bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systems perspective on placental amino acid transport
Authors: Cleal Jane K. , Lofthouse Emma M. , Sengers Bram G. , Lewis Rohan M. 
Published: July 2018

AbstractPlacental amino acid transfer is a complex process that is essential for fetal development. Impaired amino acid transfer causes fetal growth restriction, which may have lifelong health consequences. Transepithelial transfer of amino acids across the placental syncytiotrophoblast requires accumulative, exchange and facilitated transporters on the apical and basal membranes to work in concert. However, transporters alone do not determine amino acid transfer and factors that affect substrate availability, such as blood flow and metabolism, may also become rate‐limiting for transfer. In order to determine the rate‐limiting processes, it is necessary to take a systems approach which recognises the interdependence of these processes. New technologies have the potential to deliver targeted interventions to the placenta and help poorly growing fetuses. While many factors are necessary for amino acid transfer, novel therapies need to target the rate‐limiting factors if they are going to be effective. This review will outline the factors which determine amino acid transfer and describe how they become interdependent. It will also highlight the role of computational modelling as a tool to understand this process.
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Restricted Localization of Photosynthetic Intracytoplasmic Membranes (ICMs) in Multiple Genera of Purple Nonsulfur Bacteria
Authors: LaSarre Breah , Kysela David T. , Stein Barry D. , Ducret Adrien , Brun Yves V. , McKinlay James B. 
Published: July 2018

ABSTRACT
In bacteria and eukaryotes alike, proper cellular physiology relies on robust subcellular organization. For the phototrophic purple nonsulfur bacteria (PNSB), this organization entails the use of a light-harvesting, membrane-bound compartment known as the intracytoplasmic membrane (ICM). Here we show that ICMs are spatially and temporally localized in diverse patterns among PNSB. We visualized ICMs in live cells of 14 PNSB species across nine genera by exploiting the natural autofluorescence of the photosynthetic pigment bacteriochlorophyll (BChl). We then quantitatively characterized ICM localization using automated computational analysis of BChl fluorescence patterns within single cells across the population. We revealed that while many PNSB elaborate ICMs along the entirety of the cell, species across as least two genera restrict ICMs to discrete, nonrandom sites near cell poles in a manner coordinated with cell growth and division. Phylogenetic and phenotypic comparisons established that ICM localization and ICM architecture are not strictly interdependent and that neither trait fully correlates with the evolutionary relatedness of the species. The natural diversity of ICM localization revealed herein has implications for both the evolution of phototrophic organisms and their light-harvesting compartments and the mechanisms underpinning spatial organization of bacterial compartments.

IMPORTANCE
Many bacteria organize their cellular space by constructing subcellular compartments that are arranged in specific, physiologically relevant patterns. The purple nonsulfur bacteria (PNSB) utilize a membrane-bound compartment known as the intracytoplasmic membrane (ICM) to harvest light for photosynthesis. It was previously unknown whether ICM localization within cells is systematic or irregular and if ICM localization is conserved among PNSB. Here we surveyed ICM localization in diverse PNSB and show that ICMs are spatially organized in species-specific patterns. Most strikingly, several PNSB resolutely restrict ICMs to regions near the cell poles, leaving much of the cell devoid of light-harvesting machinery. Our results demonstrate that bacteria of a common lifestyle utilize unequal portions of their intracellular space to harvest light, despite light harvesting being a process that is intuitively influenced by surface area. Our findings therefore raise fundamental questions about ICM biology and evolution.
The Actinomyosin Motor Drives Malaria Parasite Red Blood Cell Invasion but Not Egress
Authors: Perrin Abigail J. , Collins Christine R. , Russell Matthew R. G. , Collinson Lucy M. , Baker David A. , Blackman Michael J. 
Published: July 2018

ABSTRACT

Apicomplexa are obligate intracellular parasites that actively invade, replicate within, and egress from host cells. The parasite actinomyosin-based molecular motor complex (often referred to as the glideosome) is considered an important mediator of parasite motility and virulence. Mature intracellular parasites often become motile just prior to egress from their host cells, and in some genera, this motility is important for successful egress as well as for subsequent invasion of new host cells. To determine whether actinomyosin-based motility is important in the red blood cell egress and invasion activities of the malaria parasite, we have used a conditional genetic approach to delete
GAP45
, a primary component of the glideosome, in asexual blood stages of
Plasmodium falciparum
. Our results confirm the essential nature of GAP45 for invasion but show that
P. falciparum
does not require a functional motor complex to undergo egress from the red blood cell. Malarial egress therefore differs fundamentally from induced egress in the related apicomplexan
Toxoplasma gondii
.

IMPORTANCE
Clinical malaria results from cycles of replication of single-celled parasites of the genus
Plasmodium
in red blood cells. Intracellular parasite replication is followed by a highly regulated, protease-dependent process called egress, in which rupture of the bounding membranes allows explosive release of daughter merozoites which rapidly invade fresh red cells. A parasite actinomyosin-based molecular motor (the glideosome) has been proposed to provide the mechanical force to drive invasion. Studies of the related parasite
Toxoplasma gondii
have shown that induced egress requires parasite motility, mediated by a functional glideosome. However, whether the glideosome has a similar essential role in egress of malaria merozoites from red blood cells is unknown. Here, we show that although a functional glideosome is required for red blood cell invasion by
Plasmodium falciparum
merozoites, it is not required for egress. These findings place further emphasis on the key role of the protease cascade in malarial egress.
cAMP Receptor Protein Controls Vibrio cholerae Gene Expression in Response to Host Colonization
Authors: Manneh-Roussel Jainaba , Haycocks James R. J. , Magán Andrés , Perez-Soto Nicolas , Voelz Kerstin , Camilli Andrew , Krachler Anne-Marie , Grainger David C. 
Published: July 2018

ABSTRACT

The bacterium
Vibrio cholerae
is native to aquatic environments and can switch lifestyles to cause disease in humans. Lifestyle switching requires modulation of genetic systems for quorum sensing, intestinal colonization, and toxin production. Much of this regulation occurs at the level of gene expression and is controlled by transcription factors. In this work, we have mapped the binding of cAMP receptor protein (CRP) and RNA polymerase across the
V. cholerae
genome. We show that CRP is an integral component of the regulatory network that controls lifestyle switching. Focusing on a locus necessary for toxin transport, we demonstrate CRP-dependent regulation of gene expression in response to host colonization. Examination of further CRP-targeted genes reveals that this behavior is commonplace. Hence, CRP is a key regulator of many
V. cholerae
genes in response to lifestyle changes.

IMPORTANCE
Cholera is an infectious disease that is caused by the bacterium
Vibrio cholerae
. Best known for causing disease in humans, the bacterium is most commonly found in aquatic ecosystems. Hence, humans acquire cholera following ingestion of food or water contaminated with
V. cholerae
. Transition between an aquatic environment and a human host triggers a lifestyle switch that involves reprogramming of
V. cholerae
gene expression patterns. This process is controlled by a network of transcription factors. In this paper, we show that the cAMP receptor protein (CRP) is a key regulator of
V. cholerae
gene expression in response to lifestyle changes.
Acinetobacter baumannii Gastrointestinal Colonization Is Facilitated by Secretory IgA Which Is Reductively Dissociated by Bacterial Thioredoxin A
Authors: Ketter Patrick M. , Yu Jieh-Juen , Guentzel M. Neal , May Holly C. , Gupta Rishein , Eppinger Mark , Klose Karl E. , Seshu J. , Chambers James P. , Cap Andrew P. , Arulanandam Bernard P. 
Published: July 2018

ABSTRACTMultidrug-resistantAcinetobacter baumanniiis among the most common causes of infectious complications associated with combat-related trauma in military personnel serving overseas. However, little is currently known about its pathogenesis. While the gastrointestinal (GI) tract has been found to be a major reservoir forA. baumannii, as well as to potentially contribute to development of multidrug resistance, no studies have addressed the mechanisms involved in gut colonization. In this study, we address this critical gap in knowledge by first assessing the interaction between secretory IgA (SIgA), the principal humoral immune defense on mucosal surfaces, and theA. baumanniiclinical isolate Ci79. Surprisingly, SIgA appeared to enhanceA. baumanniiGI tract colonization, in a process mediated by bacterial thioredoxin A (TrxA), as evidenced by reduction of bacterial attachment in the presence of TrxA inhibitors. Additionally, atrxAtargeted deletion mutant (ΔtrxA) showed reduced bacterial burdens within the GI tract 24 h after oral challenge byin vivolive imaging, along with loss of thiol-reductase activity. Surprisingly, not only was GI tract colonization greatly reduced but the associated 50% lethal dose (LD50) of theΔtrxAmutant was increased nearly 100-fold in an intraperitoneal sepsis model. These data suggest that TrxA not only mediatesA. baumanniiGI tract colonization but also may contribute to pathogenesis inA. baumanniisepsis following escape from the GI tract under conditions when the intestinal barrier is compromised, as occurs with cases of severe shock and trauma.IMPORTANCEAcinetobacter baumanniiis an emerging bacterial pathogen recently classified as a serious threat to U.S. and global health by both the Centers for Disease Control and Prevention and the World Health Organization. It also is one of the leading causes of combat-related infections associated with injured military personnel serving overseas. Little is known regarding mechanisms of gastrointestinal tract colonization despite this site being shown to serve as a reservoir for multidrug-resistant (MDR)A. baumanniiisolates. Here, we establish that secretory IgA, the major immunoglobulin of mucosal surfaces, promotesA. baumanniiGI tract colonization via bacterial thioredoxin A as evidenced through significant reduction in colonization in IgA-deficient animals. Additionally, bacterial colonization and mortality were significantly reduced in animals challenged with a thioredoxin A-deficientA. baumanniimutant. Combined, these data suggest that thioredoxin A is a novel virulence factor, for which antithioredoxin therapies could be developed, for this important multidrug-resistant pathogen.
Fine mapping MHC associations in Graves’ disease and its clinical subtypes in Han Chinese
Authors: Chu Xun , Yang Minjun , Song Zhen-Ju , Dong Yan , Li Chong , Shen Min , Zhu Yong-Qiang , Song Huai-Dong , Chen Sai-Juan , Chen Zhu , Huang Wei 
Published: July 2018

BackgroundThe classical human leucocyte antigen (HLA) genes were the most important genetic determinant for Graves’ disease (GD). The aim of the study was to fine map causal variants of the HLA genes.MethodsWe applied imputation with a Pan-Asian HLA reference panel to thoroughly investigate themajor histocompatibility complex (MHC) associations with GD down to the amino acid level of classical HLA genes in 1468 patients with GD and 1490 controls of Han Chinese.ResultsThe strongest finding across the HLA genes was the association with HLA-DPβ1 position 205 (Pomnibus=2.48×10−33). HLA-DPA1*02:02 was the strongest association among the classical HLA alleles, which was in perfect linkage disequilibrium with HLA-DPα1 residue Met11 (OR=1.90, Pbinary=1.76×10−31). Applying stepwise conditional analysis, we identified amino acid position 205 in HLA-DPβ1, position 66 and 99 in HLA-B and position 28 in HLA-DRβ1 explain majority of the MHC association to GD risk. We further evaluated risk of two clinical subtypes of GD, namely persistent thyroid stimulating hormone receptor antibody -positive (pTRAb+) group and ‘non-persistent TRAb positive’ (pTRAb−) group after antithyroid drug therapy. We found that HLA-B residues Lys66-Arg69-Val76 could drive pTRAb− GD risk alone, while HLA-DPβ1 position 205, HLA-B position 69 and 199 and HLA-DRβ1 position 28 drive pTRAb+ GD risk. The risk heterogeneity between pTRAb+ and pTRAb− GD might be driven by HLA-DPα1 Met11.ConclusionsFour amino acid positions could account for the associations of MHC with GD in Han Chinese. These distinct HLA association patterns indicated the two subtypes have distinct molecular mechanisms of pathogenesis.
Unilateral pallidal stimulation for disabling dystonia due to Rasmussen’s disease
Authors: Carreño Mar , Martí Maria José , Aldecoa Ibán , Painous Celia , Conde Estefanía , Valldeoriola Francesc , Valls-Solé Josep , Bargalló Núria , Gil Francisco , Manzanares Isabel , Setoain Xavier , Donaire Antonio , Muñoz Esteban , Roldán Pedro , Boget Teresa , Pintor Luis , Bailles Eva , Rumià Jordi 
Published: July 2018

ObjectiveTo describe an adult patient with Rasmussen’s disease with focal dystonia as the most disabling symptom and the good response to unilateral globus pallidus internus (GPi) deep brain stimulation (DBS).MethodsRetrospective review of clinical records and diagnostic tests.ResultsThe patient had displayedmild focal seizures with sensory and motor symptoms on the left arm and hemiface since the age of 22. Ten years later she experienced abrupt onset of focal left dystonia involving mainly the leg. Brain MRI showed progressive right hemisphere atrophy, and 18fluorodeoxyglucose-positron emission tomography (18FDG-PET) showed right hypometabolism mainly over the frontal and insular regions. Brain biopsy confirmed chronic encephalitis. The dystonia became very severe and made walking extremely difficult. Different treatments including dopaminergic, anticholinergic, immunomodulatory drugs and botulinum toxin were ineffective. Finally the patient was treated with unilateral GPi DBS. Shortly after the onset of the stimulation, the dystonia started to improve. Parameters have been adjusted, and 18 months after surgery the patient is able to walk and run unaided, although a mild left leg dystonia persists.ConclusionRasmussen’s disease may be difficult to diagnose in adult patients. Associated movement disorders may be more disabling than seizures. Focal dystonia may be treated successfully with DBS.
Salivary cotinine concentration and carbon monoxide levels in young adults smoking midwakh in comparison with cigarette smokers
Authors: Shaikh Rizwana Burhanuddin , Sreedharan Jayadevan , Al Sharbatti Shatha , Muttappallymyalil Jayakumary , Lee Lily , Weitzman Michael 
Published: July 2018

Objectives
To estimate and compare the salivary cotinine levels using a semiquantitative method, called NicAlert, between three groups: non-smokers, daily smokers of cigarettes and daily smokers of midwakh, and to compare the carbon monoxide (CO) levels among these groups.

Materials and methods
A total of 159 adult male volunteers aged 20 and above were included, with 54 current cigarette smokers, 52 current midwakh smokers and 53 non-smokers. Estimate of breath carbon monoxide and salivary cotinine were collected, as well as sociodemographic characteristics and details of smoking habits and second-hand smoke exposure among participants. Institutional review board approval was obtained and data were analysed using SPSS V.21 with the Kruskal-Wallis test used to obtain differences in the distribution.

Results
There was no significant difference in the median breath CO and salivary cotinine levels between cigarette and midwakh smokers. Levels of breath CO were significantly higher in cigarette and midwakh smokers as compared with non-smokers (19.5, 17.5 and 6.0, respectively, p<0.05); the same relationship was observed for cotinine levels among cigarette and midwakh smokers as compared with non-smokers (4.0, 3.0 and 0.0, respectively, p≤0.05). Additionally, the values of both salivary cotinine and breath CO increased with the frequency of tobacco use.

Conclusion
These are the first data that we are aware of that demonstrate that in terms of at least two key biomarkers of tobacco use, there are comparable levels of exposure between cigarettes and midwakh users, demonstrating a need for intensified attention to the use of midwakh.
The large-Nc limit of borelized spectral sum rules and the slope of radial Regge trajectories
Authors: Afonin S. S. , Solomko T. D. 
Published: July 2018

We put forward a new phenomenological method for calculating the slope of radial trajectories from values of ground states and vacuum condensates. The method is based on a large-[Formula: see text] extension of borelized spectral sum rules. The approach is applied to the light nonstrange vector, axial and scalar mesons. The extracted values of slopes proved to be approximately universal and are in the interval [Formula: see text] GeV2. As a by-product, the given method leads to prediction of the second radial trajectory with ground state mass lying near 0.6 GeV.
How Do Resuscitation Teams at Top-Performing Hospitals for In-Hospital Cardiac Arrest Succeed?
Authors: Nallamothu Brahmajee K. , Guetterman Timothy C. , Harrod Molly , Kellenberg Joan E. , Lehrich Jessica L. , Kronick Steven L. , Krein Sarah L. , Iwashyna Theodore J. , Saint Sanjay , Chan Paul S. 
Published: July 2018

Background:
In-hospital cardiac arrest (IHCA) is common, and outcomes vary substantially across US hospitals, but reasons for these differences are largely unknown. We set out to better understand how top-performing hospitals organize their resuscitation teams to achieve high survival rates for IHCA.

Methods:
We calculated risk-standardized IHCA survival to discharge rates across American Heart Association Get With The Guidelines–Resuscitation registry hospitals between 2012 and 2014. We identified geographically and academically diverse hospitals in the top, middle, and bottom quartiles of survival for IHCA and performed a qualitative study that included site visits with in-depth interviews of clinical and administrative staff at 9 hospitals. With the use of thematic analysis, data were analyzed to identify salient themes of perceived performance by informants.

Results:
Across 9 hospitals, we interviewed 158 individuals from multiple disciplines including physicians (17.1%), nurses (45.6%), other clinical staff (17.1%), and administration (20.3%). We identified 4 broad themes related to resuscitation teams: (1) team design, (2) team composition and roles, (3) communication and leadership during IHCA, and (4) training and education. Resuscitation teams at top-performing hospitals demonstrated the following features: dedicated or designated resuscitation teams; participation of diverse disciplines as team members during IHCA; clear roles and responsibilities of team members; better communication and leadership during IHCA; and in-depth mock codes.

Conclusions:
Resuscitation teams at hospitals with high IHCA survival differ from non–top-performing hospitals. Our findings suggest core elements of successful resuscitation teams that are associated with better outcomes and form the basis for future work to improve IHCA.
Intrapulmonary Vein Ablation Without Stenosis: A Novel Balloon‐Based Direct Current Electroporation Approach
Authors: Witt Chance M. , Sugrue Alan , Padmanabhan Deepak , Vaidya Vaibhav , Gruba Sarah , Rohl James , DeSimone Christopher V. , Killu Ammar M. , Naksuk Niyada , Pederson Joanne , Suddendorf Scott , Ladewig Dorothy J. , Maor Elad , Holmes David R. , Kapa Suraj , Asirvatham Samuel J. 
Published: July 2018

Background

Current thermal ablation methods for atrial fibrillation, including radiofrequency and cryoablation, have a suboptimal success rate. To avoid pulmonary vein (PV) stenosis, ablation is performed outside of the PV, despite the importance of triggers inside the vein. We previously reported on the acute effects of a novel direct current electroporation approach with a balloon catheter to create lesions
inside
the PVs in addition to the antrum. In this study, we aimed to determine whether the effects created by this nonthermal ablation method were associated with irreversible lesions and whether PV stenosis or other adverse effects occurred after a survival period.

Methods and Results
Initial and survival studies were performed in 5 canines. At the initial study, the balloon catheter was inflated to contact the antrum and interior of the PV. Direct current energy was delivered between 2 electrodes on the catheter in ECG‐gated 100 μs pulses. A total of 10 PVs were treated demonstrating significant acute local electrogram diminution (mean amplitude decrease of 61.2±19.8%). After the survival period (mean 27 days), computed tomography imaging showed no PV stenosis. On histologic evaluation, transmural, although not circumferential, lesions were seen in each treated vein. No PV stenosis or esophageal injury was present.

Conclusions
Irreversible, transmural lesions can be created inside the PV without evidence of stenosis after a 27‐day survival period using this balloon‐based direct current ablation approach. These early data show promise for an ablation approach that could directly treat PV triggers in addition to traditional PV antrum ablation.