bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microtubule mechanics in the working myocyte
Authors: Robison Patrick , Prosser Benjamin L. 
Published: January 2017

AbstractThe mechanical role of cardiac microtubules (MTs) has been a topic of some controversy. Early studies, which relied largely on pharmacological interventions that altered the MT cytoskeleton as a whole, presented no consistent role. Recent advances in the ability to observe and manipulate specific properties of the cytoskeleton have strengthened our understanding. Direct observation of MTs in working myocytes suggests a spring‐like function, one that is surprisingly tunable by post‐translational modification (PTM). Specifically, detyrosination of MTs facilitates an interaction with intermediate filaments that complex with the sarcomere, altering myocyte stiffness, contractility, and mechanosignalling. Such results support a paradigm of cytoskeletal regulation based on not only polymerization, but also associations with binding partners and PTMs that divide the MT cytoskeleton into functionally distinct subsets. The evolutionary costs and benefits of tuning cytoskeletal mechanics remain an open question, one that we discuss herein. Nevertheless, mechanically distinct MT subsets provide a rich new source of therapeutic targets for a variety of phenomena in the heart.
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In vitro models of the cardiac microenvironment to study myocyte and non‐myocyte crosstalk: bioinspired approaches beyond the polystyrene dish
Authors: Kofron Celinda M. , Mende Ulrike 
Published: January 2017

AbstractThe heart is a complex pluricellular organ composed of cardiomyocytes and non‐myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non‐myocytes are known to communicate and exert mutual regulatory effects. In concert, they determine the structural, electrical and mechanical characteristics in the healthy and remodelled myocardium. Dynamic crosstalk between myocytes and non‐myocytes plays a crucial role in stress/injury‐induced hypertrophy and fibrosis development that can ultimately lead to heart failure and arrhythmias. Investigations of heterocellular communication in the myocardium are hampered by the intricate interspersion of the different cell types and the complexity of the tissue architecture. In vitro models have facilitated investigations of cardiac cells in a direct and controllable manner and have provided important functional and mechanistic insights. However, these cultures often lack regulatory input from the other cell types as well as additional topographical, electrical, mechanical and biochemical cues from the cardiac microenvironment that all contribute to modulating cell differentiation, maturation, alignment, function and survival. Advancements in the development of more complex pluricellular physiological platforms that incorporate diverse cues from the myocardial microenvironment are expected to lead to more physiologically relevant cardiac tissue‐like in vitro models for mechanistic biological research, disease modelling, therapeutic target identification, drug testing and regeneration.
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Relationship between cortical state and spiking activity in the lateral geniculate nucleus of marmosets
Authors: Pietersen Alexander N.J. , Cheong Soon Keen , Munn Brandon , Gong Pulin , Martin Paul R. , Solomon Samuel G. 
Published: January 2017

Key points
How parallel are the primate visual pathways? In the present study, we demonstrate that parallel visual pathways in the dorsal lateral geniculate nucleus (LGN) show distinct patterns of interaction with rhythmic activity in the primary visual cortex (V1).
In the V1 of anaesthetized marmosets, the EEG frequency spectrum undergoes transient changes that are characterized by fluctuations in delta‐band EEG power.
We show that, on multisecond timescales, spiking activity in an evolutionary primitive (koniocellular) LGN pathway is specifically linked to these slow EEG spectrum changes. By contrast, on subsecond (delta frequency) timescales, cortical oscillations can entrain spiking activity throughout the entire LGN.
Our results are consistent with the hypothesis that, in waking animals, the koniocellular pathway selectively participates in brain circuits controlling vigilance and attention.
AbstractThe major afferent cortical pathway in the visual system passes through the dorsal lateral geniculate nucleus (LGN), where nerve signals originating in the eye can first interact with brain circuits regulating visual processing, vigilance and attention. In the present study, we investigated how ongoing and visually driven activity in magnocellular (M), parvocellular (P) and koniocellular (K) layers of the LGN are related to cortical state. We recorded extracellular spiking activity in the LGN simultaneously with local field potentials (LFP) in primary visual cortex, in sufentanil‐anaesthetized marmoset monkeys. We found that asynchronous cortical states (marked by low power in delta‐band LFPs) are linked to high spike rates in K cells (but not P cells or M cells), on multisecond timescales. Cortical asynchrony precedes the increases in K cell spike rates by 1–3 s, implying causality. At subsecond timescales, the spiking activity in many cells of all (M, P and K) classes is phase‐locked to delta waves in the cortical LFP, and more cells are phase‐locked during synchronous cortical states than during asynchronous cortical states. The switch from low‐to‐high spike rates in K cells does not degrade their visual signalling capacity. By contrast, during asynchronous cortical states, the fidelity of visual signals transmitted by K cells is improved, probably because K cell responses become less rectified. Overall, the data show that slow fluctuations in cortical state are selectively linked to K pathway spiking activity, whereas delta‐frequency cortical oscillations entrain spiking activity throughout the entire LGN, in anaesthetized marmosets.
Rifampin Enhances the Activity of Amphotericin B against Fusarium solani Species Complex and Aspergillus flavus Species Complex Isolates from Keratitis Patients
Authors: He Yi , Zhou Lutan , Gao Chuanwen , Han Lei , Xu Yan 
Published: January 2017

ABSTRACT

The
in vitro
activities of amphotericin B in combination with rifampin were assessed against 95 ocular fungal isolates. The interactions between amphotericin B and rifampin at 4, 8, 16, and 32 μg/ml were synergistic for 11.8%, 51.0%, 90.2%, and 94.1%, respectively, of
Fusarium solani
species complex isolates and for 13.6%, 45.5%, 93.2%, and 95.5%, respectively, of
Aspergillus flavus
species complex isolates. Antagonism was never observed for the amphotericin B-rifampin combinations.
Perturbations of Phosphatidate Cytidylyltransferase (CdsA) Mediate Daptomycin Resistance in Streptococcus mitis/oralis by a Novel Mechanism
Authors: Mishra Nagendra N. , Tran Truc T. , Seepersaud Ravin , Garcia-de-la-Maria Cristina , Faull Kym , Yoon Alex , Proctor Richard , Miro Jose M. , Rybak Michael J. , Bayer Arnold S. , Arias Cesar A. , Sullam Paul M. 
Published: January 2017

ABSTRACT

Streptococcus mitis/oralis
is an important pathogen, causing life-threatening infections such as endocarditis and severe sepsis in immunocompromised patients. The β-lactam antibiotics are the usual therapy of choice for this organism, but their effectiveness is threatened by the frequent emergence of resistance. The lipopeptide daptomycin (DAP) has been suggested for therapy against such resistant
S. mitis/oralis
strains due to its
in vitro
bactericidal activity and demonstrated efficacy against other Gram-positive pathogens. Unlike other bacteria, however,
S. mitis/oralis
has the unique ability to rapidly develop stable, high-level resistance to DAP upon exposure to the drug both
in vivo
and
in vitro
. Using isogenic DAP-susceptible and DAP-resistant
S. mitis/oralis
strain pairs, we describe a mechanism of resistance to both DAP and cationic antimicrobial peptides that involves loss-of-function mutations in
cdsA
(encoding a phosphatidate cytidylyltransferase). CdsA catalyzes the synthesis of cytidine diphosphate-diacylglycerol, an essential phospholipid intermediate for the production of membrane phosphatidylglycerol and cardiolipin. DAP-resistant
S. mitis/oralis
strains demonstrated a total disappearance of phosphatidylglycerol, cardiolipin, and anionic phospholipid microdomains from membranes. In addition, these strains exhibited cross-resistance to cationic antimicrobial peptides from human neutrophils (i.e., hNP-1). Interestingly, CdsA-mediated changes in phospholipid metabolism were associated with DAP hyperaccumulation in a small subset of the bacterial population, without any binding by the remaining larger population. Our results indicate that CdsA is the major mediator of high-level DAP resistance in
S. mitis/oralis
and suggest a novel mechanism of bacterial survival against attack by antimicrobial peptides of both innate and exogenous origins.
Interactions of Freshwater Cyanobacteria with Bacterial Antagonists
Authors: Osman Omneya Ahmed , Beier Sara , Grabherr Manfred , Bertilsson Stefan 
Published: January 2017

ABSTRACTCyanobacterial and algal mass development, or blooms, have severe effects on freshwater and marine systems around the world. Many of these phototrophs produce a variety of potent toxins, contribute to oxygen depletion, and affect water quality in several ways. Coexisting antagonists, such as cyanolytic bacteria, hold the potential to suppress, or even terminate, such blooms, yet the nature of this interaction is not well studied. We isolated 31 cyanolytic bacteria affiliated with the generaPseudomonas,Stenotrophomonas,Acinetobacter, andDelftiafrom three eutrophic freshwater lakes in Sweden and selected four phylogenetically diverse bacterial strains with strong-to-moderate lytic activity. To characterize their functional responses to the presence of cyanobacteria, we performed RNA sequencing (RNA-Seq) experiments on coculture incubations, with an initial predator-prey ratio of 1:1. Genes involved in central cellular pathways, stress-related heat or cold shock proteins, and antitoxin genes were highly expressed in both heterotrophs and cyanobacteria. Heterotrophs in coculture expressed genes involved in cell motility, signal transduction, and putative lytic activity.l,d-Transpeptidase was the only significantly upregulated lytic gene inStenotrophomonas rhizophilaEK20. Heterotrophs also shifted their central metabolism from the tricarboxylic acid cycle to the glyoxylate shunt. Concurrently, cyanobacteria clearly show contrasting antagonistic interactions with the four tested heterotrophic strains, which is also reflected in the physical attachment to their cells. In conclusion, antagonistic interactions with cyanobacteria were initiated within 24 h, and expression profiles suggest varied responses for the different cyanobacteria and studied cyanolytes.IMPORTANCEHere, we present how gene expression profiles can be used to reveal interactions between bloom-forming freshwater cyanobacteria and antagonistic heterotrophic bacteria. Species-specific responses in both heterotrophs and cyanobacteria were identified. The study contributes to a better understanding of the interspecies cellular interactions underpinning the persistence and collapse of cyanobacterial blooms.
Ursodeoxycholic Acid and Its Taurine- or Glycine-Conjugated Species Reduce Colitogenic Dysbiosis and Equally Suppress Experimental Colitis in Mice
Authors: Van den Bossche Lien , Hindryckx Pieter , Devisscher Lindsey , Devriese Sarah , Van Welden Sophie , Holvoet Tom , Vilchez-Vargas Ramiro , Vital Marius , Pieper Dietmar H. , Vanden Bussche Julie , Vanhaecke Lynn , Van de Wiele Tom , De Vos Martine , Laukens Debby 
Published: January 2017

ABSTRACT

The promising results seen in studies of secondary bile acids in experimental colitis suggest that they may represent an attractive and safe class of drugs for the treatment of inflammatory bowel diseases (IBD). However, the exact mechanism by which bile acid therapy confers protection from colitogenesis is currently unknown. Since the gut microbiota plays a crucial role in the pathogenesis of IBD, and exogenous bile acid administration may affect the community structure of the microbiota, we examined the impact of the secondary bile acid ursodeoxycholic acid (UDCA) and its taurine or glycine conjugates on the fecal microbial community structure during experimental colitis. Daily oral administration of UDCA, tauroursodeoxycholic acid (TUDCA), or glycoursodeoxycholic acid (GUDCA) equally lowered the severity of dextran sodium sulfate-induced colitis in mice, as evidenced by reduced body weight loss, colonic shortening, and expression of inflammatory cytokines. Illumina sequencing demonstrated that bile acid therapy during colitis did not restore fecal bacterial richness and diversity. However, bile acid therapy normalized the colitis-associated increased ratio of
Firmicutes
to
Bacteroidetes
. Interestingly, administration of bile acids prevented the loss of
Clostridium
cluster XIVa and increased the abundance of
Akkermansia muciniphila
, bacterial species known to be particularly decreased in IBD patients. We conclude that UDCA, which is an FDA-approved drug for cholestatic liver disorders, could be an attractive treatment option to reduce dysbiosis and ameliorate inflammation in human IBD.

IMPORTANCE
Secondary bile acids are emerging as attractive candidates for the treatment of inflammatory bowel disease. Although bile acids may affect the intestinal microbial community structure, which significantly contributes to the course of these inflammatory disorders, the impact of bile acid therapy on the fecal microbiota during colitis has not yet been considered. Here, we studied the alterations in the fecal microbial abundance in colitic mice following the administration of secondary bile acids. Our results show that secondary bile acids reduce the severity of colitis and ameliorate colitis-associated fecal dysbiosis at the phylum level. This study indicates that secondary bile acids might act as a safe and effective drug for inflammatory bowel disease.
Osmotolerance in Escherichia coli Is Improved by Activation of Copper Efflux Genes or Supplementation with Sulfur-Containing Amino Acids
Authors: Xiao Mengyong , Zhu Xinna , Fan Feiyu , Xu Hongtao , Tang Jinlei , Qin Ying , Ma Yanhe , Zhang Xueli 
Published: January 2017

ABSTRACT

Improvement in the osmotolerance of
Escherichia coli
is essential for the production of high titers of various bioproducts. In this work, a
cusS
mutation that was identified in the previously constructed high-succinate-producing
E. coli
strain HX024 was investigated for its effect on osmotolerance. CusS is part of the two-component system CusSR that protects cells from Ag(I) and Cu(I) toxicity. Changing
cusS
from strain HX024 back to its original sequence led to a 24% decrease in cell mass and succinate titer under osmotic stress (12% glucose). When cultivated with a high initial glucose concentration (12%), introduction of the
cusS
mutation into parental strain Suc-T110 led to a 21% increase in cell mass and a 40% increase in succinate titer. When the medium was supplemented with 30 g/liter disodium succinate, the
cusS
mutation led to a 120% increase in cell mass and a 492% increase in succinate titer. Introducing the
cusS
mutation into the wild-type strain ATCC 8739 led to increases in cell mass of 87% with 20% glucose and 36% using 30 g/liter disodium succinate. The
cusS
mutation increased the expression of
cusCFBA
, and gene expression levels were found to be positively related to osmotolerance abilities. Because high osmotic stress has been associated with deleterious accumulation of Cu(I) in the periplasm, activation of CusCFBA may alleviate this effect by transporting Cu(I) out of the cells. This hypothesis was confirmed by supplementing sulfur-containing amino acids that can chelate Cu(I). Adding methionine or cysteine to the medium increased the osmotolerance of
E. coli
under anaerobic conditions.

IMPORTANCE
In this work, an activating Cus copper efflux system was found to increase the osmotolerance of
E. coli
. In addition, new osmoprotectants were identified. Supplementation with methionine or cysteine led to an increase in osmotolerance of
E. coli
under anaerobic conditions. These new strategies for improving osmotolerance will be useful for improving the production of chemicals in industrial bioprocesses.
Genome-Wide Identification of Host-Segregating Epidemiological Markers for Source Attribution in Campylobacter jejuni
Authors: Thépault Amandine , Méric Guillaume , Rivoal Katell , Pascoe Ben , Mageiros Leonardos , Touzain Fabrice , Rose Valérie , Béven Véronique , Chemaly Marianne , Sheppard Samuel K. 
Published: January 2017

ABSTRACT

Campylobacter
is among the most common worldwide causes of bacterial gastroenteritis. This organism is part of the commensal microbiota of numerous host species, including livestock, and these animals constitute potential sources of human infection. Molecular typing approaches, especially multilocus sequence typing (MLST), have been used to attribute the source of human campylobacteriosis by quantifying the relative abundance of alleles at seven MLST loci among isolates from animal reservoirs and human infection, implicating chicken as a major infection source. The increasing availability of bacterial genomes provides data on allelic variation at loci across the genome, providing the potential to improve the discriminatory power of data for source attribution. Here we present a source attribution approach based on the identification of novel epidemiological markers among a reference pan-genome list of 1,810 genes identified by gene-by-gene comparison of 884 genomes of
Campylobacter jejuni
isolates from animal reservoirs, the environment, and clinical cases. Fifteen loci involved in metabolic activities, protein modification, signal transduction, and stress response or coding for hypothetical proteins were selected as host-segregating markers and used to attribute the source of 42 French and 281 United Kingdom clinical
C. jejuni
isolates. Consistent with previous studies of British campylobacteriosis, analyses performed using STRUCTURE software attributed 56.8% of British clinical cases to chicken, emphasizing the importance of this host reservoir as an infection source in the United Kingdom. However, among French clinical isolates, approximately equal proportions of isolates were attributed to chicken and ruminant reservoirs, suggesting possible differences in the relative importance of animal host reservoirs and indicating a benefit for further national-scale attribution modeling to account for differences in production, behavior, and food consumption.

IMPORTANCE
Accurately quantifying the relative contribution of different host reservoirs to human
Campylobacter
infection is an ongoing challenge. This study, based on the development of a novel source attribution approach, provides the first results of source attribution in
Campylobacter jejuni
in France. A systematic analysis using gene-by-gene comparison of 884 genomes of
C. jejuni
isolates, with a pan-genome list of genes, identified 15 novel epidemiological markers for source attribution. The different proportions of French and United Kingdom clinical isolates attributed to each host reservoir illustrate a potential role for local/national variations in
C. jejuni
transmission dynamics.
Development of
oriC
-Based Plasmids for Mesoplasma florum
Authors: Matteau Dominick , Pepin Marie-Eve , Baby Vincent , Gauthier Samuel , Arango Giraldo Mélissa , Knight Thomas F. , Rodrigue Sébastien 
Published: January 2017

ABSTRACT

The near-minimal bacterium
Mesoplasma florum
constitutes an attractive model for systems biology and for the development of a simplified cell chassis in synthetic biology. However, the lack of genetic engineering tools for this microorganism has limited our capacity to understand its basic biology and modify its genome. To address this issue, we have evaluated the susceptibility of
M. florum
to common antibiotics and developed the first generation of artificial plasmids able to replicate in this bacterium. Selected regions of the predicted
M. florum
chromosomal origin of replication (
oriC
) were used to create different plasmid versions that were tested for their transformation frequency and stability. Using polyethylene glycol-mediated transformation, we observed that plasmids harboring both
rpmH-dnaA
and
dnaA-dnaN
intergenic regions, interspaced or not with a copy of the
dnaA
gene, resulted in a frequency of ∼4.1 × 10
−6
transformants per viable cell and were stably maintained throughout multiple generations. In contrast, plasmids containing only one
M. florum
oriC
intergenic region or the heterologous
oriC
region of
Mycoplasma capricolum
,
Mycoplasma mycoides
, or
Spiroplasma citri
failed to produce any detectable transformants. We also developed alternative transformation procedures based on electroporation and conjugation from
Escherichia coli
, reaching frequencies up to 7.87 × 10
−6
and 8.44 × 10
−7
transformants per viable cell, respectively. Finally, we demonstrated the functionality of antibiotic resistance genes active against tetracycline, puromycin, and spectinomycin/streptomycin in
M. florum
. Taken together, these valuable genetic tools will facilitate efforts toward building an
M. florum
-based near-minimal cellular chassis for synthetic biology.

IMPORTANCE
Mesoplasma florum
constitutes an attractive model for systems biology and for the development of a simplified cell chassis in synthetic biology.
M. florum
is closely related to the mycoides cluster of mycoplasmas, which has become a model for whole-genome cloning, genome transplantation, and genome minimization. However,
M. florum
shows higher growth rates than other
Mollicutes
, has no known pathogenic potential, and possesses a significantly smaller genome that positions this species among some of the simplest free-living organisms. So far, the lack of genetic engineering tools has limited our capacity to understand the basic biology of
M. florum
in order to modify its genome. To address this issue, we have evaluated the susceptibility of
M. florum
to common antibiotics and developed the first artificial plasmids and transformation methods for this bacterium. This represents a strong basis for ongoing genome engineering efforts using this near-minimal microorganism.