bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstruction and analysis of a Kluyveromyces marxianus genome-scale metabolic model
Authors: Marcišauskas Simonas , Ji Boyang , Nielsen Jens 
Published: November 2019

Abstract

Background
Kluyveromyces marxianus is a thermotolerant yeast with multiple biotechnological potentials for industrial applications, which can metabolize a broad range of carbon sources, including less conventional sugars like lactose, xylose, arabinose and inulin. These phenotypic traits are sustained even up to 45 °C, what makes it a relevant candidate for industrial biotechnology applications, such as ethanol production. It is therefore of much interest to get more insight into the metabolism of this yeast. Recent studies suggested, that thermotolerance is achieved by reducing the number of growth-determining proteins or suppressing oxidative phosphorylation. Here we aimed to find related factors contributing to the thermotolerance of K. marxianus.

Results
Here, we reported the first genome-scale metabolic model of Kluyveromyces marxianus, iSM996, using a publicly available Kluyveromyces lactis model as template. The model was manually curated and refined to include the missing species-specific metabolic capabilities. The iSM996 model includes 1913 reactions, associated with 996 genes and 1531 metabolites. It performed well to predict the carbon source utilization and growth rates under different growth conditions. Moreover, the model was coupled with transcriptomics data and used to perform simulations at various growth temperatures.

Conclusions
K. marxianus iSM996 represents a well-annotated metabolic model of thermotolerant yeast, which provides a new insight into theoretical metabolic profiles at different temperatures of K. marxianus. This could accelerate the integrative analysis of multi-omics data, leading to model-driven strain design and improvement.
The effect of alignment uncertainty, substitution models and priors in building and dating the mammal tree of life
Authors: Du Yan , Wu Shaoyuan , Edwards Scott V. , Liu Liang 
Published: November 2019

AbstractBackgroundThe flood of genomic data to help build and date the tree of life requires automation at several critical junctures, most importantly during sequence assembly and alignment. It is widely appreciated that automated alignment protocols can yield inaccuracies, but the relative impact of various sources error on phylogenomic analysis is not yet known. This study employs an updated mammal data set of 5162 coding loci sampled from 90 species to evaluate the effects of alignment uncertainty, substitution models, and fossil priors on gene tree, species tree, and divergence time estimation. Additionally, a novel coalescent likelihood ratio test is introduced for comparing competing species trees against a given set of gene trees.ResultsThe aligned DNA sequences of 5162 loci from 90 species were trimmed and filtered using trimAL and two filtering protocols. The final dataset contains 4 sets of alignments - before trimming, after trimming, filtered by a recently proposed pipeline, and further filtered by comparing ML gene trees for each locus with the concatenation tree. Our analyses suggest that the average discordance among the coalescent trees is significantly smaller than that among the concatenation trees estimated from the 4 sets of alignments or with different substitution models. There is no significant difference among the divergence times estimated with different substitution models. However, the divergence dates estimated from the alignments after trimming are more recent than those estimated from the alignments before trimming.ConclusionsOur results highlight that alignment uncertainty of the updated mammal data set and the choice of substitution models have little impact on tree topologies yielded by coalescent methods for species tree estimation, whereas they are more influential on the trees made by concatenation. Given the choice of calibration scheme and clock models, divergence time estimates are robust to the choice of substitution models, but removing alignments deemed problematic by trimming algorithms can lead to more recent dates. Although the fossil prior is important in divergence time estimation, Bayesian estimates of divergence times in this data set are driven primarily by the sequence data.
Increase of reactive oxygen species contributes to growth inhibition by fluconazole in Cryptococcus neoformans
Authors: Dbouk Nadir Hani , Covington Madison Bailey , Nguyen Kenny , Chandrasekaran Srikripa 
Published: November 2019

Abstract

Background
Cryptococcus neoformans, a basidiomycetous yeast, is a fungal pathogen that can colonize the lungs of humans causing pneumonia and fungal meningitis in severely immunocompromised individuals. Recent studies have implied that the antifungal drug fluconazole (FLC) can induce oxidative stress in C. neoformans by increasing the production of reactive oxygen species (ROS), as presence of the antioxidant ascorbic acid (AA) could reverse the inhibitory effects of FLC on C. neoformans. However, in Candida albicans, AA has been shown to stimulate the expression of genes essential for ergosterol biosynthesis. Hence, the contribution of ROS in FLC-mediated growth inhibition remains unclear.

Results
In order to determine whether counteracting ROS generated by FLC in C. neoformans can contribute to diminishing inhibitory effects of FLC, we tested three other antioxidants in addition to AA, namely, pyrrolidine dithiocarbamate (PDTC), retinoic acid (RA), and glutathione (GSH). Our data confirm that there is an increase in ROS in the presence of FLC in C. neoformans. Importantly, all four antioxidants reversed FLC-mediated growth inhibition of C. neoformans to various extents. We further verified the involvement of increased ROS in FLC-mediated growth inhibition by determining that ROS-scavenging proteins, metallothioneins (CMT1 and CMT2), contribute to growth recovery by PDTC and AA during treatment with FLC.

Conclusion
Our study suggests that ROS contributes to FLC-mediated growth inhibition and points to a complex nature of antioxidant-mediated growth rescue in the presence of FLC.
Prevalence and antibiotic susceptibility patterns of enteric bacterial pathogens in human and non-human sources in an urban informal settlement in Cape Town, South Africa
Authors: Kalule John Bosco , Smith Anthony M. , Vulindhlu Mjikisile , Tau Nomsa P. , Nicol Mark P. , Keddy Karen H. , Robberts Lourens 
Published: November 2019

AbstractBackgroundIn light of rampant childhood diarrhoea, this study investigated bacterial pathogens from human and non-human sources in an urban informal settlement.Meat from informal abattoirs (n = 85), river water (n = 64), and diarrheic stool (n = 66) were collected between September 2015 and May 2016. A duplex real-time PCR, gel-based PCR, and CHROMagar™STEC were used to screen Tryptic Soy Broth (TSB) for diarrheicE. coli. Standard methods were used to screen for other selected food and waterborne bacterial pathogens.ResultsPathogens isolated from stool, meat, and surface water includedSalmonella enterica(6, 5, 0%),Plesiomonas shigelloides(9, 0, 17%),Aeromonas sobria(3, 3, 0%),Campylobacter jejuni(5, 5, 0%),Shigella flexneri(17, 5, 0%),Vibrio vulnificus(0, 0, 9%), and diarrheicE. coli(21, 3, 7%) respectively. All the isolates were resistant to trimethoprim–sulphamethoxazole.ConclusionsThere was a high burden of drug resistant diarrheal pathogens in the stool, surface water and meat from informal slaughter. Integrated control measures are needed to ensure food safety and to prevent the spread of drug resistant pathogens in similar settings.
Bacterial co-infection of the respiratory tract in ventilated children with bronchiolitis; a retrospective cohort study
Authors: Wiegers Hanke M. G. , van Nijen Lisa , van Woensel Job B. M. , Bem Reinout A. , de Jong Menno D. , Calis Job C. J. 
Published: November 2019

Abstract

Background
Viral bronchiolitis is the most common cause of respiratory failure requiring invasive ventilation in young children. Bacterial co-infections may complicate and prolong paediatric intensive care unit (PICU) stay. Data on prevalence, type of pathogens and its association with disease severity are limited though. These data are especially important as bacterial co-infections may be treated using antibiotics and could reduce disease severity and duration of PICU stay. We investigated prevalence of bacterial co-infection and its association with disease severity and PICU stay.

Methods
Retrospective cohort study of the prevalence and type of bacterial co-infections in ventilated children performed in a 14-bed tertiary care PICU in The Netherlands. Children less than 2 years of age admitted between December 2006 and November 2014 with a diagnosis of bronchiolitis and requiring invasive mechanical ventilation were included. Tracheal aspirates (TA) and broncho-alveolar lavages (BAL) were cultured and scored based on the quantity of bacteria colony forming units (CFU) as: co-infection (TA > 10^5/BAL > 10^4 CFU), low bacterial growth (TA < 10^5/BAL < 10^4 CFU), or negative (no growth). Duration of mechanical ventilation and PICU stay were collected using medical records and compared against the presence of co-infection using univariate and multivariate analysis.

Results
Of 167 included children 63 (37.7%) had a bacterial co-infection and 67 (40.1%) low bacterial growth. Co-infections occurred within 48 h from intubation in 52 out 63 (82.5%) co-infections. H.influenza (40.0%), S.pneumoniae (27.1%), M.catarrhalis (22.4%), and S.aureus (7.1%) were the most common pathogens. PICU stay and mechanical ventilation lasted longer in children with co-infections than children with negative cultures (9.1 vs 7.7 days, p = 0.04 and 8.1vs 6.5 days, p = 0.02).

Conclusions
In this large study, bacterial co-infections occurred in more than a third of children requiring invasive ventilation for bronchiolitis and were associated with longer PICU stay and mechanical ventilation. These findings support a clinical trial of antibiotics to test whether antibiotics can reduce duration of PICU stay.
Identification of a novel mutation of NOG in family with proximal symphalangism and early genetic counseling
Authors: Ma Cong , Liu Lv , Wang Fang-Na , Tian Hai-Shen , Luo Yan , Yu Rong , Fan Liang-Liang , Li Ya-Li 
Published: November 2019

AbstractBackgroundProximal symphalangism is a rare disease with multiple phenotypes including reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger, as well as hearing loss. At present, at least two types of proximal symphalangism have been identified in the clinic. One is proximal symphalangism-1A (SYM1A), which is caused by genetic variants inNoggin(NOG), another is proximal symphalangism-1B (SYM1B), which is resulted fromGrowth Differentiation Factor 5(GDF5) mutations.Case presentationHere, we reported a Chinese family with symphalangism of the 4th and/or 5th finger and moderate deafness. The proband was a 13-year-old girl with normal intelligence but symphalangism of the 4th finger in the left hand and moderate deafness. Hearing testing and inner ear CT scan suggested that the proband suffered from structural deafness. Family history investigation found that her father (II-3) and grandmother (I-2) also suffered from hearing loss and symphalangism. Target sequencing identified a novel heterozygousNOGmutation, c.690C > G/p.C230W, which was the genetic lesion of the affected family. Bioinformatics analysis and public databases filtering further confirmed the pathogenicity of the novel mutation. Furthermore, we assisted the family to deliver a baby girl who did not carry the mutation by genetic counseling and prenatal diagnosis using amniotic fluid DNA sequencing.ConclusionIn this study, we identified a novelNOGmutation (c.690C > G/p.C230W) by target sequencing and helped the family to deliver a baby who did not carry the mutation. Our study expanded the spectrum ofNOGmutations and contributed to genetic diagnosis and counseling of families with SYM1A.
mHealth communication to strengthen postnatal care in rural areas: a systematic review
Authors: Mbuthia Florence , Reid Marianne , Fichardt Annali 
Published: November 2019

AbstractBackgroundPostnatal care (PNC) in rural areas is characterised by low uptake, with possible effect on maternal and neonatal mortality rates. Mobile health (mHealth) communication has been proposed to promote the uptake of health services; however, there is limited information on how mHealth can strengthen PNC in rural areas. The objective of this review was to gather the best available evidence regarding mHealth communication to strengthen PNC in rural areas.MethodsStudies published between 1 January 2008 and 31 August 2018 were searched in electronic databases hosted by EBSCO Host. Reference list checking and contact with authors were also done. Critical appraisal of the eligible studies was also done.ResultsThe results of 11 articles were synthesised to report the determinants of PNC uptake. Determinants were aligned to the Integrative Model of Behaviural Prediction (IMBP). One-way mobile phone messaging was the most common type of mHealth communication used. mHealth communication influenced mothers’ intentions, skills, and environmental constraints associated with uptake of PNC. Intentions were influenced by attitudes, perceived norms and self-efficacy. Positive attitudes, as well as changed attitudes toward PNC practices were observed. Perceived norms that were enhanced were delivery at a health facility with immediate PNC, seeking of reinforcement and professional health support of newborn care practices, and male partner support. Improved self-efficacy was demonstrated by mothers who attended scheduled appointments and they were confident with regard to newborn care practices. Skills for PNC that were improved included cord care, thermal care, appropriate breastfeeding and problem-solving. The environmental constraints faced and which were addressed in the studies included inaccessibility, unavailability and unaffordability of PNC services in rural areas.ConclusionsResults from the literature included in this study show that one-way mobile phone messaging is the common type of mHealth communication used to strengthen PNC in rural areas. mHealth communication can influence intentions, skills and environmental constraints as determinants of PNC uptake. mHealth communication is recommended to strengthen PNC in rural areas. To widen the evidence, more studies in the field of mHealth communication that report a variety of both maternal and neonatal outcomes are needed.
LncRNA WT1-AS up-regulates p53 to inhibit the proliferation of cervical squamous carcinoma cells
Authors: Zhang Yunxia , Na Renhua , Wang Xinling 
Published: November 2019

AbstractBackgroundIt has been reported that the development of cervical squamous cell carcinoma (CSCC) requires the involvement of a large number of lncRNAs. In a recent study lncRNA, WT1-AS was been characterized as a tumor-suppressive lncRNA in gastric cancer. In our study we aim to explore the involvement of WT1-AS in CSCC.MethodsSeventy-six CSCC patients (20 to 63 years, 40.1 ± 6.1 year) from the 233 CSCC patients who were admitted by the Affiliated Tumour Hospital of Xinjiang Medical University between august 2010 and January 2014. RT-qPCR, cell proliferation rate measurement, cell transfection, and western blot were carried out to analyze the samples.ResultsWe found that HPV infection failed to affect WT1-AS expression in CSCC tissues, while WT1-AS was down-regulated in CSCC tissues compared with non-cancer tissues. P53 was also down-regulated in CSCC tissues and positively correlated with WT1-AS. Analysis of the survival of CSCC patients revealed that low levels of WT1-AS were accompanied by poor survival. Significantly up-regulated p53 was observed after WT1-AS over-expression in CSCC cells, while p53 over-expression failed to affect WT1-AS. P53 and WT1-AS over-expression resulted in the inhibited proliferation of CSCC cells.ConclusionTherefore, WT1-AS is down-regulated in CSCC and it may inhibit CSCC cell proliferation at least partially by up-regulating p53.
Role of protein arginine methyltransferase 5 in group 3 (MYC-driven) Medulloblastoma
Authors: Chaturvedi Nagendra K. , Mahapatra Sidharth , Kesherwani Varun , Kling Matthew J. , Shukla Mamta , Ray Sutapa , Kanchan Ranjana , Perumal Naveenkumar , McGuire Timothy R. , Sharp J. Graham , Joshi Shantaram S. , Coulter Don W. 
Published: November 2019

Abstract

Background
MYC amplification or overexpression is common in Group 3 medulloblastoma and is associated with the worst prognosis. Recently, protein arginine methyl transferase (PRMT) 5 expression has been closely associated with aberrant MYC function in various cancers, including brain tumors such as glioblastoma. However, the role of PRMT5 and its association with MYC in medulloblastoma have not been explored. Here, we report the role of PRMT5 as a novel regulator of MYC and implicate PRMT5 as a potential therapeutic target in MYC-driven medulloblastoma.

Methods
Expression and association between PRMT5 and MYC in primary medulloblastoma tumors were investigated using publicly available databases. Expression levels of PRMT5 protein were also examined using medulloblastoma cell lines and primary tumors by western blotting and immunohistochemistry, respectively. Using MYC-driven medulloblastoma cells, we examined the physical interaction between PRMT5 and MYC by co-immunoprecipitation and co-localization experiments. To determine the functional role of PRMT5 in MYC-driven medulloblastoma, PRMT5 was knocked-down in MYC-amplified cells using siRNA and the consequences of knockdown on cell growth and MYC expression/stability were investigated. In vitro therapeutic potential of PRMT5 in medulloblastoma was also evaluated using a small molecule inhibitor, EPZ015666.

Results
We observed overexpression of PRMT5 in MYC-driven primary medulloblastoma tumors and cell lines compared to non-MYC medulloblastoma tumors and adjacent normal tissues. We also found that high expression of PRMT5 is inversely correlated with patient survival. Knockdown of PRMT5 using siRNA in MYC-driven medulloblastoma cells significantly decreased cell growth and MYC expression. Mechanistically, we found that PRMT5 physically associated with MYC by direct protein-protein interaction. In addition, a cycloheximide chase experiment showed that PRMT5 post-translationally regulated MYC stability. In the context of therapeutics, we observed dose-dependent efficacy of PRMT5 inhibitor EPZ015666 in suppressing cell growth and inducing apoptosis in MYC-driven medulloblastoma cells. Further, the expression levels of PRMT5 and MYC protein were downregulated upon EPZ015666 treatment. We also observed a superior efficacy of this inhibitor against MYC-amplified medulloblastoma cells compared to non-MYC-amplified medulloblastoma cells, indicating specificity.

Conclusion
Our results reveal the regulation of MYC oncoprotein by PRMT5 and suggest that targeting PRMT5 could be a potential therapeutic strategy for MYC-driven medulloblastoma.
Residential immersive life skills programs for youth with disabilities: a case study of youth developmental trajectories of personal growth and caregiver perspectives
Authors: Kingsnorth Shauna , Rudzik Alanna E. F. , King Gillian , McPherson Amy C. 
Published: November 2019

AbstractBackgroundProfessional support in pediatric and rehabilitation care environments has been recommended as a means to build youth competence in life skills during their transition to adulthood. Life skills are the essential psychosocial competencies and interpersonal skills needed to manage one’s life. Residential immersive life skills (RILS) programs offer youth with physical disabilities enriched learning environments to acquire these skills. This study explored trajectories of personal growth in life skills and positive psychological outcomes among youth participating in a RILS program and related caregiver perspectives.MethodDelivered by a multidisciplinary healthcare team,The Independence Programis an intensive summer program housed in a college residence that provides realistic experiences of living away from home for small groups of youth between 17 and 21 years of age who have congenital and/or acquired physical disabilities. Using a longitudinal case study and qualitative descriptive design, four youth and their parents/guardians participated in semi-structured interviews prior to, and then 1 month, and 3 to 4 months after the program. A conventional content analysis yielded chronological narratives for each youth and caregiver dyad of their experiences, perceptions and outcomes over time. These narratives were further summarized using a ‘line of development’ perspective to describe individual developmental trajectories of personal growth.ResultsAll four of the youth returned from the program with positive reports about the new life skills acquired and new behaviours they engaged in. These positive reports generally continued post-program, albeit with differing trajectories unique to each youth and varying levels of congruence with their caregivers’ readiness to support, accommodate and facilitate these changes. Caregivers differed in their capacity to shift in their parenting role to support consolidation of youth life skill competencies following program participation.ConclusionsRILS programs can be transformative. Varied youth trajectories identified significant personal growth through enhanced self-determination, self-efficacy and self-advocacy. Congruence in youth and caregiver perceptions of post-program changes was an important transactional factor. Professional support addressing caregiver needs may be beneficial to facilitate developmentally appropriate shifts in parenting roles. This shift is central to a model of shared management whereby adolescents take on greater responsibility for their own care and life choices.