Genetics of vegetarianism: A genome-wide association study.

A substantial body of evidence points to the heritability of dietary preferences. While vegetarianism has been practiced for millennia in various societies, its practitioners remain a small minority of people worldwide, and the role of genetics in choosing a vegetarian diet is not well understood. Dietary choices involve an interplay between the physiologic effects of dietary items, their metabolism, and taste perception, all of which are strongly influenced by genetics.

Sustained therapeutic benefits by transient reduction of TDP-43 using ENA-modified antisense oligonucleotides in ALS/FTD mice.

The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although how TDP-43 forms cytoplasmic aggregates and causes neurodegeneration in patients with ALS/FTD remains unclear, reducing cellular TDP-43 levels is likely to prevent aggregation and to rescue neurons from TDP-43 toxicity. To address this issue, here we developed gapmer-type antisense oligonucleotides (ASOs) against human TDP-43 using 2'-,4'--ethylene nucleic acids (ENAs), which are modified nucleic acids with high stability, and tested the therapeutic potential of lowering TDP-43 levels using ENA-modified ASOs.

Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy.

Astrocyte abnormalities have received great attention for their association with various diseases in the brain but not so much in the eye. Recent independent genome-wide association studies of glaucoma, optic neuropathy characterized by retinal ganglion cell (RGC) degeneration, and vision loss found that single-nucleotide polymorphisms near the ABCA1 locus were common risk factors. Here, we show that loss in retinal astrocytes causes glaucoma-like optic neuropathy in aged mice.

Comparison of serum and plasma as a source of blood extracellular vesicles: Increased levels of platelet-derived particles in serum extracellular vesicle fractions alter content profiles from plasma extracellular vesicle fractions.

Extracellular vesicles (EVs) have attracted much attention as potential diagnostic biomarkers for human diseases. Although both plasma and serum are utilized as a source of blood EVs, it remains unclear whether, how and to what extent the choice of plasma and serum affects the experimental results. To address this issue, in this study, we performed comprehensive characterization of EV fractions derived from plasma and serum, and investigated the differences between these blood EVs.

Introduction of Extracorporeal Membrane Oxygenation on Ninth Day of Ventilator Management for Severe Acute Respiratory Distress Syndrome due to COVID-19: A Case Report.

The reported case is of a 68-year-old man who was admitted to the ICU at our tertiary care medical center with severe COVID-19. He was admitted to the ICU due to a worsening respiratory condition during his hospitalization at the same medical center, which included the development of severe acute respiratory distress syndrome (ARDS). Ventilator management was started with alveolar protection in mind.

Are lifestyle pattern changes associated to poor subjective sleep quality?: a cross-sectional study by gender among the general Japanese population underwent specified medical check-ups in 2014 and 2015.

Objectives: Subjective sleep quality (SSQ) is defined by the satisfaction of one's overall sleep experience and is composed of sleep depth and restfulness. It has not been clarified how poor SSQ is associated to changes in lifestyles. The purpose is to reveal the association of lifestyle pattern changes and poor SSQ.

Theory and Algorithms for Shapelet-Based Multiple-Instance Learning.

We propose a new formulation of multiple-instance learning (MIL), in which a unit of data consists of a set of instances called a bag. The goal is to find a good classifier of bags based on the similarity with a "shapelet" (or pattern), where the similarity of a bag with a shapelet is the maximum similarity of instances in the bag. In previous work, some of the training instances have been chosen as shapelets with no theoretical justification.

Arginine is a disease modifier for polyQ disease models that stabilizes polyQ protein conformation.

The polyglutamine (polyQ) diseases are a group of inherited neurodegenerative diseases that include Huntington's disease, various spinocerebellar ataxias, spinal and bulbar muscular atrophy, and dentatorubral pallidoluysian atrophy. They are caused by the abnormal expansion of a CAG repeat coding for the polyQ stretch in the causative gene of each disease. The expanded polyQ stretches trigger abnormal β-sheet conformational transition and oligomerization followed by aggregation of the polyQ proteins in the affected neurons, leading to neuronal toxicity and neurodegeneration.

A Novel Immunogen Selectively Eliciting CD8 T Cells but Not CD4 T Cells Targeting Immunodeficiency Virus Antigens.

Optimization of immunogen is crucial for induction of effective T-cell responses in the development of a human immunodeficiency virus (HIV) vaccine. Conventional T-cell-based vaccines have been designed to induce virus-specific CD4 T as well as CD8 T cells. However, it has been indicated that induction of HIV-specific CD4 T cells, preferential targets for HIV infection, by vaccination may be detrimental and accelerate viral replication after HIV exposure.

Unhealthy changes in eating habits cause acute onset hypertension in the normotensive community-dwelling elderly-3 years cohort study.

The aim of this study was to determine what lifestyle changes can predict acute onset hypertension in the normotensive community-dwelling elderly.This study targeted elderly people enrolled in National Health Insurance in Fukushima Prefecture, Japan. The subjects were 24,490 people who took all of the specific health examination conducted by National Health Insurance in fiscal years 2013, 2014, and 2015 continuously and had a recorded systolic blood pressure (BP) <130 mm Hg and diastolic BP <85 mm Hg in the first 2 fiscal years.

Microglia mediate non-cell-autonomous cell death of retinal ganglion cells.

Excitotoxicity is well known in the neuronal death in the brain and is also linked to neuronal damages in the retina. Recent accumulating evidence show that microglia greatly affect excitotoxicity in the brain, but their roles in retina have received only limited attention. Here, we report that retinal excitotoxicity is mediated by microglia.

Purinergic dysregulation causes hypertensive glaucoma-like optic neuropathy.

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs) and visual loss. Although one of the highest risk factors for glaucoma is elevated intraocular pressure (IOP) and reduction in IOP is the only proven treatment, the mechanism of IOP regulation is poorly understood. We report that the P2Y6 receptor is critical for lowering IOP and that ablation of the P2Y6 gene in mice (P2Y6KO) results in hypertensive glaucoma-like optic neuropathy.

Robustness of learning algorithms using hinge loss with outlier indicators.

We propose a unified formulation of robust learning methods for classification and regression problems. In the learning methods, the hinge loss is used with outlier indicators in order to detect outliers in the observed data. To analyze the robustness property, we evaluate the breakdown point of the learning methods in the situation that the outlier ratio is not necessarily small.

Co-administration of Cyclosporin A and Ondansetron decreases transient local cerebral ischemic injury in the mouse.

Objectives: Several studies indicate that cyclosporin A has a protective effect against brain infarction. In this study, we aimed to determine if co-administration of cyclosporin A and ondansetron could reduce damage caused by cerebral ischemia.

Methods: ICR (Charles River Laboratories) mice were subjected to transient focal cerebral ischemia and divided into 4 groups (O, V, C, and Mix).

DC Algorithm for Extended Robust Support Vector Machine.

Nonconvex variants of support vector machines (SVMs) have been developed for various purposes. For example, robust SVMs attain robustness to outliers by using a nonconvex loss function, while extended [Formula: see text]-SVM (E[Formula: see text]-SVM) extends the range of the hyperparameter by introducing a nonconvex constraint. Here, we consider an extended robust support vector machine (ER-SVM), a robust variant of E[Formula: see text]-SVM.

Outlier detection at the transcriptome-proteome interface.

Background: In high-throughput experimental biology, it is widely acknowledged that while expression levels measured at the levels of transcriptome and the corresponding proteome do not, in general, correlate well, messenger RNA levels are used as convenient proxies for protein levels. Our interest is in developing data-driven computational models that can bridge the gap between these two levels of measurement at which different mechanisms of regulation may act on different molecular species causing any observed lack of correlations. To this end, we build data-driven predictors of protein levels using mRNA levels and known proxies of translation efficiencies as covariates.

Distinct Transcriptomic Features are Associated with Transitional and Mature B-Cell Populations in the Mouse Spleen.

Splenic transitional B-cells (T1 and T2) are selected to avoid self-reactivity and to safeguard against autoimmunity, then differentiate into mature follicular (FO-I and FO-II) and marginal zone (MZ) subsets. Transcriptomic analysis by RNA-seq of the five B-cell subsets revealed T1 cell signature genes included RAG suggesting a potential for receptor revision. T1 to T2 B-cell differentiation was marked by a switch from Myb to Myc, increased expression of the PI3K adapter DAP10 and MHC class II.

Vaccine-induced CD107a+ CD4+ T cells are resistant to depletion following AIDS virus infection.

Unlabelled: CD4(+) T-cell responses are crucial for effective antibody and CD8(+) T-cell induction following virus infection. However, virus-specific CD4(+) T cells can be preferential targets for human immunodeficiency virus (HIV) infection. HIV-specific CD4(+) T-cell induction by vaccination may thus result in enhancement of virus replication following infection.

Extended robust support vector machine based on financial risk minimization.

Financial risk measures have been used recently in machine learning. For example, ν-support vector machine ν-SVM) minimizes the conditional value at risk (CVaR) of margin distribution. The measure is popular in finance because of the subadditivity property, but it is very sensitive to a few outliers in the tail of the distribution.

Using financial risk measures for analyzing generalization performance of machine learning models.

We propose a unified machine learning model (UMLM) for two-class classification, regression and outlier (or novelty) detection via a robust optimization approach. The model embraces various machine learning models such as support vector machine-based and minimax probability machine-based classification and regression models. The unified framework makes it possible to compare and contrast existing learning models and to explain their differences and similarities.

Detection of RBM15-MKL1 fusion was useful for diagnosis and monitoring of minimal residual disease in infant acute megakaryoblastic leukemia.

Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category of myeloid leukemia by WHO classification and mainly reported in infants and young children. Accurate diagnosis of this type of AMKL can be difficult, because a subset of patients have a bone marrow (BM) blast percentage of less than 20% due to BM fibrosis. Therefore, it is possible that past studies have underestimated this type of AMKL.

Nucleoporins and nucleocytoplasmic transport in hematologic malignancies.

Hematologic malignancies are often associated with chromosomal rearrangements that lead to the expression of chimeric fusion proteins. Rearrangements of the genes encoding two nucleoporins, NUP98 and NUP214, have been implicated in the pathogenesis of several types of hematologic malignancies, particularly acute myeloid leukemia. NUP98 rearrangements result in fusion of an N-terminal portion of NUP98 to one of numerous proteins.