Identification and characterization of MADS-box gene family in flax, L. and its role under abiotic stress.

MADS-box transcription factors play critical roles in plant development and stress responses. In this study, we identified 114 genes in flax ( L.) and analyzed their phylogenetic relationships, gene structure, conserved motifs, miRNA targets, and expression patterns.

Astrocyte TrkB promotes brain injury and edema formation in ischemic stroke.

Following ischemic stroke astrocytes undergo rapid molecular and functional changes that may accentuate tissue damage. In this study we identified the neurotrophin receptor TrkB in astrocytes as a key promoter of acute CNS injury in ischemic stroke. In fact, TrkB protein was strongly upregulated in astrocytes after human and experimental stroke, and transgenic mice lacking astrocyte TrkB displayed significantly smaller lesion volume, lower brain atrophy and better motor performance than control animals after transient middle cerebral artery occlusion.

CNS cell-derived exosome signatures as blood-based biomarkers of neurodegenerative diseases.

Molecular biomarkers require the reproducible capture of disease-associated changes and are ideally sensitive, specific and accessible with minimal invasiveness to patients. Exosomes are a subtype of extracellular vesicles that have gained attention as potential biomarkers. They are released by all cell types and carry molecular cargo that reflects the functional state of the cells of origin.

Siponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways.

Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS), consisting of heterogeneous clinical courses varying from relapsing-remitting MS (RRMS), in which disability is linked to bouts of inflammation, to progressive disease such as primary progressive MS (PPMS) and secondary progressive MS (SPMS), in which neurological disability is thought to be linked to neurodegeneration. As a result, successful therapeutics for progressive MS likely need to have both anti-inflammatory and direct neuroprotective properties. The modulation of sphingosine-1-phosphate (S1P) receptors has been implicated in neuroprotection in preclinical animal models.

Assessing the host range of , an egg parasitoid of spotted lanternfly ( using Eastern U.S. non-target species.

The spotted lanternfly, (Hemiptera: Fulgoridae), an invasive planthopper discovered in Pennsylvania, U.S. in 2014, has spread to many surrounding states despite quarantines and control efforts, and further spread is anticipated.

Retrospective observational study of aged care facility residents presenting to ED post fall: A case for person-centred shared decision making.

Objective: Identify the incidence of intracranial haemorrhage in people from residential aged care facilities following falls who had a CT head performed. The secondary objectives were to identify predictor variables for intracranial haemorrhage to inform person-centred shared decision making.

Methods: Retrospective chart review of aged care residents who presented to ED with a triage of fall.

Imaging chronic active lesions in multiple sclerosis: a consensus statement.

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery of innovative MRI and PET-derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with multiple sclerosis, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted and T2-weighted scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL.

The effectiveness of manual and exercise therapy on headache intensity and frequency among patients with cervicogenic headache: a systematic review and meta-analysis.

Background: Cervicogenic headache is a secondary headache, and manual therapy is one of the most common treatment choices for this and other types of headache. Nonetheless, recent guidelines on the management of cervicogenic headache underlined the lack of trials comparing manual and exercise therapy to sham or no-treatment controls. The main objective of this systematic review and meta-analysis was to assess the effectiveness of different forms of manual and exercise therapy in people living with cervicogenic headache, when compared to other treatments, sham, or no treatment controls.

Magnetic Susceptibility Source Separation Solely from Gradient Echo Data: Histological Validation.

Quantitative susceptibility mapping (QSM) facilitates mapping of the bulk magnetic susceptibility of tissue from the phase of complex gradient echo (GRE) MRI data. QSM phase processing combined with an R2* model of magnitude of multiecho gradient echo data (R2*QSM) allows separation of dia- and para-magnetic components (e.g.

Clinical trials in multiple sclerosis: past, present, and future.

For the past four decades, multiple sclerosis (MS) has been a focus for clinical trial development and execution. Advances in translational neuroimmunology have led to the development of effective disease-modifying therapies (DMTs) that greatly benefit patients with MS and mitigate their burden of disease. These achievements also stem from continued progress made in the definition and discovery of sensitive disease diagnostic criteria, objective disability assessment scales, precise imaging techniques, and disease-specific biomarkers.

Susceptibility source separation from gradient echo data using magnitude decay modeling.

Background And Purpose: The objective is to demonstrate feasibility of separating magnetic sources in quantitative susceptibility mapping (QSM) by incorporating magnitude decay rates in gradient echo (GRE) MRI.

Methods: Magnetic susceptibility source separation was developed using and compared with a prior method using that required an additional sequence to measure the transverse relaxation rate R . Both susceptibility separation methods were compared in multiple sclerosis (MS) patients (n = 17).

Efficacy of Disease Modifying Therapies in Progressive MS and How Immune Senescence May Explain Their Failure.

The advent of disease modifying therapies (DMT) in the past two decades has been the cornerstone of successful clinical management of multiple sclerosis (MS). Despite the great strides made in reducing the relapse frequency and occurrence of new signal changes on neuroimaging in patients with relapsing remitting MS (RRMS) by approved DMT, it has been challenging to demonstrate their effectiveness in non-active secondary progressive MS (SPMS) and primary progressive MS (PPMS) disease phenotypes. The dichotomy of DMT effectiveness between RRMS and progressive MS informs on distinct pathogeneses of the different MS phenotypes.

Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions.

Background And Objectives: To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro.

Methods: This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans.

Astrocyte Heterogeneity in Multiple Sclerosis: Current Understanding and Technical Challenges.

The emergence of single cell technologies provides the opportunity to characterize complex immune/central nervous system cell assemblies in multiple sclerosis (MS) and to study their cell population structures, network activation and dynamics at unprecedented depths. In this review, we summarize the current knowledge of astrocyte subpopulations in MS tissue and discuss the challenges associated with resolving astrocyte heterogeneity with single-nucleus RNA-sequencing (snRNA-seq). We further discuss multiplexed imaging techniques as tools for defining population clusters within a spatial context.

Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes.

β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells.

In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing-remitting multiple sclerosis.

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS ( H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis.

QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions.

Background: Inflammation in chronic active lesions occurs behind a closed blood-brain barrier and cannot be detected with MRI. Activated microglia are highly enriched for iron and can be visualized with quantitative susceptibility mapping (QSM), an MRI technique used to delineate iron.

Objective: To characterize the histopathological correlates of different QSM hyperintensity patterns in MS lesions.

Modeling risks from natural hazards with generalized additive models for location, scale and shape.

We investigate a new framework for estimating the frequency and severity of losses associated with catastrophic risks such as bushfires, storms and floods. We explore generalized additive models for location, scale and shape (GAMLSS) for the quantification of regional risk factors - geographical, weather and climate variables - with the aim of better quantifying the frequency and severity of catastrophic losses from natural perils. Due to the flexibility of the GAMLSS approach, we find a superior fit to empirical loss data for the applied models in comparison to generalized linear regression models typically applied in the literature.

Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS.

Objective: To identify coinhibitory immune pathways important in the brain, we hypothesized that comparison of T cells in lesions from patients with MS with tumor-infiltrating T cells (TILs) from patients with glioblastoma multiforme may reveal novel targets for immunotherapy.

Methods: We collected fresh surgical resections and matched blood from patients with glioblastoma, blood and unmatched postmortem CNS tissue from patients with MS, and blood from healthy donors. The expression of TIGIT, CD226, and their shared ligand CD155 as well as PD-1 and PDL1 was assessed by both immunohistochemistry and flow cytometry.

Quantifying the Metabolic Signature of Multiple Sclerosis by Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker.

Proton magnetic resonance spectroscopy (H-MRS) offers a growing variety of methods for querying potential diagnostic biomarkers of multiple sclerosis in living central nervous system tissue. For the past three decades, H-MRS has enabled the acquisition of a rich dataset suggestive of numerous metabolic alterations in lesions, normal-appearing white matter, gray matter, and spinal cord of individuals with multiple sclerosis, but this body of information is not free of seeming internal contradiction. The use of H-MRS signals as diagnostic biomarkers depends on reproducible and generalizable sensitivity and specificity to disease state that can be confounded by a multitude of influences, including experiment group classification and demographics; acquisition sequence; spectral quality and quantifiability; the contribution of macromolecules and lipids to the spectroscopic baseline; spectral quantification pipeline; voxel tissue and lesion composition; and relaxation; B field characteristics; and other features of study design, spectral acquisition and processing, and metabolite quantification about which the experimenter may possess imperfect or incomplete information.

The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions.

Activated myeloid cells and astrocytes are the predominant cell types in active multiple sclerosis (MS) lesions. Both cell types can adopt diverse functional states that play critical roles in lesion formation and resolution. In order to identify phenotypic subsets of myeloid cells and astrocytes, we profiled two active MS lesions with thirteen glial activation markers using imaging mass cytometry (IMC), a method for multiplexed labeling of histological sections.

Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry.

Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation.

Domestication of cattle: Two or three events?

Cattle have been invaluable for the transition of human society from nomadic hunter-gatherers to sedentary farming communities throughout much of Europe, Asia and Africa since the earliest domestication of cattle more than 10,000 years ago. Although current understanding of relationships among ancestral populations remains limited, domestication of cattle is thought to have occurred on two or three occasions, giving rise to the taurine () and indicine () species that share the aurochs () as common ancestor ~250,000 years ago. Indicine and taurine cattle were domesticated in the Indus Valley and Fertile Crescent, respectively; however, an additional domestication event for taurine in the Western Desert of Egypt has also been proposed.

Demography and rapid local adaptation shape Creole cattle genome diversity in the tropics.

The introduction of Iberian cattle in the Americas after Columbus' arrival imposed high selection pressures on a limited number of animals over a brief period of time. Knowledge of the genomic regions selected during this process may help in enhancing climatic resilience and sustainable animal production. We first determined taurine and indicine contributions to the genomic structure of modern Creole cattle.