Genetic Variants Linked to Opioid Addiction: A Genome-Wide Association Study.

Opioid use disorder (OUD) affects millions of people worldwide. While it is known that OUD originates from many factors, including social and environmental factors, the role of genetic variants in developing the disease has also been reported. This study aims to investigate the genetic variants associated with the risk of developing OUD upon exposure.

Drosophila Toxicogenomics: genetic variation and sexual dimorphism in susceptibility to 4-Methylimidazole.

Background: 4-methylimidazole is a ubiquitous and potentially carcinogenic environmental toxicant. Genetic factors that contribute to variation in susceptibility to its toxic effects are challenging to assess in human populations. We used the Drosophila melanogaster Genetic Reference Panel (DGRP), a living library of natural genetic variation, to identify genes with human orthologs associated with variation in susceptibility to 4-methylimidazole.

Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.

Background: We previously demonstrated the successful use of in vivo CRISPR gene editing to delete 4-hydroxyphenylpyruvate dioxygenase (HPD) to rescue mice deficient in fumarylacetoacetate hydrolase (FAH), a disorder known as hereditary tyrosinemia type 1 (HT1). The aim of this study was to develop an ex vivo gene-editing protocol and apply it as a cell therapy for HT1.

Methods: We isolated hepatocytes from wild-type (C57BL/6J) and Fah-/- mice and then used an optimized electroporation protocol to deliver Hpd-targeting CRISPR-Cas9 ribonucleoproteins into hepatocytes.

Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.

Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I) were recently identified in mature OLG and shown to play a role in regulating myelin length.

coordinates neuroprogenitor differentiation.

Neural stem cells (NSCs) of the ventricular-subventricular zone (V-SVZ) generate numerous cell types. The uncoupling of mRNA transcript availability and translation occurs during the progression from stem to differentiated states. The mTORC1 kinase pathway acutely controls proteins that regulate mRNA translation.

Natural genetic variation in a dopamine receptor is associated with variation in female fertility in .

Fertility is a major component of fitness but its genetic architecture remains poorly understood. Using a full diallel cross of 50 Genetic Reference Panel inbred lines with whole genome sequences, we found substantial genetic variation in fertility largely attributable to females. We mapped genes associated with variation in female fertility by genome-wide association analysis of common variants in the fly genome.

Revisiting the comparative phylogeography of unglaciated eastern North America: 15 years of patterns and progress.

In a landmark comparative phylogeographic study, "Comparative phylogeography of unglaciated eastern North America," Soltis et al. (, 2006, 15, 4261) identified geographic discontinuities in genetic variation shared across taxa occupying unglaciated eastern North America and proposed several common biogeographical discontinuities related to past climate fluctuations and geographic barriers. Since 2006, researchers have published many phylogeographical studies and achieved many advances in genotyping and analytical techniques; however, it is unknown how this work has changed our understanding of the factors shaping the phylogeography of eastern North American taxa.

Physiological and metabolomic consequences of reduced expression of the Drosophila brummer triglyceride Lipase.

Disruption of lipolysis has widespread effects on intermediary metabolism and organismal phenotypes. Defects in lipolysis can be modeled in Drosophila melanogaster through genetic manipulations of brummer (bmm), which encodes a triglyceride lipase orthologous to mammalian Adipose Triglyceride Lipase. RNAi-mediated knock-down of bmm in all tissues or metabolic specific tissues results in reduced locomotor activity, altered sleep patterns and reduced lifespan.

Rationale for hyperbaric oxygen therapy in traumatic injury and wound care in small animal veterinary practice.

Hyperbaric oxygen therapy is in wide use in human medicine around the world. Although hyperbaric oxygen therapy is available for veterinary use, it is still significantly underutilised. The physical principles, gas laws and physiologic mechanisms by which hyperbaric oxygen therapy is therapeutic, especially in traumatic injuries and complicated wound care, are discussed.

Functional Diversification, Redundancy, and Epistasis among Paralogs of the Drosophila melanogaster Obp50a-d Gene Cluster.

Large multigene families, such as the insect odorant-binding proteins (OBPs), are thought to arise through functional diversification after repeated gene duplications. Whereas many OBPs function in chemoreception, members of this family are also expressed in tissues outside chemosensory organs. Paralogs of the Obp50 gene cluster are expressed in metabolic and male reproductive tissues, but their functions and interrelationships remain unknown.

Genotype by environment interaction for gene expression in Drosophila melanogaster.

The genetics of phenotypic responses to changing environments remains elusive. Using whole-genome quantitative gene expression as a model, here we study how the genetic architecture of regulatory variation in gene expression changed in a population of fully sequenced inbred Drosophila melanogaster strains when flies developed in different environments (25 °C and 18 °C). We find a substantial fraction of the transcriptome exhibited genotype by environment interaction, implicating environmentally plastic genetic architecture of gene expression.

Gene expression networks in the Genetic Reference Panel.

A major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. This question is best addressed in a genetic mapping population in which all molecular polymorphisms are known and for which molecular endophenotypes and complex traits are assessed on the same genotypes. Here, we performed deep RNA sequencing of 200 Genetic Reference Panel inbred lines with complete genome sequences and for which phenotypes of many quantitative traits have been evaluated.

Batten disease and perioperative complications: a retrospective descriptive study.

Purpose: Batten disease or neuronal ceroid lipofuscinosis is the most prevalent neurodegenerative disorder of childhood. Previously reported perioperative complications in children with Batten disease have come mainly from single case reports. The primary aim of the current study was to investigate perioperative complications of patients with Batten disease in the largest cohort known to date.

Misunderstanding graphs: The confusion of biological clade diversity diagrams and archaeological frequency seriation diagrams.

Graph perception involves the accurate decipherment of (often quantitative) data displayed in visual form. Because graph style may reflect discipline-specific tradition, similar graph styles in distinct disciplines can be subject to misinterpretation. Both archaeologist James A.

Characterization of Injury Induced by Routine Surgical Manipulations of Nasal Septal Cartilage.

Importance: This study characterizes and compares common surgical manipulations' effects on septal cartilage to understand their implications for rhinoplasty outcomes based on cell viability and cartilage health.

Objective: To illustrate distinct differences in the impact of various surgical manipulations on septal cartilage in an in vitro septal cartilage model. A secondary objective is to better understand the chondrocyte's response to injury as well as how alterations in the extracellular matrix correspond to chondrocyte viability.

Short communication: Effect of 3 phytoceutical products on elimination of bacteria in experimentally induced Streptococcus uberis clinical mastitis.

Our objective was to assess the ability of 3 herbal products to eliminate experimentally induced Streptococcus uberis mastitis. These herbal products, also known as phytoceuticals, are used in organically managed dairy cattle to maintain or promote udder health. The products tested were an intramammary product, a topical product, and a product applied to the vulvar area.

Three-Dimensional (3D) Printed Microneedles for Microencapsulated Cell Extrusion.

Cell-hydrogel based therapies offer great promise for wound healing. The specific aim of this study was to assess the viability of human hepatocellular carcinoma (HepG2) cells immobilized in atomized alginate capsules (3.5% (w/v) alginate, d = 225 µm ± 24.

A Centered Genetic Network Contributes to Alcohol-Induced Variation in Drosophila Development.

Prenatal exposure to ethanol causes a wide range of adverse physiological, behavioral and cognitive consequences. However, identifying allelic variants and genetic networks associated with variation in susceptibility to prenatal alcohol exposure is challenging in human populations, since time and frequency of exposure and effective dose cannot be determined quantitatively and phenotypic manifestations are diverse. Here, we harnessed the power of natural variation in the Genetic Reference Panel (DGRP) to identify genes and genetic networks associated with variation in sensitivity to developmental alcohol exposure.

Effective Instruction for Persisting Dyslexia in Upper Grades: Adding Hope Stories and Computer Coding to Explicit Literacy Instruction.

Children in grades 4 to 6 (=14) who despite early intervention had persisting dyslexia (impaired word reading and spelling) were assessed before and after computerized reading and writing instruction aimed at subword, word, and syntax skills shown in four prior studies to be effective for treating dyslexia. During the 12 two-hour sessions once a week after school they first completed HAWK Letters in Motion© for manuscript and cursive handwriting, HAWK Words in Motion© for phonological, orthographic, and morphological coding for word reading and spelling, and HAWK Minds in Motion© for sentence reading comprehension and written sentence composing. A reading comprehension activity in which sentences were presented one word at a time or one added word at a time was introduced.

Allostery between two binding sites in the ion channel subunit TRIP8b confers binding specificity to HCN channels.

Tetratricopeptide repeat (TPR) domains are ubiquitous structural motifs that mediate protein-protein interactions. For example, the TPR domains in the peroxisomal import receptor PEX5 enable binding to a range of type 1 peroxisomal targeting signal motifs. A homolog of PEX5, tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b), binds to and functions as an auxiliary subunit of hyperpolarization-activated cyclic nucleotide (HCN)-gated channels.

Using milk leukocyte differentials for diagnosis of subclinical bovine mastitis.

This research study aimed to evaluate the use of the milk leukocyte differential (MLD) to: (a) identify quarter milks that are culture-positive; and (b) characterize the milk leukocyte responses to specific groups of pathogens causing subclinical mastitis. The MLD measures the absolute number and relative percentage of inflammatory cells in milk samples. Using the MLD in two dairy herds (170 and 172 lactating cows, respectively), we studied all lactating cows with a most recent monthly Dairy Herd Improvement Association somatic cell count (SCC) >200 × 103 cells/ml.