Flexor hallucis longus and tibialis anterior: A synergistic relationship.

Flexor hallucis longus (FHL) is an important muscle of the foot and ankle during locomotion, contributing to hallux and plantar flexion. For optimal hallux flexion the ankle needs to be stabilized against plantar flexion which may require action of the dorsiflexors. Due to the deep location of the FHL contractile drive assessed by electromyography (EMG) has not been explored systematically.

Golgi pH elevation due to loss of V-ATPase subunit V0a2 function correlates with tissue-specific glycosylation changes and globozoospermia.

Loss-of-function variants in ATP6V0A2, encoding the trans Golgi V-ATPase subunit V0a2, cause wrinkly skin syndrome (WSS), a connective tissue disorder with glycosylation defects and aberrant cortical neuron migration. We used knock-out (Atp6v0a2) and knock-in (Atp6v0a2) mice harboring the R755Q missense mutation selectively abolishing V0a2-mediated proton transport to investigate the WSS pathomechanism. Homozygous mutants from both strains displayed a reduction of growth, dermis thickness, and elastic fiber formation compatible with WSS.

Structure of the ciliary tip central pair reveals the unique role of the microtubule-seam binding protein SPEF1.

Motile cilia are unique organelles with the ability to autonomously move. Force generated by beating cilia propels cells and moves fluids. The ciliary skeleton is made of peripheral doublet microtubules and a central pair (CP) with a distinct structure at the tip.

Dysregulation of PI4P in the trans Golgi regions activates the mammalian Golgi stress response.

The Golgi stress response is an important cytoprotective system that enhances Golgi function in response to cellular demand, while cells damaged by prolonged Golgi stress undergo cell death. OSW-1, a natural compound with anticancer activity, potently inhibits OSBP that transports cholesterol and phosphatidylinositol-4-phosphate (PI4P) at contact sites between the endoplasmic reticulum and the Golgi apparatus. Previously, we reported that OSW-1 induces the Golgi stress response, resulting in Golgi stress-induced transcription and cell death.

Automated non-invasive laser speckle imaging of the chick heart rate and extraembryonic blood vessels and their response to Nifedipine and Amlodipine drugs.

Using our recently developed laser speckle contrast imaging (LSCI) to visualize blood vessels and monitor blood flow noninvasively, we test the utility of the developing chick heart as a functional model for drug screening. To this end, we examined the effects of antihypertensive agents Nifedipine and Amlodipine, belonging to the L-type calcium channel antagonist family, on blood flow visualized noninvasively through the intact shell. Guided by the live view mode, the drugs were injected through the shell and ventral to HH16-19 chick embryos.

An amino acid-resolution interactome for motile cilia identifies the structure and function of ciliopathy protein complexes.

Motile cilia are ancient, evolutionarily conserved organelles whose dysfunction underlies motile ciliopathies, a broad class of human diseases. Motile cilia contain a myriad of different proteins that assemble into an array of distinct machines, and understanding the interactions and functional hierarchies among them presents an important challenge. Here, we defined the protein interactome of motile axonemes using cross-linking mass spectrometry in Tetrahymena thermophila.

Pseudosuchia: Masters of survival and diversification.

In the context of an increasing interest for Pseudosuchia, we have compiled a Special Issue, comprising 14 collaborative studies that deepen our understanding of pseudosuchian evolution. These contributions range from the description of a new taxon to exhaustive reviews of thermometabolism, morphological adaptation, systematics, and detailed investigations into ontogeny, paleoneurology, paleohistology, and paleobiology. Through these papers, we explore the evolutionary history of pseudosuchian archosaurs, spotlighting their rise and diversification following the end-Permian mass extinction.

Maternal aspartame exposure alters lung Th1/Th2 cytokine balance in offspring through nuclear factor-κB activation.

Background: Epidemiological evidence suggests that maternal intake of nonnutritive sweeteners is positively associated with early childhood asthma incidence. We investigated the effects of maternal aspartame exposure during pregnancy and lactation on lung Th1/Th2 cytokine balance and intestinal microbiota in offspring and explored the mechanisms that mediate these effects.

Method: Pregnant BALB/c mice were randomly divided on gestational day 7 into two dietary intervention groups: control (drinking water only) and aspartame (drinking water +0.

MXene Nanoconfinement of SAM-Modified Molecularly Imprinted Electrochemical Biosensor for Point-of-Care Monitoring of Carcinoembryonic Antigen.

The high rate of cancer worldwide and the heavy costs imposed on governments and humanity have always motivated researchers to develop point-of-care (POC) biosensors for easy diagnosis and monitoring of cancer treatment. Herein, we report on a label-free impedimetric biosensor based on TiCT MXene and imprinted ortho-phenylenediamine (o-PD) for the detection of carcinoembryonic antigen (CEA), a biomarker for various cancers surveillance, especially colorectal cancer (CRC). Accordingly, MXene was drop-casted on the surface of a disposable silver electrode to increase the sensitivity and create high-energy nanoareas on the surface, which are usable for protein immobilization and detection.

-related disorder in 87 adults: Natural history and self-sustainability.

Purpose: is one of the most frequently mutated genes in intellectual disability cohorts. Thus, far few adult-aged patients with -related disorder have been described, which limits our understanding of the disease's natural history and our ability to counsel patients and their families.

Methods: Data on patients aged 18+ years with -related disorder were collected through an online questionnaire completed by clinicians and parents.

Poor bone health in Duchenne muscular dystrophy: a multifactorial problem beyond corticosteroids and loss of ambulation.

Duchenne muscular dystrophy (DMD) is a progressive, fatal muscle wasting disease caused by X-linked mutations in the dystrophin gene. Alongside the characteristic muscle weakness, patients face a myriad of skeletal complications, including osteoporosis/osteopenia, high susceptibility to vertebral and long bone fractures, fat embolism post-fracture, scoliosis, and growth retardation. Those skeletal abnormalities significantly compromise quality of life and are sometimes life-threatening.

Lymphovascular Tumoral Emboli in Inflammatory Breast Cancer Result from Haptotaxis-Mediated Encircling Lymphangiogenesis.

Inflammatory breast cancer (IBC) is characterized by numerous tumor emboli within lymphatics. In a recent study, we observed tumor embolic budding both in vitro and in vivo within lymphovascular spaces and proposed this to account for the plethora of tumor emboli seen in IBC. These observations did not address, however, how lymphovascular invasion is initiated or the mechanisms involved.

Iron regulatory protein 1-deficient mice exhibit hypospermatogenesis.

Imbalances in testicular iron levels are linked to compromised sperm production and male infertility. Iron regulatory proteins (IRP) 1 and 2 play crucial roles in cellular iron regulation. We investigated the role of IRP1 on spermatogenesis using Irp1-deficient mice (Irp1).

Workflow automation of SEM acquisitions and feature tracking.

Acquiring multiple high magnification, high resolution images with scanning electron microscopes (SEMs) for quantitative analysis is a time consuming and repetitive task for microscopists. We propose a workflow to automate SEM image acquisition and demonstrate its use in the context of nanoparticle (NP) analysis. Acquiring multiple images of this type of specimen is necessary to obtain a complete and proper characterization of the NP population and obtain statistically representative results.

Saltational Episodes of Reticulate Evolution in the Drosophila saltans Species Group.

Phylogenomics reveals reticulate evolution to be widespread across taxa, but whether reticulation is due to low statistical power or it is a true evolutionary pattern remains a field of study. Here, we investigate the phylogeny and quantify reticulation in the Drosophila saltans species group, a Neotropical clade of the subgenus Sophophora comprising 23 species whose relationships have long been problematic. Phylogenetic analyses revealed conflicting topologies between the X chromosome, autosomes and the mitochondria.

TUDCA modulates drug bioavailability to regulate resistance to acute ER stress in .

Cells counter accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER) through activation of the Unfolded Protein Response (UPR). Small molecules termed chemical chaperones can promote protein folding to alleviate ER stress. The bile acid tauroursodeoxycholic acid (TUDCA), has been described as a chemical chaperone.

Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy.

Ionizable lipids are a key component of lipid nanoparticles, the leading nonviral messenger RNA delivery technology. Here, to advance the identification of ionizable lipids beyond current methods, which rely on experimental screening and/or rational design, we introduce lipid optimization using neural networks, a deep-learning strategy for ionizable lipid design. We created a dataset of >9,000 lipid nanoparticle activity measurements and used it to train a directed message-passing neural network for prediction of nucleic acid delivery with diverse lipid structures.

Sphingolipids modulate redox signalling during human sperm capacitation.

Study Question: What role do sphingolipids have in mediating human sperm capacitation?

Summary Answer: Sphingosine 1-phosphate (S1P) mediates the acquisition of fertilizing competency in human spermatozoa by engaging with its Gi-coupled receptor S1PR1 and promoting production of reactive oxygen species such as nitric oxide and superoxide anion.

What Is Known Already: Bioactive sphingolipids, such as S1P, are fundamental for regulating numerous physiological domains and processes, such as cell membranes and signalling, cell death and proliferation, cell migration and invasiveness, inflammation, and central nervous system development.

Study Design, Size, Duration: Semen samples were obtained from a cohort of 10 healthy non-smoking volunteers (18-30 years old) to investigate the role of S1P in sperm.

The binding of RbgA to a critical 50S assembly intermediate facilitates YphC function in bacterial ribosomal assembly.

The intricate process of 50S ribosomal subunit assembly in Bacillus subtilis involves multiple parallel pathways converging into a crucial intermediate known as the 45S particle. RbgA and YphC, play pivotal roles in completing the maturation of the functional sites in the 45S particle. In this work, we found that RbgA and YphC can independently bind the 45S particle with high affinity, but when RbgA binds first to the particle, it significantly increases the binding affinity of YphC.

Compensatory adaptation of parallel motor pathways promotes skilled forelimb recovery after spinal cord injury.

Skilled forelimb patterning is regulated by the corticospinal tract (CST) with support from brainstem regions. When the CST is lesioned, there is a loss of forelimb function; however, if indirect pathways remain intact, rehabilitative training can facilitate recovery. Following spinal cord injury, rehabilitation is thought to enhance the reorganization and plasticity of spared supraspinal-propriospinal circuits, aiding functional recovery.

Animal origins free products in cell culture media: a new frontier.

Despite the importance of finding replacements for fetal bovine serum (FBS), very few studies have focused on this subject. Historically, the use of animals and their derivatives in growth, reproduction, and physiological studies has raised several concerns. The supplementation of culture media with FBS, also known as fetal calf serum, continues to be widespread, despite its limitations in quality, reproducibility, and implications for animal welfare.

Thermally induced neuronal plasticity in the hypothalamus mediates heat tolerance.

Heat acclimation is an adaptive process that improves physiological performance and supports survival in the face of increasing environmental temperatures, but the underlying mechanisms are not well understood. Here we identified a discrete group of neurons in the mouse hypothalamic preoptic area (POA) that rheostatically increase their activity over the course of heat acclimation, a property required for mice to become heat tolerant. In non-acclimated mice, peripheral thermoafferent pathways via the parabrachial nucleus activate POA neurons and mediate acute heat-defense mechanisms.

Impacts of an environmental ototoxic pollutant on fish fighting behaviors.

Numerous environmental pollutants exhibit ototoxicity and cause damage to the lateral line structures in fish, including the neuromast and its hair cells. The lateral line is used to detect hydrodynamic changes and is thought to play a significant role in aggressive interactions. Fighting behaviors in fish are crucial for establishing social hierarchy and obtaining limited resources.