bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Management of Gunshot Injury to the Temporomandibular Joint
Authors: Santos Marcelo Soares dos , Gonçalves Kalyne Kelly Negromonte , Silva Caio César Gonçalves , Diniz Demóstenes Alves , Vasconcelos Belmiro Cavalcanti do Egito
Published: September 2019

One of the indications of the surgical approach of the temporomandibular joint is the presence of foreign body in its interior. However, joint handling offers risks, especially bleeding. In these cases, angiography and embolization of the arteries involved with the projectile play an important role in the prevention of complications. In this report, the authors describe a case of a 23-year-old male victim of firearm attack with comminuted fracture of the right mandibular condyle. The patient underwent angiography and prophylactic embolization of the arteries adjacent to the foreign body. A surgical procedure was performed to remove the projectile and bone fragments with the aid of the X-ray image intensifier, which resulted in the restoration of mandibular function, absence of joint pain, and satisfactory dental occlusion. This case shows the importance of auxiliary imaging methods for performing a safe surgical procedure for removal of ballistic and bony fragments from the interior of the temporomandibular joint.
EP2 Receptor Blockade Attenuates COX-2 Upregulation During Intestinal Inflammation
Authors: Golden Jamie , Illingworth Laura , Kavarian Patil , Escobar Oswaldo , Delaplain Patrick , Isani Mubina , Wang Jin , Lim Joanna , Bowling Jordan , Bell Brandon , Gayer Christopher P. , Grishin Anatoly , Ford Henri R.
Published: September 2019

High levels of PGE2 have been implicated in the pathogenesis of intestinal inflammatory disorders such as necrotizing enterocolitis (NEC) and peritonitis. However, PGE2 has a paradoxical effect: its low levels promote intestinal homeostasis, whereas high levels may contribute to pathology. These concentration-dependent effects are mediated by four receptors, EP1-EP4. In this study, we evaluate the effect of blockade of the low affinity pro-inflammatory receptors EP1 and EP2 on expression of COX-2, the rate-limiting enzyme in PGE2 biosynthesis, and on gut barrier permeability using cultured enterocytes and three different models of intestinal injury. PGE2 upregulated COX-2 in IEC-6 enterocytes, and this response was blocked by the EP2 antagonist PF-04418948, but not by the EP1 antagonist ONO-8711 or EP4 antagonist E7046. In the neonatal rat model of NEC, EP2 antagonist and low dose of COX-2 inhibitor Celecoxib, but not EP1 antagonist, reduced NEC pathology as well as COX-2 mRNA and protein expression. In the adult mouse endotoxemia and cecal ligation/puncture models, EP2, but not EP1 genetic deficiency decreased COX-2 expression in the intestine. Our results indicate that the EP2 receptor plays a critical role in the positive feedback regulation of intestinal COX-2 by its end-product PGE2 during inflammation and may be a novel therapeutic target in the treatment of NEC.
True Short Esophagus in Gastroesophageal Reflux Disease
Authors: Lugaresi Marialuisa , Mattioli Benedetta , Daddi Niccolò , Bassi Francesco , Pilotti Vladimiro , Ferruzzi Luca , Mattioli Sandro
Published: September 2019

Objective:

To explore the true short esophagus (TSE) frequency and long-term results of patients undergoing gastroesophageal reflux disease (GERD) or hiatus hernia (HH) surgery.

Background:

The existence and treatment of TSE during GERD/HH surgery is controversial. Satisfactory long-term results have been achieved with and without surgical techniques dedicated to TSE.

Methods:

In 311 consecutive patients undergoing minimally invasive surgery for GERD/HH, the distance between the endoscopically-localized gastroesophageal junction (GEJ) and the apex of the diaphragmatic hiatus after maximal thoracic esophagus mobilization was measured. A standard Nissen fundoplication (SN) was performed in cases with an abdominal length >1.5 cm; in cases of TSE (abdominal length <1.5 cm), a Collis-Nissen (CN) or stomach around the stomach fundoplication (SASF) in elderly patients was performed. The fundoplication superior margin was fixed below the hiatus, but over the GEJ. The patients’ symptoms, and radiological and endoscopic data were pre/postoperatively recorded.

Results:

After intrathoracic esophageal mobilization (median 9 cm), TSE was diagnosed in 31.8% of 311 cases. With a median follow-up of 96 months (309 patients), HH relapse was radiologically diagnosed in 3.2% of patients, with excellent, good, fair, and poor outcomes in 45.6%, 44.3%, 6.2%, and 3.9% of cases, respectively, and no significant differences among SN (68.5%), CN (26.4%), and SASF (5.2%).

Conclusions:

TSE was present in 31.8% of patients routinely submitted to GERD/HH surgery. In the presence of TSE, CN and SASF performed according to determined surgical principles may achieve similar satisfactory results. This finding warrants confirmation with a prospective multicenter study.
Alcohol-related trauma reinjury prevention with hospital-based screening in adult populations: An Eastern Association for the Surgery of Trauma evidence-based systematic review
Authors: Kodadek Lisa M. , Freeman Jennifer J. , Tiwary Devesh , Drake Mack Dillon , Schroeder M. Elizabeth , Dultz Linda , White Cassandra , Abdel Aziz Hiba , Crandall Marie , Como John J. , Rattan Rishi
Published: September 2019

BACKGROUND

Unaddressed alcohol use among injured patients may result in recurrent injury or death. Many trauma centers incorporate alcohol screening, brief intervention, and referral to treatment for injured patients with alcohol use disorders, but systematic reviews evaluating the impact of these interventions are lacking.

METHODS

An evidence-based systematic review was performed to answer the following population, intervention, comparator, outcomes question: Among adult patients presenting for acute injury, should emergency department, trauma center, or hospital-based alcohol screening with brief intervention and/or referral to treatment be instituted compared with usual care to prevent or decrease reinjury, hospital readmission, alcohol-related offenses, and/or alcohol consumption? A librarian-initiated query of PubMed, MEDLINE, and the Cochrane Library was performed. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of the evidence and create recommendations. The study was registered with PROSPERO (registration number CRD42019122333).

RESULTS

Eleven studies met criteria for inclusion, with a total of 1,897 patients who underwent hospital-based alcohol screening, brief intervention, and/or referral to treatment for appropriate patients. There was a relative paucity of data, and studies varied considerably in terms of design, interventions, and outcomes of interest. Overall evidence was assessed as low quality, but a large effect size of intervention was present.

CONCLUSION

In adult trauma patients, we conditionally recommend emergency department, trauma center, or hospital-based alcohol screening with brief intervention and referral to treatment for appropriate patients in order to reduce alcohol-related reinjury.

LEVEL OF EVIDENCE

Systematic review, Level III.
Opioid Overdose in Ohio: Comprehensive Analysis of Associated Socioeconomic Factors
Authors: Park Chihyun , Crawford Sara , Lopez Rocio , Seballos Anna , Clemenceau Jean R. , Coy Tyler , Atluri Gowtham , Hwang Tae Hyun
Published: September 2019

Objective

Our study focused on identifying socioeconomic factors associated with death by opioid overdose in Ohio communities at the census tract level.

Materials and Methods

A large-scale vital statistic dataset from Ohio Department of Health (ODH) and U.S. Census datasets were used to obtain opioid-related death rate and socioeconomic characteristics for all census tracts in Ohio. Regression analysis was performed to identify the relationships between socioeconomic factors of census tracts and the opioid-related death rate for both urban and rural tracts.

Results

In Ohio from 2010-2016, whites, males, and people aged 25-44 had the highest opioid-related death rates. At the census tract level, higher death rates were associated with certain socioeconomic characteristics (e.g. percentage of the census tract population living in urban areas, percentage divorced/separated, percentage of vacant housing units). Predominately rural areas had a different population composition than urban areas, and death rates in rural areas exhibited fewer associations with socioeconomic characteristics.

Discussion

Predictive models of opioid-related death rates based on census tract-level characteristics held for urban areas more than rural ones, reflecting the recently observed rural-to-urban geographic shift in opioid-related deaths. Future research is needed to examine the geographic distribution of opioid abuse throughout Ohio and in other states.

Conclusion

Regression analysis identified associations between population characteristics and opioid-related death rates of Ohio census tracts. These analyses can help government officials and law official workers prevent, predict and combat opioid abuse at the community level.
Increased Frequency of Acute Illness and Hospitalizations in Infants and Toddlers with Congenital Adrenal Hyperplasia
Authors: Tseng Teresa , Seagroves Amy , Koppin Christina M. , Keenan Madison , Putterman Elana , Nguyen Eugene , Chand Sanjay , Geffner Mitchell E. , Chang Todd P. , Kim Mimi S.
Published: September 2019

Purpose

Infants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for adrenal crisis and associated sequelae. To better understand acute illness at this early age, we determined the frequency and severity of acute illness and hospitalizations between 0-4 years of age, both within CAH and compared to controls. We also evaluated the impact of pre-hospital stress-dose hydrocortisone on Emergency Department (ED) visits and hospitalizations.

Methods

We performed a retrospective study of 40 CAH youth and 27 age-matched controls at a tertiary center. Characteristics of acute illnesses during the first 4 years of life were recorded, including fever, vomiting, diarrhea, ED visits, hospitalizations, abnormal electrolytes, and stress-dose hydrocortisone usage.

Results

CAH youth had more frequent illnesses requiring stress-dosing when they were younger than 2 years old [4.0 (1.0-6.0)] compared to when they were 2-4 years old [3.0 (1.0-4.0), P < 0.05], with the most illnesses during their first year of life. As well, CAH infants and toddlers had more hospitalizations younger than 2 years old compared to 2-4 years old (36 vs 2). 25% (3/12) of CAH youth with abnormal electrolytes in the ED did not receive any stress-dosing (oral/IM) prior to the ED, and only 25% (3/12) had received intramuscular hydrocortisone at home. CAH youth had more frequent ED visits (7.4 times as many) and hospitalizations (38 to 0) compared to controls.

Conclusions

Very young children with classical CAH are at high risk for acute illness and hospitalizations during their first 2 years of life, and do not receive adequate stress-dosing prior to the ED despite appropriate education. Our findings underscore the need for earlier recognition of acute illness in this vulnerable population and improved education regarding administration of stress-dose hydrocortisone to prevent morbidity.
Bat coronavirus phylogeography in the Western Indian Ocean
Authors: Joffrin Léa , Goodman Steven M. , Wilkinson David A. , Ramasindrazana Beza , Lagadec Erwan , Gomard Yann , Minter Gildas Le , Dos Santos Andréa , Schoeman M. Corrie , Sookhareea Rajendraprasad , Tortosa Pablo , Julienne Simon , Gudo Eduardo S. , Mavingui Patrick , Lebarbenchon Camille
Published: September 2019

Bats provide key ecosystem services such as crop pest regulation, pollination, seed dispersal, and soil fertilization. Bats are also major hosts for biological agents responsible for zoonoses, such as coronaviruses (CoVs). The islands of the Western Indian Ocean are identified as a major biodiversity hotspot, with more than 50 bat species. In this study, we tested 1,013 bats belonging to 36 species from Mozambique, Madagascar, Mauritius, Mayotte, Reunion Island and Seychelles, based on molecular screening and partial sequencing of the RNA-dependent RNA polymerase gene. In total, 88 bats (8.7%) tested positive for coronaviruses, with higher prevalence in Mozambican bats (20.5% ± 4.9%) as compared to those sampled on islands (4.5% ± 1.5%). Phylogenetic analyses revealed a large diversity of α- and β-CoVs and a strong signal of co-evolution between CoVs and their bat host species, with limited evidence for host-switching, except for bat species sharing day roost sites.

Importance

This is the first study to report the presence of coronaviruses (CoVs) in bats in Mayotte, Mozambique and Reunion Island, and in insectivorous bats in Madagascar. Eight percent of the tested bats were positive for CoVs, with higher prevalence in continental Africa than on islands. A high genetic diversity of α- and β-CoVs was found, with strong association between bat host and virus phylogenies, supporting a long history of co-evolution between bats and their associated CoVs in the Western Indian Ocean. These results highlight that strong variation between islands does exist and is associated with the composition of the bat species community on each island. Future studies should investigate whether CoVs detected in these bats have a potential for spillover in other hosts.
New Additions to the CRISPR Toolbox: CRISPR-CLONInG and CRISPR-CLIP for Donor Construction in Genome Editing
Authors: Shola Dorjee T.N. , Yang Chingwen , Kewaldar Vhy-Shelta , Kar Pradip , Bustos Victor
Published: September 2019

CRISPR-Cas has proven to be the most versatile genetic tinkering system of our time, predominantly as a precision genome editing tool. Here, we demonstrate two additions to the repertoire of CRISPR’s application for constructing donor DNA templates. (i) CRISPR-CLONInG (CRISPR-Cutting & Ligation Of Nucleic acid In vitro via Gibson) was devised to enable efficient cut-and-paste of multiple complex DNA fragments by using CRISPR/Cas9 as a digestion alternative with precision and exclusivity features, followed by joining the digested products via Gibson Assembly, to rapidly construct dsDNA and AAV donor vectors without cloning scars. (ii) CRISPR-CLIP (CRISPR-Clipped Long ssDNA via Incising Plasmid) was devised as a DNA clipping tool to efficiently retrieve long single-stranded DNA (lssDNA) from plasmid, up to 3.5 kbases, which can be supplied as the donor template for creating genetically engineered mice via Easi-CRISPR. We utilized two different Cas types (Cpf1 and Cas9n) to induce two distinct incisions at the respective ends of the lssDNA cassette junctions on the plasmid, yielding three independent single-stranded DNA units of unique sizes eligible for strand separation, followed by target strand clip-out through gel extraction. The retrieval of the lssDNA donor circumvents involvements of restriction enzymes and DNA polymerase-based steps, hence not only retains sequence fidelity but carries virtually no restriction on sequence composition, further mitigating limitations on current Easi-CRISPR method. With the add-on feature of universal DNA-tag sequences of Cpf1-Cas9 duo PAM, CRISPR-CLIP can be facile and applicable to generate lssDNA templates for any genomic target of choice. Additionally, we demonstrate robust gene editing efficiencies in neuroblastoma cell line as well as in mice attained with the AAV and lssDNA donors constructed herein.
Differential gene expression and functional pathway enrichment in colon cell line CCD 841 CoN (CRL-1790) transfected with miR-mimics miR-18b, miR-142-3p, miR-155, and miR-890
Authors: Robinson JM
Published: September 2019

This report is a bioinformatic analysis of samples from NCBI GEO database series GS132501. It includes previously un-reported data for miR-mimic over-expression of the miRNAs miR-18b, miR-155, miR-142-3p, and miR-890 in the ATCC CRL-1790 cell line. Data analysis was performed using Nanostring nSolver 4.0 and Advanced Analysis Module 2.0 plugin (Nanostring MAN-10030-03). Bioinformatic methods utilized include pathway scoring, differential expression (DE), and gene-set enrichment (GSE) analyses. Findings, with full supplementary data, provide a community resource for effects of dysregulation of these miRNAs in a colon ‘epithelial-like’ cell line.
Disrupting the leukemia niche in the central nervous system attenuates leukemia chemoresistance
Authors: Jonart Leslie M. , Ebadi Maryam , Basile Patrick , Johnson Kimberly , Makori Jessica , Gordon Peter M.
Published: September 2019

Protection from acute lymphoblastic leukemia (ALL) relapse in the central nervous system (CNS) is crucial to survival and quality of life for ALL patients. Current CNS-directed therapies cause significant toxicities and are only partially effective. Moreover, the impact of the CNS microenvironment on leukemia biology is poorly understood. Herein, we showed that leukemia cells associated with the meninges of xenotransplanted mice, or co-cultured with meningeal cells, exhibit enhanced chemoresistance due to effects on both apoptosis balance and quiescence. From a mechanistic standpoint, we identified that leukemia chemoresistance is primarily mediated by direct leukemia-meningeal cell interactions and overcome by detaching the leukemia cells from the meninges. Next, we used a co-culture adhesion assay to identify drugs that disrupted leukemia-meningeal adhesion. In addition to identifying several drugs that inhibit canonical cell adhesion targets we found that Me6TREN, a novel hematopoietic stem cell (HSC) mobilizing compound, also disrupts leukemia-meningeal adhesion in vitro and in vivo. Finally, Me6TREN enhanced the efficacy of cytarabine in treating CNS leukemia in xenotransplanted mice. This work demonstrates that the meninges exert a critical influence on leukemia chemoresistance, elucidates mechanisms of CNS relapse beyond the well-described role of the blood-brain barrier, and identifies novel therapeutic approaches for overcoming chemoresistance.
Predicting Adverse Drug-Drug Interactions with Neural Embedding of Semantic Predications
Authors: Burkhardt Hannah A. , Subramanian Devika , Mower Justin , Cohen Trevor
Published: September 2019

The identification of drug-drug interactions (DDIs) is important for patient safety; yet, compared to other pharmacovigilance work, a limited amount of research has been conducted in this space. Recent work has successfully applied a method of deriving distributed vector representations from structured biomedical knowledge, known as Embedding of Semantic Predications (ESP), to the problem of predicting individual drug side effects. In the current paper we extend this work by applying ESP to the problem of predicting polypharmacy side-effects for particular drug combinations, building on a recent reconceptualization of this problem as a network of drug nodes connected by side effect edges. We evaluate ESP embeddings derived from the resulting graph on a side-effect prediction task against a previously reported graph convolutional neural network approach, using the same data and evaluation methods. We demonstrate that ESP models perform better, while being faster to train, more re-usable, and significantly simpler.
Human oocytes harbouring damaged dna can complete meiosis-i
Authors: Rémillard-Labrosse Gaudeline , Dean Nicola , Allais Adélaïde , Mihajlović Aleksandar I. , Jin Shao Guang , Son Weon-Young , Chung Jin-Tae , Pansera Melissa , Henderson Sara , Mahfoudh Alina , Steiner Naama , Agapitou Kristy , Marangos Petros , Buckett William , Ligeti-Ruiter Jacob , FitzHarris Greg
Published: September 2019

Chromosomal abnormalities such as aneuploidies and DNA damage are considered a major threat to the establishment of healthy eggs and embryos. Recent landmark studies showed that mouse oocytes with damaged DNA can resume meiosis and undergo Germinal Vesicle Breakdown (GVBD), but then arrest in metaphase of meiosis-I in a process involving Spindle Assembly Checkpoint (SAC) signalling. Such a mechanism could help prevent the generation of metaphase-II (Met-II) eggs with damaged DNA. However we report that this is not the case in the human oocyte. DNA damage prevents human oocytes from undergoing GVBD in some cases. Strikingly however, most oocytes harbouring DNA damage progress through meiosis-I and subsequently extrude the first polar body (PB1) to form a metaphase-II egg, revealing the absence of a DNA-damage-induced SAC response. Analysis of the resulting metaphase-II eggs revealed highly disorganised spindles with misaligned and heavily damaged chromosomes. Our results suggest that DNA damage accumulated in meiosis-I, such as could occur during in vitro maturation procedures, does not prevent polar body extrusion and therefore could persist in morphologically normal looking metaphase-II eggs.
Sawfish, Read in Tooth and Saw: rostral teeth as endogenous chemical records of movement and life-history in a critically endangered species
Authors: Hegg Jens C. , Graves Breanna , Fisher Chris M.
Published: September 2019

The ecology of endangered and rare species can be difficult to study due to their low abundances and legal limits on scientist’s ability to catch, sample, and track them. This is particularly true of sawfish (family Pristidae) whose numbers have declined precipitously, placing all five species on the IUCN Red List of Threatened Species worldwide. Best known for their distinctive, toothed rostrum, the ecology, movement, and life-history of sawfish is poorly understood.

Sawfish rostral teeth are modified placoid scales, which grow continuously throughout the life of the fish. This continuous growth, combined with their stable calcified makeup, makes sawfish rostral teeth a potential source of temporal records of chemical and isotopic changes through the life of the fish.

Rostral teeth are often preserved in museums and as curios, potentially providing a source of life-history data to inform conservation actions without the need for field study, or as an important compliment to it. This is the first study to recover temporally explicit chemical data from sawfish rostral teeth.

Using archived samples of largetooth sawfish (Pristis pristis) we show that multiple chemical tracers can be recovered from sawfish rostral teeth, and that these tracers can be used to understand movement across salinity gradients. We further show that sawfish rostral teeth contain repeated structures and indistinct banding which could potentially be used for aging or growth analysis of fish.
Immune genes,IL1βandCasp9,show sexual dimorphic methylation patterns in the zebrafish gonads
Authors: Caballero-Huertas M. , Moraleda-Prados J. , Joly S. , Ribas L.
Published: September 2019

There is a crosstalk between the immune and the reproductive systems in which sexual dimorphism is a common pattern in vertebrates. In the last years, epigenetics has emerged as a way to study the molecular mechanisms involved during gonadal development, which are responsible to integrate environmental information that contributes to assign a specific sexual phenotype (either an ovary or a testis). In the fish gonads, it is known of the existence of the reproduction-immune system interactions although the epigenetic mechanisms involved are far to be elucidated. Here, we used the zebrafish (Danio rerio) as a model to study the DNA methylation patterns of two well-known innate immune genes:IL1βandCasp9. DNA methylation levels were studied by a candidate gene approach at single nucleotide resolution and further, gene expression analysis were carried out. Results showed that there was clear sexual dimorphism in the DNA methylation levels of the two immune studied genes, being significantly higher in the testes when compared to the ovaries. In summary, and although much research is needed, here we present two potential candidates as epimarkers with forthcoming applications in the livestock and fish farming production, for example, in immune fish diseases or sexual control programs.
Bioremediation of hydrocarbon contaminated soil from Carlini Station, Antarctica: effectiveness of different nutrient sources as biostimulation agents
Authors: Villalba Primitz Julia , Vázquez Susana , Ruberto Lucas , Lo Balbo Alfredo , Mac Cormack Walter
Published: September 2019

Logistics and scientific activities carried out in Antarctic stations entail the risk of contamination by fuels. Among remediation strategies, biostimulation of chronically contaminated Antarctic soils significantly improves the efficiency of hydrocarbons (HCs) removal. The aim of this study was to evaluate the performance of different nutrient formulations as biostimulation agents, in order to improve the elimination of diesel fuel from Antarctic soils, in both oxic and anoxic conditions. A field test was performed in microcosms (15 kg of soil each) as experimental systems. Each microcosm was prepared by triplicate, sampled every 10 days over a 50-days period and sampled again one year later. Changes in bacterial communities, and qualitative and quantitative HCs analysis were determined. Our results showed that, during the early stages of the process, a multi-component commercial product like OSEII®(containing nutrients, enzymes and surfactants) determines a rapid elimination of HCs with changes in the structure of the bacterial soil community, whereas a more cost-effective slow-release fertilizer like Nitrofoska®would be efficient in a long-term bioremediation process.
Are methylation beta-values simplex distributed?
Authors: Nonell Lara , González Juan R
Published: September 2019

DNA methylation plays an important role in the development and progression of disease. Beta-values are the standard methylation measures. Different statistical methods have been proposed to assess differences in methylation between conditions. However, most of them do not completely account for the distribution of beta-values. The simplex distribution can accommodate beta-values data. We hypothesize that simplex is a quite flexible distribution which is able to model methylation data.

To test our hypothesis, we conducted several analyses using four real data sets obtained from microarrays and sequencing technologies. Standard data distributions were studied and modelled in comparison to the simplex. Besides, some simulations were conducted in different scenarios encompassing several distribution assumptions, regression models and sample sizes. Finally, we compared DNA methylation between females and males in order to benchmark the assessed methodologies under different scenarios.

According to the results obtained by the simulations and real data analyses, DNA methylation data are concordant with the simplex distribution in many situations. Simplex regression models work well in small sample size data sets. However, when sample size increases, other models such as the beta regression or even the linear regression can be employed to assess group comparisons and obtain unbiased results. Based on these results, we can provide some practical recommendations when analyzing methylation data: 1) use data sets of at least 10 samples per studied condition for microarray data sets or 30 in NGS data sets, 2) apply a simplex or beta regression model for microarray data, 3) apply a linear model in any other case.
The effect of autopolyploidy on population genetic signals of hard sweeps
Authors: Monnahan Patrick , Brandvain Yaniv
Published: September 2019

Searching for population genomic signals left behind by positive selection is a major focus of evolutionary biology, particularly as sequencing technologies develop and costs decline. The effect of the number of chromosome copies (i.e. ploidy) on the manifestation of these signals remains an outstanding question, despite a wide appreciation of ploidy being a fundamental parameter governing numerous biological processes. We clarify the principal forces governing the differential manifestation and persistence of the signal of selection by separating the effects of polyploidy on rates of fixation versus rates of diversity (i.e. mutation and recombination) with a set of coalescent simulations. We explore what the major consequences of polyploidy, such as a more localized signal, greater dependence on dominance, and longer persistence of the signal following fixation, mean for within- and across-ploidy inference on the strength and prevalence of selective sweeps. As genomic advances continue to open doors for interrogating natural systems, studies such as this aid our ability to anticipate, interpret, and compare data across ploidy levels.
Precise annotation of tick mitochondrial genomes reveals multiple STR variation and one transposon-like element
Authors: Chen Ze , Xu Xiaofeng , Yang Xiaolong , Yu Zhijun , Hu Yonghong , Wang Duo , Bu Wenjun , Liu Jingze , Gao Shan
Published: September 2019

In this study, we used long-PCR amplification combined with Next-Generation Sequencing (NGS) to obtain complete mitochondrial genomes of individual ticks and performed precise annotation of these genomes. These annotations were confirmed by the PacBio full-length transcriptome data to cover both entire strands of the mitochondrial genomes without any gaps or overlaps. Based on these annotations, most of our findings were consistent with those from previous studies. Moreover, two important findings were reported for the first time, contributing fundamental knowledge to mitochondrial biology. The first was the discovery of a transposon-like element that may reveal the mechanisms of mitochondrial gene order rearrangement and genomic structural variation. Another finding was that Short Tandem Repeat (STRs) are the dominant variation type causing mitochondrial sequence diversity within an individual tick, insect, mouse and human. Comparisons between interindividual and intraindividual variation showed that polynucleotides and STRs with longer repeat units had the same variation pattern. Particularly, mitochondria containing deleterious mutations can accumulate in cells and deleterious STR mutations irreversibly change the proteins made from their mRNAs. Therefore, we proposed that deleterious STR mutations in mitochondria cause aging and diseases. This finding helped to ultimately reveal the mechanisms of mitochondrial DNA variation and its consequences (e.g., aging and diseases) in animals. Our study will give rise to the reconsideration of the importance of STRs and a unified study of STR variation with longer and shorter repeat units (particularly polynucleotides) in both nuclear and mitochondrial genomes. The complete mitochondrial genome sequence of Dermacentor silvarum is available at the NCBI GenBank database under the accession number MN347015 and the raw data is available at the NCBI SRA database under the accession number SRP178347.
A simple method to quantify protein abundances from one thousand cells
Authors: Vitrinel Burcu , Iannitelli Dylan E. , Mazzoni Esteban O. , Christiaen Lionel , Vogel Christine
Published: September 2019

The rise of single-cell transcriptomics has created an urgent need for similar approaches that use a minimal number of cells to quantify expression levels of proteins. We integrated and optimized multiple recent developments to establish a proteomics workflow to quantify proteins from as few as 1,000 mammalian stem cells. The method uses chemical peptide labeling, does not require specific equipment other than cell lysis tools, and quantifies >2,500 proteins with high reproducibility. We validated the method by comparing mouse embryonic stem cells and in vitro differentiated motor neurons. We identify differentially expressed proteins with small fold-changes, and a dynamic range in abundance similar to that of standard methods. Protein abundance measurements obtained with our protocol compare well to corresponding transcript abundance and to measurements using standard inputs. The protocol is also applicable to other systems, such as FACS-purified cells from the tunicate Ciona. Therefore, we offer a straightforward and accurate method to acquire proteomics data from minimal input samples.
Hybrid incompatibility between D. virilis and D. lumei is stronger in the presence of transposable elements
Authors: Castillo Dean M. , Moyle Leonie C.
Published: September 2019

Mismatches between parental genomes in selfish elements are frequently hypothesized to underlie hybrid dysfunction and drive speciation. However, because the genetic basis of most hybrid incompatibilities is unknown, testing the contribution of selfish elements to reproductive isolation is difficult. Here we evaluated the role of transposable elements (TEs) in hybrid incompatibilities between Drosophila virilis and D. lummei by experimentally comparing hybrid incompatibility in a cross where active TEs are present in D. virilis (TE+) and absent in D. lummei, to a cross where these TEs are absent from both D. virilis (TE-) and D. lummei genotypes. Using genomic data, we confirmed copy number differences in TEs between the D. virilis (TE+) strain and both the D. virilis (TE-) strain and D. lummei. We observed F1 postzygotic reproductive isolation exclusively in the interspecific cross involving TE+ D. virilis but not in crosses involving TE- D. virilis. This mirrors intraspecies dysgenesis where atrophied testes only occur when TE+ D. virilis is the paternal parent. A series of backcross experiments, that accounted for alternative models of hybrid incompatibility, showed that both F1 hybrid incompatibility and intrastrain dysgenesis are consistent with the action of TEs rather than genic interactions. Thus, our data suggest that this TE mechanism manifests as two different incompatibility phenotypes. A further Y-autosome interaction contributes to additional, sex-specific, inviability in one direction of this cross combination. These experiments demonstrate that TEs that cause intraspecies dysgenesis can increase reproductive isolation between closely related lineages, thereby adding to the processes that consolidate speciation.
Putatively cancer-specific alternative splicing is shared across patients and present in developmental and other non-cancer cells
Authors: David Julianne K. , Maden Sean K. , Weeder Benjamin R. , Thompson Reid F. , Nellore Abhinav
Published: September 2019

We compared cancer and non-cancer RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) Project, and the Sequence Read Archive (SRA). We found that: 1) averaging across cancer types, 80.6% of exon-exon junctions thought to be cancer-specific based on comparison with tissue-matched samples are in fact present in other adult non-cancer tissues throughout the body; 2) 30.8% of junctions not present in any GTEx or TCGA normal tissues are shared by multiple samples within at least one cancer type cohort, and 87.4% of these distinguish between different cancer types; and 3) many of these junctions not found in GTEx or TCGA normal tissues (15.4% on average) are also found in embryological and other developmentally associated cells. This study probes the distribution of putatively cancer-specific junctions across a broad set of publicly available non-cancer human RNA-seq datasets. Overall, we identify a subset of shared cancer-specific junctions that could represent novel sources of cancer neoantigens. We further describe a framework for characterizing possible origins of these junctions, including potential developmental and embryological sources, as well as cell type-specific markers particularly related to cell types of cancer origin. These findings refine the meaning of RNA splicing event novelty, particularly with respect to the human neoepitope repertoire. Ultimately, cancer-specific exon-exon junctions may affect the anti-cancer immune response and may have a substantial causal relationship with the biology of disease.
Reconstruction of plant–pollinator networks from observational data
Authors: Young Jean-Gabriel , Valdovinos Fernanda S. , Newman M. E. J.
Published: September 2019

Empirical measurements of ecological networks such as food webs and mutualistic networks are often rich in structure but also noisy and error-prone, particularly for rare species for which observations are sparse. Focusing on the case of plant-pollinator networks, we here describe a Bayesian statistical technique that allows us to make accurate estimates of network structure and ecological metrics from such noisy observational data. Our method yields not only estimates of these quantities, but also estimates of their statistical errors, paving the way for principled statistical analyses of ecological variables and outcomes. We demonstrate the use of the method with an application to previously published data on plant-pollinator networks in the Seychelles archipelago, calculating estimates of network structure, network nestedness, and other characteristics.
Chromosomal rearrangements and loss of subtelomeric adhesins linked to clade-specific phenotypes in Candida auris
Authors: Muñoz José F. , Welsh Rory M. , Shea Terrance , Batra Dhwani , Gade Lalitha , Litvintseva Anastasia P. , Cuomo Christina A.
Published: September 2019

Candida auris is an emerging fungal pathogen of rising concern due to its increasing incidence, its ability to cause healthcare-associated outbreaks and antifungal resistance. Genomic analysis revealed that early cases of C. auris that were detected contemporaneously were geographically stratified into four major clades. Clade II, also termed East Asian clade, consists of the initial isolates described from cases of ear infection, is less frequently resistant to antifungal drugs and to date, the isolates from this group have not been associated with outbreaks. Here, we generate nearly complete genomes (“telomere-to-telomere”) of an isolate of this clade and of the more widespread Clade IV. By comparing these to genome assemblies of the other two clades, we find that the Clade II genome appears highly rearranged, with 2 inversions and 9 translocations resulting in a substantially different karyotype. In addition, large subtelomeric regions have been lost from 10 of 14 chromosome ends in the Clade II genomes. We find that shorter telomeres and genome instability might be a consequence of a naturally occurring loss-of-function mutation in DCC1 exclusively found in Clade II isolates, resulting in a hypermutator phenotype. We also determine that deleted subtelomeric regions might be linked to clade-specific adaptation as these regions are enriched in Hyr/Iff-like cell surface proteins, novel candidate cell surface proteins, and an ALS-like adhesin. The presence of these cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggests an explanation for the different phenotypes observed between clades.

IMPORTANCE

Candida auris was unknown prior to 2009 and since then it has quickly spread around the world, causing outbreaks in healthcare facilities and representing a high fraction of candidemia cases in some regions. The emergence of C. auris is a major concern, since it is often multidrug-resistant, easily spread between patients, and causes invasive infections. While isolates from three global clades cause invasive infections, isolates from Clade II primarily cause ear infections and have not been implicated in outbreaks, though cases of Clade II infections have been reported on different continents. Here, we describe genetic differences between Clade II and Clades I, III and IV, including a loss-of-function mutation in a gene associated with telomere length maintenance and genome stability, and the loss of cell wall proteins involved in adhesion and biofilm formation, that may suggest an explanation for the lower virulence and potential for transmission of Clade II isolates.
A collection of genetic mouse lines and related tools for inducible and reversible intersectional misexpression
Authors: Ahmadzadeh Elham , Bayin N. Sumru , Qu Xinli , Singh Aditi , Madisen Linda , Stephen Daniel , Zeng Hongkui , Joyner Alexandra L. , Rosello-Diez Alberto
Published: September 2019

Thanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches utilizing two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach utilizes available lines expressing tTA/rTA to control timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf) and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms.

Summary statement

Ahmadzadeh et al. present a collection of four mouse lines and genetic tools for misexpression-mediated manipulation of cellular activity with high spatiotemporal control, in a reversible manner.
Gaze stabilisation behaviour is anisotropic across visual field locations in zebrafish
Authors: Dehmelt Florian A. , Meier Rebecca , Hinz Julian , Yoshimatsu Takeshi , Simacek Clara A. , Wang Kun , Baden Tom , Arrenberg Aristides B.
Published: September 2019

Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs, measured the optokinetic response gain of immobilised zebrafish larvae, and related behaviour to previously published retinal photoreceptor densities. We measured tuning to steradian stimulus size and spatial frequency, and show it to be independent of visual field position. However, zebrafish react most strongly and consistently to lateral, nearly equatorial stimuli, consistent with previously reported higher spatial densities in the central retina of red, green and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.

Author summary

The visual system of larval zebrafish mirrors many features present in the visual system of other vertebrates, including its ability to mediate optomotor and optokinetic behaviour. Although the presence of such behaviours and some of the underlying neural correlates have been firmly established, previous experiments did not consider the large visual field of zebrafish, which covers more than 160° for each eye. Given that different parts of the visual field likely carry unequal amount of behaviourally relevant information for the animal, this raises the question whether optic flow is integrated across the entire visual field or just parts of it, and how this shapes behaviour such as the optokinetic response. We constructed a spherical LED arena to present visual stimuli almost anywhere across their visual field, while tracking horizontal eye movements. By displaying moving gratings on this LED arena, we demonstrate that the optokinetic response, one of the most prominent visually induced behaviours of zebrafish, indeed strongly depends on stimulus location and stimulus size, as well as on other parameters such as the spatial and temporal frequency of the gratings. This location dependence is consistent with areas of high retinal photoreceptor densities, though evidence suggests further extraretinal processing.
Similar somatotopy for active and passive digit representation in primary somatosensory cortex
Authors: Sanders Zeena-Britt , Wesselink Daan B , Dempsey-Jones Harriet , Makin Tamar R
Published: September 2019

Scientists traditionally use passive stimulation to examine organisational properties of the primary somatosensory cortex (SI). Recent research has, however, emphasised the close and bidirectional relationship between somatosensory and motor systems. This suggests active contributions (e.g., direct inputs from the motor system to SI) should also be considered when studying SI representations. Under such a framework, discrepant results are possible when different tasks are used to study the same underlying somatosensory representation. Here we examined whether SI hand representation is consistent when compared between active and passive tasks. Moreover, we ask whether this holds when task demands and stimulus properties are not directly matched. Using 7T fMRI, we examined three key digit representation features – spatial location, activity gradient profiles and multivariate representational structure. We show that although activity was increased overall in the active task, all key features of digit somatotopy were consistent over tasks, using both traditional univariate (activity-level) and multivariate (pattern structure) measurements. Despite overall comparability, when investigating fine-grained features of somatotopy using multivariate analysis, the active task was superior for individuating the representation across digits. We suggest that the information produced by an active task is more aligned with typical, ecologically relevant patterns of hand sensory input, resulting in more optimal SI activity patterns. Our findings validate the utilisation of active tasks for studying SI somatotopy.
Genome-wide association analyses of multiple traits in Duroc pigs using low-coverage whole-genome sequencing strategy
Authors: Yang Ruifei , Guo Xiaoli , Zhu Di , Bian Cheng , Zhao Yiqiang , Tan Cheng , Wu Zhenfang , Wang Yuzhe , Hu Xiaoxiang , Li Ning
Published: September 2019

High-density markers discovered in large size samples are essential for mapping complex traits at the gene-level resolution for agricultural livestock and crops. However, the unavailability of large reference panels and array designs for a target population of agricultural species limits the improvement of array-based genotype imputation. Recent studies showed very low coverage sequencing (LCS) of a large number of individuals is a cost-effective approach to discover variations in much greater detail in association studies. Here, we performed cohort-wide whole-genome sequencing at an average depth of 0.73× and identified more than 11.3 M SNPs. We also evaluated the data set and performed genome-wide association analysis (GWAS) in 2885 Duroc boars. We compared two different pipelines and selected a proper method (BaseVar/STITCH) for LCS analyses and determined that sequencing of 1000 individuals with 0.2× depth is enough for identifying SNPs with high accuracy in this population. Of the seven association signals derived from the genome-wide association analysis of the LCS variants, which were associated with four economic traits, we found two QTLs with narrow intervals were possibly responsible for the teat number and back fat thickness traits and identified 7 missense variants in a single sequencing step. This strategy (BaseVar/STITCH) is generally applicable to any populations and any species which have no suitable reference panels. These findings show that the LCS strategy is a proper approach for the construction of new genetic resources to facilitate genome-wide association studies, fine mapping of QTLs, and genomic selection, and implicate that it can be widely used for agricultural animal breeding in the future.