bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular localization and stability of MITF are modulated by the bHLH‐Zip domain
Authors: Fock Valerie , Gudmundsson Sigurdur Runar , Gunnlaugsson Hilmar Orn , Stefansson Jon August , Ionasz Vivien , Schepsky Alexander , Viarigi Jade , Reynisson Indridi Einar , Pogenberg Vivian , Wilmanns Matthias , Ogmundsdottir Margret Helga , Steingrimsson Eirikur 
Published: June 2018

SummaryMicrophthalmia‐associated transcription factor (MITF) is a member of the basic helix–loop–helix leucine zipper (bHLH‐Zip) family and functions as the master regulator of the melanocytic lineage. MITF‐M is the predominant isoform expressed in melanocytes and melanoma cells, and, unlike other MITF isoforms, it is constitutively nuclear. Mutational analysis revealed three karyophilic signals in the bHLH‐Zip domain of MITF‐M, spanning residues 197–206, 214–217, and 255–265. Structural characterization of the MITF protein showed that basic residues within these signals are exposed for interactions in the absence of DNA. Moreover, our data indicate that neither DNA binding nor dimerization of MITF‐M are required for its nuclear localization. Finally, dimerization‐deficient MITF‐M mutants exhibited a significantly reduced stability in melanoma cells when compared to the wild‐type protein. Taken together, we have shown that, in addition to its well‐established role in DNA binding and dimer formation, the bHLH‐Zip domain of MITF modulates the transcription factor's subcellular localization and stability.
Preservation of common carp germ cells under hypothermic conditions: Whole tissue vs isolated cells
Authors: Lujić Jelena , Marinović Zoran , Kása Eszter , Šćekić Ilija , Urbányi Béla , Horváth Ákos 
Published: June 2018

AbstractThe aim of this study was to optimize the conditions for hypothermic storage of spermatogonial stem cells (SSCs) and oogonial stem cells (OSCs) of common carp Cyprinus carpio. This was conducted by storing gonadal tissue or isolated cells for 24 hr under hypothermic conditions in the first experiment and by testing two different storage media (L‐15 or DMEM supplemented with 10% FBS and 25 mM HEPES) and regular medium change (every 4 days) during two weeks of hypothermic storage in the second experiment. During the first 24 hr, isolated cells showed no decrease in viability, while cells obtained from hypothermically stored tissues displayed significantly lower viability after only 6 hr (Tukey's HSD, p < 0.01) indicating that hypothermic storage of isolated cells is superior to storing tissue pieces. The 2‐week trial demonstrated that storage media have a profound influence, while regular medium exchange does not have a positive effect on cell viability. Viability of SSCs and OSCs after two weeks was approximately 40% and 25%, respectively; however, survival of ~70% was obtained after 10 days of storage for SSCs and 7 days for OSCs. Hypothermic storage developed in this study has many practical applications during the development of surrogate broodstock technologies for common carp, but also in carp hatcheries and for the conservation of genetic resources of closely related cyprinid species.
Heterogeneity in Short‐Term Suicidal Ideation Trajectories: Predictors of and Projections to Suicidal Behavior
Authors: Allan Nicholas P. , Gros Daniel F. , Lancaster Cynthia L. , Saulnier Kevin G. , Stecker Tracy 
Published: June 2018

ObjectiveLittle is known about suicidal ideation stability, including whether stability is heterogeneous or homogeneous between individuals. Studies of this kind are necessary to understand the progression from suicidal ideation to action.MethodThis study examined suicidal ideation trajectories, using growth mixture modeling, in a sample of 359 past/current military service members (M age = 32.1 years, SD = 7.7; 88.3% male). Self‐reported suicidal ideation information was collected at baseline and follow‐up sessions at months 1, 3, 6, and 12. Following extraction of the best‐fitting solution, predictors of trajectory status were examined and trajectory status was used to predict suicidal behavior between baseline and month 12 assessments.ResultsResults revealed four trajectories, Low‐Stable (n = 125), Moderate‐Stable (n = 101), High‐Stable (n = 76), and High‐Rapidly Declining (n = 57). In general, the High‐Stable trajectory had the highest levels of perceived burdensomeness, thwarted belongingness, PTSD symptoms, and drug use. The High‐ and Moderate‐Stable trajectories had the highest rates of suicidal behavior between baseline and month 12.ConclusionsSuicidal ideation, even in individuals with elevated ideation, is not a homogeneous construct over time. Stability of suicidal ideation might be an important risk factor, even if ideation is only moderately elevated.
Population density and proximity to junior developmental teams affect the development of National Hockey League draftees
Authors: Farah Lou , Schorer Jörg , Baker Joseph , Wattie Nick 
Published: June 2018

Inconsistencies in community size effects found between and within countries (Baker et al Eur J Sport Sci. 2009;9:329‐339; Bruner et al J Sports Sci. 2011;29:1337‐1344; Wattie et al J Sports Sci. 2018;36:436‐444) suggest population size may not be an accurate predictor of athlete development and that other proxies of early environmental characteristics are needed. Researchers have begun to explore the influence of population density and proximity to local sport clubs on athlete development in European countries; however, similar analysis remains to be conducted in Canadian ice hockey. The current study focused on National Hockey League (NHL) draftees and explored whether population density and proximity to Canadian Hockey League teams were associated with the number of draftees produced. Linear regression analyses showed a significant positive relationship between population density and the development of draftees in all provincial regions; however, a significant negative relationship between proximity to CHL teams and NHL draftee development was observed in four out of six provincial regions (British Columbia, Ontario, Quebec, and the Atlantic Provinces). Moreover, population density appeared to be a better predictor of NHL talent development than proximity to CHL teams. Future research may benefit from exploring the effects of these two variables within population size categories, as well as between different regions within provinces.
Struma ovarii – ultrasound features of a rare tumor mimicking ovarian cancer
Authors: Weinberger Vit , Kadlecova Jana , Minář Luboš , Felsinger Michal , Anton Milan , Ovesna Petra , Bednaříková Markéta , Číhalová Marta , Jandáková Eva , Hausnerová Jitka , Zikán Michal 
Published: June 2018

Aims: To describe the ultrasound features of benign struma ovarii that often mimic ovarian cancer in the background of complex clinical and histopathological pictures.Material and methods: We retrospectively identified patients with histologically confirmed benign struma ovarii, treated in our institution between 2003–2016 with complete imaging, clinical, nd histopathological data available. Ultrasound findings were drawn from images, and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied.Results: In all, 19 patients were identified; 10 with pure and 9 with impure struma. Median age was 47 (range 24–69); 10 (53%) were premenopausal. Only four (21%) patients presented with pain, others were asymptomatic. Using pattern recognition, 74% strumas (14/19) were uni-/multilocular solid or solid tumors. The solid components were roundish with smooth contours. Six struma pearls were detected. The subjective color score was moderate or abundant in the majority of solid components. Only 5 (26%) tumors were purely cystic.Conclusions: The ultrasound characteristics differ widely from typical mature ovarian teratoma. Features such as, solid roundish components with smooth contours, struma pearls, acoustic shadowing and occasionally signs of dermoid are clues and may help preoperatively to differentiate benign struma from malignant adnexal lesions.
A Novel Method of Serum Resistance by Escherichia coli That Causes Urosepsis
Authors: Coggon Carrie F. , Jiang Andrew , Goh Kelvin G. K. , Henderson Ian R. , Schembri Mark A. , Wells Timothy J. 
Published: June 2018

ABSTRACTUropathogenicEscherichia coli(UPEC) is the most common cause of urinary tract infection, which in some patients can develop into life-threatening urosepsis. Serum resistance is a key virulence trait of strains that cause urosepsis. Recently, we identified a novel method of serum resistance in patients withPseudomonas aeruginosalung infections, where patients possessed antibodies that inhibited complement-mediated killing (instead of protecting against infection). These inhibitory antibodies were of the IgG2 subtype, specific to the O-antigen component of lipopolysaccharide (LPS) and coated the bacterial surface, preventing bacterial lysis by complement. As this mechanism could apply to any Gram-negative bacterial infection, we hypothesized that inhibitory antibodies may represent an uncharacterized mechanism of serum resistance in UPEC. To test this, 45 urosepsis patients with paired blood culture UPEC isolates were screened for serum titers of IgG2 specific for their cognate strain’s LPS. Eleven patients had sufficiently high titers of the antibody to inhibit serum-mediated killing of UPEC isolates by pooled healthy control sera. Depletion of IgG or removal of O-antigen restored sensitivity of the isolates to the cognate patient serum. Importantly, the isolates from these 11 patients were more sensitive to killing by serum than isolates from patients with no inhibitory antibodies. This suggests the presence of inhibitory antibodies may have allowed these strains to infect the bloodstream. The high prevalence of patients with inhibitory antibodies (24%) suggests that this phenomenon is an important mechanism of UPEC serum resistance. LPS-specific inhibitory antibodies have now been identified against three Gram-negative pathogens that cause disparate diseases.IMPORTANCEDespite improvements in the early detection and management of sepsis, morbidity and mortality are still high. Infections of the urinary tract are one of the most frequent sources of sepsis withEscherichia colithe main causative agent. Serum resistance is vital for bacteria to infect the bloodstream. Here we report a novel method of serum resistance found in patients with UPEC-mediated sepsis. Antibodies in sera usually protect against infection, but here we found that 24% of patients expressed “inhibitory antibodies” capable of preventing serum-mediated killing of their infecting isolate. Our data suggest that these antibodies would allow otherwise serum-sensitive UPEC strains to cause sepsis. The high prevalence of patients with inhibitory antibodies in this cohort suggests that this is a widespread mechanism of resistance to complement-mediated killing in urosepsis patients, invoking the potential for the application of new methods to prevent and treat sepsis.
Shigella
-Induced Emergency Granulopoiesis Protects Zebrafish Larvae from Secondary Infection
Authors: Willis Alexandra R. , Torraca Vincenzo , Gomes Margarida C. , Shelley Jennifer , Mazon-Moya Maria , Filloux Alain , Lo Celso Cristina , Mostowy Serge 
Published: June 2018

ABSTRACT

Emergency granulopoiesis is a hematopoietic program of stem cell-driven neutrophil production used to counteract immune cell exhaustion following infection.
Shigella flexneri
is a Gram-negative enteroinvasive pathogen controlled by neutrophils. In this study, we use a
Shigella
-zebrafish (
Danio rerio
) infection model to investigate emergency granulopoiesis
in vivo
. We show that stem cell-driven neutrophil production occurs in response to
Shigella
infection and requires macrophage-independent signaling by granulocyte colony-stimulating factor (Gcsf). To test whether emergency granulopoiesis can function beyond homoeostasis to enhance innate immunity, we developed a reinfection assay using zebrafish larvae that have not yet developed an adaptive immune system. Strikingly, larvae primed with a sublethal dose of
Shigella
are protected against a secondary lethal dose of
Shigella
in a type III secretion system (T3SS)-dependent manner. Collectively, these results highlight a new role for emergency granulopoiesis in boosting host defense and demonstrate that zebrafish larvae can be a valuable
in vivo
model to investigate innate immune memory.

IMPORTANCE
Shigella
is an important human pathogen of the gut. Emergency granulopoiesis is the enhanced production of neutrophils by hematopoietic stem and progenitor cells (HSPCs) upon infection and is widely considered a homoeostatic mechanism for replacing exhausted leukocytes. In this study, we developed a
Shigella
-zebrafish infection model to investigate stem cell-driven emergency granulopoiesis. We discovered that zebrafish initiate granulopoiesis in response to
Shigella
infection, via macrophage-independent signaling of granulocyte colony-stimulating factor (Gcsf). Strikingly, larvae primed with a sublethal dose of
Shigella
are protected against a secondary lethal dose of
Shigella
in a type III secretion system (T3SS)-dependent manner. Taken together, we show that zebrafish infection can be used to capture
Shigella
-mediated stem cell-driven granulopoiesis and provide a new model system to study stem cell biology
in vivo
. Our results also highlight the potential of manipulating stem cell-driven granulopoiesis to boost innate immunity and combat infectious disease.
The Rickettsial Ankyrin Repeat Protein 2 Is a Type IV Secreted Effector That Associates with the Endoplasmic Reticulum
Authors: Lehman Stephanie S. , Noriea Nicholas F. , Aistleitner Karin , Clark Tina R. , Dooley Cheryl A. , Nair Vinod , Kaur Simran Jeet , Rahman M. Sayeedur , Gillespie Joseph J. , Azad Abdu F. , Hackstadt Ted 
Published: June 2018

ABSTRACTStrains ofRickettsia rickettsii, the tick-borne agent of Rocky Mountain spotted fever, vary considerably in virulence. Genomic comparisons ofR. rickettsiistrains have identified a relatively small number of genes divergent in an avirulent strain. Among these is one annotated asRickettsiaankyrin repeat protein 2 (RARP-2). Homologs of RARP-2 are present in all strains ofR. rickettsii, but the protein in the avirulent strain Iowa contains a large internal deletion relative to the virulent Sheila Smith strain. RARP-2 is secreted in a type IV secretion system-dependent manner and exposed to the host cell cytosol. RARP-2 of Sheila Smith colocalizes with multilamellar membranous structures bearing markers of the endoplasmic reticulum (ER), whereas the Iowa protein shows no colocalization with host cell organelles and evidence of proteolytic degradation is detected. Overexpression of Sheila Smith RARP-2 inR. rickettsiiIowa converts this avirulent strain’s typically nonlytic or opaque plaque type to a lytic plaque phenotype similar to that of the virulent Sheila Smith strain. Mutation of a predicted proteolytic active site of Sheila Smith RARP-2 abolished the lytic plaque phenotype but did not eliminate association with host membrane. RARP-2 is thus a type IV secreted effector and released from the rickettsiae into the host cytosol to modulate host processes during infection. Overexpression of Sheila Smith RARP-2 did not, however, restore the virulence of the Iowa strain in a guinea pig model, likely due to the multifactorial nature of rickettsial virulence.IMPORTANCEMembers of the genusRickettsiaare obligate intracellular bacteria that exhibit a range of virulence from harmless endosymbionts of arthropods to the etiologic agents of severe disease. Despite the growing number of available genomes, little is known regarding virulence determinants of rickettsiae. Here, we have characterized an ankyrin repeat-containing protein, RARP-2, which differs between a highly virulent and an avirulent strain ofR. rickettsii, the agent of Rocky Mountain spotted fever. RARP-2 is secreted by a type IV secretion system into the cytosol of the host cell, where it interacts with and manipulates the structure of the endoplasmic reticulum. RARP-2 from the avirulent strain is truncated by the loss of seven of 10 ankyrin repeat units but, although secreted, fails to alter ER structure. Recognition of those rickettsial factors associated with virulence will facilitate understanding of regional and strain-specific variation in severity of disease.
Long-Term
In Vitro
Culture of the Syphilis Spirochete
Treponema pallidum
subsp.
pallidum
Authors: Edmondson Diane G. , Hu Bo , Norris Steven J. 
Published: June 2018

ABSTRACT

Investigation of
Treponema pallidum
subsp.
pallidum
, the spirochete that causes syphilis, has been hindered by an inability to culture the organism continuously
in vitro
despite more than a century of effort. In this study, long-term logarithmic multiplication of
T. pallidum
was attained through subculture every 6 to 7 days and periodic feeding using a modified medium (
T. pallidum
culture medium 2 [TpCM-2]) with a previously described microaerobic, rabbit epithelial cell coincubation system. Currently, cultures have maintained continuous growth for over 6 months with full retention of viability as measured by motility and rabbit infectivity. This system has been applied successfully to the well-studied Nichols strain of
T. pallidum
, as well as to two recent syphilis isolates, UW231B and UW249B. Light microscopy and cryo-electron microscopy showed that
in vitro
-cultured
T. pallidum
retains wild-type morphology. Further refinement of this long-term subculture system is expected to facilitate study of the physiological, genetic, pathological, immunologic, and antimicrobial susceptibility properties of
T. pallidum
subsp.
pallidum
and closely related pathogenic
Treponema
species and subspecies.

IMPORTANCE
Syphilis, a sexually transmitted disease with a global distribution, is caused by a spiral-shaped bacterium called
Treponema pallidum
subspecies
pallidum
. Previously,
T. pallidum
was one of the few major bacterial pathogens that had not been cultured long-term
in vitro
(in a test tube), greatly hindering efforts to better understand this organism and the disease that it causes. In this article, we report the successful long-term cultivation of
T. pallidum
in a tissue culture system, a finding that is likely to enhance our ability to obtain new information applicable to the diagnosis, treatment, and prevention of syphilis.
Minimally invasive perventricular versus open surgical ventricular septal defect closure in infants and children: a randomised clinical trial
Authors: Liu Hong , Lu Feng-xia , Zhou Jie , Yan Fei , Qian Si-chong , Li Xin-ya , Zheng Si-qiang , Chen Jun-quan , Zhong Ji-sheng , Feng Qiao-Ling , Ding Tong , Fan Jun , Gu Hai-tao , Liu Xiao-cheng 
Published: June 2018

BackgroundRobust evidence is lacking regarding the clinical efficacy, safety and cardiopulmonary performance of perventricular closure. This study investigated the perioperative efficacy, safety and cardiorespiratory performance of perventricular closure of perimembranous ventricular septal defects (pmVSDs).MethodsOperation-naïve infants and young children aged 5–60 months with isolated pmVSDs were randomised to receive either standard open surgical or minimally invasive perventricular closure via direct entry into the ventricle with a catheter from a subxiphoid incision. The primary outcomes included complete closure at discharge, major and minor adverse events and the changes in perioperative cardiorespiratory performance from baseline. Complete closure was mainly analysed in the modified intention-to-treat (mITT) population, with sensitivity analyses for the ITT, per-protocol (PP) and as-treated (AT) populations (non-inferiority margin −5.0%).ResultsWe recruited 200 patients with pmVSDs for this study (mean age 24.38 months, range 7–58 months, 104 girls), of whom 100 were randomly allocated to one of the study groups. The non-inferiority of perventricular to surgical closure regarding complete closure at discharge was not shown in the ITT (absolute difference −0.010 (95% CI −0.078 to 0.058)) and mITT populations (−0.010 (95% CI −0.069 to 0.048)), but was shown in the PP (0.010 (95% CI −0.043 to 0.062)) and AT populations (0.048 (95% CI −0.009 to 0.106)). Perventricular closure reduced the rate of compromising cardiac haemodynamics, electrophysiological responses, cardiomyocyte viability, respiratory mechanics, ventilatory and gas exchange function and oxygenation and tissue perfusion compared with surgical closure (all between-group P<0.05).ConclusionsFor infants and young children with pmVSD, perventricular closure reduced the rate of postoperative cardiorespiratory compromise compared with surgical closure, but the non-inferiority regarding complete closure should be interpreted in the context of the specific population.Trial registration numberNCT02794584 ;Results.
Limiting access to lethal means: applying the social ecological model for firearm suicide prevention
Authors: Allchin Adelyn , Chaplin Vicka , Horwitz Joshua 
Published: June 2018

This paper outlines a novel application of the social ecological model (SEM) for firearm suicide prevention. It focuses on four levels of intervention (societal, relationship, community and individual) to reduce access to firearms, a practical contributor to the capacity to attempt suicide, from individuals when they are at an elevated risk for suicide. There is substantive research linking easy access to firearms with an increased risk of firearm suicide, and suicide prevention interventions that address access to lethal means are critical components of a comprehensive suicide prevention strategy. Potential interventions using the SEM framework include: at the policy level—extreme risk laws, voluntary self-prohibition policies and policies that reduce the availability of firearms; at the community level—gun shop projects; at the relationship level—lethal means safety counselling; and at the individual level—safer storage. Taken together with upstream interventions, such as increased access to mental health services and substance use treatment, a multilevel approach for suicide prevention that addresses access to firearms can save lives.
Association of serum tumor markers with interstitial lung disease in patients with or without connective tissue disease: A cross-sectional study
Authors: Xu Fei , Cui Wenqaing , Wei Ying , Dong Jingcheng , Liu Baojun 
Published: June 2018

Background: Serum markers, such as Krebs von den Lungen-6 (KL-6), are reported to reflect the severity, progression and prognosis of idiopathic pulmonary fibrosis (IPF). We aimed to evaluate whether tumor markers could improve the diagnosis of connective tissue diseases (CTDs) and predict CTD-related interstitial lung diseases (ILDs) (CTD–ILD); and whether there was a significant difference between ILD patients with CTD and without CTD (non-CTD–ILD). Methods: In this study, 146 patients with ILD only, 61 with CTD–ILD, 102 with lung cancer (LC), 111 with COPD, and 46 with CTD were enrolled. Serum levels of several tumor markers were collected. Results: Compared with COPD, the serum levels of CEA, NSE, CYFRA21-1, CA19-9 and CA125 were higher, but the level of SCC was lower; meanwhile, there were significant differences in NSE, SCC, CYFRA21-1 and CA125 between CTD–ILD and non-CTD–ILD groups. Conclusions: It appears that tumor-associated antigens may be the predictive factors for CTD–ILD that could be used to identify CTD from ILD before it is detected on autoimmune symptoms or auto-antibodies. However, further studies are needed to validate our findings and determine whether serum tumor markers have prognostic value or predict progressive CTD–ILD.