Flumequine, a fluoroquinolone in disguise.

Fluoroquinolone resistance in E. coli isolates from livestock in Europe remains high despite EMA restrictions on fluoroquinolone use in animals. However, flumequine, a quinolone not classified as a fluoroquinolone by various regulatory bodies, is still used in livestock in the Netherlands, Belgium, Greece and France.

Substrate adaptors are flexible tethering modules that enhance substrate methylation by the arginine methyltransferase PRMT5.

Protein arginine methyltransferase (PRMT) 5 is an essential arginine methyltransferase responsible for the majority of cellular symmetric dimethyl-arginine (SDMA) marks. PRMT5 uses substrate adaptors such as pICln, RIOK1, and COPR5, to recruit and methylate a wide range of substrates. Although the substrate adaptors play important roles in substrate recognition, how they direct PRMT5 activity towards specific substrates remains incompletely understood.

Efficacy of a vein visualisation device for facilitating peripheral venous line placement in adult patients with sickle cell disease: A randomised clinical trial.

Background: Intravenous (IV) access is often required for the treatment of vaso-occlusive crises in patients with sickle cell disease, but can be particularly challenging due to recurrent venous damage. The AccuVein® device, uses near-infrared light technology to visualise veins for easier venepuncture.

Methods: A randomised, controlled trial of the efficacy of the AccuVeinAV400® device in the replacement of peripheral venous lines during a vaso-occlusive crisis was conducted at two centres in France.

Chemical cues of conspecific predation elicit distinct behavioural responses in cannibalistic poison frog tadpoles.

In cannibalistic species, conspecifics can be both predators and prey. As a result, conspecifics present a unique conflict at the intersection of predation, competition and nutritional resources in these species. To better understand how individuals respond to the complex information of conspecific chemical cues, we studied aggressive and cannibalistic tadpoles of the dyeing poison frog, .

Solar energy resource availability under extreme and historical wildfire smoke conditions.

By 2050, the U.S. plans to increase solar energy from 3% to 45% of the nation's electricity generation.

Advances in assessment and cognitive neurorehabilitation of HIV-related neurocognitive impairment.

Neurocognitive impairment (NCI) is present in around 40% of people with HIV and substantially affects everyday life, adherence to combined antiretroviral therapy (cART) and overall life expectancy. Suboptimal therapy regimen, opportunistic infections, substance abuse and highly prevalent psychiatric co-morbidities contribute to NCI in people with HIV. In this review, we highlight the need for efficacious treatment of HIV-related NCI through pharmacological approaches and cognitive neurorehabilitation, discussing recent randomized controlled trials in this domain.

FLEXIBILITY IN GENE COEXPRESSION AT DEVELOPMENTAL AND EVOLUTIONARY TIMESCALES.

The explosion of next-generation sequencing technologies has allowed researchers to move from studying single genes, to thousands of genes, and thereby to also consider the relationships within gene networks. Like others, we are interested in understanding how developmental and evolutionary forces shape the expression of individual genes, as well as the interactions among genes. To this end, we characterized the effects of genetic background and developmental environment on brain gene coexpression in two parallel, independent evolutionary lineages of Trinidadian guppies ().

The differential interactomes of the KRAS splice variants identify BIRC6 as a ubiquitin ligase for KRAS4A.

Transcripts of the KRAS locus are alternatively spliced to generate two proteins, KRAS4A and KRAS4B, which differ in their membrane-targeting sequences. These splice variants have been conserved for more than 450 million years, suggesting non-overlapping functions driven by differential membrane association. Here, we use proximity labeling to map the differential interactomes of the KRAS splice variants.

Investigating a propagation of emerging carbapenemase-producing Enterobacteriaceae in Dutch broiler production pyramid through stochastic simulation.

Simulating resistant bacteria transmission in livestock informs surveillance strategies for emerging threats like Carbapenem-resistant Enterobacteriaceae (CPE), aiding targeted surveillance and detecting CPE through active methods. We employed a simulation model to assess three potential scenarios for introducing CPE: 1) a single import of live animals, 2) the use of contaminated feed, and 3) multiple imports of live animals. Employing the SimInf package, we constructed a population model for broiler production, encompassing rearing farms, multiplier farms, hatcheries, and broiler farms.

SMAC mimetics induce human macrophages to phagocytose live cancer cells.

Macrophages engulf apoptotic bodies and cellular debris as part of homeostasis, but they can also phagocytose live cells such as aged red blood cells. Pharmacologic reprogramming with the SMAC mimetic LCL161 in combination with T cell-derived cytokines can induce macrophages to phagocytose live cancer cells in mouse models. Here we extend these findings to encompass a wide range of monovalent and bivalent SMAC mimetic compounds, demonstrating that live cell phagocytosis is a class effect of these agents.

A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development.

Bifunctional molecules such as targeted protein degraders induce proximity to promote gain-of-function pharmacology. These powerful approaches have gained broad traction across academia and the pharmaceutical industry, leading to an intensive focus on strategies that can accelerate their identification and optimization. We and others have previously used chemical proteomics to map degradable target space, and these datasets have been used to develop and train multiparameter models to extend degradability predictions across the proteome.

Early-twentieth-century cold bias in ocean surface temperature observations.

The observed temperature record, which combines sea surface temperatures with near-surface air temperatures over land, is crucial for understanding climate variability and change. However, early records of global mean surface temperature are uncertain owing to changes in measurement technology and practice, partial documentation, and incomplete spatial coverage. Here we show that existing estimates of ocean temperatures in the early twentieth century (1900-1930) are too cold, based on independent statistical reconstructions of the global mean surface temperature from either ocean or land data.

Vascular Point-of-Care Ultrasound.

The use of point-of-care ultrasound (POCUS) of the vasculature has expanded beyond procedural guidance and is utilized by multiple specialties in varied clinical settings. Evidence supports the use of POCUS for diagnosing deep venous thrombosis in the lower extremities, while for thrombosis in the upper extremities or abdominal aortic aneurysm screening, the evidence is still nascent. Here, we review POCUS of the extremity veins and abdominal aorta with a summary of the pertinent literature, review of the relevant anatomy, description of the appropriate acquisition technique, introduction to associated pathology, and discussion of pitfalls one could encounter.

Focal segmental glomerulosclerosis (FSGS) in pregnancy: The case of a 27-year-old woman with nephrotic syndrome at 22 weeks of gestation.

Nephrotic syndrome (NS) in pregnancy has been associated with poor fetal outcomes. Focal segmental glomerulosclerosis (FSGS) is one of the common causes of NS and can be primary or secondary. However, there are few case reports of FSGS diagnosed in the peripartum period and the approaches to management.

Veterans' Experiences of and Preferences for Patient-Centered, Measurement-Based PTSD Care.

Background: Up to 50% of veterans drop out of trauma-focused evidence-based psychotherapies (TF-EBP) without completing treatment or recovering; evidence suggests this is in part because their posttraumatic stress disorder (PTSD) care is insufficiently patient-centered. There is also evidence that measurement-based care (MBC) for mental health should be personalized to the patient, yet this is not common practice in VA PTSD care.

Objectives: To explore veterans' experiences and preferences for aligning measurement-based PTSD care with their own treatment goals.

Discovery of CRBN-Dependent WEE1 Molecular Glue Degraders from a Multicomponent Combinatorial Library.

Small molecules promoting protein-protein interactions produce a range of therapeutic outcomes. Molecular glue degraders exemplify this concept due to their compact drug-like structures and ability to engage targets without reliance on existing cognate ligands. While cereblon molecular glue degraders containing glutarimide scaffolds have been approved for treatment of multiple myeloma and acute myeloid leukemia, the design of new therapeutically relevant monovalent degraders remains challenging.

Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.

An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID] ∼100) on a 208-strain panel.

Stimulation of the withdrawal reflex in gait training after stroke: A systematic review and meta-analysis.

Background: After a stroke many people experience hemiparesis, resulting in walking difficulties which affects independence, mobility, and participation in activities of daily living. Activating the nociceptive withdrawal reflex (NWR) during gait training aims to support the initiation and facilitation of the swing phase of the paretic leg. The aim of this review is to investigate the orthotic and therapeutic effects of a NWR stimulation intervention to improve gait in patients after a stroke.

Cavity-modified local and non-local electronic interactions in molecular ensembles under vibrational strong coupling.

Resonant vibrational strong coupling (VSC) between molecular vibrations and quantized field modes of low-frequency optical cavities constitutes the conceptual cornerstone of vibro-polaritonic chemistry. In this work, we theoretically investigate the role of complementary nonresonant electron-photon interactions in the cavity Born-Oppenheimer (CBO) approximation. In particular, we study cavity-induced modifications of local and non-local electronic interactions in dipole-coupled molecular ensembles under VSC.

One-size measures do not fit all areas: Evaluation of area-specific control of foot and mouth disease in Thailand using bioeconomic modelling.

Information on the epidemiological and economic consequences of control measures is fundamental to design effective foot and mouth disease (FMD) control measures. One approach to obtaining this information is through bioeconomic modelling. In this study, a bioeconomic model was used to evaluate FMD control in two different study areas in Thailand: a high farm density area predominantly consisting of dairy farms and a low farm density area with mixed farm types.

Adenosquamous Carcinoma of the Lung: Survival, Radiologic Findings, PD-L1, and Driver Mutations.

Adenosquamous carcinoma of the lung (ASC) is a rare non-small-cell lung cancer (NSCLC) subtype combining components of squamous cell carcinoma (SCC) and adenocarcinoma (AC). Data on ASC, particularly in Caucasian populations, are limited. We reviewed clinicopathological and radiological characteristics of ASC patients diagnosed between 1996 and 2023.

Discovery of electrophilic degraders that exploit SAr chemistry.

Targeted covalent inhibition (TCI) and targeted protein degradation (TPD) have proven effective in pharmacologically addressing formerly 'undruggable' targets. Integration of both methodologies has resulted in the development of electrophilic degraders where recruitment of a suitable E3 ubiquitin ligase is achieved through formation of a covalent bond with a cysteine nucleophile. Expanding the scope of electrophilic degraders requires the development of electrophiles with tempered reactivity that enable selective ligase recruitment and reduce cross-reactivity with other cellular nucleophiles.

pr-independent biogenesis of infectious mature Zika virus particles.

Flavivirus assembly at the endoplasmic reticulum is driven by the structural proteins envelope (E) and premembrane (prM). Here, contrary to the established paradigm for flavivirus assembly, we demonstrate that the biogenesis of flavivirus particles does not require an intact prM nor proteolytic activation. The expression of E preceded by a truncated version of prM (M-E) was sufficient for the formation of non-infectious Zika virus subviral particles and pseudo-infectious reporter virions.