolve resistance to them.

Its a first step toward fulfilling the promise of the genomics era to inform how we combat disease, Ardell said.

The two ways doctors treat infections now are with vaccines, which program the immune system to fight off specific invading organisms such as the ones that cause measles, mumps and polio; or with antibiotics, anti-fungals or anti-parasitics, which poison the harmful organisms. But because parasites are more closely related to humans than other pathogens, anti-parasitics also tend to be toxic to humans and are harder to discover.

Our method targets the evolving cellular language of the parasites instead of their chemistry, he said. Thats why well be able to apply this to bacterial infections, too its applicable to any disease-causing organism for which the genome has been sequenced.

Ardell said he and the other team members were pleased to find they could predict and identify functional differences in the enzymes from humans and trypanosome parasites based on genomic sequences alone and show that these differences are highly conserved over 250 million years of trypanosome evolution.

There are several types of infectious agents including bacterial, parasitic, viral, fungal and prion that cause all kinds of illnesses, from common colds and flus to such potentially life-threatening diseases as coronavirus, Zika, MERSA, C-Dif, Mad Cow disease, HIV, Ebola, African sleeping sickness, Dengue Fever and many others.

The immune system is usually an effective barrier against infectious agents, but colonies of pathogens can grow too large for the immune system to fight. Thats when infections become harmful.

For example, the Centers for Disease Control (CDC) estimates there are 1.7 million healthcare-acquired infections each year in American hospitals, and 99,000 associated deaths each year. The majority are urinary tract infections, but people also get surgical-site infections, pneumonia and other lung infections, and bloodstream infections.

However, after decades of over-prescription and overuse, antibiotics have become increasingly ineffective, and pharmaceutical companies are not often developing new ones.

Ardell established the collaboration developing this novel approach seven years ago. A project grant focusing on trypanosomes, which cause diseases such as sleeping sickness, was funded by a grant from the National Institutes for Health to Ardell, Ohio State University Professor Michael Ibba, a University Distinguished Scholar of Microbiology, and other collaborators including Roger Linington, Canada Research Chair in High-Throughput Screening and Chemical Biology at Simon Fraser University.

Ardell and his co-authors, including Quantitative and Systems Biology graduate student Fatemeh Hadi-Nezhad; former doctoral student Travis Lawrence, now at Oak Ridge National Lab Biosciences Division; and biochemists and parasitologists from The Ohio State University and chemists from Simon Fraser University, detailed their findings in a paper entitled "Targeting tRNA-Synthetase Interactions Toward Novel Therapeutic Discovery Against Eukaryotic Pathogens published today in the journal PLOS Neglected Tropical Diseases.

Ardell, a member of the Department of Molecular and Cell Biology in the School of Natural Sciences and an affiliate of the Health Sciences Research Institute, said the study carries enough experimental validation to allow the research to move to the next steps, including more testing.

He plans to expand the project through a collaboration with Professor Clarissa Nobile, who examines Candida auris, a fungal infection that has made headlines in the past few years as hospitals experience outbreaks of drug-resistant strains.

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Researchers Forge a New Weapon to Fight Parasites and Other Infections | Newsroom - UC Merced University News

Cell Biology

Jounce Therapeutics, Inc. (JNCE) Q4 2019 Earnings Call Transcript – Motley Fool

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Jounce Therapeutics, Inc.(NASDAQ:JNCE)Q42019 Earnings CallFeb 27, 2020, 8:00 a.m. ET

Operator

Good morning ladies and gentlemen and welcome to the Jounce Therapeutics Fourth Quarter and Full Year 2019 Earnings Conference Call. [Operator Instructions].

I will now turn the call over to your host Komal Joshi with Jounce Therapeutics. Please go ahead.

Komal Joshi -- Head of Investor Relations

Thank you operator. Good morning and welcome to the Jounce Therapeutics Quarter and Full Year 2019 Financial Results Conference Call. This morning we issued a press release which outlines the topics that we plan to discuss today. The release is available in the Investors and media section of our website at http://www.jouncetex.com. Speaking on today's call will be our CEO and President Dr. Rich Murray who will discuss our pipeline progress and key milestones for 2020 followed by our CMO Dr. Beth Trehu who will provide an update on our clinical activities. And lastly our CFO Kim Drapkin will review our full year 2019 financial results and 2020 guidance. We will then open the call for your questions.

Before we begin I would like to remind everyone that today's discussion will include statements about our future expectations plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including the risk factors discussed in our SEC filings. In addition any forward-looking statements represent our views only as of today February 27 2020 and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future we specifically disclaim any obligation to do so even if our views change.

With that I will now turn the call over to Rich.

Richard Murray, Ph.D. -- Chief Executive Officer and President

Thanks Komal and good morning everyone. As we reflect on 2019 I'd like to note the meaningful advancements Johns has made to further progress our growing IO pipeline toward several key milestones that we set forth in early 2019. That progress stems from our translational science platform driving new IO therapies to the clinic as well as analyzing patient samples from our clinical trials to inform new science-driven development paths. The latter is best illustrated by our lead Phase II program vopratelimab which represents what we believe will be necessary to make a meaningful impact for patients who are not benefiting from today's IO therapies. For vopra we made significant progress over the course of 2019. First the introduction of our two vopra development paths. Based on the results of extensive reverse translation allowances we identified important biomarker differences between responding and non responding patients enabling the emerge and select trials. Next the exciting data from ICONIC at AACR where we showed improved responses progression-free survival and overall survival directly linked to the treatment-emergent ICOS hi CD4 T cells.

These cells are a vopra-associated pharmacodynamic biomarker not seen with PD-1 inhibitors. Next the identification of a predictive biomarker TIs vopra to be used for patient selection in upcoming select trial which we believe will allow us to select patients more likely to generate ICOS hi CD4 T cells in the presence of vopra and potentially experience clinical benefit. And the work we've done with dosing and schedule which may be an important feature of how to optimize activity of stimulatory rather than inhibitory based immunotherapies. As we look to 2020 the significant unmet need faced by many cancer patients continues to be at the forefront of everything we do. Beth will take you through more details on both EMERGE and SELECT in a moment. But before turning the call over to her I'd like to take this opportunity to reflect on the unmet need vopra could have a major impact starting in non-small cell lung cancer. The last decade has been very exciting with game-changing treatment advances in oncology made by approved checkpoint inhibitors. As PD-1 inhibitors expand further and further into frontline therapy a growing number of patients who have progressed on these therapies need new treatment options. For example we estimate approximately 90% and of non-driver mutation frontline non-small cell lung cancer patients in the U.S. receive a PD-1 or PD-L one inhibitor as part of their initial therapy.

And the majority of those patients either relapse or do not respond creating a new growing area of unmet need. Standard of care for this patient population is docetaxel which has a low response rate and the challenging toxicities associated with chemotherapy. Part of the vote provision is to provide better treatment options for patients in this setting. And that market opportunity is substantial. With more than 40000 patients in the U.S. each year in just this particular setting. We continue to believe that novel approaches that are independent of the PD-1 inhibitor CD8 focused biology will be required to derive meaningful benefit in the growing population of patients who progressed on PD-1 inhibitors. Fundamental immunology research over the decades emphasize the importance of CD4 T cells and their central role in orchestrating a more complete overall immune response and speaks to the potential opportunity for vopra. Our vopra strategy is highly differentiated from the majority of other studies in this patient population most of which employ retreatment of patients who have already progressed on a PD-1 inhibitor with a PD-1 inhibitor again along with another agent. In the PD-1 inhibitor naive population the use of a predictive biomarker may support improved outcomes in a chemo-free immunotherapy combo regimen.

As we recently presented our upcoming select trial uses the TIs vopra biomarker to select patients for treatment with vopra plus our PD-1 inhibitor JTX-4014. We believe TIs vopra positive patients at baseline have a higher likelihood of generating ICOS hi CD4 T cells in the presence of vopra and that's a potentially greater chance of clinical benefit. Beyond our clinical programs we continue to make progress advancing our earlier-stage pipeline using our translational science platform. We continue to believe that our strategy of discovery and developing IO therapies aimed at immune cell types beyond the traditional CD8 cell is an area of opportunity to bring more benefit to patients. Notably we advanced our next development candidate to come from our platform JTX-1811 which is currently an IND-enabling activities and is on track for first half 2021 IND filing. JTX-1811 is a monoclonal antibody engineered to deplete tumor resident T regulatory cells. While sparing other types of T cells.

We tried to present additional scientific data supporting the development of JTX-1811 at the upcoming AACR meeting in April. On the corporate development front we demonstrated external validation with the out-licensing of our macrophage candidate JTX-8064 to celgene. That was part of a broader renegotiation with Celgene and we now have the full unencumbered global rights to vopra JTX-4014 GTX-1811 and our entire discovery pipeline. On the heels of a strong 2019 of pipeline execution and corporate development we are poised for an important year of new clinical data and key milestones in 2020. To reiterate we plan to report preliminary efficacy and related biomarker data for vopra from the IMERGE trial in the second half of 2020 initiate the SELECT trial using TIs vopra in mid-2020 present data on JTX-1811 at the 2020 AACR meeting continue IND-enabling activities for JTX-1811 with an expected IND filing in the first half of 2021 and continue to work on advancing multiple new targets from our discovery pipeline.

With that I'll now turn the call over to Beth to further discuss our clinical pipeline and science in more detail.

Elizabeth Trehu, M.D. -- Chief Medical Officer

Thanks Rich and good morning everyone. As Rich mentioned 2020 is an important year of new clinical data and key milestones for Jounce building on our key clinical learnings in 2019. Beginning with our vopra program we continue to make significant progress and have introduced two different development paths based on our reverse translational analyses. The first approach is our induction strategy in the EMERGE trial; and the second is our patient selection strategy in the SELECT trial using our predictive biomarker TIs vopra. Both EMERGE and select trials are based on three major learnings from ICONIC. First we identified treatment-emergent ICOS hi CD4 T cells in the peripheral blood of patients treated with vopra alone or in combination with nivolumab that are associated with clinical benefit including response rate progression-free survival and overall survival. We've shown that emergence of these cells does not occur with PD-1 inhibitor therapy and therefore we believe that they are vopra-specific cells. We have also demonstrated that ICOS hi CD4 T cells expand and persist throughout durable responses some over two years. Second we identified an RNA signature in baseline tumor biopsies which we call TIS vopra which is optimized for prediction of emergence of ICOS hi CD4 T cells and predicted clinical benefit in ICONIC. And third we identified what we believe is a more optimal dosing regimen for vopra.

All of our vopra trials are built upon the fundamental science of our founders coupled with the reverse translational analyses from our ICONIC trial. Another key learning has been that vopra activity requires the presence of primed ICOS hi CD4 T cells. All of this work has culminated in our two vopra development paths. First the induction path in which ICOS hi CD4 T cells are induced by another agent prior to administration of vopra. The study for the induction path is the EMERGE trial which is a Phase II open-label multicenter trial using ipilimumab or ipi to induce ICOS hi CD4 T cells prior to vopra administration. The trial is under way in PD-1 experienced patients with non-small cell lung cancer. As Rich mentioned this is an area of high unmet need as PD-1 inhibitors have moved into frontline settings. As we have detailed previously we are implementing a new combination dosing strategy for the EMERGE and SELECT trials which we believe is more appropriate for an agonist. Given our understanding of the kinetics of induction and expansion of ICOS hi CD4 T cells by ipi and vopra respectively we believe that the unique combination dosing and sequencing strategy that we are using in EMERGE optimizes both ICOS hi CD4 T cells and co-stimulatory biology. We believe JOunce has a compelling and differentiated approach to immuno-oncology combination therapy.

We expect to report data from the EMERGE trial including preliminary efficacy and biomarker relationships to clinical outcomes for up to 40 non-small cell lung cancer patients in the second half of 2020. The study investigating the predictive biomarker path is the SELECT trial. Based on the evaluation of baseline tumor samples from patients in ICONIC we identified the gene signature and threshold to store which predicts rope associated ICOS hi CD4 T cells emergence as well as improved response rate overall survival and six and nine month progression-free survival in TIS vopra positive patients. The SELECT trial is designed to determine if patients with TIS vopra positive tumors will have a higher likelihood of generating ICOS hi CD4 T cells T cells in the presence of vopra resulting in potentially greater clinical benefit. TIS is an 18-gene signature that was originally developed as a predictive biomarker for PD-1 inhibitors. However TIS also includes genes associated with integral elements of CD4 T cell biology that may contribute to a more comprehensive immune response. In the upcoming Phase II select trial patients will be selected using TIS vopra. SELECT is a randomized ex U.S. trial in non-small cell lung cancer comparing vopra plus JTX-4014 RPD-1 inhibitor to JTX-4014 alone. We expect to enroll approximately 75 immunotherapy naive second line non-small cell lung cancer patients who will be selected using the TIs poker biomarker.

We estimate that approximately 20% of second-line non-small cell lung cancer patients will be above the h-hh. TIs for threshold and potentially eligible for the trial. We expect to initiate the select trial in mid-2020 and report interim clinical data in 2021. Turning to JTX-4014 we presented Phase I safety and preliminary efficacy data at the 2019 SITC meeting in November. Of note antitumor activity was observed with an overall response rate of 16.7% including one complete response and two partial responses all confirmed resist responses and with an acceptable safety profile in a difficult-to-treat population with no therapeutic options. Using our own PD-1 inhibitor in combination with vopra provides flexibility and cost savings. I'm proud of the accomplishments of our team in 2019 and look forward to continued progress in 2020 on clinical trial execution and readouts on clinical and biomarker data.

Now I would like to turn the call over to Tim for a discussion of our year-end financial results. Kim?

Kim Drapkin, CPA -- Chief Financial Officer

Thanks Beth and good morning everyone. As we reported in this morning's press release we ended 2019 with cash cash equivalents and investments totaling $170.4 million compared to $195.9 million for 2018. The decrease was primarily due to operating costs incurred during the year offset by the $50 million license fee received in July 2019 pursuant to our JTX-8064 license agreement with Celgene. Turning to the P&L. Our license and collaboration revenue was $147.9 million for full year 2019 compared to $65.2 million for 2018. The year-over-year increase includes $50 million of cash received under the JTX-8064 license agreement with Celgene and $97.9 million of noncash revenue recognition related to the Celgene upfront payment of $225 million that we received in 2016. During 2019 we incurred $67.1 million in research and development expenses compared to $70.1 million for 2018. The decrease in R&D expenses for the full year 2019 was due to $6 million of decreased manufacturing and IND-enabling costs and $0.9 million of decreased lab consumable costs. The decrease was partially offset by $3.1 million of increased employee compensation costs. General and administrative expenses were $27.9 million for 2019 compared to $26.4 million for 2018. The increase in G&A expenses is primarily the result of increased employee compensation costs.

Net income for 2019 was $56.8 million or basic net income per share of $1.72 and diluted net income per share of $1.66 as compared to a net loss of $27.4 million in 2018 or a basic and diluted net loss per share of $0.84. This increase was driven by the $147.9 million of license and collaboration revenue recognized under our agreement with Celgene. We reiterate the 2020 financial guidance we provided in January. We continue to expect gross cash burn on operating expenses and capital expenditures for the full year 2020 to be approximately $80 million to $95 million. We are no longer providing license and collaboration revenue guidance as potential future payments under our JTX-8064 license agreement with Celgene our royalty and milestone based. Given the strength of our balance sheet we expect our existing cash cash equivalents and investments to be sufficient to enable the funding of our operating expenses and capital expenditure requirements through the end of 2021. Additionally we continue to have the flexibility to drive our innovative immunotherapy pipeline while efficiently executing against our strategic plans and goals.

With that I'll hand the call to Rich for a final thought.

Richard Murray, Ph.D. -- Chief Executive Officer and President

Thanks Kim. Before we open the call for questions I'd like to bring the conversation back to the patients that we're trying to help. The success of the initial checkpoints has created benefit for patients where none was not possible less than a decade ago. But with that new challenges and therefore opportunities have arisen to treat patients who've progressed on PD-1 inhibitors in broader topic of moving IO therapies closer to a precision medicine concept. I believe our new trials reflect the scientific advancements that will need to be made from data gleaned from the lab and the clinic so that we can continue to envision a future with longer and broader durable benefit for patients that do not have those options today. As we look forward to updating you in the future.

And with that we'd now like to open the call for your questions. Operator?

Operator

[Operator Instructions]. Your First question comes from the line of Boris Speaker from Cowen Your line is open.

Boris Speaker -- Cowen -- Analyst

Good morning, Congratulations on all the progress. So question number one on the merge trial are you selecting out patients that don't show ICOS hi CD cells from IP induction? And maybe kind of a little more broadly what is the dosing in the EMERGE trial? And does it make sense to add an ipi booster in the middle of treatment.

Elizabeth Trehu, M.D. -- Chief Medical Officer

Sure. So I'll start with the second question. So the dosing is it is given every six weeks for up to four doses alternating with vopra so you get it on day one and three weeks later the patients get vopra. And then three weeks later they get another dose of ipi then vopra. So we do that alternating sequence for up up to four doses of ipi after which they receive vopra alone. So in terms of the ICOS CD4 cells it's a really interesting question. So we are tracking those cells very closely. So we're watching what they do after ipi and then before vopra and then after ipi again. Right now we're not doing any kind of selection. But we are following that very carefully and it certainly is something to think about in the future. We also although we're not using any selection in this study. We have we are testing a number of potential predictive biomarkers in baseline tumor samples that we'll be able to go back and look at. So right now the strategy is to induce the ICOS CD4 cells with vopra with it sorry and then to treat with vopra which as we expect to cause proliferation sustained activation of those cells over time which in our iCONIC study was associated with long-term clinical benefit.

Boris Speaker -- Cowen -- Analyst

Got you. My last question on the TIS vopra a biomarker test. If the SELECT trial is successful it looks like a very useful biomarker. What would you have to do to make the test approval by the FDA?

Elizabeth Trehu, M.D. -- Chief Medical Officer

Sure. So it's already a validated test so it's run on the nanostring platform. And there's just there's a series of steps to go through to create a companion diagnostic. And we've already mapped out what that path would look like. We would work with a vendor that would actually be the one to develop the companion diagnostic in partnership with us on our clinical trial.

Boris Speaker -- Cowen -- Analyst

So it wouldn't be limiting in terms of the regulatory strategy to do? that's all I wanted to know...

Kim Drapkin, CPA -- Chief Financial Officer

No. No no not at all.

Boris Speaker -- Cowen -- Analyst

Right. Thank you very much for taking my questions.

Kim Drapkin, CPA -- Chief Financial Officer

You're welcome.

Operator

Your next question comes from the line of James Birchenough Alfaro Your line is open.

James Birchenough -- Alfaro -- Analyst

Hi, guys. Thanks for all the details for taking the questions. A couple. So just on the EMERGE study is there any early insights you have on the tolerability of the modified dosing protocol that you're pursuing? And any early indication of success at induction about ICOS hi CD4 T cells with ipi. And then maybe related to that is there a predictive rate of ipi induction how reliable is it the induction of like those high CD4 cells? And then I've got a follow-up.

Elizabeth Trehu, M.D. -- Chief Medical Officer

Sure. So all I can really tell you right now is enrollment is on track to support the interim analysis that we're planning to do later this year and that's when we'll report data. So we don't typically provide any information on data from the ongoing trial. As I said enrollment is going well and we're on track to have data in the second half of the year. And then to your other question...

James Birchenough -- Alfaro -- Analyst

J Just thinking about historical date on ipi for ICOS hi CD4 T cell for.

Elizabeth Trehu, M.D. -- Chief Medical Officer

Sure So it's a little hard to interpret sometimes. We've heard people say that all the cells get induced ICOS gets induced on all the cells but then it drops off very quickly. So it's a little bit hard to discern from the literature exactly what the expected rate of ICOS induction from just it would be. But of course our trial will answer that because we are measuring that in a prospective manner. Most of the studies in which that's been done it's been more of a retrospective finding so I think ours will be the first study to my knowledge that's prospectively looking at how the kinetics of ICOS induction after ipi and then with vopra added on.

Richard Murray, Ph.D. -- Chief Executive Officer and President

Yes what is published Jim and they tend to be a fairly decent number of small studies but with kind of a common theme to that and that tends to be done in PD-1 naive patients. And of course we're looking at a PD-1 experience. But from that kind of collection of small studies the numbers are always north of 50%. Some will claim almost all the patients but really what we think is extremely important is the maintenance and sustainability of these cells. And that's what we think our trial will be able to uniquely answer.

James Birchenough -- Alfaro -- Analyst

And then just one final question. Just on the SELECT study and what you learned from ICONIC. Were there other RNA signatures that you evaluated? Or was this the one that you prospectively thought would make sense and really the only one you evaluated? Just wondering if there were other RNA signatures that had a decent predictive value.

Elizabeth Trehu, M.D. -- Chief Medical Officer

Sure. So we actually we had a long list of genes that we looked at and a number of pre determined signatures that we assess. And this one came out as the one that looks the most predictive for clinical benefit. But then what we thought was really really important was to see if it also tracked with the ICOS hi CD4 T cells T cells. And so first it looked like it predicted clinical benefit. But since many of these patients were also treated with a PD-1 inhibitor we then took this biomarker and applied it to see its predictive value for ICOS hi CD4 T cells emergence and then it clearly predicted for that. And then we selected the threshold based on the ability to predict ICOS hi CD4 T cells. And then when we apply that to the clinical data it was clearly also predicted for clinical benefit. But yes we looked at a number of different genes isolated genes and gene signatures prospectively and this was the one that appeared to be the best.

James Birchenough -- Alfaro -- Analyst

Great, thanks for taking the questions.

Elizabeth Trehu, M.D. -- Chief Medical Officer

You're welcome.

Operator

Your next question comes from the line of Michael from Baird Your line is open.

James Birchenough -- Alfaro -- Analyst

Hey, guys, thanks for taking the question. Just another one on EMERGE and in terms of the interim update expect in the second half of this year. Can you just give us a sense of what types of biomarker data you plan to provide?

Elizabeth Trehu, M.D. -- Chief Medical Officer

Sure. Definitely the ICOS hi CD4 T cells target engagement since we're doing a new dosing schedule that other than what we've done before. So those are the two primary ones. We also as I said we plan to do some relooking at some baseline biomarkers and some other aspects of biology.

Michael -- Baird -- Analyst

Got it. And maybe just in terms of patient numbers you've mentioned potentially up to 40 patients. But can you maybe give us a sense of sort of average follow-up at that point in time. Just trying to get a sense of how meaningful?

Elizabeth Trehu, M.D. -- Chief Medical Officer

Yes. Yes yes absolutely. So yes so we've timed the interim analysiS to be done after every subject has had at least two post-treatment or on-treatment CT scans. So we'll have at least 18 weeks of data on all of those patients before we report any data.

Michael -- Baird -- Analyst

Okay, great. Thank you.

Elizabeth Trehu, M.D. -- Chief Medical Officer

You're welcome.

Operator

Your next question comes from the line of Debjit Chattopadhyay for H.C. Wainwright Your line is open.

Aaron Welch -- H.C. Wainwright -- Analyst

This is Aaron on for Debjit. So I have some questions about how you plan on tackling the enrollment challenges for the SELECT trial like given COVID-19 disruptions? And how do you expect enrollment to go in the SELECT study given that many of the non-small cell lung cancer patients are likely to have previously been treated with an anti-PD-1?

Elizabeth Trehu, M.D. -- Chief Medical Officer

Sure. So we're doing this study ex U.S. because there actually are many countries in which there's very limited access to the PD-1 inhibitors that are approved in this country. So there are places where patients are anxious to enroll in a clinical trial to be able to get access to a PD-1 inhibitor. So we're really happy that we're providing them with that opportunity. Regarding the challenges of enrollment probably the biggest challenge is posed by having a requirement for a selective biomarker. However if you think about some selective biomarkers like ALK or VET where you're talking about 3% to 7% of a population we estimate that the TIS vopra will select about 20% of the second line non-small cell lung cancer patients. And in our conversations with investigators 20% is they're very comfortable with screening one inside of their patients is likely to be positive for the trial. So we have a number of different strategies in place to tackle this. We have enough sites and have a a strategy to screen for patients in a way to enable us to enroll those 75 patients and have data preliminary data in 2021.

Richard Murray, Ph.D. -- Chief Executive Officer and President

And maybe could I jump in there. Sorry to interrupt Aaron just to be clear the study is on IO naive patients not PD-1 experienced patients ex U.S. right.

Aaron Welch -- H.C. Wainwright -- Analyst

Right. And just real quick will could we expect to see any TIS vopra evaluations of patients coming out of the EMERGE study?

Elizabeth Trehu, M.D. -- Chief Medical Officer

Yes. We are looking at tippin baseline samples in the EMERGE study as well as well as other predictive biomarkers but that's obviously the one that we're the most interested in right now.

Aaron Welch -- H.C. Wainwright -- Analyst

Okay, thank you.

Elizabeth Trehu, M.D. -- Chief Medical Officer

Thank you. You're welcome. [Operator Instructions] Your next question comes from the line of Steve Seedhouse from Raymond James Your line is open.

Daniel H. McMahon -- Raymond James -- Analyst

This is Daniel on for Steve. So some checkpoint inhibitors are approved in PD-L1 expressing patients after showing greater benefits in those populations compared to those that do not express PD-1 and that you have a biomarker for ICOS hi what are your thoughts on targeting patients that are both PD-L1 and also have biomarkers for ICOS hi.

Elizabeth Trehu, M.D. -- Chief Medical Officer

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Cell Biology

Rare disease in children: the key role of a protein revealed – Canada NewsWire

Children affected by Batten disease are born with no symptoms and develop normally, learning to walk, talk, and interact with others.Between 5 and 8years of age, however, they start to regress."The first symptom that leads parents to seek medical attention for their child is a loss of vision caused by retinal degeneration.This is followed by cognitive regression characterized by speech and mobility impairment.The life expectancy for people with the disease is usually around 30 years," explains Lefranois, who has been working on Batten disease for more than ten years.

A key protein

Professor Lefranois and his team in Laval are delving into the cellular biology of the CLN3 protein, which has been synthesized with the help of its namesake gene, in order to better understand the protein's function and identify therapeutic targets.They recently published findings about a key role played by CLN3 in the Journal of Cell Science.In the absence of the disease, CLN3 ensures a constant supply of proteins to the endosome, an intracellular compartment that serves as a sorting centre for proteins within the cell.

"Under this cellular process, a receptor acts as a truck that carries proteins from the Golgi apparatus, the production factory, to the sorting centre.Thanks to CLN3, this truck normally returns to the Golgi to pick up another load of proteins in an ongoing cycle," the researcher explains."In the presence of the mutations, however, the truck doesn't make the return trip.Instead, it is redirected to the lysosomes, where it's broken down as cellular waste."

Because the receptor is degraded, the proteins vital to lysosome function can't reach their destination.In consequence, these organelles are no longer able to break down cellular waste, so they accumulate and cause cellular degeneration."We think that children with the disease develop normally in their early years because their cells compensate by making more trucks.It's possible that the cells can't keep up, so the system becomes dysfunctional and starts to degrade," adds Professor Lefranois.

Professor Lefranois is working with a team of European researchers to re-establish normal CLN3 function with a promising drug. The aim is to prevent degradation of the receptor so it can continue carrying proteins.

Worldwide, it is estimated thatone person in 100,000has Batten's disease in all its forms.

About the study

The article entitled CLN3 regulates endosomal function by modulating Rab7A effector interactions, by Seda Yasa, Graziana Modica, Etienne Sauvageau, Abuzar Kaleem, Guido Hermey, Stephane Lefrancois, was published in the Journal of Cell Science. The research was supported by the Joint Programme on Neurodegenerative Diseases Grant, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the National Contest for Life Foundation Germany and by the Deutsche Forschungsgemeinschaft, the Fondation Armand-Frappieret du Fonds de recherche du Qubec Sant (FRQS).DOI : 10.1242/jcs.234047

About the INRSThe Institut National de la Recherche Scientifique (INRS) is the only institution in Qubec dedicated exclusively to graduate level university research and training. The impacts of its faculty and students are felt around the world. INRS proudly contributes to societal progress in partnership with industry and community stakeholders, both through its discoveries and by training new researchers and technicians to deliver scientific, social, and technological breakthroughs in the future.

SOURCE Institut National de la recherche scientifique (INRS)

For further information: Audrey-Maude Vzina, Communications, INRS, 418-254-2156 (cell), [emailprotected]

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Cell Biology

University researchers win Canada-UK funding to develop AI-powered microrobots to capture brain – Mirage News

Researchers at the University of Torontos Donnelly Centre for Cellular and Biomolecular Research have received a funding boost to help realize their vision of using tiny robots controlled by artificial intelligence to one day find and capture rare stem cells from brain tissue for therapy.

Working with Mike Shaw, a machine learning expert at the University College London, U of Ts Aaron Wheeler and Cindi Morshead will receive more than $1 million from the new Canada-UK Artificial Intelligence Initiative.

Supported by the two countries federal governments, the initiative seeks to harness AI for societal benefit by bringing together experts from diverse disciplines.

We have previously developed microrobots for manipulating individual cells in a dish, says Wheeler, a professor in U of Ts department of chemistry in the Faculty of Arts & Science and the Institute of Biomaterials and Biomedical Engineering in the Faculty of Applied Science & Engineering.

Now we want to take it to the next level to design robots that can isolate single cells from a crowded environment such as brain tissue and make the system fully automated.

A total of 10 international teams shared approximately $5 million and 5 million over three years, according to an announcement made earlier this week by Navdeep Bains, Canadas minister of innovation, science and industry, and British High Commissioner to Canada Susan le Jeune dAllegeershecque. Other projects funded through the program, a collaboration between Canadas three research funding agencies and four UK research councils, seek to harness AI across different sectors, from countering abusive online language to improving labour market equality and monitoring global disease outbreaks.

Artificial intelligence is transforming all industries and sectors, opening up more opportunities for Canadians, Bains said in a statement. Today we take one step further toward ensuring that AI innovation and growth builds competitive and resilient economies, and maximizes the social and health benefits in both Canada and the UK.

Stem cells hold promise for regenerative medicine thanks to their ability to self-renew and turn into specialized cells in the body. Scientists around the world are exploring how resident stem cells in the brain can be harnessed to treat neurodegenerative diseases or repair injury.

Morshead, who is chair of anatomy in the department of surgery in the Faculty of Medicine and a stem cell scientist, and her team previously showed that brain stem cells can be directed to repair stroke injury in miceand they continue to investigate how to make the repair more efficient.

Optoelectronic microrobots designed by U of T researchers Shuailong Zhang and Aaron Wheeler can load, transport and deliver cellular material (photo courtesy of Shuailong Zhang)

The clues likely lie in the stem cells tissue microenvironment, where they are influenced by molecular signals released by neighbouring cells. Scientists are keen to map out this cellular cross-talk, which remains largely unexplored. A tool that can reproducibly pick out defined and intact cells from a complex mix of cells in brain tissue would be a huge asset. And tiny robots, working at the sub-millimetre scale, could be up for the task.

Having very methodical repetitive dissections will allow us to feel confident that the behaviours of cells will be similar across samples, which is important for stem cell biology and regenerative medicine, says Morshead.

With the help of their UK collaborators, the U of T researchers aim to teach the microrobots how to distinguish stem cells and their neighbours from microscopy images of brain tissue through AI and image-recognition algorithms.

A more immediate goal is to pair AI with the existing microrobotic platform developed by Wheeler and Morsheads teams for manipulating individual stem cells in the dish to gain insight into their molecular makeup and behavior. They previously demonstrated how cog-wheel shaped microrobots can scoop up and move the cells about. With AIs help, it should be possible to teach the microrobots how to recognize different types of cells based on their appearance and deliver them to various pipelines for molecular profiling.

In the long term, we would like to have one platform that can start with a slab of tissue and go to collecting the cells of interest, says Wheeler. We will end up with a tool thats useful for lots of folks in the life sciences who are trying to streamline and reproducibly collect interesting cells for further analysis.

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Physiology

My True Self Partners With The Winters Group to Launch The Physiology of Inclusion(TM) – Daily Record-News

EASTSOUND, Wash., Feb. 26, 2020 /PRNewswire/ --To support diversity, equity and inclusion (DEI) leaders in restoring their health and being physically prepared for the challenges that come their way, My True Self is partnering with The Winters Group, Inc. to launch The Physiology of Inclusion.

The Physiology of Inclusion is a whole-body system to improve physical, mental and emotional health so that DEI executives, practitioners and advocates can lead inclusively. This system comprises the three foundational elements of eating, sleeping and exercising that precede the three enabling elements necessary for enacting inclusion, thinking, being and interacting.

"Executives, administrators, and managers face the difficult challenge of leading organizations and teams through economic uncertainty, increased competition, and growing division in society," said Carter. "The Physiology of Inclusion is like Navy Seal Training for the DEI leader to prepare them physically, mentally and emotionally to succeed in these polarizing times."

"We are excited to partner with My True Self on this very important program. Too often we hear about the emotional, mental and physical toll DEI can take on a person's health and ability to stay in the fight," said Mary-Frances Winters, President and Founder of The Winters Group, Inc. "We must do the work to prioritize our well-being if we're truly going to be effective in shifting organizational cultures and influencing systems."

Gigi Carter is founder of My True Self, PLLC, a socially conscious wellness coaching and consulting practice. My True Self helps individuals, families, businesses, and organizations establish goals and create customized action plans towards sustainable wellness. Carter is author of The Plant-Based Workplace and co-author of the children's book The Spinach in My Teeth.

The Winters Group, Inc. is a global diversity and inclusion consulting firm. For over three decades, The Winters Group has supported leaders and organizations with developing transformative, sustainable solutions for equity and inclusion.

Contact: Gigi Carter (601) 201-5486 or 234839@email4pr.com

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Physiology

Study: Sugary drinks linked to lower levels of ‘good cholesterol’ – WCAX

NEW YORK (CBS) New research shows that sugary drinks can cause a lot more damage than just weight gain.

They're filled with calories and lack nutrients, yet sugar-sweetened beverages like sodas, sports drinks and fruit-flavored drinks are the largest source of added sugars in the American diet. Now, new research in the Journal of the American Heart Association finds drinking more than 12 ounces of sugary drinks a day is linked to lower levels of so-called good cholesterol, or HDL cholesterol, and higher levels of triglycerides in middle aged and older adults.

"This is important because both of those findings have been associated with an increased risk of cardiovascular disease," said Dr Luke Laffin, a preventive cardiologist with the Cleveland Clinic.

Previous studies have shown the negative health effects of added sugars. Dr. Laffin says most of that data was related to weight gain. "This study shows that there is a more clear link or association between changes in cholesterol patterns, so lends to the theory that it's not just the weight gain that contributes, it actually changes physiology with respect to blood cholesterol," he said.

The American Heart Association recommends eliminating sugary drinks for better heart health and lower risk of heart attack and stroke. And, no surprise, water is preferred and healthiest.

"Really getting rid of those sugary drinks, starting with our kids, it's going to be helpful to setting those examples because the effect can be cumulative over a life time as well," Laffin said.

Low calorie sweetened drinks did not negatively impact blood lipids in the study, but researchers say that doesn't mean those drinks don't have other health consequences.

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Study: Sugary drinks linked to lower levels of 'good cholesterol' - WCAX

Physiology

SIUE’s Fernandez del Valle Committed to Optimizing Women’s Health – RiverBender.com

EDWARDSVILLE Which mode of exercise most effectively reduces cardiac fat in women? How can different modes of exercise improve cardiac function? These are among the questions Southern Illinois University Edwardsvilles Maria Fernandez del Valle, PhD, is asking through her research aimed at optimizing womens health.

Fernandez del Valle is an assistant professor of exercise physiology in the School of Education, Health and Human Behaviors Department of Applied Health. She is a prime example of a teacher-scholar who has established effective multi-disciplinary collaborations and consistently involves undergraduate and graduate students in the Exercise Physiology Lab to pursue high impact research.

My research focuses on improving exercise prescription through different lines of study to help individuals optimize their health, Fernandez del Valle explained. Currently, were targeting women, and conducting research on cardiac fat and function to determine how different modes of exercise can help us improve both.

Unsatisfied with a meta-analysis that concluded exercise didnt have a significant effect as a strategy to reduce cardiac fat, Fernandez del Valle is investigating further for the benefit of womens health.

I want to improve the way we prescribe exercise, she said. We need a larger sample size to clearly see data trends, but early indications show that we can have a high impact on cardiac fat around the heart with resistance training alone. The implication then would be that obese women should do resistance training to target more internal fat rather than the fat you see on the outside. Because, internal fat is what I linked to the development of metabolic and cardiac diseases.

Two of Fernandez del Valles primary collaborators are Jon Klingensmith, PhD, assistant professor in the SIUE School of Engineerings Department of Electrical and Computer Engineering, and Pamela Woodard, PhD, with the Washington University School of Medicine.

Upon meeting Dr. Fernandez del Valle when we both arrived at SIUE, I was excited to learn of her expertise in obesity and her research in how to reduce the fat around our internal organs, Klingensmith said. Our interdisciplinary collaboration has opened new avenues of study at SIUE, including the use of cardiac MRI to quantify and map cardiac fat, and the development of ultrasound-based algorithms for identification of cardiac fat. These efforts would not be possible for either of us alone. The interdisciplinary nature of the work allows us to pursue ideas and funding that otherwise wouldnt be available.

Fernandez del Valle is also an active research mentor for multiple undergraduate and graduate students, most of whom have earned competitive research awards and Undergraduate Research and Creative Activities (URCA) accolades.

We can teach in the classroom and explain concepts, but when students are in a lab, I can see their faces and how it just clicks that oh, now thats what this means and this is connecting with this, Fernandez del Valle said. Without my collaborators and students assistance, this work would not be possible. It involves human subjects, assessment training and implementation, data reporting and much more.

Working in Dr. Fernandez del Valles lab has helped me connect with people, said graduate student and research assistant JaiLin Allen. Working with her has helped me gain not only experience in exercise physiology and knowing how the body works, but also how to tie in that experience with personal interactions and my future career.

Before working in this lab, I wasnt sure what I wanted to do post-graduation, added graduate student and research assistant Paige Davis. Now, I know I want to work in a research lab at a college or government agency. I love the mix of human interaction and data entry, and how everything comes together to achieve interesting results.

The SIUE School of Education, Health and Human Behavior prepares students in a wide range of fields including community and public health, exercise science, nutrition, instructional technology, psychology, speech-language pathology and audiology, educational administration, and teaching. Faculty members engage in leading-edge research, which enhances teaching and enriches the educational experience. The School supports the community through on-campus clinics, outreach to children and families, and a focused commitment to enhancing individual lives across the region.

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Physiology

Blame it on your genes – a genetic mutation reduces the ability to exercise – Yahoo News

It's easier for some people to exercise than others. (Getty Images)

Its long been thought that some people find exercising easier than others.

While some will happily jog off to the gym, others are left daunted by the prospect of doing anything that might cause perspiration or shortness of breath.

This might not just be a theory after all.

Scientists have found a link between certain genes and a persons ability to exercise efficiently.

Read more: Vogue Williams shared post-baby exercise tips

The research, which was published in the New England Journal of Medicine, discovered a genetic mutation in some people which made it harder for them to workout.

The genetic mutation can affect cellular oxygen sensing which is linked to a persons ability to exercise effectively.

The team involved in the research - which included researchers from King's College London - found that people with the gene had reduced rate of growth, persistent low blood sugar, a limited exercise capacity and a very high number of red blood cell.

In order to try to figure out why people with a limited exercise capacity behaved the way they did, the researchers tested one case study.

Read more: The top rated fitness trackers

After numerous tests - which included a genetic analysis and high-altitude testing - the scientists discovered that the mutated gene in question was the von Hippel-Lindau (VHL) gene.

The VHL gene plays an important role in our genetic make up, primarily because it helps our cells survive when our ability to take in oxygen is reduced.

The scientists found that the VHL gene was impaired in some people who struggle to exercise.

Thats because this gene is linked to the mitochondria and when the mitochondria isnt firing on all cylinders - which is the case in people with a mutated VHL - then it makes it harder to exercise.

Read more: Experts say we should walk during our lunch breaks

Dr Federico Formenti, School of Basic & Medical Biosciences, one of the leading authors of the study, said: The discovery of this mutation and the associated phenotype is exciting because it enables a deeper understanding of human physiology, especially in terms of how the human body senses and responds to reduced oxygen availability.

Story continues

It also goes a long way to explain why some people can train and run a marathon whilst others would struggle with training, even if they were mentally motivated enough to complete it.

More research will need to be done in order to determine just how much this gene can affect people, but its a great step in the right direction for the study of human physiology.

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Blame it on your genes - a genetic mutation reduces the ability to exercise - Yahoo News