PEANUTS

New $3 million grant supports research on leading cause of maternal mortality worldwide

MU researcher Laura Schulz has dedicated her career to studying the intricacies of maternal health related to the placenta, research that advances knowledge on common diseases like preeclampsia

Grant and Award Announcement

UNIVERSITY OF MISSOURI-COLUMBIA

University of Missouri researchers are striving to find solutions to the leading cause of maternal mortality in the world — preeclampsia. For Laura Schulz, an associate professor of obstetrics, gynecology and women’s health in the University of Missouri School of Medicine, understanding the root causes of preeclampsia and other complicated, life-threatening maternal conditions is pivotal in advancing women’s health care.

Supported by a renewed $3 million grant from the National Institute of Child Health and Human Development (NICHD), Schulz and her team will use trophoblast cells, which are cells that develop in the placenta and provide nutrients to the growing embryo, to understand how placental defects that cause preeclampsia function. The goal is to learn the disease’s tell-tale signs, which would enable doctors to diagnose, treat, and, ultimately, prevent preeclampsia.

Joining Schulz on the project is co-principal investigator R. Michael Roberts at MU and co-investigators Toshihiko Ezashi at the Colorado Center for Reproductive Medicine and Danny Schust at Duke University.

“Preeclampsia is characterized by high blood pressure and protein in the urine, and it can progress to multisystem organ failure,” Schulz said. “It can also cause stroke, postpartum hemorrhage or, commonly, premature birth, which has all kinds of consequences for the baby.”

While scientists can easily observe the placenta at birth, one of the challenges in studying this disease is that the remodeling of spiral arteries in the uterus — those that supply blood to the placenta — occurs in the first trimester, making it particularly difficult to study as it’s happening. Spiral artery remodeling appears to go wrong in preeclampsia. To study the early stages of pregnancy, without impacting the pregnancy, the researchers are examining umbilical cord cells after the birth occurs.

“What we do is take umbilical cord cells from either a normal pregnancy, or one complicated by preeclampsia after the baby’s been born,” Schulz said. “Then we re-program these cells to turn them into trophoblast cells. That way we can look at cells that resemble placental cells and try to figure out what might be going on in early pregnancy that can lead to the development of all these problems.”

In a prior study, the research team developed umbilical cord-based cell models to test whether they could recapitulate any of the features that are often seen in preeclampsia patients. This new funding will allow for an expansion of this work to make organoids — three-dimensional tissue cultures derived from trophoblast cells — so the researchers can understand the architecture of the tissues and to make specific kinds of trophoblast, the cells of the placenta, to learn more about how this organ works.

“I started off as a comparative reproductive biologist,” Schulz said. “I was mostly interested in how pregnancy happens in different kinds of animals and species-specific factors. And then I got more interested in human pregnancy when I joined an OB-GYN department and learned the implications for women's health and their babies. Now, I’m broadly interested in how we make healthier pregnancies and a more favorable maternal environment during pregnancy while optimizing fetal bone and muscle growth.”

Childbearing, infertility, and career trajectories among women in medicine

JAMA Network Open

Peer-Reviewed Publication

JAMA NETWORK

About The Study: In this survey study, women physicians reported that career-related pressures influenced the timing of childbearing and led to marked alterations to career trajectories to accommodate family building and parenthood. These findings suggest that fertility and family building concerns among women in medicine may contribute to ongoing gender disparities and attrition and represent a potentially critical area for policy reform and future change. 

Authors: Jennifer B. Bakkensen, M.D., of the Northwestern University Feinberg School of Medicine in Chicago, is the corresponding author. 

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamanetworkopen.2023.26192)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

 http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2023.26192?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=072723

About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication. 

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JOURNAL

JAMA Network Open

Investigators identify translation gaps in instrument that measures nursing practice environment

Peer-Reviewed Publication

UNIVERSITY OF PENNSYLVANIA SCHOOL OF NURSING

 

IMAGE: EILEEN T. LAKE, PH.D. RN, FAAN, PROFESSOR OF NURSING, THE EDITH CLEMMER STEINBRIGHT PROFESSOR IN GERONTOLOGY, ASSOCIATE DIRECTOR OF THE CENTER FOR HEALTH OUTCOMES AND POLICY RESEARCH view more 

CREDIT: UNIVERSITY COMMUNICATIONS

PHILADELPHIA (July 27, 2023) – Two decades ago, the Practice Environment Scale of the Nursing Work Index was published to measure the nursing practice environment. Although the instrument's use has resulted in advances in science and quality improvement efforts, its potential may be limited by the availability and quality of translations into different languages.

Researchers from the University of Pennsylvania School of Nursing (Penn Nursing) investigated published translations of the instrument and have identified translations into 24 languages and 15 language variants representing 35 countries. Languages in Europe, Southeast Asia, and the Middle East comprise most translations. Translation gaps are noted for countries in Africa, Asia, and South America. While most translations exhibited cross-cultural equivalence and sound psychometric properties, the gaps indicate an area of opportunity that, when addressed, could further support worldwide quality and safety of care, and improve patient health outcomes as well as nurse job outcomes.

“In countries and regions where a translation is available, managers can survey their registered nurses to assess the quality of their work environments and compare them with published referents,” suggests Penn Nursing’s Eileen T. Lake, Ph.D. RN, FAAN, Professor of Nursing, the Edith Clemmer Steinbright Professor in Gerontology, Associate Director of the Center for Health Outcomes and Policy Research, and lead author of the article. “In countries without published translations, healthcare managers should consider collaborating with regional schools of nursing to support translation efforts by permitting their staff nurses to volunteer as research participants.”

The research suggests that additional cultural equivalence or psychometric evaluation is warranted for half of the available translations. In addition, more robust reporting of the translation processes and results is needed. The article “Translations of the Practice Environment Scale of the Nursing Work Index: A Systematic Review” details the findings. It has been published in Nursing & Health Sciences and is available online.

Co-authors of the article include Kathleen E. Fitzpatrick Rosenbaum, BSN, RN, RNC-NIC, CCRN-K, Christina Sauveur, BSN, Catherine Buren, and Priscilla Cho, BSN, all of Penn Nursing. Kathleen E. Fitzpatrick Rosenbaum's predoctoral fellowship is supported by funding from the National Institute of Nursing Research, National Institutes of Health (Aiken, PI; T32NR007104).

# # #

About the University of Pennsylvania School of Nursing

The University of Pennsylvania School of Nursing is one of the world’s leading schools of nursing. For the eighth year in a row, it is ranked the #1 nursing school in the world by QS University. For the second year in a row, our Bachelor of Science in Nursing (BSN) program is ranked # 1 in the 2023 U.S. News & World Report’s Best Colleges rankings. Penn Nursing is also consistently ranked highly in the U.S. News & World Report annual list of best graduate schools and is ranked as one of the top schools of nursing in funding from the National Institutes of Health. Penn Nursing prepares nurse scientists and nurse leaders to meet the health needs of a global society through innovation in research, education, and practice. Follow Penn Nursing on: Facebook, Twitter, LinkedIn, & Instagram.  

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JOURNAL

Nursing and Health Sciences

ARTICLE TITLE

Translations of the Practice Environment Scale of the Nursing Work Index: A Systematic Review

ARTICLE PUBLICATION DATE

28-Jul-2023

 

WAIT! ITS A NON EXISTANT LIMB

Johns Hopkins Applied Physics Laboratory restores cold sensation in amputees’ phantom limbs

Peer-Reviewed Publication

JOHNS HOPKINS UNIVERSITY APPLIED PHYSICS LABORATORY

 

IMAGE: JOHNNY MATHENY, A PROSTHETICS TESTER, DETERMINES WHICH COLA CAN IS THE COLDEST USING A MODULAR PROSTHETIC LIMB AND THIN-FILM THERMOELECTRIC DEVICE, BOTH DEVELOPED BY THE JOHNS HOPKINS APPLIED PHYSICS LABORATORY. view more 

CREDIT: ED WHITMAN / JOHNS HOPKINS UNIVERSITY APPLIED PHYSICS LABORATORY

Johns Hopkins Applied Physics Laboratory (APL) researchers have developed one of the world’s smallest, most intense and fastest refrigeration devices, the wearable thin-film thermoelectric cooler (TFTEC), and teamed with neuroscientists to help amputees perceive a sense of temperature with their phantom limbs. This advancement, one of the first of its kind, enables a useful new capability for a variety of applications, including improved prostheses, haptics for new modalities in augmented reality (AR) and thermally-modulated therapeutics for applications such as pain management. The technology also has a variety of potential industrial and research applications, such as cooling electronics and lasers and energy harvesting in satellites.

TFTEC development at APL started in 2016, when Rama Venkatasubramanian, a semiconductor device engineer and chief technologist for APL’s thermoelectrics research, began developing advanced nano-engineered thermoelectric materials and devices for the Defense Advanced Research Projects Agency (DARPA) MATRIX program. To support MATRIX, APL developed advanced thin-film thermoelectric materials called Controlled Hierarchically Engineered Superlattice Structures (CHESS), to enable an entirely new set of transduction capabilities for several Department of Defense applications, including cooling computer chips and engine components.

Venkatasubramanian’s strides in CHESS thermoelectrics were so significant by the end of 2019 that Bobby Armiger, who supervises APL’s Exploratory Science Branch, wondered if his devices could be used to facilitate temperature sensation in phantom limbs of amputees for improved prostheses. Since 2006, APL had been leading DARPA’s Revolutionizing Prosthetics program, an effort focused on creating a mentally controlled artificial limb that will restore near-natural motor and sensory capability to upper-extremity amputee patients.

“We’ve known that we can stimulate specific parts of someone’s amputated limb to feel sensations of touch and vibration, but no one has been able to create a cooling sensation with the speed, intensity, and efficiency to restore natural thermal perception with a prosthetic system,” Armiger said. “Restoring temperature sensation has practical applications — like identifying a cold beverage — as well as having the potential to improve the emotional embodiment of the prosthetic device, perhaps by feeling the warmth of a loved one’s hand.”

Venkatasubramanian and the thermoelectrics team began collaborating with Armiger and a team of neuroscientists and roboticists as part of a study supported by the Center for Rehabilitation Sciences Research within the Department of Physical Medicine & Rehabilitation (PM&R) at the Uniformed Services University of the Health Sciences (USU), through a subaward from The Henry M. Jackson Foundation for the Advancement of Military Medicine to create a wearable thermoelectric cooler fast and intense enough to match the human body’s ability to rapidly sense temperature changes.

From that, the wearable TFTEC was created.

“Our TFTEC is just a little more than one millimeter thick, weighs only 0.05 grams, similar to a thin adhesive bandage, and can provide intense cooling in less than a second,” said Venkatasubramanian. “It’s also two times more energy efficient than today’s most common thermoelectric devices, and can be readily manufactured using semiconductor tools that are also used for manufacturing light-emitting diodes [LEDs]. It’s an exciting development that could have huge implications for prostheses and haptics applications.”

To test the TFTEC’s efficacy, researchers mapped thermal sensations in the phantom hands of four amputees.

“When someone loses part of a limb, the nerves within the residual limb are still there, which can lead to the ‘phantom’ limb sensation,” said Luke Osborn, a neuroengineering researcher who leads much of APL’s noninvasive nerve simulation work. “You can place electrodes on different parts of an amputee’s upper arm where those nerves have regrown and stimulate sensation — typically pressure, but in the current case, temperature —and the individual can tell us where in their phantom hand they feel those sensations.”

Nature Biomedical Engineering recently published results from APL’s extensive TFTEC research for such sensory applications, which included lab-scale characterization, trials with amputees and a real-life demonstration of the approach. The study notes that the TFTEC elicited cooling sensations in the phantom limbs of all participants during a cold detection task, whereas traditional thermoelectric technology only did so in half of them — and the TFTEC did so eight times faster and with three times the intensity. Additionally, TFTEC used half the energy compared to current thermoelectric devices.

“We found that the TFTEC device was significantly better at creating faster and more intense cooling sensations compared to traditional devices, even though the target temperature was the same,” said Osborn. “And that helped participants make faster decisions and observations.”

The stimulation sites on test participants remained the same over 48 weeks of testing, suggesting that the technology could enable users to feel temperature in their missing hands for years. This temporal stability along with a wearable noninvasive procedure are attractive for adoption to real-world use.

“When we started our work in March 2020, we realized that within just a couple of trials we could stimulate the phantom limbs of an amputee,” said Venkatasubramanian. “We heard participants say, ‘Yes, I felt an immediate cold feeling here and a tingle there.’”

The APL team continued to perfect its approach through testing on several individuals with amputation along with those with an intact limb. “These are the developments we dream of as scientists,” Venkatasubramanian continued. “We spend years in the lab, and to see our technology have an impact on someone’s quality of life, like an amputee to perceive the natural thermal world, is incredibly satisfying.”

Capable of generating realistic and informative thermal signals for human perception — at a fraction of the energy and size compared to today’s cooling technologies — the devices’ low-profile, high-speed, and lightweight nature make them suitable for skin surface applications without hindrances that could affect movement.

“It has been great to see the translation of this APL-developed thermoelectric technology into the healthcare domain through this first-of-kind demonstration in an amputee,” said David Drewry, a biomedical engineer and program manager within APL’s National Health Mission Area. “We look forward to expanding the results in more robust clinical trials and integrating the device into other wearable form factors that can be readily deployed to individuals in need of sensory restoration or haptic feedback.”

Katy Carneal, a biomedical engineer and assistant program manager a biomedical engineer and assistant program manager who leads innovative health-related research at APL sees a vast set of future applications for the miniaturized thermoelectric technology. “There are so many ways that pressure and temperature sensations impact the human body,” said Carneal. “In addition to improving quality of life for amputees, we’ve opened a lot of research doors that can help us study and find new treatments for neuromuscular diseases or chronic pain.”

Dr. Paul Pasquina, the chair of PM&R at USU, echoed that enthusiasm while praising the work of the APL team. “What a privilege it is to work with such expert engineers to come up with solutions to help real-world patients, including our wounded warriors with limb loss,” he said.

APL is uniquely qualified to advance the art-of-the-possible for novel health applications by exploring this intersection of materials science and electronic device engineering with biology and neuroscience. In addition to the Revolutionizing Prosthetics program, APL is making significant advances in neural interface research, improving genomics tools and monitoring physical fatigue to prevent warfighter injuries among many other advancements in the National Health Mission Area.

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JOURNAL

Nature Biomedical Engineering

DOI

10.1038/s41551-023-01070-w 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Evoking natural thermal perceptions using a thin-film thermoelectric device with high cooling power density and speed

ARTICLE PUBLICATION DATE

27-Jul-2023

COI STATEMENT

R.V., L.E.O., M.H., J.M.P. and R.S.A. are inventors on intellectual property pertaining to thin-#ilm thermoelectric devices and US patents 11,227,988 and 11,532,778 and application 18/071,789. R.V. and J.M.P. are inventors on US patent 10,903,139. The Johns Hopkins University is the applicant on these patents. The other authors declare no competing interests.

 Nerve cells in the brain can halt all movement in the body – even breathing

A group of nerve cells in the brain has the remarkable ability to completely stop all forms of movement, a new mouse study shows. The discovery provides valuable insight into how the nervous system can control our movements.

Peer-Reviewed Publication

UNIVERSITY OF COPENHAGEN - THE FACULTY OF HEALTH AND MEDICAL SCIENCES

When a hunting dog picks up the scent of a deer, it sometimes freezes. On the spot. The same thing can happen to people who need to concentrate on a challenging task.

Now researchers have made a discovery that adds to our knowledge of what happens in the brain when we suddenly stop moving.

“We have found a group of nerve cells in the midbrain which, when stimulated, stop all movement. Not just walking; all forms of motor activity. They even make the mice stop breathing or breathe more slowly, and the heart rate slow down,” explains Professor Ole Kiehn, who is co-author on the study.

“There are various ways to stop movement. What is so special about these nerve cells is that once activated they cause the the movement to be paused or freeze. Just like setting a film on pause. The actors movement suddenly stop on the spot,” says Ole Kiehn.

When the researchers ended activating the nerve cells, the mice would start the movement exactly where it stopped. Just like when pressing “play” again.

“This ‘pause-and-play pattern’ is very unique; it is unlike anything we have seen before. It does not resemble other forms of movement or motor arrest we or other researchers have studied. There, the movement does not necessarily start where it stopped, but may start over with a new pattern,” says PhD Haizea Goñi-Erro, who is first author of the study.

The nerve cells stimulated by the researchers are found in the midbrain in an area called the pedunculopontine nucleus (PPN), and they differ from other nerve cells there by expressing a specific molecular marker called Chx10. The PPN is common to all vertebrates including humans. So even though the study was performed in mice, the researchers expect the phenomenon to apply to humans too.

Not related to fear

Some might suggest that the nerve cells are activated by fear. Most people are familiar with the phenomenon of “freezing” caused by extreme fear. But that is not the case.

“We have compared this type of motor arrest to motor arrest or freezing caused by fear, and they are not identical. We are very sure that the movement arrest observe here is not related to fear. Instead, we believe it has something to do with attention or alertness, which is seen in certain situations,” says Assistant Professor Roberto Leiras, who is co-author of the study.

The researchers believe it is an expression of a focused attention. However, they stress that the study has not revealed if this is indeed the case. It is something that requires more research to demonstrate.

May be able to understand Parkinson’s symptoms.

The new study may be able to help us understand some of the mechanisms of Parkinson’s disease.

“Motor arrest or slow movement is one of the cardinal symptoms of Parkinson’s disease. We speculate that these special nerve cells in PPN are over-activated in Parkinson’s disease. That would inhibit movement. Therefore, the study, which primarily has focused on the fundamental mechanisms that control movement in the nervous system, may eventually help us to understand the cause of some of the motor symptoms in Parkinson’s disease,” Ole Kiehn concludes.

You can read the full study, ”Pedunculopontine Chx10+ neurons for global motor arrest in mice”, by Haizea Goñi-Erro, Raghavendra Selvan, Roberto Leiras and Ole Kiehn  in Nature Neuroscience.

The study is funded by the Novo Nordisk Foundation, the Lundbeck Foundation and the Swedish Research Council.

What the researchers did Among other things, the researchers used optogenetics to stimulate the nerve cells in the brainstem. In short, optogenetics is a biological technique that involves genetically modifying specific brain cells to make them more sensitive to light. This means that the cells can be activated by a flash of light. In the study, the researchers were able to stimulate the specific group of nerve cells in mice and thus determine the motor function of these cells.

 

 

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JOURNAL

Nature Neuroscience

DOI

10.1038/s41593-023-01396-3 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Pedunculopontine Chx10+ neurons control global motor arrest in mice

ARTICLE PUBLICATION DATE

27-Jul-2023

 

A butterfly effect

Protein Kinase C delta activity triggered by the plasticity of just a few synapses regulates cell-wide changes in gene transcription

Peer-Reviewed Publication

MAX PLANCK FLORIDA INSTITUTE FOR NEUROSCIENCE

 

IMAGE: WHEN YOU LEARN, SYNAPTIC COMPARTMENTS ON YOUR NEURONS GROW AND STRENGTHEN, REPRESENTED ABSTRACTLY AS BUDS OPENING INTO FULL BLOOM. NEW RESEARCH HAS DISCOVERED THAT DURING THIS PROCESS, SIGNALING ENZYMES NAMED PKCD, DRAWN ABOVE AS FLUTTERING BUTTERFLIES, ARE ACTIVATED TO SUPPORT THE STRENGTHENING AND GROWTH OF SYNAPSES WHILE ALSO SENDING SIGNALS THAT SPREAD, LIKE THE POLLEN FROM THE FLOWERS, FROM THE SYNAPSES TO THE NUCLEUS OF THE NEURON TO REGULATE CELL WIDE GENE EXPRESSION. IMAGE CREDIT: HELENA PINHEIRO view more 

CREDIT: HELENA PINHEIRO

When you interact with the world around you, your experiences are recorded as changes in the connection strengths between neurons in your brain. This process, called synaptic plasticity, alters how information flows through your brain and is critical for learning, memory, and even injury recovery.

New research guided by MPFI Scientific Director Dr. Ryohei Yasuda and published this week in the Journal of Neuroscience, has identified a critical role for a signaling enzyme called Protein Kinase C delta (PKCd) in this process. The team of scientists developed biosensors to track the activity of PKCd during plasticity, overcoming long-standing challenges in studying its function. Through this new approach, they found that PKCd created a “butterfly effect” transmitting local signals from a few of the thousands of synapses in a neuron to regulate cell-wide changes in gene expression.

Synaptic plasticity consists of hundreds of coordinated biochemical reactions that alter the structure and function of individual synapses, the tiny compartments where information is transferred between neurons. These biochemical reactions are the work of enzymes, specialized proteins in your cells that function together during plasticity to physically grow or shrink your synapses and make them stronger or weaker. Interestingly, when just a few synapses of the thousands in a neuron undergo plasticity, these reactions extend beyond individual synaptic compartments and spread throughout the neuron to the nucleus, where neuron-wide changes in gene-expression occur.

The coordination of local plasticity at the synapses with changes in the nucleus enables lasting changes in information transfer in the brain during learning. However, the enzymes and reactions coordinating synapse-to-nucleus signaling were not fully understood. By developing new approaches to studying old questions, scientists at MPFI were able to identify that PKCd is essential for this critical process.

PKCd is part of the PKC family, a group of 12 closely related enzymes, that has been known to be necessary for synaptic plasticity. However, the role of individual enzymes in the PKC family in synaptic plasticity was not clear. This uncertainty was due primarily to scientists lacking tools that would allow them to distinguish the unique roles of these closely related family members. 

To overcome this limitation, the scientists developed biosensors to visualize the activity of the specific members of the PKC family of enzymes. The team found that one of these enzymes, PKCd, was indispensable for synaptic plasticity. Blocking its function prevented the increase in the strength and size of synaptic connections.

Most notably, the study revealed that the activity of PKCd varied depending on the nature of the plasticity stimulus. PKCd was activated to a greater degree and for a longer time when several synapses were being strengthened. Moreover, its activity spread throughout the neuron, regulating biochemical reactions from the synapses throughout the neuron to the nucleus, where they activated gene transcription.

"This work provides new tools, which overcome long-standing limitations in studying the functions of individual PKC enzymes and provides greater understanding of synaptic plasticity, a critical process in brain function," describes Dr. Lesley Colgan, the study's lead researcher. "Through this approach, we discovered an efficient mechanism for information exchange between synapses and gene transcription within the nucleus, converting short-term plasticity into longer lasting forms of plasticity that likely underly memory formation."

Like the spreading of PKCd activity from a few synapses throughout the neuron, the scientists hope that the development of new biosensors for the PKC family of enzymes will have an impact beyond the field of synaptic plasticity.

As Dr. Colgan remarked, "The PKC family of enzymes is involved in many cellular functions and has been implicated in many diseases, including Alzheimer's disease, cancer, and heart disease. We hope the tools developed in this paper will be used by others in the scientific community to address many different questions and make an impact in these important scientific fields." 

Lesley A. Colgan, Paula Parra-Bueno, Heather L. Holman, Xun Tu, Anant Jain, Mariah F. Calubag, Jaime A. Misler, Chancellor Gary, Goksu Oz, Irena Suponitsky-Kroyter, Elwy Okaz, & Ryohei Yasuda. (2023). Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKCδ during Plasticity. The Journal of Neuroscience, 43(30), 5432. https://doi.org/10.1523/JNEUROSCI.0208-22.2023  https://www.jneurosci.org/content/43/30/5432

This research was supported by the National Institutes of Health under award numbers R35-NS-116804 (RY), R01-MH-080047 (RY), and F32MH101954 (LAC). This content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.

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JOURNAL

JNeurosci

DOI

10.1523/JNEUROSCI.0208-22.2023 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animal tissue samples

ARTICLE TITLE

Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKCδ during Plasticity

ARTICLE PUBLICATION DATE

26-Jul-2023

COI STATEMENT

R.Y. is the owner of Florida Lifetime Imaging LLC, a company that sells integrated solutions for performing fluorescence lifetime imaging and fluorescence resonance energy transfer imaging. The remaining authors declare no competing financial interests.

 

Special package: Social media and elections

Peer-Reviewed Publication

AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE (AAAS)

Removing Facebook and Instagram users from seeing default algorithmic feeds – which are designed to optimize the order in which content is presented – reduced time users spent on the platforms, a new study by Andrew M. Guess et al. shows, but it did not change users’ political attitudes, knowledge, and offline behaviors. The study is one of three in this issue involving collaboration between Meta and academic researchers to study social media’s impact on elections. The package is accompanied by a Policy Forum by the project’s independent rapporteur. The algorithms used by social media companies are largely opaque to users. As a result, there are various “folk theories” about how they work and disagreements about their effects. “The notion that such algorithms create political ‘filter bubbles’, foster polarization, exacerbate existing social inequalities, and enable the spread of disinformation has become rooted in the public consciousness,” write Guess and colleagues. Here, Guess and team sought to examine the effect of algorithmic feed-ranking systems on individuals’ political attitudes and behaviors as related to the U.S. presidential election in 2020. Participants were recruited through survey invitations placed on the top of their Facebook and Instagram feeds in August 2020. In a three-month analysis that ensued, the researchers compared participants in a control condition (i.e., no changes were made to status quo algorithmic feeds) to participants in a treatment condition (i.e., participants saw chronological feeds, where the most recent posts appeared on top). The treatment group spent less time on and were less engaged with content on platforms and were exposed to more ideologically diverse content. However, this did not lead to detectable changes in downstream political attitudes, knowledge, or offline behavior, including survey-based measures of polarization and political participation. The authors say there are several possible explanations for the disconnect between the large changes in online behavior caused by their treatment and the few discernible changes in political attitudes, including length of intervention period and background in which the study was conducted (i.e., a highly polarized election campaign when political conversations were occurring at relatively higher frequencies).

In a second study in the same issue, research also led by Guess studied the impact of reshared Facebook content – which constitutes more than one-fourth of posts Facebook users see – on exposure to political news during the 2020 U.S. election. They report that suppressing reshared content substantially decreased the amount of political news – including from untrustworthy sources – to which users were exposed but did not affect political opinions. On Facebook, resharing content is a core feature. Prior research suggests that reshared content may increase political polarization and political knowledge. Guess et al. undertook a randomized controlled experiment during the 2020 U.S. presidential election to examine the effects of withholding reshared content. They compared a control group for whom no changes were made to Facebook feeds to a treatment group for whom reshared content was removed from feeds. Removing reshared content decreased users’ clicks on partisan news links, the proportion of political news they saw, and their exposure to untrustworthy content. However, despite these changes, the authors were not able to reliably detect shifts in users’ political attitudes or behaviors, with the exception of a decrease in news knowledge within the sample. “[T]hough reshares may have been a powerful mechanism for directing users’ attention and behavior on Facebook during the 2020 election campaign,” conclude the authors, “they had limited impact on politically relevant attitudes and offline behaviors.”

In a third study, Sandra González-Bailón and colleagues tackled the question of whether Facebook enables ideological segregation in political news consumption. They report that politically conservative users are much more segregated and encounter far more misinformation on the platform. “Our analyses highlight that Facebook… is substantially segregated ideologically—far more than previous research on internet news consumption based on browsing behavior has found,” write González-Bailón et al. People form beliefs from political news they encounter, and there has been a vigorous debate about the role of the internet in shaping the policy-relevant information that people see, with some suggesting that platforms like Facebook may facilitate “ideological segregation.” Using a sample of 208 million U.S. Facebook users during the U.S. 2020 presidential election, González-Bailón et al. examined the flow of political content: all content users could potentially see; content they actually did see on feeds (selectively curated by Facebook's algorithms); and content engaged with through clicks, reshares, or other reactions. Compared to liberals, the authors found that politically conservative users were far more siloed in their news sources and exposed to much more misinformation. Both algorithmic processes (data-driven and automated) and social amplification processes (related to choices made by users) played a part in this ideological segregation. It primarily surfaced in Facebook's Pages and Groups – areas policymakers may target to combat misinformation – as opposed to from content posted by friends. An important direction for further research is to understand how individuals discover and decide to follow or join Pages and/or Groups, say the authors.

In a related Policy Forum, Mike Wagner, who was asked to serve as the project’s independent rapporteur in order “increase the confidence that the public and the scholarly community would have in the project,” discusses results from these studies – the first publicly shared outcomes of the U.S. 2020 Election Project. Wagner, in his role, was charged with commenting on the nature of the collaboration between Meta and the outside academics and whether the project might serve as a model for future industry–academy collaborations. He concludes that the team conducted “rigorous, carefully checked, transparent, ethical, and path-breaking studies.” He cites several strengths of the related research approach, including the outside academics having “control rights” for the papers – meaning that in the event of a dispute between the outside academics and the Meta research­ers over how to interpret a finding or what to include in a research paper, the lead author – which would always be an outside academic – would have the final decision. But he goes on to write that though the work is trustworthy, “I argue that the project is not a model for future industry–academy collaborations” for various reasons. “Creative so­cial media–academy-funder partnerships, or, more likely, government regulation and data-sharing requirements…that also provide privacy protections, as well as de­fined structures to encourage and protect industry-employed researchers to collabo­rate, are necessary to foster opportunities for path-breaking, comprehensive scholar­ship that does not require a social media platform’s permission,” he writes.

The package is accompanied by an introduction by Science Associate Editor Ekeoma Uzogara and an editorial by Science Editor-in-Chief Holden Thorp.

*** A related embargoed news briefing was held at 11:00 a.m. U.S. ET on Tuesday, 25 July, as a Zoom Webinar. Recordings are available here. Questions about META policy should be directed to press@meta.com.

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JOURNAL

Science

DOI

10.1126/science.abp9364 

ARTICLE TITLE

How do social media feed algorithms affect attitudes and behavior in an election campaign?

ARTICLE PUBLICATION DATE

28-Jul-2023

 

Total recall on HIV

Researchers create total synthesis of HIV replication inhibitor

Peer-Reviewed Publication

KYOTO UNIVERSITY

 

IMAGE: FLOW OF STRUCTURE REVISION AND SYNTHESIS OF LANCILACTONE C view more 

CREDIT: KYOTOU/ AYUMI UCHINO

Kyoto, Japan -- Having control over how a dish is cooked is always a good idea. Taking a hint from the kitchen, scientists appear to have discovered a way to produce a true structure of the rare but naturally-occurring anti-HIV compound Lancilactone C from start to finish.

Its non-cytotoxicity in mammals could make this triterpenoid an ideal candidate for treating AIDS if its biological activity were clear -- and if only it were abundant in nature.

Now, a research group at Kyoto University has succeeded in creating a domino-like synthesis of Lancilactone C's unique seven-membered ring structure. 

"Our synthetic method revealed that the proposed structure of Lancilactone C was initially incorrect," says Chihiro Tsukano of Kyoto University's Graduate School of Agriculture. "But we successfully derived its true structure from our spectral data and understanding of its biosynthesis."

In addition to this revelation, Tsukano realized that the electrocyclization -- a rearrangement reaction in organic chemistry -- used in the total synthesis also occurs in biosynthesis. Ironically, it remains a mystery of whether the proposed structure containing an unsaturated seven-membered ring might exist in nature as an analog -- or equivalent compound -- and how it might affect the expression of biological activity.

Tsukano's team utilized the domino-like reaction to enable the total synthesis of lancilactones and related triterpenoids. This outcome has inspired the team to further their research in optimizing compound structures, leading to possible development of novel antivirals.

The endless loop of required medication and multi-drug therapies often correlates with a lower quality of life for economically burdened patients. 

"Our synthetic method for Lancilactone C, with its known efficacy, may lead to developing less problematic anti-HIV drugs," concludes Tsukano.

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The paper "Total Synthesis and Structure Revision of (+)-Lancilactone C" appeared on 16 June 2023 in the Journal of the American Chemical Society, with doi: 10.1021/jacs.3c04124
 
About Kyoto University
Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at undergraduate and graduate levels complements several research centers, facilities, and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en

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JOURNAL

Journal of the American Chemical Society

DOI

10.1021/jacs.3c04124 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Total Synthesis and Structure Revision of (+)-Lancilactone C

Pandemic paycheck protection loans boosted nursing home staffing, study finds

AN INVESTMENT WALL ST. LOSES ITS MIND OVER

Loans increased staffing hours among certified nursing assistants and licensed practical nurses and went to the facilities most in need

NEW YORK UNIVERSITY

The COVID-19 pandemic magnified long-standing problems within nursing homes, including staffing shortages. However, a new study published in JAMA Network Open reveals that the federal government’s Paycheck Protection Program (PPP) was effective in supporting nursing homes by improving staffing levels at the height of the pandemic.

 

In addition, understaffed nursing homes were more likely to receive PPP loans, suggesting that the forgivable loans reached the small businesses most in need and funding was not diverted to less-needy nursing homes—unlike PPP loans that supported celebrities and other well-off business owners.

 

Not enough nursing staff

“The COVID-19 pandemic has been the 9-11 moment for nursing homes,” said Jasmine Travers, PhD, RN, assistant professor at NYU Rory Meyers College of Nursing, testifying to the U.S. House of Representatives in 2022.

 

Nursing home staff were already stretched thin before 2020, but the pandemic was a breaking point for many. Research shows that COVID-19 outbreaks in nursing homes drove increased absences and significant turnover.

 

“Staffing shortages in nursing homes threaten the quality of care for residents, especially when these shortages occur among frontline care staff,” said Travers, the lead author of the JAMA Network Open study.

 

Nursing homes that receive more funding tend to be better staffed. In 2020, PPP loans emerged as a new source of funding for nursing homes and other small businesses, the result of a program established to support small businesses in keeping their workers on payroll during the pandemic. PPP loans were forgiven if recipients used at least 60-75% of their loans toward payroll and staffing.

 

Loans linked to better staffing

The researchers sought to understand whether nursing homes that received PPP loans were able to increase their staff hours. They analyzed multiple national datasets involving nursing homes, including PPP data from the Small Business Administration and payroll data from the Centers for Medicare and Medicaid Services.

 

They focused on the period of January 1, 2020 through December 23, 2020 to be able to compare staffing levels—specifically, the hours worked by registered nurses (RNs), licensed practical nurses (LPNs), and certified nursing assistants (CNAs)—before and after nursing homes received PPP loans.

 

Of the 6,008 U.S. nursing homes studied, 1,807 (30%) received a PPP loan and 4,201 (70%) did not. The average loan amount was $664,349.

 

Nursing homes that received PPP loans had increased staffing—nearly 46 more staffing hours per week three months after receiving a loan—compared to nursing homes that did not receive PPP loans. The greatest improvements in staffing were among CNAs (26 more hours per week), followed by LPNs (seven more hours per week); RN staffing did not change significantly.

 

“Nursing homes were able to fairly quickly improve their CNA staffing after receiving a PPP loan, which equated to two additional shifts per week one month after receiving a loan and four additional shifts per week six months after receiving a loan,” said Travers.

 

The study also revealed that the nursing homes most in need of funding—those with lower staffing levels, more Medicaid-funded residents, and lower quality scores—were more likely to receive PPP loans.

 

“While we found that PPP loans reached understaffed nursing homes and boosted staff hours, these loans were only a temporary fix,” said Travers. “We need federal and state policies that provide sustainable support and incentivize nursing homes to invest in their staff long-term. This might look like increased Medicaid reimbursements and requiring that a percentage of nursing home revenue directly goes to paying for frontline staff.”

 

Additional study authors include Brian McGarry of the University of Rochester Medical Center, Steven Friedman of NYU Grossman School of Medicine, Louisa W. Holaday of Icahn School of Medicine at Mount Sinai, Joseph S. Ross of Yale School of Medicine, Leo Lopez of the Institute for Public Health, University Health, University Medicine Associates in San Antonio, Texas, and Kevin Chen of NYC Health + Hospitals and NYU Grossman School of Medicine. The research was supported by grants from the Robert Wood Johnson Foundation (77872) and the National Institute on Aging (K76 AG074922).

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JOURNAL

JAMA Network Open

DOI

10.1001/jamanetworkopen.2023.26122 

ARTICLE TITLE

Association of Receipt of Paycheck Protection Program Loans With Staffing Patterns Among US Nursing Homes

ARTICLE PUBLICATION DATE

27-Jul-2023