Enlarged perivascular spaces in the brain are common but generally overlooked and of uncertain pathophysiology. They may reflect underlying cerebral small vessel disease. We determined whether ...enlarged perivascular spaces were associated with lacunar stroke subtype and white matter hyperintensities, markers of established small vessel disease.
We prospectively recruited patients with acute ischemic lacunar or cortical stroke. Age-matched nonstroke control subjects were also recruited. We rated basal ganglia and centrum semiovale enlarged perivascular spaces 0 to 4 (0=none, 4=>40) on T2-weighted MRI and white matter hyperintensities. We compared enlarged perivascular spaces between stroke subtypes and control subjects and assessed associations with vascular risk factors and white matter hyperintensities.
We recruited 350 patients; 129 lacunar, 124 cortical stroke, and 97 age-matched control subjects. Adjusting for vascular risk factors and white matter hyperintensities, total enlarged perivascular spaces were associated with lacunar stroke subtype (P=0.04) in the acute stroke group (n=253); basal ganglia enlarged perivascular spaces were associated with lacunar stroke subtype (P=0.003), deep (P=0.02) and periventricular white matter hyperintensities (P=0.01); in all 350 subjects, total enlarged perivascular spaces were associated with deep (P<0.001) and periventricular (P<0.001) white matter hyperintensities.
Although prevalent in patients with vascular risk factors and stroke, enlarged perivascular spaces are specifically associated with lacunar ischemic stroke and white matter hyperintensities. Further studies should determine the mechanism of this association while including adequate controls to account for stroke and vascular risk factors. Enlarged perivascular spaces should not be overlooked in studies of small vessel disease.
We review changes in the status of butterflies in Europe, focusing on long-running population data available for the United Kingdom, the Netherlands, and Belgium, based on standardized monitoring ...transects. In the United Kingdom, 8% of resident species have become extinct, and since 1976 overall numbers declined by around 50%. In the Netherlands, 20% of species have become extinct, and since 1990 overall numbers in the country declined by 50%. Distribution trends showed that butterfly distributions began decreasing long ago, and between 1890 and 1940, distributions declined by 80%. In Flanders (Belgium), 20 butterflies have become extinct (29%), and between 1992 and 2007 overall numbers declined by around 30%. A European Grassland Butterfly Indicator from 16 European countries shows there has been a 39% decline of grassland butterflies since 1990. The 2010 Red List of European butterflies listed 38 of the 482 European species (8%) as threatened and 44 species (10%) as near threatened (note that 47 species were not assessed). A country level analysis indicates that the average Red List rating is highest in central and mid-Western Europe and lowest in the far north of Europe and around the Mediterranean. The causes of the decline of butterflies are thought to be similar in most countries, mainly habitat loss and degradation and chemical pollution. Climate change is allowing many species to spread northward while bringing new threats to susceptible species. We describe examples of possible conservation solutions and a summary of policy changes needed to conserve butterflies and other insects.
We present high resolution (0.̋4) IRAM PdBI and ALMA mm and submm observations of the (ultra) luminous infrared galaxies ((U)LIRGs) IRAS 17208-0014, Arp220, IC 860 and Zw049.057 that reveal intense ...line emission from vibrationally excited (ν2 = 1) J = 3–2 and 4–3 HCN. The emission is emerging from buried, compact (r< 17–70 pc) nuclei that have very high implied mid-infrared surface brightness > 5 × 1013 L⊙ kpc-2. These nuclei are likely powered by accreting supermassive black holes (SMBHs) and/or hot (>200 K) extreme starbursts. Vibrational, ν2 = 1, lines of HCN are excited by intense 14 μm mid-infrared emission and are excellent probes of the dynamics, masses, and physical conditions of (U)LIRG nuclei when H2 column densities exceed 1024 cm-2. It is clear that these lines open up a new interesting avenue to gain access to the most obscured AGNs and starbursts. Vibrationally excited HCN acts as a proxy for the absorbed mid-infrared emission from the embedded nuclei, which allows for reconstruction of the intrinsic, hotter dust SED. In contrast, we show strong evidence that the ground vibrational state (ν = 0), J = 3–2and 4–3 rotational lines of HCN and HCO+ fail to probe the highly enshrouded, compact nuclear regions owing to strong self- and continuum absorption. The HCN and HCO+ line profiles are double-peaked because of the absorption and show evidence of non-circular motions – possibly in the form of in- or outflows. Detections of vibrationally excited HCN in external galaxies are so far limited to ULIRGs and early-type spiral LIRGs, and we discuss possible causes for this. We tentatively suggest that the peak of vibrationally excited HCN emission is connected to a rapid stage of nuclear growth, before the phase of strong feedback.
RNA-seq is a high-throughput sequencing technology widely used for gene transcript discovery and quantification under different biological or biomedical conditions. A fundamental research question in ...most RNA-seq experiments is the identification of differentially expressed genes among experimental conditions or sample groups. Numerous statistical methods for RNA-seq differential analysis have been proposed since the emergence of the RNA-seq assay. To evaluate popular differential analysis methods used in the open source R and Bioconductor packages, we conducted multiple simulation studies to compare the performance of eight RNA-seq differential analysis methods used in RNA-seq data analysis (edgeR, DESeq, DESeq2, baySeq, EBSeq, NOISeq, SAMSeq, Voom). The comparisons were across different scenarios with either equal or unequal library sizes, different distribution assumptions and sample sizes. We measured performance using false discovery rate (FDR) control, power, and stability. No significant differences were observed for FDR control, power, or stability across methods, whether with equal or unequal library sizes. For RNA-seq count data with negative binomial distribution, when sample size is 3 in each group, EBSeq performed better than the other methods as indicated by FDR control, power, and stability. When sample sizes increase to 6 or 12 in each group, DESeq2 performed slightly better than other methods. All methods have improved performance when sample size increases to 12 in each group except DESeq. For RNA-seq count data with log-normal distribution, both DESeq and DESeq2 methods performed better than other methods in terms of FDR control, power, and stability across all sample sizes. Real RNA-seq experimental data were also used to compare the total number of discoveries and stability of discoveries for each method. For RNA-seq data analysis, the EBSeq method is recommended for studies with sample size as small as 3 in each group, and the DESeq2 method is recommended for sample size of 6 or higher in each group when the data follow the negative binomial distribution. Both DESeq and DESeq2 methods are recommended when the data follow the log-normal distribution.
Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological ...disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modulate the course of the disease. Over the past two decades, the treatment landscape has changed tremendously. Currently, more than a dozen drugs representing 1 substances with different mechanisms of action have been approved (interferon beta preparations, glatiramer acetate, fingolimod, siponimod, mitoxantrone, teriflunomide, dimethyl fumarate, cladribine, alemtuzumab, ocrelizumab, and natalizumab). Ocrelizumab was the first medication to be approved for primary progressive MS. The objective of this review is to present the modes of action of these drugs and their effects on the immunopathogenesis of MS. Each agent's clinical development and potential side effects are discussed.
Within aquaculture, prebiotics are composed of complex carbohydrate molecules that cannot be digested by the fish directly but are metabolised by the microbial communities within the host gut, with ...the desire that “healthy” bacterial species are promoted with subsequently improved performance of the fish, there are likely some direct responses of intestinal cells to these dietary components. The sources and processing of prebiotics, which fall under the overarching theme of “functional feeds” are highly varied between species and types of prebiotics administered. How these feeds exert their effect, and the host responses are hard to determine, but new technologies and the development of high-throughput technologies (omics) are enabling the mechanisms and methods of action to be further understood. The recent advances in the availability of ‘omics’ technologies with the transition from single gene assays to microarray and RNA-seq in fish health have enabled novel functional ingredients to be analysed. This review will focus on recent studies on targeted gene expression and ‘omics’ technologies to characterize immune responses. Comparisons between the immunomodulatory effect of different prebiotics have been made and specific examples of how transcriptomics techniques have been used to identify immune responses to prebiotics are given.
•The type of prebiotic and tissue type alters the host immune response.•“omics” have identified specific immune pathways that are modulated by prebiotics.•Prebiotics can offer tolerance against bacterial pathogens.•Prebiotics can stimulate pro-inflammatory and complement responses in Salmonids.•Novel methodologies to study prebiotics can detect specific immune responses.
γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm ...relates to human Vδ2
T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2
T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1
T cells have therefore evolved a distinct biology from the Vδ2
subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance.
The effects of power and time conditions of in situ N 2 plasma treatment, prior to silicon nitride (SiN) passivation, were investigated on an AlGaN/GaN high-electron mobility transistor (HEMT). These ...studies reveal that N 2 plasma power is a critical parameter to control the SiN/AlGaN interface quality, which directly affects the 2-D electron gas density. Significant enhancement in the HEMT characteristics was observed by using a low power N 2 plasma pretreatment. In contrast, a marked gradual reduction in the maximum drain-source current density ( IDS max) and maximum transconductance (g m max ), as well as in fT and f max , was observed as the N 2 plasma power increases (up to 40% decrease for 210 W). Different mechanisms were proposed to be dominant as a function of the discharge power range. A good correlation was observed between the device electrical characteristics and the surface assessment by atomic force microscopy and Kelvin force microscopy techniques.
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