bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue Localization and Variation of Major Symbionts in Haemaphysalis longicornis, Rhipicephalus haemaphysaloides, and Dermacentor silvarum in China
Authors: Wang Mengfei , Zhu Dan , Dai Jianfeng , Zhong Zhengwei , Zhang Yi , Wang Jingwen 
Published: March 2018

ABSTRACT

Ticks are important disease vectors, as they transmit a variety of human and animal pathogens worldwide. Symbionts that coevolved with ticks confer crucial benefits to their host in nutrition metabolism, fecundity, and vector competence. Although over 100 tick species have been identified in China, general information on tick symbiosis is limited. Here, we visualized the tissue distribution of
Coxiella
sp. and
Rickettsia
sp. in lab-reared
Haemaphysalis longicornis
and
Rhipicephalus haemaphysaloides
by fluorescent
in situ
hybridization. We found that
Coxiella
sp. colonized exclusively the Malpighian tubules and ovaries of
H. longicornis
, while
Rickettsia
sp. additionally colonized the midgut of
R. haemaphysaloides
. We also investigated the population structure of microbiota in
Dermacentor silvarum
ticks collected from Inner Mongolia, China, and found that
Coxiella
,
Rickettsia
, and
Pseudomonas
are the three dominant genera. No significant difference in microbiota composition was found between male and female
D. silvarum
ticks. We again analyzed the tissue localization of
Coxiella
sp. and
Rickettsia
sp. and found that they displayed tissue tropisms similar to those in
R. haemaphysaloides
, except that
Rickettsia
sp. colonized the nuclei of spermatids instead of ovaries in
D. silvarum
. Altogether, our results suggest that
Coxiella
sp. and
Rickettsia
sp. are the main symbionts in the three ticks and reside primarily in midgut, Malpighian tubules, and reproductive tissues, but their tissue distribution varies in association with species and sexes.

IMPORTANCE
Tick-borne diseases constitute a major public health burden, as they are increasing in frequency and severity worldwide. The presence of symbionts helps ticks to metabolize nutrients, promotes fecundity, and influences pathogen infections. Increasing numbers of tick-borne pathogens have been identified in China; however, knowledge of native ticks, especially tick symbiosis, is limited. In this study, we analyze the distribution of
Coxiella
sp. and
Rickettsia
sp. in tissues of laboratory-reared
Haemaphysalis longicornis
and
Rhipicephalus haemaphysaloides
and field-collected
Dermacentor silvarum
. We found that the localization patterns of
Coxiella
sp. in three Chinese tick species were similar to those of other tick species. We also found a previously undefined intracellular localization of
Rickettsia
sp. in tick midgut and spermatids. In addition, we demonstrate that tissue tropisms of symbionts vary between species and sexes. Our findings provide new insights into the tissue localization of symbionts in native Chinese ticks and pave the way for further understanding of their functional capabilities and symbiotic interactions with ticks.
The Adjuvant Bordetella Colonization Factor A Attenuates Alum-Induced Th2 Responses and Enhances Bordetella pertussis Clearance from Mouse Lungs
Authors: Jennings-Gee Jamie , Quataert Sally , Ganguly Tridib , D'Agostino Ralph , Deora Rajendar , Dubey Purnima 
Published: March 2018

ABSTRACTThe reemergence of pertussis or whooping cough in several countries highlights the need for better vaccines. Acellular pertussis vaccines (aPV) contain alum as the adjuvant and elicit Th2-biased immune responses that are less effective in protecting against infection than the reactogenic whole-cell pertussis vaccines (wPV), which elicit primarily a Th1/Th17 response. An important goal for the field is to devise aPV that will induce immune responses similar to those of wPV. We show that Bordetella colonization factor A (BcfA), an outer membrane protein fromBordetella bronchiseptica, has strong adjuvant function and elicits cellular and humoral immune responses to heterologous andBordetella pertussisantigens. Addition of BcfA to a commercial aPV resulted in greater reduction ofB. pertussisnumbers from the lungs than that elicited by aPV alone. The more-efficient pathogen clearance was accompanied by increased interleukin-17 (IL-17) and reduced IL-5 and an increased ratio of IgG2/IgG1 antibodies. Thus, our results suggest that BcfA improves aPV-induced responses by modifying the alum-induced Th2-biased aPV response toward Th1/Th17. A redesigned aPV containing BcfA may allow better control of pertussis reemergence by reshaping immune responses to resemble those elicited by wPV immunization.
Antigenic Variation in
Streptococcus pneumoniae
PspC Promotes Immune Escape in the Presence of Variant-Specific Immunity
Authors: Georgieva M. , Kagedan L. , Lu Ying-Jie , Thompson C. M. , Lipsitch M. 
Published: March 2018

ABSTRACT

Genomic analysis reveals extensive sequence variation and hot spots of recombination in surface proteins of
Streptococcus pneumoniae
. While this phenomenon is commonly attributed to diversifying selection by host immune responses, there is little mechanistic evidence for the hypothesis that diversification of surface protein antigens produces an immune escape benefit during infection with
S. pneumoniae
. Here, we investigate the biological significance of sequence variation within the
S. pneumoniae
cell wall-associated pneumococcal surface protein C (PspC) protein antigen. Using
pspC
allelic diversity observed in a large pneumococcal collection, we produced variant-specific protein constructs that span the sequence variability within the
pspC
locus. We show that antibodies raised against these PspC constructs are variant specific and prevent association between PspC and the complement pathway mediator, human factor H. We found that PspC variants differ in their capacity to bind factor H, suggesting that sequence variation within
pspC
reflects differences in biological function. Finally, in an antibody-dependent opsonophagocytic assay,
S. pneumoniae
expressing a PspC variant matching the antibody specificity was killed efficiently. In contrast, killing efficacy was not evident against
S. pneumoniae
expressing mismatched PspC variants. Our data suggest that antigenic variation within the PspC antigen promotes immune evasion and could confer a fitness benefit during infection.

IMPORTANCE
Loci encoding surface protein antigens in
Streptococcus pneumoniae
are highly polymorphic. It has become a truism that these polymorphisms are the outcome of selective pressure on
S. pneumoniae
to escape host immunity. However, there is little mechanistic evidence to support the hypothesis that diversifying protein antigens produces a benefit for the bacteria. Using the highly diverse
pspC
locus, we have now characterized the functional and immune implications of sequence diversity within the PspC protein. We have characterized the spectrum of biological function among diverse PspC variants and show that
pspC
sequence diversity reflects functional differences. Further, we show that sequence variation in PspC confers an immune escape benefit in the presence of anti-PspC variant-specific immunity. Overall, the results of our studies provide insights into the functional implications of protein sequence diversity and the role of variant-specific immunity in its maintenance.
Antibody-Mediated Killing of Carbapenem-Resistant ST258
Klebsiella pneumoniae
by Human Neutrophils
Authors: Kobayashi Scott D. , Porter Adeline R. , Freedman Brett , Pandey Ruchi , Chen Liang , Kreiswirth Barry N. , DeLeo Frank R. 
Published: March 2018

ABSTRACT

Carbapenem-resistant
Klebsiella pneumoniae
is a problem worldwide. A carbapenem-resistant
K. pneumoniae
lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils. We first demonstrated that an isogenic
wzy
deletion strain is significantly more susceptible to killing by human heparinized blood, serum, and neutrophils than a wild-type ST258 strain. Consistent with the importance of capsule as an immune evasion molecule, rabbit immune serum and purified IgG specific for ST258 capsule polysaccharide type 2 (CPS2) enhanced killing by human blood and serum
in vitro
. Moreover, antibodies specific for CPS2 promoted phagocytosis and killing of ST258 by human neutrophils. Collectively, our findings suggest that ST258 CPS2 is a viable target for immunoprophylactics and/or therapeutics.

IMPORTANCE
Infections caused by carbapenem-resistant
K. pneumoniae
are difficult to treat, and mortality is high. New prophylactic approaches and/or therapeutic measures are needed to prevent or treat infections caused by these multidrug-resistant bacteria. A strain of carbapenem-resistant
K. pneumoniae
, classified by multilocus sequence typing as ST258, is present in many regions of the world and is the most prominent carbapenem-resistant
K. pneumoniae
lineage in the United States. Here we show that rabbit antibodies specific for capsule polysaccharide of ST258 significantly enhance human serum bactericidal activity and promote phagocytosis and killing of this pathogen by human neutrophils. These studies have provided strong support for the idea that development of an immunotherapy (vaccine) for carbapenem-resistant
K. pneumoniae
infections is feasible and has merit.
Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to InvasiveChlamydia trachomatisBiovars
Authors: Patton Michael John , Chen Chih-Yu , Yang Chunfu , McCorrister Stuart , Grant Chris , Westmacott Garrett , Yuan Xin-Yong , Ochoa Estela , Fariss Robert , Whitmire William M. , Carlson John H. , Caldwell Harlan D. , McClarty Grant 
Published: March 2018

ABSTRACTChlamydia trachomatisis an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease.C. trachomatisisolates are classified into 2 biovars—lymphogranuloma venereum (LGV) and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. TheC. trachomatisplasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-curedC. trachomatisserovars A and D (trachoma biovar), a L2 serovar (LGV biovar), and the L2 serovar transformed with a plasmid containing a nonsense mutation inpgp4to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within bothC. trachomatisbiovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF) for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature.IMPORTANCETheChlamydia trachomatisplasmid is an important virulence factor in the pathogenesis of chlamydial infection. It is known that plasmid protein 4 (Pgp4) functions in the transcriptional regulation of the plasmid virulence protein 3 (Pgp3) and multiple chromosomal loci of unknown function. Since many gene regulatory functions can be post-transcriptional, we undertook a comparative proteomic analysis to better understand the plasmid’s role in chlamydial and host protein expression. We report that Pgp4 is a potent and specific master positive regulator of a common core of plasmid and chromosomal virulence genes shared by multipleC. trachomatisserovars. Notably, we show that the plasmid is a negative regulator of the expression of the chlamydial virulence factor CPAF. The plasmid regulation of CPAF is independent of Pgp4 and restricted to aC. trachomatismacrophage-tropic strain. These findings are important because they define a previously unknown role for the plasmid in the pathophysiology of invasive chlamydial infection.
On average, a professional rugby union player is more likely than not to sustain a concussion after 25 matches
Authors: Rafferty James , Ranson Craig , Oatley Giles , Mostafa Mohamed , Mathema Prabhat , Crick Tom , Moore Isabel S 
Published: March 2018

ObjectivesTo investigate concussion injury rates, the likelihood of sustaining concussion relative to the number of rugby union matches and the risk of subsequent injury following concussion.MethodsA four-season (2012/2013–2015/2016) prospective cohort study of injuries in professional level (club and international) rugby union. Incidence (injuries/1000 player-match-hours), severity (days lost per injury) and number of professional matches conferring a large risk of concussion were determined. The risk of injury following concussion was assessed using a survival model.ResultsConcussion incidence increased from 7.9 (95% CI 5.1 to 11.7) to 21.5 injuries/1000 player-match-hours (95% CI 16.4 to 27.6) over the four seasons for combined club and international rugby union. Concussion severity was unchanged over time (median: 9 days). Players were at a greater risk of sustaining a concussion than not after an exposure of 25 matches (95% CI 19 to 32). Injury risk (any injury) was 38% greater (HR 1.38; 95% CI 1.21 to 1.56) following concussion than after a non-concussive injury. Injuries to the head and neck (HR 1.34; 95% CI 1.06 to 1.70), upper limb (HR 1.59; 95% CI 1.19 to 2.12), pelvic region (HR 2.07; 95% CI 1.18 to 3.65) and the lower limb (HR 1.60; 95% CI 1.21 to 2.10) were more likely following concussion than after a non-concussive injury.ConclusionConcussion incidence increased, while severity remained unchanged, during the 4 years of this study. Playing more than 25 matches in the 2015/2016 season meant that sustaining concussion was more likely than not sustaining concussion. The 38% greater injury risk after concussive injury (compared with non-concussive injury) suggests return to play protocols warrant investigation.
Feasibility of a blended group treatment (bGT) for major depression: uncontrolled interventional study in a university setting
Authors: Schuster Raphael , Fichtenbauer Isabelle , Sparr Verena Maria , Berger Thomas , Laireiter Anton-Rupert 
Published: March 2018

ObjectiveThis study investigated the feasibility of a novel blended (face-to-face and computer-based) group intervention for the reduction of depressive symptoms in major depression.DesignPatient-centred uncontrolled interventional study.SettingUniversity setting in a general community sample. A multimodal recruitment strategy (public health centres and public areas) was applied.ParticipantsBased on independent interviews, 26 participants, diagnosed with major depressive disorder (81% female; 23% comorbidity >1 and 23% comorbidity >2), entered treatment.InterventionAcceptance and mindfulness based, as well as self-management and resource-oriented psychotherapy principles served as the theoretical basis for the low-threshold intervention. The blended format included face-to-face sessions, complemented with multimedia presentations and a platform featuring videos, online work sheets, an unguided group chat and remote therapist–patient communication.Main outcome measuresThe Center for Epidemiological Studies-Depression scale and the 12-item General Health Questionnaire.ResultsLarge to very large within group effect sizes were found on self-reported depression (F(2, 46.37)=25.69, p<0.001;d=1.80), general health (F(2,46.73)=11.47, p<0.001;d=1.32), personal resources (F(2,43.36)=21.17, p<0.001;d=0.90) and mindfulness (F(2,46.22)=9.40, p<0.001;d=1.12) after a follow-up period of 3 months. Treatment satisfaction was high, and 69% ranked computer and multimedia use as a therapeutic factor. Furthermore, participants described treatment intensification as important advantage of the blended format. Half of the patients (48%) would have preferred more time for personal exchange.ConclusionThe investigated blended group format seems feasible for the reduction of depressive symptoms in major depression. The development of blended interventions can benefit from assuring that highly structured treatments actually meet patients’ needs. As a next step, the intervention should be tested in comparative trials in routine care.Trial registration numberDRKS00010894; Pre-results.
Scholarly-Judicial Dialogue in International Law
Authors: Helmersen Sondre Torp 
Published: March 2018

Abstract
Much has been written about “judicial dialogue” in international law. This article explores a related, but much less studied, concept: “dialogue” between judges and scholars. Through examples taken from the International Court of Justice, the article proposes a classification of such dialogue and argues that it plays an important role in the development of international law.
Surface Irradiances of Edition 4.0 Clouds and the Earth’s Radiant Energy System (CERES) Energy Balanced and Filled (EBAF) Data Product
Authors: Kato Seiji , Rose Fred G. , Rutan David A. , Thorsen Tyler J. , Loeb Norman G. , Doelling David R. , Huang Xianglei , Smith William L. , Su Wenying , Ham Seung-Hee 
Published: March 2018

Abstract
The algorithm to produce the Clouds and the Earth’s Radiant Energy System (CERES) Edition 4.0 (Ed4) Energy Balanced and Filled (EBAF)-surface data product is explained. The algorithm forces computed top-of-atmosphere (TOA) irradiances to match with Ed4 EBAF-TOA irradiances by adjusting surface, cloud, and atmospheric properties. Surface irradiances are subsequently adjusted using radiative kernels. The adjustment process is composed of two parts: bias correction and Lagrange multiplier. The bias in temperature and specific humidity between 200 and 500 hPa used for the irradiance computation is corrected based on observations by Atmospheric Infrared Sounder (AIRS). Similarly, the bias in the cloud fraction is corrected based on observations by Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) and CloudSat. Remaining errors in surface, cloud, and atmospheric properties are corrected in the Lagrange multiplier process. Ed4 global annual mean (January 2005 through December 2014) surface net shortwave (SW) and longwave (LW) irradiances increase by 1.3 W m−2 and decrease by 0.2 W m−2, respectively, compared to EBAF Edition 2.8 (Ed2.8) counterparts (the previous version), resulting in an increase in net SW + LW surface irradiance of 1.1 W m−2. The uncertainty in surface irradiances over ocean, land, and polar regions at various spatial scales are estimated. The uncertainties in all-sky global annual mean upward and downward shortwave irradiance are 3 and 4 W m−2, respectively, and the uncertainties in upward and downward longwave irradiance are 3 and 6 W m−2, respectively. With an assumption of all errors being independent, the uncertainty in the global annual mean surface LW + SW net irradiance is 8 W m−2.
Diurnal Cycle of Surface Air Temperature within China in Current Reanalyses: Evaluation and Diagnostics
Authors: Du Jizeng , Wang Kaicun , Wang Jiankai , Jiang Shaojing , Zhou Chunlüe 
Published: March 2018

Abstract
Diurnal cycle of surface air temperature T is an important metric indicating the feedback of land–atmospheric interaction to global warming, whereas the ability of current reanalyses to reproduce its variation had not been assessed adequately. Here, we evaluate the daily maximum temperature Tmax, daily minimum temperature Tmin, and diurnal temperature range (DTR) in five reanalyses based on observations collected at 2253 weather stations over China. Our results show that the reanalyses reproduce Tmin very well; however, except for Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA-2), they substantially underestimate Tmax and DTR by 1.21°–6.84°C over China during the period of 1980–2014. MERRA-2 overestimates Tmax and DTR by 0.35° and 0.81°C, which are closest with observation. The reanalyses are skillful in reproducing the interannual variability of Tmax and Tmin but relatively poor for DTR. All reanalyses underestimate the warming trend of Tmin by 0.13°–0.17°C (10 yr)−1 throughout China during 1980–2014, and underestimate the warming trend of Tmax by 0.24°–0.40°C (10 yr)−1 in northwestern China while overestimating this quantity by 0.18°–0.33°C (10 yr)−1 in southeastern China. These trend biases in Tmax and Tmin introduce a positive trend bias in DTR of 0.01°–0.26°C (10 yr)−1 within China, especially in the north China plain and southeastern China. In the five reanalyses, owing to the sensitivity discrepancies and trend biases, the surface solar radiation Rs and precipitation frequency (PF) are notable deviation sources of the diurnal cycle of air temperature, which explain 31.0%–38.7% (31.9%–37.8%) and 9.8%–22.2% (7.4%–15.3%) of the trend bias in Tmax (DTR) over China, respectively.
The Effect of Housing Demolitions on Crime in Buffalo, New York
Authors: Wheeler Andrew P. , Kim Dae-Young , Phillips Scott W. 
Published: March 2018

Objectives: From 2010 through 2015, the city of Buffalo demolished over 2,000 residences. This study examines whether those demolitions resulted in crime reductions. Methods: Analysis was conducted at microplaces matching demolished parcels to comparable control parcels with similar levels of crime. In addition, spatial panel regression models were estimated at the census tract and quarterly level, taking into account demographic characteristics of neighborhoods. Results: We find that at the microplace level, demolitions cause a steep drop in reported crime at the exact parcel and result in additional crime decreases at buffers of up to 1,000 feet away. At the census tract level, results indicated that demolitions reduced part 1 crimes, but the effect was not statistically significant across different models. Conclusions: While concerns over crime and disorder are common for vacant houses, the evidence that housing demolitions are an effective crime reduction solution is only partially supported by the analyses here. Future research should compare demolitions in reference to other neighborhood revitalization processes.