bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokeratin 8 Is an Epithelial Cell Receptor for Pet, a Cytotoxic Serine Protease Autotransporter of
Enterobacteriaceae
Authors: Nava-Acosta Raul , Navarro-Garcia Fernando 
Published: December 2013

ABSTRACT

The group of proteins known as serine protease autotransporters of
Enterobacteriaceae
(SPATE) is a growing family of serine proteases secreted to the external milieu by the type V secretion system. Pet toxin and some other SPATE belong to the class 1 cytotoxic SPATE, which have comparable protease strength on fodrin. Pet is internalized and is directed to its intracellular substrate by retrograde transport. However, the epithelial cell receptor for Pet has yet to be identified. We show that Pet has affinity for the epithelial cell surface until the saturation of the binding sites at 100 nM Pet. Affinity column assays and matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) analysis identified a cytokeratin (CK8) which directly binds to Pet, and both proteins colocalized on the cell surface. Interestingly, CK8 is not present in kidney cell lines, which are not susceptible to Pet. Inhibition experiments by using anti-CK8 and
ck8
small interfering RNA (siRNA) blocked the cytotoxic effect induced by Pet, while exogenous CK8 expression in kidney cells made them susceptible to Pet intoxication. Recombinant CK8 showed a Pet-binding pattern similar to that seen by using fixed cells. Remarkably, Pet colocalized with CK8 and clathrin at early times (receptor-mediated endocytosis), and subsequently, Pet colocalized with CK8 and Rab5b in the early endosomes. These data support the idea that CK8 is an important receptor for Pet on epithelial cells for starting its cytotoxic effects. These data suggest that therapeutics that block Pet-CK8 interaction may improve outcome of diseases caused by Pet-secreting
Enterobacteriaceae
such as enteroaggregative
Escherichia coli
.

IMPORTANCE
Receptor-ligand binding is one mechanism by which cells sense and respond to external cues. Receptors may also be utilized by toxins to mediate their own internalization. Pet toxin is secreted by enteroaggregative
Escherichia coli
, an organism that causes persistent diarrhea in children, traveler’s diarrhea, and acute and persistent diarrhea in patients with HIV. Pet is a member of the family of serine protease autotransporters of
Enterobacteriaceae
(SPATE). SPATE in different pathogens are virulence factors, and Pet belongs to the class 1 cytotoxic SPATE, which have comparable protease strength on their biological substrate, fodrin (a cytoskeletal protein important for maintaining cell viability). To cleave fodrin, Pet enters the cells by clathrin-mediated endocytosis. This mechanism includes receptor-mediated endocytosis (a receptor-ligand complex triggers the endocytosis). We show that CK8 is an important receptor for Pet on epithelial cells and that it may be useful for identifying molecules that block the interaction of CK8 with Pet.
The Histone Code of Toxoplasma gondii Comprises Conserved and Unique Posttranslational Modifications
Authors: Nardelli Sheila C. , Che Fa-Yun , Silmon de Monerri Natalie C. , Xiao Hui , Nieves Edward , Madrid-Aliste Carlos , Angel Sergio O. , Sullivan William J. , Angeletti Ruth H. , Kim Kami , Weiss Louis M. 
Published: December 2013

ABSTRACT

Epigenetic gene regulation has emerged as a major mechanism for gene regulation in all eukaryotes. Histones are small, basic proteins that constitute the major protein component of chromatin, and posttranslational modifications (PTM) of histones are essential for epigenetic gene regulation. The different combinations of histone PTM form the histone code for an organism, marking functional units of chromatin that recruit macromolecular complexes that govern chromatin structure and regulate gene expression. To characterize the repertoire of
Toxoplasma gondii
histone PTM, we enriched histones using standard acid extraction protocols and analyzed them with several complementary middle-down and bottom-up proteomic approaches with the high-resolution Orbitrap mass spectrometer using collision-induced dissociation (CID), higher-energy collisional dissociation (HCD), and/or electron transfer dissociation (ETD) fragmentation. We identified 249 peptides with unique combinations of PTM that comprise the
T. gondii
histone code.
T. gondii
histones share a high degree of sequence conservation with human histones, and many modifications are conserved between these species. In addition,
T. gondii
histones have unique modifications not previously identified in other species. Finally,
T. gondii
histones are modified by succinylation, propionylation, and formylation, recently described histone PTM that have not previously been identified in parasitic protozoa. The characterization of the
T. gondii
histone code will facilitate in-depth analysis of how epigenetic regulation affects gene expression in pathogenic apicomplexan parasites and identify a new model system for elucidating the biological functions of novel histone PTM.

IMPORTANCE
Toxoplasma gondii
is among the most common parasitic infections in humans. The transition between the different stages of the
T. gondii
life cycle are essential for parasite virulence and survival. These differentiation events are accompanied by significant changes in gene expression, and the control mechanisms for these transitions have not been elucidated. Important mechanisms that are involved in the control of gene expression are the epigenetic modifications that have been identified in several eukaryotes.
T. gondii
has a full complement of histone-modifying enzymes, histones, and variants. In this paper, we identify over a hundred PTM and a full repertoire of PTM combinations for
T. gondii
histones, providing the first large-scale characterization of the
T. gondii
histone code and an essential initial step for understanding how epigenetic modifications affect gene expression and other processes in this organism.
The prevalence of latex sensitisation and allergy and associated risk factors among healthcare workers using hypoallergenic latex gloves at King Edward VIII Hospital, KwaZulu-Natal South Africa: a cross-sectional study
Authors: Phaswana Shumani Makwarela , Naidoo Saloshni 
Published: December 2013

ObjectivesThe present study describes latex sensitisation and allergy prevalence and associated factors among healthcare workers using hypoallergenic latex gloves at King Edward VIII Hospital in KwaZulu-Natal, South Africa.DesignCross-sectional study.SettingA tertiary hospital in eThekwini municipality, KwaZulu-Natal, South Africa.Participants600 healthcare workers were randomly selected and 501 (337 exposed and 164 unexposed) participated. Participants who were pregnant, with less than 1 year of work as a healthcare worker and a history of anaphylactic reaction were excluded from the study.Primary and secondary outcome measuresLatex sensitisation and latex allergy were the outcome of interest and they were successfully measured.ResultsThe prevalence of latex sensitisation and allergy was observed among exposed workers (7.1% and 5.9%) and unexposed workers (3.1% and 1.8%). Work-related allergy symptoms were significantly higher in exposed workers (40.9%, p<0.05). Duration of employment was inversely associated with latex allergy (OR 0.9; 95% CI 0.8 to 0.9). The risk of latex sensitisation (OR 4.2; 95% CI 1.2 to 14.1) and allergy (OR 5.1; 95% CI 1.2 to 21.2) increased with the exclusive use of powder-free latex gloves. A dose–response relationship was observed for powdered latex gloves (OR 1.1; 95% CI 1.0 to 1.2). Atopy (OR 1.5; 95% CI 0.7 to 3.3 and OR 1.4; 95% CI 0.6 to 3.2) and fruit allergy (OR 2.3; 95% CI 0.8 to 6.7 and OR 3.1; 95% CI 1.1 to 9.2) also increased the risk of latex sensitisation and allergy.ConclusionsThis study adds to previous findings that healthcare workers exposed to hypoallergenic latex gloves are at risk for developing latex sensitisation highlighting its importance as an occupational hazard in healthcare. More research is needed to identify the most cost effective way of implementing a latex-free environment in resource-limited countries, such as South Africa. In addition more cohort analysis is required to better understand the chronicity of illness and disability associated with latex allergy.
Differences in research funding for women scientists: a systematic comparison of UK investments in global infectious disease research during 1997–2010
Authors: Head Michael G , Fitchett Joseph R , Cooke Mary K , Wurie Fatima B , Atun Rifat 
Published: December 2013

ObjectivesThere has not previously been a systematic comparison of awards for research funding in infectious diseases by sex. We investigated funding awards to UK institutions for all infectious disease research from 1997 to 2010, across disease categories and along the research and development continuum.DesignSystematic comparison.MethodsData were obtained from several sources for awards from the period 1997 to 2010 and each study assigned to—disease categories; type of science (preclinical, phases I–III trials, product development, implementation research); categories of funding organisation. Fold differences and statistical analysis were used to compare total investment, study numbers, mean grant and median grant between men and women.Results6052 studies were included in the final analysis, comprising 4357 grants (72%) awarded to men and 1695 grants (28%) awarded to women, totalling £2.274 billion. Of this, men received £1.786 billion (78.5%) and women £488 million (21.5%). The median value of award was greater for men (£179 389; IQR £59 146–£371 977) than women (£125 556; IQR £30 982–£261 834). Awards were greater for male principal investigators (PIs) across all infectious disease systems, excepting neurological infections and sexually transmitted infections. The proportion of total funding awarded to women ranged from 14.3% in 1998 to 26.8% in 2009 (mean 21.4%), and was lowest for preclinical research at 18.2% (£285.5 million of £1.573 billion) and highest for operational research at 30.9% (£151.4 million of £489.7 million).ConclusionsThere are consistent differences in funding received by men and women PIs: women have fewer funded studies and receive less funding in absolute and in relative terms; the median funding awarded to women is lower across most infectious disease areas, by funder, and type of science. These differences remain broadly unchanged over the 14-year study period.
Return to work following unintentional injury: a prospective follow-up study
Authors: Hepp Urs , Schnyder Ulrich , Hepp-Beg Sofia , Friedrich-Perez Josefina , Stulz Niklaus , Moergeli Hanspeter 
Published: December 2013

ObjectiveThe aim of this study was to predict time off work following unintentional injuries due to accidents leading to hospital admission.DesignProspective 6-month follow-up study.SettingDepartment of Trauma Surgery of a University Hospital.ParticipantsConsecutively recruited victims of unintentional injuries (n=221) hospitalised for a minimum of 32 h including two consecutive nights. All the participants were aged 18–65 years and were able to participate in an assessment within 30 days of the accident.Main outcome measuresInterview-assessed number of days off work during the 6 months immediately following the accident.ResultsThe patients’ subjective appraisals of (1) accident severity and (2) their ability to cope with the resulting injury and its job-related consequences predicted time off work following the accident beyond the impact of the objective severity of their injury and the type of accident involved.ConclusionsThe patients’ subjective appraisals of the accident severity and of their ability to cope with its consequences are highly relevant for return to work after accidents. Extending the findings from previous studies on severely injured and otherwise preselected accident victims, this seems to apply to the whole spectrum of patients hospitalised with unintentional injuries.
The Variable Rate Intravenous Insulin Infusion Protocol
Authors: Collard Benjamin , Sturgeon Jonathan , Patel Natasha , Asharia Shabbar 
Published: December 2013

AbstractInsulin use among inpatients is high and associated with severe and regular medication errors. An initial baseline audit showed a wide variation in the prescription of intravenous insulin within the trust. These included variation in the choice of fluid prescribed, electrolyte levels not consistently checked, handwritten illegible prescriptions, and varying parameters set for adjustment of the prescription.A Variable Rate Intravenous Insulin Infusion protocol (VRIII)) was introduced to standardize intravenous insulin prescription throughout the trust by all members of the clinical team. We looked at and measured uptake and effects of the VRIII protocol in improving standardization of insulin prescription for inpatients on insulin at St George's NHS trust. The protocol was uploaded to the intranet to allow access 24 hours a day and the staff educated about it.The VRIII protocol was routinely used successfully throughout the trust. Any initial problems were addressed through education of clinical staff. The protocol has shown decreased prescribing and administrative errors, whilst demonstrating good glucose and electrolyte control.Use of a standardized protocol helps reduce medication errors and demonstrates good glycaemic control. Regular and continued education of clinical staff is necessary to maintain its efficacy.
Improvement in institutional protocols leads to decreased mortality in patients with haemodynamically unstable pelvic fractures
Authors: Cheng Mina , Cheung Moon-Tong , Lee Kin-Yan , Lee Kin-Bong , Chan Susan-C H , Wu Amy-C Y , Chow Yu-Fat , Chang Annice-M L , Ho Hiu-Fai , Yau Kelvin-K W 
Published: December 2013

BackgroundThe mortality rate in patients with haemodynamically unstable pelvic fractures is as high as 40–60%. In recent years, angioembolisation and pelvic packing have been introduced as part of a multimodality treatment for these patients. Protocol-driven management has been shown to improve outcomes.Patients and methodsThis is a Level III retrospective cohort study of patients suffering from unstable pelvic fractures from 1 January 1996 to 30 September 2011. The aim of the study was to review our results, particularly in terms of mortality through the evolution of three phases of treatment protocols: preangiography, angiography and pelvic packing.ResultsThe overall 30-day mortality rate for all patients was 47.2%, with a rate of 63.5% in the preangiography phase, 42.1% in the angiography phase and 30.6% in the pelvic packing phase. Multivariate logistic regression analysis identified the use of retroperitoneal packing as a significant independent predictive factor for 24 h mortality.ConclusionsOur results showed an improvement in patient survival with sequential protocols over the study period, during which we incorporated a multidisciplinary approach to managing these complicated pelvic fractures. The results strongly suggest that retroperitoneal packing should be highly recommended for bleeding subsequent to pelvic fracture, in addition to other modalities of treatment.
Exercise capacity and paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy
Authors: Azarbal Farnaz , Singh Maneesh , Finocchiaro Gherardo , Le Vy-Van , Schnittger Ingela , Wang Paul , Myers Jonathan , Ashley Euan , Perez Marco 
Published: December 2013

BackgroundAtrial fibrillation (AF) is the most common arrhythmia among patients with hypertrophic cardiomyopathy (HCM). The relationship between paroxysmal AF and exercise capacity in this population is incompletely understood.MethodsPatients with HCM underwent symptom-limited cardiopulmonary testing with expired gas analysis at Stanford Hospital between October 2006 and October 2012. Baseline demographics, medical histories and resting echocardiograms were obtained for all subjects. Diagnosis of AF was established by review of medical records and baseline ECG. Those with paroxysmal AF were in sinus rhythm at the time of cardiopulmonary testing with expired gas analysis. Exercise intolerance was defined as peak VO2<20 mL/kg/min. We used multivariate logistic regression to evaluate the association between exercise intolerance and paroxysmal AF.ResultsAmong the 265 patients recruited, 55 had AF (28 paroxysmal and 27 permanent). Compared with those without AF, subjects with paroxysmal AF were older, more likely to use antiarrhythmic and anticoagulant medications, and had larger left atria. Patients with paroxysmal AF achieved lower peak VO2 (21.9±9.2 mL/kg/min vs 26.9±10.8 mL/kg/min, p=0.02) and were more likely to have exercise intolerance (61% vs 28%, p<0.001) compared with those without AF. After adjustment for age, sex and body mass index (BMI) exercise intolerance remained significantly associated with paroxysmal AF (OR 4.65, 95% CI 1.83 to 11.83, p=0.001).ConclusionsPatients with HCM and paroxysmal AF demonstrate exercise intolerance despite being in sinus rhythm at the time of exercise testing.
Patterns of vulnerability to non-fatal injuries in Sudan: initial evidence from a national cross-sectional survey
Authors: Abdalla Safa 
Published: December 2013

BackgroundSuccessful injury prevention requires identification and targeting of particularly vulnerable groups. Little is known about injury vulnerability patterns in Sudan. This paper aimed to fill this gap using survey data.MethodsData from the Sudan Household Health Survey were used. This was a national cross-sectional interview survey of 83 510 individuals selected by multistage cluster random sampling. Multivariable Poisson regression was used to investigate the association of cause-specific injury that received care by traditional healers, outpatient care and inpatient care, and those that received only inpatient care, with age, gender, area of residence (urban or rural), socioeconomic status and education. Relevant interactions were tested.ResultsIndependent of other sociodemographic variables, men were at higher risk of road traffic injury (prevalence ratio (PR): 3.3 95% CI 2.4 to 4.7), falls (PR: 1.5, 95% CI 1.3 to 1.9), assault (PR: 3.0 95% CI 1.8–5) and mechanical injury (PR: 2.0 95% CI 1.2 to 3.1) that received any form of healthcare. Those aged 65 years and over also had the highest risk of those injury causes, while children under 5 years were the most likely to suffer burn injuries. Socioeconomic status was associated with assault (PR for the richest group 0.4 95% CI 0.2 to 0.8). Vulnerability patterns for injury that received inpatient care were fairly similar for some causes.ConclusionsIn Sudan, existing disease prevention and health promotion programmes should expand to target men, children under 5 years, elderly people and those of low socioeconomic status with injury prevention interventions. Further research is needed to investigate the context-specific proximal risk factors that shape the various vulnerability patterns observed.
Republished: Recent advances in the epidemiology, diagnosis and treatment of endomyocardial fibrosis in Africa
Authors: Mocumbi Ana Olga H , Falase Ayodele O 
Published: December 2013

Abstract
Endomyocardial fibrosis (EMF) continues to be an important and disabling disease in many parts of Africa, although its prevalence has declined in some parts of the continent. Increased access to medical care in general and increased availability of echocardiography in some parts of the continent have led to recognition of the disease in areas in which the disease had not been previously reported, and this has given new insights into its natural history. However, the early manifestations of EMF continue to elude clinicians and researchers, and no progress has been made in defining its aetiology. Advances have, however, been made in establishing the epidemiology and improving clinical diagnosis and management, through modern medical therapy and improved surgical techniques. Research is still required to define clinical, biological and echocardiographic markers of early stages of EMF, so that advances in the knowledge of its pathogenesis and pathophysiology can be made. This will hopefully determine preventive measures and avoid the burden of this debilitating condition in this continent.
Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines
Authors: Hernández Wilfredo , Paz Juan , Carrasco Fernando , Vaisberg Abraham , Spodine Evgenia , Manzur Jorge , Hennig Lothar , Sieler Joachim , Blaurock Steffen , Beyer Lothar 
Published: December 2013

The palladium(II) bis-chelate complexes of the type [Pd(TSC1-5)2] (6–10), with their corresponding ligands 4-phenyl-1-(acetone)-thiosemicarbazone, HTSC1(1), 4-phenyl-1-(2′-chloro-benzaldehyde)-thiosemicarbazone, HTSC2(2), 4-phenyl-1-(3′-hydroxy-benzaldehyde)-thiosemicarbazone, HTSC3(3), 4-phenyl-1-(2′-naphthaldehyde)-thiosemicarbazone, HTSC4(4), and 4-phenyl-1-(1′-nitro-2′-naphthaldehyde)-thiosemicarbazone, HTSC5(5), were synthesized and characterized by elemental analysis and spectroscopic techniques (IR and1H- and13C-NMR). The molecular structure of HTSC3, HTSC4, and [Pd(TSC1)2] (6) have been determined by single crystal X-ray crystallography. Complex6shows a square planar geometry with two deprotonated ligands coordinated toPdIIthrough the azomethine nitrogen and thione sulfur atoms in acisarrangement. Thein vitrocytotoxic activity measurements indicate that the palladium(II) complexes (IC50=0.01–9.87 μM) exhibited higher antiproliferative activity than their free ligands (IC50=23.48–70.86 and >250 μM) against different types of human tumor cell lines. Among all the studied palladium(II) complexes, the [Pd(TSC3)2] (8) complex exhibited high antitumor activity on the DU145 prostate carcinoma and K562 chronic myelogenous leukemia cells, with low values of the inhibitory concentration (0.01 and 0.02 μM, resp.).Corrigendum to “Synthesis and Characterization of New Palladium(II) Thiosemicarbazone Complexes and Their Cytotoxic Activity against Various Human Tumor Cell Lines”
Inhibition of GSK-3 Induces Differentiation and Impaired Glucose Metabolism in Renal Cancer
Authors: Pal Krishnendu , Cao Ying , Gaisina Irina N. , Bhattacharya Santanu , Dutta Shamit K. , Wang Enfeng , Gunosewoyo Hendra , Kozikowski Alan P. , Billadeau Daniel D. , Mukhopadhyay Debabrata 
Published: December 2013

AbstractGlycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell-cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pathogenesis of various human diseases, including type II diabetes, Alzheimer disease, bipolar disorder, inflammation, and cancer. Consequently, it is recognized as an attractive target for the development of new drugs. In the present study, we investigated the effect of both pharmacologic and genetic inhibition of GSK-3 in two different renal cancer cell lines. We have shown potent antiproliferative activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The antiproliferative activity is most likely caused by G0–G1 and G2–M phase arrest as evident from cell-cycle analysis. We have established that inhibition of GSK-3 imparted a differentiated phenotype in renal cancer cells. We have also shown that GSK-3 inhibition induced autophagy, likely as a result of imbalanced energy homeostasis caused by impaired glucose metabolism. In addition, we have demonstrated the antitumor activity of 9-ING-41 in two different subcutaneous xenograft renal cell carcinoma tumor models. To our knowledge, this is the first report describing autophagy induction due to GSK-3 inhibition in renal cancer cells. Mol Cancer Ther; 13(2); 285–96. ©2013 AACR.