Strategies to boost antibody selectivity in oncology.

Antibodies in oncology are being equipped with toxic cargoes and effector functions that can kill cells at very low concentrations. A key challenge is that most targets on cancer cells are also present on at least some healthy cells. Shared targets can result in off-tumor binding and compromise the safety and potential of therapeutic candidates.

Seroprevalence, incidence estimates, and environmental risk factors for dengue, chikungunya, and Zika infection amongst children living in informal urban settlements in Indonesia and Fiji.

Background: The burden of -transmitted viruses such as dengue, chikungunya, and Zika are increasing globally, fueled by urbanization and climate change, with some of the highest current rates of transmission in Asia. Local factors in the built environment have the potential to exacerbate or mitigate transmission.

Methods: In 24 informal urban settlements in Makassar, Indonesia and Suva, Fiji, we tested children under 5 years old for evidence of prior infection with dengue, chikungunya, and Zika viruses by IgG serology.

Pathological microcircuits initiate epileptiform events in patient hippocampal slices.

How seizures begin at the level of microscopic neural circuits remains unknown. High-density CMOS microelectrode arrays provide a new avenue for investigating neuronal network activity, with unprecedented spatial and temporal resolution. We use high-density CMOS-based microelectrode arrays to probe the network activity of human hippocampal brain slices from six patients with mesial temporal lobe epilepsy in the presence of hyperactivity promoting media.

INTERSPECIES ORGANOIDS REVEAL HUMAN-SPECIFIC MOLECULAR FEATURES OF DOPAMINERGIC NEURON DEVELOPMENT AND VULNERABILITY.

The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release.

Multiscale Cloud-Based Pipeline for Neuronal Electrophysiology Analysis and Visualization.

Electrophysiology offers a high-resolution method for real-time measurement of neural activity. Longitudinal recordings from high-density microelectrode arrays (HD-MEAs) can be of considerable size for local storage and of substantial complexity for extracting neural features and network dynamics. Analysis is often demanding due to the need for multiple software tools with different runtime dependencies.

Phospholipid Scramblase 1 (PLSCR1) Regulates Interferon-Lambda Receptor 1 (IFN-λR1) and IFN-λ Signaling in Influenza A Virus (IAV) Infection.

Phospholipid scramblase 1 (PLSCR1) is an antiviral interferon-stimulated gene (ISG) that has several known anti-influenza functions such as interfering with viral nuclear import, regulating toll-like receptor (TLR) 9 and potentiating the expression of other ISGs. However, the exact mechanisms of anti-flu activity of PLSCR1 in relation to its expression compartment and enzymatic activity, and the molecular and cellular mechanisms involved have not been completely explored. Moreover, only limited animal models have been studied to delineate its role at the tissue level in influenza infections.

Opportunities to design better computer vison-assisted food diaries to support individuals and experts in dietary assessment: An observation and interview study with nutrition experts.

Automatic visual recognition for photo-based food diaries is increasingly prevalent. However, existing tools in food recognition often focus on food classification and calorie counting, which may not be sufficient to support the variety of food and healthy eating goals people have. To understand how to better design computer-vision-based food diaries to support healthy eating, we began to examine how nutrition experts, such as dietitians, use the visual features of food photos to evaluate diet quality.

Synthesis and structural characterization of the heavy tricysteinylpnictines, models of protein-bound As(III), Sb(III), and Bi(III).

The heavier group 15 elements As, Sb, and Bi are more restricted in their biochemistry than the nearly ubiquitous lighter congeners N and P, but organisms do encounter compounds of these elements as environmental toxins, starting materials for secondary metabolite biosynthesis, substrates for primary metabolism, or exogenously applied medicines. Under many physiological conditions, these compounds are transformed into pnictogen(III) species, the soft Lewis acidic character of which leads them to interact strongly with biologically relevant soft Lewis bases such as small-molecule thiols or cysteine residues of proteins and peptides. The archetypal complexes As(Cys), Sb(Cys), and Bi(Cys) have been studied in the past but a lack of detailed information about their molecular structures has hampered the analysis of protein structures featuring As(III), Sb(III), and Bi(III) bound to cysteine thiolate residues.

A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage in .

Apical extracellular matrices (aECMs) act as crucial barriers, and communicate with the epidermis to trigger protective responses following injury or infection. In , the skin aECM, the cuticle, is produced by the epidermis and is decorated with periodic circumferential furrows. We previously showed that mutants lacking cuticle furrows exhibit persistent immune activation (PIA).

Ship collision risk threatens whales across the world's oceans.

After the near-complete cessation of commercial whaling, ship collisions have emerged as a primary threat to large whales, but knowledge of collision risk is lacking across most of the world's oceans. We compiled a dataset of 435,000 whale locations to generate global distribution models for four globally ranging species. We then combined >35 billion positions from 176,000 ships to produce a global estimate of whale-ship collision risk.

Ecological diversification of sea catfishes is accompanied by genome-wide signatures of positive selection.

Habitat transitions have shaped the evolutionary trajectory of many clades. Sea catfishes (Ariidae) have repeatedly undergone ecological transitions, including colonizing freshwaters from marine environments, leading to an adaptive radiation in Australia and New Guinea alongside non-radiating freshwater lineages elsewhere. Here, we generate and analyze one long-read reference genome and 66 short-read whole genome assemblies, in conjunction with genomic data for 54 additional species.

Reproductive success and offspring survival decline for female elephant seals past prime age.

Maternal age can influence reproductive success and offspring fitness, but the timing, magnitude and direction of those impacts are not well understood. Evolutionary theory predicts that selection on fertility senescence is stronger than maternal effect senescence, and therefore, the rate of maternal effect senescence will be faster than fertility senescence. We used a 36-year study of northern elephant seals (Mirounga angustirostris) to investigate reproductive senescence.

Field-Testing Multiple-Choice Questions With AI Examinees: English Grammar Items.

Field-testing is an essential yet often resource-intensive step in the development of high-quality educational assessments. I introduce an innovative method for field-testing newly written exam items by substituting human examinees with artificially intelligent (AI) examinees. The proposed approach is demonstrated using 466 four-option multiple-choice English grammar questions.

Metabolic regulation of RNA methylation by the mA-reader IGF2BP3.

The interplay of RNA modifications - deposited by "writers", removed by "erasers" and identified by RNA binding proteins known as "readers" - forms the basis of the epitranscriptomic gene regulation hypothesis. Recent studies have identified the oncofetal RNA-binding protein IGF2BP3 as a "reader" of the N6-methyladenosine (mA) modification and crucial for regulating gene expression. Yet, how its function as a reader overlaps with its critical oncogenic function in leukemia remains an open question.

Mother-child collaboration in an Indigenous community: Changing and enduring across generations.

Changes in family life related to globalization may include reduction in the collaborativeness observed in many Indigenous American communities. The present study examined longitudinal changes and continuities in collaboration in a Guatemalan Maya community experiencing rapid globalization. Fluid collaboration was widespread 3 decades ago among triads of mothers and 1- to 6-year-olds in 24 Mayan families exploring novel objects during home visits (Dayton et al.

Heat-inactivated Streptococcus pneumoniae augments circadian clock gene expression in zebrafish cells.

The circadian clock is a cell-autonomous process that regulates daily internal rhythms by interacting with environmental signals. Reports across species show that infection can alter the expression of circadian genes; however, in teleosts, these effects are influenced by light exposure. Currently, no reports analyze the direct effects of bacterial exposure on the zebrafish clock.

Correlation of Performance on the ENTRUST Assessment Platform With Other Variables in Competency-Based Surgical Education.

Objective: With the implementation of American Board of Surgery (ABS) Entrustable Professional Activities (EPAs), there is continued need for objective, evidence-based assessment tools to augment existing microassessments and inform readiness for entrustment. The ENTRUST Assessment Platform is an online virtual-patient simulation platform to assess trainees' surgical decision-making competence across preoperative, intraoperative, and postoperative phases of care. This study collects additional validity evidence for the ENTRUST platform in its relationship to other established variables in competency-based surgical education.

Habitat selection and influence on hunting success in female Australian fur seals.

Determining the factors influencing habitat selection and hunting success in top predators is crucial for understanding how these species may respond to environmental changes. For marine top predators, such factors have been documented in pelagic foragers, with habitat use and hunting success being linked to chlorophyll-a concentrations, sea surface temperature and light conditions. In contrast, little is known about the determinants of benthic marine predators.

Gapless assembly of complete human and plant chromosomes using only nanopore sequencing.

The combination of ultra-long (UL) Oxford Nanopore Technologies (ONT) sequencing reads with long, accurate Pacific Bioscience (PacBio) High Fidelity (HiFi) reads has enabled the completion of a human genome and spurred similar efforts to complete the genomes of many other species. However, this approach for complete, "telomere-to-telomere" genome assembly relies on multiple sequencing platforms, limiting its accessibility. ONT "Duplex" sequencing reads, where both strands of the DNA are read to improve quality, promise high per-base accuracy.

A genome assembly for the California endemic liverwort Calasterella californica.

Calasterella californica belongs to a monotypic genus of liverworts endemic to the west coast of North America, primarily distributed in California. This dioicous species occurs in a variety of ecosystems from deserts to redwood forest; little is known about how this species is adapted to live in those seemingly contrasting environments. In this paper, we report the assembly of the nuclear genome of Calasterella californica.

Cell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim. However, the precise cell type composition of such niches, their interactions and changes between chronic active and inactive stages are incompletely understood.

Spatio-Temporal Attention and Gaussian Processes for Personalized Video Gaze Estimation.

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Synthesizing High-Resolution Dual-Energy Radiographs from Coronary Artery Calcium CT Images.

Generating realistic radiographs from CT is mainly limited by the native spatial resolution of the latter. Here we present a general approach for synthesizing high-resolution digitally reconstructed radiographs (DRRs) from an arbitrary resolution CT volume. Our approach is based on an upsampling framework where tissues of interest are first segmented from the original CT volume and then upsampled individually to the desired voxelization (here ~1 mm → 0.