Microglial activation without peripheral immune cell infiltration characterises mouse and human cerebral small vessel disease.

Aims: Cerebral small vessel diseases (SVDs) involve diverse pathologies of the brain's small blood vessels, leading to cognitive deficits. Cerebral magnetic resonance imaging (MRI) reveals white matter hyperintensities (WMHs), lacunes, microbleeds and enlarged perivascular spaces in SVD patients. Although correlations of MRI and histopathology help to understand the pathogenesis of SVD, they do not explain disease progression.

Epileptic activity triggers rapid ROCK1-dependent astrocyte morphology changes.

Long-term modifications of astrocyte function and morphology are well known to occur in epilepsy. They are implicated in the development and manifestation of the disease, but the relevant mechanisms and their pathophysiological role are not firmly established. For instance, it is unclear how quickly the onset of epileptic activity triggers astrocyte morphology changes and what the relevant molecular signals are.

Existence of HLA-Mismatched Unrelated Donors Closes the Gap in Donor Availability Regardless of Recipient Ancestry.

In patients without a matched sibling donor (MSD) or well-matched unrelated donor (MUD), hematopoietic cell transplantation (HCT) can still be successful when using an HLA-mismatched unrelated donor (MMUD) in combination with post-transplantation cyclophosphamide (PTCy), abatacept, or other novel approaches. This may allow clinicians to choose a suitable donor from a wide range of donor options while optimizing other donor selection characteristics, including donor age. We hypothesized that allowing for a 5/8 HLA match level considering high-resolution matching at HLA-A, -B, -C and -DRB1, there is a potential to close the donor availability gap for all patients regardless of their race/ethnicity.

The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation.

Germinal center (GC) formation and antibody production in lymph node follicles require coordinated interactions between B-cells, T-cells and dendritic cells (DCs), orchestrated by the extracellular matrix-rich reticular fiber (RF) network. We describe a unique laminin 523-containing RF network around and between follicles that associates with PDGFrecβCCL19gp38 fibroblastic reticular cells (FRC). In the absence of FRC expression of laminin α5 (), pre-Tfh-cells, B-cells and DCs are displaced from follicle borders, correlating with fewer Tfh-cells and GC B-cells.

Near perfect classification of cardiac biomarker Troponin-I in human serum assisted by SnS-CNT composite, explainable ML, and operating-voltage-selection-algorithm.

The high worldwide mortality and disproportionate impact of cardiovascular diseases have emerged as the most significant global health burden, unfortunately, unmet by the traditional detection methods. Therefore, developing a rapid, sensitive, selective, and rugged biosensor for the precise classification/quantification of cardiac biomarkers is a stepping stone for the future generation of cardiac healthcare. We demonstrate a facile, time-efficient, and scalable biosensor for classifying the FDI approved gold standard cardiac biomarker Troponin-I (cTnI) in untreated human serum matrix, built-on 2-D SnS and 1-D MWCNT composite transducer and decision-tree based explainable machine learning (ML) algorithm.

Cell death of hippocampal CA1 astrocytes during early epileptogenesis.

Objective: Growing evidence suggests that dysfunctional astrocytes are crucial players in the development of mesial temporal lobe epilepsy (MTLE). Using a mouse model closely recapitulating key alterations of chronic human MTLE with hippocampal sclerosis, here we asked whether death of astrocytes contributes to the initiation of the disease and investigated potential underlying molecular mechanisms.

Methods: Antibody staining was combined with confocal imaging and semiquantitative real-time polymerase chain reaction analysis to identify markers of different cellular death mechanisms between 4 h and 3 days after epilepsy induction.

Constitutive deletion of astrocytic connexins aggravates kainate-induced epilepsy.

The astroglial gap junctional network formed by connexin (Cx) channels plays a central role in regulating neuronal activity and network synchronization. However, its involvement in the development and progression of epilepsy is not yet understood. Loss of interastrocytic gap junction (GJ) coupling has been observed in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy (MTLE) and in mouse models of MTLE, leading to the suggestion that it plays a causative role in the pathogenesis.

Adhesion strength and viscoelastic properties of polydimethylsiloxane (PDMS) based elastomeric nanocomposites with embedded electrospun nanofibers.

In the present study, the adhesive and viscoelastic properties of polydimethylsiloxane (PDMS) based nanocomposite pressure sensitive adhesives (PSAs) with embedded electrospun polyacrylonitrile (PAN) and polyvinyl alcohol (PVA) nanofibers as fillers were investigated. PDMS nanocomposite adhesive films using PAN and PVA nanofibers were synthesized by dispersing fillers in the matrix by a solvent mixing process. The adhesion strength and reusability of the prepared nanocomposite PSA films were measured using peel tests as the fraction of nanofibers in the polymer matrix is increased.

To study surface and sub-surface nanomechanical properties of electrospun polyacrylonitrile (PAN) nanofibers/polydimethylsiloxane (PDMS) composites.

We investigate surface and sub-surface nanomechanical properties of nanocomposites based on a crosslinked polydimethylsiloxane (PDMS) elastomer and electrospun polyacrylonitrile (PAN) nanofibers. Fabrication of PDMS substrates with anisotropy with respect to surface elasticity and their characterization in terms of local nanomechanical properties are important for many areas of adhesion applications. PDMS nanocomposite substrates with variations in surface elasticity over large areas are prepared by controllably embedding electrospun PAN nanofibers (∼600 nm) in a PDMS matrix using the solution casting technique.

Making Nonsticky Surfaces of Sticky Materials: Self-Organized Microtexturing of Viscoelastic Elastomeric Layers by Tearing.

Fabrication of large area, multiscale microtextured surfaces engineered for antiadhesion properties remains a challenge. Compared to an elastic surface, viscoelastic solids show much higher surface stickiness, tack, and adhesion owing to the increased contact area and energy dissipation. Here, we show a simple, low cost, large-area and high throughput method with roll-to-roll compatibility to fabricate multiscale, rough microstructures resistant to adhesion in a viscoelastic layer by controlled tearing of viscous film.

Molecular characterization of perivascular drainage pathways in the murine brain.

Perivascular compartments surrounding central nervous system (CNS) vessels have been proposed to serve key roles in facilitating cerebrospinal fluid flow into the brain, CNS waste transfer, and immune cell trafficking. Traditionally, these compartments were identified by electron microscopy with limited molecular characterization. Using cellular markers and knowledge on cellular sources of basement membrane laminins, we here describe molecularly distinct compartments surrounding different vessel types and provide a comprehensive characterization of the arachnoid and pial compartments and their connection to CNS vessels and perivascular pathways.

Subcellular reorganization and altered phosphorylation of the astrocytic gap junction protein connexin43 in human and experimental temporal lobe epilepsy.

Dysfunctional astrocytes are increasingly recognized as key players in the development and progression of mesial temporal lobe epilepsy (MTLE). One of the dramatic changes astrocytes undergo in MTLE with hippocampal sclerosis (HS) is loss of gap junction coupling. To further elucidate molecular mechanism(s) underlying this alteration, we assessed expression, cellular localization and phosphorylation status of astrocytic gap junction proteins in human and experimental MTLE-HS.

Cavity shape transformation during peeling on elastic microchannel-patterned substrates filled with a viscous liquid.

Inspired by the detachment mechanics of natural adhesive pads, we studied the change in cavity shape during peel tests on a 10% cross-linked polydimethylsiloxane (PDMS) elastic microchannel filled with 1% cross-linked viscous PDMS liquid (patterned bilayer). During peeling, we explored cavity shape as a function of microchannel dimensions and correlated the dimensionless cavity shape factor (CSF) and characteristic stress decay length, K. The peel test on the liquid-filled elastic microchannel shows three distinct cavity-shape regimes, elliptical, circular, and binary, based on the values of CSF and K.

Experimental febrile seizures impair interastrocytic gap junction coupling in juvenile mice.

Prolonged and focal febrile seizures (FSs) have been associated with the development of temporal lobe epilepsy (TLE), although the underlying mechanism and the contribution of predisposing risk factors are still poorly understood. Using a kainate model of TLE, we previously provided strong evidence that interruption of astrocyte gap junction-mediated intercellular communication represents a crucial event in epileptogenesis. To elucidate this aspect further, we induced seizures in immature mice by hyperthermia (HT) to study the consequences of FSs on the hippocampal astrocytic network.

Astrocyte uncoupling as a cause of human temporal lobe epilepsy.

Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K(+) concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens.

Production of hydrogen and volatile fatty acid by Enterobacter sp. T4384 using organic waste materials.

In a study of hydrogen-producing bacteria, strain T4384 was isolated from rice field samples in the Republic of Korea. The isolate was identified as Enterobacter sp. T4384 by phylogenetic analysis of 16S rRNA and rpoB gene sequences.

Targeting endothelin receptors for pharmacotherapy of ischemic stroke: current scenario and future perspectives.

Increased expression of endothelin (ET) peptide and its receptors following ischemic stroke is found to regulate many critical aspects of stroke pathophysiology. Many attempts have been made to target ET receptors in various animal models of stroke, but it is very difficult to draw a definite line of conclusion, because these studies differ in many aspects, such as animal model, treatment schedule, parameters and techniques used for assessing these parameters. A meta-analysis of all studies showed a significant reduction in the lesion volume and improvement in functional outcome in focal cerebral ischemia.