Publisher Health

Several cereals, granola bars and other snack foods were recalled in December. The company added more products to the list this week.The Quaker Oats Company added more products this week to a recall that started last month over possible salmonella contamination, raising the total number of products to more than 60.Quaker Oats, which is owned by PepsiCo, initially recalled 43 products, including granola bars, cereals and various snack foods. On Thursday, the company added 24 products to the list.The newly recalled items include Quaker Chewy Granola Bars, Gatorade protein bars, Cap’n Crunch bars, Quaker Simply Granola Cereals, Gamesa Marias Cereal and other cereals.“To date, Quaker has received no confirmed reports of illness related to the products covered by this recall,” the U.S. Food and Drug Administration said in December. It is unclear if any illnesses have been reported since then.It was not immediately clear how the potential contamination occurred or how or when it first came to the attention of federal regulators or the company. Quaker Oats did not immediately respond to a request for comment on Saturday.On its website, the company listed the recalled products and provided an option to request reimbursement.Customers should check their pantries for any of the products and dispose of them, the F.D.A. said.Salmonella is an organism that can cause serious and sometimes fatal infections in young children, frail or older adults, and people with weakened immune systems.Common symptoms of salmonella include fever, nausea, vomiting, abdominal pain and diarrhea, which may be bloody. In rare cases, salmonella can get into the bloodstream and result in more severe illnesses, such as infected arteries, according to the F.D.A.Individuals who are exposed usually start to feel sick six hours to six days later. Most infections are mild and last between four and seven days.Other recent salmonella-related recalls have been linked to a variety of foods, such as vegetables, fruits and meats. At least two people died in a salmonella outbreak linked to cantaloupes that the Centers for Disease Control and Prevention announced in November.Salmonella bacteria cause about 1.35 million infections, 26,500 hospitalizations and 420 deaths in the United States every year, according to the C.D.C.

A study published in Nature Nanotechnology presents an innovative graphene-based neurotechnology with the potential for a transformative impact in neuroscience and medical applications. This research, spearheaded by the Catalan Institute of Nanoscience and Nanotechnology (ICN2) together with the Universitat Autònoma de Barcelona (UAB) and other national and international partners, is currently being developed for therapeutic applications through the spin-off INBRAIN Neuroelectronics.
Key Features of Graphene Technology
Following years of research under the European Graphene Flagship project, ICN2 spearheaded in collaboration with the University of Manchester the development of EGNITE (Engineered Graphene for Neural Interfaces), a novel class of flexible, high-resolution, high-precision graphene-based implantable neurotechnology. The results published today in Nature Neurotechnology aim to contribute with innovative technologies to the blooming landscape of neuroelectronics and brain-computer interfaces.
EGNITE builds on the vast experience of its inventors in fabrication and medical translation of carbon nanomaterials. This innovative technology based on nanoporous graphene integrates fabrication processes standard in the semiconductor industry to assemble graphene microelectrodes of a mere 25 µm in diameter. The graphene microelectrodes exhibit low impedance and high charge injection, essential attributes for flexible and efficient neural interfaces.
Preclinical Validation of Functionality
Preclinical studies by various neuroscience and biomedical experts that partnered with ICN2, using different models for both the central and peripheral nervous system, demonstrated the capacity of EGNITE in recording high-fidelity neural signals with exceptional clarity and precision and, more importantly, afford highly targeted nerve modulation. The unique combination of high-fidelity signal recording and precise nerve stimulation offered by EGNITE technology represents a potentially critical advancement in neuroelectronic therapeutics.
This innovative approach addresses a critical gap in neurotechnology, which has seen little advancement in materials over the last two decades. The development of EGNITE electrodes has the capacity to place graphene at the forefront of neurotechnological materials.

International Collaboration and Scientific Leadership
The technology presented today builds on the legacy of the Graphene Flagship, a European initiative that during the last decade strived to advance European strategic leadership in technologies that rely on graphene and other 2D materials. Behind this scientific breakthrough is a collaborative effort led by ICN2 researchers Damià Viana (now at INBRAIN Neuroelectronics), Steven T. Walston (now at University of Southern California), and Eduard Masvidal-Codina, under the guidance of ICREA Jose A. Garrido, leader of the ICN2Advanced Electronic Materials and Devices Group, and ICREA Kostas Kostarelos, leader of the ICN2Nanomedicine Lab and the Faculty of Biology, Medicine & Health at the University of Manchester (UK). The research has had the participation of Xavier Navarro, Natàlia de la Oliva, Bruno Rodríguez-Meana and Jaume del Valle, from the Institute of Neurosciences and the Department of Cellular Biology, Physiology and Immunology of the Universitat Autònoma de Barcelona (UAB).
The collaboration includes the contribution from leading national and international institutions, such as the Institut de Microelectrònica de Barcelona — IMB-CNM (CSIC), the National Graphene Institute in Manchester (UK), and the Grenoble Institut des Neurosciences — Université Grenoble Alpes (France) and the University of Barcelona. The technology integration into the standard semiconductor fabrication processes has been performed at the Micro and Nanofabrication cleanroom of the IMB-CNM (CSIC), under the supervision of CIBER researcher Dr Xavi Illa.
Clinical Translation: Next Steps
The EGNITE technology described in the Nature Nanotechnology article has been patented and licensed to INBRAIN Neuroelectronics, a spin-off based in Barcelona from ICN2 and ICREA, with support from IMB-CNM (CSIC). The company, also a partner in the Graphene Flagship project, is leading the translation of the technology into clinical applications and products. Under the direction of CEO Carolina Aguilar, INBRAIN Neuroelectronics is gearing up for the first-in-human clinical trials of this innovative graphene technology.
The industrial and innovation landscape on semiconductor engineering in Catalonia, where ambitious national strategies plan to build state-of-the-art facilities to produce semiconductor technologies based on emerging materials, offer an unprecedented opportunity to accelerate the translation of such results presented today into clinical applications.
Closing Remarks
The Nature Nanotechnology article describes an innovative graphene-based neurotechnology that can be upscaled using established semiconductor fabrication processes, holding the potential for a transformative impact. ICN2 and its partners continue to advance and mature the described technology with the aim to translate it into a real efficacious and innovative therapeutic neurotechnology.

To combat viruses, bacteria and other pathogens, synthetic biology offers new technological approaches whose performance is being validated in experiments. Researchers from the Würzburg Helmholtz Institute for RNA-based Infection Research and the Helmholtz AI Cooperative applied data integration and artificial intelligence (AI) to develop a machine learning approach that can predict the efficacy of CRISPR technologies more accurately than before. The findings were published today in the journal Genome Biology.
The genome or DNA of an organism incorporates the blueprint for proteins and orchestrates the production of new cells. Aiming to combat pathogens, cure genetic diseases or achieve other positive effects, molecular biological CRISPR technologies are being used to specifically alter or silence genes and inhibit protein production.
One of these molecular biological tools is CRISPRi (from “CRISPR interference”). CRISPRi blocks genes and gene expression without modifying the DNA sequence. As with the CRISPR-Cas system also known as “gene scissors,” this tool involves a ribonucleic acid (RNA), which serves as a guide RNA to direct a nuclease (Cas). In contrast to gene scissors, however, the CRISPRi nuclease only binds to the DNA without cutting it. This binding results in the corresponding gene not being transcribed and thus remaining silent.
Until now, it has been challenging to predict the performance of this method for a specific gene. Researchers from the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI) in cooperation with the University of Würzburg and the Helmholtz Artificial Intelligence Cooperation Unit (Helmholtz AI) have now developed a machine learning approach using data integration and artificial intelligence (AI) to improve such predictions in the future.
The approach
CRISPRi screens are a highly sensitive tool that can be used to investigate the effects of reduced gene expression. In their study, published today in the journal Genome Biology, the scientists used data from multiple genome-wide CRISPRi essentiality screens to train a machine learning approach. Their goal: to better predict the efficacy of the engineered guide RNAs deployed in the CRISPRi system.
“Unfortunately, genome-wide screens only provide indirect information about guide efficiency. Hence, we have applied a new machine learning method that disentangles the efficacy of the guide RNA from the impact of the silenced gene,” explains Lars Barquist. The computational biologist initiated the study and heads a bioinformatics research group at the Würzburg Helmholtz Institute, a site of the Braunschweig Helmholtz Centre for Infection Research in cooperation with the Julius-Maximilians-Universität Würzburg.

Supported by additional AI tools (“Explainable AI”), the team established comprehensible design rules for future CRISPRi experiments. The study authors validated their approach by conducting an independent screen targeting essential bacterial genes, showing that their predictions were more accurate than previous methods.
“The results have shown that our model outperforms existing methods and provides more reliable predictions of CRISPRi performance when targeting specific genes,” says Yanying Yu, PhD student in Lars Barquist’s research group and first author of the study.
The scientists were particularly surprised to find that the guide RNA itself is not the primary factor in determining CRISPRi depletion in essentiality screens. “Certain gene-specific characteristics related to gene expression appear to have a greater impact than previously assumed,” explains Yu.
The study also reveals that integrating data from multiple data sets significantly improves the predictive accuracy and enables a more reliable assessment of the efficiency of guide RNAs. “Expanding our training data by pulling together multiple experiments is essential to create better prediction models. Prior to our study, lack of data was a major limiting factor for prediction accuracy,” summarizes junior professor Barquist. The approach now published will be very helpful in planning more effective CRISPRi experiments in the future and serve both biotechnology and basic research. “Our study provides a blueprint for developing more precise tools to manipulate bacterial gene expression and ultimately help to better understand and combat pathogens,” says Barquist.
The results at a glance
• Gene features matter: The characteristics of targeted genes have a significant impact on guide RNA depletion in genome-wide screens.

• Data integration improves predictions: Combining data from multiple CRISPRi screens significantly improves the accuracy of prediction models and enables more reliable estimates of guide RNA efficiency.
• Designing better CRISPRi experiments: The study provides valuable insights for designing more effective CRISPRi experiments by predicting guide RNA efficiency, enabling precise gene-silencing strategies.
Funding
The study was supported by funds from the Bavarian State Ministry of Science and Art through the bayresq.net research network.

Researchers have been studying the transcription factor SREBP, a critical regulator of lipid biosynthesis. Precursor SREBP proteins, located in the endoplasmic reticulum (ER) of the cell, are transported through the golgi apparatus to the nucleus. Here, they promote the transcription of genes associated with lipid biosynthesis, playing a pivotal role in regulating cholesterol. SREBP-1c, a specific member of the SREBP family, is known to activate fatty acid synthesis. Interestingly, this process is inhibited by polyunsaturated fatty acids. The exact mechanism behind this regulation, however, remains to be elucidated.
The research team elucidated a novel cleavage mechanism of SREBP-1c, a protein involved in fatty acid synthesis, and confirmed its regulation by fatty acids. The cleavage of SREBP-1c occurs in the endoplasmic reticulum, with the rhomboid protease RHBDL4, located in the ER membrane, identified as a new cleavage enzyme for SREBP-1c. This cleavage process is activated by saturated fatty acids and deactivated by polyunsaturated fatty acids, suggesting that RHBDL4’s activity is modulated by the type of fatty acid. Additionally, the team discovered a unique mechanism where the VCP complex extracts the cleaved SREBP-1c protein from the endoplasmic reticulum. In the livers of mice deficient in the RHBDL4 gene and fed a high-fat and high-cholesterol diet, the activation of SREBP-1c cleavage was suppressed. This inhibited the expression of a group of target genes involved in fatty acid synthesis, polyunsaturated fatty acid synthesis and uptake, and lipoprotein secretion, which improved fatty liver pathophysiology, as observed in wild-type mice.
The RHBDL4-SREBP-1c pathway, uncovered in this study, represents a lipid homeostasis mechanism regulated by fatty acids. This groundbreaking discovery is anticipated to pave the way for developing new therapeutic strategies for metabolic disorders and lifestyle-related diseases stemming from abnormal lipid metabolism.
This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas program (Inflammation Cellular Sociology) JP17H06395 (to H.S.), Scientific Research (A) 15H02541 and 18H04051 (to H.S.), and Scientific Research (C) 16K01811 and 19K11737 (to S.-I.H.) from the Ministry of Science, Education, Culture, and Technology of Japan; AMED-CREST Grant Number 16gm0910003h0002 (to H.S.) from the Japan Agency for Medical Research and Development, AMED; and Ono Medical Research Foundation (to S.-I.H.).

The number of infections by the tick-borne TBE virus that are not detected by health services is far higher than previously assumed. This has been shown in a new study of Swedish blood donors from Uppsala University and the University Hospital in Uppsala. The results have been published in the journal Eurosurveillance, which is associated with the EU’s Centre for Disease Prevention and Control.
“We were very surprised that such a high proportion of the blood donors showed traces of a previous TBE virus infection. This is far more than could have been suspected based on the number of reported cases,” says Bo Albinsson, doctoral student at Uppsala University, one of the first authors of the article.
Tick-borne encephalitis (TBE) is a very serious disease that is increasingly common in large parts of Europe. According to statistics from the Public Health Agency of Sweden, 597 cases of the disease had been reported in Sweden by November 2023, the highest number ever registered in a single year.
TBE has been a notifiable disease since 2004 under the Communicable Diseases Act and all cases must therefore be reported to the regional infection control doctor and the Public Health Agency of Sweden. However, people who only develop mild symptoms or no symptoms at all are not detected by the health services and therefore do not show up in the statistics. Until now, the relationship between the number of reported cases and the proportion of people infected was unknown.
Traditional methods of investigating whether someone has previously been infected by the virus are not completely reliable as individuals who have been vaccinated against TBE can also test positive. On top of this, it is not known exactly how many people have been vaccinated, since Sweden has no national vaccination register for TBE.
In the new study, the result of a Swedish collaboration, the researchers have investigated blood tests from 2,700 anonymous blood donors from nine regions in Sweden. The method they used is called TBE-SMIA (suspension multiplex immunoassay) and was developed at the Zoonosis Science Center (ZSC) at Uppsala University in collaboration with the Clinical Microbiology Department at Uppsala University Hospital. It makes it possible for the first time to effectively distinguish the antibody response after TBE virus infection from the response after TBE vaccination. This has enabled the researchers to identify how many people have had the infection. They were also able to estimate the proportion of the population in each region that is vaccinated.
The results showed that the proportion of blood donors with a history of TBE virus infection varied from 1 per cent to 7 per cent between the different regions. Based on the population sizes of the regions, the researchers estimated that this corresponds to a total of more than 160,000 people aged 15-65, which is significantly higher than previous estimates.
The researchers also found that the proportion of blood donors vaccinated against TBE varied between 8.7 per cent and 57 per cent in the different regions. In total, this translates to over 1.6 million Swedes (aged 15-65) in the regions investigated.
“It is noteworthy that the number of confirmed TBE cases is increasing despite relatively good vaccination coverage. Further research is therefore needed, for example by carefully mapping the distribution of the virus in different tick populations. Our results provide an important background for future vaccination strategies and we believe it would be well worth considering establishing a national vaccination register for TBE,” says Tove Hoffman, researcher at the ZSC and the study’s other first author.

Advancements in the study of two rare heart conditions — peripartum cardiomyopathy (PPCM), and dilated cardiomyopathy (DCM) — contributed by researchers at the Perelman School of Medicine at the University of Pennsylvania may serve as critical guides in future work toward developing therapies for the conditions. The lab of Zoltan Arany, MD, PhD, the Samuel Bellet Professor of Cardiology and a professor of Cell and Developmental Biology, published their findings this month in the New England Journal of Medicine (NEJM), adding to separate research they recently published in the Journal of Clinical Investigation (JCI).
PPCM is a severe cardiac condition affecting approximately 1 in 1,000 pregnant or recently pregnant women, characterized by the weakening of the heart muscle, leading to reduced cardiac function. Certain factors increase the risk of developing PPCM, including advanced maternal age, multiple gestations (twins or more), anemia, and hypertensive disorders of pregnancy. Black women in the United States are at a much higher risk compared to White women, for reasons that remain unclear. Treatment for PPCM generally involves standard heart failure management strategies, including medications like diuretics, beta-blockers, and ACE inhibitors. In severe cases, advanced therapies such as LVADs or heart transplantation may be considered.
Unlike PPCM, DCM can occur at any age and is not specifically related to pregnancy and affects about 1 in 100 people. Risk factors for DCM can include a family history of heart disease, certain infections, exposure to toxins, and other underlying heart conditions.
The recent JCI study focused on the role of genetic variants in the TTN gene, which encodes for a crucial protein called titin. Titin acts like a spring, playing a vital role in the assembly and regulation of heart muscle contraction. The study sheds light on how specific genetic variants, known as truncating variants (TTNtvs), in the TTN gene may contribute to DCM. Arany and his team developed a patient-specific antibody to detect these TTNtvs in human heart tissue. Using this novel approach, they found that TTNtvs are present in hearts affected by DCM, indicating a potential link between these genetic variants and the development of the disease.
The study also revealed that the truncated titin proteins associated with TTNtvs integrate into the heart’s muscle structure. This suggests that these genetic variants may impact the sarcomere, the basic unit of heart muscle, influencing its structure and function.
Meanwhile, the recent article in the NEJM consolidates the current state of knowledge about PPCM, while providing a roadmap for navigating the complexities of the disease. Past research from the Arany lab has highlighted the racial disparities in PPCM, with Black women in the US being four times more likely than White women to develop the disease. The NEJM article emphasizes the critical need for early diagnosis and the development of effective management strategies, given that PPCM is now a leading cause of maternal mortality in many parts of the world.
“There is a great need for further research into long-term outcomes, racial disparities, and the underlying mechanisms of PPCM,” said Arany. “We hope our recent research signals a call to action for the medical community to address this critical issue affecting young women, their families, and newborns.”
There is a profound lack of research in peripartum cardiomyopathy (PPCM), which limits expert’s ability to find the best way to treat, and ultimately prevent it. In order to make important discoveries, doctors at the Perelman School of Medicine created PPCM-R, the first patient-focused registry about PPCM. Among the goals of the PPCM-R is to create a database of PPCM survivor medical records driven by patients, and to answer important research questions and ultimately prevent PPCM.
The work was supported by grants from the National Heart, Lung, and Blood Institute (HL152446, HL126797, HL149891), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-53461-12), the Children’s Hospital of Philadelphia Frontier Program, Foundation Leducq Research Grant no. 20CVD01, and by the Center for Engineering Mechanobiology through a grant from the National Science Foundation’s Science and Technology program (15-48571).

Much like ripples on the water can betray powerful currents below the surface, small changes in our bodies can sometimes be an indicator of a serious condition. Now, researchers from Japan say that cells in the blood may provide telltale signs of important immune dysfunction.
In a study recently published in Cell Genomics, researchers from Osaka University have revealed that subtle changes in specific immune cell populations may signal the presence of an autoimmune disease.
In autoimmune conditions, which affect up to 5% of the population, the body’s immune cells attack the body instead of disease-causing agents. A subset of immune cells known as CD4+ T cells are known to play a key role in the onset and progression of many autoimmune diseases.
“CD4+ T cells can exist in a naive or memory state, can exhibit polarization to a Th1, Th2, Th17, or Tfh phenotype, or can be regulatory T cells,” says lead author of the study Yoshiaki Yasumizu. “However, there is still a lot of heterogeneity among the cells in these categories, and the effect that this has on autoimmune disease remains largely unclear.”
To address this, the researchers used single-cell RNA sequencing and an analytical approach known as non-negative matrix factorization to analyze the gene expression profiles of CD4+ T cells in healthy individuals and patients with autoimmune diseases. This analysis identified 18 different types of CD4+ T cells and 12 distinct gene programs, which were then used as a reference to analyze almost 2 million CD4+ T cells from nearly 1000 people with 20 different autoimmune diseases.
“The results were very exciting,” explains Shimon Sakaguchi, senior author. “We found that characteristic changes in CD4+ T cells defined by the 18 categories and 12 gene programs were associated with specific autoimmune diseases, suggesting that these conditions have a detectable ‘signature’.”
In addition, the researchers detected distinctive changes in CD4+ T cell categories and gene programs that were linked to aging and sex, two factors that are known to influence the risk of developing an autoimmune disorder. Furthermore, genetic factors that promote disease development accumulated in CD4+ T cells exhibiting specific gene programs.
“Our study presents a comprehensive catalog of the CD4+ T cell changes that are seen in 20 different autoimmune diseases, providing an invaluable resource for researchers,” says Yasumizu.
In the future, this catalog could potentially be used to detect autoimmune disease in patients by simply taking a blood sample and analyzing the CD4+ T cell features, thus paving the way for precision medicine.

Salmonella is notorious for surviving and replicating in macrophages, which are normally lethal to invading bacteria because of their inhospitable environment. In a new study, researchers have discovered how a system of proteins, called TamAB, helps Salmonella survive under the harsh conditions inside macrophages.
Salmonella is a foodborne pathogen that causes more than a million infections each year in the U.S. Concerningly, it can kill young, old, and immunocompromised individuals. What makes these bacteria especially dangerous is their ability to evade our immune responses.
Macrophages are designed to kill bacteria by spraying them with antibacterial products, exposing them to acidic environments, and withholding magnesium, all of which target the outer layers of the bacteria. Salmonella, however, has evolved mechanisms to survive and grow in this environment.
Under normal conditions, Salmonella uses a complex called Bam to assemble certain proteins that are transported to its outer membrane layer. In previous studies, the group have shown that inside macrophages, the complex is compromised and, as a result, Salmonella depends on the PhoPQ system to sense the environment and orchestrate necessary changes in the outer membrane.
Studies in other bacteria have shown that the TamAB complex performs similar functions to Bam, which led the researchers of the present study to ask whether it might be important in Salmonella. They found that the genes that were responsible for producing TamAB were being controlled by PhoPQ.
“We knew from other studies that TamA was similar to BamA in its structure. When we realized that PhoPQ was controlling this TamAB complex, we hypothesized that the Bam complex struggles in the macrophage and TamA is induced by PhoPQ to help,” said James Slauch (IGOH), a professor of microbiology.
To test their hypothesis, the researchers first removed TamAB from Salmonella. To their surprise, these mutants were still able to cause an infection in mice. However, when they also crippled the Bam complex, the mutants that lacked TamAB struggled.

The researchers also saw similar results when they recreated the macrophage-like conditions in test tubes and tested the different Salmonella mutants. They observed that mutants that lacked both the Bam and TamAB complexes were sensitive to vancomycin. This result is particularly intriguing because vancomycin is not used to treat Salmonella since it can’t cross the outer membrane. This sensitivity suggests that the two complexes have a function in creating or maintaining the outer membrane, although the mechanism is not clear.
“Basically, TamAB helps create favorable conditions for the Bam complex to work but it’s indirect,” said Yekaterina Golubeva, a research scientist in the Slauch lab.
It is still unclear what the indirect effect might be. “The problem is that studying the outer membrane is complicated because everything is interconnected. If you mess up the Bam complex, it disrupts additional machineries required for synthesis of the outer membrane. As a result, understanding the contributions of these proteins is difficult,” Slauch said.
Nonetheless, the researchers are now interested in figuring out how TamAB helps. To do so, they will be using suppressor mutants that have accumulated different types of mutations that can help them grow even if their Bam and Tam complexes are defective, providing insights into Salmonella’s outer membrane structure and function.
“There are efforts underway in biotechnology companies that are targeting the Bam complex as a way to treat Salmonella infections,” Slauch said. “Understanding the structure of the outer membrane when Salmonella is in a macrophage can help us understand what will affect its sensitivity to drugs and our results with vancomycin is consistent with that.”
The study “TamAB is regulated by PhoPQ and functions in outer membrane homeostasis during Salmonella pathogenesis” was published in the Journal of Bacteriology. The work was funded by the National Institutes of Health.

Pancreatic cancer presents a challenging prognosis, marked by a five-year overall survival rate of merely 12.5%. Diagnosis frequently occurs at an advanced stage, characterized by metastasis to distant sites. The intricate molecular mechanisms governing pancreatic cancer metastasis remain a subject of ongoing research and exploration. In a recent article published in Nature Communications, Moffitt Cancer Center researchers, in collaboration with The Tisch Cancer Institute; St. Jude Children’s Research Hospital; the Agency for Science, Technology and Research in Singapore; and the University of Otago in New Zealand, demonstrate that deregulation of a protein called RBFOX2, involved in RNA splicing, contributes to the progression and metastasis of pancreatic cancer.
RNA is a nucleic acid that promotes the synthesis of proteins. While the nucleotide sequence of RNA is encoded by the DNA of the genome, RNA molecules undergo several modifications before eventually entering the ribosome to make protein. An important process that modifies RNA sequences is alternative splicing, whereby specific sequences within the RNA molecule may be rearranged, included or excluded. This process results in different versions of RNA molecules generated from a single DNA sequence that will produce protein variants with potentially different activities. Alternative RNA splicing is critical for many cellular processes; however, the involvement of alternative RNA splicing in cancer development is not entirely understood.
The research team wanted to assess whether alternative RNA splicing is involved in the development and progression of pancreatic cancer. Through molecular-based laboratory experiments and mouse models, they discovered that RNA-binding proteins involved in splicing regulation were involved in pancreatic cancer progression. One of the key proteins they identified is RBFOX2.
Results showed RBFOX2 protein levels were lower in pancreatic cancer cells that had metastasized to other sites. These observations suggest that RBFOX2 may be a tumor suppressor protein that normally functions to inhibit cancer metastasis. The researchers confirmed this hypothesis by demonstrating that loss of RBFOX2 in pancreatic cell lines and mouse models increased cell migration, invasion, tumor development and metastasis.
The researchers performed additional experiments to determine the downstream pathways impacted by RBFOX2 that lead to pancreatic cancer progression. They found that RBFOX2 regulates the splicing of RNA molecules that code for proteins involved in cytoskeletal remodeling, with one of the critical molecules being RNA that codes for the protein ABI1. In cells without RBFOX2, the location of ABI1 is redistributed to the cell periphery, where it impacts the cell cytoskeleton and promotes cell migration.
These combined observations demonstrate the importance of alternative RNA splicing to pancreatic cancer progression and suggest the need for additional studies to understand the mechanisms regulating RBFOX2 splicing activity fully.
“While analyses to date have identified few splicing regulators with prognostic implications in pancreatic cancer, the incidence of exon splicing events conserved across pancreatic tumors and other cancers suggests the processes regulated by alternatively spliced transcripts are integral to cancer progression,” said Karen Mann, Ph.D., assistant member of the Department of Molecular Oncology at Moffitt.
This study was supported by a Skip Viragh Career Development Award from the Pancreatic Cancer Action Network, the National Cancer Institute (R01CA279713, R01CA244780, R01CA244780, R03CA270679, R61CA278402, P30 CA196521), the Irma T. Hirschl Trust, the Emerging Leader Award from the Mark Foundation and the Ramon Areces Foundation.

For individuals who experience chronic pain, weather can be a significant factor in their day-to-day plans. In a recent study from the University of Georgia, about 70% of respondents said they would alter their behavior based on weather-based pain forecasts.
“We’re finding more consistent relationships between weather patterns and pain, so it seems more possible to make weather-based pain forecasts,” said lead author and geography/atmospheric sciences lecturer Christopher Elcik. “This study was to survey and see what the audience was for this type of forecast.”
The study surveyed more than 4,600 individuals, and among migraine sufferers, 89% identified weather as something that impacts their pain level, and 79% saw weather as a trigger for pain. Among individuals with other conditions, 64% said weather patterns could trigger pain and 94% identified weather as a factor that impacts pain.
Elcik built on previous research regarding specific weather patterns and pain-related conditions to gauge public interest in a weather-based pain forecast, which could indicate high or moderate risk for migraines or chronic pain.
“I see how much people can be affected by these types of pain, so if I can provide someone with insight into the level of risk for a day, maybe people can take steps to prevent the pain from happening,” Elcik said. “There are preventative measures people can take if risks are higher.”
If the hypothetical risk was high, more than half of respondents said they were likely to take preventive measures, such as medication, resting or avoiding compounding triggers, and about 47% of respondents with migraines and 46% with pain-related conditions were “extremely likely” to take such measures.
Desire for a forecasting tool was quite high, Elcik said, with 72% of those living with migraine and 66% with pain-related conditions saying they would alter their behavior by canceling plans or taking preventive measures in response to a weather-based pain forecast. Some respondents reported already using web-based tools, such as AccuWeather’s arthritis or migraine forecast, which predicts low-to-high risk according to atmospheric conditions. With existing tools, however, there is little available information about the variables considered or how the predictions are made.

Likelihood to continue with plans also depended on the length of the activity. If plans were about 30 minutes long, 57% of respondents with migraines and 52% with pain-related conditions said they were “extremely likely” to continue plans despite a moderate risk of pain, and about 43% from each group would continue with a highest risk forecast.
With an activity lasting more than three hours, however, that number dropped to around 23% for moderate risk and 18% for high risk with migraines and 21% or 23%, respectively, for other pain-related conditions. As level for risk increased, so did the likelihood to alter plans.
“This was across the board,” Elcik said. “Everyone was more likely to cancel plans if the forecast risk was higher.”
While additional research and studies are needed to create a reliable pain-based weather forecast, Elcik said this study highlights the importance of developing such a resource.
“This publication shows there’s an audience that’s willing and eager to try something new, and there are probably many more people who would benefit — more than we even thought,” he said. “I think these results can push other researchers to also look at similar, larger-scale weather phenomena and help the community better understand how the atmosphere does impact pain.”