- Central Noradrenergic Agonists in the Treatment of Ischemic Stroke-an Overview. [Review]
- TSTransl Stroke Res 2019 Jul 20
- Ischemic stroke is the leading cause of morbidity and mortality with a significant health burden worldwide and few treatment options. Among the short- and long-term effects of ischemic stroke is the …
Ischemic stroke is the leading cause of morbidity and mortality with a significant health burden worldwide and few treatment options. Among the short- and long-term effects of ischemic stroke is the cardiovascular sympathetic autonomic dysfunction, presented in part as the by-product of the ischemic damage to the noradrenergic centers of the brain. Unlike high levels in the plasma, the brain may face suboptimal levels of norepinephrine (NE), with adverse effects on the clinical and functional outcomes of ischemic stroke. The intravenous administration of NE and other sympathomimetic agents, in an attempt to increase cerebral perfusion pressure, often aggravates the ischemia-induced rise in blood pressure (BP) with life-threatening consequences for stroke patients, the majority of whom present with hypertension at the time of admission. Unlike the systemic administration, the central administration of NE reduces BP while exerting anti-inflammatory and neuroprotective effects. These characteristics of centrally administered NE, combined with the short latency of response, make it an ideal candidate for use in the acute phase of stroke, followed by the use of centrally acting noradrenergic agonists, such as NE reuptake inhibitors and B2-adrenergic receptor agonists for stroke rehabilitation. In addition, a number of nonpharmacological strategies, such as transcutaneous vagus nerve stimulation (tVNS) and trigeminal nerve stimulation (TNS), have the potential to enhance the central noradrenergic functional activities and improve stroke clinical outcomes. Many factors could influence the efficacy of the noradrenergic treatment in stroke patients. These factors include the type of the noradrenergic agent; the dose, frequency, and duration of administration; the timing of administration in relation to the acute event; and the site and characteristics of the ischemic lesions. Having this knowledge, combined with the better understanding of the regulation of noradrenergic receptors in different parts of the brain, would pave the path for the successful use of the centrally acting noradrenergic agents in the management of ischemic stroke.
- Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases. [Journal Article]
- BBrain 2019 Jul 20
- Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now pro…
Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological manifestations in Alzheimer's disease, atypical neurodegenerative dementias and Parkinson's disease. Moreover, as the functional sensitivity of the noradrenergic system is likely to change with disease progression, in vivo measures of locus coeruleus integrity could provide new pathophysiological insights into cognitive and behavioural symptoms. Locus coeruleus imaging also holds the promise to stratify patients into clinical trials according to noradrenergic dysfunction. In this article, we present a consensus on how non-invasive in vivo assessment of locus coeruleus integrity can be used for clinical research in neurodegenerative diseases. We outline the next steps for in vivo, post-mortem and clinical studies that can lay the groundwork to evaluate the potential of locus coeruleus imaging as a biomarker for neurodegenerative diseases.
- Characterization of previously identified novel DNA fragment associated with Pathogenicity Island III536 reveals new blaCTX-M gene. [Journal Article]
- IGInfect Genet Evol 2019 Jul 18; :103971
- In the Kingdom of Bahrain a high percentage of extra-intestinal infectious diseases are reported as urinary tract infections UTIs. These UTIs are repeatedly diagnosed as multidrug resistant isolates.…
In the Kingdom of Bahrain a high percentage of extra-intestinal infectious diseases are reported as urinary tract infections UTIs. These UTIs are repeatedly diagnosed as multidrug resistant isolates. In a recent investigation, a novel DNA segment was identified in a UTI cefotaxime resistant Escherichia coli isolate. The DNA sequence was associated to pathogenicity island III536 locus. The current work is investigating/elucidating the genomic context of the newly identified locus in the UTI isolate using Single Genome Specific Primer-PCR (SGSP-PCR) approach. The isolate was characterized and redefined as strain EC1091 (genotype: blaTEM, blaCTX-M, gyrB, chuA, yjaA, TSpE4.C2) and its novel genomic contents were found to acquire antibiotic resistance genes: blaCTX-M and aac (3). The blaCTX-M was found to be a new beta-lactamase allele with no significant BLASTN results in the National Center for Biotechnology Information (NCBI), but a protein PSI-BLAST against non-redundant database revealed a remote similarity to CTX-M proteins.
- Further analyses on the phylogeny of the subclass Scuticociliatia (Protozoa, Ciliophora) based on both nuclear and mitochondrial data. [Journal Article]
- MPMol Phylogenet Evol 2019 Jul 18; :106565
- So far, the phylogenetic studies on ciliated protists have mainly based on single locus, the nuclear ribosomal DNA (rDNA). In order to avoid the limitations of single gene/genome trees and to add mor…
So far, the phylogenetic studies on ciliated protists have mainly based on single locus, the nuclear ribosomal DNA (rDNA). In order to avoid the limitations of single gene/genome trees and to add more data to systematic analyses, information from mitochondrial DNA sequence has been increasingly used in different lineages of ciliates. The systematic relationships in the subclass Scuticociliatia are extremely confused and largely unresolved based on nuclear genes. In the present study, we have characterized 72 new sequences, including 40 mitochondrial cytochrome oxidase c subunit I (COI) sequences, 29 mitochondrial small subunit ribosomal DNA sequences and three small subunit ribosomal DNA sequences from 47 isolates of 44 morphospecies. Phylogenetic analyses based on single gene as well as concatenated data were performed and revealed: 1) compared to mtSSU-rDNA, COI gene reveals more consistent relationships with those of nSSU-rDNA; 2) the secondary structures of mtSSU-rRNA V4 region are predicted and compared in scuticociliates, which can contribute to discrimination of closely related species; 3) neither nuclear nor mitochondrial data support the monophyly of the order Loxocephalida, which may represent some divergent and intermediate lineages between the subclass Scuticociliatia and Hymenostomatia; 4) the assignments of thigmotrichids to the order Pleuronematida and the confused taxon Sulcigera comosa to the genus Histiobalantium are verified by mitochondrial genes; 5) both nuclear and mitochondrial data reveal that the species in the family Peniculistomatidae always group in the genus Pleuronema, suggesting that peniculistomatids are more likely evolved from Pleuronema-like ancestors; 6) mitochondrial genes support the monophyly of the order Philasterida, but the relationships among families of the order Philasterida remain controversial due to the discrepancies between their morphological and molecular data.
- Molecular genetics of congenital myotonic dystrophy. [Review]
- NDNeurobiol Dis 2019 Jul 18; :104533
- Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease showing strong genetic anticipation, and is caused by the expansion of a CTG repeat tract in the 3'-UTR of the DMPK gene. Congenital Myotoni…
Myotonic Dystrophy type 1 (DM1) is a neuromuscular disease showing strong genetic anticipation, and is caused by the expansion of a CTG repeat tract in the 3'-UTR of the DMPK gene. Congenital Myotonic Dystrophy (CDM1) represents the most severe form of the disease, with prenatal onset, symptoms distinct from adult onset DM1, and a high rate of perinatal mortality. CDM1 is usually associated with very large CTG expansions, but this correlation is not absolute and cannot explain the distinct clinical features and the strong bias for maternal transmission. This review focuses upon the molecular and epigenetic factors that modulate disease severity and might be responsible for CDM1. Changes in the epigenetic status of the DM1 locus and in gene expression have recently been observed. Increasing evidence supports a role of a CTCF binding motif as a cis-element, upstream of the DMPK CTG tract, whereby CpG methylation of this site regulates the interaction of the insulator protein CTCF as a modulating trans-factor responsible for the inheritance and expression of CDM1.
- Prevalence, fecal egg counts, and species identification of gastrointestinal nematodes in replacement dairy heifers in Canada. [Journal Article]
- JDJ Dairy Sci 2019 Jul 17
- Information is scarce regarding the epidemiology of gastrointestinal nematodes in Canadian dairy heifers. The objectives of this study were to estimate the prevalence and fecal egg counts of gastroin…
Information is scarce regarding the epidemiology of gastrointestinal nematodes in Canadian dairy heifers. The objectives of this study were to estimate the prevalence and fecal egg counts of gastrointestinal nematodes in dairy heifers, and using a novel deep-amplicon sequencing approach, to identify the predominant gastrointestinal nematode species in Canadian dairy replacement heifers. Fresh environmental fecal samples (n = 2,369) were collected from replacement heifers on 306 dairy farms across western Canada, Ontario, Québec, and Atlantic Canada. Eggs per gram of feces (EPG) were determined using a modified Wisconsin double-centrifugation sugar flotation technique. Predominant nematode species at the farm level were identified by deep-amplicon nemabiome sequencing of the internal transcribed spacer-2 rDNA locus of nematode third-stage larvae. Generalized estimating equations were used to estimate predicted parasite prevalence and mean EPG in all heifers and by province, allowing for clustering within herds. Individual heifer egg counts ranged from 0 to 141 EPG (median: 0 EPG; interquartile range: 0 to 71 EPG). Gastrointestinal nematodes were detected in 20.9% (95% confidence interval: 17.2 to 24.6%) of heifers, and the predicted mean strongylid EPG accounting for clustering on farms was 1.1 (95% confidence interval: 0.6 to 1.6). The predominant parasite species were Cooperia oncophora and Ostertagia ostertagi. This is the first study in Canada to use a combination of deep-amplicon nemabiome sequencing and a traditional egg count method to describe the epidemiology of gastrointestinal nematodes in dairy heifers.
- Ethylene response factor NtERF91 positively regulates alkaloid accumulations in tobacco (Nicotiana tabacum L.). [Journal Article]
- BBBiochem Biophys Res Commun 2019 Jul 18
- Tobacco alkaloid metabolism is regulated by various transcription factors (TFs). Here, we have characterized a non-NIC2 locus gene, Ethylene Response Factor 91 (ERF91), function in regulation of alka…
Tobacco alkaloid metabolism is regulated by various transcription factors (TFs). Here, we have characterized a non-NIC2 locus gene, Ethylene Response Factor 91 (ERF91), function in regulation of alkaloid accumulation in tobacco. NtERF91 was preferentially expressed in roots and induced by jasmonic acid. Additionally, NtERF91 was able to in vitro bind to the NtPMT2 and NtQPT2 promoters via directly targeting the GCC-box elements and transactivate NtQPT2 gene expression. Ectopic overexpression of NtERF91 not only increased the expression of most nicotine biosynthetic genes, but also altered alkaloid accumulation profile, resulting in dramatically anatabine accumulation. We conclude that NtERF91 plays an overlapped but distinct role in regulating tobacco alkaloid accumulations.
- First genomic insights into carbapenem-resistant Klebsiella pneumoniae from Malaysia. [Journal Article]
- JGJ Glob Antimicrob Resist 2019 Jul 17
- CONCLUSIONS: We report the first genomic resources for carbapenem-resistant K. pneumoniae from Malaysia. The high diversity of carbapenem resistance genes and sequence types uncovered from only 8 isolates from the same hospital is worrying and indicates an urgent need to improve the genomic surveillance of clinical K. pneumoniae in Malaysia.
- Integrating three comprehensive datasets shows that mitochondrial DNA variation is linked to species traits and paleogeographic events in European butterflies. [Journal Article]
- MEMol Ecol Resour 2019 Jul 20
- Understanding the dynamics of biodiversity, including the spatial distribution of genetic diversity, is critical for predicting responses to environmental changes, as well as for effective conservati…
Understanding the dynamics of biodiversity, including the spatial distribution of genetic diversity, is critical for predicting responses to environmental changes, as well as for effective conservation measures. This task requires tracking changes in biodiversity at large spatial scales and correlating with species functional traits. We provide three comprehensive resources to understand the determinants for mitochondrial DNA differentiation represented by i) 15,609 COI sequences and ii) 14 traits belonging to 307 butterfly species occurring in Western-Central Europe and iii) the first multi-locus phylogenetic tree of all European butterfly species. By applying phylogenetic regressions we show that mitochondrial DNA spatial differentiation (as measured with Gst, G'st, D and Dst) is negatively correlated with species traits determining dispersal capability and colonization ability. Thanks to the high spatial resolution of the COI data, we also provide the first zoogeographic regionalization maps based on intraspecific genetic variation. The overall pattern obtained by averaging the spatial differentiation of all Western-Central European butterflies shows that the paradigm of long-term glacial isolation followed by rapid pulses of post-glacial expansion has been a pervasive phenomenon in European butterflies. The results and the extensive datasets we provide here constitute the basis for genetically-informed conservation plans for a charismatic group in a continent where flying insects are under alarming decline. This article is protected by copyright. All rights reserved.
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- Genome-wide association study of pre-harvest sprouting tolerance using a 90K SNP array in common wheat (Triticum aestivum L.). [Journal Article]
- TATheor Appl Genet 2019 Jul 19
- Three major loci for pre-harvest sprouting tolerance (PHST) were mapped on chromosomes 1AL, 3BS, and 6BL, and two CAPS and one dCAPS markers were validated. Sixteen lines with favorable alleles and i…
Three major loci for pre-harvest sprouting tolerance (PHST) were mapped on chromosomes 1AL, 3BS, and 6BL, and two CAPS and one dCAPS markers were validated. Sixteen lines with favorable alleles and increased PHST were identified. Pre-harvest sprouting (PHS) significantly affects wheat grain yield and quality. In the present study, the PHS tolerance (PHST) of 192 wheat varieties (lines) was evaluated by assessment of field sprouting, seed germination index, and period of dormancy in different environments. A high-density Illumina iSelect 90K SNP array was used to genotype the panel. A genome-wide association study (GWAS) based on single- and multi-locus mixed linear models was used to detect loci for PHST. The single-locus model identified 23 loci for PHST (P < 0.0001) and explained 6.0-18.9% of the phenotypic variance. Twenty loci were consistent with known quantitative trait loci (QTLs). Three single-nucleotide polymorphism markers closely linked with three major loci (Qphs.ahau-1A, Qphs.ahau-3B, and Qphs.ahau-6B) on chromosomes 1AL, 3BS, and 6BL, respectively, were converted to two cleaved amplified polymorphic sequences (CAPS) and one derived-CAPS markers, and validated in 374 wheat varieties (lines). The CAPS marker EX06323 for Qphs.ahau-6B co-segregated with a novel major QTL underlying PHST in a recombinant inbred line population raised from the cross Jing 411 × Wanxianbaimaizi. Linear regression showed a clear dependence of PHST on the number of favorable alleles. Sixteen varieties showing an elevated degree of PHST were identified and harbored more than 16 favorable alleles. The multi-locus model detected 39 marker-trait associations for PHST (P < 0.0001), of which five may be novel. Six loci common to the two models were identified. The combination of the two GWAS methods contributes to efficient dissection of the complex genetic mechanism of PHST.