The human leukemic oncogene MLL-AF4 promotes hyperplastic growth of hematopoietic tissues in larvae.

-rearranged (-r) leukemias are among the leukemic subtypes with poorest survival, and treatment options have barely improved over the last decades. Despite increasing molecular understanding of the mechanisms behind these hematopoietic malignancies, this knowledge has had poor translation into the clinic. Here, we report a model system to explore the pathways affected in -r leukemia.

Toward computing attributions for dimensionality reduction techniques.

Summary: We describe the problem of computing local feature attributions for dimensionality reduction methods. We use one such method that is well established within the context of supervised classification-using the gradients of target outputs with respect to the inputs-on the popular dimensionality reduction technique t-SNE, widely used in analyses of biological data. We provide an efficient implementation for the gradient computation for this dimensionality reduction technique.

Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4 and CD8 T cells.

Spontaneous transcription and translation of HIV can persist during suppressive antiretroviral therapy (ART). The quantity, phenotype, and biological relevance of this spontaneously "active" reservoir remain unclear. Using multiplexed single-cell RNAflow-fluorescence in situ hybridization (FISH), we detect active HIV transcription in 14/18 people with HIV on suppressive ART, with a median of 28/million CD4 T cells.

Correction: and antiproliferative activity of organo-nickel SCS-pincer complexes on estrogen responsive MCF7 and MC4L2 breast cancer cells. Effects of amine fragment substitutions on BSA binding and cytotoxicity.

Correction for ' and antiproliferative activity of organo-nickel SCS-pincer complexes on estrogen responsive MCF7 and MC4L2 breast cancer cells. Effects of amine fragment substitutions on BSA binding and cytotoxicity' by Mahboubeh Hosseini-Kharat , , 2018, , 16944-16957, https://doi.org/10.

Experiences of adults living with refractory epilepsy and their views and expectations on receiving results from whole genome sequencing.

Introduction: Researchers, clinicians and patients are turning to new innovations in research and clinical practice to further their knowledge in the genetic domain and improve diagnostics or treatment. However, with increased knowledge in genetics, societal issues may arise. Being conscious of these issues is crucial in order to implement standardized and efficient testing on a wider scale that is accessible to a greater number of individuals while simultaneously returning test results, including incidental findings, in a timely manner.

[I lead, follow me! How cells coordinate during collective migrations.].

During development and wound healing, cells frequently move in a so-called "collective cell migration" process. The same type of migration is used by some cancer cells during metastasis formation. A powerful model to study collective cell migration is the border cell cluster in Drosophila as it allows the observation and manipulation of a collective cell migration in its normal environment.

Association between cardiovascular diseases and dementia among various age groups: a population-based cohort study in older adults.

The link between cardiovascular (CV) risk factors or diseases and dementia is documented. There is conflicting evidence whether age moderates the association. We need to study this gap so that research and clinical initiatives target appropriate age groups.

Simplifying glycan monitoring of complex antigens such as the SARS-CoV-2 spike to accelerate vaccine development.

Glycosylation is a key quality attribute that must be closely monitored for protein therapeutics. Established assays such as HILIC-Fld of released glycans and LC-MS of glycopeptides work well for glycoproteins with a few glycosylation sites but are less amenable for those with multiple glycosylation sites, resulting in complex datasets that are time consuming to generate and difficult to analyze. As part of efforts to improve preparedness for future pandemics, researchers are currently assessing where time can be saved in the vaccine development and production process.

Toxicokinetics of praseodymium and cerium administered as chloride salts in Sprague-Dawley rats: impacts of the dose and of co-exposure with additional rare earth elements.

We conducted a rat exposure study to assess the impacts of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). We first determined the kinetic profiles of elemental Pr and Ce in blood, urine and feces along with tissue levels at sacrifice on the seventh day following intravenous injection of PrCl or CeCl at 0.3 or 1 mg/kg bw (of the chloride salts) in adult male Sprague-Dawley rats (n = 5 per group).

How Does Sexual Subjectivity Vary on the Basis of Gender and Sexual Orientation? Validation of the Short Sexual Subjectivity Inventory (SSSI-11) in Cisgender, Heterosexual and Sexual and Gender Minority Adolescents.

Through sexual exploration, adolescents learn that they are sexual beings with choices, desires, and are deserving of pleasure, which corresponds to sexual subjectivity. However, the two measures of this construct (i.e.

A new way to mitigate pathological Tau?

In this issue of Neuron, Wang et al. show that the RNA-binding protein G3BP2 interacts with Tau in human neurons and in brains of patients with Alzheimer's disease (AD), suggesting a new role for G3BP2 with implications for therapeutic sequestration of Tau in neurodegenerative diseases.

Image-encoded biological and non-biological variables may be used as shortcuts in deep learning models trained on multisite neuroimaging data.

Objective: This work investigates if deep learning (DL) models can classify originating site locations directly from magnetic resonance imaging (MRI) scans with and without correction for intensity differences.

Material And Methods: A large database of 1880 T1-weighted MRI scans collected across 41 sites originally for Parkinson's disease (PD) classification was used to classify sites in this study. Forty-six percent of the datasets are from PD patients, while 54% are from healthy participants.

Variable selection in high dimensions for discrete-outcome individualized treatment rules: Reducing severity of depression symptoms.

Despite growing interest in estimating individualized treatment rules, little attention has been given the binary outcome setting. Estimation is challenging with nonlinear link functions, especially when variable selection is needed. We use a new computational approach to solve a recently proposed doubly robust regularized estimating equation to accomplish this difficult task in a case study of depression treatment.

Hypomyelination, hypodontia and craniofacial abnormalities in a Polr3b mouse model of leukodystrophy.

RNA polymerase III (Pol III)-related hypomyelinating leukodystrophy (POLR3-HLD), also known as 4H leukodystrophy, is a severe neurodegenerative disease characterized by the cardinal features of hypomyelination, hypodontia and hypogonadotropic hypogonadism. POLR3-HLD is caused by biallelic pathogenic variants in genes encoding Pol III subunits. While approximately half of all patients carry mutations in POLR3B encoding the RNA polymerase III subunit B, there is no in vivo model of leukodystrophy based on mutation of this Pol III subunit.

Cortical contribution to visuomotor coordination in locomotion and reaching.

One of the hallmarks of mammals is their ability to make precise visually guided limb movements to attain objects. This is best exemplified by the reach and grasp movements of primates, although it is not unique to this mammalian order. Precise, coordinated, visually guided movements are equally as important during locomotion in many mammalian species, especially in predators.

Promoting Health through Accessible Public Playgrounds.

Every child, irrespective of socioeconomic status, ethnicity, or ability, deserves the fundamental right to experience play, which is a powerful and enriching activity that fosters their physical and mental health. Regrettably, most public play spaces hinder the complete inclusion of children with disabilities, with the main reason being a lack of universal accessibility. This study identified existing international and Canadian policies and community best practices related to inclusive playgrounds, and gathered stakeholders' opinions on the present condition of playgrounds, including challenges faced by children with disabilities and recommendations to make playgrounds inclusive.

An Evaluation of Interactive mHealth Applications for Adults Living with Cancer.

This study evaluated the quality and usefulness of interactive mobile health (mHealth) applications (apps) for adults with cancer. The PRISMA guidelines were followed to add rigor to the search, as well as to the data collection and analysis. The apps available in the most used app stores (Google Play and Apple) with interactive tailored features were identified.

The Pathways study: a cohort study of new food-aid users in rural, semi urban, and urban areas of Quebec, Canada.

Background: While considerable research has been conducted on household food insecurity (HFI), little research has examined the effects of food donation programs on users' living conditions. The Pathways study was established to investigate the long-term effects of food donation programs on food insecurity as well as other critical outcomes, such as diet, health, and social support. Herein, we describe the design of the Pathways Study and the participants' characteristics at baseline.

G Protein-Biased Agonists for Intracellular Angiotensin Receptors Promote Collagen Secretion in Myofibroblasts.

Photoactivatable ligands remain valuable tools to study the spatiotemporal aspects of cellular signaling. However, the synthesis, handling, and biological validation of such compounds remain challenging, especially when dealing with peptides. We report an optimized synthetic strategy, where laborious preparation of dimethoxy-nitrobenzyl-tyrosine building blocks was replaced by direct functionalization of amino acid side chains while peptides remained coupled to resin, reducing both preparation time and cost.

ArfGAP1 regulates the endosomal sorting of guidance receptors to promote directed collective cell migration .

Chemotaxis drives diverse migrations important for development and involved in diseases, including cancer progression. Using border cells in the egg chamber as a model for collective cell migration, we characterized the role of ArfGAP1 in regulating chemotaxis during this process. We found that ArfGAP1 is required for the maintenance of receptor tyrosine kinases, the guidance receptors, at the plasma membrane.

Anatomo-functional correspondence in the voice-selective regions of human prefrontal cortex.

Group level analyses of functional regions involved in voice perception show evidence of 3 sets of bilateral voice-sensitive activations in the human prefrontal cortex, named the anterior, middle and posterior Frontal Voice Areas (FVAs). However, the relationship with the underlying sulcal anatomy, highly variable in this region, is still unknown. We examined the inter-individual variability of the FVAs in conjunction with the sulcal anatomy.

Pou3f1 orchestrates a gene regulatory network controlling contralateral retinogeniculate projections.

The balance of contralateral and ipsilateral retinogeniculate projections is critical for binocular vision, but the transcriptional programs regulating this process remain ill defined. Here we show that the Pou class homeobox protein POU3F1 is expressed in nascent mouse contralateral retinal ganglion cells (cRGCs) but not ipsilateral RGCs (iRGCs). Upon Pou3f1 inactivation, the proportion of cRGCs is reduced in favor of iRGCs, leading to abnormal projection ratios at the optic chiasm.

BamQuery: a proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens.

MHC-I-associated peptides deriving from non-coding genomic regions and mutations can generate tumor-specific antigens, including neoantigens. Quantifying tumor-specific antigens' RNA expression in malignant and benign tissues is critical for discriminating actionable targets. We present BamQuery, a tool attributing an exhaustive RNA expression to MHC-I-associated peptides of any origin from bulk and single-cell RNA-sequencing data.

Weyl's Law for the Steklov Problem on Surfaces with Rough Boundary.

The validity of Weyl's law for the Steklov problem on domains with Lipschitz boundary is a well-known open question in spectral geometry. We answer this question in two dimensions and show that Weyl's law holds for an even larger class of surfaces with rough boundaries. This class includes domains with interior cusps as well as "slow" exterior cusps.