Nonsmall cell lung cancer (NSCLC) is a leading cause of cancer-related deaths. While mutations in Kras and overexpression of Myc are commonly found in patients, the role of altered lipid metabolism in lung cancer and its interplay with oncogenic Myc is poorly understood. Here we use a transgenic mouse model of Kras-driven lung adenocarcinoma with reversible activation of Myc combined with surface analysis lipid profiling of lung tumors and transcriptomics to study the effect of Myc activity on cholesterol homeostasis. Our findings reveal that the activation of Myc leads to the accumulation of cholesteryl esters (CEs) stored in lipid droplets. Subsequent Myc deactivation leads to further increases in CEs, in contrast to tumors in which Myc was never activated. Gene expression analysis linked cholesterol transport and storage pathways to Myc activity. Our results suggest that increased Myc activity is associated with increased cholesterol influx, reduced efflux, and accumulation of CE-rich lipid droplets in lung tumors. Targeting cholesterol homeostasis is proposed as a promising avenue to explore for novel treatments of lung cancer, with diagnostic and stratification potential in human NSCLC.

Synaptic transmission leading to release of neurotransmitters in the nervous system is a fast and highly dynamic process. Previously, protein interaction and phosphorylation have been thought to be the main regulators of synaptic transmission. Here we show that sialylation of N-linked glycosylation is a novel potential modulator of neurotransmitter release mechanisms by investigating depolarization-dependent changes of formerly sialylated N-linked glycopeptides. We suggest that negatively charged sialic acids can be modulated, similarly to phosphorylation, by the action of sialyltransferases and sialidases thereby changing local structure and function of membrane glycoproteins. We characterized site-specific alteration in sialylation on N-linked glycoproteins in isolated rat nerve terminals after brief depolarization using quantitative sialiomics. We identified 1965 formerly sialylated N-linked glycosites in synaptic proteins and found that the abundances of 430 glycosites changed after 5 s depolarization. We observed changes on essential synaptic proteins such as synaptic vesicle proteins, ion channels and transporters, neurotransmitter receptors and cell adhesion molecules. This study is to our knowledge the first to describe ultra-fast site-specific modulation of the sialiome after brief stimulation of a biological system.

Cross-linking MS (XL-MS) has been recognized as an effective source of information about protein structures and interactions. In contrast to regular peptide identification, XL-MS has to deal with a quadratic search space, where peptides from every protein could potentially be cross-linked to any other protein. To cope with this search space, most tools apply different heuristics for search space reduction. We introduce a new open-source XL-MS database search algorithm, OpenPepXL, which offers increased sensitivity compared with other tools. OpenPepXL searches the full search space of an XL-MS experiment without using heuristics to reduce it. Because of efficient data structures and built-in parallelization OpenPepXL achieves excellent runtimes and can also be deployed on large compute clusters and cloud services while maintaining a slim memory footprint. We compared OpenPepXL to several other commonly used tools for identification of noncleavable labeled and label-free cross-linkers on a diverse set of XL-MS experiments. In our first comparison, we used a data set from a fraction of a cell lysate with a protein database of 128 targets and 128 decoys. At 5% FDR, OpenPepXL finds from 7% to over 50% more unique residue pairs (URPs) than other tools. On data sets with available high-resolution structures for cross-link validation OpenPepXL reports from 7% to over 40% more structurally validated URPs than other tools. Additionally, we used a synthetic peptide data set that allows objective validation of cross-links without relying on structural information and found that OpenPepXL reports at least 12% more validated URPs than other tools. It has been built as part of the OpenMS suite of tools and supports Windows, macOS, and Linux operating systems. OpenPepXL also supports the MzIdentML 1.2 format for XL-MS identification results. It is freely available under a three-clause BSD license at https://openms.org/openpepxl.

The early detection of pancreatic ductal adenocarcinoma is a complex clinical obstacle yet is key to improving the overall likelihood of patient survival. Current and prospective carbohydrate biomarkers CA19-9 and sTRA are sufficient for surveilling disease progression yet are not approved for delineating PDAC from other abdominal cancers and non-cancerous pancreatic pathologies. To further understand these glycan epitopes, an imaging mass spectrometry approach was utilized to assess the N-glycome of the human pancreas and pancreatic cancer in a cohort of PDAC patients represented by tissue microarrays and whole tissue sections. Orthogonally, these same tissues were characterized by multi-round immunofluorescence which defined expression of CA19-9 and sTRA as well as other lectins towards carbohydrate epitopes with the potential to improve PDAC diagnosis. These analyses revealed distinct differences not only in N-glycan spatial localization across both healthy and diseased tissues but importantly between different biomarker-categorized tissue samples. Unique sulfated bi-antennary N-glycans were detected specifically in normal pancreatic islets. N-glycans from CA19-9 expressing tissues tended to be bi-, tri- and tetra-antennary structures with both core and terminal fucose residues and bisecting N-acetylglucosamines. These N-glycans were detected in less abundance in sTRA-expressing tumor tissues, which favored tri- and tetra-antennary structures with polylactosamine extensions. Increased sialylation of N-glycans was detected in all tumor tissues. A candidate new biomarker derived from IMS was further explored by fluorescence staining with selected lectins on the same tissues. The lectins confirmed the expression of the epitopes in cancer cells and revealed different tumor-associated staining patterns between glycans with bisecting GlcNAc and those with terminal GlcNAc. Thus, the combination of lectin-IHC and IMS techniques produces more complete information for tumor classification than the individual analyses alone. These findings potentiate the development of early assessment technologies to rapidly and specifically identify PDAC in the clinic that may directly impact patient outcomes.

This positive personality trait linked to more suicidal thoughts and suicide itself.

Neural responses are naturally variable from one moment to the next, even when the stimulus is held constant. What factors might underlie this variability in neural population activity? We hypothesized that spontaneous fluctuations in cortical stimulus representations are created by changes in arousal state. We tested the hypothesis using a combination of fMRI, probabilistic decoding methods, and pupillometry. Human participants (20 female, 12 male) were presented with gratings of random orientation. Shortly after viewing the grating, participants reported its orientation and gave their level of confidence in this judgment. Using a probabilistic fMRI decoding technique, we quantified the precision of the stimulus representation in the visual cortex on a trial-by-trial basis. Pupil size was recorded and analyzed to index the observer's arousal state. We found that the precision of the cortical stimulus representation, reported confidence, and variability in the behavioral orientation judgments varied from trial to trial. Interestingly, these trial-by-trial changes in cortical and behavioral precision and confidence were linked to pupil size and its temporal rate of change. Specifically, when the cortical stimulus representation was more precise, the pupil dilated more strongly prior to stimulus onset and remained larger during stimulus presentation. Similarly, stronger pupil dilation during stimulus presentation was associated with higher levels of subjective confidence, a secondary measure of sensory precision, as well as improved behavioral performance. Taken together, our findings support the hypothesis that spontaneous fluctuations in arousal state modulate the fidelity of the stimulus representation in the human visual cortex, with clear consequences for behavior.

Hay River RCMP say they believe two weekend incidents, including one in which a person was shot, are linked to drugs and organized crime.

Ontario Provincial Police (OPP) have released dashcam footage of a crash that sent two people to hospital in life-threatening condition, linked to an ongoing investigation into rocks being thrown at moving vehicles in the GTA.

No studies sufficiently answer the question, finds the GAO, which means debates over whether newer restorative-justice approaches help or harm safety are likely to continue.

A consistent bedtime may be more important to a child’s ability to control their emotions and behavior than the duration or quality of their sleep, according to a new publication by researchers in the Penn State College of Health and Human Development and Penn State College of Medicine. 

Loneliness and cognitive performance were related in the short term for older adults, according to a new study from researchers in the Penn State College of Health and Human Development.

When teachers have experienced stressful events in their own childhoods, it could shape the way that they build classroom climate for their students, a study suggests.

Attorney General Kathy Jennings announced Friday that the DOJ’s Fraud Division has secured revocations of the corporate charters or certificates of formation of multiple Delaware-registered business entities connected to criminal entities, including a Venezuelan cartel and a federally sanctioned online pharmacy based in Argentina. “Delaware’s central role in the business community is both a privilege and a responsibility,” said […]

washington — The U.S. military said Monday that it had carried out strikes against nine targets associated with Iranian groups in Syria.  In a statement, the U.S. military said the strikes were made against two locations in Syria and were a response to several attacks on U.S. personnel in Syria in the past 24 hours.  The U.S. has occasionally carried out strikes against targets linked to Iran in both Iraq and Syria. In February, the U.S. launched airstrikes in Iraq and Syria against more than 85 targets linked to Iran's Islamic Revolutionary Guard Corps and militias it backs, in retaliation for a deadly attack on U.S. troops.  "These strikes will degrade the Iranian backed groups' ability to plan and launch future attacks on U.S. and coalition forces," the U.S. military said after the most recent strikes.  The U.S. has 900 troops in Syria and 2,500 in neighboring Iraq, on a mission to advise and assist local forces trying to prevent a resurgence of Islamic State, which in 2014 seized large swaths of both countries but was later defeated.  The U.S. has sent warships and fighter aircraft to the region since the Israel-Hamas conflict erupted on October 7, 2023, to try to deter Iran and Iran-backed groups from getting involved in the conflict.  U.S. forces have also helped shoot down projectiles that Iran launched toward Israel this year. 

BUENOS AIRES — Three people have been charged in connection with the death of Liam Payne, a former member of musical group One Direction who died after falling from the balcony of his hotel room in Buenos Aires last month, Argentine prosecutors said Thursday. Prosecutor Andrés Madrea charged the three suspects, whose identities were not revealed, with the crimes of "abandonment of a person followed by death" and "supplying and facilitating the use of narcotics," the prosecutor's office said. Madrea also requested their arrest to judge Laura Bruniard, who ruled the three cannot leave the country. Payne fell from his room's balcony on the third floor of his hotel in the upscale neighborhood of Palermo, in the Argentine capital. His autopsy said he died from multiple injuries and external bleeding. Prosecutors also said that Payne's toxicological exams showed that his body had "traces of alcohol, cocaine and a prescribed antidepressant" in the moments before his death. Investigators said hours after Payne's death that he was by himself when he fell. But the prosecutors' office said Thursday that one of the people charged was often with the singer during his time in Buenos Aires. The second is a hotel staffer who allegedly gave Payne cocaine during his stay between October 13 and 16. And the third is a drug dealer. The charges in Payne's case bear some resemblance to the U.S. cases stemming from the death of Friends star Matthew Perry a year ago. The actor's personal assistant and a longtime friend are among those charged with helping supply him with ketamine in the final months of his life, leading up to his overdose on the anesthetic. Three young men were similarly charged in the opioid-overdose death of rapper Mac Miller in 2018. Local authorities gathered, among other pieces of evidence, Payne's cellphone records, material for forensics and testimonies. They are yet to unlock the singer's personal computer – which is damaged – and other devices that were seized. Payne's autopsy showed his injuries were neither caused by self-harm nor by physical intervention of others. The document also said that he did not have the reflex of protecting himself in the fall, which suggests he might have been unconscious. Prosecutors in Argentina also ruled out the chances of Payne dying by suicide. One Direction was among the most successful boy bands of recent times. It announced an indefinite hiatus in 2016 and Payne — like his former bandmates Zayn Malik, Harry Styles, Niall Horan, and Louis Tomlinson — pursued a solo career. The singer had posted on his Snapchat account that he traveled to Argentina to attend Horan's concert in Buenos Aires on October 2. He shared videos of himself dancing with his girlfriend, American influencer Kate Cassidy, and singing along in the stands. Cassidy had left Argentina after the show, but Payne stayed behind. 

The strikes were in response to attacks on US personnel over the past 24 hours, CENTCOM reported.

Last year’s marine heatwaves saw an unprecedented decline in the growth of phytoplankton and algae, which many animals in the oceans depend on for food

Millions of years ago, our ancestors lost a gene for producing vitamin C and got a taste for citrus. Since then, we've cultivated the tangy fruits into global staples like sweet oranges and sour lemons

Title: PFAS 'Forever Chemicals' Linked With Liver Cancer
Category: Health News
Created: 8/10/2022 12:00:00 AM
Last Editorial Review: 8/10/2022 12:00:00 AM

Title: RA Drugs Linked to Slight Skin Cancer Risk
Category: Health News
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Title: Propofol Linked to Michael Jackson's Death
Category: Health News
Created: 8/25/2009 12:00:00 AM
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Title: Pesticide Exposure Linked to ADHD Risk
Category: Health News
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Title: Chronic Drinking Linked to Circadian Disruptions
Category: Health News
Created: 8/25/2010 12:00:00 AM
Last Editorial Review: 8/26/2010 12:00:00 AM

Title: Study: BPA Linked to Higher Testosterone Levels
Category: Health News
Created: 8/27/2010 10:12:00 AM
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Title: Gallstones in Kids, Teens Linked to Obesity
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Title: Some Antibiotics Linked to Serious Nerve Damage
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Title: Migraines Linked to Changes in Brain Structure
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Created: 8/28/2013 4:36:00 PM
Last Editorial Review: 8/29/2013 12:00:00 AM

Title: Facebook Use Linked to Brain's Reward Center
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Created: 8/29/2013 4:36:00 PM
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Title: Anxiety Linked to a Need for More Personal Space
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Created: 8/29/2013 2:35:00 PM
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Title: 'Sleep Drunkenness' Is Common and Linked to Other Behavior Issues
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Created: 8/25/2014 4:35:00 PM
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Title: Pot Belly Linked to Heavy Smoking
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Created: 8/22/2015 12:00:00 AM
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Title: Blood Pressure Drugs Linked to Longer Ovarian Cancer Survival
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Created: 8/24/2015 12:00:00 AM
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Title: Mom's Healthy Diet Linked to Lower Heart Defect Risk at Birth
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Created: 8/25/2015 12:00:00 AM
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Title: Obesity May Be Linked to Greater Risk of Stillbirth
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Created: 8/28/2015 12:00:00 AM
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Title: Antibiotics Linked to Type 2 Diabetes Risk
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Title: Use of Cancer-Linked Fibroid Device Declines After FDA Warning
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Created: 8/23/2016 12:00:00 AM
Last Editorial Review: 8/24/2016 12:00:00 AM

Title: Scans Show Range of Zika-Linked Infant Brain Defects
Category: Health News
Created: 8/23/2016 12:00:00 AM
Last Editorial Review: 8/24/2016 12:00:00 AM

Title: Autism-Linked Genes Often Differ Between Siblings
Category: Health News
Created: 8/25/2016 12:00:00 AM
Last Editorial Review: 8/26/2016 12:00:00 AM

Title: Smoking Linked to Frailty in Seniors
Category: Health News
Created: 8/29/2017 12:00:00 AM
Last Editorial Review: 8/30/2017 12:00:00 AM

Title: Fentanyl Drives Rise in Opioid-Linked Deaths in U.S.
Category: Health News
Created: 8/31/2017 12:00:00 AM
Last Editorial Review: 9/1/2017 12:00:00 AM

Title: Salmonella Outbreak in 4 States Linked to Kosher Chicken: CDC
Category: Health News
Created: 8/30/2018 12:00:00 AM
Last Editorial Review: 8/30/2018 12:00:00 AM