bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Noncanonical Autophagy Pathway Restricts Toxoplasma gondii Growth in a Strain-Specific Manner in IFN-γ-Activated Human Cells
Authors: Selleck Elizabeth M. , Orchard Robert C. , Lassen Kara G. , Beatty Wandy L. , Xavier Ramnik J. , Levine Beth , Virgin Herbert W. , Sibley L. David 
Published: September 2015

ABSTRACT

A core set of autophagy proteins is required for gamma interferon (IFN-γ)-mediated clearance of
Toxoplasma gondii
in the mouse because of their control of several downstream effectors, including immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs). However, these effectors are absent (i.e., IRGs) from or nonessential (i.e., GBPs) in IFN-γ-activated human cells, raising the question of how these cells control parasite replication. Here, we define a novel role for ubiquitination and recruitment of autophagy adaptors in the strain-specific control of
T. gondii
replication in IFN-γ-activated human cells. Vacuoles containing susceptible strains of
T. gondii
became ubiquitinated, recruited the adaptors p62 and NDP52, and were decorated with LC3. Parasites within LC3-positive vacuoles became enclosed in multiple layers of host membranes, resulting in stunting of parasite replication. However, LC3-positive
T. gondii
-containing vacuoles did not fuse with endosomes and lysosomes, indicating that this process is fundamentally different from xenophagy, a form of autophagy involved in the control of intracellular bacterial pathogens. Genetic knockout of ATG16L or ATG7 reverted the membrane encapsulation and restored parasite replication, indicating that core autophagy proteins involved in LC3 conjugation are important in the control of parasite growth. Despite a role for the core autophagy machinery in this process, upstream activation through Beclin 1 was not sufficient to enhance the ubiquitination of
T. gondii
-containing vacuoles, suggesting a lack of reliance on canonical autophagy. These findings demonstrate a new mechanism for IFN-γ-dependent control of
T. gondii
in human cells that depends on ubiquitination and core autophagy proteins that mediate membrane engulfment and restricted growth.

IMPORTANCE
Autophagy is a process of cellular remodeling that allows the cell to recycle senescent organelles and recapture nutrients. During innate immune responses in the mouse, autophagy is recruited to help target intracellular pathogens and thus eliminate them. However, the antimicrobial mediators that depend on autophagy in the mouse are not conserved in humans, raising the issue of how human cells control intracellular pathogens. Our study defines a new pathway for the control of the ubiquitous intracellular parasite
T. gondii
in human cells activated by IFN-γ. Recruitment of autophagy adaptors resulted in engulfment of the parasite in multiple membranes and growth impairment. Although susceptible type 2 and 3 stains of
T. gondii
were captured by this autophagy-dependent pathway, type 1 strains were able to avoid entrapment.
The Complete Genome Sequence of Clostridium aceticum: a Missing Link between Rnf- and Cytochrome-Containing Autotrophic Acetogens
Authors: Poehlein Anja , Cebulla Martin , Ilg Marcus M. , Bengelsdorf Frank R. , Schiel-Bengelsdorf Bettina , Whited Gregg , Andreesen Jan R. , Gottschalk Gerhard , Daniel Rolf , Dürre Peter 
Published: September 2015

ABSTRACT

Clostridium aceticum
was the first isolated autotrophic acetogen, converting CO
2
plus H
2
or syngas to acetate. Its genome has now been completely sequenced and consists of a 4.2-Mbp chromosome and a small circular plasmid of 5.7 kbp. Sequence analysis revealed major differences from other autotrophic acetogens.
C. aceticum
contains an Rnf complex for energy conservation (via pumping protons or sodium ions). Such systems have also been found in
C. ljungdahlii
and
Acetobacterium woodii
. However,
C. aceticum
also contains a cytochrome, as does
Moorella thermoacetica
, which has been proposed to be involved in the generation of a proton gradient. Thus,
C. aceticum
seems to represent a link between Rnf- and cytochrome-containing autotrophic acetogens. In
C. aceticum
, however, the cytochrome is probably not involved in an electron transport chain that leads to proton translocation, as no genes for quinone biosynthesis are present in the genome.

IMPORTANCE
Autotrophic acetogenic bacteria are receiving more and more industrial focus, as CO
2
plus H
2
as well as syngas are interesting new substrates for biotechnological processes. They are both cheap and abundant, and their use, if it results in sustainable products, also leads to reduction of greenhouse gases.
Clostridium aceticum
can use both gas mixtures, is phylogenetically not closely related to the commonly used species, and may thus become an even more attractive workhorse. In addition, its energy metabolism, which is characterized here, and the ability to synthesize cytochromes might offer new targets for improving the ATP yield by metabolic engineering and thus allow use of
C. aceticum
for production of compounds by pathways that currently present challenges for energy-limited acetogens.
Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis
Authors: Wang Yanqun , Liu Di , Shi Weifeng , Lu Roujian , Wang Wenling , Zhao Yanjie , Deng Yao , Zhou Weimin , Ren Hongguang , Wu Jun , Wang Yu , Wu Guizhen , Gao George F. , Tan Wenjie 
Published: September 2015

ABSTRACT
The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus.

IMPORTANCE
The recent outbreak of MERS-CoV in South Korea has attracted global media attention due to the speed of spread and onward transmission. Here, we present the complete genome of the first imported MERS-CoV case in China and demonstrate genetic recombination events between group 3 and group 5 of clade B that may have implications for the transmissibility of MERS-CoV.
Modeling the Context-Dependent Associations between the Gut Microbiome, Its Environment, and Host Health
Authors: Sharpton Thomas J. , Gaulke Christopher A. 
Published: September 2015

ABSTRACT
Changes in the gut microbiome are often associated with disease. One of the major goals in microbiome research is determining which components of this complex system are responsible for the observed differences in health state. Most studies apply a reductionist approach, wherein individual organisms are evaluated independently of the surrounding context of the microbiome. While such methods have yielded valuable insights into the microbiome, they fail to identify patterns that may be obscured by contextual variation. A recent report by Schubert et al. [A. M. Schubert, H. Sinani, and P. D. Schloss, mBio 6(4):e00974-15, 2015, doi: 10.1128/mBio.00974-15] communicates an alternative approach to the study of the microbiome's association with host health. By coupling a multifactored experimental design with regression modeling, the authors are able to profile context-dependent changes in the microbiome and predict health status. This work underscores the value of incorporating model-based procedures into the investigation of the microbiome and illustrates the potential clinical transformations that may arise through their use.
Infections Associated with Exotic Cuisine: The Dangers of Delicacies
Authors: Hochberg Natasha S. , Bhadelia Nahid 
Published: September 2015

ABSTRACT

“Exotic” food dishes are an expression of regional culture, religion, and ethnicity worldwide. With the increase in international travel to remote areas of the world, globalization of the food supply, and changes in food habits, more people are consuming dishes once considered exotic. Such behavioral changes require awareness by consumers and clinicians about the risks of food-borne infections. This chapter addresses pathogens associated with consumption of raw or undercooked seafood including anisakidosis,
Diphyllobothrium latum
infection, flukes, and other infectious and toxin-mediated diseases. We discuss the geographic distribution of the pathogens, symptomatology, and basic principles of treatment. Food products derived from turtles, snakes, and other reptiles are reviewed, and we address the risk of gnathostomiasis, sparganosis, trichinellosis, and other pathogens. In discussing infections associated with undercooked beef, pork, and bush meat, we address dysentery, amebiasis, toxoplasmosis,
Taenia
infections, and risks of novel viral infections, among others. We also review infectious risks from poultry, dairy, and other food items, focusing on those organisms encountered less frequently by clinicians in developed countries. The wide range of infectious organisms related to exotic cuisine underscores the importance of educating the adventurous traveler and warrants continued vigilance on the part of the clinician.
Diseases Transmitted by Cats
Authors: Goldstein Ellie J. C. , Abrahamian Fredrick M. 
Published: September 2015

ABSTRACT

Humans and cats have shared a close relationship since ancient times. Millions of cats are kept as household pets, and 34% of households have cats. There are numerous diseases that may be transmitted from cats to humans. General modes of transmission, with some overlapping features, can occur through inhalation (e.g., bordetellosis); vector-borne spread (e.g., ehrlichiosis); fecal-oral route (e.g., campylobacteriosis); bite, scratch, or puncture (e.g., rabies); soil-borne spread (e.g., histoplasmosis); and direct contact (e.g., scabies). It is also likely that the domestic cat can potentially act as a reservoir for many other zoonoses that are not yet recognized. The microbiology of cat bite wound infections in humans is often polymicrobial with a broad mixture of aerobic (e.g.,
Pasteurella
,
Streptococcus
,
Staphylococcus
) and anaerobic (e.g.,
Fusobacterium
,
Porphyromonas
,
Bacteroides
) microorganisms. Bacteria recovered from infected cat bite wounds are most often reflective of the oral flora of the cat, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim’s own skin or the physical environment at the time of injury.
Asymptomatic Bacteriuria and Bacterial Interference
Authors: Nicolle Lindsay E. 
Published: September 2015

ABSTRACT

Asymptomatic bacteriuria is very common. In healthy women, asymptomatic bacteriuria increases with age, from <1% in newborns to 10% to 20% of women age 80 years, but is uncommon in men until after age 50 years. Individuals with underlying genitourinary abnormalities, including indwelling devices, may also have a high frequency of asymptomatic bacteriuria, irrespective of age or gender. The prevalence is very high in residents of long-term–care facilities, from 25% to 50% of women and 15% to 40% of men.
Escherichia coli
is the most frequent organism isolated, but a wide variety of other organisms may occur. Bacteriuria may be transient or persist for a prolonged period. Pregnant women with asymptomatic bacteriuria identified in early pregnancy and who are untreated have a risk of pyelonephritis later in pregnancy of 20% to 30%. Bacteremia is frequent in bacteriuric subjects following mucosal trauma with bleeding, with 5% to 10% of patients developing severe sepsis or septic shock. These two groups with clear evidence of negative outcomes should be screened for bacteriuria and appropriately treated. Asymptomatic bacteriuria in other populations is benign and screening and treatment are not indicated. Antimicrobial treatment has no benefits but is associated with negative outcomes including reinfection with antimicrobial resistant organisms and a short-term increased frequency of symptomatic infection post-treatment. The observation of increased symptomatic infection post-treatment, however, has led to active investigation of bacterial interference as a strategy to prevent symptomatic episodes in selected high risk patients.
Lung protective ventilation in patients undergoing major surgery: a systematic review incorporating a Bayesian approach
Authors: Zhang Zhongheng , Hu Xiaoyun , Zhang Xia , Zhu Xiuqi , Chen Liqian , Zhu Li , Hu Caibao , Du Bin 
Published: September 2015

ObjectiveProtective ventilation (PV) has been validated in patients with acute respiratory distress syndrome. However, the effect of PV in patients undergoing major surgery is controversial. The study aimed to explore the beneficial effect of PV on patients undergoing a major operation by systematic review and meta-analysis.SettingVarious levels of medical centres.ParticipantsPatients undergoing general anaesthesia.InterventionsPV with low tidal volume.Primary and secondary outcome measuresStudy end points included acute lung injury (ALI), pneumonia, atelectasis, mortality, length of stay (LOS) in intensive care unit (ICU) and hospital.MethodsDatabases including PubMed, Scopus, EBSCO and EMBASE were searched from inception to May 2015. Search strategies consisted of terms related to PV and anaesthesia. We reported OR for binary outcomes including ALI, mortality, pneumonia, atelectasis and other adverse outcomes. Weighted mean difference was reported for continuous outcomes such as LOS in the ICU and hospital, pH value, partial pressure of carbon dioxide, oxygenation and duration of mechanical ventilation (MV).Main resultsA total of 22 citations were included in the systematic review and meta-analysis. PV had protective effect against the development of ALI as compared with the control group, with an OR of 0.41 (95% CI 0.19 to 0.87). PV tended to be beneficial with regard to the development of pneumonia (OR 0.46, 95% CI 0.16 to 1.28) and atelectasis (OR 0.68, 95% CI 0.46 to 1.01), but statistical significance was not reached. Other adverse outcomes such as new onset arrhythmia were significantly reduced with the use of PV (OR 0.47, 95% CI 0.48 to 0.93).ConclusionsThe study demonstrates that PV can reduce the risk of ALI in patients undergoing major surgery. However, there is insufficient evidence that such a beneficial effect can be translated to more clinically relevant outcomes such as mortality or duration of MV.Trial registration numberThe study was registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42013006416.
Capturing the experiences of patients across multiple complex interventions: a meta-qualitative approach
Authors: Webster Fiona , Christian Jennifer , Mansfield Elizabeth , Bhattacharyya Onil , Hawker Gillian , Levinson Wendy , Naglie Gary , Pham Thuy-Nga , Rose Louise , Schull Michael , Sinha Samir , Stergiopoulos Vicky , Upshur Ross , Wilson Lynn 
Published: September 2015

ObjectivesThe perspectives, needs and preferences of individuals with complex health and social needs can be overlooked in the design of healthcare interventions. This study was designed to provide new insights on patient perspectives drawing from the qualitative evaluation of 5 complex healthcare interventions.SettingPatients and their caregivers were recruited from 5 interventions based in primary, hospital and community care in Ontario, Canada.ParticipantsWe included 62 interviews from 44 patients and 18 non-clinical caregivers.InterventionOur team analysed the transcripts from 5 distinct projects. This approach to qualitative meta-evaluation identifies common issues described by a diverse group of patients, therefore providing potential insights into systems issues.Outcome measuresThis study is a secondary analysis of qualitative data; therefore, no outcome measures were identified.ResultsWe identified 5 broad themes that capture the patients’ experience and highlight issues that might not be adequately addressed in complex interventions. In our study, we found that: (1) the emergency department is the unavoidable point of care; (2) patients and caregivers are part of complex and variable family systems; (3) non-medical issues mediate patients’ experiences of health and healthcare delivery; (4) the unanticipated consequences of complex healthcare interventions are often the most valuable; and (5) patient experiences are shaped by the healthcare discourses on medically complex patients.ConclusionsOur findings suggest that key assumptions about patients that inform intervention design need to be made explicit in order to build capacity to better understand and support patients with multiple chronic diseases. Across many health systems internationally, multiple models are being implemented simultaneously that may have shared features and target similar patients, and a qualitative meta-evaluation approach, thus offers an opportunity for cumulative learning at a system level in addition to informing intervention design and modification.
Work conditions, mental workload and patient care quality: a multisource study in the emergency department
Authors: Weigl Matthias , Müller Andreas , Holland Stephan , Wedel Susanne , Woloshynowych Maria 
Published: September 2015

BackgroundWorkflow interruptions, multitasking and workload demands are inherent to emergency departments (ED) work systems. Potential effects of ED providers’ work on care quality and patient safety have, however, been rarely addressed. We aimed to investigate the prevalence and associations of ED staff's workflow interruptions, multitasking and workload with patient care quality outcomes.MethodsWe applied a mixed-methods design in a two-step procedure. First, we conducted a time-motion study to observe the rate of interruptions and multitasking activities. Second, during 20-day shifts we assessed ED staff's reports on workflow interruptions, multitasking activities and mental workload. Additionally, we assessed two care quality indicators with standardised questionnaires: first, ED patients’ evaluations of perceived care quality; second, patient intrahospital transfers evaluated by ward staff. The study was conducted in a medium-sized community ED (16 600 annual visits).ResultsED personnel's workflow was disrupted on average 5.63 times per hour. 30% of time was spent on multitasking activities. During 20 observations days, data were gathered from 76 ED professionals, 239 patients and 205 patient transfers. After aggregating daywise data and controlling for staffing levels, prospective associations revealed significant negative associations between ED personnel's mental workload and patients’ perceived quality of care. Conversely, workflow interruptions were positively associated with patient-related information on discharge and overall quality of transfer.ConclusionsOur investigation indicated that ED staff's capability to cope with demanding work conditions was associated with patient care quality. Our findings contribute to an improved understanding of the complex effects of interruptions and multitasking in the ED environment for creating safe and efficient ED work and care systems.
PKCα Attenuates Jagged-1–Mediated Notch Signaling in ErbB-2–Positive Breast Cancer to Reverse Trastuzumab Resistance
Authors: Pandya Kinnari , Wyatt Debra , Gallagher Brian , Shah Deep , Baker Andrew , Bloodworth Jeffrey , Zlobin Andrei , Pannuti Antonio , Green Andrew , Ellis Ian O. , Filipovic Aleksandra , Sagert Jason , Rana Ajay , Albain Kathy S. , Miele Lucio , Denning Mitchell F. , Osipo Clodia 
Published: September 2015

Abstract
Purpose: Breast cancer is the second leading cause of cancer mortality among women worldwide. The major problem with current treatments is tumor resistance, recurrence, and disease progression. ErbB-2–positive breast tumors are aggressive and frequently become resistant to trastuzumab or lapatinib. We showed previously that Notch-1 is required for trastuzumab resistance in ErbB-2–positive breast cancer.
Experimental Design: Here, we sought to elucidate mechanisms by which ErbB-2 attenuates Notch signaling and how this is reversed by trastuzumab or lapatinib.
Results: The current study elucidates a novel Notch inhibitory mechanism by which PKCα downstream of ErbB-2 (i) restricts the availability of Jagged-1 at the cell surface to transactivate Notch, (ii) restricts the critical interaction between Jagged-1 and Mindbomb-1, an E3 ligase that is required for Jagged-1 ubiquitinylation and subsequent Notch activation, (iii) reverses trastuzumab resistance in vivo, and (iv) predicts better outcome in women with ErbB-2–positive breast cancer.
Conclusions: The clinical impact of these studies is PKCα is potentially a good prognostic marker for low Notch activity and increased trastuzumab sensitivity in ErbB-2–positive breast cancer. Moreover, women with ErbB-2–positive breast tumors expressing high Notch activation and low PKCα expression could be the best candidates for anti-Notch therapy. Clin Cancer Res; 22(1); 175–86. ©2015 AACR.
ROS-Induced CXCR4 Signaling Regulates Mantle Cell Lymphoma (MCL) Cell Survival and Drug Resistance in the Bone Marrow Microenvironment via Autophagy
Authors: Chen Zheng , Teo Albert E. , McCarty Nami 
Published: September 2015

AbstractPurpose: Patients with advanced stages of mantle cell lymphoma (MCL) have a poor prognosis after standard therapies. MCL cells in those patients often spread into tissues other than lymph nodes, such as the bone marrow. Apart from directed migration and homing, there is little understanding of the function of the CXCR4/SDF-1 signaling axis in MCL. In this report, we aim to understand mechanisms of MCL cell survival in the bone marrow.Experimental Design: For comprehensive analyses of MCL interactions with bone marrow stromal cells, we have generated gene knockout cells using CRISPR-CAS9 system and gene knockdown cells to reveal novel roles of the CXCR4/SDF-1 signaling.Results: CXCR4 silencing in MCL cells led to a significant reduction in proliferation, cell adhesion to bone marrow stromal cells, and colony formation in PHA-LCM methylcellulose medium, which were reversed upon the addition of SDF-1–neutralizing antibodies. In addition, tracking MCL cell engraftment in vivo revealed that quiescent MCL cells are significantly reduced in the bone marrow upon CXCR4 silencing, indicating that CXCR4/SDF-1 signaling is required for the survival and maintenance of the quiescent MCL cells. Further analysis revealed novel mechanisms of ROS-induced CXCR4/SDF-1 signaling that stimulate autophagy formation in MCL cells for their survival.Conclusions: Our data, for the first time, revealed new roles of the CXCR/SDF-1 signaling axis on autophagy formation in MCL, which further promoted their survival within the bone marrow microenvironment. Targeting the CXCR4/SDF-1/autophagy signaling axis may contribute to an enhanced efficacy of current therapies. Clin Cancer Res; 22(1); 187–99. ©2015 AACR.