bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Adaptations of Intracellullar Bacterial Pathogens and their Mammalian Host Cells during Infection (“Pathometabolism”)
Authors: Eisenreich Wolfgang , Heesemann Jürgen , Rudel Thomas , Goebel Werner 
Published: June 2015

ABSTRACTSeveral bacterial pathogens that cause severe infections in warm-blooded animals, including humans, have the potential to actively invade host cells and to efficiently replicate either in the cytosol or in specialized vacuoles of the mammalian cells. The interaction between these intracellular bacterial pathogens and the host cells always leads to multiple physiological changes in both interacting partners, including complex metabolic adaptation reactions aimed to promote proliferation of the pathogen within different compartments of the host cells. In this chapter, we discuss the necessary nutrients and metabolic pathways used by some selected cytosolic and vacuolar intracellular pathogens and - when available - the links between the intracellular bacterial metabolism and the expression of the virulence genes required for the intracellular bacterial replication cycle. Furthermore, we address the growing evidence that pathogen-specific factors may also trigger metabolic responses of the infected mammalian cells affecting the carbon and nitrogen metabolism as well as defense reactions. We also point out that many studies on the metabolic host cell responses induced by the pathogens have to be scrutinized due to the use of established cell lines as model host cells, as these cells are (in the majority) cancer cells that exhibit a dysregulated primary carbon metabolism. As the exact knowledge of the metabolic host cell responses may also provide new concepts for antibacterial therapies, there is undoubtedly an urgent need for host cell models that more closely reflect thein vivoinfection conditions.
Bacterial Metabolism in the Host Environment: Pathogen Growth and Nutrient Assimilation in the Mammalian Upper Respiratory Tract
Authors: Armstrong Sandra K. 
Published: June 2015

ABSTRACT

Pathogens evolve in specific host niches and microenvironments that provide the physical and nutritional requirements conducive to their growth. In addition to using the host as a source of food, bacterial pathogens must avoid the immune response to their presence. The mammalian upper respiratory tract is a site that is exposed to the external environment, and is readily colonized by bacteria that live as resident flora or as pathogens. These bacteria can remain localized, descend to the lower respiratory tract, or traverse the epithelium to disseminate throughout the body. By virtue of their successful colonization of the respiratory epithelium, these bacteria obtain the nutrients needed for growth, either directly from host resources or from other microbes. This chapter describes the upper respiratory tract environment, including its tissue and mucosal structure, prokaryotic biota, and biochemical composition that would support microbial life.
Neisseria meningitidis
and the
Bordetella
species are discussed as examples of bacteria that have no known external reservoirs but have evolved to obligately colonize the mammalian upper respiratory tract.
Pathogenesis — Thoughts from the Front Line
Authors: Nataro James P. 
Published: June 2015

ABSTRACT
The field of bacterial pathogenesis has advanced dramatically in the last decade. High throughput molecular technologies have empowered scientists as never before. However, there remain some limitations, misconceptions and ambiguities in the field that may bedevil even the experienced investigator. Here, I consider some of the unanswered questions that are not readily tractable to even the most powerful technology.
Sialic acid and N-acetylglucosamine Regulate type 1 Fimbriae Synthesis
Authors: Blomfield Ian C. 
Published: June 2015

ABSTRACT

Type 1 fimbriae of
E. coli
, a chaperon-usher bacterial adhesin, are synthesized by the majority of strains of the bacterium. Although frequently produced by commensal strains, the adhesin is nevertheless a virulence factor in Extraintestinal Pathogenic
E. coli
(ExPEC). The role of the adhesin in pathogenesis is best understood in Uropathogenic
E. coli
(UPEC). Host attachment and invasion by type 1 fimbriate bacteria activates inflammatory pathways, with TLR4 signaling playing a predominant role. In a mouse model of cystitis, type 1 fimbriation not only enhances UPEC adherence to the surface of superficial umbrella cells of the bladder urothelium, but is both necessary and sufficient for their invasion. Moreover the adhesin plays a role in the formation of transient intracellular bacterial communities (IBCs) within the cytoplasm of urothelial cells as part of UPEC cycles of invasion. The expression of type 1 fimbriation is controlled by phase variation at the transcriptional level, a mode of gene regulation in which bacteria switch reversibly between fimbriate and afimbriate phases. Phase variation has been widely considered to be a mechanism enabling immune evasion. Notwithstanding the apparently random nature of phase variation, switching of type 1 fimbrial expression is nevertheless controlled by a range of environmental signals that include the amino sugars sialic acid and N-acetylglucosamine (GlcNAc). Sialic acid plays a pivotal role in innate immunity, including signaling by the toll-like receptors. Here how sialic acid and GlcNAc control type 1 fimbriation is described and the potential significance of this regulatory response is discussed.
Multifunctional-autoprocessing repeats-in-toxin (MARTX) Toxins of
Vibrios
Authors: Satchell Karla J. F. 
Published: June 2015

ABSTRACT

Multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins are a heterogeneous group of toxins found in a number of
Vibrio
species and other Gram-negative bacteria. The toxins are composed of conserved repeat regions and an autoprocessing protease domain that together function as a delivery platform for transfer of cytotoxic and cytopathic domains into target eukaryotic cell cytosol. Within the cells, the effectors can alter biological processes such as signaling or cytoskeletal structure, presumably to the benefit of the bacterium. Ten effector domains are found in the various
Vibrio
MARTX toxins, although any one toxin carries only two to five effector domains. The specific toxin variant expressed by a species can be modified by homologous recombination to acquire or lose effector domains, such that different strains within the same species can express distinct variants of the toxins. This review examines the conserved structural elements of the MARTX toxins and details the different toxin arrangements carried by
Vibrio
species and strains. The catalytic function of domains and how the toxins are linked to pathogenesis of human and animals is described.
Optimising the Pre-Operative Investigative Work Up for Elective Surgical Patients
Authors: Hack-Adams Nadine , king natalie , Ahuja Manisha , M Higgs Simon 
Published: June 2015

AbstractEffective pre-operative assessment of patients awaiting elective surgery should entail appropriate use of scarce NHS resources, as well as underpin patient safety. The pre-operative admissions service in district general hospitals is often junior doctor led, with a new cohort of clinicians taking over its running every four months. Lack of familiarity on the part of these clinicians with the investigative work up required for certain surgical procedures often results in over investigation of patients in the pre-admission setting, wasting time and NHS resources. A retrospective audit of 53 patients who underwent laparoscopic cholecystectomy over a representative two month period demonstrated that 33% of patients received unnecessary pre-admission blood tests, including clotting screen and 'group and save'. Design and implementation of a “Pre-Admission Handbook”, for use by junior doctors and nurse practitioners in the pre-operative setting, reduced the rate of over investigation to 12% in a subsequent, prospective audit cycle of 50 patients, and has improved patient care by standardising the pre-admissions process for elective surgery at Gloucester Royal Hospital.
Does the level of socioeconomic deprivation at the location of cardiac arrest in an English region influence the likelihood of receiving bystander-initiated cardiopulmonary resuscitation?
Authors: Moncur Lyle , Ainsborough Neil , Ghose Rajiv , Kendal Simon Peter , Salvatori Marcus , Wright John 
Published: June 2015

BackgroundOut-of-hospital cardiac arrest (OHCA) is a leading cause of mortality. Administration of cardiopulmonary resuscitation (CPR) by a bystander witnessing a cardiac arrest has been shown to increase the likelihood of return of spontaneous circulation and survival. This study analyses the association between the socioeconomic status of the location where a person suffers a cardiac arrest and the proportion of victims with OHCA receiving bystander CPR.MethodsRetrospective analysis of all OHCAs occurring in North East England from 1 January 2011 to 31 December 2011: data obtained from the North East Cardiac Arrest Network Registry.ResultsOf 3179 OHCAs with an attempt at resuscitation, 623 patients received bystander-initiated CPR (19.6%). From quintile (Q) 1 to Q5 (most deprived to least deprived), bystander-initiated CPR rates increased from 14.5% to 23.3% (p for trend <0.001). Patients in the least deprived quintile were significantly more likely to receive bystander-initiated CPR when compared with those in the most deprived quintile (OR=1.78, 95% CI 1.32 to 2.39, p≤0.001).ConclusionsIncreasing socioeconomic status at the location of cardiac arrest is positively associated with the likelihood of bystander CPR for OHCA in this region of England.
Oncogenic G Protein GNAQ Induces Uveal Melanoma and Intravasation in Mice
Authors: Huang Jenny Li-Ying , Urtatiz Oscar , Van Raamsdonk Catherine D. 
Published: June 2015

Abstract
GNAQ and GNA11 are heterotrimeric G protein alpha subunits, which are mutated in a mutually exclusive pattern in most cases of uveal melanoma, one of the most aggressive cancers. Here we introduce the first transgenic mouse model of uveal melanoma, which develops cancers induced by expression of oncogenic GNAQQ209L under control of the Rosa26 promoter. Disease penetrance is 100% by 3 months of age, with 94% of mice also developing lung tumors. In this model, the Yap protein of the Hippo pathway is activated in the eyes, and blood vessels near the lesions in the head and lungs exhibit melanocytic invasion. While full transcription levels are not necessary for GNAQQ209L to transform mouse melanocytes, we obtained suggestive evidence of a selective advantage for increased GNAQQ209L expression in human tumors. Intriguingly, enforced expression of GNAQQ209L progressively eliminated melanocytes from the interfollicular epidermis in adults, possibly explaining the near absence of GNAQQ209 mutations in human epithelial melanomas. The mouse model also exhibited dermal nevi and melanocytic neoplasms of the central nervous system, accompanied by impaired hearing and balance, identifying a novel role for GNAQ in melanocyte-like cells of the inner ear. Overall, this model offers a new tool to dissect signaling by oncogenic GNAQ and to test potential therapeutics in an in vivo setting where GNAQQ209L mutations contribute to both the initiation and metastatic progression of uveal melanoma. Cancer Res; 75(16); 3384–97. ©2015 AACR.
Carotid Arterial Stiffness and Risk of Incident Cerebral Microbleeds in Older People
Authors: Ding Jie , Mitchell Gary F. , Bots Michiel L. , Sigurdsson Sigurdur , Harris Tamara B. , Garcia Melissa , Eiriksdottir Gudny , van Buchem Mark A. , Gudnason Vilmundur , Launer Lenore J. 
Published: June 2015

Objective—
Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs.

Approach and Results—
In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01–1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05–1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04–1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02–1.37]; 1.24 [1.08–1.42]; and 1.23 [1.07–1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted.

Conclusions—
Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension.
Segmental Aortic Stiffness in Children and Young Adults With Connective Tissue Disorders
Authors: Prakash Ashwin , Adlakha Himanshu , Rabideau Nicole , Hass Cara J. , Morris Shaine A. , Geva Tal , Gauvreau Kimberlee , Singh Michael N. , Lacro Ronald V. 
Published: June 2015

Background—
Aortic diameter is an imperfect predictor of aortic complications in connective tissue disorders (CTDs). Novel indicators of vascular phenotype severity such as aortic stiffness and vertebral tortuosity index have been proposed. We assessed the relation between aortic stiffness by cardiac MRI, surgical root replacement, and rates of aortic root dilation in children and young adults with CTDs.

Methods and Results—

Retrospective analysis of cardiac MRI data on children and young adults with a CTD was performed to derive aortic stiffness measures (strain, distensibility, and β-stiffness index) at the aortic root, ascending aorta, and descending aorta. Vertebral tortuosity index was calculated as previously described. Rate of aortic root dilation before cardiac MRI was calculated as change in echocardiographic aortic root diameter
z
score per year. In 83 CTD patients (median age, 24 years; range, 1–55; 17% <18 years of age; 60% male), ascending aorta distensibility was reduced in comparison with published normative values: median
z
score, –1.93 (range, –8.7 to 1.3;
P
<0.0001 versus normals). Over a median follow-up period of 2.7 years, there were no aortic dissections or deaths, but 16 of 83 (19%) patients underwent surgical aortic root replacement. In multivariable analysis, lower aortic root strain (
P
=0.05) and higher vertebral tortuosity index (
P
=0.01) were independently associated with aortic root replacement. Lower ascending aorta strain (
P
=0.02) was associated with a higher rate of aortic root dilation.

Conclusions—
Higher aortic stiffness is associated with higher rates of surgical aortic replacement and aortic root dilation in children and young adults with CTDs.
Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism
Authors: Shibata Tatsuhiro , Kawakami Shoji , Noguchi Teruo , Tanaka Tomotaka , Asaumi Yasuhide , Kanaya Tomoaki , Nagai Toshiyuki , Nakao Kazuhiro , Fujino Masashi , Nagatsuka Kazuyuki , Ishibashi-Ueda Hatsue , Nishimura Kunihiro , Miyamoto Yoshihiro , Kusano Kengo , Anzai Toshihisa , Goto Yoichi , Ogawa Hisao , Yasuda Satoshi 
Published: June 2015

Background—
Coronary artery embolism (CE) is recognized as an important nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical features, and prognosis remain insufficiently characterized.

Methods and Results—

We screened 1776 consecutive patients who presented with de novo acute myocardial infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing histological, angiographic, and other diagnostic imaging findings. The prevalence, clinical characteristics, treatment strategies, in-hospital outcomes, and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and the median international normalized ratio was 1.42 (range, 0.95–1.80). Eighteen of the 30 CE patients with nonvalvular atrial fibrillation had a CHADS
2
score of 0 or 1. When those patients were reevaluated using CHA
2
DS
2
-VASc, 61% were reassigned to a higher risk category. During a median follow-up of 49 months, CE and thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of major adverse cardiac and cerebrovascular events was 27.1%. In the propensity score–matched cohorts (n=45 each), Kaplan–Meier analysis showed a significantly higher incidence of cardiac death in the CE group than in the non-CE group (hazard ratio, 9.29; 95% confidence interval, 1.13–76.5;
P
<0.001).

Conclusions—
Atrial fibrillation is the most frequent cause of CE. Patients with CE represent a high-risk subgroup of patients with acute myocardial infarction and require close follow-up.
White Matter Lesions Double the Risk of Post-Thrombolytic Intracerebral Hemorrhage
Authors: Curtze Sami , Haapaniemi Elena , Melkas Susanna , Mustanoja Satu , Putaala Jukka , Sairanen Tiina , Sibolt Gerli , Tiainen Marjaana , Tatlisumak Turgut , Strbian Daniel 
Published: June 2015

Background and Purpose—
Cerebral white matter lesions (WMLs), a surrogate for small-vessel disease, are common in patients with stroke and may be related to an increased intracranial bleeding risk after intravenous thrombolysis in acute ischemic stroke. We aimed to investigate the risk of symptomatic intracerebral hemorrhage (sICH) in the presence of WMLs in a large cohort of ischemic stroke patients treated with intravenous thrombolysis.

Methods—
We included 2485 consecutive patients treated with intravenous thrombolysis at the Helsinki University Central Hospital. WMLs were scored according to 4 previously published computed tomography visual rating scales from all baseline head scans. A sICH was classified according to the European Cooperative Acute Stroke Study II criteria. The associations of sICH with nominal, ordinal, and continuous variables were analyzed in a univariate binary regression model and adjusted in multivariate binary regression models.

Results—
In univariate and multivariate regression analyses, all 4 tested visual WML rating scales (as continuous variables or dichotomized at different cutoff points) were associated with increased risk of sICH. In binary analyses, WML doubled the bleeding risk: the odds ratios of all 4 visual rating scales ranged from 2.22 (95% confidence interval, 1.49–3.30) to 2.70 (1.87–3.90) in univariable and from 2.00 (1.26–3.16) to 2.62 (1.71–4.02) in multivariable analyses. The multivariable-adjusted odds ratio for the association of high load of WMLs with remote parenchymal hemorrhage was 4.11 (2.38–7.10).

Conclusions—
WMLs visible on computed tomography are associated with a more than doubled risk of sICH in patients treated with intravenous thrombolysis for acute ischemic stroke.
Rare Coding Variation and Risk of Intracerebral Hemorrhage
Authors: Radmanesh Farid , Falcone Guido J. , Anderson Christopher D. , McWilliams David , Devan William J. , Brown W. Mark , Battey Thomas W.K. , Ayres Alison M. , Raffeld Miriam R. , Schwab Kristin , Sun Guangyun , Deka Ranjan , Viswanathan Anand , Goldstein Joshua N. , Greenberg Steven M. , Tirschwell David L. , Silliman Scott L. , Selim Magdy , Meschia James F. , Brown Devin L. , Worrall Bradford B. , Langefeld Carl D. , Woo Daniel , Rosand Jonathan 
Published: June 2015

Background and Purpose—
Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage.

Methods—
A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed.

Results—

No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing
TOMM40, APOE
, and
APOC1
, met genome-wide significance (
P
<5e−08). After adjusting for the
APOE
epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing.

Conclusions—
Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects.
The genus Diploneis Ehrenberg ex Cleve (Bacillariophyta) from Lake Hövsgöl, Mongolia
Authors: JOVANOVSKA ELENA , LEVKOV ZLATKO , EDLUND MARK B. 
Published: June 2015

Lake Hövsgöl is an ancient lake situated in north-central Mongolia at the southern end of the Baikal Rift Zone. Throughout its limnological history, Lake Hövsgöl has developed an extraordinary diversity in different groups of organisms, such as fish and invertebrates. However, the one group that presumably holds the largest taxonomic diversity in the lake—the diatoms—has been largely overlooked. This study presents a detailed taxonomic overview of the genus Diploneis from Lake Hövsgöl as well as a few localities from the neighboring Arkhangai province. A total of 25 taxa were identified, five of which are new and potentially endemic. Alongside the endemic species, this study confirms the presence of several taxa recently described from other Mongolian lakes (e.g., Diploneis linearielliptica, Diploneis aff. heteromorphiforma and Diploneis cf. eximia), presumably peculiar for this mid-Asian region. A relatively high number of widespread species were identified in Lake Hövsgöl, commonly reported from Europe and elsewhere. Interestingly, a population of Diploneis praeclara that is morphologically closely related to populations from Neogene fossil deposits in Romania was also observed in Lake Hövsgöl. Detailed LM and SEM observations are provided, together with species descriptions and comparisons to morphologically related species. Greater knowledge of the genus Diploneis opens and guides the way towards better and more comprehensive approaches of uncovering biological diversity and biogeographical patterns on the Eurasian continent and among the ancient lakes.