Henry Schein (NASDAQ:HSIC): Q1 Non-GAAP EPS of $0.94 beats by $0.20; GAAP EPS of $0.91 beats by $0.15.
Revenue of $2.4B (+1.7% Y/Y) beats by $80M.
https://seekingalpha.com/news/3568973-henry-schein-eps-beats-0_20-beats-on-revenueTuesday, May 5, 2020
Alexion buying Portola for $18/share
“Andexxa is a strategic fit with our existing
portfolio of transformative medicines and is well-aligned with our
demonstrated expertise in hematology, neurology and critical care,” says
Alexion (NASDAQ:ALXN) CEO Ludwig Hantson.
The $18 per share all-cash deal is more than double Portola’s (NASDAQ:PTLA) close last night of $7.76. It’s set to close in Q3.
A conference call to discuss is set for 8 ET.
https://seekingalpha.com/news/3568985-alexion-buying-portola-for-18-shareRegeneron Pharmaceuticals EPS beats by $0.51, beats on revenue
Regeneron Pharmaceuticals (NASDAQ:REGN): Q1 Non-GAAP EPS of $6.60 beats by $0.51; GAAP EPS of $5.43 misses by $0.07.
Revenue of $1.83B (+33.6% Y/Y) beats by $20M.
https://seekingalpha.com/news/3568910-regeneron-pharmaceuticals-eps-beats-0_51-beats-on-revenueMonday, May 4, 2020
Exercise boosts motor skill learning via changes in brain’s transmitters
Doctors have relentlessly impressed upon us the many benefits of
exercise. Energy, mood, sleep and motor skills all improve with a
regular fitness regimen that includes activities such as running. This
has become of particular interest in the time of the COVID-19 pandemic.
But what happens in the brain during these improved states of health? The underlying neurological changes that open the door to these benefits have been unclear.
Now, Assistant Project Scientist Hui-quan Li and Distinguished Professor Nick Spitzer of the University of California San Diego have identified key neurological modifications following sustained exercise. Comparing the brains of mice that exercised with those that did not, Li and Spitzer found that specific neurons switched their chemical signals, called neurotransmitters, following exercise, leading to improved learning for motor-skill acquisition.
“This study provides new insight into how we get good at things that require motor skills and provides information about how these skills are actually learned,” said Spitzer, the Atkinson Family Chair in the Biological Sciences Section of Neurobiology and a director of the Kavli Institute for Brain and Mind.
The study’s results are published May 4 in Nature Communications.
Spitzer’s laboratory discovered neurotransmitter switching in the adult mammalian brain and has led groundbreaking research on the ability of neurons to change their transmitter identity in response to sustained stimuli, typically leading to changes in behavior. After carrying out research that described neurotransmitter switching in depression, Spitzer and his colleagues began to turn their attention to how such switching might be involved in healthy conditions.
Li says the results underscore the importance of exercise, even at home during the current pandemic quarantine situation.
“This study shows that it’s good for the brain to add more plasticity,” said Li. “For people who would like to enhance their motor skill learning, it may be useful to do some exercise to promote this form of plasticity to benefit the brain. For example, if you hope to learn and enjoy challenging sports such as surfing or rock climbing when we’re no longer sheltering at home, it can be good to routinely run on a treadmill or maintain a yoga practice at home now.”
During the new study, Li and Spitzer compared mice that completed a week’s worth of exercise on running wheels with mice that had no access to running wheels. They found that the exercised group acquired several demanding motor skills such as staying on a rotating rod or crossing a balance beam more rapidly than the non-exercised group.
When the brains of the running mice were examined, a group of neurons in the brain region known as the caudal pedunculopontine nucleus (cPPN) that regulates motor coordination was discovered to have switched neurotransmitters from acetylcholine to GABA.
To confirm their findings, the researchers used molecular tools to block the newly identified transmitter switch resulting from exercise. They found that the enhancement of motor skill learning in these mice was prevented. Based on their findings, the researchers propose a new model in which conversion of cPPN excitatory cholinergic neurons to inhibitory GABAergic neurons provides feedback control regulating motor coordination and skill learning.
The researchers say the discovery could lead to further findings where neurotransmitter switching leads to key motor skill changes. The researchers say they’d like to test ideas such as whether neurotransmitters could be deliberately switched to benefit motor skills, even without exercise. They also plan to conduct research on whether exercise similarly triggers benefits of motor skill learning in those with neurological disorders.
“We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a target for clinical treatment of movement disorders,” the authors conclude in the paper.
Says Spitzer: “With an understanding of this mechanism comes the opportunity to manipulate and to harness it for further beneficial purposes. In the injured or diseased individual, it could be a way of turning things around… to give the nervous system a further boost.”
https://www.eurekalert.org/pub_releases/2020-05/uoc–ebm043020.php
But what happens in the brain during these improved states of health? The underlying neurological changes that open the door to these benefits have been unclear.
Now, Assistant Project Scientist Hui-quan Li and Distinguished Professor Nick Spitzer of the University of California San Diego have identified key neurological modifications following sustained exercise. Comparing the brains of mice that exercised with those that did not, Li and Spitzer found that specific neurons switched their chemical signals, called neurotransmitters, following exercise, leading to improved learning for motor-skill acquisition.
“This study provides new insight into how we get good at things that require motor skills and provides information about how these skills are actually learned,” said Spitzer, the Atkinson Family Chair in the Biological Sciences Section of Neurobiology and a director of the Kavli Institute for Brain and Mind.
The study’s results are published May 4 in Nature Communications.
Spitzer’s laboratory discovered neurotransmitter switching in the adult mammalian brain and has led groundbreaking research on the ability of neurons to change their transmitter identity in response to sustained stimuli, typically leading to changes in behavior. After carrying out research that described neurotransmitter switching in depression, Spitzer and his colleagues began to turn their attention to how such switching might be involved in healthy conditions.
Li says the results underscore the importance of exercise, even at home during the current pandemic quarantine situation.
“This study shows that it’s good for the brain to add more plasticity,” said Li. “For people who would like to enhance their motor skill learning, it may be useful to do some exercise to promote this form of plasticity to benefit the brain. For example, if you hope to learn and enjoy challenging sports such as surfing or rock climbing when we’re no longer sheltering at home, it can be good to routinely run on a treadmill or maintain a yoga practice at home now.”
During the new study, Li and Spitzer compared mice that completed a week’s worth of exercise on running wheels with mice that had no access to running wheels. They found that the exercised group acquired several demanding motor skills such as staying on a rotating rod or crossing a balance beam more rapidly than the non-exercised group.
When the brains of the running mice were examined, a group of neurons in the brain region known as the caudal pedunculopontine nucleus (cPPN) that regulates motor coordination was discovered to have switched neurotransmitters from acetylcholine to GABA.
To confirm their findings, the researchers used molecular tools to block the newly identified transmitter switch resulting from exercise. They found that the enhancement of motor skill learning in these mice was prevented. Based on their findings, the researchers propose a new model in which conversion of cPPN excitatory cholinergic neurons to inhibitory GABAergic neurons provides feedback control regulating motor coordination and skill learning.
The researchers say the discovery could lead to further findings where neurotransmitter switching leads to key motor skill changes. The researchers say they’d like to test ideas such as whether neurotransmitters could be deliberately switched to benefit motor skills, even without exercise. They also plan to conduct research on whether exercise similarly triggers benefits of motor skill learning in those with neurological disorders.
“We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a target for clinical treatment of movement disorders,” the authors conclude in the paper.
Says Spitzer: “With an understanding of this mechanism comes the opportunity to manipulate and to harness it for further beneficial purposes. In the injured or diseased individual, it could be a way of turning things around… to give the nervous system a further boost.”
###
The research was funded by grants from the Ellison Medical
Foundation, the W. M. Keck Foundation, the National Institutes of Health
(NS047101) and the Overland Foundation.https://www.eurekalert.org/pub_releases/2020-05/uoc–ebm043020.php
U Missouri researcher identifies four possible treatments for COVID-19
A researcher at the University of Missouri has found that four
antiviral drugs, including remdesivir, a drug originally developed to
treat Ebola, are effective in inhibiting the replication of the
coronavirus causing COVID-19.
Kamlendra Singh, an associate professor in the College of Veterinary Medicine, and his team used computer-aided drug design to examine the effectiveness of remdesivir, 5-fluorouracil, ribavirin and favipiravir in treating COVID-19. Singh found that all four drugs were effective in inhibiting, or blocking, the coronavirus’ RNA proteins from making genomic copies of the virus.
“As researchers, we have an obligation to search for possible treatments given that so many people are dying from this virus,” Singh said. “These antiviral drugs, if they turn out to be effective, all have some limitations. But in the midst of a global pandemic, they are worth taking a deeper look at because based on our research, we have reason to believe that all of these drugs could potentially be effective in treating COVID-19.”
The coronavirus (SARS-CoV-2) that causes COVID-19, like all viruses, can mutate and develop resistance to antiviral drugs. Therefore, further testing in a laboratory setting and in patients is needed to better evaluate how the proposed treatments interact with the virus’ RNA polymerase.
“Our goal is to help doctors by providing options for possible treatments of COVID-19, and to ultimately contribute in improving the health outcomes of patients suffering from the infectious disease,” Singh said. “As researchers, we are simply playing our part in the fight against the pandemic.”
Singh’s research is an example of translational medicine, a key component of the University of Missouri System’s NextGen Precision Health Initiative. The NextGen initiative aims to improve large-scale interdisciplinary collaboration in pursuit of life-changing precision health advancements and research.
https://www.eurekalert.org/pub_releases/2020-05/uom-mri050420.php
Kamlendra Singh, an associate professor in the College of Veterinary Medicine, and his team used computer-aided drug design to examine the effectiveness of remdesivir, 5-fluorouracil, ribavirin and favipiravir in treating COVID-19. Singh found that all four drugs were effective in inhibiting, or blocking, the coronavirus’ RNA proteins from making genomic copies of the virus.
“As researchers, we have an obligation to search for possible treatments given that so many people are dying from this virus,” Singh said. “These antiviral drugs, if they turn out to be effective, all have some limitations. But in the midst of a global pandemic, they are worth taking a deeper look at because based on our research, we have reason to believe that all of these drugs could potentially be effective in treating COVID-19.”
The coronavirus (SARS-CoV-2) that causes COVID-19, like all viruses, can mutate and develop resistance to antiviral drugs. Therefore, further testing in a laboratory setting and in patients is needed to better evaluate how the proposed treatments interact with the virus’ RNA polymerase.
“Our goal is to help doctors by providing options for possible treatments of COVID-19, and to ultimately contribute in improving the health outcomes of patients suffering from the infectious disease,” Singh said. “As researchers, we are simply playing our part in the fight against the pandemic.”
Singh’s research is an example of translational medicine, a key component of the University of Missouri System’s NextGen Precision Health Initiative. The NextGen initiative aims to improve large-scale interdisciplinary collaboration in pursuit of life-changing precision health advancements and research.
###
“Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs,” was recently published in Pathogens.https://www.eurekalert.org/pub_releases/2020-05/uom-mri050420.php
Two drugs show promise against COVID-19
Korean researchers have screened 48 FDA-approved drugs against
SARS-CoV-2, and found that two, that are already FDA-approved for other
illnesses, seem promising. The FDA approval for other uses would greatly
reduce the time needed to gain FDA approval of use in COVID-19. The
research is published in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.
The investigators tested the drugs in Vero cells, a cell line developed from kidney cells of the African Green Monkey, which are commonly used to grow viruses for vaccine production.
An anti-helminthic drug called niclosamide demonstrated “very potent” antiviral activity against SARS-CoV-2, according to coauthors Sangeun Jeon, Meehyun Ko, and their collaborators, of the Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam, Korea. “Not surprisingly, its broad-spectrum antiviral effect has been well documented in the literature, including antiviral properties against SARS- and MERS-CoV,” they write.
A downside of niclosamide is low absorption, which undercuts the drug’s power by reducing the dose that reaches the target tissue. However, “Further development or drug formulation could enable an effective delivery of this drug to the target tissue,” according to the report.
Despite substantially lower antiviral potency, ciclesonide, an inhaled corticosteroid used to treat asthma and allergic rhinitis, also showed promise against SARS-CoV-2. Intriguingly, the investigators note that a study published earlier this year ( by Matsuyama et al.) a treatment report of 3 patients infected by SARS-CoV-2, demonstrated antiviral activity and revealed the drug’s molecular target to be a viral protein called Nsp15.
“With its proven anti-inflammatory activity, ciclesonide may represent as a potent drug which can manifest [the] dual roles [of antiviral and anti-inflammatory] for the control of SARS-CoV-2 infection,” the investigators conclude. The anti-inflammatory activity might play a critical role in dampening or preventing the cytokine storms, an immune inflammatory overreaction that can kill COVID-19 patients.
https://www.eurekalert.org/pub_releases/2020-05/asfm-tds050420.php
The investigators tested the drugs in Vero cells, a cell line developed from kidney cells of the African Green Monkey, which are commonly used to grow viruses for vaccine production.
An anti-helminthic drug called niclosamide demonstrated “very potent” antiviral activity against SARS-CoV-2, according to coauthors Sangeun Jeon, Meehyun Ko, and their collaborators, of the Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam, Korea. “Not surprisingly, its broad-spectrum antiviral effect has been well documented in the literature, including antiviral properties against SARS- and MERS-CoV,” they write.
A downside of niclosamide is low absorption, which undercuts the drug’s power by reducing the dose that reaches the target tissue. However, “Further development or drug formulation could enable an effective delivery of this drug to the target tissue,” according to the report.
Despite substantially lower antiviral potency, ciclesonide, an inhaled corticosteroid used to treat asthma and allergic rhinitis, also showed promise against SARS-CoV-2. Intriguingly, the investigators note that a study published earlier this year ( by Matsuyama et al.) a treatment report of 3 patients infected by SARS-CoV-2, demonstrated antiviral activity and revealed the drug’s molecular target to be a viral protein called Nsp15.
“With its proven anti-inflammatory activity, ciclesonide may represent as a potent drug which can manifest [the] dual roles [of antiviral and anti-inflammatory] for the control of SARS-CoV-2 infection,” the investigators conclude. The anti-inflammatory activity might play a critical role in dampening or preventing the cytokine storms, an immune inflammatory overreaction that can kill COVID-19 patients.
https://www.eurekalert.org/pub_releases/2020-05/asfm-tds050420.php
Recently recovered COVID-19 patients produce varying virus-specific antibodies
Most newly discharged patients who recently recovered from COVID-19
produce virus-specific antibodies and T cells, suggests a study
published on May 3rd in the journal Immunity, but the responses
of different patients are not all the same. While the 14 patients
examined in the study showed wide-ranging immune responses, results from
the 6 of them that were assessed at two weeks after discharge suggest
that antibodies were maintained for at least that long. Additional
results from the study indicate which parts of the virus are most
effective at triggering these immune responses and should therefore be
targeted by potential vaccines.
It is not clear why immune responses varied widely across the patients. The authors say this variability may be related to the initial quantities of virus that the patients encountered, their physical states, or their microbiota. Other open questions include whether these immune responses protect against COVID-19 upon re-exposure to SARS-CoV-2, as well as which types of T cells are activated by infection with the virus. It is also important to note that the laboratory tests that are used to detect antibodies to SARS-CoV-2 in humans still need further validation to determine their accuracy and reliability.
“These findings suggest both B and T cells participate in immune-mediated protection against the viral infection,” says co-senior study author Chen Dong of Tsinghua University. “Our work has provided a basis for further analysis of protective immunity and for understanding the mechanism underlying the development of COVID-19, especially in severe cases. It also has implications for designing an effective vaccine to protect against infection.”
Relatively little is known about the protective immune responses induced by the disease-causing virus, SARS-CoV-2, and addressing this gap in knowledge may accelerate the development of an effective vaccine, adds co-senior study author Cheng-Feng Qin of the Academy of Military Medical Sciences in Beijing, China.
With this goal in mind, the researchers compared the immune responses of 14 COVID-19 patients who had recently become virus-free to those of six healthy donors. Eight of the patients were newly discharged, and the remaining six were follow-up patients who were discharged two weeks prior to the analyses. Specifically, the researchers collected blood samples and assessed the levels of immunoglobulin M (IgM) antibodies, which are the first to appear in response to an infection, as well as immunoglobulin G (IgG) antibodies, which are the most common type found in blood circulation.
Compared to healthy controls, both newly discharged and follow-up patients showed higher levels of IgM and IgG antibodies that bind to the SARS-CoV-2 nucleocapsid protein, which encapsulates the viral genomic RNA, as well as the S protein’s receptor-binding domain (S-RBD), which binds to receptors on host cells during the process of viral entry. Taken together, these findings show that COVID-19 patients can mount antibody responses to SARS-CoV-2 proteins and suggest that these antibodies are maintained for at least two weeks after discharge.
In addition, five newly discharged patients had high concentrations of neutralizing antibodies that bind to a pseudovirus expressing the SARS-CoV-2 S protein. Neutralizing antibodies prevent infectious particles from interacting with host cells. In addition, all except one follow-up patient had detectable neutralizing antibodies against the pseudovirus.
Compared to healthy controls, five newly discharged patients had higher concentrations of T cells that secrete interferon gamma (IFNγ) – a signaling molecule that plays a critical role in immunity – in response to the SARS-CoV-2 nucleocapsid protein. These are the same patients who had high concentrations of neutralizing antibodies. In addition, three newly discharged patients showed detectable levels of IFNγ-secreting T cells specific to the SARS-CoV-2 main protease – a protein that plays a critical role in viral replication. Meanwhile, seven newly discharged patients showed detectable levels of IFNγ-secreting T cells specific to the S-RBD of SARS-CoV-2. By contrast, only one follow-up patient had a high concentration of IFNγ-secreting T cells responsive to the nucleocapsid protein, the main protease, and S-RBD.
One finding with potential clinical relevance is that the amount of neutralizing antibodies was positively associated with IgG antibodies against S-RBD, but not with those that bind to the nucleocapsid protein. Moreover, S-RBD induced both antibody and T cell responses. “Our results suggest that S-RBD is a promising target for SARS-CoV-2 vaccines,” says co-senior study author Fang Chen of Chui Yang Liu Hospital affiliated to Tsinghua University. “But our findings need further confirmation in a large cohort of COVID-19 patients.”
Immunity, Ni, Ye, and Cheng et al.: “Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals” https://www.cell.com/immunity/fulltext/S1074-7613(20)30181-3
https://www.eurekalert.org/pub_releases/2020-05/cp-rrc050420.php
It is not clear why immune responses varied widely across the patients. The authors say this variability may be related to the initial quantities of virus that the patients encountered, their physical states, or their microbiota. Other open questions include whether these immune responses protect against COVID-19 upon re-exposure to SARS-CoV-2, as well as which types of T cells are activated by infection with the virus. It is also important to note that the laboratory tests that are used to detect antibodies to SARS-CoV-2 in humans still need further validation to determine their accuracy and reliability.
“These findings suggest both B and T cells participate in immune-mediated protection against the viral infection,” says co-senior study author Chen Dong of Tsinghua University. “Our work has provided a basis for further analysis of protective immunity and for understanding the mechanism underlying the development of COVID-19, especially in severe cases. It also has implications for designing an effective vaccine to protect against infection.”
Relatively little is known about the protective immune responses induced by the disease-causing virus, SARS-CoV-2, and addressing this gap in knowledge may accelerate the development of an effective vaccine, adds co-senior study author Cheng-Feng Qin of the Academy of Military Medical Sciences in Beijing, China.
With this goal in mind, the researchers compared the immune responses of 14 COVID-19 patients who had recently become virus-free to those of six healthy donors. Eight of the patients were newly discharged, and the remaining six were follow-up patients who were discharged two weeks prior to the analyses. Specifically, the researchers collected blood samples and assessed the levels of immunoglobulin M (IgM) antibodies, which are the first to appear in response to an infection, as well as immunoglobulin G (IgG) antibodies, which are the most common type found in blood circulation.
Compared to healthy controls, both newly discharged and follow-up patients showed higher levels of IgM and IgG antibodies that bind to the SARS-CoV-2 nucleocapsid protein, which encapsulates the viral genomic RNA, as well as the S protein’s receptor-binding domain (S-RBD), which binds to receptors on host cells during the process of viral entry. Taken together, these findings show that COVID-19 patients can mount antibody responses to SARS-CoV-2 proteins and suggest that these antibodies are maintained for at least two weeks after discharge.
In addition, five newly discharged patients had high concentrations of neutralizing antibodies that bind to a pseudovirus expressing the SARS-CoV-2 S protein. Neutralizing antibodies prevent infectious particles from interacting with host cells. In addition, all except one follow-up patient had detectable neutralizing antibodies against the pseudovirus.
Compared to healthy controls, five newly discharged patients had higher concentrations of T cells that secrete interferon gamma (IFNγ) – a signaling molecule that plays a critical role in immunity – in response to the SARS-CoV-2 nucleocapsid protein. These are the same patients who had high concentrations of neutralizing antibodies. In addition, three newly discharged patients showed detectable levels of IFNγ-secreting T cells specific to the SARS-CoV-2 main protease – a protein that plays a critical role in viral replication. Meanwhile, seven newly discharged patients showed detectable levels of IFNγ-secreting T cells specific to the S-RBD of SARS-CoV-2. By contrast, only one follow-up patient had a high concentration of IFNγ-secreting T cells responsive to the nucleocapsid protein, the main protease, and S-RBD.
One finding with potential clinical relevance is that the amount of neutralizing antibodies was positively associated with IgG antibodies against S-RBD, but not with those that bind to the nucleocapsid protein. Moreover, S-RBD induced both antibody and T cell responses. “Our results suggest that S-RBD is a promising target for SARS-CoV-2 vaccines,” says co-senior study author Fang Chen of Chui Yang Liu Hospital affiliated to Tsinghua University. “But our findings need further confirmation in a large cohort of COVID-19 patients.”
###
This work was supported by from the National Key Research and
Development Program of China, Natural Science Foundation of China,
Beijing Municipal Science and Technology, Zhejiang University
Foundation, and Tsinghua University. L.N., Y.F., W.P., and C.D. have
filed a provisional patent on the methodology of detecting
SARS-CoV-2-specific antibody responses.Immunity, Ni, Ye, and Cheng et al.: “Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals” https://www.cell.com/immunity/fulltext/S1074-7613(20)30181-3
https://www.eurekalert.org/pub_releases/2020-05/cp-rrc050420.php
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