bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inbreeding and inbreeding avoidance in wild giant pandas
Authors: Hu Yibo , Nie Yonggang , Wei Wei , Ma Tianxiao , Van Horn Russell , Zheng Xiaoguang , Swaisgood Ronald R. , Zhou Zhixin , Zhou Wenliang , Yan Li , Zhang Zejun , Wei Fuwen 
Published: August 2017

AbstractInbreeding can have negative consequences on population and individual fitness, which could be counteracted by inbreeding avoidance mechanisms. However, the inbreeding risk and inbreeding avoidance mechanisms in endangered species are less studied. The giant panda, a solitary and threatened species, lives in many small populations and suffers from habitat fragmentation, which may aggravate the risk of inbreeding. Here, we performed long‐term observations of reproductive behaviour, sampling of mother–cub pairs and large‐scale genetic analyses on wild giant pandas. Moderate levels of inbreeding were found in 21.1% of mating pairs, 9.1% of parent pairs and 7.7% of panda cubs, but no high‐level inbreeding occurred. More significant levels of inbreeding may be avoided passively by female‐biased natal dispersal rather than by breeding dispersal or active relatedness‐based mate choice mechanisms. The level of inbreeding in giant pandas is greater than expected for a solitary mammal and thus warrants concern for potential inbreeding depression, particularly in small populations isolated by continuing habitat fragmentation, which will reduce female dispersal and increase the risk of inbreeding.
Agent‐based computational model of retinal angiogenesis simulates microvascular network morphology as a function of pericyte coverage
Authors: Walpole Joseph , Mac Gabhann Feilim , Peirce Shayn M , Chappell John C 
Published: August 2017

AbstractObjectiveDefine a role for perivascular cells during developmental retinal angiogenesis in the context of EC Notch1‐DLL4 signaling at the multicellular network level.MethodsThe retinal vasculature is highly sensitive to growth factor‐mediated intercellular signaling. Although EC signaling has been explored in detail, it remains unclear how PC function to modulate these signals that lead to a diverse set of vascular network patterns in health and disease. We have developed an ABM of retinal angiogenesis that incorporates both ECs and PCs to investigate the formation of vascular network patterns as a function of pericyte coverage. We use our model to test the hypothesis that PC modulate Notch1‐DLL4 signaling in endothelial cell‐endothelial cell interactions.ResultsAgent‐based model (ABM) simulations that include PCs more accurately predict experimentally observed vascular network morphologies than simulations that lack PCs, suggesting that PCs may influence sprouting behaviors through physical blockade of endothelial intercellular connections.ConclusionsThis study supports a role for PCs as a physical buffer to signal propagation during vascular network formation—a barrier that may be important for generating healthy microvascular network patterns.
The inositol pyrophosphate synthesis pathway in Trypanosoma brucei is linked to polyphosphate synthesis in acidocalcisomes
Authors: Cordeiro Ciro D. , Saiardi Adolfo , Docampo Roberto 
Published: August 2017

SummaryInositol pyrophosphates are novel signaling molecules possessing high‐energy pyrophosphate bonds and involved in a number of biological functions. Here, we report the correct identification and characterization of the kinases involved in the inositol pyrophosphate biosynthetic pathway in Trypanosoma brucei: inositol polyphosphate multikinase (TbIPMK), inositol pentakisphosphate 2‐kinase (TbIP5K) and inositol hexakisphosphate kinase (TbIP6K). TbIP5K and TbIP6K were not identifiable by sequence alone and their activities were validated by enzymatic assays with the recombinant proteins or by their complementation of yeast mutants. We also analyzed T. brucei extracts for the presence of inositol phosphates using polyacrylamide gel electrophoresis and high‐performance liquid chromatography. Interestingly, we could detect inositol phosphate (IP), inositol 4,5‐bisphosphate (IP2), inositol 1,4,5‐trisphosphate (IP3), and inositol hexakisphosphate (IP6) in T. brucei different stages. Bloodstream forms unable to produce inositol pyrophosphates, due to downregulation of TbIPMK expression by conditional knockout, have reduced levels of polyphosphate and altered acidocalcisomes. Our study links the inositol pyrophosphate pathway to the synthesis of polyphosphate in acidocalcisomes, and may lead to better understanding of these organisms and provide new targets for drug discovery.
A sigh of relief or a sigh of expected relief: Sigh rate in response to dyspnea relief
Authors: Vlemincx Elke , Meulders Michel , Luminet Olivier 
Published: August 2017

AbstractResearch has suggested that sighs may serve a regulatory function during stress and emotions by facilitating relief. Evidence supports the hypotheses that sighs both express and induce relief from stress. To explore the potential role of sighs in the regulation of symptoms, the present study aimed to investigate the relationship between sighs and relief of symptoms, and relief of dyspnea, specifically. Healthy volunteers participated in two studies (N = 44, N = 47) in which dyspnea was induced by mild (10 cmH2O/l/s) or high (20 cmH20/l/s) inspiratory resistances. Dyspnea relief was induced by the offset of the inspiratory resistances (transitions from high and mild inspiratory resistance to no resistance). Control comparisons included dyspnea increases (transitions from no or mild inspiratory resistance to high inspiratory resistance) and dyspnea continuations (continuations of either no resistance or a high resistance). In Experiment 1, dyspnea levels were cued. In Experiment 2, no cues were provided. Sigh rate during dyspnea relief was significantly higher compared to control conditions, and sigh rate increased as self‐reported dyspnea decreased. Additionally, sigh rate was higher during cued dyspnea relief compared to noncued dyspnea relief. These results suggest that sighs are important markers of dyspnea relief. Moreover, sighs may importantly express dyspnea relief, as they are related to experiential dyspnea decreases and occur more frequently during expected dyspnea relief. These findings suggest that sighs may not only be important in the regulation of stress and emotions, but also may be functional in the regulation of dyspnea.
Seed Potatoes, Virus Management, and the Nonadoption of an Agricultural Innovation
Authors: Beissinger Abby , Goldberger Jessica R. , Benedict Christopher A. , Inglis Debra Ann 
Published: August 2017

AbstractBeginning in 2012, seed potatoes in Washington State were associated with an outbreak of Potato virus Y (PVY), one of the oldest known plant viruses. The PVY outbreak seriously impacted commercial potato growers, who unknowingly purchased infected seed potatoes. Commercial potato growers, university researchers, and extension personnel blamed Washington seed potato growers for the PVY outbreak. Drawing on the literature about perceptions of innovation attributes, nonadoption of agricultural innovations, and farm‐level disease management, we offer a broader perspective on PVY management among Washington seed potato growers. We explore the reasons behind seed potato growers' nonadoption of a specific innovation that has the potential to protect potatoes from PVY problems. We argue that seed potato growers approach PVY management in logical and intentional ways, and have distinct reasons for choosing not to adopt certain PVY management practices. Our study contributes to scholarship on the perceived attributes and nonadoption of agricultural innovations, as well as interdisciplinary work on plant disease management. A better understanding of PVY management decision making can help efforts to ensure agricultural biosecurity, maintain crop quality and yield, and prevent economic losses within the potato industry in Washington State, the second largest producer of potatoes in the United States.
Proximity, Prosperity, and Participation: Examining Access to Postsecondary Education among Youth in Canada's Provincial North
Authors: Zarifa David , Hango Darcy , Pizarro Milian Roger 
Published: August 2017

AbstractDespite increased proportions of students attending some form of postsecondary education (PSE), some social groups continue to face significant barriers and encounter difficulties making the transition. Previous research suggests that proximity to postsecondary institutions may have a positive impact on PSE participation rates, even more so for lower‐ and middle‐income families. We know comparatively less, however, about how these processes operate for social groups in varied social and economic contexts. In Canada, many highly ranked, prestigious universities and colleges (with greater arrays of fields) tend to be clustered in large, urban centers, and in the southernmost parts of Canadian provinces, but it is not clear whether these differences impact PSE outcomes. Drawing on cycles 1 to 4 of Statistics Canada's Youth in Transition Survey (YITS−Cohort A), our findings reveal that individuals from the northernmost parts of Canadian provinces do experience difficulties accessing various types of PSE (and in the timing of doing so). Moreover, our results suggest that much of these location effects are attributable to not only economic differences in terms of parental income but also cultural and dispositional differences related to parental education and their aspirations for their children's education.
Cooperative Federalism and Fair Housing Enforcement*
Authors: Bullock Charles S. , Lamb Charles M. , Wilk Eric M. 
Published: August 2017

ObjectiveWe investigate how three levels of government have enforced the Fair Housing Act as a cooperative federalism program.MethodsBased on data obtained from the Department of Housing and Urban Development (HUD), we test a multivariate fixed effects logistic regression model.ResultsFirst, the Fair Housing Act's substantial equivalency requirement and HUD's Fair Housing Assistance Program have enabled state and local civil rights agencies to play an essential role in enforcing national fair housing policy. Second, there is little difference in the extent to which federal, state, and local agencies provide outcomes favorable to fair housing complainants. Third, local agencies have been most likely to provide favorable outcomes in recent years.ConclusionEncouraging state and particularly local agencies to participate more actively in fair housing enforcement would strengthen American federalism without significantly affecting complainants’ outcomes. Research involving effectiveness and efficiency in fair housing enforcement reinforces this argument.
The present perfect in Irish English
Authors: KIRK JOHN M. 
Published: August 2017

ABSTRACTThis article begins with an introduction to language corpora and the approach to linguistic description arising from corpus linguistic approaches to the description of varieties. It stresses the importance of a well‐balanced, representative corpus for general language description and demonstrates the benefits of a quantitative as well as a qualitative approach. It introduces the International Corpus of English: Ireland Component (ICE‐Ireland) and presents a case study of the present perfect, with particular reference to the HAVE + –ed participle construction, the after perfect, the medial‐object perfect, the BE perfect, the extended‐now perfect, and the use of present and past tense with perfective meanings. Throughout the case study, the article underlines the importance of quantitative patterns in the data uncovered by a corpus linguistics approach.
The language of Irish films
Authors: WALSHE SHANE 
Published: August 2017

ABSTRACTThis study compares evidence taken from two corpora of Irish films (40 southern and 40 northern Irish films) with data from the northern and southern spoken components of ICE‐Ireland. The results of the investigation indicate that there are numerous parallels in the findings regarding not only the relative frequency of feature occurrences, but also the contexts in which they can occur. It is hoped that, by proving the validity of studying variation in Irish English using data taken from Irish feature films, other scholars may be encouraged to do likewise for other world Englishes, such as Indian English in Bollywood or Nigerian English in Nollywood.
Molecular Tests That Target the RTX Locus Do Not Distinguish between Kingella kingae and the Recently Described Kingella negevensis Species
Authors: El Houmami Nawal , Bzdrenga Janek , Durand Guillaume André , Minodier Philippe , Seligmann Hervé , Prudent Elsa , Bakour Sofiane , Bonacorsi Stéphane , Raoult Didier , Yagupsky Pablo , Fournier Pierre-Edouard 
Published: August 2017

ABSTRACT

Kingella kingae
is an important invasive pathogen in early childhood. The organism elaborates an RTX toxin presumably restricted to this species. Consequently, real-time quantitative PCR (qPCR) assays targeting the RTX locus have been developed in recent years and are gaining increasing use for the molecular diagnosis of
K. kingae
infections. However, the present study shows that
Kingella negevensis
, a
Kingella
species newly identified in young children, harbors an identical
Kingella
RTX locus, raising the question of whether
K. negevensis
can be misidentified as
K. kingae
by clinical microbiology laboratories.
In silico
comparison of
Kingella
sp. RTX and
groEL
genes and
in vitro
studies provided evidence that targeting the
rtxA
and
rtxB
genes could not differentiate between strains of
K. kingae
and
K. negevensis
, whereas targeting the
groEL
gene could. This prompted the design of a highly specific and sensitive qPCR assay targeting
K. negevensis groEL
(
kngroEL
). Ninety-nine culture-negative osteoarticular specimens from 99 children younger than 4 years of age were tested with a conventional 16S rRNA gene-based broad-range PCR assay and
Kingella
-specific
rtxB
,
K. kingae
-specific
groEL
(
kkgroEL
), and
kngroEL
qPCR assays. Forty-two specimens were
rtxB
positive, including 41 that were also
kkgroEL
positive and 1 (the remaining one) that was
kngroEL
positive. Thus, this study discloses an invasive infection caused by
K. negevensis
in humans and demonstrates that targeting the RTX locus cannot be used for the formal diagnosis of
K. kingae
infections. These findings stress the need for further studies on the epidemiology of asymptomatic carriage and invasive infections caused by
K. negevensis
in humans.
Pathogenicity Locus, Core Genome, and Accessory Gene Contributions to
Clostridium difficile
Virulence
Authors: Lewis Brittany B. , Carter Rebecca A. , Ling Lilan , Leiner Ingrid , Taur Ying , Kamboj Mini , Dubberke Erik R. , Xavier Joao , Pamer Eric G. 
Published: August 2017

ABSTRACT

Clostridium difficile
is a spore-forming anaerobic bacterium that causes colitis in patients with disrupted colonic microbiota. While some individuals are asymptomatic
C. difficile
carriers, symptomatic disease ranges from mild diarrhea to potentially lethal toxic megacolon. The wide disease spectrum has been attributed to the infected host’s age, underlying diseases, immune status, and microbiome composition. However, strain-specific differences in
C. difficile
virulence have also been implicated in determining colitis severity. Because patients infected with
C. difficile
are unique in terms of medical history, microbiome composition, and immune competence, determining the relative contribution of
C. difficile
virulence to disease severity has been challenging, and conclusions regarding the virulence of specific strains have been inconsistent. To address this, we used a mouse model to test 33 clinical
C. difficile
strains isolated from patients with disease severities ranging from asymptomatic carriage to severe colitis, and we determined their relative
in vivo
virulence in genetically identical, antibiotic-pretreated mice. We found that murine infections with
C. difficile
clade 2 strains (including multilocus sequence type 1/ribotype 027) were associated with higher lethality and that
C. difficile
strains associated with greater human disease severity caused more severe disease in mice. While toxin production was not strongly correlated with
in vivo
colonic pathology, the ability of
C. difficile
strains to grow in the presence of secondary bile acids was associated with greater disease severity. Whole-genome sequencing and identification of core and accessory genes identified a subset of accessory genes that distinguish high-virulence from lower-virulence
C. difficile
strains.

IMPORTANCE
Clostridium difficile
is an important cause of hospital-associated intestinal infections, and recent years have seen an increase in the number and severity of cases in the United States. A patient’s antibiotic history, immune status, and medical comorbidities determine, in part, the severity of
C. difficile
infection. The relative virulence of different clinical
C. difficile
strains, although postulated to determine disease severity in patients, has been more difficult to consistently associate with mild versus severe colitis. We tested 33 distinct clinical
C. difficile
isolates for their ability to cause disease in genetically identical mice and found that
C. difficile
strains belonging to clade 2 were associated with higher mortality. Differences in survival were not attributed to differences in toxin production but likely resulted from the distinct gene content in the various clinical isolates.
Contrast sensitivity to spatial gratings in moderate and dim light conditions in patients with diabetes in the absence of diabetic retinopathy
Authors: Safi Sare , Rahimi Anoushiravan , Raeesi Afsaneh , Safi Hamid , Aghazadeh Amiri Mohammad , Malek Mojtaba , Yaseri Mehdi , Haeri Mohammad , Middleton Frank A , Solessio Eduardo , Ahmadieh Hamid 
Published: August 2017

ObjectiveTo evaluate the ability of contrast sensitivity (CS) to discriminate loss of visual function in diabetic subjects with no clinical signs of retinopathy relative to that of normal subjects.Research design and methodsIn this prospective cross-sectional study, we measured CS in 46 diabetic subjects with a mean age of 48±6 years, a best-corrected visual acuity of 20/20 and no signs of diabetic retinopathy. The CS in these subjects was compared with CS measurements in 46 normal control subjects at four spatial frequencies (3, 6, 12, 18 cycles per degree) under moderate (500 lux) and dim (less than 2 lux) background light conditions.ResultsCS was approximately 0.16 log units lower in patients with diabetes relative to controls both in moderate and in dim background light conditions. Logistic regression classification and receiver operating characteristic curve analysis indicated that CS analysis using two light conditions was more accurate (0.78) overall compared with CS analysis using only a single illumination condition (accuracy values were 0.67 and 0.70 in moderate and dim light conditions, respectively).ConclusionsOur results showed that patients with diabetes without clinical signs of retinopathy exhibit a uniform loss in CS at all spatial frequencies tested. Measuring the loss in CS at two spatial frequencies (3 and 6 cycles per degree) and two light conditions (moderate and dim) is sufficiently robust to classify diabetic subjects with no retinopathy versus control subjects.
High prevalence of CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations
Authors: Shoemark Amelia , Moya Eduardo , Hirst Robert A , Patel Mitali P , Robson Evelyn A , Hayward Jane , Scully Juliet , Fassad Mahmoud R , Lamb William , Schmidts Miriam , Dixon Mellisa , Patel-King Ramila S , Rogers Andrew V , Rutman Andrew , Jackson Claire L , Goggin Patricia , Rubbo Bruna , Ollosson Sarah , Carr Siobhán , Walker Woolf , Adler Beryl , Loebinger Michael R , Wilson Robert , Bush Andrew , Williams Hywel , Boustred Christopher , Jenkins Lucy , Sheridan Eamonn , Chung Eddie M K , Watson Christopher M , Cullup Thomas , Lucas Jane S , Kenia Priti , O’Callaghan Christopher , King Stephen M , Hogg Claire , Mitchison Hannah M 
Published: August 2017

RationalePrimary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of primary ciliary dyskinesia in the UK South Asian population is 1:2265. Early, accurate diagnosis is key to implementing appropriate management but clinical diagnostic tests can be equivocal.ObjectivesTo determine the importance of genetic screening for primary ciliary dyskinesia in a UK South Asian population with a typical clinical phenotype, where standard testing is inconclusive.MethodsNext-generation sequencing was used to screen 86 South Asian patients who had a clinical history consistent with primary ciliary dyskinesia. The effect of a CCDC103 p.His154Pro missense variant compared with other dynein arm-associated gene mutations on diagnostic/phenotypic variability was tested. CCDC103 p.His154Pro variant pathogenicity was assessed by oligomerisation assay.ResultsSixteen of 86 (19%) patients carried a homozygous CCDC103 p.His154Pro mutation which was found to disrupt protein oligomerisation. Variable diagnostic test results were obtained including normal nasal nitric oxide levels, normal ciliary beat pattern and frequency and a spectrum of partial and normal dynein arm retention. Fifteen (94%) patients or their sibling(s) had situs inversus suggesting CCDC103 p.His154Pro patients without situs inversus are missed.ConclusionsThe CCDC103 p.His154Pro mutation is more prevalent than previously thought in the South Asian community and causes primary ciliary dyskinesia that can be difficult to diagnose using pathology-based clinical tests. Genetic testing is critical when there is a strong clinical phenotype with inconclusive standard diagnostic tests.
Amiloride, An Old Diuretic Drug, Is a Potential Therapeutic Agent for Multiple Myeloma
Authors: Rojas Elizabeta A. , Corchete Luis Antonio , San-Segundo Laura , Martínez-Blanch Juan F. , Codoñer Francisco M. , Paíno Teresa , Puig Noemí , García-Sanz Ramón , Mateos María Victoria , Ocio Enrique M. , Misiewicz-Krzeminska Irena , Gutiérrez Norma C. 
Published: August 2017

Abstract
Purpose: The search for new drugs that control the continuous relapses of multiple myeloma is still required. Here, we report for the first time the potent antimyeloma activity of amiloride, an old potassium-sparing diuretic approved for the treatment of hypertension and edema due to heart failure.
Experimental Design: Myeloma cell lines and primary samples were used to evaluate cytotoxicity of amiloride. In vivo studies were carried out in a xenograft mouse model. The mechanisms of action were investigated using RNA-Seq experiments, qRT-PCR, immunoblotting, and immunofluorescence assays.
Results: Amiloride-induced apoptosis was observed in a broad panel of multiple myeloma cell lines and in a xenograft mouse model. Moreover, amiloride also had a synergistic effect when combined with dexamethasone, melphalan, lenalidomide, and pomalidomide. RNA-Seq experiments showed that amiloride not only significantly altered the level of transcript isoforms and alternative splicing events, but also deregulated the spliceosomal machinery. In addition, disruption of the splicing machinery in immunofluorescence studies was associated with the inhibition of myeloma cell viability after amiloride exposure. Although amiloride was able to induce apoptosis in myeloma cells lacking p53 expression, activation of p53 signaling was observed in wild-type and mutated TP53 cells after amiloride exposure. On the other hand, we did not find a significant systemic toxicity in mice treated with amiloride.
Conclusions: Overall, our results demonstrate the antimyeloma activity of amiloride and provide a mechanistic rationale for its use as an alternative treatment option for relapsed multiple myeloma patients, especially those with 17p deletion or TP53 mutations that are resistant to current therapies. Clin Cancer Res; 23(21); 6602–15. ©2017 AACR.