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Physiology

Fish oil may be an effective treatment for depression, study shows – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Jun 11 2020

A study published in Molecular Psychiatry shows that patient-derived adult stem cells can be used to model major depressive disorder and test how a patient may respond to medication.

Using stem cells from adults with a clinical diagnosis of depression, the University of Illinois at Chicago researchers who conducted the study also found that fish oil, when tested in the model, created an antidepressant response.

UIC's Mark Rasenick, principal investigator of the study, says that the research provides a number of novel findings that can help scientists better understand how the brain works and why some people respond to drug treatment for depression, while others experience limited benefits from antidepressant medication.

It was also exciting to find scientific evidence that fish oil -- an easy-to-get, natural product -- may be an effective treatment for depression."

Mark Rasenick, UIC distinguished professor of physiology and biophysics and psychiatry at the College of Medicine

Major depressive disorder, or depression, is the most common psychiatric disorder. Around one in six individuals will experience at least one depressive episode in their lifetime. However, antidepressant treatment fails in about one-third of patients.

In the study, the UIC researchers used skin cells from adults with depression that were converted into stem cells at Massachusetts General Hospital and then directed those stem cells to develop into nerve cells. The skin biopsies were taken from two types of patients: people who previously responded to antidepressant treatment and people who have previously been resistant to antidepressants.

When fish oil was tested, the models from treatment-sensitive and treatment-resistant patients both responded.

Rasenick says the response was similar to that seen from prescription antidepressants, but it was produced through a different mechanism.

"We saw that fish oil was acting, in part, on glial cells, not neurons," said Rasenick, who is also a research career scientist at Jesse Brown VA Medical Center and president and chief scientific officer at Pax Neuroscience, a UIC startup company. "For many years, scientists have paid scant attention to glia -- a type of brain cell that surrounds neurons -- but there is increasing evidence that glia may play a role in depression. Our study suggests that glia may also be important for antidepressant action.

"Our study also showed that a stem cell model can be used to study response to treatment and that fish oil as a treatment, or companion to treatment, for depression warrants further investigation," Rasenick said.

Source:

Journal reference:

Yu, J., et al. (2020) N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells. Molecular Psychiatry. doi.org/10.1038/s41380-020-0786-5.

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Fish oil may be an effective treatment for depression, study shows - News-Medical.Net

Physiology

Treatment with vitamin A analog improves visual function in diabetic mice – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Jun 11 2020

Diabetic retinopathy is a common complication of diabetes and a leading cause of blindness among the working-age population. A new study in the American Journal of Pathology reports that visual function in diabetic mice was significantly improved after treatment with a single dose of visual chromophore 9-cis-retinal, a vitamin A analog that can form a visual pigment in the retina cells, thereby producing a light sensitive element of the retina.

"In an earlier study we found that diabetes causes vitamin A deficiency in the retina, which results in deterioration of vision, even before any vascular changes can be seen. That finding led to the assumption that early changes in vision in diabetes are probably caused by vitamin A deficiency in the retina," explained lead investigator Gennadiy Moiseyev, PhD, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

In the current study investigators hypothesized that treating diabetic mice with 11-cis-retinal could rescue visual function. They investigated its effect in Akita mice, a genetic model of type 1 diabetes, by measuring electroretinogram (ERG) responses, retinal oxidative stress, and neuronal apoptosis (cell death). ERG was performed on two groups of three-month-old Akita mice and one group of non-diabetic control mice matched for age and genetic background. One group of Akita mice was treated with 9-cis-retinal and the other with a vehicle solution. Average blood glucose concentrations and body weights of the mice were measured monthly during the study. Akita mice showed high glucose concentrations throughout the study. ERG recordings and rhodopsin assay were performed two hours after 9-cis-retinal injection, whereas assessment of cell death by ELISA and TUNEL assay were both performed 24 hours after the injection.

Results showed that the visual function in diabetic mice improved significantly after treatment with the single dose of 9-cis-retinal. In addition, researchers reported that the treatment reduced oxidative stress in the retina, decreased retina cell death and retina degeneration, and improved visual function.

This work supports our novel hypothesis that diabetes-induced disturbance of the vitamin A metabolism in the eye is responsible for reduced visual function in early stages of diabetic retinopathy. Currently, there is no available therapy to prevent the development of the retinal complication in patients suffering from diabetes. This study suggests that the delivery of visual chromophore to the diabetic eye may represent a potential therapeutic strategy for the early stages of diabetic retinopathy to prevent vision loss in patients with diabetes."

Gennadiy Moiseyev, Ph.D., Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

Traditionally, diabetic retinopathy was considered a disease caused by the pathology of blood vessels in the retina, whereby light-sensitive tissue at the back of the eye (fundus) becomes damaged. Patients with diabetes often experience functional deficits in dark adaptation, contrast sensitivity, and color perception before any microvascular pathologies are detected on the eye fundus. However, recent data underscore the importance of vitamin A for normal visual function. It serves as a precursor for light-sensitive 11-cis-retinal, the chromophore of visual pigments that can produce a light-sensitive protein in the retina.

Source:

Journal reference:

Malechka, V.V., et al. (2020) The Single Administration of a Chromophore Alleviates Neural Defects in Diabetic Retinopathy. American Journal of Pathology. doi.org/10.1016/j.ajpath.2020.03.009.

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Treatment with vitamin A analog improves visual function in diabetic mice - News-Medical.Net

Physiology

Interferons being tested for COVID-19 may increase susceptibility to bacterial infections – News-Medical.Net

Two separate studies in mice suggest that a class of interferons being evaluated in clinical trials as a therapy for COVID-19 may increase susceptibility to bacterial infections, depending on how long patients are exposed to it, and when they receive it.

The results suggest that the timing and duration of this treatment may need to be carefully selected, as trials move forward, to avoid deleterious effects.

Interferons (IFNs) help fight viral infections in the lung. In particular, type III IFNs (IFN- ) have attracted much attention, because, unlike other IFNs, they show antiviral effects without driving inflammatory responses.

Already, a clinical trial exploring the use of IFN- against SARS-CoV-2 has begun. Despite interest in the use of IFN- to treat viral infections, the long-term effects IFN- on lung physiology - and in possibly impairing bacterial control by the lung epithelium - remain largely overlooked.

Here, to directly evaluate whether SARS-CoV-2 induces IFNs, Achille Broggi and colleagues tested swabs of COVID-19 patients and healthy controls, as well as the bronchoalveolar lavage fluid of severe SARS-CoV-2-positive patients.

In the latter group, levels of type I and III interferons were high, the report. Next, to better understand the effects of IFN- signaling in the lung, Broggi, and colleagues studied the lungs of mice exposed to synthetic viral RNA.

In these animals, IFN- secreted by dendritic cells caused damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. In a separate study using a mouse model to investigate the dynamics of influenza virus infection, Jack Major et al. report that IFN signaling (especially that of IFN-) hampered lung repair.

This pair of papers suggests that the timing and duration of IFN- exposure are critical parameters underlying the success or failure of antiviral therapeutics, the authors say.

[O]ur data enjoin clinicians to carefully analyze the duration of IFN- administration and to take into consideration the severity of the disease when IFN- is used as a therapeutic agent against lung viral infections,"

Broggi and Colleagues, American Association for the Advancement of Science

"Optimal protection would be achieved by strong induction of IFN-stimulated genes early during infection to curb viral replication, followed by timely down-regulation of IFN responses, enabling efficient lung epithelial repair," says Major et al.

Source:

Journal reference:

Broggi, A., et al. (2020) Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science. doi.org/10.1126/science.abc3545.

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Interferons being tested for COVID-19 may increase susceptibility to bacterial infections - News-Medical.Net

Physiology

‘Tsunami’ of distress could hit with healthcare workers at particular risk – Cork Beo

Ireland's government needs to prioritise mental health as a "tsunami of psychological distress" could be on the way.

That is the warning coming from the Irish Medical Journal after a leading doctor took a look at the potential impact of the pandemic's aftermath.

Dr Joe Jordan from The Royal College of Surgeons Ireland looked at the similar SARS and MERS epidemics and wrote that the country needs to learn from them and pump funding into services so they're ready for what could come next.

Although it's not clear what the Covid-19 aftermath will look like, he says looking at SARS and MERS might give some clues.

In one study of SARS survivors, 44 percent developed PTSD at some stage over four years of monitoring.

He said that the effect of the epidemic in Hong King saw "reduced subjective levels of wellbeing" amongst people with characteristics including "unemployment, low education, and chronic illness".

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There was also a reported psychological impact on people due to quarantine and that it can be "wide-ranging, substantial, long-lasting, and lead to high levels of stress and psychological distress".

Dr Jordan warned that healthcare workers who were involved in the care of SARS patients suffered higher levels of burnout, physiological distress, and PTSD compared to those who weren't involved.

Similarly, MERS patients saw anxiety symptoms and "anger" for four to six months after being released from isolation.

Although they say the long-term impact of coronavirus is unknown, "particular attention" needs to be given to healthcare workers over the coming years.

He wrote that "robust community and hospital based mental health services" will need to be available along with online physiology services.

"Timely and adequate access will need to be a priority for healthcare systems both during and after the pandemic

"Robust community and hospital based mental health services, in addition to online psychological supports will be required.

"We propose healthcare workers, the elderly, patients with active or psychiatric histories and the homeless sector to be at particular risk of psychological distress and targeted interventions in these groups will be needed.

"We believe exercise therapies will play a key role in the rehabilitation of Covid-19 survivors."

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'Tsunami' of distress could hit with healthcare workers at particular risk - Cork Beo

Physiology

Oblique Therapeutics AB has Identified a Potentially Important Epitope for Generation of SARS-CoV-2 antibodies – BioSpace

GOTHENBURG, Sweden, June 11, 2020 /PRNewswire/ -- Using the AbiprotTMantibody discovery platform, a team of researchers has identified a potentially important epitope in SARS-CoV-2 that may facilitate generation of neutralizing antibodies to treat Covid-19 patients. The epitope is part of the spike protein which mediates the virus entry into cells. It was identified in a pilot study using virus material from the nasal swab of a Covid-19 patient.

This early proof-of-concept result is very encouraging and has prompted Oblique Therapeutics and their collaborators to continue the work to map additional epitopes on the SARS-CoV-2 virion surface. The company will make all results freely available for vaccine and antibody-developing Pharma and Biotech companies.

Dr. Sreesha P Srinivasa, Ph.D., Senior Vice President, Translational R&D, Oblique Therapeutics, commented "As an innovation-driven biotechnology company and a responsible member of the scientific community, Oblique Therapeutic is committed to contribute towards a long lasting solution to the Covid-19 pandemic. In this effort, we decided to employ our unique AbiprotTMplatform to interrogate the surface of SARS-CoV-2 virion for identification of novel epitopes that could potentially be accessible to antibodies. We are very encouraged by the results from a pilot experiment with limited virus material that has led to the identification of a potential epitope in the spike protein. We are motivated to continue this effort and identify more epitopes on the surface of the virion. We will make results from this collaborative project freely available to the scientific community upon request"

Collaboration

The research was conducted by Oblique Therapeutics AB in collaboration with scientists from the Department of Clinical Microbiology at Sahlgrenska University Hospital and The Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and the Department of Physiology and Pharmacology at Karolinska Institutet, Solna, Sweden with support from Nanoxis Consulting AB, Gothenburg, Sweden.

About Abiprot TM

Oblique Therapeutics has developed a unique, proprietary methodology to identify epitopes on protein targets that have previously proven difficult to address with antibodies. AbiprotTM can identify high-affinity antibody binding sites in any given protein with single amino acid resolution. It is based on using a tailored molecular reporter system and proteomics. The platform yields detailed sequence and structure information for epitope identification and development. Oblique is applying this technology for discovery of selective antibody therapeutics targeting, for example, KRAS for the treatment of cancers and several ion channel targets to treat pain.

About Oblique Therapeutics

Oblique Therapeutics is a privately held Swedish biotech developing innovative new medicines for severe diseases with a large unmet medical need focusing on pain and advanced cancer. The company uses AbiprotTM, an in-house-invented, next-generation antibody platform that can generate antibodies with programmed function against the full human proteome. The portfolio comprises three in-house programs - two antibody candidates: aKRAS in advanced cancer, aTRPA1 in pain; and the small molecule OT-1096 in triple-negative breast cancer. In addition, there are three antibodies programs in collaboration with pharma. Oblique Therapeutics makes medicines that matter to patients.https://obliquet.com/

For more information, please contact:Dr. Sreesha P SrinivasaPh.D.Senior Vice PresidentTranslational R&D Oblique TherapeuticsEmail: Sreesh@obliquet.com

For more information in the Scandinavian countries, please contact:Prof. Owe OrwarCEOOblique TherapeuticsEmail: owe@obliquet.com

This information was brought to you by Cision http://news.cision.com

https://news.cision.com/oblique-therapeutics-ab/r/press-release-june-11--2020,c3132564

View original content:http://www.prnewswire.com/news-releases/oblique-therapeutics-ab-has-identified-a-potentially-important-epitope-for-generation-of-sars-cov-2-antibodies-301074513.html

SOURCE Oblique Therapeutics AB

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Oblique Therapeutics AB has Identified a Potentially Important Epitope for Generation of SARS-CoV-2 antibodies - BioSpace

Physiology

Scientists and economists from Honoris United Universities in global selection for Lindau Nobel Laureate Meetings – How we made it in Africa

MoU signing with the Council and Foundation for the Lindau Nobel Laureate Meetings and Honoris United Universities in 2019.

Press Office:Honoris United Universities

The selection of eight young scientists and economists from the network represents the strengthening of ties between Honoris and Lindau Nobel Laureate Meetings in promoting research in Africa

Honoris United Universities, the first and largest pan-African network of private higher education institutions, today announced that five science and three economics students from across the network have been selected amongst 1,034 young scientists and economists from over 100 countries to participate in the 70th Lindau Nobel Laureate Meeting and the 7th Lindau Meeting on Economic Sciences in 2021.

The Meetings, which will bring together young scientists and economists alongside Nobel Laureates in physics, chemistry, physiology and medicine, as well as economic sciences from across the world, form part of a partnership established between Honoris United Universities and Lindau Nobel Laureate Meetings last year, to increase participation and research in the natural sciences and in economics across Africa.

The selected Honoris scientists and economists successfully completed a multi-stage selection process, which involved 144 academic partners of the Lindau Nobel Laureate Meetings and German universities in the field of economics including the Wirtschafts und Sozialwissenschaftliche Fakulttentag (WISOFT Association of Economics and Social Sciences Faculties). The successful students were selected from leading African universities within the Honoris network including Universit Mundiapolis in Morocco, Universit Centrale in Tunisia, and REGENT Business School in South Africa.

CEO of Honoris United Universities, Luis Lopez said, As an Academic Partner to the Lindau Nobel Laureate Meetings, we are extremely proud to support and promote the development of world-class African talent as evidenced by our exemplary students, selected to participate in this extremely competitive and prestigious event. They are a testament to the learning being undertaken in our institutions and to the faculty members focused on student success and institutional research. This is a superb opportunity for our students to represent research in economics and in natural sciences from Africa as part of a landmark global event.

Due to the Covid-19 pandemic, the onsite interdisciplinary 70th Lindau Nobel Laureate Meeting and the Lindau Meeting on Economic Sciences, originally planned for 2020, are postponed to 2021. The 70th Lindau Nobel Laureate Meeting will now take place from 27 June 2 July 2021 and 7th Lindau Meeting on Economic Sciences will take place from 24 28 August 2021.

For 2020, the Lindau Nobel Laureate Meetings will be introducing two exciting online forums, bringing together some 40 Nobel Laureates, Lindau Alumni and the selected young scientists and economists from across the world to exchange knowledge, ideas and questions via a series of interactive and high level activities.

This will include the Online Sciathon 2020 2020 (19 21 June), a 48-hour hackathon-style event involving Lindau Alumni and the young scientists and economists on topics relating to global, sustainable and cooperative open science, climate change and capitalism after Covid-19.

The Sciathon will be followed by the Online Science Days 2020 (28 June 1 July) for Nobel Laureates, Lindau Alumni and the young scientists and economists invited for 2021. They will participate in debates, conversations, talks and next gen science sessions with each comprising live Q&A sessions. Invited guests as well as media representatives will be able to follow the whole programme online and interested parties may register for access, including future young scientists or economists, prospective academic partners or benefactors.

Since its foundation in 1951, around 400 Nobel Laureates have attended the Lindau Nobel Laureate Meetings, held each year as a forum for scientists of different generations, cultures and disciplines to convene and exchange knowledge, ideas and experiences. The theme is alternated each year and is based on the three natural science Nobel Prize disciplines physics, chemistry and physiology and medicine. An interdisciplinary meeting based around all three natural sciences is held every five years and a Lindau Meeting on economic sciences is held every three years.

The Lindau Nobel Laureate Meetings foster the exchange among scientists of different generations, cultures, and disciplines. Once every year, around 30-40 Nobel Laureates convene in Lindau to meet the next generation of leading scientists: 600 undergraduates, PhD students, and post-doc researchers from all over the world. The Lindau Meetings cooperate with more than 200 of the most renowned science and research institutions worldwide to identify the most qualified participants. The scientific programme of each Lindau Meeting is based on the principle of dialogue. The different sessions lectures, Agora Talks, masterclasses, and panel discussions are designed to activate the exchange of knowledge, ideas, and experience between and among Nobel Laureates and young scientists.

http://www.honoris.net

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Scientists and economists from Honoris United Universities in global selection for Lindau Nobel Laureate Meetings - How we made it in Africa

Cell Biology

Growth of the Life Science Tools Market has been on the back of all-encompassing Demand for High throughput Measurement Techniques – BioSpace

The drive for application in life sciences tools between life science researcher stems from the need for bioinformatics for unearthing a diverse array of scientific data. The research fraternity and industry alike leverage life science tools for gaining insights into various elements: DNA and RNA sequences, protein structures, biological pathways in drug making, and biological signals useful for disease prognosis. The major application areas in life sciences market include genetics and cell biology. Life sciences tools hold potential in biological data acquisition, data mining, and analysis. The life sciences industry affinity to leverage the potential of computation tools in synthetic and systems biology has led to the evolution of the life sciences tools market.

The report on the life sciences tools market provides a scrutiny of key growth dynamics, insights into emerging regulatory landscape, and elements of the competitive dynamics. The study offers a qualitative and quantitative analysis of new technological avenues. In addition, it offers a measure of potential of these developments for vaccine development and drug making.

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Global Life Science Tools Market: Growth Dynamics

The growth of the life science tools market has been on the back of all-encompassing demand for high throughput measurement techniques across all domains of life sciences. Advances in omics, emerging avenues in synthetic and systems biology have unlocked new potential for market players. Perhaps, the most significant impetus to the expansion of life sciences market comes from the growing application of bioinformatics tools. The veritable explosion of sequencing data, notably from cancer research, has spurred demand for life sciences tools. Over the years, such research initiatives have formed a part of large-scale genomic research for precision medicine. A wide array of tools have been unveiled that will make collaborative approaches easy to adopt for life science researchers, such as cloud technology for cancer medicines.

Global Life Science Tools Market: Notable Developments

The life sciences tools market has in recent years witnessed a number of large-scale acquisition and strategic collaborations. Technology players has expanded their portfolio by forging collaborations with research institutes. A notable instance is Intel collaborating with Oregon Health & Science University to develop next-generation life sciences tools for advancing industry efforts in developing precision medicine for cancer. The project, concedes the partners, is one of its kind as it will enable life sciences researchers to offer clinicians tools for diagnosis disease based just on genome of a personprobably by the end of 2020. Several research institutes are expected to make a foray to make such initiatives reach fruition faster, thereby opening vast revenues streams in the life science tools market.

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Some of the well-entrenched players in the life sciences tools market are Merck KGaA, Hitachi, Ltd., Danaher Corporation, Bio-Rad Laboratories, Inc., F. Hoffmann-La Roche Ltd., and Agilent Technologies.

Global Life Science Tools Market: Regional Assessment

Developed regions are seeing the growing trend of technology players unveiling scalable solutions for various omics projects. Markets such as North America has thus been hotbed of opportunities for the past several years. Countries such as the U.S. is seeing the rapid uptake of advances data analytics solutions by life sciences researchers, resulting in incredible scope in these markets.

On the other hand, the growing research in precision medicine has spurred the demand for life sciences tools in emerging markets. A notable emerging market is that of Asia Pacific. Life sciences organization in countries such as China have ramped up their efforts to unlock the potential of computation tools for systems biology. Other key regions in the life science tools market are Europe, the Middle East, and Latin America. These regional markets are seeing vast potential due to growing focus on governments on omics research that increasingly need technologically advanced life sciences tools.

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Growth of the Life Science Tools Market has been on the back of all-encompassing Demand for High throughput Measurement Techniques - BioSpace

Cell Biology

Linking glutamate receptor movements and synapse function – Science Magazine

Receptors moving in and out of the synapse

The number of neurotransmitter receptors and their spatial organization on the postsynaptic site is a central determinant of synaptic efficacy. Sophisticated techniques to visualize and track the movement of single molecules have provided us with profound new insights into these dynamics. We now know that neurotransmitter receptors undergo movements on different scales. Groc and Choquet review our present understanding of the mechanisms that regulate glutamate receptor localization and clustering. Receptor movements are fundamental to basic synaptic function and participate in many forms of synaptic plasticity.

Science, this issue p. eaay4631

Since it was established that the cognitive brain is formed mostly by an interconnected network of neurons that communicate at contact sites termed synapses, intense research has aimed at identifying their molecular composition and physiological roles. The discovery that the efficacy of synaptic transmission can be modified by neuronal activity has undoubtedly been a major step in understanding brain function. The various forms of activity-dependent synaptic plasticity were early on proposed to play central roles in brain adaptation, learning, and memory. This motivated neurophysiologists to understand the mechanisms of synaptic plasticity, initially within the sole framework of the quantal properties of transmitter release, largely ignoring the cell biology revolution that was occurring in parallel. In the 1970s, at the same time that synaptic plasticity was discovered, the fluidity of cell membranes was established. Surprisingly, these contemporary findings seldom crossed paths. As cell biologists established the major roles of receptor trafficking in cell function, neurophysiologists still largely viewed synapse function as based on unitary receptor properties and control of transmitter release. It has been only about 20 years since the two fields cross-fertilized and the regulation of receptor movements into and out of synapses emerged as a fundamental mechanism for synaptic plasticity.

Largely based on the development of imaging approaches, including single-molecule tracking, receptors have been demonstrated to undergo a variety of movements, from long-range rapid motor-based intracellular transport, to short-range Brownian surface diffusion, and intercompartment exchange by membrane trafficking. For efficient synaptic transmission, receptors must accumulate in front of neurotransmitter release sites. This is accomplished through a set of interactions with intracellular scaffold proteins, transmembrane auxiliary subunits, or adhesion proteins and other extracellular elements. This duality of receptor movements and stabilization has led to the important concept that the number of functionally responsive receptors at synapses results from the interplay between reversible receptor stabilization and dynamic equilibrium between pools of receptors in the synaptic, extrasynaptic, and intracellular compartments. Coarse receptor distribution along dendrites is largely achieved by intracellular transport. Because exchange of receptors between surface and intracellular compartments seems to occur largely at extrasynaptic sites, reversible surface receptor diffusion trapping at synapses has emerged as a central mechanism to control their availability for synaptic activation. Receptor stabilization and movements are all profoundly regulated by short- and long-term neuronal activity patterns. Reciprocally, evidence has accumulated that receptor movements participate in many forms of synaptic plasticity. Notably, altered receptor movements are observed in many neurodevelopmental, psychiatric, or neurodegenerative pathological models as indicated in the figure [the + and signs indicate the reported positive and negative modulation of the indicated trafficking and stabilization processes during either normal (blue) or pathological (red) synaptic function]. Whether altered receptor trafficking represents the primum movens of some neurological diseases remains to be established, but is certainly an attractive hypothesis.

Most receptor trafficking studies have been performed in reduced experimental systems such as neuronal cultures. This has limited our understanding of the physiological impact of these processes. The development of brighter and smaller probes together with new imaging modalities are on the verge of allowing routine measurement of receptor movements in more physiological settings such as brain slices and in vivo. There is little doubt that qualitatively comparable trafficking modalities will be identified. Reciprocally, tools are being developed to control the various types of receptor movements, from blocking surface diffusion by receptor cross-linking to stopping receptor exocytosis with light-activated toxins. Often, these trafficking tools do not impair basic synaptic function, because resilience of the synapse to trafficking alterations is high owing to the amount of available receptors, as well as the trapping capacities and nanoscale organization of the synapse. Combining measurement and control of receptor movements will not only allow better understanding of their contribution to synaptic and neuronal function but also provide valuable tools for identifying the role of synaptic plasticity in higher brain functions. Controlling receptor movements or stabilization may eventually represent an alternative therapeutic strategy to receptor activity modulation approaches in a variety of synaptic and network-based brain diseases.

Movements of large amplitude constantly reshuffle the receptor distribution (e.g., surface diffusion and intracellular transport). Movements at interfaces (e.g., between synaptic and extrasynaptic sites, between intracellular and surface compartments) are of small amplitude but have huge functional impacts. Each of these movements is highly regulated and finely tuned in physiological and pathological conditions.

Regulation of neurotransmitter receptor content at synapses is achieved through a dynamic equilibrium between biogenesis and degradation pathways, receptor stabilization at synaptic sites, and receptor trafficking in and out synapses. In the past 20 years, the movements of receptors to and from synapses have emerged as a series of highly regulated processes that mediate postsynaptic plasticity. Our understanding of the properties and roles of receptor movements has benefited from technological advances in receptor labeling and tracking capacities, as well as from new methods to interfere with their movements. Focusing on two key glutamatergic receptors, we review here our latest understanding of the characteristics of receptor movements and their role in tuning the efficacy of synaptic transmission in health and brain disease.

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Linking glutamate receptor movements and synapse function - Science Magazine

Cell Biology

COVID 19 Impact on Cell Culture Market: 2020 Global Industry Size, Segments, Future Trends, Growth Factors, Company Profiles and Forecast till 2026 -…

The Cell Culture Market is expected to grow during the forecast period owing to the increase in awareness regarding the potential benefits regarding cell culture based vaccines. Additionally, the rising demand for monoclonal antibodies can also help in augmenting the market growth. However, high cost of cell biology research might impede the growth of the market.

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Report Covers Market Segment by Manufacturers: Becton, Dickinson and Company Cellgenix Corning Danaher Eppendorf Fujifilm Irvine Scientific (Acquired By Fujifilm Corporation).

Cell culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. Cell culture is one of the major tools used in cellular and molecular biology, since it provides excellent model systems for studying the normal physiology and biochemistry of cells and the effects of drugs and toxic compounds on the cells. It is also used in the development of biological compounds.

Cell Culture Industry report offers a comprehensive insight into the development policies and plans in addition to manufacturing processes and cost structures. On the basis of product, this report displays the cost structure, sales revenue, sales volume, gross margin, market share and growth rate.

Pharmaceutical & Biotechnology Companies Hospitals and Diagnostic Laboratories Research Institutes Cell Banks

Key Benefits of the Report:

Global, and regional, product type & application market size and their forecast from 2019-2026 Identification and detailed analysis on key market dynamics, such as, drivers, restraints, opportunities, and challenges influencing the growth of the market

Detailed analysis on industry outlook with market specific PEST analysis, and Supply Chain to better understand the market and build expansion strategies Identification of key market players and comprehensively analyze their market share and core competencies, detailed financial positions, key products, and unique selling points Analysis on key players strategic initiatives and competitive developments, such as agreements & joint ventures, mergers & acquisitions, expansion, and new product launches in the market Expert interviews and their insights on market trends, market shift, current and future outlook, and factors impacting vendors short term & long term strategies Detailed insights on emerging regions, product type and application with qualitative and quantitative information and facts Identification of the key patents filed in the field of Cell Culture equipment and other related technologies.

Target Audience: Cell Culture providers Traders, Importer and Exporter Raw material suppliers and distributors Research and consulting firms Government and research organizations Associations and industry bodies

We have assigned weights to these parameters and quantified their market impacts using the weighted average analysis to derive the expected market growth rate.The market estimates and forecasts have been verified through exhaustive primary research with theKey Industry Participants (KIPs) which typically include: Original Equipment Manufacturer Component Supplier Distributors Government Body & Associations Research Institute

Orian Research is one of the most comprehensive collections of market intelligence reports on the World Wide Web. Our reports repository boasts of over 500000+ industry and country research reports from over 100 top publishers. We continuously update our repository so as to provide our clients easy access to the worlds most complete and current database of expert insights on global industries, companies, and products. We also specialize in custom research in situations where our syndicate research offerings do not meet the specific requirements of our esteemed clients.

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COVID 19 Impact on Cell Culture Market: 2020 Global Industry Size, Segments, Future Trends, Growth Factors, Company Profiles and Forecast till 2026 -...

Cell Biology

Majority of Evaluable Patients Across Genotypes Achieve Transfusion Independence and Maintain It with Near-Normal Hemoglobin Levels in Phase 3 Studies…

89% of evaluable patients (17/19) with transfusion-dependent -thalassemia who do not have a 0/0 genotype achieved transfusion independence with 11.9 g/dL median weighted average total hemoglobin (Hb) level in HGB-207

Data from exploratory analyses of HGB-207 show improved markers of blood cell production and bone marrow function in patients who achieved transfusion independence

85% of patients (11/13) with a 0/0 genotype or IVS-I-110 mutation in HGB-212 have been transfusion-free for at least 7 months

bluebird bio, Inc. (Nasdaq: BLUE) today announced that new data from ongoing Phase 3 studies of betibeglogene autotemcel (beti-cel; formerly LentiGlobin for -thalassemia gene therapy) show pediatric, adolescent and adult patients with a range of genotypes of transfusion-dependent -thalassemia (TDT) achieve and maintain transfusion independence with hemoglobin (Hb) levels that are near-normal (10.5 g/dL). These data are being presented at the Virtual Edition of the 25th European Hematology Association (EHA25) Annual Congress.

"With more than a decade of clinical experience evaluating gene therapy in patients with transfusion dependent -thalassemia across a wide range of ages and genotypes, we have built the most comprehensive understanding of treatment outcomes in the field," said David Davidson, M.D., chief medical officer, bluebird bio. "Seeing patients achieve transfusion independence and maintain that positive clinical benefit over time with robust hemoglobin levels reflects our initial vision of the potential of beti-cel. The accumulating long-term data demonstrating improvements in bone marrow histology, iron balance and red cell biology support the potential of beti-cel to correct the underlying pathophysiology of transfusion-dependent -thalassemia."

A total of 60 pediatric, adolescent and adult patients across genotypes of TDT have been treated with beti-cel in the Phase 1/2 Northstar (HGB-204) and HGB-205 studies, and the Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies as of March 3, 2020. In studies of beti-cel, transfusion independence is defined as no longer needing red blood cell transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.

TDT is a severe genetic disease caused by mutations in the -globin gene that results in significantly reduced or absent adult hemoglobin (HbA). In order to survive, people with TDT maintain Hb levels through lifelong, chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

"Patients with transfusion-dependent -thalassemia do not make enough healthy red blood cells and cannot live without chronic transfusions; for patients that means a lifetime of necessary visits to a hospital or clinic and reliance on an often unreliable blood supply, which compounds the challenges of managing this disease," said presenting study author Professor John B. Porter, MA, M.D., FRCP, FRCPath, University College London Hospital, London, UK. "These results showing patients free from transfusions and maintaining near-normal hemoglobin levels after treatment with beti-cel is a positive outcome for people living with transfusion-dependent -thalassemia. In addition, we now have more data that provide further evidence that most of these patients have a measurable improvement in markers of healthy red blood cell production."

Beti-cel is a one-time gene therapy designed to address the underlying genetic cause of TDT by adding functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). This means there is no need for donor HSCs from another person, as is required for allogeneic HSC transplantation (allo-HSCT). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived Hb, at levels that eliminate or significantly reduce the need for transfusions.

As of March 3, 2020, all 23 patients in HGB-207 were treated and have been followed for a median of 19.4 months. These patients ranged in age from four to 34 years, including eight pediatric (<12 years of age) and 15 adolescent/adult (>12 years of age) patients. Only 19 patients were evaluable for transfusion independence; four additional patients do not yet have sufficient follow-up to be assessed for transfusion independence.

Eighty-nine percent of evaluable patients (17/19) achieved transfusion independence, with median weighted average total Hb levels of 11.9 g/dL (min-max: 9.4 12.9 g/dL) over a median of 19.4 months of follow-up to date (min-max: 12.3 31.4 months). These 17 patients previously required a median of 17.5 transfusions per year (min-max: 11.5 37 transfusions per year).

Improved iron levels, as measured by serum ferritin and hepcidin levels (proteins involved in iron storage and homeostasis), were observed and trends toward improved iron management were seen. Over half of patients stopped chelation therapy, which is needed to reduce excess iron caused by chronic blood transfusions. Seven out of 23 patients began using phlebotomy for iron reduction.

Analysis of Healthy Red Blood Cell Production

In exploratory analyses, biomarkers of ineffective erythropoiesis (red blood cell production) were evaluated in patients who achieved transfusion independence in HGB-207.

The myeloid to erythroid (M:E) ratio in bone marrow from patients who achieved transfusion independence increased from a median of 1:3 (n=17) at baseline to 1:1.2 (n=16) at Month 12. Improvement of the M:E ratio, the ratio of white blood cell and red blood cell precursors in the bone marrow, suggests an improvement in mature red blood cell production. Images illustrating the bone marrow cellularity at baseline, Month 12 and Month 24 are available in the EHA25 presentation (abstract #S296): "Improvement in erythropoiesis in patients with transfusion-dependent -thalassemia following treatment with betibeglogene autotemcel (LentiGlobin for -thalassemia) in the Phase 3 HGB-207 study".

Additionally, biomarkers of erythropoiesis continue to demonstrate a trend toward normalization in patients who achieved transfusion independence, including improved levels over time of erythropoietin, a hormone involved in red blood cell production; reticulocytes, immature red blood cells; and soluble transferrin receptor, a protein measured to help evaluate iron status. The continued normalization of red blood cell production over time among some patients who achieved transfusion independence supports the disease-modifying potential of beti-cel in patients with TDT.

Northstar-3 (HGB-212) Efficacy

As of March 3, 2020, 15 patients (genotypes: 9 0/0, 3 0/ +IVS1-110, 3 homozygous IVS-1-110 mutation) were treated and had a median follow-up of 14.4 months (min-max: 1.124.0 months). Median age at enrollment was 15 (min-max: 4 33 years).

Six of eight evaluable patients achieved transfusion independence, with median weighted average total Hb levels of 11.5 g/dL (min-max: 9.5 13.5 g/dL), and continued to maintain transfusion independence for a median duration of 13.6 months (min-max: 12.2 21.2 months) as of the data cutoff.

Eighty-five percent of patients (11/13) with at least seven months of follow-up had not received a transfusion in more than seven months at time of data cutoff. These 11 patients previously required a median of 18.5 transfusions per year (min-max: 11.0 39.5 transfusions per year). In these patients, gene therapy-derived HbAT87Q supported total Hb levels ranging from 8.814.0 g/dL at last visit.

Betibeglogene autotemcel Safety

Non-serious adverse events (AEs) observed during the HGB-207 and HGB-212 trials that were considered related or possibly related to beti-cel were tachycardia, abdominal pain, pain in extremities, leukopenia, neutropenia and thrombocytopenia. One serious event of thrombocytopenia was considered possibly related to beti-cel.

In HGB-207, serious events post-infusion in two patients included three events of veno-occlusive liver disease and two events of thrombocytopenia. In HGB-212, serious events post-infusion in two patients included two events of pyrexia.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

In both Phase 3 studies, there have been no deaths, no graft failure, no cases of vector-mediated replication competent lentivirus or clonal dominance, no leukemia and no lymphoma.

The presentations are now available on demand on the EHA25 website:

About betibeglogene autotemcel

The European Commission granted conditional marketing authorization (CMA) for betibeglogene autotemcel (beti-cel; formerly LentiGlobin gene therapy for -thalassemia), marketed as ZYNTEGLO gene therapy, for patients 12 years and older with transfusion-dependent -thalassemia (TDT) who do not have a 0/0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor is not available. On April 28, 2020, the European Medicines Agency (EMA) renewed the CMA for ZYNTEGLO, supported by data from 32 patients treated with ZYNTEGLO, including three patients with up to five years of follow-up.

TDT is a severe genetic disease caused by mutations in the -globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

Beti-cel adds functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once a patient has the A-T87Q-globin gene, they have the potential to produce HbAT87Q, which is gene therapy-derived hemoglobin, at levels that may eliminate or significantly reduce the need for transfusions.

Non-serious adverse events (AEs) observed during clinical studies that were attributed to beti-cel included abdominal pain, thrombocytopenia, leukopenia, neutropenia, hot flush, dyspnea, pain in extremity and non-cardiac chest pain. Two serious adverse events (SAE) of thrombocytopenia was considered possibly related to beti-cel.

Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease.

The CMA for beti-cel is valid in the 27 member states of the EU as well as UK, Iceland, Liechtenstein and Norway. For details, please see the Summary of Product Characteristics (SmPC).

The U.S. Food and Drug Administration (FDA) granted beti-cel orphan drug designation and Breakthrough Therapy designation for the treatment of transfusion-dependent -thalassemia. Beti-cel is not approved in the U.S.

Beti-cel continues to be evaluated in the ongoing Phase 3 Northstar-2 and Northstar-3 studies. For more information about the ongoing clinical studies, visit http://www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207) and NCT03207009 for Northstar-3 (HGB-212).

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of betibeglogene autotemcel or LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT02633943 for LTF-303.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders including cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma using three gene therapy technologies: gene addition, cell therapy and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

ZYNTEGLO, LentiGlobin, and bluebird bio are trademarks of bluebird bio, Inc.

bluebird bio Forward-Looking Statements

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that the COVID-19 pandemic and resulting impact on our operations and healthcare systems will affect the execution of our development plans or the conduct of our clinical studies; the risk that the efficacy and safety results observed in the patients treated in our prior and ongoing clinical trials of beti-cel may not persist; and the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated with additional patients in our ongoing or planned clinical trials or in the commercial context; the risk that the FDA will require additional information regarding beti-cel, resulting in a delay to our anticipated timelines for regulatory submissions, including submission of our BLA. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200612005084/en/

Contacts

Media:Catherine Falcetti, 339-499-9436cfalcetti@bluebirdbio.com

Investors:Ingrid Goldberg, 410-960-5022igoldberg@bluebirdbio.com

Elizabeth Pingpank, 617-914-8736epingpank@bluebirdbio.com

See the article here:
Majority of Evaluable Patients Across Genotypes Achieve Transfusion Independence and Maintain It with Near-Normal Hemoglobin Levels in Phase 3 Studies...