Generation of LexA enhancer-trap lines in Drosophila by an international scholastic network.

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons.

Stepping up to the thermogradient plate: a data framework for predicting seed germination under climate change.

Background And Aims: Seed germination is strongly influenced by environmental temperatures. With global temperatures predicted to rise, the timing of germination for thousands of plant species could change, leading to potential decreases in fitness and ecosystem-wide impacts. The thermogradient plate (TGP) is a powerful but underutilized research tool that tests germination under a broad range of constant and alternating temperatures, giving researchers the ability to predict germination characteristics using current and future climates.

Interactions of Both Pathogenic and Nonpathogenic CUG Clade Species with Macrophages Share a Conserved Transcriptional Landscape.

species are a leading cause of opportunistic, hospital-associated bloodstream infections with high mortality rates, typically in immunocompromised patients. Several species, including Candida albicans, the most prevalent cause of infection, belong to the monophyletic CUG clade of yeasts. Innate immune cells such as macrophages are crucial for controlling infection, and C.

Evaluation of the Impact of Prior-to-Admission Sleep Aid Prescribing Practices on Sleep and Delirium in the Intensive Care Unit.

Background: Sleep disruptions in the intensive care unit (ICU) may lead to complications such as delirium. There is limited evidence addressing how sleep aid use before and during ICU admission affects outcomes.

Objective: The purpose of this study is to evaluate the impact of prior-to-admission sleep aid prescribing practices in the ICU on delirium and sleep outcomes.

Distribution of seed dormancy classes across a fire-prone continent: effects of rainfall seasonality and temperature.

Background And Aims: Different seed dormancy classes control the timing of germination via different cues. The ecological dissimilarities between classes therefore suggest that they are likely to be subject to different selective pressures, and that species within each class will have diverse functional responses. We aimed to investigate this by assessing how variation in the distribution of dormancy classes is correlated with regional environmental factors, in particular rainfall seasonality and temperature.

Membrane Tension Can Enhance Adaptation to Maintain Polarity of Migrating Cells.

Migratory cells are known to adapt to environments that contain wide-ranging levels of chemoattractant. Although biochemical models of adaptation have been previously proposed, here, we discuss a different mechanism based on mechanosensing, in which the interaction between biochemical signaling and cell tension facilitates adaptation. We describe and analyze a model of mechanochemical-based adaptation coupling a mechanics-based physical model of cell tension coupled with the wave-pinning reaction-diffusion model for Rac GTPase activity.

The cytoplasmic tail of human mannosidase Man1b1 contributes to catalysis-independent quality control of misfolded alpha1-antitrypsin.

The failure of polypeptides to achieve conformational maturation following biosynthesis can result in the formation of protein aggregates capable of disrupting essential cellular functions. In the secretory pathway, misfolded asparagine (N)-linked glycoproteins are selectively sorted for endoplasmic reticulum-associated degradation (ERAD) in response to the catalytic removal of terminal alpha-linked mannose units. Remarkably, ER mannosidase I/Man1b1, the first alpha-mannosidase implicated in this conventional N-glycan-mediated process, can also contribute to ERAD in an unconventional, catalysis-independent manner.

Bicycling Exercise Helps Maintain a Youthful Metabolic Cost of Walking in Older Adults.

The decline of walking performance is a key determinant of morbidity among older adults. Healthy older adults have been shown to have a 15-20% lower walking economy compared with young adults. However, older adults who run for exercise have a higher walking economy compared with older adults who walk for exercise.

Enhancement of Breast Cancer Cell Aggressiveness by lncRNA and its Mir-675 Derivative: Insight into Shared and Different Actions.

Breast cancer is a major public health problem and the leading world cause of women death by cancer. Both the recurrence and mortality of breast cancer are mainly caused by the formation of metastasis. The long non-coding RNA , the precursor of miR-675, is involved in breast cancer development.

A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer.

Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and transferred to the Golgi complex by interaction with the Batten disease protein CLN8 (ceroid lipofuscinosis, neuronal, 8). Here we investigated the relationship of this pathway with CLN6, an ER-associated protein of unknown function that is defective in a different Batten disease subtype. Experiments focused on protein interaction and trafficking identified CLN6 as an obligate component of a CLN6-CLN8 complex (herein referred to as EGRESS: ER-to-Golgi relaying of enzymes of the lysosomal system), which recruits lysosomal enzymes at the ER to promote their Golgi transfer.

Evidence for physiological seed dormancy cycling in the woody shrub Asterolasia buxifolia and its ecological significance in fire-prone systems.

Dormancy cycling is a key mechanism that contributes to the maintenance of long-term persistent soil seed banks, but has not been recorded in long-lived woody shrub species from fire-prone environments. Such species rely on seed banks and dormancy break as important processes for post-fire recruitment and recovery. We used germination experiments with smoke treatments on fresh seeds and those buried for 1 year (retrieved in spring) and 1.

An Interscholastic Network To Generate LexA Enhancer Trap Lines in .

Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology, and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the index line.

A kinome-wide RNAi screen identifies ERK2 as a druggable regulator of Shank3 stability.

Neurons are sensitive to changes in the dosage of many genes, especially those regulating synaptic functions. Haploinsufficiency of SHANK3 causes Phelan-McDermid syndrome and autism, whereas duplication of the same gene leads to SHANK3 duplication syndrome, a disorder characterized by neuropsychiatric phenotypes including hyperactivity and bipolar disorder as well as epilepsy. We recently demonstrated the functional modularity of Shank3, which suggests that normalizing levels of Shank3 itself might be more fruitful than correcting pathways that function downstream of it for treatment of disorders caused by alterations in SHANK3 dosage.

CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis.

Organelle biogenesis requires proper transport of proteins from their site of synthesis to their target subcellular compartment. Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and traffic through the Golgi complex before being transferred to the endolysosomal system, but how they are transferred from the ER to the Golgi is unknown. Here, we show that ER-to-Golgi transfer of lysosomal enzymes requires CLN8, an ER-associated membrane protein whose loss of function leads to the lysosomal storage disorder, neuronal ceroid lipofuscinosis 8 (a type of Batten disease).

Regulation of Human Breast Cancer by the Long Non-Coding RNA H19.

Breast cancer is one of the most common causes of cancer related deaths in women. Despite the progress in early detection and use of new therapeutic targets associated with development of novel therapeutic options, breast cancer remains a major problem in public health. Indeed, even if the survival rate has improved for breast cancer patients, the number of recurrences within five years and the five-year relative survival rate in patients with metastasis remain dramatic.

-Glial and stem cell expression of murine Fibroblast Growth Factor Receptor 1 in the embryonic and perinatal nervous system.

Background: Fibroblast growth factors (FGFs) and their receptors (FGFRs) are involved in the development and function of multiple organs and organ systems, including the central nervous system (CNS). FGF signaling via FGFR1, one of the three FGFRs expressed in the CNS, stimulates proliferation of stem cells during prenatal and postnatal neurogenesis and participates in regulating cell-type ratios in many developing regions of the brain. Anomalies in FGFR1 signaling have been implicated in certain neuropsychiatric disorders.

Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia.

Background: Fibroblast growth factors (FGFs) and their receptors (FGFRs) have numerous functions in the developing and adult central nervous system (CNS). For example, the FGFR1 receptor is important for proliferation and fate specification of radial glial cells in the cortex and hippocampus, oligodendrocyte proliferation and regeneration, midline glia morphology and soma translocation, Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1 signaling in astrocytes is required for postnatal maturation of interneurons expressing parvalbumin (PV).

Creating a chimeric clathrin heavy chain that functions independently of yeast clathrin light chain.

Clathrin facilitates vesicle formation during endocytosis and sorting in the trans-Golgi network (TGN)/endosomal system. Unlike in mammals, yeast clathrin function requires both the clathrin heavy (CHC) and clathrin light (CLC) chain, since Chc1 does not form stable trimers without Clc1. To further delineate clathrin subunit functions, we constructed a chimeric CHC protein (Chc-YR) , which fused the N-terminus of yeast CHC (1-1312) to the rat CHC residues 1318-1675, including the CHC trimerization region.

One injection of platelet-rich plasma associated to a submaximal eccentric protocol to treat chronic jumper's knee.

Aim: Jumper's knee is a frequent chronic overuse syndrome of the proximal part of the patellar tendon. Platelets contain lots of growth factors which could enhance the healing process of tendons. The aim of this study was to clarify the possible efficacy of one injection of Platelet-rich plasma (PRP) in cases of rebel jumper's knees.

Candida albicans suppresses nitric oxide generation from macrophages via a secreted molecule.

Macrophages and neutrophils generate a potent burst of reactive oxygen and nitrogen species as a key aspect of the antimicrobial response. While most successful pathogens, including the fungus Candida albicans, encode enzymes for the detoxification of these compounds and repair of the resulting cellular damage, some species actively modulate immune function to suppress the generation of these toxic compounds. We report here that C.

Republished: Value of biomarkers in osteoarthritis: current status and perspectives.

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis.

Correction of vitamin D insufficiency with combined strontium ranelate and vitamin D3 in osteoporotic patients.

Objective: This study aims to investigate the efficacy and safety of oral fixed-dose combination of strontium ranelate 2  g/vitamin D₃ 1000  IU daily vs strontium ranelate 2  g daily for correcting vitamin D insufficiency in osteoporosis.

Design: A 6-month international, randomized, double-blind, parallel-group, phase 3 study.

Methods: A total of 518 men and postmenopausal women aged ≥50 years with primary osteoporosis (T-score ≤-2.

Value of biomarkers in osteoarthritis: current status and perspectives.

Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis.

Serum sclerostin levels in men with idiopathic osteoporosis.

Objective: Sclerostin inhibits osteoblast differentiation and bone formation. If aberrant sclerostin action is involved in less efficient bone acquisition in men with idiopathic low bone mass, this might be reflected in higher serum sclerostin levels.

Methods: In 116 men with idiopathic osteoporosis (≤65 years old), 40 of their sons and healthy controls, areal bone parameters were measured using dual-energy X-ray absorptiometry, and volumetric and geometric bone parameters were measured using peripheral quantitative computed tomography.

Effect on bone turnover markers of once-yearly intravenous infusion of zoledronic acid versus daily oral risedronate in patients treated with glucocorticoids.

Objective: Long-term glucocorticoid use is accompanied by rapid bone loss; however, early treatment with bisphosphonates prevents bone loss and reduces fracture risk. The aim of this study was to examine the effects of two bisphosphonates, i.v.