Spotlight: efficient automated global optimization in rietveld analysis of diffraction data.

Performing reliable Rietveld analysis on tens or hundreds of powder diffraction datasets from parametric or time-resolved experiments often poses a bottleneck in extracting meaningful results from the data. While automated analysis of data has recently been demonstrated, high temperature annealing studies, during which phase transformations occur and lattice parameters may change due to repartitioning of elements, are prime examples where automation by a simple phase identification from a database of room temperature structures or automation by sequential refinements is likely to fail. To enable reliable, efficient, automated Rietveld analysis, we present a Python package named Spotlight, building on established Rietveld packages such as MAUD, GSAS, or GSAS-II, which extends the refinement of best fit parameters to a global optimization using an ensemble of optimizers leveraging hierarchical parallel execution on high-performance computing clusters.

PD-1 transcriptomic landscape across cancers and implications for immune checkpoint blockade outcome.

Programmed cell death protein 1 (PD-1) is a critical immune checkpoint receptor and a target for cancer immune checkpoint inhibitors (ICI). We investigated PD-1 transcript expression across cancer types and its correlations to clinical outcomes. Using a reference population, PD-1 expression was calculated as percentiles in 489 of 514 patients (31 cancer types) with advanced/metastatic disease.

New remarkably complete skeleton of Mixodectes reveals arboreality in a large Paleocene primatomorphan mammal following the Cretaceous-Paleogene mass extinction.

Mixodectids are poorly understood placental mammals from the Paleocene of western North America that have variably been considered close relatives of euarchontan mammals (primates, dermopterans, and scandentians) with hypothesized relationships to colugos, extinct plagiomenids, and/or microsyopid plesiadapiforms. Here we describe the most complete dentally associated skeleton yet recovered for a mixodectid, specifically Mixodectes pungens from the early Paleocene of the San Juan Basin, New Mexico. A partial skull with all the teeth erupted and associated axial skeleton, forelimbs, and hind limbs, with epiphyses fused, indicate that it was a mature adult.

DeltaC and DeltaD ligands play different roles in the segmentation clock dynamics.

The vertebrate segmentation clock drives periodic somite segmentation during embryonic development. Her1 and Her7 clock proteins generate oscillatory expression of their own genes as well as that of deltaC in zebrafish. In turn, DeltaC and DeltaD ligands activate Notch signaling, which then activates transcription of clock genes in neighboring cells.

VDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes.

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity.

The control of movement gradually transitions from feedback control to feedforward adaptation throughout childhood.

The ability to adjust movements in response to perturbations is key for an efficient and mature nervous system, which relies on two complementary mechanisms - feedforward adaptation and feedback control. We examined the developmental trajectory of how children employ these two mechanisms using a previously validated visuomotor rotation task, conducted remotely in a large cross-sectional cohort of children aged 3-17 years and adults (n = 656; 353 males & 303 females). Results revealed a protracted developmental trajectory, with children up to ~13-14 years showing immature adaptation.

Epigenetics in persons living with HIV: trauma, coping, and and methylation.

Aim: People living with HIV (PLWH) have an increased risk for lifetime trauma and mental health difficulties. However, no studies have evaluated stress-related genes in relation to early-life adversity, lifetime trauma, or post-traumatic stress disorder (PTSD) in PLWH.

Methods: Using bisulfite pyrosequencing, we evaluated DNA methylation (DNAm) in intron 7 of FKBP5, a glucocorticoid feedback regulator, and in the promoter of SLC6A4, the serotonin transporter gene, in whole blood of a random sample of 70 PLWH recruited from an HIV program, and 51 individuals 2 years later ( = 48 at both time points).

Emulation of Schrödinger dynamics with metamaterials.

The exploration of metamaterials with artificial sub-wavelength structures has empowered researchers to engineer the propagation of classical waves, enabling advancements in areas such as imaging, sensing, communication, and energy harvesting. Concurrently, the investigation into topology and symmetry has not only unveiled valuable insights into fundamental physics, but also expanded our ability to manipulate waves effectively. Combined with the remarkable flexibility and diversity of artificial metamaterials, these considerations have sparked a focused research interest.

Atherogenic lipoproteins associate with loss of glycemic control in youth-onset type 2 diabetes: Results from the TODAY study.

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Clinical Manifestations of SARS-CoV-2 Infection in Immunocompetent Adults in the Era of Widespread Population Immunity and Omicron Sublineage Viruses.

While most SARS-CoV-2 infections and reinfections in the era of widespread population immunity with omicron subsub-lineage variants are mild for immunocompetent individuals, any manifestation previously seen during the pandemic phase is still possible. COVID-19 may affect any organ system. Previous infections and prior vaccines protect against symptomatic future SARS-CoV-2 infections, though this protection wanes over time.

The neural basis of dialectical thinking: recent advances and future prospects.

Dialectical thinking represents a cognitive style emphasizing change, contradiction, and holism. Cross-cultural studies reveal a stark contrast of dialectical thinking between East Asian and Western cultures, highlighting East Asians' superior ability to embrace contradictions and foresee transformation, fostering psychological resilience through emotional complexity and tolerance for contradictions. Despite its importance, the neural basis of dialectical thinking remains underexplored.

A Quality Improvement Project to Increase Adolescent Vaping Capture and Provider Awareness of Use.

Adolescent vaping has dramatically increased, causes adverse health outcomes, and is considered a priority public health concern. Current screening is not age-appropriate, poorly captures vaping use, and inadequately prompts the provider, reducing awareness of use. The aim of the study is to improve adolescent vaping capture and increase provider awareness of use by implementing an age-appropriate screening tool.

Incidence of food allergic reactions among adolescents engaged in food allergy management.

Background: While fatal food-induced anaphylaxis is rare, adolescence is the period of highest risk. However, we lack strong estimates of the incidence of food allergic reactions among adolescents.

Objective: To estimate the incidence of food allergic reactions and anaphylactic reactions among adolescents with food allergy who have a prescription for epinephrine.

Right heart failure and mortality in patients undergoing transcatheter tricuspid valve interventions.

Aims: To assess the association between right heart failure (RHF) and mortality in patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI), and to determine whether clinical RHF status reduces the survival benefit of successful versus failed TTVI.

Methods And Results: The TriValve International Registry (Transcatheter Tricuspid Valve Therapies) is a multicenter registry collecting data of patients with symptomatic, severe or greater TR undergoing TTVI. The population was stratified according to RHF status defined by the following clinical criteria: history of previous hospitalization for RHF (<1 year) OR presence of signs of RHF (jugular venous distension, ascites, peripheral oedema) OR high dose diuretic (≥125 mg/day of furosemide or equivalent).

Defining the patient acceptable symptom state (PASS) for PROMIS after Hallux Rigidus correction surgery.

It is unclear which patient reported outcome metric correlates best with clinical improvement. The patient acceptable symptom state (PASS) incorporates the patient's subjective outcome experience into the outcome measurement. This study aims to establish PASS thresholds using Patient-Reported Outcome Measurement Information System (PROMIS) scores in patients undergoing hallux rigidus (HR) correction.

Orderly specification and precise laminar deployment of mouse cortical projection neuron types through intermediate progenitors.

The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis (dNG) or indirect neurogenesis (iNG) via intermediate progenitors (IPs). A foundational concept in corticogenesis is the "inside-out" model, whereby successive generations of PNs sequentially migrate first to deep and then progressively to more superficial layers. However, its biological significance remains unclear, and the role of iNG in this process is unknown.

Polarity-guided uneven mitotic divisions control brassinosteroid activity in proliferating plant root cells.

Brassinosteroid hormones are positive regulators of plant organ growth, yet their function in proliferating tissues remains unclear. Here, through integrating single-cell RNA sequencing with long-term live-cell imaging of the Arabidopsis root, we reveal that brassinosteroid activity fluctuates throughout the cell cycle, decreasing during mitotic divisions and increasing during the G1 phase. The post-mitotic recovery of brassinosteroid activity is driven by the intrinsic polarity of the mother cell, resulting in one daughter cell with enhanced brassinosteroid signaling, while the other supports brassinosteroid biosynthesis.

Engineering mtDNA deletions by reconstituting end joining in human mitochondria.

Recent breakthroughs in the genetic manipulation of mitochondrial DNA (mtDNA) have enabled precise base substitutions and the efficient elimination of genomes carrying pathogenic mutations. However, reconstituting mtDNA deletions linked to mitochondrial myopathies remains challenging. Here, we engineered mtDNA deletions in human cells by co-expressing end-joining (EJ) machinery and targeted endonucleases.

Exportin-1 functions as an adaptor for transcription factor-mediated docking of chromatin at the nuclear pore complex.

Nuclear pore proteins (nucleoporins [Nups]) physically interact with hundreds of chromosomal sites, impacting transcription. In yeast, transcription factors mediate interactions between Nups and enhancers and promoters. To define the molecular basis of this mechanism, we exploited a separation-of-function mutation in the Gcn4 transcription factor that blocks its interaction with the nuclear pore complex (NPC).

Hawaiian love songs: Coevolutionary conflict between mate attraction and parasite escape.

The recent introduction of an acoustic parasitoid fly to Hawaii has profoundly disrupted the singing behavior of the Island's only field cricket, resulting in a coevolutionary arms race involving rapid alteration of both the songs the crickets produce and the ability of eavesdropping flies to hear the songs.

Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients.

The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8 T cell activation without exhaustion.