bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of evidence of mastitis as a causal factor for postpartum dysgalactia syndrome in sows123
Authors: Kaiser Marianne , Jacobson Magdalena , Bækbo Poul , Dahl Jan , Jacobsen Stine , Guo Yong Z , Larsen Torben , Andersen Pia H
Published: October 2019

To investigate the prevalence of mastitis in sows suffering from postpartum dysgalactia syndrome (PDS), we examined milk constituents and concentrations of lipopolysaccharides (LPS) obtained from the udder vein (v. epigastrica). As part of a case–cohort study, 109 sows were monitored daily from 60 h antepartum (a.p.) to 36 h postpartum (p.p.). Over time, 38 sows were diagnosed with PDS (PDS+) and were retrospectively matched with 38 healthy sows (PDS−). The study period was divided into 7 smaller time periods (A, B, C, D, E, F, G, H, and E), allowing the studied values, in period B to G, to be compared with period A that served as a baseline, and PDS+ and PDS− sows were compared within the time periods. All sows were subjected to a thorough daily clinical examination and blood was sampled from v. epigastrica for LPS detection. Milk samples were obtained for bacteriological evaluation and detection of N-acetyl-beta-d-glucosaminidase (NAGase), lactate dehydrogenase (LDH), β-glucuronidase (β-glu; for evaluation of mastitis), isocitrate (isoC), free glucose, uric acid (UA; for evaluation of the mammary energy status), β-hydroxybutyrate acid (BHBA; for evaluation of ketosis), and milk urea (for evaluation of the protein status). The results revealed that PDS+ sows had decreased concentrations of UA in milk (P < 0.0001), increased heart rates (P < 0.01), increased mammary edema (P < 0.05), and prolonged capillary refill time in the vulvar mucosa (P < 0.01) compared with PDS− sows. Compared with baseline, feces became more solid 0 to 36 h p.p. (P < 0.0001) and the respiration rate decreased 12 to 24 h p.p. (P < 0.0001) for both PDS+ and PDS− sows. No differences were found between PDS+ and PDS− sows for severe bacterial infections, concentrations of LPS in blood or LDH, NAGase, BHBA, free glucose, isoC, or urea in milk. Concentrations of LPS in blood were not associated with signs of mastitis or edema in the mammary glands. However, a difference over time was seen for redness (P < 0.0001), warmth (P < 0.0001), and hardness (P < 0.05) of the 6 most anterior glands in both PDS+ and PDS− sows from 60 h a.p to 36 h p.p. The PDS− sows had greater concentrations of β-glu than the PDS+ sows, but no change over time was demonstrated for this marker. In conclusion, signs of mastitis were not consistently linked to PDS in sows. However, the cardiovascular system seemed to be compromised in PDS+ sows and the cause should be investigated to elucidate the pathogenesis of PDS.
Randomized controlled trial of OnTrack, a just-in-time adaptive intervention designed to enhance weight loss
Authors: Forman Evan M , Goldstein Stephanie P , Crochiere Rebecca J , Butryn Meghan L , Juarascio Adrienne S , Zhang Fengqing , Foster Gary D
Published: October 2019

This randomized trial demonstrated qualified support for the ability of a machine learning-powered, smartphone-based just-in-time, adaptive intervention to enhance weight loss over and above a commercial weight loss program.
Identification and characterization of primordial germ cells in a vocal learning Neoaves species, the zebra finch
Authors: Jung Kyung Min , Kim Young Min , Keyte Anna L. , Biegler Matthew T. , Rengaraj Deivendran , Lee Hong Jo , Mello Claudio V. , Velho Tarciso A. F. , Fedrigo Olivier , Haase Bettina , Jarvis Erich D. , Han Jae Yong
Published: October 2019

The zebra finch has been used as a valuable vocal learning animal model for human spoken language. It is representative of vocal learning songbirds specifically, which comprise half of all bird species, and of Neoaves broadly, which comprise 95% of all bird species. Although transgenesis in the zebra finch has been accomplished, it is with a very low efficiency of germ‐line transmission and far from the efficiency with a more genetically tractable but vocal nonlearning species, the chicken (a Galloanseriformes). To improve germ‐line transmission in the zebra finch, we identified and characterized its primordial germ cells (PGCs) and compared them with chicken. We found striking differences between the 2 species, including that zebra finch PGCs were more numerous, more widely distributed in early embryos before colonization into the gonads, had slower timing of colonization, and had a different developmental gene‐expression program. We improved conditions for isolating and culturing zebra finch PGCs in vitro and were able to transfect them with gene‐expression vectors and incorporate them into the gonads of host embryos. Our findings demonstrate important differences in the PGCs of the zebra finch and advance the first stage of creating PGC‐mediated germ‐line transgenics of a vocal learning species.—Jung, K. M., Kim, Y. M., Keyte, A. L., Biegler, M. T., Rengaraj, D., Lee, H. J., Mello, C. V., Velho, T. A. F., Fedrigo, O., Haase, B., Jarvis, E. D., Han, J. Y. Identification and characterization of primordial germ cells in a vocal learning Neoaves species, the zebra finch. FASEB J. 33, 13825‐13836 (2019). www.fasebj.org
The Use of Test-negative Controls to Monitor Vaccine Effectiveness
Authors: Chua Huiying , Feng Shuo , Lewnard Joseph A. , Sullivan Sheena G. , Blyth Christopher C. , Lipsitch Marc , Cowling Benjamin J.
Published: October 2019

Background:

The test-negative design is an increasingly popular approach for estimating vaccine effectiveness (VE) due to its efficiency. This review aims to examine published test-negative design studies of VE and to explore similarities and differences in methodological choices for different diseases and vaccines.

Methods:

We conducted a systematic search on PubMed, Web of Science, and Medline, for studies reporting the effectiveness of any vaccines using a test-negative design. We screened titles and abstracts and reviewed full texts to identify relevant articles. We created a standardized form for each included article to extract information on the pathogen of interest, vaccine(s) being evaluated, study setting, clinical case definition, choices of cases and controls, and statistical approaches used to estimate VE.

Results:

We identified a total of 348 articles, including studies on VE against influenza virus (n = 253), rotavirus (n = 48), pneumococcus (n = 24), and nine other pathogens. Clinical case definitions used to enroll patients were similar by pathogens of interest but the sets of symptoms that defined them varied substantially. Controls could be those testing negative for the pathogen of interest, those testing positive for nonvaccine type of the pathogen of interest, or a subset of those testing positive for alternative pathogens. Most studies controlled for age, calendar time, and comorbidities.

Conclusions:

Our review highlights similarities and differences in the application of the test-negative design that deserve further examination. If vaccination reduces disease severity in breakthrough infections, particular care must be taken in interpreting vaccine effectiveness estimates from test-negative design studies.
Nursing Students' Perceptions of Just Culture in Nursing Programs
Authors: Walker Danielle , Altmiller Gerry , Hromadik Lora , Barkell Nina , Barker Nancy , Boyd Teri , Compton Michelle , Cook Pamela , Curia Marianne , Hays Deana , Flexner Randi , Jordan Janet , Jowell Vicki , Kaulback Michelle , Magpantay-Monroe Edna , Rudolph Bethany , Toothaker Rebecca , Vottero Beth , Wallace Sharon
Published: October 2019

Background

While just culture is embraced in the clinical setting, just culture has not been systematically incorporated into nursing education.

Purpose

The purpose of this study was to assess prelicensure nursing student perceptions of just culture in academia.

Methods

Following a quantitative, descriptive design, the Just Culture Assessment Tool for Nursing Education (JCAT-NE) was used to measure just culture across multiple (N = 15) nursing programs.

Results

The majority of JCAT-NE respondents (78%) reported their program has a safety reporting system, 15.4% had involvement in a safety-related event, and 12% submitted an error report. The JCAT-NE mean total score was 127.4 (SD, 23.6), with a statistically significant total score decline as students progressed from the beginning (133.6 [SD, 20.52]) to the middle (129.77 [SD, 23.6]) and end (122.2 [SD, 25.43]) of their programs (χ
2[2] = 25.09, P < .001).

Conclusions

The results from this study are a call to action for nursing education to emphasize the tenets of just culture, error reporting, and quality improvement.
Knowledge and Skills Acquisition by Plastic Surgery Residents through Digital Simulation Training: A Prospective, Randomized, Blinded Trial
Authors: Kantar Rami S. , Alfonso Allyson R. , Ramly Elie P. , Cohen Oriana , Rifkin William J. , Maliha Samantha G. , Diaz-Siso J. Rodrigo , Eisemann Bradley S. , Saadeh Pierre B. , Flores Roberto L.
Published: October 2019

Background:

Simulation is a standard component of residency training in many surgical subspecialties, yet its impact on knowledge and skills acquisition in plastic surgery training remains poorly defined. The authors evaluated the potential benefits of simulation-based cleft surgery learning in plastic surgery resident education through a prospective, randomized, blinded trial.

Methods:

Thirteen plastic surgery residents were randomized to a digital simulator or textbook demonstrating unilateral cleft lip repair. The following parameters were evaluated before and after randomization: knowledge of surgical steps, procedural confidence, markings performance on a three-dimensional stone model, and surgical performance using a hands-on/high-fidelity three-dimensional haptic model. Participant satisfaction with either educational tool was also assessed. Two expert reviewers blindly graded markings and surgical performance. Intraclass correlation coefficients were calculated. Wilcoxon signed rank and Mann-Whitney U tests were used.

Results:

Interrater reliability was strong for preintervention and postintervention grading of markings [preintervention intraclass correlation coefficient, 0.97 (p < 0.001); postintervention intraclass correlation coefficient, 0.96 (p < 0.001)] and surgical [preintervention intraclass correlation coefficient, 0.83 (p = 0.002); postintervention intraclass correlation coefficient, 0.81 (p = 0.004)] performance. Postintervention surgical knowledge (40.3 ± 4.4 versus 33.5 ± 3.7; p = 0.03), procedural confidence (24.0 ± 7.0 versus 14.7 ± 2.3; p = 0.03), markings performance (8.0 ± 2.5 versus 2.9 ± 3.1; p = 0.03), and surgical performance (12.3 ± 2.5 versus 8.2 ± 2.3; p = 0.04) significantly improved in the digital simulation group compared with before intervention, but not in the textbook group. All participants were more satisfied with the digital simulator as an educational tool (27.7 ± 2.5 versus 14.4 ± 4.4; p < 0.001).

Conclusion:

The authors present evidence suggesting that digital cognitive simulators lead to significant improvement in surgical knowledge, procedural confidence, markings performance, and surgical performance.
Classifying post-traumatic stress disorder using the magnetoencephalographic connectome and machine learning
Authors: Zhang Jing , Richardson J. Don , Dunkley Benjamin T.
Published: October 2019

Given the subjective nature of conventional diagnostic methods for post-traumatic stress disorder (PTSD), an objectively measurable biomarker is highly desirable. Macroscopic neural circuits measured using magnetoencephalography (MEG) has previously been shown to be indicative of the PTSD phenotype and severity. In the present study, we employed a machine learning-based classification framework using MEG neural synchrony to distinguish combat-related PTSD from trauma-exposed controls. Support vector machine (SVM) was used as the core classification algorithm. A recursive random forest feature selection step was directly incorporated in the nested SVM cross validation process (CV-SVM-rRF-FS) for identifying the most important features for PTSD classification. For the five frequency bands tested, the nested CV-SVM-rRF-FS analysis selected the minimum numbers of edges per frequency that could serve as a PTSD signature and be used as the basis for SVM modelling. Many of the selected edges have been reported previously to be core in PTSD pathophysiology, with frequency-specific patterns also observed. Furthermore, the independent partial least squares discriminant analysis suggested low bias in the nested CV-SVM-rRF-FS process. The final SVM models built with selected features showed excellent PTSD classification performance (area-under-curve value up to 0.9). Testament to its robustness when distinguishing individuals from a heavily-traumatised control group, these developments for a classification model for PTSD also provide a comprehensive machine learning-based computational framework for classifying other mental health challenges using MEG connectome profiles.
Dynamic interactions of influenza viruses in Hong Kong during 1998-2018
Authors: Yang Wan , Lau Eric H. Y. , Cowling Benjamin J.
Published: October 2019

Influenza epidemics cause substantial morbidity and mortality every year worldwide. Currently, two influenza A subtypes, A(H1N1) and A(H3N2), and type B viruses co-circulate in humans and infection with one type/subtype could provide cross-protection against the others. However, it remains unclear how such ecologic competition via cross-immunity and antigenic mutations that allow immune escape impact influenza epidemic dynamics at the population level. Here we develop a comprehensive model-inference system and apply it to study the evolutionary and epidemiological dynamics of the three influenza types/subtypes in Hong Kong, a city of global public health significance for influenza epidemic and pandemic control. Utilizing long-term influenza surveillance data since 1998, we are able to estimate the strength of cross-immunity between each virus-pairs, the timing and frequency of punctuated changes in population immunity in response to antigenic mutations in influenza viruses, and key epidemiological parameters over the last 20 years including the 2009 pandemic. We find evidence of cross-immunity in all types/subtypes, with strongest cross-immunity from A(H1N1) against A(H3N2). Our results also suggest that A(H3N2) may undergo antigenic mutations in both summers and winters and thus monitoring the virus in both seasons may be important for vaccine development. Overall, our study reveals intricate epidemiological interactions and underscores the importance of simultaneous monitoring of population immunity, incidence rates, and viral genetic and antigenic changes.
Association of rs12722 COL5A1 with Pulmonary Tuberculosis infection: a preliminary case-control study in a Kazakhstani population
Authors: Zhetkenev Sanzhar , Khassan Ayauly , Khamzina Armanay , Issanov Alpamys , Crape Byron , Akilzhanova Ainur , Kozhamkulov Ulan , Yerezhepov Dauren , Chan Chee Kai
Published: October 2019

Background

Lung cavitation is the classic hallmark of TB, which facilitates the disease development and transmission. It involves the degradation of lung parenchyma which is mainly made up of collagen fibers by metalloproteinases (MMPs) produced by activated monocyte-derived cells, neutrophils and stromal cells.

Objective

The following population-based preliminary case-control study of adults with TB and controls without TB will check the possible association between rs1800012 in COL1A1, rs1272222 in COL5A1 genes to human TB susceptibility in Kazakhstan.

Methods

In this case-control study including 165 samples we examined the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and adjusted logistic regression was performed to find out relationships between SNPS and other predictors.

Results

Preliminary findings suggest that there is a statistically significant association of age (OR=0.44, 95% CI:0.21-0.92, p-value=0.03), social status (OR=0.42, 95% CI:0.201 −0.87, p-value=0.020), HIV status(OR=6.9, 95% CI:1.86 - 25.6, p-value=0.004) and heterozygous rs12722 SNP (OR=2.45, 95% CI:1.16 −5.16 p-value=0.019) polymorphism of COL5A1 gene with TB susceptibility.

Conclusion

The association of collagen genes with TB pathogenesis indicates that anti TB programs should develop new drug regimens that include MMP inhibitors. Therapeutic targeting of MMPs will prevent extracellular matrix degradation and granuloma maturation.
Whole genome analysis identifies the association of TP53 genomic deletions with lower survival in Stage III colorectal cancer
Authors: Xia Li C , Van Hummelen Paul , Kubit Matthew , Lee Hojoon , Bell John M , Grimes Susan M. , Wood-Bouwens Christina , Greer Stephanie U. , Barker Tyler , Haslem Derrick S , Ford James , Fulde Gail , Ji Hanlee P , Nadauld Lincoln D
Published: October 2019

DNA copy number aberrations (CNA) were frequently observed in colorectal cancers (CRC). There is an urgent call for CNA-based biomarkers in clinics, in particular for Stage III CRC, if combined with imaging or pathologic evidence, promise more precise care at the timing. We conducted this Stage III specific biomarker discovery with a cohort of 134 CRCs, and with a newly developed high-efficiency CNA profiling protocol. Specifically, we developed the profiling protocol for tumor-normal matched tissue samples based on low-coverage clinical whole-genome sequencing (WGS). We demonstrated the protocol’s accuracy and robustness by a systematic benchmark with microarray, high-coverage whole-exome and -genome approaches, where the low-coverage WGS-derived CNA segments were highly accordant (PCC>0.95) with those derived from microarray, and they were substantially less variable if compared to exome-derived segments. A lasso-based model and multivariate cox regression analysis identified a chromosome 17p loss, containing the TP53 tumor suppressor gene, that was significantly associated with reduced survival (P=0.0139, HR=1.688, 95% CI = [1.112-2.562]), which was validated by an independent cohort of 187 Stage III CRCs. In summary, the new low-coverage WGS protocol has high sensitivity, high resolution and low cost and the identified 17p-loss is an effective poor prognosis marker for Stage III patients.
Out of the abyss: Genome and metagenome mining reveals unexpected environmental distribution of abyssomicins
Authors: Iglesias Alba , Latorre-Pérez Adriel , Stach James E. M. , Porcar Manuel , Pascual Javier
Published: October 2019

Natural products have traditionally been discovered through the screening of culturable microbial isolates from all sort of environments. The sequencing revolution allowed the identification of dozens of biosynthetic gene clusters (BGCs) within single bacterial genomes, either from cultured or uncultured strains. However, we are still far from fully exploiting the microbial reservoir, as most of the species are non-model organisms with complex regulatory systems and yet recalcitrant to be engineered. Today, genomic and metagenomic data produced by laboratories worldwide covering the most different natural and artificial environments on Earth, are an invaluable source of raw information from which natural product biosynthesis can be accessed. In the present work, we describe the environmental distribution and evolution of the abyssomicin BGC through the analysis of publicly available genomic and metagenomic data. Our results demonstrate that the selection of a pathway-specific enzyme to direct the genome mining is an excellent strategy that led to the identification of 74 new Diels-Alderase homologs and unveiled a surprising prevalence of the abyssomicin BGC within terrestrial habitats, mainly soil and plant-associated, where we have identified five complete and 12 partial new abyssomicin BGCs and 23 new potential abyssomicin BGCs. Our results strongly support the potential of genome and metagenome mining as a key preliminary tool to inform bioprospecting strategies aiming at the identification of new bioactive compounds such as -but not restricted to-abyssomicins.
Identification and Utilization of Copy Number Information for Correcting Hi-C Contact Map of Cancer Cell Line
Authors: Khalil Ahmed Ibrahim Samir , Muzaki Siti Rawaidah Mohammad , Chattopadhyay Anupam , Sanyal Amartya
Published: October 2019

Motivation

Hi-C and its variant techniques have been developed to capture the spatial organization of chromatin. Normalization of Hi-C contact maps is essential for accurate modeling and interpretation of genome-wide chromatin conformation. Most Hi-C correction methods are originally developed for normal cell lines and mainly target systematic biases. In contrast, cancer genomes carry multi-level copy number variations (CNVs). Copy number influences interaction frequency between genomic loci. Therefore, CNV-driven bias needs to be corrected for generating euploid-equivalent chromatin contact maps.

Results

We developed HiCNAtra framework that extracts read depth (RD) signal from Hi-C or 3C-seq reads to generate the high-resolution CNV profile and use this information to correct the contact map. We proposed the “entire restriction fragment” counting for better estimation of the RD signal and generation of CNV profiles. HiCNAtra integrates CNV information along with other systematic biases for explicitly correcting the interaction matrix using Poisson regression model. We demonstrated that RD estimation of HiCNAtra recapitulates the whole-genome sequencing (WGS)-derived coverage signal of the same cell line. Benchmarking against OneD method (only explicit method to target CNV bias) showed that HiCNAtra fared better in eliminating the impact of CNV on the contact maps.

Availability and implementation

HiCNAtra is an open source software implemented in MATLAB and is available athttps://github.com/AISKhalil/HiCNAtra.
Occasion setters determine responses of putative dopamine neurons to discriminative stimuli
Authors: Aquili Luca , Bowman Eric M. , Schmidt Robert
Published: October 2019

Midbrain dopamine (DA) neurons are involved in the processing of rewards and reward-predicting stimuli, possibly analogous to reinforcement learning reward prediction errors. Here we studied the activity of putative DA neurons (n=41) recorded in the ventral tegmental area of rats (n=6) performing a behavioural task involving occasion setting. In this task an occasion setter (OS) indicated that the relationship between a discriminative stimulus (DS) and reinforcement is in effect, so that reinforcement of bar pressing occurred only after the OS (tone or houselight) was followed by the DS (houselight or tone). We found that responses of putative DA cells to the DS were enhanced when preceded by the OS, as were behavioural responses to obtain rewards. Surprisingly though, we did not find a population response of putative DA neurons to the OS, contrary to predictions of standard temporal-difference models of DA neurons. However, despite the absence of a population response, putative DA neurons exhibited a heterogeneous response on a single unit level, so that some units increased and others decreased their activity as a response to the OS. Similarly, putative non-DA cells did not respond to the DS on a population level, but with heterogeneous responses on a single unit level. The heterogeneity in the responses of putative DA cells may reflect how DA neurons encode context and point to local differences in DA signalling.
Differences in directed functional brain connectivity related to age, sex and mental health
Authors: Lund Martina J. , Alnæs Dag , Schwab Simon , van der Meer Dennis , Andreassen Ole A. , Westlye Lars T. , Kaufmann Tobias
Published: October 2019

Objective

Functional interconnections between brain regions define the ‘connectome’ which is of central interest for understanding human brain function. Resting-state functional magnetic resonance (rsfMRI) work has revealed changes in static connectivity related to age, sex, cognitive abilities and psychiatric symptoms, yet little is known how these factors may alter the information flow. The commonly used approach infers functional brain connectivity using stationary coefficients yielding static estimates of the undirected connection strength between brain regions. Dynamic graphical models (DGMs) are a multivariate model with dynamic coefficients reflecting directed temporal associations between nodes, and can yield novel insight into directed functional connectivity. Here, we leveraged this approach to test for associations between edge-wise estimates of direction flow across the brain connectome and age, sex, intellectual abilities and mental health.

Methods

We applied DGM to investigate patterns of information flow in data from 984 individuals from the Human Connectome Project (HCP) and 10,249 individuals from the UK Biobank.

Results

Our analysis yielded patterns of directed connectivity in independent HCP and UK Biobank data similar to those previously reported, including that the cerebellum consistently receives information from other networks. We show robust associations between information flow and age and sex for several connections, with strongest effects of age observed in the sensorimotor network. Visual, auditory and sensorimotor nodes were also linked to mental health.

Discussion

Our findings support the use of DGM as a measure of directed connectivity in rsfMRI data and provide new insight into the shaping of the connectome during aging.
Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction
Authors: Post Kathryn L. , Belmadani Manuel , Ganguly Payel , Meili Fabian , Dingwall Riki , McDiarmid Troy A. , Meyers Warren M. , Herrington Caitlin , Young Barry P. , Callaghan Daniel B. , Rogic Sanja , Edwards Matthew , Niciforovic Ana , Cau Alessandro , Rankin Catharine H. , O’Connor Timothy P. , Bamji Shernaz X. , Loewen Christopher J. , Allan Douglas W. , Pavlidis Paul , Haas Kurt
Published: October 2019

Functional variomics provides the foundation for personalized medicine by linking genetic variation to disease expression, outcome and treatment, yet its utility is dependent on appropriate assays to evaluate mutation impact on protein function. To fully assess the effects of 106 missense and nonsense variants of PTEN associated with autism spectrum disorder, somatic cancer and PHTS, we take a deep phenotypic profiling approach using 18 assays in 5 model systems spanning diverse cellular environments ranging from molecular function to neuronal morphogenesis and behavior. Variants inducing instability occurred across the protein, resulting in partial to complete loss of function (LoF), which was well correlated across models. However, assays were selectively sensitive to variants located in substrate binding and catalytic domains, which exhibited complete LoF or dominant negativity independent of effects on stability. Our results indicate that full characterization of variant impact requires assays sensitive to instability and a range of protein functions.
Genetic signatures of evolutionary rescue by a selective sweep
Authors: Osmond Matthew M. , Coop Graham
Published: October 2019

One of the most useful models in population genetics is that of a selective sweep and the consequent hitch-hiking of linked neutral alleles. While variations on this model typically assume constant population size, many instances of strong selection and rapid adaptation in nature may co-occur with complex demography. Here we extend the hitch-hiking model to evolutionary rescue, where adaptation and demography not only co-occur but are intimately entwined. Our results show how this feedback between demography and evolution determines – and restricts – the genetic signatures of evolutionary rescue, and how these differ from the signatures of sweeps in populations of constant size. In particular, we find rescue to harden sweeps from standing variance or new mutation (but not from migration), reduce genetic diversity both at the selected site and genome-wide, and increase the range of observed Tajima’sDvalues. For a given initial rate of population decline, the feedback between demography and evolution makes all of these differences more dramatic under weaker selection, where bottlenecks are prolonged. Nevertheless, it is likely difficult to infer the co-incident timing of the sweep and bottleneck from these simple signatures, never-mind a feedback between them. Temporal samples spanning contemporary rescue events may offer one way forward.
Drosophila suzukii wing spot size is robust to developmental temperature
Authors: Varón-González Ceferino , Fraimout Antoine , Debat Vincent
Published: October 2019

Phenotypic plasticity is an important mechanism allowing adaptation to new environments and as such it has been suggested to facilitate biological invasions. Under this assumption, invasive populations are predicted to exhibit stronger plastic responses than native populations. Drosophila suzukii is an invasive species whose males harbor a spot on the wing tip. In this study, by manipulating developmental temperature, we compare the phenotypic plasticity of wing spot size of two invasive populations with that of a native population. We then compare the results with data obtained from wild-caught flies from different natural populations. While both wing size and spot size are plastic to temperature, no difference in plasticity was detected between native and invasive populations, rejecting the hypothesis of a role of the wing-spot plasticity in the invasion success. In contrast we observed a remarkable stability in the spot-to-wing ratio across temperatures, as well as among geographic populations. This stability suggests either that the spot relative size is under stabilizing selection, or that its variation might be constrained by a tight developmental correlation between spot size and wing size. Our data show that this correlation was lost at high temperature, leading to an increased variation in the relative spot size, particularly marked in the two invasive populations. This suggests (i) that D. suzukii’s development is impaired by hot temperatures, in agreement with the cold-adapted status of this species; (ii) that the spot size can be decoupled from wing size, rejecting the hypothesis of an absolute constraint and suggesting that the wing color pattern might be under stabilizing (sexual) selection; (iii) that such sexual selection might be relaxed in the invasive populations. Finally, a subtle but consistent directional asymmetry in spot size was detected in favor of the right side in all populations and temperatures, possibly indicative of a lateralized sexual behavior.
Primary myeloid cell proteomics and transcriptomics: importance of ß tubulin isotypes for osteoclast function
Authors: Guérit David , Marie Pauline , Morel Anne , Maurin Justine , Verollet Christel , Raynaud-Messina Brigitte , Urbach Serge , Blangy Anne
Published: October 2019

Among hematopoietic cells. osteoclasts (Oc) and immature dendritic cells (Dc) are closely related myeloid cells with distinct functions; Oc participate skeleton maintenance while Dc sample the environment for foreign antigens. Such specificities rely on profound modifications of gene and protein expression during Oc and Dc differentiation. We provide global proteomic and transcriptomic analyses of primary mouse Oc and Dc. based on original SILAC and RNAseq data. We established specific signatures for Oc and Dc including genes and proteins of unknown functions. In particular. we showed that Oc and Dc have the same α and β tubulin isotypes repertoire but that Oc express much more β tubulin isotype Tubb6. In both mouse and human Oc. we demonstrate that elevated expression of Tubb6 in Oc is necessary for correct podosomes organization and thus for the structure of the sealing zone. which sustains the bone resorption apparatus. Hence. lowering Tubb6 expression hindered Oc resorption activity. Overall. we highlight here potential new regulators of Oc and Dc biology and illustrate the functional importance of the tubulin isotype repertoire in the biology of differentiated cells.

Summary statement

This study provides original proteomic and transcriptomic data of primary myeloid cells. The analysis led to signatures for osteoclasts and for immature dendritic cells including potential new regulators of their specific biology. RNA interference showed in particular that ß tubulin isotype Tubb6 participates in osteoclast podosome patterning. sealing zone structure and in the resorption activity.
Resolving cellular systems by ultra-sensitive and economical single-cell transcriptome filtering
Authors: Vallejo Andres F. , Davies James , Grover Amit , Tsai Ching-Hsuan , Jepras Robert , Polak Marta E. , West Jonathan
Published: October 2019

Single-cell transcriptomics has sensitivity limits that restrict low abundance transcript identification, affects clustering and introduce artefact. Here, we describe Constellation DropSeq (C-DropSeq), a molecular transcriptome filter that delivers two orders of magnitude sensitivity gains by maximising read utility while reducing sequencing depth and costs. The simple and powerful method is broadly compatible with library preparation routines and was demonstrated by identifying and characterizing the activation of rare dendritic cell sub-populations.
Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway
Authors: Du Shanshan , Shao Jingzhi , Xie Dandan , Zhang Fengyan
Published: October 2019

Purpose

To determine the effect of decorin on oxidative stress and apoptosis of human lens epithelial (HLE) cells under high glucose condition.

Methods

HLE cell line (HLEB3) was incubated in normal glucose (5.5 mM) or high glucose (60 mM) medium. Decorin (50 nM) was applied 2 hours before high glucose medium was added. Apoptosis detection was executed by flow cytometry and western blotting (analysis of bcl-2 and bax). Oxidative stress level was measured by the generation of reactive oxygen species (ROS), glutathione peroxidase (GSH) and superoxide dismutase (SOD). P38 mitogen-activated protein kinase (MAPK) phosphorylation, the expression of p22phox of HLE cells and human lens anterior capsules were detected by western blotting. Small interfering RNA transfection to p22phox and p38 MAPK was also carried out on HLEB3.

Results

High glucose caused HLE cells oxidative stress and apoptosis exhibiting the increase of apoptotic cells and ROS production and decrease of bcl-2/bax ratio, GSH/GSSG ration and SOD activity. P22phox and phospho-p38 MAPK were upregulated in high glucose treated HLEB3 cells. Knocking down p22phox or p38 by siRNAs can reduce high glucose induced cell apoptosis and oxidative stress level. Silencing p22phox by siRNA can downregulate p38 MAPK activation. Decorin can inhibit the apoptosis, oxidative stress level and the induction of p22phox and p-p38 of HLEB3 induced by high glucose. Furthermore, the expression of p22phox and p38 were found significantly increased in lens anterior capsules of diabetic cataract patients compared to that of normal age-related cataract patients.

Conclusions

Results showed that p22phox-p38 pathway may be particepated in high glucose induced lens epithelial cell injury, decorin may inhibit the high glucose induced apoptosis and oxidative stress injury by suppressing this pathway in part.
Thyroid hormone receptor beta mutations alter photoreceptor development and function inDanio rerio(zebrafish)
Authors: Deveau Ciana , Jiao Xiaodong , Suzuki Sachihiro , Krishnakumar Asha , Yoshimatsu Takeshi , Hejtmancik J Fielding , Nelson Ralph F.
Published: October 2019

We investigate a splice variant ofthrbisolated in the retina,trβ2, identifying functional changes in larval and adult mutant zebrafish lacking trβ2. We constructed two CRISPR mutant zebrafish with mutations located in the N-terminus region. The first is a6BP+1insertion deletion frameshift resulting in a truncated protein. The second is a3BPin frame deletion with intact binding domains. ERG recordings showed that the6BP+1mutants did not respond to red wavelengths of light while the3BPmutants did respond.6BP+1mutants lacked optomotor and optokinetic responses to red/black and green/black contrasts. Adult6BP+1mutants exhibit a loss of red-cone contribution to the ERG, and an increase in green and UV contributions. Anatomical markers show loss of red-cones in the6BP+1mutant but increase in blue, green, and UV cone density. Our results confirmtrβ2’s role in retinal cone development.

Author Summary

There are four cone photoreceptors responsible for color vision in zebrafish: red, green, blue, and UV. The thyroid hormone receptortrβ2is localized in the vertebrate retina. We know that it is necessary for the development of long-wavelength-sensitive cones (red), but here we investigate the functional alterations that accompany a loss oftrβ2. Our work contributes to the ongoing investigations of retinal development and the involvement of thyroid hormone receptors. Confirming previous morphological findings, we see that the fish become red colorblind whentrβ2is knocked out, but the contributions of the other three cone types shift in response. Our work highlights the plasticity of the retinal circuit as we see changes in opsin peaks and cone sensitivity, increases in contributions of UV cones, and an attempt at a mosaic pattern in the adult retina all in the absence oftrβ2and red cones. We now have an increased understanding of mechanisms underlying retinal development
Visual discrimination of optical material properties: a large-scale study
Authors: Sawayama Masataka , Dobashi Yoshinori , Okabe Makoto , Hosokawa Kenchi , Koumura Takuya , Saarela Toni , Olkkonen Maria , Nishida Shin’ya
Published: October 2019

Complex visual processing involved in perceiving the object materials can be better elucidated by taking a variety of research approaches. Sharing stimulus and response data is an effective strategy to make the results of different studies directly comparable and can assist researchers with different backgrounds to jump into the field. Here, we constructed a database containing several sets of material images annotated with visual discrimination performance. We created the material images using physically-based computer graphics techniques and conducted psychophysical experiments with them in both laboratory and crowdsourcing settings. The observer’s task was to discriminate materials on one of six dimensions (gloss contrast, gloss distinctness-of-image, translucent vs. opaque, metal vs. plastic, metal vs. glass, and glossy vs. painted). The illumination consistency and object geometry were also varied. We used a non-verbal procedure (an oddity task) applicable for diverse use-cases such as cross-cultural, cross-species, clinical, or developmental studies. Results showed that the material discrimination depended on the illuminations and geometries and that the ability to discriminate the spatial consistency of specular highlights in glossiness perception showed larger individual differences than in other tasks. In addition, analysis of visual features showed that the parameters of higher-order color texture statistics can partially, but not completely, explain task performance. The results obtained through crowdsourcing were highly correlated with those obtained in the laboratory, suggesting that our database can be used even when the experimental conditions are not strictly controlled in the laboratory. Several projects using our dataset are underway.
BiomeSeq: A Tool for the Characterization of Animal Microbiomes from Metagenomic Data
Authors: Mulholland Kelly A. , Keeler Calvin L.
Published: October 2019

The complete characterization of a microbiome is critical in elucidating the complex ecology of the microbial composition within healthy and diseased animals. Many microbiome studies characterize only the bacterial component, for which there are several well-developed sequencing methods, bioinformatics tools and databases available. The lack of comprehensive bioinformatics workflows and databases have limited efforts to characterize the other components existing in a microbiome. BiomeSeq is a tool for the analysis of the complete animal microbiome using metagenomic sequencing data. With its comprehensive workflow, customizable parameters and microbial databases, BiomeSeq can rapidly quantify the viral, fungal, bacteriophage and bacterial components of a sample and produce informative tables for analysis. BiomeSeq was employed in detecting and quantifying the respiratory microbiome of a commercial poultry broiler flock throughout its grow-out cycle from hatching to processing. It successfully processed 780 million reads, of which 5,163 aligned to avian DNA viral genomes, 71,936 aligned to avian RNA viral genomes, 469,937 aligned to bacterial genomes, 504,682 aligned to bacteriophage genomes and 1,964 aligned to fungal genomes. For each microbial species detected, BiomeSeq calculated the normalized abundance, percent relative abundance, and coverage as well as the diversity for each sample. BiomeSeq provides for the detection and quantification of the microbiome from next-generation metagenomic sequencing data. This tool is implemented into a user-friendly container that requires one command and generates a table consisting of taxonomical information for each microbe detected as well as normalized abundance, percent relative abundance, coverage and diversity calculations.
Transposable elements contribute to regulatory hub stress-related long noncoding RNAs in Maize
Authors: Lv Yuanda , Hu Fengqin , Zhou Yongfeng , Wu Feilong , Zhou Ling , Gaut Brandon S.
Published: October 2019

Several studies have mined short-read RNA sequencing datasets to identify lncRNAs, and others have focused on the function of individual lncRNA in abiotic stress response. However, our understanding of the complement, function and origin of long-non-coding RNA (lncRNAs) response to abiotic stress, especially transposon derived lncRNA (TE-lncRNA), is still in its infancy. To discover and study lncRNAs in maize (Zea mays ssp. mays), we utilized a dataset of 127 RNA sequencing samples that included PacBio fl-cDNA and total RNA-Seq datasets. Overall, we identified 23,309 candidate lncRNAs, 60% of which were identified in polyadenylated (polyA+) samples. The majority (65%) of the 23,309 lncRNAs had sequence similarity to transposable elements (TEs). Most had similarity to long-terminal-repeat retrotransposons from the Copia and Gypsy superfamilies, representing the high proportion of these elements in the genome, but class II, DNA transposons were enriched for lncRNAs relative to their genomic representation by 2-fold. By assessing the fraction of lncRNAs that respond to abiotic stresses like heat, cold, salt and drought, we identified 1,077 differentially expressed lncRNA transcripts. Their expression was correlated (r2=0.48) with their nearest gene, suggesting that lncRNAs are subject to some of the cis regulatory features as neighboring genes. By inferring co-expression networks across our large dataset, we found that 39 lncRNAs act as major hubs in co-expression networks, of which 18 appeared to be derived from TEs. These results suggest that lncRNAs, especially TE-lncRNAs, may play key regulatory roles in moderating abiotic responses.
Enrichment of heterozygous germline RECQL4 loss-of-function variants in pediatric osteosarcoma
Authors: Maciaszek Jamie L. , Oak Ninad , Chen Wenan , Hamilton Kayla V. , McGee Rose B. , Nuccio Regina , Mostafavi Roya , Hines-Dowell Stacy , Harrison Lynn , Taylor Leslie , Gerhardt Elsie L. , Ouma Annastasia , Edmonson Michael N. , Patel Aman , Nakitandwe Joy , Pappo Alberto S. , Azzato Elizabeth M. , Shurtleff Sheila A. , Ellison David W. , Downing James R. , Hudson Melissa M. , Robison Leslie L. , Santana Victor , Newman Scott , Zhang Jinghui , Wang Zhaoming , Wu Gang , Nichols Kim E. , Kesserwan Chimene A.
Published: October 2019

Patients harboring germline pathogenic biallelic variants in genes involved in the recognition and repair of DNA damage are known to have a substantially increased cancer risk. Emerging evidence suggests that individuals harboring heterozygous variants in these same genes may also be at heightened, albeit lesser, risk for cancer. Herein, we sought to determine whether heterozygous variants in RECQL4, the gene encoding an essential DNA helicase that is defective in children with the autosomal recessive cancer-predisposing condition Rothmund–Thomson syndrome (RTS), are associated with increased risk for childhood cancer. To address this question, we interrogated germline sequence data from 4435 pediatric cancer patients at St. Jude Children's Research Hospital and 1127 from the National Cancer Institute Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and identified 24 (0.43%) who harbored loss-of-function (LOF) RECQL4 variants, including five of 249 (2.0%) with osteosarcoma (OS). These RECQL4 variants were significantly overrepresented in children with OS, the cancer most frequently observed in patients with RTS, as compared to 134,187 noncancer controls in the Genome Aggregation Database (gnomAD v2.1; P = 0.00087, odds ratio [OR] = 7.1, 95% CI, 2.9–17). Nine of the 24 (38%) individuals possessed the same c.1573delT (p.Cys525Alafs) variant located in the highly conserved DNA helicase domain, suggesting that disruption of this domain is central to oncogenesis. Altogether these data expand our understanding of the genetic factors predisposing to childhood cancer and reveal a novel association between heterozygous RECQL4 LOF variants and development of pediatric OS.