Gmerice Hammond

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Phosphoinositides are rare membrane lipids that act as zip codes, marking different compartments inside the cell and directing the signaling that happens there. This review surveys 50 years of research on where each of the eight phosphoinositide species lives inside the cell and what that location means for function. The authors conclude that these lipids act as spatial organizers of cell signaling rather than just transient messengers.

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Lipids in cells are much harder to study than proteins because standard molecular biology tools — antibodies, genetic tags — don't work well on them. This review describes the current toolkit for tracking and manipulating specific membrane lipids in cells, covering imaging approaches, chemical inhibitors, and engineered systems that can add or remove lipids on demand. The goal is to make lipid biology accessible to cell biologists who primarily work with proteins.

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Scientists analyzed the gravitational wave signal GW250114 — the strongest ever detected — to test whether the black hole produced by the merger behaves exactly as Einstein's general relativity predicts. The analysis confirmed at least two distinct oscillation modes in the signal and measured their frequencies to within a few percent of theoretical predictions, providing the most stringent single-event test of general relativity to date. These results validate both the theory and the Kerr description of black holes with unprecedented precision.

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Tracking lipids inside living cells is technically difficult because most methods require killing the cell first. This protocol describes how to use a genetically encoded protein sensor to image a key membrane lipid (PI(4,5)P2) in live cells, using either standard confocal microscopy or single-molecule TIRF microscopy for higher sensitivity.

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Cells use an enzyme family called diacylglycerol kinases (DGKs) to produce phosphatidic acid (PA), a signaling lipid, but it has been unclear which specific enzyme is responsible in a given context. This study tested two chemical inhibitors and found that one (BMS-502) selectively and safely blocks DGKalpha, while the other paradoxically increases PA and kills cells. Using live-cell imaging, the researchers showed that both DGKalpha and a second enzyme family (PLDs) must be blocked together to meaningfully reduce PA levels during cell signaling.

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The cancer protein KRAS must attach to the cell membrane to drive tumor growth, which requires a specific lipid environment maintained by a chain of lipid-processing steps. This study identified a group of phosphatases (MTMR 2/3/4/7) whose activity is required to keep that lipid environment intact, and showed that silencing them disrupts KRAS membrane binding by depleting an essential upstream lipid (PI4P). This reveals a new set of potential targets for therapies aimed at blocking KRAS in cancer.

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Phosphatidic acid (PA) is a signaling lipid in cells, but tools to track it in living cells have been inadequate. This study developed PILS-Nir1, a new biosensor based on a structural domain from the lipid transfer protein Nir1, and demonstrated it is more sensitive than existing PA sensors. It detected low-level PA production from an enzyme (PLD) downstream of muscarinic receptors for the first time, opening new possibilities for studying this lipid in real time.

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When lipid biosensors are expressed at levels high enough to see under a microscope, they compete with the cell's own proteins for the lipid they are designed to detect, potentially corrupting the very signal they are meant to report. This study demonstrated that a commonly used PIP3 biosensor blocks the cancer-related protein AKT from reaching the membrane in individual cells, even though the effect is masked in a population of cells. Reducing biosensor expression to single-molecule levels eliminated the interference and improved both the range and timing accuracy of the measurements.

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A protein called corticosteroid-binding globulin (CBG) carries most of the body's stress hormone (cortisol/corticosterone) in the blood, and an enzyme made by immune cells (neutrophil elastase) can cleave CBG to release more free hormone. This study showed that in male mice on a high-fat diet, neutrophil elastase increases specifically in abdominal fat tissue, raising local glucocorticoid levels there and worsening glucose tolerance — an effect that disappeared when the adrenal glands were removed. Humans with low levels of a CBG-protecting protein also showed elevated glucocorticoid levels in fat tissue, connecting this enzyme axis to metabolic disease.

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Lipid biosensors — proteins that glow when they bind a specific lipid — are widely used to study cell signaling, but using them at high levels can interfere with the very process being studied by sequestering the lipid away from its natural targets. This study showed that standard overexpression of a PI3-kinase biosensor blocks the normal activation of AKT, a key cancer-related signaling protein, while expressing the same sensor at very low (single-molecule) levels avoids this problem and actually provides sharper measurements. The approach establishes a best practice for using lipid biosensors without disrupting the signaling they are meant to observe.

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This study enrolled 212 men attending a fertility clinic in Ghana to examine how lifestyle choices affect sperm quality and reproductive hormones. Smoking, psychological stress, and higher body weight were all linked to worse sperm counts, motility, and lower testosterone. The findings support public health efforts to address modifiable lifestyle factors as a practical way to improve male fertility outcomes.

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Emergency responders often encounter opioid overdose patients who refuse hospital transport, leaving a gap in connecting them to treatment. This study examined the experiences of overdose survivors and team members in a Columbus, Ohio post-overdose outreach program (RREACT), finding that fear of withdrawal, stigma, and limited treatment availability were major barriers while strong personal relationships and immediate practical support were key facilitators. The results offer lessons for designing EMS-based interventions to improve treatment engagement after overdose.

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Medicare launched the ACO REACH payment model in 2023, designed to improve care equity by financially supporting providers that serve higher-risk, underserved patients. Comparing ACO REACH enrollees to the broader Medicare population and to an older program (MSSP), this study found that REACH beneficiaries were actually older, more likely to be White, less likely to be Black or Hispanic, and less likely to live in rural or high-poverty areas. In its first year, the program did not attract providers serving the most disadvantaged beneficiaries.

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The cancer-driving protein KRAS must anchor to the cell's outer membrane to function, and it does so partly through a lipid called phosphatidylserine. This study found that a group of phosphatases called MTMRs maintains the right lipid environment at the membrane for KRAS to stay anchored, by controlling the levels of a lipid (PI4P) that a transfer protein (ORP5) needs to deliver phosphatidylserine. Silencing these phosphatases displaces KRAS from the membrane and reduces its activity, pointing to a new vulnerability in KRAS-driven cancers.

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Medicare's Skilled Nursing Facility Value-Based Purchasing program ties payments to 30-day hospital readmission rates, but most facilities end up penalized. This analysis found that facilities serving more Black or Hispanic patients, for-profit facilities, and those in socioeconomically deprived urban areas in the South were substantially more likely to receive the maximum penalty. The findings suggest the program may inadvertently penalize facilities that face the greatest structural challenges rather than rewarding genuine quality differences.

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Phosphatidic acid (PA) is a lipid that coordinates membrane trafficking and lipid balance, but existing tools for tracking it in living cells are not sensitive enough to detect modest changes. This study identified a new biosensor, PILS-Nir1, derived from structural analysis of a lipid transfer protein, and showed it specifically detects PA at cellular membranes with greater sensitivity than previous sensors. The tool revealed PA production by an enzyme (PLD) downstream of a common receptor type that had previously been too small to detect.

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The gravitational wave event GW250114 was detected with exceptional signal strength, making it the loudest gravitational wave observed so far. Analysis of the post-merger signal confirmed it matches the predicted vibrations of a Kerr black hole, and Hawking's area law — which says black hole surface area cannot decrease — was verified to high confidence. The event provides an unusually precise single-observation test of general relativity.

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PIP5K enzymes produce most of the cell's supply of PI(4,5)P2, a lipid essential for plasma membrane function, and they work more efficiently as dimers on the membrane surface. This study developed a single-molecule imaging assay to watch PIP5K dimerization in real time and found that a related enzyme, PIP4K, suppresses PIP5K activity by preventing it from forming these active dimers. The findings explain a key mechanism by which cells keep PI(4,5)P2 levels stable.

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Black residents are more likely to live in nursing homes with lower quality care, and racial segregation of nursing homes may worsen this gap. Using 2023 national data, this study found that facilities with more Black residents had worse inspection deficiency scores, and this gap was larger in counties with more racially segregated nursing home markets. The results support targeted policy action to address chronic underinvestment in facilities that predominantly serve Black residents.

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PI(3,5)P2 is a rare lipid found on endosomes whose loss is linked to neurodegenerative diseases, but studying it in living cells has been difficult due to a lack of good sensors. This study compared available biosensors and demonstrated that a newly described sensor, SnxA, is more sensitive and more faithfully reports PI(3,5)P2 levels than previous tools. The results validate SnxA as the preferred biosensor for real-time imaging of this lipid in cells.

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Diacylglycerol kinase-alpha (DGKα) acts as a brake on T cell immune responses, and blocking it is a potential strategy for cancer immunotherapy. This study developed a stereospecific covalent inhibitor (AHL-7160) that selectively targets DGKα, identified exactly where it attaches to the protein, and showed that it enhances T cell killing of a glioblastoma cell line. Prolonged treatment also caused selective degradation of DGKα, establishing this compound as a potential therapeutic tool for boosting anti-tumor immunity.

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The actin-binding protein profilin1 (Pfn1) was deleted from cells using CRISPR, which unexpectedly caused a drop in a major signaling lipid (PIP2) at the cell surface. Further experiments showed this effect depends on Pfn1's ability to regulate actin and on the activity of an enzyme that breaks down PIP2. Broad lipid profiling also revealed that losing Pfn1 disrupts many other lipid species, identifying it as a previously unrecognized regulator of overall lipid balance in cells.

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Researchers transplanted a pig kidney-thymus combination into a deceased human and tracked the immune response over 61 days. T cells from the recipient infiltrated the organ and specific clones expanded in blood, tissue, and lymph nodes around rejection events. This reveals that T cell-driven rejection of pig organs in humans closely mirrors what happens with human-to-human transplants, informing how future immunosuppression strategies must be designed.

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The cell surface maintains precise amounts of a key lipid (PI4P) through proteins that shuttle it to the interior of the cell for breakdown, but the exact mechanism was debated. This study redirected a PI4P-degrading enzyme to mitochondria — away from its usual location — and found it still accelerated PI4P removal from the plasma membrane, with the protein ORP2 playing a major role. The results show that plasma membrane PI4P can be regulated without direct physical contact between the degrading enzyme and the cell surface.

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People with depression tend to interpret ambiguous information in a negative way, but it was unclear whether this bias depends on thinking about oneself specifically. This study presented ambiguous information to participants either as self-relevant or as describing someone else, while measuring emotional reactions. Only when the information was framed as self-relevant did people with high depression scores show a stronger negative interpretive bias, supporting a specific role for self-referential thinking in depressive cognition.

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The actin-binding protein profilin1 (Pfn1) is known to bind membrane lipids in test tubes, but whether it does so inside cells was unclear. This study found that removing Pfn1 from cells causes a drop in PI(4,5)P2 and an increase in downstream PI3-kinase lipids at the plasma membrane — not through direct lipid binding, but apparently through an interaction with the phosphatase SHIP2 that controls those lipids. The findings challenge a long-standing model of how Pfn1 relates to membrane lipids and connect it to cancer-relevant PI3-kinase signaling.

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The Golgi apparatus uses PI4P as a master regulator of membrane traffic and lipid sorting, and maintaining the right PI4P level there is essential for normal cell function. Using acute and chronic genetic manipulation of OSBP — a protein that consumes PI4P while transporting cholesterol — this study demonstrated that OSBP directly sets PI4P levels at the Golgi. The effect is specific to the Golgi; OSBP does not regulate PI4P at the plasma membrane.

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A lipid called PI4P at the cell surface controls how other lipids, including phosphatidylserine, are distributed between cellular membranes. This study used an engineered approach to redirect a PI4P-degrading enzyme to a non-natural location (mitochondria) and found that a protein called ORP2 plays a major role in depleting PI4P at the plasma membrane, even without physical contact between those compartments. The results reveal a previously unrecognized pathway for regulating cell surface lipid composition.

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Pharmacists and pharmacy technicians experienced dramatically worsened burnout during the COVID-19 pandemic, but are often overlooked in healthcare workforce studies. A 2021 survey of over 1,400 Ohio pharmacy professionals found a 360% increase in daily emotional exhaustion during the pandemic, along with increased depression, suicidal thoughts, and substance use concerns compared to before COVID-19. The authors call for urgent policy and organizational interventions to address pharmacy workforce wellbeing.

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The Golgi apparatus, a key organelle for processing and shipping proteins, maintains precise levels of the lipid PI4P to coordinate its activities. This study used multiple genetic and pharmacological tools to show that a cholesterol-transport protein (OSBP) is a primary consumer and regulator of PI4P at the Golgi, with high capacity to turn PI4P over. Importantly, OSBP's PI4P-consuming activity is confined to the Golgi and does not affect PI4P at the plasma membrane.

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The teat canal of a cow must close between milkings to prevent infection, but whether and when full closure occurs was not well characterized. This ultrasound study measured teat dimensions in dry cows and at multiple time points after milking in lactating cows, finding that canal closure is never complete — even in dry cows the canal has nonzero diameter. In lactating cows, canal dimensions fluctuate throughout the milking cycle and do not return to pre-milking values until about 9 hours after milking.

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Clot-busting treatment (IV thrombolysis) for stroke has been available since the 1990s but remains underused, with well-documented disparities by race, sex, age, and location. This analysis of over 6.5 million hospitalizations from 2002 to 2015 found that use increased substantially overall, and the gap narrowed for Hispanic patients and women. However, Black patients, rural patients, elderly patients, and those on government insurance continued to receive thrombolysis at substantially lower rates, pointing to persistent structural barriers.

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A dog presented with neck pain caused by a rare tumor — a melanocytic mass growing inside a neck vertebra — whose imaging features had not been previously documented. MRI showed the mass was bright on T1-weighted images, a pattern that helped distinguish it from other tumor types. The dog was treated with surgery, radiation, and a melanoma vaccine, and survived 18 months before disease recurrence.

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A 6-year-old Husky dog developed high blood calcium alongside a tumor of the salivary gland, a combination that had not previously been reported. After surgical removal of the tumor, calcium levels returned to normal within 24 hours. Unusually, the standard hormone marker for cancer-related hypercalcemia (PTHrP) was not elevated, suggesting this tumor caused high calcium through a different mechanism.

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Adding a trifluoromethylthio group (SCF3) to drug molecules can improve their properties, but reagents that do this are typically unstable or limited in scope. This study synthesized a new reagent (MTTP) in a single step from cheap starting materials and showed it can attach SCF3 groups even to electron-poor aromatic rings, a challenging class of targets. Activation with a simple acid also enabled reactions with active methylene compounds, expanding the range of molecules accessible by this method.

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Healthcare workers in Ohio already had high rates of burnout before COVID-19, but the pandemic made conditions substantially worse. A 2021 survey found that fewer than 25% of Ohio healthcare professionals had used employee assistance or professional health programs during the pandemic, citing lack of awareness, time constraints, and fears about confidentiality and job consequences. The authors call for more accessible, confidential wellness programs tailored to the healthcare workforce.

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US hospitals operate under payment programs that reward quality and efficiency, but which specific strategies they actually use is poorly documented. This survey of hospital leaders found that most hospitals report implementing a wide range of care improvement strategies across inpatient, outpatient, and community domains. Hospitals in a bundled payment program (BPCI-A) were notably more likely to actively reduce use of skilled nursing facilities post-discharge compared to non-participating hospitals.

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Opioid overdose is a major cause of death in the US, and connecting survivors to treatment in the chaotic aftermath of an overdose is difficult. This paper describes a five-year review of RREACT, a fire/EMS-led mobile team in Columbus, Ohio that pairs paramedics, law enforcement, and social workers to reach overdose patients after emergency calls. Over five years, the team made over 22,000 outreach attempts, achieved 3,194 direct patient contacts, and transported or connected 1,200 people to treatment.

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When a hormone binds to a receptor on a cell's surface, the receptor must then recruit a protein called beta-arrestin to regulate the signal — but how this happens in real time was unclear. Using single-molecule imaging in live cells, this study tracked the parathyroid hormone receptor and found that it assembles into a three-part complex through a defined sequence: the hormone binds first, then a membrane lipid (PIP2) helps recruit beta-arrestin, and finally the complex moves into clathrin clusters. The results map out a non-random pathway for receptor signaling that has implications for understanding how hormones control calcium and bone metabolism.

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A leaf beetle native to Eurasia, which feeds on garlic mustard (an invasive weed in North America), has now been found in multiple US states and one Canadian province. DNA analysis revealed significant genetic diversity within European populations, suggesting possible cryptic species. The beetle's potential spread in North America is limited to humid eastern regions, though known records already span areas not predicted to be highly suitable, likely reflecting sampling gaps.

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Medicare and other payers are shifting physician reimbursement from fee-for-service toward value-based models that reward quality and efficiency, but these programs have mostly failed to deliver on their goals. This American Heart Association policy statement reviews existing cardiovascular value-based payment programs and recommends design principles including strong quality measurement, explicit equity goals, and flexible funding that lets clinicians focus on what actually helps patients. The statement calls for making equity a central pillar of future program design rather than an afterthought.

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Cells must keep levels of the membrane lipid PI(4,5)P2 stable to support normal signaling, but how they sense and correct deviations was unknown. This study found that a family of enzymes called PIP4Ks act as sensors: when PI(4,5)P2 rises, PIP4Ks move to the cell surface and put the brakes on the main PI(4,5)P2-producing enzymes. Disrupting this feedback loop revealed that different cellular processes driven by PI(4,5)P2 have different sensitivity thresholds, which may explain why some disease-linked mutations cause selective rather than global signaling defects.

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A new biosensor for the lipid PI(3,5)P2 — a molecule that helps direct traffic inside cells — was recently described, and this commentary explains its significance. PI(3,5)P2 has been hard to study because it is present in tiny amounts and existing biosensors were unreliable, so having a validated real-time imaging tool opens up new ways to study diseases linked to its dysregulation, including neurodegenerative conditions.

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IV thrombolysis, the only clot-dissolving treatment approved for stroke in the 1990s, is still used in only a small fraction of eligible patients. This national analysis from 2002 to 2015 found overall use grew from 1% to 6.8%, with some narrowing of gaps for women and Hispanic patients. Persistent disparities remained for Black patients, elderly patients, rural patients, and those with Medicare, with urban teaching hospitals pulling even further ahead of rural hospitals over time.

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Black and White Medicare patients tend to receive hospital care at different hospitals, and this segregation varies widely across US regions. This study used 2018 Medicare data to show that greater hospital segregation is associated with more preventable hospitalizations and deaths for both groups, but the harm is significantly larger for Black patients. The findings frame hospital segregation as a direct contributor to health disparities and call for payment and coverage policies that reduce it.

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The liver produces corticosteroid-binding globulin (CBG), a protein that carries most of the body's stress hormones in the blood, and this production differs between male and female rats. Deleting the gene for CBG in rats showed that it normally slows the removal of stress hormones by reducing their uptake by the liver. In adult females, CBG deficiency abolished the sexual dimorphism of roughly 10% of liver genes, including those involved in cholesterol, inflammation, and metabolism — revealing CBG as a key factor in how sex hormones shape liver biology.

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Social prescribing — connecting patients to community-based social and wellness resources rather than just medical treatment — has been adopted in many countries, but the evidence base is fragmented. This review of 87 studies across 13 countries catalogued 347 distinct outcomes that have been measured, with mental health, lifestyle change, and patient experience being the most common. The authors argue that standardizing a core set of outcomes would enable better evidence synthesis and more targeted investment in these programs.