Cell Biology

Cell Therapy Shows Promise in Parkinson’s – MedPage Today

Dopaminergic progenitor cells derived from a Parkinson's disease patient's own skin cells and injected into his putamen showed evidence of survival and were associated with improved motor scores and quality of life measures.

The cells were implanted into the 69-year-old Parkinson's patient's putamen in two procedures, left hemisphere followed by right hemisphere, 6 months apart. PET imaging with a dopaminergic activity tracer up to 24 months suggested graft survival, reported Jeffrey Schweitzer, MD, PhD, of Massachusetts General Hospital, and colleagues, in the New England Journal of Medicine.

Over 24 months, the patient's MDS-UPDRS, part III (evaluating parkinsonian motor signs) and PDQ-39 (assessing Parkinson's disease-related quality of life) scores also improved. His Parkinson's drug regimen at 24 months was similar to his pre-procedure treatment, but his levodopa equivalents were reduced from 904 mg to 847 mg.

The patient required no immunosuppression. "We have shown for the first time in this study that these reprogrammed cells are still recognized as self by the patient's immune system and won't be rejected," senior author Kwang-Soo Kim, PhD, of McLean Hospital in Belmont, Massachusetts, said in a statement.

"The study is interesting and promising, but should be interpreted with caution given that it reports on only one patient with limited and incomplete clinical data," noted Malin Parmar, PhD, of Lund University's Developmental and Regenerative Neurobiology department in Sweden, who wasn't involved with the research.

"Nevertheless, it is an important milestone in the field as it reports on survival of stem cell-derived dopamine neurons in a human brain," she told MedPage Today.

"The study takes an autologous approach, where the patient's own cells are used for transplantation," Parmar noted. "It points to the feasibility of such an approach, but also the weaknesses associated with it relating to using different batches of cells for each transplant and each patient, which is likely to result in a high variation in outcome."

Cell replacement has been studied in Parkinson's disease for several decades. Fetal tissue-derived cell transplants have had variable outcomes, due in part to limitations of fetal tissue as a cell source and lack of standardization. Recent advances in developmental and stem cell biology have led to cell-replacement therapies involving dopamine neurons derived from human pluripotent stem cells.

In this study, researchers first performed a skin biopsy on the patient and harvested fibroblasts to generate lines of induced pluripotent stem cells (iPSCs), which were screened for pluripotent differentiation potential and to eliminate potentially harmful mutations.

They identified an iPSC clone capable of becoming midbrain dopaminergic progenitor cells (mDAPs) and guided its differentiation into 28-day mDAPs. The mDAP-derived neurons secreted dopamine and had electrophysiologic properties similar to substantia nigra dopaminergic midbrain neurons. The final cell product used for injection was then treated to eliminate undifferentiated iPSCs and ensure the absence of serotonergic cells that might contribute to graft-induced dyskinesia.

The patient had 4 million cells implanted in his left putamen and a similar injection on the right 6 months later. He was discharged after overnight observation for each procedure.

PET imaging at 24 months showed uptake bilaterally, greater on the right. A semi-quantitative change from baseline was reported as -4.0% to 13.5% on the right, and -4.8% to 9.8% on the left.

The researchers reported no adverse events. Over 24 months, the patient's PDQ-39 score (a quality of life measurement with a scale of 0 to 156; lower scores are better) improved from 62 from the time of his first injection to 2.

"Off" period MDS-UPDRS part III motor scores (on a scale of 0 to 132; higher scores are worse) were 43 at 4 weeks, and improved to 33 at 24 months. "On" motor scores were 38 at the time of first injection, and improved to 29 at 24 months.

Both the patient and raters knew about the intervention and this may have influenced motor and symptom scores, the researchers pointed out. A longer follow-up period may be needed to reach definitive conclusions about graft survival, they added.

"These results reflect the experience of one individual patient and a formal clinical trial will be required to determine if the therapy is effective," Schweitzer noted.

Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimers, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinsons, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

The research was supported by NIH grants, the philanthropic support of the Parkinson's Cell Therapy Research Fund at McLean Hospital and Massachusetts General Hospital, and the William and Elizabeth Sweet Endowed Professorship in Neuroscience at Harvard Medical School.

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Cell Therapy Shows Promise in Parkinson's - MedPage Today

Cell Biology

Synthetic Biology Could Lead to Clean Energy Using Light and Carbon… – Labiotech.eu

Researchers in Germany and France have combined synthetic biology with microfluidics to create artificial photosynthetic droplets, which could lead to the production of organic chemicals and clean fuels that is more efficient than nature can achieve alone.

In a study recently published in Science, the research team developed an automated way to produce artificial versions of chloroplasts, the center of photosynthesis in plants. These chloroplasts made within tiny droplets were capable of capturing carbon dioxide using light as much as 100 times more efficiently than previous synthetic biology approaches.

To make these artificial chloroplasts, members of the team at the Max Planck Institute for Terrestrial Microbiology in Germany coupled natural chloroplast membranes from spinach with a synthetic enzymatic module called the CETCH cycle. The CETCH cycle is made up of 18 biocatalysts designed to convert carbon dioxide more efficiently than plants.

These two components were combined in a cell-sized droplet using a microfluidic technology platform with the help of researchers based at the Centre de Recherch Paul Pascal, France.

Our work shows that you can realize alternative, autonomous photosynthetic systems at the microscale from individual biological parts and not by modifying cells through genetic engineering, said Tobias Erb, Professor at the Max Planck Institute for Terrestrial Microbiology, and one of the leaders of the study. This is a step forward towards creating biological systems that show life-like properties from the bottom up.

This synthetic biology technology is currently in its early stages, but the potential applications are limited only by what can be produced by the enzymatic pathway, and the contents of the droplet. For example, this could lead to breakthroughs in biofuel production, or large-scale manufacturing of chemicals like antibiotics.

Currently, this is a proof of principle. There are several challenges to be overcome before we can employ artificial chloroplasts in an industrial setup, Erb explained. Most importantly: stability and robustness of the individual components.

However, if we think about an immediate application, there is huge potential in using our artificial chloroplasts in high-throughput screening of enzymes and prototyping metabolic pathways.

As an example of the immediate commercial potential of the microfluidics platform, another one of the team leaders, Jean-Christophe Baret at the Centre de Recherch Paul Pascal, co-founded the startup Emulseo on the back of similar droplet technology in 2018.

This is not the first attempt at applying synthetic biology to photosynthesis. In a study published last year, the Earth-Life Science Institute in Tokyo constructed artificial cells using minimal components able to supply the energy to drive gene expression in a microcompartment.

They used this energy module to operate one single enzyme, but not a complex metabolic network with multiple reactions like in our case, said Erb. This did not allow the continuous fixation of carbon dioxide into multi-carbon compounds and was notably one to two orders of magnitude slower.

Synthetic biology companies have drawn major investor interest in recent years. One of the latest examples is a 6.4M Series A round raised by the Swedish startup Enginzyme to fund the development of cell-free technology to manufacture plastics and rubber more sustainably than with fossil fuels.

Images from Shutterstock and Synthetic Biology Max Planck Institute for Terrestrial Microbiology:Erb

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Synthetic Biology Could Lead to Clean Energy Using Light and Carbon... - Labiotech.eu

Cell Biology

Innate Pharma to Present New Efficacy Data for Monalizumab in Combination With Cetuximab in Head and Neck Cancer at the ASCO20 Virtual Scientific…

MARSEILLE, France, May 14, 2020 (GLOBE NEWSWIRE) -- Innate Pharma SA (Euronext Paris: IPH ISIN: FR0010331421; Nasdaq: IPHA) (Innate or the Company) today announced that it will present new data on its lead partnered asset, monalizumab, at the ASCO20 Virtual Scientific Program being held May 29-31, 2020. The presentation will highlight a Phase II expansion cohort investigating the combination of monalizumab and cetuximab in patients with recurrent or metastatic head and neck squamous cell cancer (R/M SCCHN) who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors (IO-pretreated). Monalizumab is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.

We are pleased to present additional data on the combination of monalizumab and cetuximab in head and neck cancer at this years ASCO Virtual Scientific Program. These data further strengthen the encouraging response rates previously reported in our head and neck clinical trial program,commented Pierre Dodion, Chief Medical Officer of Innate Pharma. While the study was not randomized, numerically, these data compare favorably with historical data reported for cetuximab alone or for immuno-oncology (IO) single agent in recurrent or metastatic head and neck cancer after one line of previous systemic therapy.

The poster discussion presentation (#177, abstract #6516), entitled Combination of Monalizumab and Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Cancer Previously Treated with Platinum-based Chemotherapy and PD-(L)1 Inhibitors, will be available on demand beginning at 8 a.m. ET on Friday, May 29 under the Head and Neck Cancer track.

Key Highlights from Phase II Expansion Study Cohort 2 (IO-pretreated)

As of March 2020, 40 platinum and IO-pretreated patients achieved an overall response rate (ORR) of 20%, which confirms the activity previously reported in the post-hoc analysis in the IO-pretreated subgroup in cohort 1 (ORR = 17%, n=18). Responses were observed in platinum-sensitive (3/21) and platinum-resistant patients (5/19), as well as in IO-sensitive (3/17) and IO-resistant patients (5/23), in patients exposed to IO as last previous therapy (5/34) and IO as earlier treatment (3/6).

The combination of monalizumab and cetuximab demonstrated a manageable safety profile, supporting continued investigation. No adverse events led to treatment discontinuation. Seventeen patients (42%) experienced grade 3-4 adverse events. Only one patient (2%) experienced a grade 3-4 adverse event considered related to monalizumab: peripheral sensory neuropathy and asthenia. No treatment-related deaths were reported.

The additional findings from this Phase II study are encouraging and validate the overall response rates previously observed with the combination of monalizumab and cetuximab for the treatment of recurrent or metastatic head and neck cancer, a malignancy with poor prognosis where novel, effective and tolerable therapies continue to be needed for this patient population,said Dr. Roger B. Cohen, Professor of Medicine at the Hospital of the University of Pennsylvania. The dual-targeting action exhibited by the combination of this NKG2A monoclonal antibody, monalizumab, when paired with cetuximab has the potential to provide greater antitumor activity than cetuximab alone, the current standard of care. We look forward to further studies evaluating this novel combination.

As previously disclosed, the start of the Phase III trial of monalizumab in combination with cetuximab in IO-pretreated patients suffering from R/M SCCHN, which will be conducted by AstraZeneca (LSE/STO/NYSE: AZN), is expected in 2020.

About the Monalizumab Phase II Trial

This trial is an open-label, Phase Ib/II study testing monalizumab in combination with cetuximab in patients with R/M SCCHN. The Phase II portion of the trial is comprised of three expansion cohorts:

The primary endpoint for the Phase II portion of the trial is objective response rate. Secondary endpoints for the Phase II portion of the trial include duration of response, progression-free survival and overall survival.

In expansion cohort 1, the combination of monalizumab and cetuximab demonstrated a manageable safety profile and a response rate of 27.5% (36% and 17% in IO-nave and IO-pretreated patients, respectively). Data were presented at the ESMO 2019 Congress. Expansion cohorts 2 and 3 are currently ongoing.

About Monalizumab:

Monalizumab is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.

NKG2A is an inhibitory checkpoint receptor for HLA-E. By expressing HLA-E, cancer cells can protect themselves from killing by NKG2A+ immune cells. HLA-E is frequently overexpressed in the cancer cells of many solid tumors and hematological malignancies. Monalizumab may re-establish a broad anti-tumor response mediated by NK and T cells, and may enhance the cytotoxic potential of other therapeutic antibodies.

AstraZeneca obtained full oncology rights to monalizumab in October 2018 through a co-development and commercialization agreement initiated in 2015. The ongoing Phase II development for monalizumab is focused on investigating monalizumab in various combination strategies in different malignancies.

About Cetuximab:

Cetuximab is an anti-EGFR monoclonal antibody. NK cells mediate cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) against SCCHN. Genetic and preclinical experiments suggest that ADCC can be enhanced by NK-stimulators.

The activity of cetuximab as a single agent in recurrent and/or metastatic SCCHN is limited, with a 12.6% overall response rate, a median time to progression of 2.3 months and a median overall survival of 5.8 months (Vermorken et al, JCO 2007).

About Innate Pharma:

Innate Pharma S.A. is a commercial stage oncology-focused biotech company dedicated to improving treatment and clinical outcomes for patients through therapeutic antibodies that harness the immune system to fight cancer.

Innate Pharmas commercial-stage product, Lumoxiti, in-licensed from AstraZeneca in the US, EU and Switzerland, was approved by the FDA in September 2018. Lumoxiti is a first-in class specialty oncology product for hairy cell leukemia. Innate Pharmas broad pipeline of antibodies includes several potentially first-in-class clinical and preclinical candidates in cancers with high unmet medical need.

Innate has been a pioneer in the understanding of natural killer cell biology and has expanded its expertise in the tumor microenvironment and tumor-antigens, as well as antibody engineering. This innovative approach has resulted in a diversified proprietary portfolio and major alliances with leaders in the biopharmaceutical industry including Bristol-Myers Squibb, Novo Nordisk A/S, Sanofi, and a multi-products collaboration with AstraZeneca.

Based in Marseille, France, Innate Pharma is listed on Euronext Paris and Nasdaq in the US.

Learn more about Innate Pharma at http://www.innate-pharma.com

Information about Innate Pharma shares:

Disclaimer:

This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995.The use of certain words, including believe, potential, expect and will and similar expressions, is intended to identify forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Companys commercialization efforts, the Companys continued ability to raise capital to fund its development and the overall impact of the COVID-19 outbreak on the global healthcare system as well as the Companys business, financial condition and results of operations. For an additional discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (AMF), which is available on the AMF website http://www.amf-france.org or on Innate Pharmas website, and public filings and reports filed with the U.S. Securities and Exchange Commission (SEC), including the Companys Annual Report on Form 20-F for the year ended December 31, 2019, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company.

This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.

For additional information, please contact:

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Innate Pharma to Present New Efficacy Data for Monalizumab in Combination With Cetuximab in Head and Neck Cancer at the ASCO20 Virtual Scientific...

Cell Biology

High Content Screening Market to Witness Growth Acceleration During 2017-2025 – Cole of Duty

Global High Content Screening Market: Snapshot

High-content screening technologies have the ability of simultaneously studying multiple parameters in complex biological systems, a factor that is also one of the key factors driving the global market for high-content screening. Considering the steady rise in the prevalence of various genetic disorders and neurological diseases, the demand for effective screening methods and techniques has significantly increased in the past few years. This scenario has had a positive impact on the global high-content screening market. However, owing to factors such as stringent regulatory framework in many countries, high cost of sophisticated infrastructure, dearth of skilled and trained professionals, and low R&D yields the growth prospects of the market are impaired to a certain extent.

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Some of the most popular high-content screening products include flow cytometers, cell imaging systems, consumables, and software. Cell imaging systems have been witnessing strong demand in the recent past, thanks to ongoing advancement in automation and instrumentation techniques. Key end users of high-content screening are industries such as biotechnology and pharmaceutical, government organizations, educational institutions, and contract research organizations (CROs). High-content screening is commonly used by biotechnology and pharmaceutical companies for various clinical and preclinical studies.

High-content screening finds application in target identification and validation, primary and secondary screening, compound profiling, and toxicity studies. High-content screening is mostly used in primary and secondary screening owing to its usage in assessing bioavailability and in qualitative assays. Geographically, North America holds a significant share in the high-content screening market, fueled by a strong regional economy, the presence of sophisticated research and healthcare facilities, and increased focus on overall health and wellbeing.

Global High Content Screening Market: Overview

High-content screening (HCS) refers to a technique used in biological research and drug discovery to discover substances such as peptides, small molecules, or RNAi that change the phenotype of a cell as desired. Phenotypic changes may include increase or decrease in the production of cellular components such as protein and/or alterations in the visual appearance of the cell.

High-content screening merges the molecular tools of cell biology with automated robotic handling, high-resolution microscopy, and automated analysis.

Global High Content Screening Market: Key Trends

The high-content screening market is driven by increasing funding and venture capital investments for cellular research, technological developments in HCS solutions, and cost containment in pharma R&D. However, factors such as high cost of HCS equipment and lack of expert and skilled personnel for operation of equipment are posing a challenge to the markets growth. In addition, inadequate research infrastructure and insufficient funding for R&D in emerging nations is limiting this markets growth.

The high-content screening market is segmented in terms of product, application, end user, and region. In terms of product, instruments, software, consumables, services, and accessories are the segments of this market. The segment of instrument held the leading share of the market in the recent past. The cell imaging and analysis segment held the leading share of the instrument segment of the HCS market. The instrument segment holds the leading share due to advances in instrumentation and automation techniques.

On the basis of application, target identification and validation, toxicity studies, primary and secondary screening, compound profiling, and others are the segments of the HCS market. The segment of primary and secondary screening dominated the market in the recent past. The dominance of this segment is due to its large-scale usage in qualitative assays for lead specificity, evaluation of bioavailability, and exclusion of compounds with unintended modes of action.

In terms of end user, the HCS market is segmented into academic and government institutes, pharmaceutical and biotechnology companies, and contract research organizations. The segment of pharmaceutical and biotechnology companies held the leading share of the global HCS market in the recent past. The dominance of this segment is owing to the extensive usage of HCS in preclinical and clinical studies in the biotechnology and pharmaceutical industries.

Global High Content Screening Market: Market Potential

Beyond its conventional application in biological resaerch, high-content screening is being used in studying fat accumulation in cells. Researchers at the Department of Environmental Science at University of Georgia College of Public Health carried out studies to determine how exposure to phthalates in the form of nail polish or soap is related to the amount of fat stored in our bodies.

High-content screening employs image processing algorithms and computer machine language to measure multiple parameters objectively in no time.

Global High Content Screening Market: Regional Outlook

North America is the leading market for high-content screening trailed by the regions of Europe, Asia Pacific, Latin America, and the Middle East and Africa. High research and development expenditures, government support for research initiatives, and the presence of leading lifescience market players are attributed to the dominance of North America high content screening market.

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Global High Content Screening Market: Competitive Landscape

The key players in the global high content screening market includeGE Healthcare, PerkinElmer Inc., Becton, Dickinson and Company, Danaher Corporation, and Thermo Fisher Scientific Inc. Some other players in the market include BioTek Instruments Inc., Tecan Group Ltd., Merck Millipore, Bio-rad Laboratories Inc, and Yokogawa Electric Corporation.

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High Content Screening Market to Witness Growth Acceleration During 2017-2025 - Cole of Duty

Physiology

Neuroscientists Think They’ve Found a Previously Unknown Form of Neural Communication – ScienceAlert

Scientists think they've identified a previously unknown form of neural communication that self-propagates across brain tissue, and can leap wirelessly from neurons in one section of brain tissue to another even if they've been surgically severed.

The discovery, made in February 2019, offers some radical new insights about the way neurons might be talking to one another, via a mysterious process unrelated to conventionally understood mechanisms, such assynaptic transmission, axonal transport, and gap junction connections.

"We don't know yet the 'So what?' part of this discovery entirely," saidneural and biomedical engineer Dominique Durand from Case Western Reserve University last year.

"But we do know that this seems to be an entirely new form of communication in the brain, so we are very excited about this."

Before this, scientists already knew there was more to neural communication than the above-mentioned connections that have been studied in detail, such as synaptic transmission.

For example, researchers have been aware for decades that the brain exhibits slow waves of neural oscillations whose purpose we don't understand, but which appear in the cortex and hippocampus when we sleep, and so are hypothesised to play a part in memory consolidation.

"The functional relevance of this input and outputdecoupled slow network rhythm remains a mystery," explained neuroscientist Clayton Dickinson from the University of Alberta, who wasn't involved in the new research but has discussed it in a perspective article.

"But [it's] one that will probably be solved by an elucidation of both the cellular and the intercellular mechanisms giving rise to it in the first place."

To that end, Durand and his team investigated slow periodic activity in vitro, studying the brain waves in hippocampal slices extracted from decapitated mice.

What they found was that slow periodic activity can generate electric fields which in turn activate neighbouring cells, constituting a form of neural communication without chemical synaptic transmission or gap junctions.

"We've known about these waves for a long time, but no one knows their exact function and no one believed they could spontaneously propagate," Durand said.

"I've been studying the hippocampus, itself just one small part of the brain, for 40 years and it keeps surprising me."

This neural activity can actually be modulated - strengthened or blocked - by applying weak electrical fields and could be an analogue form of another cell communication method, called ephaptic coupling.

The team's most radical finding was that these electrical fields can activate neurons through a complete gap in severed brain tissue, when the two pieces remain in close physical proximity.

"To ensure that the slice was completely cut, the two pieces of tissue were separated and then rejoined while a clear gap was observed under the surgical microscope," the authors explained in their paper.

"The slow hippocampal periodic activity could indeed generate an event on the other side of a complete cut through the whole slice."

If you think that sounds freaky, you're not the only one. The review committee at The Journal of Physiology in which the research has been published insisted the experiments be completed again before agreeing to print the study.

Durand et al. dutifully complied, but sound pretty understanding of the cautiousness, all things considered, given the unprecedented weirdness of the observation they're reporting.

"It was a jaw-dropping moment," Durand said, "for us and for every scientist we told about this so far."

"But every experiment we've done since to test it has confirmed it so far."

It'll take a lot more research to figure out if this bizarre form of neural communication is taking place in human brains let alone decoding what exact function it performs but for now, we've got new science that's shocking in all kinds of ways, as Dickson adroitly observes.

"While it remains to be seen if the [findings] are relevant to spontaneous slow rhythms that occur in both cortical and hippocampal tissue in situ during sleep and sleeplike states," Dickson wrote, "they should probably (and quite literally) electrify the field."

The findings are reported in The Journal of Physiology.

A version of this article was first published in February 2019.

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Neuroscientists Think They've Found a Previously Unknown Form of Neural Communication - ScienceAlert

Physiology

Scientists generate millions of mature human cells, far more than have ever been produced – UB Now: News and views for UB faculty and staff -…

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

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

The research was published on May 13 in Science Advances.

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

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

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

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

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

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

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

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

We know that up to 4% of the total number of cells in the mouse embryo were human cells, Feng says. This is a low estimate because we cannot quantify the large amount of human red blood cells generated in the mouse embryo.

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

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

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

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

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

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

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

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

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

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Scientists generate millions of mature human cells, far more than have ever been produced - UB Now: News and views for UB faculty and staff -...

Physiology

Pastor Vern Saile at Northgate church presents addiction recovery workshop based on book ‘Addiction and Grace: Love and Spirituality in the Healing of…

Pastor Vern Saile, of Northgate Free Methodist Church in Batavia,will present aworkshop for individuals in recovery and their friends, family and allies based on the book "Addiction and Grace:Love and Spirituality in the Healing of Addiction."

It will take place at 1 p.m. on Wednesday,May 20, via Zoom. Register here.

The intention is to providing safe, sober health and wellness activities geared towardindividuals in recovery from a substance use disorder and their families.

Any questions, please call (585)815-5248.

About the Book

"Addiction and Grace:Love and Spirituality in the Healing of Addiction"isself-help Christian literature published in 1988 by Gerald May and now considered a classic in the field ofpsychology and physiology of addiction.

It offers an inspiring and hope-filled vision for those who desire to explore the mystery of who and what they really are.

May examines the "processes of attachment" that lead to addiction and describes the relationship betweenaddiction and spiritual awareness. He also details the various addictions from which we can suffer, not only to substances like alcohol and drugs, but to work, sex, performance, responsibility, and intimacy.

Drawing on his experience as a psychiatrist working with the chemically dependent, May emphasizes that addiction represents an attempt to assert complete control over our lives. "Addiction and Grace"is a compassionate and wise treatment of a topic of major concern in these most addictive of times, one that can provide a critical yet hopeful guide to a place of freedom based on contemplative spirituality.

The book can be accessed in Hoopla through the Richmond Memorial Library, andyou'll need a library card and pin number to do so.

Another resource for electronic content is the New York Public Library. Any New York State resident can access their digital content by creating an account on their Simply E app.

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Pastor Vern Saile at Northgate church presents addiction recovery workshop based on book 'Addiction and Grace: Love and Spirituality in the Healing of...

Physiology

What We Are Reading Today: Sunny Days – Arab News

Authors:William H. Karasov and Carlos Martinez Del Rio

Unlocking the puzzle of how animals behave and how they interact with their environments is impossible without understanding the physiological processes that determine their use of food resources. but long overdue is a user-friendly introduction to the subject that systematically bridges the gap between physiology and ecology.

Ecologistsfor whom such knowledge can help clarify the consequences of global climate change, the biodiversity crisis, and pollutionoften find themselves wading through an unwieldy, technically top- heavy literature.

Here, WilliamKarasov and Carlos martinez del rio present the first accessible and authoritative one-volume overview of the physiological and biochemical principles that shape how animals procure energy and nutrients and free themselves of toxinsand how this relates to broader ecological phenomena.

After introducing primary concepts, the authors review the chemical ecology of food, and then discuss how animals digest and process food. their broad view includes symbioses and extends even to ecosystem phenomena such as ecological stochiometry and toxicant biomagnification.

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What We Are Reading Today: Sunny Days - Arab News

Physiology

A Special Issue Published on the Use of Symbiotic Bacteria to Enhance the Effectiveness and Efficiency of the Sterile Insect Technique – International…

Insects are, in many ways, the dominant multicellular lifeform on land. They are successful across multiple ecosystems and maintain intricate and complex interactions with the other organisms in their habitats. Many of the interactions between insects and plants, and insects and vertebrates have been extensively studied, but the associations between insects and microorganisms, while pervasive and of paramount ecological and evolutionary importance, are only gradually being understood. Insects depend on symbiotic associations with a variety of microorganisms, which affect many aspects of the hosts biology and physiology including their nutrition, mating behaviours, immunities and reproductive success.

Tephritid fruit flies are no exception and maintain intricate interactions with multiple micro-organisms. It is these complex relationships that are being explored by the IAEA, in partnership with the Food and Agriculture Organization of the United Nations (FAO), to help develop sustainable methods to reduce the spread of these destructive insect species.

The sterile insect technique (SIT) has been effectively deployed to reduce fruit fly populations for over 60 years. SIT is a species-specific and environment-friendly technology which is often used as a component of area-wide integrated pest management (AW-IPM) programmes. Experience has shown that the efficiency of SIT can be hampered by the quality of the mass-reared and sterilised male insects, that must remain competitive with wild males on release, and the cost effectiveness of mass-rearing the billions of insects required for a sustainable operational project. Research efforts focussed on ways to improve these processes have recognised the symbiotic relationships between tephritids and particular species of bacteria as potential targets for improving the quality of the sterilized males and reducing costs of production,

This area of research has been further explored in an IAEA Coordinated Research Project (CRP) on the Use of Symbiotic Bacteria to Reduce Mass-Rearing Costs and Increase Mating Success in Selected Fruit Pests in Support of SIT Application. The CRP was initiated in 2012 under the auspices of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture with four main objectives: To determine the effect of radiation on the symbiotic communities in target species; to develop methods of using beneficial bacteria to replace costly ingredients in larval diets; to explore the use of symbionts as probiotics provided to adult sterile males before their release to significantly improve their performance; and, to harness symbiotic microorganisms as reproductive manipulators and determine their ability to suppress target populations.

The CRP has illustrated the utility of harnessing symbiotic associations towards the reproductive manipulation and suppression of target populations. Specifically, the effect of Wolbachia infection on Ceratitis capitata has been studied, revealing the practical potential for introducing this bacterium into mass reared and wild populations. In addition, the bacteria associated with most of the tephritid pests have been identified for the first time and the role of bacteria in mass rearing facilities has been elucidated for several key pest species.

The research studied and documented the effect of sterilizing radiation on the microbiota of several mass-reared species. The use of symbionts as probiotic supplements to improve larval rearing and adult quality was also studied in several species of Anastrepha, Bactrocera, and Ceratitis capitata.

All the major achievements of the CRP were published in a dedicated Special Issue, with 19 papers, in a Cross-Journal Supplement of BMC Microbiology and BMC Biotechnology. This Special Issue provides an important contribution to our knowledge on tephritid fruit flies and their symbionts, and the related potential for enhancing applied SIT technology in the field.

In addition, an online tool for calculating distribution of operational taxonomic units generated from new generation sequencing approaches has been developed. And a compilation of all the microorganisms identified before and during the CRP was produced and included in the final report of the CRP.

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A Special Issue Published on the Use of Symbiotic Bacteria to Enhance the Effectiveness and Efficiency of the Sterile Insect Technique - International...

Physiology

Father and son celebrate marathon Guinness world record – AW – Athletics Weekly

Two Northern Ireland runners arecelebrating becomingGuinness world record-holders after receiving confirmation that their fastest parent and child attempt at theFrankfurt Marathon last year has been ratified, writesMalcolm McCausland.

Tommy and Eoin Hughes registered an aggregate time of 4:59:22 in Germany in October, with father Tommy running2:27:52 at the age of 59 and his 34-year-old son Eoin setting a PB of 2:31:20.

That took two minutes and 50 seconds off the previous record mark set at the 2014 London Marathon by Graham and Ben Green from Warrington.

Another record attempt byTommy and Eoin at theBelfast Half Marathon last September saw theCounty Derry men comeup 20 seconds short of the combined 2:20:33 goal, despite Eoin finishing second overall in 68:30.

Eoin entered the veteran ranks in January this year while Tommy turned 60 the same month and they had hoped to compete in the World Masters Championships in Canada in August before it became one of the many fixtures cancelled as a consequence of the Covid-19 pandemic.

A recent study of their Frankfurt performance, published in the Journal of Applied Physiology, has thrown up some interesting data. The study analysed the divergent physiologies and athletic histories of the father and son. Not surprisingly, it raised intriguing questions about the roles of genetics, environment and training in marathon success and it highlighted that one persons route to a fast time could be quite different from anothers, even in the case of a father and son.

The new study followed an earlier screening of Tommy following his single-age world record of 2:30:15 in Rotterdam in April 2019. That performance caught the attention of researchers at a number of institutions who study elite athletes, including the Inserm research organisation in France.

They promptly invited Tommy to their lab for a detailed examination into what made him so outstanding for his age. They were already aware that in his prime he had represented Ireland in the marathon at the Barcelona Olympics in 1992, finishing 72nd in 2:32:55, five minutes slower than he ran in Frankfurt. He then quit running for 16 years before signing up for the 2008 Belfast Marathon where, with little training, he finished sixth.

The researchers found that his aerobic capacity, even at 59, remained exceptionally high despite years without running. The scientists put this down to his training regime that sees him log at least 100 miles every week by running twice a day and using local 5km and 10km races as speed work.

During the testing, Tommy mentioned that he and his son Eoin were planning to enter the Frankfurt Marathon, with the target of breaking the Guinness world record for fastest parent and child aggregate marathon time. The researchers saw that there was a unique opportunity to carry out a compare and contrast exercise into the physiological similarities and differences of the two runners.

So, they invited both of them to the lab and completed more tests, including measuring Eoins maximum aerobic capacity, which was found to be similar to that of his father. They tracked each mans oxygen uptake (VO2) at various race paces so that the researchers could gauge how much effort they were putting in at any given time.

Then they waited for the marathon which, although it was a success in that they set a new world mark, produced divergent results for the father and son. Tommy finished almost four minutes ahead of his son with his pace hardly varying from start to finish. Eoin, on the other hand, went off hard at the start but then fell back, finishing the second half of the race about 6 per cent slower than the first 13 miles.

Eoins workload was also slightly lighter than that of his father, his average pace represented about 85 per cent of his maximal endurance capacity, meaning he was pushing himself hard. But his fathers average pace hovered at around 90 per cent of his maximal capacity, suggesting a greater tolerance to discomfort.

So what can you take from the study if you want to improve your running? The first thing is that there are more approaches to training than one. Nevertheless, high mileage and frequent races over shorter distances seems to work. The second is to choose your parents carefully. Eoin Hughes certainly did that.

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Father and son celebrate marathon Guinness world record - AW - Athletics Weekly