SigV mediates lysozyme resistance in Enterococcus faecalis via RsiV and PgdA

2021 ◽  
Author(s):  
Srivatsan Parthasarathy ◽  
Xiaofei Wang ◽  
Kristen R. Carr ◽  
Sriram Varahan ◽  
Elyssa B. Hancock ◽  
...  

Enterococcus faecalis is a gut commensal but transitions to a pathogenic state as a consequence of intestinal dysbiosis and/or the presence of indwelling medical devices causing a wide range of infections. One of the unique features of E. faecalis is its ability to display high level resistance to lysozyme, an important host defense of the innate immune response. Lysozyme resistance in E. faecalis is known to be mediated by the e xtra c ytoplasmic f unction (ECF) sigma factor, SigV. PgdA and RsiV expression is directly regulated by SigV, but pgdA and rsiV mutants display nominal changes in lysozyme resistance, suggesting that additional gene products in the SigV regulon contribute to lysozyme resistance. Using RNA-seq analysis, we compared the transcriptional profile of the parental strain to an isogenic sigV mutant and show that apart from sigV , only rsiV and pgdA expression was induced upon lysozyme exposure. The combined deletion mutant of both rsiV and pgdA rendered E. faecalis sensitive to lysozyme at a level comparable to the sigV mutant, highlighting the limited SigV regulon. Several additional genes were also induced upon lysozyme exposure, but in a SigV-independent fashion. Overexpression of pgdA from a SigV-independent promoter restored lysozyme resistance in a sigV deletion mutant and also induced cell chaining. Overexpression of rsiV from a SigV-independent promoter only partially restored lysozyme resistance in a sigV mutant. Overall, we provide evidence for a simple adaptation to lysozyme stress, in which SigV controls the expression of rsiV and pgdA , and that both gene products contribute to lysozyme resistance. Importance Enterococcus faecalis causes healthcare-associated infections and displays resistance to a variety of antibiotics and molecules of the innate immune system. SigV has been shown to play an important role in enterococcal lysozyme resistance. Even though several proteins have been implicated in enterococcal lysozyme resistance, a complete SigV-dependent regulon has not been functionally characterized as being responsible for the dramatic increase in lysozyme susceptibility displayed by a sig V mutant. Using RNA-seq, we have identified the SigV regulon to be comprised of two gene loci, sigV - rsiV and pgdA . Deletion of both rsiV and pgdA renders E. faecalis susceptible to lysozyme on par with a sigV mutant. We also demonstrate that overproduction of rsiV and pgdA contribute to lysozyme resistance in susceptible strains.

Author(s):  
V. Dodokhov ◽  
N. Pavlova ◽  
T. Rumyantseva ◽  
L. Kalashnikova

The article presents the genetic characteristic of the Chukchi reindeer breed. The object of the study was of the Chukchi reindeer. In recent years, the number of reindeer of the Chukchi breed has declined sharply. Reduced reindeer numbers could lead to biodiversity loss. The Chukchi breed of deer has good meat qualities, has high germination viability and is adapted in adverse tundra conditions of Yakutia. Herding of the Chukchi breed of deer in Yakutia are engaged only in the Nizhnekolymsky district. There are four generic communities and the largest of which is the agricultural production cooperative of nomadic tribal community «Turvaurgin», which was chosen to assess the genetic processes of breed using microsatellite markers: Rt6, BMS1788, Rt 30, Rt1, Rt9, FCB193, Rt7, BMS745, C 143, Rt24, OheQ, C217, C32, NVHRT16, T40, C276. It was found that microsatellite markers have a wide range of alleles and generally have a high informative value for identifying of genetic differences between animals and groups of animal. The number of identified alleles is one of the indicators of the genetic diversity of the population. The total number of detected alleles was 127. The Chukchi breed of deer is characterized by a high level of heterozygosity, and the random crossing system prevails over inbreeding in the population. On average, there were 7.9 alleles (Na) per locus, and the mean number of effective alleles (Ne) was 4.1. The index of fixation averaged 0.001. The polymorphism index (PIC) ranged from 0.217 to 0.946, with an average of 0.695.


2020 ◽  
Author(s):  
Sina Faizollahzadeh Ardabili ◽  
Amir Mosavi ◽  
Pedram Ghamisi ◽  
Filip Ferdinand ◽  
Annamaria R. Varkonyi-Koczy ◽  
...  

Several outbreak prediction models for COVID-19 are being used by officials around the world to make informed-decisions and enforce relevant control measures. Among the standard models for COVID-19 global pandemic prediction, simple epidemiological and statistical models have received more attention by authorities, and they are popular in the media. Due to a high level of uncertainty and lack of essential data, standard models have shown low accuracy for long-term prediction. Although the literature includes several attempts to address this issue, the essential generalization and robustness abilities of existing models needs to be improved. This paper presents a comparative analysis of machine learning and soft computing models to predict the COVID-19 outbreak as an alternative to SIR and SEIR models. Among a wide range of machine learning models investigated, two models showed promising results (i.e., multi-layered perceptron, MLP, and adaptive network-based fuzzy inference system, ANFIS). Based on the results reported here, and due to the highly complex nature of the COVID-19 outbreak and variation in its behavior from nation-to-nation, this study suggests machine learning as an effective tool to model the outbreak. This paper provides an initial benchmarking to demonstrate the potential of machine learning for future research. Paper further suggests that real novelty in outbreak prediction can be realized through integrating machine learning and SEIR models.


Author(s):  
Сергей Иванович Вележев ◽  
Антон Михайлович Седогин

В представленной статье авторами рассматриваются вопросы уголовно-правовой охраны топливно-энергетического комплекса Российской Федерации от преступных проявлений, в том числе от коррупционной противоправной деятельности должностных лиц. Такие действия причиняют значительный ущерб нормальному функционированию предприятий топливно-энергетического комплекса. Авторами приводятся результаты исследования некоторых криминологических характеристик должностных лиц, совершивших преступления коррупционного характера. Дан анализ причин и условий, способствующих совершению вышеуказанных противоправных действий. Определена типовая модель преступника для данной категории преступлений и его характеристики: в первую очередь, это высокий уровень компетентности, специальное образование и т. д. Авторами отмечается высокий уровень латентной преступности в данной отрасли. Предложены некоторые пути профилактики данной категории правонарушений. Исследование проводилось на основе анализа конкретных уголовных дел, возбужденных следственными органами по результатам оперативно-розыскной деятельности правоохранительных органов. In the article the authors consider the issues of criminal and legal protection of the fuel and energy complex of the Russian Federation from criminal activity including corrupt illegal practices of officials. The authors cite the results of some criminological characteristics study of the fuel and energy complex staff committed corruption crimes. As a result of these illegal actions significant damage is caused to the normal functioning of the fuel and energy enterprises. Such officials` actions determine not only a wide range of other illegal activities, but also lead to public outcry and discredit the industry as a whole. The analysis of the reasons and conditions contributing to the above illegal actions commission is given. A typical model of a criminal for a given crime category and its characteristics are determined. First of all it is a high level competence, special education, etc. A high level of latent crime in this industry is shown. The study results are presented on the example of specific criminal cases initiated by the investigating authorities based on the results of the operation detection activities of law enforcement agencies. Some ways of preventing this category of offenses are proposed.


2020 ◽  
Vol 02 ◽  
Author(s):  
Masood Ghori ◽  
Nadya O. Al Matrooshi ◽  
Samir Al Jabbari ◽  
Ahmed Bafadel ◽  
Gopal Bhatnagar

: Infective Endocarditis (IE), a known complication of hemodialysis (HD), has recently been categorized as Healthcare-Associated Infective Endocarditis (HAIE). Single pathogen bacteremia is common, polymicrobial endocardial infection is rare in this cohort of the patients. We report a case of endocarditis caused by Enterococcus faecalis (E. faecalis) and Burkholderia cepacia (B. cepacia), a first ever reported combination of a usual and an unusual organism, respectively, in a patient on HD. Clinical presentation of the patient, its complicated course ,medical and surgical management ,along with microbial and echocardiographic findings is presented herein. The authors believe that presentation of this case of HAIE may benefit and contribute positively to cardiac science owing to the rare encounter of this organism as a pathogen in infective endocarditis and the difficulties in treating it.


1970 ◽  
Vol 19 (1-2) ◽  
pp. 264-267 ◽  
Author(s):  
F.H. Reuling ◽  
J.T. Schwartz

In the late 1950's and early 1960's, it became evident that some glaucoma patients developed elevations of intraocular pressure, which were difficult to control, following prolonged use of systemic or ocular medications containing corticosteroids (Chandler, 1955, Alfano, 1963; Armaly, 1963). In addition, some patients without glaucoma, when treated with steroids for long periods of time, developed clinical signs of chronic simple glaucoma (McLean, 1950; François, 1954; Covell, 1958; Linner, 1959; Goldman, 1962). Fortunately, the elevation of intraocular pressure was reversible if the drug was discontinued.Over the past decade, extensive investigation of the “steroid response” has been undertaken. For this presentation, the steroid response may be considered as a gradual elevation of intraocular pressure, occurring over several weeks, in an eye being medicated with corticosteroid drops several times a day. The elevation in pressure is usually accompanied by a reduction in the facility of aqueous outflow. When relatively large numbers of subjects were tested with topical steroids, so that a wide range of responsiveness could be observed, a variation in individual sensitivity was demonstrated. Frequency distributions of intraocular pressure or change in pressure following steroids showed a skew toward the high side. On the basis of trimodal characteristics which they observed in such frequency distributions, Becker and Hahn (1964), Becker (1965) and Armaly (1965, 1966) considered the possible existence of several genetically determined subpopulations. These investigators distinguished three subpopulations on the basis of low, intermediate, and high levels of pressure response. It was hypothesized that these levels of response characterized three phenotypes, corresponding to the three possible genotypes of an allele pair, wherein one member of the pair determined a low level of response, and the other member determined a high level of response (Armaly, 1967).


2020 ◽  
Vol 21 (24) ◽  
pp. 9769
Author(s):  
Saaya Koike ◽  
Kenshi Yamasaki

The epidermis is located in the outermost layer of the living body and is the place where external stimuli such as ultraviolet rays and microorganisms first come into contact. Melanocytes and melanin play a wide range of roles such as adsorption of metals, thermoregulation, and protection from foreign enemies by camouflage. Pigmentary disorders are observed in diseases associated with immunodeficiency such as Griscelli syndrome, indicating molecular sharing between immune systems and the machineries of pigment formation. Melanocytes express functional toll-like receptors (TLRs), and innate immune stimulation via TLRs affects melanin synthesis and melanosome transport to modulate skin pigmentation. TLR2 enhances melanogenetic gene expression to augment melanogenesis. In contrast, TLR3 increases melanosome transport to transfer to keratinocytes through Rab27A, the responsible molecule of Griscelli syndrome. TLR4 and TLR9 enhance tyrosinase expression and melanogenesis through p38 MAPK (mitogen-activated protein kinase) and NFκB signaling pathway, respectively. TLR7 suppresses microphthalmia-associated transcription factor (MITF), and MITF reduction leads to melanocyte apoptosis. Accumulating knowledge of the TLRs function of melanocytes has enlightened the link between melanogenesis and innate immune system.


Author(s):  
Robin Orr ◽  
Takato Sakurai ◽  
Jordan Scott ◽  
Jason Movshovich ◽  
J. Jay Dawes ◽  
...  

Tactical personnel work in an occupation that involves tasks requiring a high level of cardiovascular fitness as well as muscular strength and endurance. The aim of this literature review was to identify and critique studies investigating the relationship between physical fitness, quantified by fitness assessment measures, and occupational task performance. Databases were searched for relevant articles which assessed a fitness measure and a measure of occupational performance. A total of 15 articles were included and were deemed to be of acceptable methodological quality (8.4/12 on the Critical Appraisal Skills Programme checklist). Included articles assessed a variety of fitness attributes and occupational tasks. Across tactical groups, there appear to be no standardized fitness tests that can determine occupational performance, with aerobic fitness, anaerobic fitness, strength, endurance, power, and agility all being associated with occupational task performance. A wide range of fitness assessments appears to be required to predict occupational performance within tactical personnel. Efforts should be made to base fitness assessments on occupational demands unique to both the environment and requirements of each individual tactical unit.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Bingran Wang ◽  
Tiancheng Lou ◽  
Lingling Wei ◽  
Wenchan Chen ◽  
Longbing Huang ◽  
...  

AbstractAlternaria alternata, a causal agent of leaf blights and spots on a wide range of hosts, has a high risk of developing resistance to fungicides. Procymidone, a dicarboximide fungicide (DCF), has been widely used in controlling Alternaria leaf blights in China for decades. However, the resistance of A. alternata against DCFs has rarely been reported from crucifer plants. A total of 198 A. alternata isolates were collected from commercial fields of broccoli and cabbage during 2018–2019, and their sensitivities to procymidone were determined. Biochemical and molecular characteristics were subsequently compared between the high-level procymidone-resistant (ProHR) and procymidone-sensitive (ProS) isolates, and also between ProHR isolates from broccoli and cabbage. Compared with ProS isolates, the mycelial growth rate, sporulation capacity and virulence of most ProHR isolates were reduced; ProHR isolates displayed an increased sensitivity to osmotic stresses and a reduced sensitivity to sodium dodecyl sulfate (SDS); all ProHR isolates showed a reduced sensitivity to hydrogen peroxide (H2O2) except for the isolate B102. Correlation analysis revealed a positive cross-resistance between procymidone and iprodione, or fludioxonil. When treated with 10 μg/mL of procymidone, both mycelial intracellular glycerol accumulations (MIGAs) and relative expression of AaHK1 in ProS isolates were higher than those in ProHR isolates. Sequence alignment of AaHK1 from ten ProHR isolates demonstrated that five of them possessed a single-point mutation (P94A, V612L, E708K or Q924STOP), and four isolates had an insertion or a deletion in their coding regions. No significant difference in biochemical characteristics was observed among ProHR isolates from two different hosts, though mutations in AaHK1 of the cabbage-originated ProHR isolates were distinct from those of the broccoli-originated ProHR isolates.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 311
Author(s):  
Zhenqiu Liu

Single-cell RNA-seq (scRNA-seq) is a powerful tool to measure the expression patterns of individual cells and discover heterogeneity and functional diversity among cell populations. Due to variability, it is challenging to analyze such data efficiently. Many clustering methods have been developed using at least one free parameter. Different choices for free parameters may lead to substantially different visualizations and clusters. Tuning free parameters is also time consuming. Thus there is need for a simple, robust, and efficient clustering method. In this paper, we propose a new regularized Gaussian graphical clustering (RGGC) method for scRNA-seq data. RGGC is based on high-order (partial) correlations and subspace learning, and is robust over a wide-range of a regularized parameter λ. Therefore, we can simply set λ=2 or λ=log(p) for AIC (Akaike information criterion) or BIC (Bayesian information criterion) without cross-validation. Cell subpopulations are discovered by the Louvain community detection algorithm that determines the number of clusters automatically. There is no free parameter to be tuned with RGGC. When evaluated with simulated and benchmark scRNA-seq data sets against widely used methods, RGGC is computationally efficient and one of the top performers. It can detect inter-sample cell heterogeneity, when applied to glioblastoma scRNA-seq data.


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