bluuebunny/crossref_metadata_2025 huggingface dataset:
6-Sulfatoxymelatonin predicts treatment response to fluoxetine in major depressive disorder
Authors: Jury Freitas Juliana , Bertuol Xavier Nicóli , Comiran Tonon André , Carissimi Alicia , Timm Pizutti Leandro , Vieira Ilgenfritz Carlos Augusto , Pekelmann Markus Regina , Paz Hidalgo Maria
Published: December 2019

Background:

To date, no biomarker has been able to predict antidepressant response at an early blockade of norepinephrine or serotonin uptake. The transient nocturnal increase in plasma melatonin levels is upregulated by blocking these uptakes. The aim of this study was to test whether fluoxetine increase in urinary 6-sulfatoxymelatonin (aMT6s) is an indicator of serotonin uptake blockade.

Methods:

A total of 20 women (35–45 years of age) recruited from the community had a diagnosis of major depressive disorder confirmed by the Structured Clinical Interview for DSM-IV. Depressive symptoms were evaluated by the Beck Depression Inventory (BDI). Participants were instructed to take 20 mg of fluoxetine every morning. Every 4 weeks, the dose could be increased by 20 mg until symptom remission. The concentration of aMT6s was evaluated in overnight urine samples collected 1 day before and 1 day after the first fluoxetine dose.

Results:

An increase in aMT6s correlated to a decrease in BDI score evaluated on day 45 (ρ = −0.67, p = 0.024) was observed.

Conclusions:

Nocturnal increase in urinary aMT6s after the first day of medication use links the early mechanism of action of fluoxetine to its clinical output 45 days later. Thus, the relationship between urinary aMT6s excretion 1 day before/1 day after is a biomarker for predicting clinical output earlier, reducing illness burden and health care costs.
Predictors of Return to Work After High Tibial Osteotomy: The Importance of Being a Breadwinner
Authors: Hoorntje Alexander , Kuijer P. Paul F.M. , van Ginneken Berbke T. , Koenraadt Koen L.M. , van Geenen Rutger C.I. , Kerkhoffs Gino M.M.J. , van Heerwaarden Ronald J.
Published: December 2019

Background:

Limited evidence exists on patient-relevant outcomes after high tibial osteotomy (HTO), including return to work (RTW). Furthermore, prognostic factors for RTW have never been described.

Purpose:

To investigate the extent and timing of RTW in the largest HTO cohort investigated for RTW to date and to identify prognostic factors for RTW after HTO.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Consecutive patients who underwent HTO between 2012 and 2015 were included. Patients received a questionnaire at a mean follow-up of 3.6 years. Questions were asked pre- and postoperatively regarding work status, job title, working hours, preoperative sick leave, employment status, and whether patients were their family’s breadwinner. The validated Work Rehabilitation Questionnaire (WORQ) was used to assess difficulty with knee-demanding activities. Prognostic factors for RTW were analyzed using a logistic regression model. Covariates were selected based on univariate analysis and a directed acyclic graph.

Results:

We identified 402 consecutive patients who underwent HTO, of whom 349 were included. Preoperatively, 299 patients worked, of whom 284 (95%) achieved RTW and 255 (90%) returned within 6 months. Patients reported significant postoperative improvements in performing knee-demanding activities. Being the family’s breadwinner was the strongest predictor of RTW (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.27-6.69). In contrast, preoperative sick leave was associated with lower odds of RTW (OR, 0.20; 95% CI, 0.08-0.46).

Conclusion:

After HTO, 95% of patients were able to RTW, of whom 9 of 10 returned within 6 months. Breadwinners were more likely to RTW, and patients with preoperative sick leave were less likely to RTW within 6 months. These findings may be used to improve preoperative counseling and expectation management and thereby enhance work-related outcomes after HTO.
Community-Based Education in Global Low-Resource Settings: A Unique Interprofessional Collaborative Experience in Primary Care Delivery
Authors: Ezeonwu Mabel
Published: December 2019

The complex nature of global health issues requires multidisciplinary efforts, namely, interprofessional education (IPE) and collaborative practice. For American students to develop skills and competencies that contribute to global primary care workforces, they must receive community-based education in various environments around the world. This article presents a global health education program that offers community-based, health-related IPE that is centered on primary care, collaborative practice, and a unique three-way partnership. Using a “classroom in the field” hybrid model, this program placed graduate and undergraduate students from different majors into experienced multidisciplinary health care teams and gave them hands-on, firsthand public health experiences in eight low-resource settings in Guatemala. The curricular design was informed by the Consortium of Universities for Global Health’s global health education competencies. At the completion of the program, all partners, participants, and local communities involved saw significant positive outcomes. Notably, students were able to articulate the essentials of primary care in a global context and demonstrate knowledge and skills in global health competencies. Such community-based approaches promote student understanding of disease prevention and health promotion as key elements of primary care that could improve health outcomes for underserved global populations.
Patterns in Opioid Prescription for Patients Operatively Treated for Ankle Fractures Following Implementation of 2017 Ohio Opioid Prescriber Law
Authors: Glogovac Georgina , Fitts Jamal , Henning Jordan , Dixon Tonya L. , Laughlin Richard T.
Published: December 2019

Background:

The purpose of this study was to report patterns of opioid prescription for patients treated operatively for ankle fractures after implementation of the 2017 Ohio Opioid Prescriber Law in comparison to the previous year.

Methods:

A total of 144 patients operatively treated for isolated ankle fractures during two 6-month periods, January 2017 to July 2017 (pre-law) and January 2018 to July 2018 (post-law), were retrospectively identified. Preoperative and postoperative patient narcotic use was reviewed using a legal prescriber database. Total number of prescriptions, quantity of pills, and morphine milligram equivalents (MMEs) per patient prescribed during the 90-day postoperative period were compared between those treated before and those treated after implementation of the Ohio prescriber law.

Results:

The average number of opioid prescriptions prescribed per patient in the 90-day postoperative period was 2.3 in the pre-law group and 2.1 in the post-law group ( P = .625). The average MMEs prescribed per patient dropped from 942.4 MME pre-law to 700.5 MME post-law ( P = .295). Differences in the average number of pills per prescription pre- and post-law (49.7 vs 36.2) and average MME per prescription (382.1 mg vs 275.2 mg) were statistically significant ( P < .001 and P = .016, respectively).

Conclusion:

Following the implementation of the 2017 Ohio Opioid Prescriber Law, there was a downward trend in the number of pills per prescription and MMEs per prescription in patients operatively treated for isolated ankle fractures. The presence of a downward trend in the quantity of opioids prescribed in this patient cohort suggests the effectiveness of the state law.

Level of Evidence:

Level III, comparative study.
Duo in a Mystical Realm—Nuclear Lipid Droplets and the Inner Nuclear Membrane
Authors: Sołtysik Kamil , Ohsaki Yuki , Fujimoto Toyoshi
Published: December 2019

The lipid droplet (LD) is a cytoplasmic organelle, but it also exists in the nucleus under some conditions or in some cell types. New studies have revealed that nuclear LDs do not occur by haphazard entry of cytoplasmic LDs. Instead, they are generated by specific mechanisms that are increasingly understood. The inner nuclear membrane (INM) plays a critical role in nuclear LD formation in both mammalian hepatocytes and budding yeast, although in significantly different ways. Hepatocyte nuclear LDs derive from precursors of very low-density lipoprotein lacking apolipoprotein B-100, which form in the endoplasmic reticulum lumen and accumulate in intranuclear extensions of the perinuclear space called type I nucleoplasmic reticulum. In contrast, nuclear LDs in yeast are generated by triglyceride synthesized in the INM. Nuclear LDs in hepatocytes and budding yeast are both instrumental in the regulation of phospholipid synthesis; however, again they function in different ways. As the full functional importance is as yet unknown, the close relationship of nuclear LDs and the INM is an attractive target of research from both physiological and pathological perspectives.
Management of spontaneous and iatrogenic perforations, leaks and fistulae of the upper gastrointestinal tract
Authors: Al-Asiry Jamal , Lord Richard , Mohammed Noor
Published: December 2019

Upper gastrointestinal perforations, leaks and fistulae are relatively common occurrences with a growing number of these complications occuring as a result of therapeutic advancement and adoption of newer and bolder endoscopic therapies. Historically, these were predominantly managed surgically; however, owing to high morbidity and mortality associated with surgical repair, endoscopic options are preferable. Over the past decade, vast expansion in the endoscopic armamentarium for the management of perforations, leaks and fistulae has led to endoscopic management now being the first-line treatment. Here, we will review the endoscopic modalities including through-the-scope clips, over-the-scope clips, stents, vacuum therapy, endoscopic sutures and sealants. In addition, we will discuss nonendoscopic approach to management including early recognition of perforations, ways to reduce septic complications and format algorithms to guide therapy for different scenarios. However, it is important to stress that there is a lack of high-quality randomised studies to clearly guide management of such complications, resulting in a wide variation of approaches in management by specialists. Each case requires some degree of individualisation due to the potential array of problems encountered and patient-specific co-morbidities. In the future, more robust studies are clearly required to better guide specialist management.
Pathogenic Bhlhe40+ GM-CSF+ CD4+ T cells promote indirect alloantigen presentation in the GI tract during GVHD
Authors: Piper Clint , Zhou Vivian , Komorowski Richard , Szabo Aniko , Vincent Benjamin , Serody Jonathan , Alegre Maria-Luisa , Edelson Brian T. , Taneja Reshma , Drobyski William R.
Published: December 2019

Gastrointestinal (GI) tract involvement is the major cause of morbidity and mortality in acute graft-versus-host disease (GVHD), and pathological damage is largely attributable to inflammatory cytokine production. Recently, granulocyte-macrophage colony stimulating factor (GM-CSF) has been identified as a cytokine that mediates inflammation in the GI tract, but the transcriptional program that governs GM-CSF production and the mechanism by which GM-CSF links adaptive to innate immunity within this tissue site have not been defined. In the current study, we identified Bhlhe40 as a key transcriptional regulator that governs GM-CSF production by CD4+ T cells and mediates pathological damage in the GI tract during GVHD. In addition, we observed that GM-CSF was not regulated by either interleukin 6 (IL-6) or IL-23, which are both potent inducers of GVHD-induced colonic pathology, indicating that GM-CSF constitutes a nonredundant inflammatory pathway in the GI tract. Mechanistically, GM-CSF had no adverse effect on regulatory T-cell reconstitution, but linked adaptive to innate immunity by enhancing the activation of donor-derived dendritic cells in the colon and subsequent accumulation of these cells in the mLNs. In addition, GM-CSF promoted indirect alloantigen presentation, resulting in the accumulation of donor-derived T cells with a proinflammatory cytokine phenotype in the colon. Thus, Bhlhe40+ GM-CSF+ CD4+ T cells constitute a colitogenic T-cell population that promotes indirect alloantigen presentation and pathological damage within the GI tract, positioning GM-CSF as a key regulator of GVHD in the colon and a potential therapeutic target for amelioration of this disease.
The crossover design for migraine preventives: an analyses of four randomized placebo-controlled trials
Authors: Jenssen Astrid Bjørke , Stovner Lars Jacob , Tronvik Erling , Sand Trond , Helde Grethe , Gravdahl Gøril Bruvik , Hagen Knut
Published: December 2019

Aims

To evaluate the crossover design in migraine preventive treatment trials by assessing dropout rate, and potential period and carryover effect in four placebo-controlled randomized controlled trials (RCTs).

Methods

In order to increase statistical power, the study combined data from four different RCTs performed from 1998 to 2015 at St. Olavs Hospital, Norway. Among 264 randomized patients, 120 received placebo treatment before and 144 after active treatment.

Results

Only 26 (10%) dropped out during the follow-up period of 30–48 weeks, the majority (n = 19) in the first 12 weeks. No period effect was found, since the treatment sequence did not influence the responder rate after placebo treatment, being respectively for migraine 30.5% vs. 27.4% (p = 0.59) and for headache 25.0% vs. 24.8% (p = 0.97, Chi-square test) when placebo occurred early or late. Furthermore, no carryover effect was identified, since the treatment sequence did not influence the treatment effect (difference between placebo and active treatment). There was no significant difference between those who received active treatment first and those who received placebo first with respect to change in number of days per 4 week of headache (− 0.9 vs. -1.3,p = 0.46) and migraine (− 1.2 vs. -0.9,p = 0.35, Student’s t-test).

Conclusions

Summary data from four crossover trials evaluating preventive treatment in adult migraine showed that few dropped out after the first period. No period or carryover effect was found. RCT studies with crossover design can be recommended as an efficient and cost-saving way to evaluate potential new preventive medicines for migraine in adults.
Correction to: Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2)
Authors: Silberstein Stephen D. , Stauffer Virginia L. , Day Katie A. , Lipsius Sarah , Wilson Maria-Carmen
Published: December 2019

After publication of our article [1] we were notified that the data presented in the upper row of Fig. 7 was inadvertently the least square mean change from baseline (standard error) at Month 6 rather than the overall average of Month 3 and Month 6. The figure legend and discussion of the data in the text were and are correct. The error was only in the upper row of Fig. 7. The legend for Fig. 7 did not require revision.
Genomic and transcriptomic analysis reveal molecular basis of salinity tolerance in a novel strong salt-tolerant rice landrace Changmaogu
Authors: Sun Bing-Rui , Fu Chong-Yun , Fan Zhi-Lan , Chen Yu , Chen Wen-Feng , Zhang Jing , Jiang Li-Qun , Lv Shuwei , Pan Da-Jian , Li Chen
Published: December 2019

Background

Salt stress is an important factor that limits rice yield. We identified a novel, strongly salt tolerant rice landrace called Changmaogu (CMG) collected from a coastal beach of Zhanjiang, Guangdong Province, China. The salt tolerance of CMG was much better than that of the international recognized salt tolerant rice cultivar Pokkali in the germination and seedling stages.

Results

To understand the molecular basis of salt tolerance in CMG, we performed BSA-seq for two extreme bulks derived from the cross between CMG and a cultivar sensitive to salt, Zhefu802. Transcriptomic sequencing was conducted for CMG at the germination and young seedling stages. Six candidate regions for salt tolerance were mapped on Chromosome 1 by BSA-seq using the extreme populations. Based on the polymorphisms identified between both parents, we detected 32 genes containing nonsynonymous coding single nucleotide polymorphisms (SNPs) and frameshift mutations in the open reading frame (ORF) regions. With transcriptomic sequencing, we detected a large number of differentially expressed genes (DEGs) at the germination and seedling stages under salt stress. KEGG analysis indicated two of 69 DEGs shared at the germination and seedling stages were significantly enriched in the pathway of carotenoid biosynthesis. Of the 169 overlapping DEGs among three sample points at the seedling stage, 13 and six DEGs were clustered into the pathways of ABA signal transduction and carotenoid biosynthesis, respectively. Of the 32 genes carrying sequence variation, only OsPP2C8 (Os01g0656200) was differentially expressed in the young seedling stage under salt stress and also showed sequence polymorphism in the ORFs between CMG and Zhefu802.

Conclusion

OsPP2C8 was identified as the target candidate gene for salinity tolerance in the seedling stage. This provides an important genetic resource for the breeding of novel salt tolerant rice cultivars.
Transcription factor regulatory modules provide the molecular mechanisms for functional redundancy observed among transcription factors in yeast
Authors: Yang Tzu-Hsien
Published: December 2019

Background

Current technologies for understanding the transcriptional reprogramming in cells include the transcription factor (TF) chromatin immunoprecipitation (ChIP) experiments and the TF knockout experiments. The ChIP experiments show the binding targets of TFs against which the antibody directs while the knockout techniques find the regulatory gene targets of the knocked-out TFs. However, it was shown that these two complementary results contain few common targets. Researchers have used the concept of TF functional redundancy to explain the low overlap between these two techniques. But the detailed molecular mechanisms behind TF functional redundancy remain unknown. Without knowing the possible molecular mechanisms, it is hard for biologists to fully unravel the cause of TF functional redundancy.

Results

To mine out the molecular mechanisms, a novel algorithm to extract TF regulatory modules that help explain the observed TF functional redundancy effect was devised and proposed in this research. The method first searched for candidate TF sets from the TF binding data. Then based on these candidate sets the method utilized the modified Steiner Tree construction algorithm to construct the possible TF regulatory modules from protein-protein interaction data and finally filtered out the noise-induced results by using confidence tests. The mined-out regulatory modules were shown to correlate to the concept of functional redundancy and provided testable hypotheses of the molecular mechanisms behind functional redundancy. And the biological significance of the mined-out results was demonstrated in three different biological aspects: ontology enrichment, protein interaction prevalence and expression coherence. About 23.5% of the mined-out TF regulatory modules were literature-verified. Finally, the biological applicability of the proposed method was shown in one detailed example of a verified TF regulatory module for pheromone response and filamentous growth in yeast.

Conclusion

In this research, a novel method that mined out the potential TF regulatory modules which elucidate the functional redundancy observed among TFs is proposed. The extracted TF regulatory modules not only correlate the molecular mechanisms to the observed functional redundancy among TFs, but also show biological significance in inferring TF functional binding target genes. The results provide testable hypotheses for biologists to further design subsequent research and experiments.
Topological structure analysis of chromatin interaction networks
Authors: Viksna Juris , Melkus Gatis , Celms Edgars , Čerāns Kārlis , Freivalds Karlis , Kikusts Paulis , Lace Lelde , Opmanis Mārtiņš , Rituma Darta , Rucevskis Peteris
Published: December 2019

Background

Current Hi-C technologies for chromosome conformation capture allow to understand a broad spectrum of functional interactions between genome elements. Although significant progress has been made into analysis of Hi-C data to identify biologically significant features, many questions still remain open, in particular regarding potential biological significance of various topological features that are characteristic for chromatin interaction networks.

Results

It has been previously observed that promoter capture Hi-C (PCHi-C) interaction networks tend to separate easily into well-defined connected components that can be related to certain biological functionality, however, such evidence was based on manual analysis and was limited. Here we present a novel method for analysis of chromatin interaction networks aimed towards identifying characteristic topological features of interaction graphs and confirming their potential significance in chromatin architecture. Our method automatically identifies all connected components with an assigned significance score above a given threshold. These components can be subjected afterwards to different assessment methods for their biological role and/or significance. The method was applied to the largest PCHi-C data set available to date that contains interactions for 17 haematopoietic cell types. The results demonstrate strong evidence of well-pronounced component structure of chromatin interaction networks and provide some characterisation of this component structure. We also performed an indicative assessment of potential biological significance of identified network components with the results confirming that the network components can be related to specific biological functionality.

Conclusions

The obtained results show that the topological structure of chromatin interaction networks can be well described in terms of isolated connected components of the network and that formation of these components can be often explained by biological features of functionally related gene modules. The presented method allows automatic identification of all such components and evaluation of their significance in PCHi-C dataset for 17 haematopoietic cell types. The method can be adapted for exploration of other chromatin interaction data sets that include information about sufficiently large number of different cell types, and, in principle, also for analysis of other kinds of cell type-specific networks.
Fast and accurate microRNA search using CNN
Authors: Tang Xubo , Sun Yanni
Published: December 2019

Background

There are many different types of microRNAs (miRNAs) and elucidating their functions is still under intensive research. A fundamental step in functional annotation of a new miRNA is to classify it into characterized miRNA families, such as those in Rfam and miRBase. With the accumulation of annotated miRNAs, it becomes possible to use deep learning-based models to classify different types of miRNAs. In this work, we investigate several key issues associated with successful application of deep learning models for miRNA classification. First, as secondary structure conservation is a prominent feature for noncoding RNAs including miRNAs, we examine whether secondary structure-based encoding improves classification accuracy. Second, as there are many more non-miRNA sequences than miRNAs, instead of assigning a negative class for all non-miRNA sequences, we test whether using softmax output can distinguish in-distribution and out-of-distribution samples. Finally, we investigate whether deep learning models can correctly classify sequences from small miRNA families.

Results

We present our trained convolutional neural network (CNN) models for classifying miRNAs using different types of feature learning and encoding methods. In the first method, we explicitly encode the predicted secondary structure in a matrix. In the second method, we use only the primary sequence information and one-hot encoding matrix. In addition, in order to reject sequences that should not be classified into targeted miRNA families, we use a threshold derived from softmax layer to exclude out-of-distribution sequences, which is an important feature to make this model useful for real transcriptomic data. The comparison with the state-of-the-art ncRNA classification tools such as Infernal shows that our method can achieve comparable sensitivity and accuracy while being significantly faster.

Conclusion

Automatic feature learning in CNN can lead to better classification accuracy and sensitivity for miRNA classification and annotation. The trained models and also associated codes are freely available at https://github.com/HubertTang/DeepMir.
Gencore: an efficient tool to generate consensus reads for error suppressing and duplicate removing of NGS data
Authors: Chen Shifu , Zhou Yanqing , Chen Yaru , Huang Tanxiao , Liao Wenting , Xu Yun , Li Zhicheng , Gu Jia
Published: December 2019

Background

Removing duplicates might be considered as a well-resolved problem in next-generation sequencing (NGS) data processing domain. However, as NGS technology gains more recognition in clinical application, researchers start to pay more attention to its sequencing errors, and prefer to remove these errors while performing deduplication operations. Recently, a new technology called unique molecular identifier (UMI) has been developed to better identify sequencing reads derived from different DNA fragments. Most existing duplicate removing tools cannot handle the UMI-integrated data. Some modern tools can work with UMIs, but are usually slow and use too much memory. Furthermore, existing tools rarely report rich statistical results, which are very important for quality control and downstream analysis. These unmet requirements drove us to develop an ultra-fast, simple, little-weighted but powerful tool for duplicate removing and sequence error suppressing, with features of handling UMIs and reporting informative results.

Results

This paper presents an efficient tool gencore for duplicate removing and sequence error suppressing of NGS data. This tool clusters the mapped sequencing reads and merges reads in each cluster to generate one single consensus read. While the consensus read is generated, the random errors introduced by library construction and sequencing can be removed. This error-suppressing feature makes gencore very suitable for the application of detecting ultra-low frequency mutations from deep sequencing data. When unique molecular identifier (UMI) technology is applied, gencore can use them to identify the reads derived from same original DNA fragment. Gencore reports statistical results in both HTML and JSON formats. The HTML format report contains many interactive figures plotting statistical coverage and duplication information. The JSON format report contains all the statistical results, and is interpretable for downstream programs.

Conclusions

Comparing to the conventional tools like Picard and SAMtools, gencore greatly reduces the output data’s mapping mismatches, which are mostly caused by errors. Comparing to some new tools like UMI-Reducer and UMI-tools, gencore runs much faster, uses less memory, generates better consensus reads and provides simpler interfaces. To our best knowledge, gencore is the only duplicate removing tool that generates both informative HTML and JSON reports. This tool is available at: https://github.com/OpenGene/gencore
The phylogenetic significance of the morphology of the syrinx, hyoid and larynx, of the southern cassowary, Casuarius casuarius (Aves, Palaeognathae)
Authors: McInerney Phoebe L. , Lee Michael S. Y. , Clement Alice M. , Worthy Trevor H.
Published: December 2019

Background

Palaeognathae is a basal clade within Aves and include the large and flightless ratites and the smaller, volant tinamous. Although much research has been conducted on various aspects of palaeognath morphology, ecology, and evolutionary history, there are still areas which require investigation. This study aimed to fill gaps in our knowledge of the Southern Cassowary,Casuarius casuarius, for which information on the skeletal systems of the syrinx, hyoid and larynx is lacking - despite these structures having been recognised as performing key functional roles associated with vocalisation, respiration and feeding. Previous research into the syrinx and hyoid have also indicated these structures to be valuable for determining evolutionary relationships among neognath taxa, and thus suggest they would also be informative for palaeognath phylogenetic analyses, which still exhibits strong conflict between morphological and molecular trees.

Results

The morphology of the syrinx, hyoid and larynx ofC. casuariusis described from CT scans. The syrinx is of the simple tracheo-bronchial syrinx type, lacking specialised elements such as the pessulus; the hyoid is relatively short with longer ceratobranchials compared to epibranchials; and the larynx is comprised of entirely cartilaginous, standard avian anatomical elements including a concave, basin-like cricoid and fused cricoid wings. As in the larynx, both the syrinx and hyoid lack ossification and all three structures were most similar toDromaius.We documented substantial variation across palaeognaths in the skeletal character states of the syrinx, hyoid, and larynx, using both the literature and novel observations (e.g. ofC. casuarius). Notably, new synapomorphies linking Dinornithiformes and Tinamidae are identified, consistent with the molecular evidence for this clade. These shared morphological character traits include the ossification of the cricoid and arytenoid cartilages, and an additional cranial character, the articulation between the maxillary process of the nasal and the maxilla.

Conclusion

Syrinx, hyoid and larynx characters of palaeognaths display greater concordance with molecular trees than do other morphological traits. These structures might therefore be less prone to homoplasy related to flightlessness and gigantism, compared to typical morphological traits emphasised in previous phylogenetic studies.
A genome-skimmed phylogeny of a widespread bryozoan family, Adeonidae
Authors: Orr Russell J. S. , Haugen Marianne N. , Berning Björn , Bock Philip , Cumming Robyn L. , Florence Wayne K. , Hirose Masato , Di Martino Emanuela , Ramsfjell Mali H. , Sannum Maja M. , Smith Abigail M. , Vieira Leandro M. , Waeschenbach Andrea , Liow Lee Hsiang
Published: December 2019

Background

Understanding the phylogenetic relationships among species is one of the main goals of systematic biology. Simultaneously, credible phylogenetic hypotheses are often the first requirement for unveiling the evolutionary history of traits and for modelling macroevolutionary processes. However, many non-model taxa have not yet been sequenced to an extent such that statistically well-supported molecular phylogenies can be constructed for these purposes. Here, we use a genome-skimming approach to extract sequence information for 15 mitochondrial and 2 ribosomal operon genes from the cheilostome bryozoan family, Adeonidae, Busk, 1884, whose current systematics is based purely on morphological traits. The members of the Adeonidae are, like all cheilostome bryozoans, benthic, colonial, marine organisms. Adeonids are also geographically widely-distributed, often locally common, and are sometimes important habitat-builders.

Results

We successfully genome-skimmed 35 adeonid colonies representing 6 genera (Adeona, Adeonellopsis, Bracebridgia, Adeonella, Laminopora and Cucullipora). We also contributed 16 new, circularised mitochondrial genomes to the eight previously published for cheilostome bryozoans. Using the aforementioned mitochondrial and ribosomal genes, we inferred the relationships among these 35 samples. Contrary to some previous suggestions, the Adeonidae is a robustly supported monophyletic clade. However, the genera Adeonella and Laminopora are in need of revision: Adeonella is polyphyletic and Laminopora paraphyletically forms a clade with some Adeonella species. Additionally, we assign a sequence clustering identity using cox1 barcoding region of 99% at the species and 83% at the genus level.

Conclusions

We provide sequence data, obtained via genome-skimming, that greatly increases the resolution of the phylogenetic relationships within the adeonids. We present a highly-supported topology based on 17 genes and substantially increase availability of circularised cheilostome mitochondrial genomes, and highlight how we can extend our pipeline to other bryozoans.
D3GRN: a data driven dynamic network construction method to infer gene regulatory networks
Authors: Chen Xiang , Li Min , Zheng Ruiqing , Wu Fang-Xiang , Wang Jianxin
Published: December 2019

Background

To infer gene regulatory networks (GRNs) from gene-expression data is still a fundamental and challenging problem in systems biology. Several existing algorithms formulate GRNs inference as a regression problem and obtain the network with an ensemble strategy. Recent studies on data driven dynamic network construction provide us a new perspective to solve the regression problem.

Results

In this study, we propose a data driven dynamic network construction method to infer gene regulatory network (D3GRN), which transforms the regulatory relationship of each target gene into functional decomposition problem and solves each sub problem by using the Algorithm for Revealing Network Interactions (ARNI). To remedy the limitation of ARNI in constructing networks solely from the unit level, a bootstrapping and area based scoring method is taken to infer the final network. On DREAM4 and DREAM5 benchmark datasets, D3GRN performs competitively with the state-of-the-art algorithms in terms of AUPR.

Conclusions

We have proposed a novel data driven dynamic network construction method by combining ARNI with bootstrapping and area based scoring strategy. The proposed method performs well on the benchmark datasets, contributing as a competitive method to infer gene regulatory networks in a new perspective.
An efficient simulated annealing algorithm for the RNA secondary structure prediction with Pseudoknots
Authors: Kai Zhang , Yuting Wang , Yulin Lv , Jun Liu , Juanjuan He
Published: December 2019

Background

RNA pseudoknot structures play an important role in biological processes. However, existing RNA secondary structure prediction algorithms cannot predict the pseudoknot structure efficiently. Although random matching can improve the number of base pairs, these non-consecutive base pairs cannot make contributions to reduce the free energy.

Result

In order to improve the efficiency of searching procedure, our algorithm take consecutive base pairs as the basic components. Firstly, our algorithm calculates and archive all the consecutive base pairs in triplet data structure, if the number of consecutive base pairs is greater than given minimum stem length. Secondly, the annealing schedule is adapted to select the optimal solution that has minimum free energy. Finally, the proposed algorithm is evaluated with the real instances in PseudoBase.

Conclusion

The experimental results have been demonstrated to provide a competitive and oftentimes better performance when compared against some chosen state-of-the-art RNA structure prediction algorithms.
Investigating host-bacterial interactions among enteric pathogens
Authors: Bose Tungadri , Venkatesh K. V. , Mande Sharmila S.
Published: December 2019

Background

In 2017, World Health Organization (WHO) published a catalogue of 12 families of antibiotic-resistant “priority pathogens” that are posing the greatest threats to human health. Six of these dreaded pathogens are known to infect the human gastrointestinal system. In addition to causing gastrointestinal and systemic infections, these pathogens can also affect the composition of other microbes constituting the healthy gut microbiome. Such aberrations in gut microbiome can significantly affect human physiology and immunity. Identifying the virulence mechanisms of these enteric pathogens are likely to help in developing newer therapeutic strategies to counter them.

Results

Using our previously published in silico approach, we have evaluated (and compared) Host-Pathogen Protein-Protein Interaction (HPI) profiles of four groups of enteric pathogens, namely, different species ofEscherichia,Shigella,SalmonellaandVibrio. Results indicate that in spite of genus/ species specific variations, most enteric pathogens possess a common repertoire of HPIs. This core set of HPIs are probably responsible for the survival of these pathogen in the harsh nutrient-limiting environment within the gut. Certain genus/ species specific HPIs were also observed.

Conslusions

The identified bacterial proteins involved in the core set of HPIs are expected to be helpful in understanding the pathogenesis of these dreaded gut pathogens in greater detail. Possible role of genus/ species specific variations in the HPI profiles in the virulence of these pathogens are also discussed. The obtained results are likely to provide an opportunity for development of novel therapeutic strategies against the most dreaded gut pathogens.
Effect of growth rate on transcriptomic responses to immune stimulation in wild-type, domesticated, and GH-transgenic coho salmon
Authors: Kim Jin-Hyoung , Macqueen Daniel J. , Winton James R. , Hansen John D. , Park Hyun , Devlin Robert H.
Published: December 2019

Background

Transcriptomic responses to immune stimulation were investigated in coho salmon (Oncorhynchus kisutch) with distinct growth phenotypes. Wild-type fish were contrasted to strains with accelerated growth arising either from selective breeding (i.e. domestication) or genetic modification. Such distinct routes to accelerated growth may have unique implications for relationships and/or trade-offs between growth and immune function.

Results

RNA-Seq was performed on liver and head kidney in four ‘growth response groups’ injected with polyinosinic-polycytidylic acid (Poly I:C; viral mimic), peptidoglycan (PGN; bacterial mimic) or PBS (control). These groups were: 1) ‘W’: wild-type, 2) ‘TF’: growth hormone (GH) transgenic salmon with ~ 3-fold higher growth-rate than W, 3) ‘TR’: GH transgenic fish ration restricted to possess a growth-rate equal to W, and 4) ‘D’: domesticated non-transgenic fish showing growth-rate intermediate to W and TF. D and TF showed a higher similarity in transcriptomic response compared to W and TR. Several immune genes showed constitutive expression differences among growth response groups, including perforin 1 and C-C motif chemokine 19-like. Among the affected immune pathways, most were up-regulated by Poly I:C and PGN. In response to PGN, the c-type lectin receptor signalling pathway responded uniquely in TF and TR. In response to stimulation with both immune mimics, TR responded more strongly than other groups. Further, group-specific pathway responses to PGN stimulation included NOD-like receptor signalling in W and platelet activation in TR. TF consistently showed the most attenuated immune response relative to W, and more DEGs were apparent in TR than TF and D relative to W, suggesting that a non-satiating ration coupled with elevated circulating GH levels may cause TR to possess enhanced immune capabilities. Alternatively, TF and D salmon are prevented from acquiring the same level of immune response as TR due to direction of energy to high overall somatic growth. Further study of the effects of ration restriction in growth-modified fishes is warranted.

Conclusions

These findings improve our understanding of the pleiotropic effects of growth modification on the immunological responses of fish, revealing unique immune pathway responses depending on the mechanism of growth acceleration and nutritional availability.
Genetic dissection of canine hip dysplasia phenotypes and osteoarthritis reveals three novel loci
Authors: Mikkola Lea , Holopainen Saila , Pessa-Morikawa Tiina , Lappalainen Anu K. , Hytönen Marjo K. , Lohi Hannes , Iivanainen Antti
Published: December 2019

Background

Hip dysplasia and osteoarthritis continue to be prevalent problems in veterinary and human medicine. Canine hip dysplasia is particularly problematic as it massively affects several large-sized breeds and can cause a severe impairment of the quality of life. In Finland, the complex condition is categorized to five classes from normal to severe dysplasia, but the categorization includes several sub-traits: congruity of the joint, Norberg angle, subluxation degree of the joint, shape and depth of the acetabulum, and osteoarthritis. Hip dysplasia and osteoarthritis have been proposed to have separate genetic etiologies.

Results

Using Fédération Cynologique Internationale -standardized ventrodorsal radiographs, German shepherds were rigorously phenotyped for osteoarthritis, and for joint incongruity by Norberg angle and femoral head center position in relation to dorsal acetabular edge. The affected dogs were categorized into mild, moderate and severe dysplastic phenotypes using official hip scores. Three different genome-wide significant loci were uncovered. The strongest candidate genes for hip joint incongruity were noggin (NOG), a bone and joint developmental gene on chromosome 9, and nanos C2HC-type zinc finger 1 (NANOS1), a regulator of matrix metalloproteinase 14 (MMP14) on chromosome 28. Osteoarthritis mapped to a long intergenic region on chromosome 1, between genes encoding for NADPH oxidase 3 (NOX3), an intriguing candidate for articular cartilage degradation, and AT-rich interactive domain 1B (ARID1B) that has been previously linked to joint laxity.

Conclusions

Our findings highlight the complexity of canine hip dysplasia phenotypes. In particular, the results of this study point to the potential involvement of specific and partially distinct loci and genes or pathways in the development of incongruity, mild dysplasia, moderate-to-severe dysplasia and osteoarthritis of canine hip joints. Further studies should unravel the unique and common mechanisms for the various sub-traits.
An atypical HLH transcriptional regulator plays a novel and important role in strawberry ripened receptacle
Authors: Medina-Puche Laura , Martínez-Rivas Félix J. , Molina-Hidalgo Francisco J. , Mercado José A. , Moyano Enriqueta , Rodríguez-Franco Antonio , Caballero José L. , Muñoz-Blanco Juan , Blanco-Portales Rosario
Published: December 2019

Background

In soft fruits, the differential expression of many genes during development and ripening is responsible for changing their organoleptic properties. In strawberry fruit, although some genes involved in the metabolic regulation of the ripening process have been functionally characterized, some of the most studied genes correspond to transcription factors. High throughput transcriptomics analyses performed in strawberry red receptacle (Fragaria x ananassa) allowed us to identify a ripening-related gene that codes an atypical HLH (FaPRE1) with high sequence homology with the PACLOBUTRAZOL RESISTANCE (PRE) genes. PRE genes are atypical bHLH proteins characterized by the lack of a DNA-binding domain and whose function has been linked to the regulation of cell elongation processes.

Results

FaPRE1 sequence analysis indicates that this gene belongs to the subfamily of atypical bHLHs that also includes ILI-1 from rice, SlPRE2 from tomato and AtPRE1 from Arabidopsis, which are involved in transcriptional regulatory processes as repressors, through the blockage by heterodimerization of bHLH transcription factors. FaPRE1 presented a transcriptional model characteristic of a ripening-related gene with receptacle-specific expression, being repressed by auxins and activated by abscisic acid (ABA). However, its expression was not affected by gibberellic acid (GA3). On the other hand, the transitory silencing of FaPRE1 transcription by agroinfiltration in receptacle produced the down-regulation of a group of genes related to the ripening process while inducing the transcription of genes involved in receptacle growth and development.

Conclusions

In summary, this work presents for the first time experimental data that support an important novel function for the atypical HLH FaPRE1 during the strawberry fruit ripening. We hypothesize that FaPRE1 modulates antagonistically the transcription of genes related to both receptacle growth and ripening. Thus, FaPRE1 would repress the expression of receptacle growth promoting genes in the ripened receptacle, while it would activate the expression of those genes related to the receptacle ripening process.
A high-density genetic map constructed using specific length amplified fragment (SLAF) sequencing and QTL mapping of seed-related traits in sesame (Sesamum indicum L.)
Authors: Du Hua , Zhang Haiyang , Wei Libin , Li Chun , Duan Yinghui , Wang Huili
Published: December 2019

Background

Sesame (Sesamum indicumL., 2n = 2x = 26) is an important oilseed crop with high oil content but small seed size. To reveal the genetic loci of the quantitative seed-related traits, we constructed a high-density single nucleotide polymorphism (SNP) linkage map of an F2population by using specific length amplified fragment (SLAF) technique and determined the quantitative trait loci (QTLs) of seed-related traits for sesame based on the phenotypes of F3progeny.

Results

The genetic map comprised 2159 SNP markers distributed on 13 linkage groups (LGs) and was 2128.51 cM in length, with an average distance of 0.99 cM between adjacent markers. QTL mapping revealed 19 major-effect QTLs with the phenotypic effect (R2) more than 10%, i.e., eight QTLs for seed coat color, nine QTLs for seed size, and two QTLs for 1000-seed weight (TSW), using composite interval mapping method. Particularly, LG04 and LG11 contained collocated QTL regions for the seed coat color and seed size traits, respectively, based on their close or identical locations. In total, 155 candidate genes for seed coat color, 22 for seed size traits, and 54 for TSW were screened and analyzed.

Conclusions

This report presents the first QTL mapping of seed-related traits in sesame using an F2population. The results reveal the location of specific markers associated with seed-related traits in sesame and provide the basis for further seed quality traits research.