bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Knowledge of Oral-Dental Health of Students Studying at a University Sufficient?
Authors: Kosan Zahide , Bedir Banu , Derelioglu Sera Simsek , Aydin Ozan Barıs , Aras Aysun
Published: November 2019

Aim:

Due to the common nature of oral and dental problems, awareness needs to be improved, expanded, and maintained. The aim of this study was to determine the oral and dental health knowledge levels of students, many of who would be teachers of the future, in this health field, and to help them work toward the elimination of the identified deficiencies.

Materials and Methods:

This cross-sectional descriptive study involved 475 students from the Erzurum Ataturk University dentistry, medicine, pharmaceutical sciences, nursing, and education faculties. Data were collected through a questionnaire by random stratified technique, investigating participants’ demographic characteristics and oral health knowledge levels.

Results:

We observed that 77.3% of students correctly answered 15 or more out of 31 questions addressing levels of knowledge of oral and dental health. This figure was 100% for students in the dentistry faculty and 56.3% for those in the education faculty. The difference between faculties in terms of students correctly answering 15 or more questions was statistically significant ( P < .001). A statistically significant difference was also determined between the faculties in terms of students’ sense of competence in oral and dental subjects ( P < .001).

Conclusion:

In the light of the data obtained, since prospective health care professionals and teachers both play an important role in raising public awareness, we recommend that a basic oral health course be introduced into the curricula of the relevant faculties.
Severe Vitamin A Deficiency After Biliopancreatic Diversion
Authors: Lemieux Lauren M. , Surampudi Vijaya
Published: November 2019

Biliopancreatic diversion is a surgical procedure that causes weight loss via volume restriction and malabsorption. It is now rarely performed due to the risk of severe nutritional deficiencies including vitamin A. We report a case of severe vitamin A deficiency due to malabsorption from a biliopancreatic diversion procedure for weight loss. By the time the patient presented to our department, she had developed blindness refractory to parenteral vitamin A treatment. A unique feature of her case is the development of a rash with vitamin A injections. This reaction has only been reported in one case series of 3 patients in the published literature. Her case highlights the importance of vitamin deficiency screening in patients after bariatric surgery, and her skin reaction to the injections is a unique side effect that is not frequently observed.
Risk of Secondary ACL Injury in Adolescents Prescribed Functional Bracing After ACL Reconstruction
Authors: Perrone Gabriel S. , Webster Kate E. , Imbriaco Chris , Portilla Gabriela M. , Vairagade Amishi , Murray Martha M. , Kiapour Ata M.
Published: November 2019

Background:

There is a high incidence of a secondary anterior cruciate ligament (ACL) injury in unbraced adolescent athletes. Little is known about the effect of functional bracing with regard to the risk of secondary ACL injuries among adolescents.

Hypothesis:

Our primary hypothesis was that adolescents would have a high rate of secondary ACL injury even with brace use. A secondary hypothesis was that the reinjury rate with brace use would be lower than that of a historical control group of unbraced patients.

Study Design:

Case series; Level of evidence, 4.

Methods:

A group of 219 patients (age <20 years at surgery) who underwent ACL reconstruction and were prescribed postoperative functional bracing during cutting and pivoting sports for 2 years after surgery completed a survey regarding reinjury to either knee. Rates of knee injuries following ACL reconstruction were calculated and compared with those reported in a similar unbraced cohort. The effect of demographic and anatomic factors on risk of secondary ACL injuries was also investigated.

Results:

The overall follow-up rate was 65% (142/219) at a mean 5.6 years after surgery. In the braced cohort, the overall graft retear rate was 10%, with the highest retear rates observed in male patients 17 years of age and younger (18%). The overall contralateral ACL injury and combined (graft or contralateral ACL) secondary injury rates were 13% and 23%, respectively, with female patients younger than 18 years having the highest contralateral and combined injury rates (17% and 26%, respectively). Younger age (odds ratio [OR], 0.70; P = .021), family history of ACL injury (OR, 2.81; P = .015), and higher lateral tibial slope (OR, 1.25; P = .016) were associated with increased risk of secondary knee injury in the braced cohort. Compared with the unbraced cohort, the braced cohort had a lower overall graft retear rate ( P = .028), a lower graft retear rate in patients younger than 18 years ( P = .012), lower early graft retear rate (within the first year after surgery) ( P = .011), and lower early graft retear rate in subjects younger than 18 years ( P = .003).

Conclusion:

Postoperative use of functional bracing can result in reduced risk of graft retear and no change in contralateral injury rates. Clinicians may want to consider the use of postoperative functional bracing in adolescent patients.
“It’s the Person, but Then the Environment, Too”: Black and Latino Males’ Narratives about Their College Successes
Authors: Brooms Derrick R.
Published: November 2019

This study relies on in-depth interviews with 30 Black and Latino males to explore how they narrate and make meaning from their college experiences at a Hispanic Serving Institution. A good deal of public and educational discourse often supposes these students’ lack of care and concern about their educational outcomes without understanding a larger context for their experiences. In this study, I explore these Black and Latino male students’ transitions to college and their success narratives. First, investigating their transition experiences allows for an opportunity to understand the strategies they deployed upon entering college and how these early experiences matter in their aspirations and sense of self. In their transitions, I find that students primarily relied on strategies and behaviors that are focused almost solely on academic effort while also isolating themselves from the college community and precluding themselves from developing social and cultural capital on campus. Second, analyzing their narratives of success allows for understanding the various networks and resources that students call upon in their college career. My findings show that students rely on a family–community nexus, including their on-campus involvement to support their college efforts. In addition to showing how social and cultural capital matter in Black and Latino males’ college experiences, this study extends our understanding of how students strive for and achieve success in college.
Repair of Superior Chorioretinal Coloboma-Associated Retinal Detachments: Case Report and Literature Review
Authors: Shaw Lincoln T. , Schechet Sidney A. , Avdagic Ema , Mieler William F. , Hariprasad Seenu M.
Published: November 2019

Purpose:

This case report discusses the management of a patient with a superior chorioretinal coloboma-associated retinal detachment (RD), including surgical management, along with a review of the literature.

Methods:

A case report is presented.

Results:

A 58-year-old man presented with a chronic RD of the right eye that was symptomatic for approximately 1 year prior to presentation. On examination, he was found to have a macula-off RD associated with superior chorioretinal coloboma. He underwent 23-gauge pars plana vitrectomy with membrane peel, endolaser, and perfluoropropane (14%) gas tamponade. Three months after his surgery, his best-corrected visual acuity in his right eye was 20/250 distance and 20/80 near, and his retina remained attached.

Conclusions:

This case report describes surgical management of a superior chorioretinal coloboma-associated RD.
The Role of Ultrasound in Juvenile Idiopathic Arthritis: A Narrative Review From an Imaging Perspective
Authors: Dima Robert S. , Appea Priya
Published: November 2019

Objective:

Musculoskeletal sonography (MSKS) is increasingly being used in the setting of juvenile idiopathic arthritis (JIA). The purpose of this narrative review was to describe the role of sonography in JIA and outline strategies for operators of pediatric MSKS.

Methods:

A literature review through multiple medical databases was conducted by restricting the search to medical subject headings (MeSH). Peer-reviewed English-language articles from 2007 to 2018 were included, which focused the on common sonographic findings of JIA.

Results:

Twenty-six articles were selected for inclusion in the study after a complete reading. Many studies aimed to address the validity of sonographic techniques in the assessment of JIA, but few studies discussed the specific sonographic appearances of JIA, scanning pitfalls, and appropriate imaging techniques.

Conclusion:

MSKS reveals subclinical manifestations of arthropathy, but the true value of detecting subclinical disease is not well understood. MSKS is limited in the evaluation of articular cartilage thinning and bony erosions. Responsiveness of MSKS in JIA remains to be formally assessed with higher quality studies.
Intrathecal alemtuzumab: a potential treatment of refractory leptomeningeal T-cell prolymphocytic leukemia
Authors: Alsawah Fares , Benitez Lydia , Choi Sarah , Marini Bernard , Perissinotti Anthony , Skyles Amy , Burke Patrick , Pettit Kristen , Crouch Ashley , Fox Heather , Bixby Dale
Published: November 2019

Key Points

This is the first report of successful treatment of therapy-resistant leptomeningeal T-PLL with intrathecal alemtuzumab. Intrathecal alemtuzumab is a potentially safe and efficacious therapeutic alternative for treatment of leptomeningeal T-PLL.
New therapies for von Willebrand disease
Authors: Mannucci Pier Mannuccio
Published: November 2019

The management of von Willebrand disease (VWD) is based upon the dual correction of the primary hemostasis defect, due to the inherited deficiency of von Willebrand factor (VWF), and of the secondary defect of factor VIII coagulant activity (FVIII:C), due to the loss of binding and stabilization by VWF of this intrinsic coagulation factor in flowing blood. The traditional therapeutic weapons (the synthetic derivative of the antidiuretic hormone desmopressin and plasma-derived VWF/FVIII concentrates) are able to transiently correct both the defects. With the goal of tackling the primary deficiency in the disease, that is, VWF, but at the same time exploiting the normal capacity of patients to produce FVIII, the novel approach of replacing only VWF was implemented in the last 10 years. Following the manufacturing of a concentrate fractionated from human plasma and of one obtained by recombinant DNA technology, clinical studies have shown that VWF-only products correct not only the primary VWF deficiency but also the secondary FVIII:C deficiency. The demonstrated efficacy of these products in various clinical situations and, ultimately, in such a hemostasis-challenging context as surgery testifies to the effectiveness and safety of this approach. It remains to be seen whether VWF-only products are efficacious and safe in still-unexplored situations, such as use in children; the long-term use for prophylaxis; and in recurrent gastrointestinal (GI) bleeding due to angiodysplasia, a major therapeutic problem in VWD.
Thrombotic thrombocytopenic purpura and defective apoptosis due to CASP8/10 mutations: the role of mycophenolate mofetil
Authors: Fioredda F. , Cappelli E. , Mariani A. , Beccaria A. , Palmisani E. , Grossi A. , Ceccherini I. , Venè R. , Micalizzi C. , Calvillo M. , Pierri F. , Mancini I. , Peyvandi F. , Corsolini F. , Dufour C. , Miano M.
Published: November 2019

Key Points

Immunological dysregulation may underlie unusual autoimmune diseases, which also deserve to be investigated from a genetic point of view.
Multifunctional graphene metasurface to generate and steer vortex waves
Authors: Wang Mengyu , Zeng Qingsheng , Deng Li , Feng Botao , Xu Ping
Published: November 2019

Graphene, an innovated 2D material with atomic thickness, is a very promising candidate and has drawn great attentions in various applications. Graphene metasurface enables dynamic control of various wavefronts, achieving distinguished functionalities. The flexibility of graphene metasurface makes it possible to implement multifunctional devices with ease. In this work, a novel design of multifunctional graphene metasurface, which can combine the functionalities of generating and steering vortex waves, has been proposed. The multifunctional graphene metasurface consists of a large array of graphene reflective unit cells. Each unit cell is controlled independently by its size and external static gate voltage. By scrutinizing the reflective property of the graphene cell, the graphene metasurface is designed to realize multi-functionalities. Simulation results show that vortex wave can be generated and steered. This work can establish a methodology to design multifunctional graphene metasurfaces, and the tunability of graphene opens the gate to the design and fabrication of reconfigurable graphene devices.
Estrogen biosynthesis in cultured skeletal muscle cells (L6) induced by amino acids
Authors: Iresjö Britt-Marie , Landin Andreas , Ohlsson Claes , Lundholm Kent
Published: November 2019

Background

Previous investigations have indicated upregulation of gene expression in cellular pathways related to the biosynthesis of steroids in response to amino acids (AA) in skeletal muscle cells. This suggests AA as modulators of de novo synthesis of sex steroids for muscle growth and improved functional capacity. The aim of the present study was to investigate if increased availability of amino acids induced biosynthesis of sex steroids in skeletal muscles.

Methods

Confluent L6 muscle cells were cultured in media with various AA concentrations (0.3 or 9 mM AA or 2.1 mM branched-chain (BCAA) only), following pre-culture in serum-free medium. Sex steroids were quantified by gas chromatography-tandem mass spectrometry (GC-MS/MS). Mevalonate (diphospho-) decarboxylase enzyme (MVD) was quantified by Western blot.

Results

The experiments confirmed that estradiol and estrone increased in both L6 cell lysates and in conditioned media at the end of experiments on confluent cells, while progesterone or androgenic steroids were not detected in either cell lysates or culture media. Estradiol (+ 31 ± 3%) and estrone (+ 18 ± 4%) increased significantly in cells cultured at 9 mM AA (p < 0.001 vs. 0.3 mM AA, n = 10). Similarly, MVD protein increased at 9 mM AA (p < 0.001 vs. 0.3 mM AA, n = 17). An addition of BCAA alone to media increased MVD-protein levels to the same extent as all AA (p < 0.01 vs. 0.3 mM AA, n = 3).

Conclusion

Female sex steroids and MVD enzyme production increased significantly in response to amino acid availability. The results indicate a role of amino acids as modulators of local muscle estrogen synthesis in muscle cells from rats at feeding.
A novel approach to carotenoid accumulation in rice callus by mimicking the cauliflower Orange mutation via genome editing
Authors: Endo Akira , Saika Hiroaki , Takemura Miho , Misawa Norihiko , Toki Seiichi
Published: November 2019

Background

β-carotene (provitamin A) is an important target for biofortification of crops as a potential solution to the problem of vitamin A deficiency that is prevalent in developing countries. A previous report showed that dominant expression of splicing variants in the Orange (Or) gene causes β-carotene accumulation in cauliflower curd. In this study, we focused on a putative orthologue of the cauliflower or gene in rice, Osor, and attempt to accumulate β-carotene in rice callus by modification of the Osor gene via genome editing using CRISPR/Cas9.

Findings

CRISPR/Cas9 vectors for the Osor gene were constructed and transformed into rice calli. Some transformed calli showed orange color due to β-carotene hyper-accumulation. Molecular analyses suggest that orange-colored calli are due to an abundance of in-frame aberrant Osor transcripts, whereas out-of-frame mutations were not associated with orange color.

Conclusions

We demonstrate that directed gene modification of the Osor gene via CRISPR/Cas9-mediated genome editing results in β-carotene fortification in rice calli. To date, golden rice, which accumulates β-carotene in rice endosperm, has been developed by conventional transgenic approaches. Our results suggest an alternative approach to enhancing β-carotene accumulation in crops.
An integrative methodology based on protein-protein interaction networks for identification and functional annotation of disease-relevant genes applied to channelopathies
Authors: Marín Milagros , Esteban Francisco J. , Ramírez-Rodrigo Hilario , Ros Eduardo , Sáez-Lara María José
Published: November 2019

Background

Biologically data-driven networks have become powerful analytical tools that handle massive, heterogeneous datasets generated from biomedical fields. Protein-protein interaction networks can identify the most relevant structures directly tied to biological functions. Functional enrichments can then be performed based on these structural aspects of gene relationships for the study of channelopathies. Channelopathies refer to a complex group of disorders resulting from dysfunctional ion channels with distinct polygenic manifestations. This study presents a semi-automatic workflow using protein-protein interaction networks that can identify the most relevant genes and their biological processes and pathways in channelopathies to better understand their etiopathogenesis. In addition, the clinical manifestations that are strongly associated with these genes are also identified as the most characteristic in this complex group of diseases.

Results

In particular, a set of nine representative disease-related genes was detected, these being the most significant genes in relation to their roles in channelopathies. In this way we attested the implication of some voltage-gated sodium (SCN1A, SCN2A, SCN4A, SCN4B, SCN5A, SCN9A) and potassium (KCNQ2, KCNH2) channels in cardiovascular diseases, epilepsies, febrile seizures, headache disorders, neuromuscular, neurodegenerative diseases or neurobehavioral manifestations. We also revealed the role of Ankyrin-G (ANK3) in the neurodegenerative and neurobehavioral disorders as well as the implication of these genes in other systems, such as the immunological or endocrine systems.

Conclusions

This research provides a systems biology approach to extract information from interaction networks of gene expression. We show how large-scale computational integration of heterogeneous datasets, PPI network analyses, functional databases and published literature may support the detection and assessment of possible potential therapeutic targets in the disease. Applying our workflow makes it feasible to spot the most relevant genes and unknown relationships in channelopathies and shows its potential as a first-step approach to identify both genes and functional interactions in clinical-knowledge scenarios of target diseases.

Methods

An initial gene pool is previously defined by searching general databases under a specific semantic framework. From the resulting interaction network, a subset of genes are identified as the most relevant through the workflow that includes centrality measures and other filtering and enrichment databases.
Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer
Authors: He Jing , Shi Xiao-Yan , Li Zhi-min , Pan Xiao-hua , Li Ze-Lian , Chen Ying , Yan Shi-Jie , Xiao Lan
Published: November 2019

Background

Several reports indicated that the expression of Yes-associated protein (YAP) was associated with multi-drug resistance. Acidic microenvironment increased by the overexpression of vacuolar-ATPase (V-ATPase) was also observed in tumor growth and drug resistance. We hypothesize that proton pump inhibitors (PPIs), currently used in the anti-acid treatment of peptic disease, could inhibit the acidification of the tumor microenvironment and increase the sensitivity of tumor cells to cytotoxic agents. Thus, our objective is to explore the reversal of drug resistance by the inhibition of YAP through specific PPIs in the epithelial ovarian carcinoma (EOC) cells. .

Results

We found that V-ATPase D1 was a positive regulator of YAP. Sub-lethal doses of the proton pump inhibitor esomeprazole (EMSO) in combination with paclitaxel (PTX) increased the PTX sensitivity in PTX-resistant EOC cells, as compared to PTX single treatments by inhibiting YAP and reserving pH gradient created by the V-ATPase D1. Moreover, sub-lethal doses of EMSO combined with PTX decreased autophagy and improved caspases independent apoptosis of PTX-resistant EOC cells.

Conclusions

These results suggested that sub-lethal doses of esomeprazole reverse YAP-mediated PTX resistance through the inhibiting of both YAP expression and acidic tumor microenvironment created by the V-ATPase D1. Therefore, we think the use of PPIs represents a promising strategy to improve the effectiveness of anti-EOC.
Survival of Polyploid hybrid salamander embryos
Authors: Charney Noah D. , Kubel Jacob E. , Woodard Craig T. , Carbajal-González Blanca I. , Avis Samantha , Blyth Julia A. , Eiseman Charles S. , Castorino John , Malone John H.
Published: November 2019

Background

Animals with polyploid, hybrid nuclei offer a challenge for models of gene expression and regulation during embryogenesis. To understand how such organisms proceed through development, we examined the timing and prevalence of mortality among embryos of unisexual salamanders in the genus Ambystoma.

Results

Our regional field surveys suggested that heightened rates of embryo mortality among unisexual salamanders begin in the earliest stages of embryogenesis. Although we expected elevated mortality after zygotic genome activation in the blastula stage, this is not what we found among embryos which we reared in the laboratory. Once embryos entered the first cleavage stage, we found no difference in mortality rates between unisexual salamanders and their bisexual hosts. Our results are consistent with previous studies showing high rates of unisexual mortality, but counter to reports that heightened embryo mortality continues throughout embryo development.

Conclusions

Possible causes of embryonic mortality in early embryogenesis suggested by our results include abnormal maternal loading of RNA during meiosis and barriers to insemination. The surprising survival rates of embryos post-cleavage invites further study of how genes are regulated during development in such polyploid hybrid organisms.
Electrochemical gradients are involved in regulating cytoskeletal patterns during epithelial morphogenesis in the Drosophila ovary
Authors: Weiß Isabel , Bohrmann Johannes
Published: November 2019

Background

DuringDrosophilaoogenesis, the follicular epithelium differentiates into several morphologically distinct follicle-cell populations. Characteristic bioelectrical properties make this tissue a suitable model system for studying connections between electrochemical signals and the organisation of the cytoskeleton. Recently, we have described stage-specific transcellular antero-posterior and dorso-ventral gradients of intracellular pH (pHi) and membrane potential (Vmem) depending on the asymmetrical distribution and/or activity of various ion-transport mechanisms. In the present study, we analysed the patterns of basal microfilaments (bMF) and microtubules (MT) in relation to electrochemical signals.

Results

The bMF- and MT-patterns in developmental stages 8 to 12 were visualised using labelled phalloidin and an antibody against acetylated α-tubulin as well as follicle-cell specific expression of GFP-actin and GFP-α-tubulin. Obviously, stage-specific changes of the pHi- and Vmem-gradients correlate with modifications of the bMF- and MT-organisation. In order to test whether cytoskeletal modifications depend directly on bioelectrical changes, we used inhibitors of ion-transport mechanisms that have previously been shown to modify pHiand Vmemas well as the respective gradients. We inhibited, in stage 10b, Na+/H+-exchangers and Na+-channels with amiloride, V-ATPases with bafilomycin, ATP-sensitive K+-channels with glibenclamide, voltage-dependent L-type Ca2+-channels with verapamil, Cl−-channels with 9-anthroic acid and Na+/K+/2Cl−-cotransporters with furosemide, respectively. The correlations between pHi, Vmem, bMF and MT observed in different follicle-cell types are in line with the correlations resulting from the inhibition experiments. While relative alkalisation and/or hyperpolarisation stabilised the parallel transversal alignment of bMF, acidification led to increasing disorder and to condensations of bMF. On the other hand, relative acidification as well as hyperpolarisation stabilised the longitudinal orientation of MT, whereas alkalisation led to loss of this arrangement and to partial disintegration of MT.

Conclusions

We conclude that the pHi- and Vmem-changes induced by inhibitors of ion-transport mechanisms simulate bioelectrical changes occurring naturally and leading to the cytoskeletal changes observed during differentiation of the follicle-cell epithelium. Therefore, gradual modifications of electrochemical signals can serve as physiological means to regulate cell and tissue architecture by modifying cytoskeletal patterns.
SNP eQTL status and eQTL density in the adjacent region of the SNP are associated with its statistical significance in GWA studies
Authors: Gorlov Ivan , Xiao Xiangjun , Mayes Maureen , Gorlova Olga , Amos Christopher
Published: November 2019

Background

Over the relatively short history of Genome Wide Association Studies (GWASs), hundreds of GWASs have been published and thousands of disease risk-associated SNPs have been identified. Summary statistics from the conducted GWASs are often available and can be used to identify SNP features associated with the level of GWAS statistical significance. Those features could be used to select SNPs from gray zones (SNPs that are nominally significant but do not reach the genome-wide level of significance) for targeted analyses.

Methods

We used summary statistics from recently published breast and lung cancer and scleroderma GWASs to explore the association between the level of the GWAS statistical significance and the expression quantitative trait loci (eQTL) status of the SNP. Data from the Genotype-Tissue Expression Project (GTEx) were used to identify eQTL SNPs.

Results

We found that SNPs reported as eQTLs were more significant in GWAS (higher -log10p) regardless of the tissue specificity of the eQTL. Pan-tissue eQTLs (those reported as eQTLs in multiple tissues) tended to be more significant in the GWAS compared to those reported as eQTL in only one tissue type. eQTL density in the ±5 kb adjacent region of a given SNP was also positively associated with the level of GWAS statistical significance regardless of the eQTL status of the SNP. We found that SNPs located in the regions of high eQTL density were more likely to be located in regulatory elements (transcription factor or miRNA binding sites).

When SNPs were stratified by the level of statistical significance, the proportion of eQTLs was positively associated with the mean level of statistical significance in the group. The association curve reaches a plateau around -log10p ≈ 5. The observed associations suggest that quasi-significant SNPs (10− 5 < p < 5 × 10− 8) and SNPs at the genome wide level of statistical significance (p < 5 × 10− 8) may have a similar proportions of risk associated SNPs.

Conclusions

The results of this study indicate that the SNP’s eQTL status, as well as eQTL density in the adjacent region are positively associated with the level of statistical significance of the SNP in GWAS.
Genetic analysis of novel phenotypes for farm animal resilience to weather variability
Authors: Sánchez-Molano Enrique , Kapsona Vanessa V. , Ilska Joanna J. , Desire Suzanne , Conington Joanne , Mucha Sebastian , Banos Georgios
Published: November 2019

Background

Climate change is expected to have a negative impact on food availability. While most efforts have been directed to reducing greenhouse gas emissions, complementary strategies are necessary to control the detrimental effects of climate change on farm animal performance. The objective of this study was to develop novel animal resilience phenotypes using reaction norm slopes, and examine their genetic and genomic parameters. A closely monitored dairy goat population was used for this purpose.

Results

Individual animals differed in their response to changing atmospheric temperature and a temperature-humidity index. Significant genetic variance and heritability estimates were derived for these animal resilience phenotypes. Furthermore, some resilience traits had a significant unfavourable genetic correlation with animal performance. Genome-wide association analyses identified several candidate genes related to animal resilience to environment change.

Conclusions

Heritable variation exists among dairy goats in their production response to fluctuating weather variables. Results may inform future breeding programmes aimed to ensure efficient animal performance under changing climatic conditions.
Characterization and discovery of miRNA and miRNA targets from apomictic and sexual genotypes of Eragrostis curvula
Authors: Garbus Ingrid , Selva Juan Pablo , Pasten María Cielo , Bellido Andrés Martín , Carballo José , Albertini Emidio , Echenique Viviana
Published: November 2019

Background

Weeping lovegrass (Eragrostis curvula[Shrad.] Nees) is a perennial grass found in semi-arid regions that is well adapted for growth in sandy soils and drought conditions.E. curvulaconstitutes a polymorphic complex that includes cytotypes with different ploidy levels (from 2x to 8x), where most polyploids are facultative apomicts, although both sexual reproduction and full apomixis have been reported in this species. Apomixis is thought to be associated with silencing of the sexual pathway, which would involve epigenetic mechanisms. However, a correlation between small RNAs and apomixis has not yet been conclusively established.

Results

Aiming to contribute to the elucidation of their role in the expression of apomixis, we constructed small RNA libraries from sexual and apomicticE. curvulagenotypes via Illumina technology, characterized the small RNA populations, and conducted differential expression analysis by comparing these small RNAs with theE. curvulareference transcriptome. We found that the expression of two genes is repressed in the sexual genotype, which is associated with specific microRNA expression.

Conclusion

Our results support the hypothesis that inE. curvulathe expression of apomixis leads to sexual repression.
Identification of loci associated with conception rate in primiparous Holstein cows
Authors: Kiser Jennifer N. , Clancey Erin , Moraes Joao G. N. , Dalton Joseph , Burns Gregory W. , Spencer Thomas E. , Neibergs Holly L.
Published: November 2019

Background

Subfertility is a major issue facing the dairy industry as the average US Holstein cow conception rate (CCR) is approximately 35%. The genetics underlying the physiological processes responsible for CCR, the proportion of cows able to conceive and maintain a pregnancy at each breeding, are not well characterized. The objectives of this study were to identify loci, positional candidate genes, and transcription factor binding sites (TFBS) associated with CCR and determine if there was a genetic correlation between CCR and milk production in primiparous Holstein cows. Cows were bred via artificial insemination (AI) at either observed estrus or timed AI and pregnancy status was determined at day 35 post-insemination. Additive, dominant, and recessive efficient mixed model association expedited (EMMAX) models were used in two genome-wide association analyses (GWAA). One GWAA focused on CCR at first service (CCR1) comparing cows that conceived and maintained pregnancy to day 35 after the first AI (n = 494) to those that were open after the first AI (n = 538). The second GWAA investigated loci associated with the number of times bred (TBRD) required for conception in cows that either conceived after the first AI (n = 494) or repeated services (n = 472).

Results

The CCR1 GWAA identified 123, 198, and 76 loci associated (P < 5 × 10− 08) in additive, dominant, and recessive models, respectively. The TBRD GWAA identified 66, 95, and 33 loci associated (P < 5 × 10− 08) in additive, dominant, and recessive models, respectively. Four of the top five loci were shared in CCR1 and TBRD for each GWAA model. Many of the associated loci harbored positional candidate genes and TFBS with putative functional relevance to fertility. Thirty-six of the loci were validated in previous GWAA studies across multiple breeds. None of the CCR1 or TBRD associated loci were associated with milk production, nor was their significance with phenotypic and genetic correlations to 305-day milk production.

Conclusions

The identification and validation of loci, positional candidate genes, and TFBS associated with CCR1 and TBRD can be utilized to improve, and further characterize the processes involved in cattle fertility.
Subsets of mononuclear phagocytes are enriched in the inflamed colons of patients with IBD
Authors: Liu Hong , Dasgupta Suryasarathi , Fu Yu , Bailey Brandi , Roy Christian , Lightcap Eric , Faustin Benjamin
Published: November 2019

Background

Myeloid cells, especially mononuclear phagocytes, which include monocytes, macrophages and dendritic cells (DC), play vital roles in innate immunity, and in the initiation and maintenance of adaptive immunity. While T cell-associated activation pathways and cytokines have been identified and evaluated in inflammatory bowel disease (IBD) patients (Neurath, Nat Rev Gastroenterol Hepatol 14:269–78, 1989), the role of mononuclear phagocytes are less understood. Recent reports support the crucial role of DC subsets in the development of acute colitis models (Arimura et al., Mucosal Immunol 10:957–70, 2017), and suggest they may contribute to the pathogenesis of ulcerative colitis (UC) by inducing Th1/Th2/Th17 responses (Matsuno et al., Inflamm Bowel Dis 23:1524–34, 2017).

Results

We performed in silico analysis and evaluated the enrichment of immune cells, with a focus on mononuclear phagocytes in IBD patient colonic biopsies. Samples were from different gut locations, with different levels of disease severity, and with treatment response to current therapies. We observe enrichment of monocytes, M1 macrophages, activated DCs (aDCs) and plasmacytoid dendritic cells (pDCs) in inflamed tissues from various gut locations. This enrichment correlates with disease severity. Additionally, the same mononuclear phagocytes subsets are among the top enriched cell types in both infliximab and vedolizumab treatment non-responder samples. We further investigated the enrichment of selected DC and monocyte subsets based on gene signatures derived from a DC- and monocyte-focused single cell RNA-seq (scRNA-seq) study (Villani et al., Science 356:eaah4573, 2017), and verified enrichment in both inflamed tissues and those with treatment resistance. Moreover, we validated an increased mononuclear phagocyte subset abundance in a Dextran Sulphate Sodium (DSS) induced colitis model in C57Bl/6 mice representative of chronic inflammation.

Conclusions

We conducted an extensive analysis of immune cell populations in IBD patient colonic samples and identified enriched subsets of monocytes, macrophages and dendritic cells in inflamed tissues. Understanding how they interact with other immune cells and other cells in the colonic microenvironment such as epithelial and stromal cells will help us to delineate disease pathogenesis.
The effect of pneumococcal immunization on total and antigen-specific B cells in patients with severe chronic kidney disease
Authors: Gaultier Gabrielle Nicole , McCready William , Ulanova Marina
Published: November 2019

Background

While the 23-valent pneumococcal polysaccharide vaccine (PPV23) is routinely used in Canada and some other countries to prevent pneumococcal infection in adults with chronic kidney disease (CKD), patients develop a suboptimal antibody response to PPV23 due to their immune dysfunction. The 13-valent pneumococcal conjugate vaccine (PCV13) has superior immunogenicity in some categories of immunocompromised adults; however, its effect on the immune response in CKD patients has only been addressed by two recent studies with conflicting results. The effect of PPV23 or PCV13 on B cells in these patients has not been previously studied. We studied the absolute numbers and proportions of B cells and subpopulations in two groups of adult patients with severe CKD pre- and 7 days post-immunization with PCV13: pneumococcal vaccine naïve and previously immunized with PPV23 (over one year ago).

Results

PPV23 immunized patients had significantly lower proportions and absolute numbers of class switched memory (CD19 + CD27 + IgM-), as well as lower absolute numbers of IgM memory (CD19 + CD27 + IgM+) and class switched B cells (CD19 + CD27-IgM-) compared to PPV23 naïve patients. Following PCV13 immunization, the differences in absolute numbers of B-cell subpopulations between groups remained significant. The PPV23 immunized group had higher proportions of CD5- B cells along with lower proportions and absolute numbers of CD5+ B cells compared to PPV23 naïve patients both pre- and post-immunization with PCV13. However, previous PPV23 immunization did not have a noticeable effect on the numbers of total IgG or serotype 6B and 14 specific antibody-secreting cells detected 7 days post-immunization with PCV13. Nevertheless, fold increase in anti-serotype 14 IgG concentrations 28 days post-PCV13 was greater in PPV23 naïve than in previously immunized patients.

Conclusions

The results suggest that immunization with PPV23 may result in long-term changes in B-cell subpopulations such as increased prevalence of CD5- B cells and decreased prevalence of class switched memory B cells in the peripheral blood. Because previous immunization with PPV23 in patients with CKD is associated with a significant decrease in the total class switched memory B cells in response to subsequent immunization with PCV13, this may reduce PCV13 immunogenicity in the setting of PPV23 followed by PCV13.

Trial registration

Registered February 24, 2015 at ClinicalTrials.gov (NCT 02370069).
Isolation, characterization, and assessment of lactic acid bacteria toward their selection as poultry probiotics
Authors: Reuben Rine Christopher , Roy Pravas Chandra , Sarkar Shovon Lal , Alam Rubayet-Ul , Jahid Iqbal Kabir
Published: November 2019

Background

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are now accepted as suitable alternatives to antibiotics in the control of animal infections and improving animal production. Lactic acid bacteria (LAB) with remarkable functional properties have been evaluated in different studies as possible probiotic candidates. The purpose of this study was to isolate, characterize and assess the potentials of LAB from poultry gastrointestinal tract as potential poultry probiotics.

Results

Potential LAB probiotics were isolated from broilers, characterized and evaluated for probiotic properties including antagonistic activity (against Escherichia coli, E. coli O157: H7, Enterococcus faecalis, Salmonella Typhimurium, S. Enteritidis and Listeria monocytogenes), survivability in simulated gastric juice, tolerance to phenol and bile salts, adhesion to ileum epithelial cells, auto and co-aggregation, hydrophobicity, α–glucosidase inhibitory activity, and antibiotic susceptibility tests. Most promising LAB strains with excellent probiotic potentials were identified by API 50 CHL and 16S rRNA sequencing as Lactobacillus reuteri I2, Pediococcus acidilactici I5, P. acidilactici I8, P. acidilactici c3, P. pentosaceus I13, and Enterococcus faecium c14. They inhibited all the pathogens tested with zones of inhibition ranging from 12.5 ± 0.71 to 20 ± 0 mm, and competitively excluded (P < 0.05) the pathogens examined while adhering to ileum epithelial cells with viable counts of 3.0 to 6.0 Log CFU/ml. The selected LAB strains also showed significant (P < 0.005) auto and co-aggregation abilities with α-glucosidase inhibitory activity ranging from 12.5 to 92.0%. The antibiotic susceptibility test showed 100.00% resistance of the LAB strains to oxacillin, with multiple antibiotic resistance indices above 0.5.

Conclusion

The selected LAB strains are ideal probiotic candidates which can be applied in the field for the improvement of poultry performance and control of pathogens in poultry, hence curtailing further transmission to humans.
Linking a rapid throughput plate-assay with high-sensitivity stable-isotope label LCMS quantification permits the identification and characterisation of low β-L-ODAP grass pea lines
Authors: Emmrich Peter M. F. , Rejzek Martin , Hill Lionel , Brett Paul , Edwards Anne , Sarkar Abhimanyu , Field Rob A. , Martin Cathie , Wang Trevor L.
Published: November 2019

Background

Grass pea (Lathyrus sativus) is an underutilised crop with high tolerance to drought and flooding stress and potential for maintaining food and nutritional security in the face of climate change. The presence of the neurotoxin β-L-oxalyl-2,3-diaminopropionic acid (β-L-ODAP) in tissues of the plant has limited its adoption as a staple crop. To assist in the detection of material with very low neurotoxin toxin levels, we have developed two novel methods to assay ODAP. The first, a version of a widely used spectrophotometric assay, modified for increased throughput, permits rapid screening of large populations of germplasm for low toxin lines and the second is a novel, mass spectrometric procedure to detect very small quantities of ODAP for research purposes and characterisation of new varieties.

Results

A plate assay, based on an established spectrophotometric method enabling high-throughput ODAP measurements, is described. In addition, we describe a novel liquid chromatography mass spectrometry (LCMS)-based method for β-L-ODAP-quantification. This method utilises an internal standard (di-13C-labelled β-L-ODAP) allowing accurate quantification of β-L-ODAP in grass pea tissue samples. The synthesis of this standard is also described. The two methods are compared; the spectrophotometric assay lacked sensitivity and detected ODAP-like absorbance in chickpea and pea whereas the LCMS method did not detect any β-L-ODAP in these species. The LCMS method was also used to quantify β-L-ODAP accurately in different tissues of grass pea.

Conclusions

The plate-based spectrophotometric assay allows quantification of total ODAP in large numbers of samples, but its low sensitivity and inability to differentiate α- and β-L-ODAP limit its usefulness for accurate quantification in low-ODAP samples. Coupled to the use of a stable isotope internal standard with LCMS that allows accurate quantification of β-L-ODAP in grass pea samples with high sensitivity, these methods permit the identification and characterisation of grass pea lines with a very low ODAP content. The LCMS method is offered as a new ‘gold standard’ for β-L-ODAP quantification, especially for the validation of existing and novel low- and/or zero-β-L-ODAP genotypes.
Characterization and T-DNA insertion sites identification of a multiple-branches mutant br in Betula platyphylla × Betula pendula
Authors: Han Rui , Gu Chenrui , Li Ranhong , Xu Wendi , Wang Shuo , Liu Chaoyi , Qu Chang , Chen Su , Liu Guifeng , Yu Qibin , Jiang Jing , Li Huiyu
Published: November 2019

Background

Plant architecture, which is mostly determined by shoot branching, plays an important role in plant growth and development. Thus, it is essential to explore the regulatory molecular mechanism of branching patterns based on the economic and ecological importance. In our previous work, a multiple-branches birch mutant br was identified from 19 CINNAMOYL-COENZYME A REDUCTASE 1 (CCR1)-overexpressed transgenic lines, and the expression patterns of differentially expressed genes in br were analyzed. In this study, we further explored some other characteristics of br, including plant architecture, wood properties, photosynthetic characteristics, and IAA and Zeatin contents. Meanwhile, the T-DNA insertion sites caused by the insertion of exogenous BpCCR1 in br were identified to explain the causes of the mutation phenotypes.

Results

The mutant br exhibited slower growth, more abundant and weaker branches, and lower wood basic density and lignin content than BpCCR1 transgenic line (OE2) and wild type (WT). Compared to WT and OE2, br had high stomatal conductance (Gs), transpiration rate (Tr), but a low non-photochemical quenching coefficient (NPQ) and chlorophyll content. In addition, br displayed an equal IAA and Zeatin content ratio of main branches’ apical buds to lateral branches’ apical buds and high ratio of Zeatin to IAA content. Two T-DNA insertion sites caused by the insertion of exogenous BpCCR1 in br genome were found. On one site, chromosome 2 (Chr2), no known gene was detected on the flanking sequence. The other site was on Chr5, with an insertion of 388 bp T-DNA sequence, resulting in deletion of 107 bp 5′ untranslated region (UTR) and 264 bp coding sequence (CDS) on CORONATINE INSENSITIVE 1 (BpCOII). In comparison with OE2 and WT, BpCOI1 was down-regulated in br, and the sensitivity of br to Methyl Jasmonate (MeJA) was abnormal.

Conclusions

Plant architecture, wood properties, photosynthetic characteristics, and IAA and Zeatin contents in main and lateral branches’ apical buds changed in br over the study’s time period. One T-DNA insertion was identified on the first exon of BpCOI1, which resulted in the reduction of BpCOI1 expression and abnormal perception to MeJA in br. These mutation phenotypes might be associated with a partial loss of BpCOI1 in birch.
Patient and provider differences in the treatment of opioid-induced constipation: a qualitative study
Authors: Keller Michelle S. , Jusufagic Alma , Spiegel Brennan M. R.
Published: November 2019

Background

Patients using opioids to treat chronic non-cancer pain often experience side effects that may affect health-related quality of life (HRQOL). These side effects include opioid-induced constipation (OIC), sedation, dizziness, and nausea. OIC can significantly affect HRQOL for patients on a daily basis. However, it is not well understood whether patients and clinicians view OIC management similarly.

Aims

In this study, we sought to elucidate the decision-making process around managing OIC by assessing patient and provider treatment preferences, experiences, and communication regarding this condition.

Methods

We conducted semi-structured interviews with 33 clinicians, and held three focus groups with patients who were currently using or had used opioids for chronic non-cancer pain. We then analyzed transcribed interviews using descriptive qualitative methods based on grounded theory methodology.

Results

Clinicians recognized OIC as a concern but prioritized pain management over constipation. They focused on medication-based treatments for OIC, but also recommended lifestyle changes (e.g., diet) and reducing opioids to relieve symptoms. Patients reported using over-the-counter treatments, but the majority focused on diet-related constipation management. Patients reported not receiving adequate information from clinicians about OIC and relevant treatments. Cost of treatment was a major concern for both patients and clinicians.

Conclusions

Assessing experiences with and preferences for OIC treatment, including cost, ease of access, and side effects, could improve patient-provider communication and HRQOL. Quality improvement efforts can target uncovered misalignments between patients and clinicians to improve communication about opioid medication adverse effects and relevant treatment options, which may help improve quality of life for patients with chronic pain.