bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Real-Time Self-Tracking and Device-Recorded Exercise Data in Subjects with Type 1 Diabetes
Authors: Groat Danielle , Kwon Hyo , Grando Maria , Cook Curtiss , Thompson Bithika
Published: December 2018

Background Insulin therapy, medical nutrition therapy, and physical activity are required for the treatment of type 1 diabetes (T1D). There is a lack of studies in real-life environments that characterize patient-reported data from logs, activity trackers, and medical devices (e.g., glucose sensors) in the context of exercise.

Objective The objective of this study was to compare data from continuous glucose monitor (CGM), wristband heart rate monitor (WHRM), and self-tracking with a smartphone application (app), iDECIDE, with regards to exercise behaviors and rate of change in glucose levels.

Methods Participants with T1D on insulin pump therapy tracked exercise for 1 month with the smartphone app while WHRM and CGM recorded data in real time. Exercise behaviors tracked with the app were compared against WHRM. The rate of change in glucose levels, as recorded by CGM, resulting from exercise was compared between exercise events documented with the app and recorded by the WHRM.

Results Twelve participants generated 277 exercise events. Tracking with the app aligned well with WHRM with respect to frequency, 3.0 (2.1) and 2.5 (1.8) days per week, respectively (p = 0.60). Duration had very high agreement, the mean duration from the app was 65.6 (55.2) and 64.8 (54.9) minutes from WHRM (p = 0.45). Intensity had a low concordance between the data sources (Cohen's kappa = 0.2). The mean rate of change of glucose during exercise was –0.27 mg/(dL*min) and was not significantly different between data sources or intensity (p = 0.21).

Conclusion We collated and analyzed data from three heterogeneous sources from free-living participants. Patients' perceived intensity of exercise can serve as a surrogate for exercise tracked by a WHRM when considering the glycemic impact of exercise on self-care regimens.
Basic Principle and Step-by-Step Procedure of Abdominal Hysterectomy: Part 2
Authors: Konishi Ikuo
Published: December 2018

Abdominal hysterectomy is the ultimate standard operation among various gynecologic surgeries. However, the actual procedure for a patient varies substantially according to the morphological changes of the uterus and adnexa. Therefore, it is important to assess the deviation from standard and the difficulties in the procedure and to plan the modification of the operation at the preoperative conference. In this chapter, a standard step-by-step procedure for abdominal hysterectomy is described.
Research Update: Beyond graphene—Synthesis of functionalized quantum dots of 2D materials and their applications
Authors: Musselman Kevin P. , Ibrahim Khaled H. , Yavuz Mustafa
Published: December 2018

Two-dimensional quantum dots (2D-QDs) are receiving considerable attention for a wide variety of applications in sensing, imaging, therapeutics, catalysis, energy storage, and optoelectronics, among others. Functionalization of the 2D-QDs can enhance their capabilities and performance in these applications. Most research to-date has focused on graphene quantum dots, but interest in the functionalization of other 2D materials, such as phosphorene, transition metal dichalcogenides, and silicene, is growing rapidly. This research update provides an overview of recent progress in the synthesis, characterization, and application of functionalized 2D-QDs other than graphene.
First laboratory results of supersaturated water nucleation characteristics at low temperatures
Authors: Agner Mary Alexandra
Published: December 2018

Researchers report nucleation rates and trends in nucleation cluster size of extremely supersaturated water vapor.
Generation of terahertz radiation from water enhanced using two-color laser excitation
Authors: DeJarnette Drew
Published: December 2018

A laser pulse and its second harmonic frequency produce significantly higher terahertz energy.
New biocompatible and degradable sensor for environmental ammonia detection
Authors: Larter Raima
Published: December 2018

An organic thin-film transistor, OTFT, in combination with gelatin, is used in a new high-sensitivity gas sensor for atmospheric pollutants.
Risks, Benefits, and Complexities: Reporting Race & Ethnicity in Forensic Mental Health Reports
Authors: Riggs Romaine Christina L. , Kavanaugh Antoinette
Published: December 2018

In legal systems with complex disparities and potential biases, the reporting of the evaluee’s race or ethnicity (ERE) in the written forensic mental health report (FMHR) has both risks and benefits, yet few resources provide guidance on when and how to include this information. Available information suggests current practice in reporting ERE varies widely, and few recommendations and best practices guidelines exist. This article examines the available information and explores reasons for and against including ERE in the FMHR, examining how each fits with established principles of assessment. Benefits and potential consequences of including ERE, including implicit bias, the potential for stereotype threat and the problems with colorblind approaches, are discussed. Available research suggests carefully considered practice is required and decisions to include ERE should be based on a culturally competent weighing of relevance.
Combining near-infrared fluorescence with Brainbow to visualize expression of specific genes within a multicolor context
Authors: Cook Zoe T. , Brockway Nicole L. , Tobias Zachary J. C. , Pajarla Joy , Boardman Isaac S. , Ippolito Helen , Nkombo Nkoula Sylvia , Weissman Tamily A.
Published: December 2018

Fluorescent proteins are a powerful experimental tool, allowing the visualization of gene expression and cellular behaviors in a variety of systems. Multicolor combinations of fluorescent proteins, such as Brainbow, have expanded the range of possible research questions and are useful for distinguishing and tracking cells. The addition of a separately driven color, however, would allow researchers to report expression of a manipulated gene within the multicolor context to investigate mechanistic effects. A far-red or near-infrared protein could be particularly suitable in this context, as these can be distinguished spectrally from Brainbow. We investigated five far-red/near-infrared proteins in zebrafish: TagRFP657, mCardinal, miRFP670, iRFP670, and mIFP. Our results show that both mCardinal and iRFP670 are useful fluorescent proteins for zebrafish expression. We also introduce a new transgenic zebrafish line that expresses Brainbow under the control of the neuroD promoter. We demonstrate that mCardinal can be used to track the expression of a manipulated bone morphogenetic protein receptor within the Brainbow context. The overlay of near-infrared fluorescence onto a Brainbow background defines a clear strategy for future research questions that aim to manipulate or track the effects of specific genes within a population of cells that are delineated using multicolor approaches.
Localization dynamics of endogenous fluorescently labeled RAF1 in EGF-stimulated cells
Authors: Surve Sachin V. , Myers Paul J. , Clayton Samantha A. , Watkins Simon C. , Lazzara Matthew J. , Sorkin Alexander
Published: December 2018

Activation of the epidermal growth factor (EGF) receptor (EGFR) at the cell surface initiates signaling through the RAS-RAF-MAPK/ERK1/2 pathway and receptor endocytosis. Whether this signaling continues from endosomes remains unclear, because RAS is predominantly located on the plasma membrane, and the localization of endogenous RAF kinases, downstream effectors of RAS, is not defined. To examine RAF localization, we labeled endogenous RAF1 with mVenus using gene editing. From 10 to 15% of RAF1-mVenus (<2000 molecules/cell), which was initially entirely cytosolic, transiently translocated to the plasma membrane after EGF stimulation. Following an early burst of translocation, the membrane-associated RAF1-mVenus was undetectable by microscopy or subcellular fractionation, and this pool was estimated to be <200 molecules per cell. In contrast, persistent EGF-dependent translocation of RAF1-mVenus to the plasma membrane was driven by the RAF inhibitor sorafenib, which increases the affinity of Ras-GTP:RAF1 interactions. RAF1-mVenus was not found in EGFR-containing endosomes under any conditions. Computational modeling of RAF1 dynamics revealed that RAF1 membrane abundance is controlled most prominently by association and dissociation rates from RAS-GTP and by RAS-GTP concentration. The model further suggested that the relatively protracted activation of the RAF-MEK1/2-ERK1/2 module, in comparison with RAF1 membrane localization, may involve multiple rounds of cytosolic RAF1 rebinding to active RAS at the membrane.
Dissociation of membrane–chromatin contacts is required for proper chromosome segregation in mitosis
Authors: Champion Lysie , Pawar Sumit , Luithle Naemi , Ungricht Rosemarie , Kutay Ulrike
Published: December 2018

The nuclear envelope (NE) aids in organizing the interphase genome by tethering chromatin to the nuclear periphery. During mitotic entry, NE–chromatin contacts are broken. Here, we report on the consequences of impaired NE removal from chromatin for cell division of human cells. Using a membrane–chromatin tether that cannot be dissociated when cells enter mitosis, we show that a failure in breaking membrane–chromatin interactions impairs mitotic chromatin organization, chromosome segregation and cytokinesis, and induces an aberrant NE morphology in postmitotic cells. In contrast, chromosome segregation and cell division proceed successfully when membrane attachment to chromatin is induced during metaphase, after chromosomes have been singularized and aligned at the metaphase plate. These results indicate that the separation of membranes and chromatin is critical during prometaphase to allow for proper chromosome compaction and segregation. We propose that one cause of these defects is the multivalency of membrane–chromatin interactions.
Computational approaches for alternative and transient secondary structures of ribonucleic acids
Authors: Fukunaga Tsukasa , Hamada Michiaki
Published: December 2018

Transient and alternative structures of ribonucleic acids (RNAs) play essential roles in various regulatory processes, such as translation regulation in living cells. Because experimental analyses for RNA structures are difficult and time-consuming, computational approaches based on RNA secondary structures are promising. In this article, we review computational methods for detecting and analyzing transient/alternative secondary structures of RNAs, including static approaches based on probabilistic distributions of RNA secondary structures and dynamic approaches such as kinetic folding and folding pathway predictions.
MoMo: discovery of statistically significant post-translational modification motifs
Authors: Cheng Alice , Grant Charles E , Noble William S , Bailey Timothy L
Published: December 2018

Motivation

Post-translational modifications (PTMs) of proteins are associated with many significant biological functions and can be identified in high throughput using tandem mass spectrometry. Many PTMs are associated with short sequence patterns called ‘motifs’ that help localize the modifying enzyme. Accordingly, many algorithms have been designed to identify these motifs from mass spectrometry data. Accurate statistical confidence estimates for discovered motifs are critically important for proper interpretation and in the design of downstream experimental validation.

Results

We describe a method for assigning statistical confidence estimates to PTM motifs, and we demonstrate that this method provides accurate P-values on both simulated and real data. Our methods are implemented in MoMo, a software tool for discovering motifs among sets of PTMs that we make available as a web server and as downloadable source code. MoMo re-implements the two most widely used PTM motif discovery algorithms—motif-x and MoDL—while offering many enhancements. Relative to motif-x, MoMo offers improved statistical confidence estimates and more accurate calculation of motif scores. The MoMo web server offers more proteome databases, more input formats, larger inputs and longer running times than the motif-x web server. Finally, our study demonstrates that the confidence estimates produced by motif-x are inaccurate. This inaccuracy stems in part from the common practice of drawing ‘background’ peptides from an unshuffled proteome database. Our results thus suggest that many of the papers that use motif-x to find motifs may be reporting results that lack statistical support.

Availability and implementation

The MoMo web server and source code are provided at http://meme-suite.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
The role of thoracic endovascular repair in elective, symptomatic and ruptured thoracic aortic diseases
Authors: Fiorucci Beatrice , Kölbel Tilo , Rohlffs Fiona , Heidemann Franziska , Carpenter Sebastian William , Debus Eike Sebastian , Tsilimparis Nikolaos
Published: December 2018

OBJECTIVES

Thoracic endovascular aortic repair (TEVAR) has emerged as a safe procedure in the treatment of a wide spectrum of descending thoracic aortic pathologies, with satisfactory results both in elective and urgent settings. We investigated the results of our elective, urgent and emergency TEVAR interventions.

METHODS

A single-centre retrospective analysis of all consecutive patients undergoing TEVAR from 2010 to 2016 was performed. Primary end point of the study was early mortality, whereas the secondary end points included major complications according to the urgency of the procedure. The analysis was further conducted comparing symptomatic, asymptomatic and ruptured cases.

RESULTS

Two hundred and eight patients were treated with TEVAR between January 2010 and April 2016 (mean age 67 ± 12 years, 142 men, 68.3%). Patients undergoing TEVAR as a first-stage procedure for complex thoraco-abdominal repair were excluded. The indication for treatment was a dissection in most cases (n = 92, 44.2%; acute dissection in 40 cases, 19.2%), followed by thoracic aneurysms (n = 64, 30.8%), penetrating aortic ulcers (n = 37, 17.8%), intramural haematomas (n = 8, 3.8%), traumatic ruptures (n = 3, 1.4%) and other indications (n = 4, 1.8%). One hundred and eight procedures were performed electively and 100 urgently. Forty-three patients were treated on an emergency bas for aortic rupture, 44 urgently for thoracic pain and 13 for acute ischaemic complications of aortic dissection or other indications. Ischaemic complications of dissection included 1 case of mesenteric ischaemia, 3 cases of acute renal failure, 4 cases of limb ischaemia and multiple ischaemic complications in 4 cases. Other causes of urgent TEVAR included 1 patient bleeding from a bronchial artery treated with TEVAR after several embolization attempts. In-hospital mortality was 7.7%, significantly higher in the urgent setting (14% vs 1.9%, P = 0.001). Urgent procedures were also more frequently associated with major adverse clinical events (7.4% vs 26%, P = 0.0003) and specifically with paraplegia (2.8% vs 10%, P = 0.043). Perioperative mortality was significantly higher in the ruptured group compared to the symptomatic group (25.6% vs 2.3%, P = 0.002). When the analysis was conducted to compare the symptomatic and the asymptomatic patients, no differences in terms of perioperative mortality were detected.

CONCLUSIONS

TEVAR is an effective treatment strategy in thoracic aortic disease. Though emergency repair of the ruptured thoracic aorta still shows high rates of perioperative mortality and morbidity, symptomatic non-ruptured and asymptomatic patients have comparable early outcomes.
Adipose Tissue Senescence and Inflammation in Aging is Reversed by the Young Milieu
Authors: Ghosh Amiya Kumar , O’Brien Martin , Mau Theresa , Qi Nathan , Yung Raymond
Published: December 2018

Visceral adipose tissue (VAT) inflammation plays a central role in longevity and multiple age-related disorders. Cellular senescence (SEN) is a fundamental aging mechanism that contributes to age-related chronic inflammation and organ dysfunction, including VAT. Recent studies using heterochronic parabiosis models strongly suggested that circulating factors in young plasma alter the aging phenotypes of old animals. Our study investigated if young plasma rescued SEN phenotypes in the VAT of aging mice. With heterochronic parabiosis model using young (3 months) and old (18 months) mice, we found significant reduction in the levels of pro-inflammatory cytokines and altered adipokine profile that are protective of SEN in the VAT of old mice. These data are indicative of protection from SEN of aging VAT by young blood circulation. Old parabionts also exhibited diminished expression of cyclin-dependent kinase inhibitors (CDKi) genes p16 (Cdkn2a) and p21 (Cdkn1a/Cip1) in the VAT. In addition, when exposed to young serum condition in an ex vivo culture system, aging adipose tissue–derived stromovascular fraction cells produced significantly lower amounts of pro-inflammatory cytokines (MCP-1 and IL-6) compared to old condition. Expressions of p16 and p21 genes were also diminished in the old stromovascular fraction cells under young serum condition. Finally, in 3T3-preadipocytes culture system, we found reduced pro-inflammatory cytokines (Mcp-1 and Il-6) and diminished expression of cyclin-dependent kinase inhibitor genes in the presence of young serum compared to old serum. In summary, this study demonstrates that young milieu is capable of protecting aging adipose tissue from SEN and thereby inflammation.
Cost-effectiveness of Hepatitis B Virus Infection Screening and Treatment or Vaccination in 6 High-risk Populations in the United States
Authors: Chahal Harinder S , Peters Marion G , Harris Aaron M , McCabe Devon , Volberding Paul , Kahn James G
Published: December 2018

Background

Two million individuals with chronic hepatitis B (CHB) in the United States are at risk for premature death due to liver cancer and cirrhosis. CHB can be prevented by vaccination and controlled with treatment.

Methods

We created a lifetime Markov model to estimate the cost-effectiveness of strategies to prevent or treat CHB in 6 high-risk populations: foreign-born Asian/Pacific Islanders (API), Africa-born blacks (AbB), incarcerated, refugees, persons who inject drugs (PWID), and men who have sex with men (MSM). We studied 3 strategies: (a) screen for HBV infection and treat infected (“treatment only”), (b) screen for HBV susceptibility and vaccinate susceptible (“vaccination only”), and (c) screen for both and follow-up appropriately (“inclusive”). Outcomes were expressed in incremental cost-effectiveness ratios (ICERs), clinical outcomes, and new infections.

Results

Vaccination-only and treatment-only strategies had ICERs of $6000–$21 000 per quality-adjusted life-year (QALY) gained, respectively. The inclusive strategy added minimal cost with substantial clinical benefit, with the following costs per QALY gained vs no intervention: incarcerated $3203, PWID $8514, MSM $10 954, AbB $17 089, refugees $17 432, and API $18 009. Clinical complications dropped in the short/intermediate (1%–25%) and long (0.4%–16%) term. Findings were sensitive to age, discount rate, health state utility in immune or susceptible stages, progression rate to cirrhosis or inactive disease, and tenofovir cost. The probability of an inclusive program costing <$50 000 per QALY gained varied between 61% and 97% by population.

Conclusions

An inclusive strategy to screen and treat or vaccinate is cost-effective in reducing the burden of hepatitis B virus among all 6 high-risk, high-prevalence populations.
An evaluation of the coverage of theoretically based implementation factors in disseminated classroom physical activity programs
Authors: Calvert Hannah G , Lane Hannah G , Bejarano Carolina M , Snow Kelli , Hoppe Kate , Alfonsin Nicole , Turner Lindsey , Carlson Jordan A
Published: December 2018

Classroom-based physical activity (CBPA) is increasingly recommended as a method to support children’s physical activity, health, and academic performance. Many adoption-ready programs exist to aid in the implementation of CBPA in schools; yet, implementation rates remain low. The purpose of this study was to evaluate the extent to which resources provided by adoption-ready CBPA programs addressed theory-based implementation contextual factors to support implementation. Existing CBPA programs (N = 37) were identified through Internet searches and all materials (e.g., implementation guides) provided by each program were coded for their inclusion of 51 implementation factors based on the Consolidated Framework for Implementation Research (CFIR). Analyses were conducted to compare inclusion of implementation factors across CFIR Domains and by three program groupings: free (yes/no), research evidence (yes/no), and targeted to teacher only (vs. school). Programs covered a mean of 25.9 per cent (SD = 18.7 per cent) of the 14 Inner Setting implementation factors, 34.2 per cent (SD = 18.0 per cent) of the 6 Characteristics of Individuals implementation factors, and 34.8 per cent (SD = 24.3 per cent) of the 8 Process implementation factors. Programs with research evidence covered more implementation factors than programs without research evidence (43.7 vs. 25.9 per cent; p < .05). Although numerous adoption-ready CBPA programs are available and have many strengths, their inclusion of theory-based factors that support or inhibit implementation is generally low. Consideration of such factors, including organizational climate and teacher-level behavior change, is likely critical to supporting ongoing school-wide implementation of CBPA. Research is needed to develop and test effective strategies for addressing these factors to support more widespread CBPA implementation.
Challenges and Management of Surgical Site Occurrences
Authors: Gabriel Allen , Gupta Subhas , Orgill Dennis P.
Published: December 2018

Postoperative complications such as surgical site infections, dehiscence, seromas, and hematomas prolong wound care and impose significant cost increases to patients and healthcare providers. Clinicians aiming to reduce the incidence of these complications should be aware of risk factors associated with surgical type, procedures used, patient characteristics, and postoperative care. Today, improved guidelines and general practices for managing surgical incisions have reduced the incidence of complications to historic lows. In addition to these standard care options, advanced wound care approaches have been extensively studied and exist as options for clinicians to provide adjunctive postoperative support and facilitate wound healing. These systems include advanced wound dressings and closed-incision negative-pressure therapy. Advanced wound care is not appropriate in all settings, and healthcare providers must assess each case for specific needs to be addressed by the available incision management plans. Emerging therapies that are intended to improve the continuum of postoperative care should continue to be evaluated in controlled clinical trials to determine their effectiveness under different circumstances and to support the creation of more robust guidelines for their use.
CBP/EP300-dependent acetylation and stabilization of HSF2 are compromised in the rare disorder, Rubinstein-Taybi syndrome
Authors: de Thonel Aurélie , Ahlskog Johanna K. , Abane Ryma , Pires Geoffrey , Dubreuil Véronique , Berthelet Jérémy , Aalto Anna L. , Naceri Sarah , Cordonnier Marion , Benasolo Carène , Sanial Matthieu , Duchateau Agathe , Vihervaara Anniina , Puustinen Mikael C. , Miozzo Federico , Henry Mathilde , Bouvier Déborah , Concordet Jean-Paul , Fergelot Patricia , Lebigot Élise , Verloes Alain , Gressens Pierre , Lacombe Didier , Gobbo Jessica , Garrido Carmen , Westerheide Sandy D. , Petitjean Michel , Taboureau Olivier , Rodrigues-Uma Fernando , Lancaster Madeline , Passemart Sandrine , Sabéran-Djoneidi Délara , Sistonen Lea , Mezger Valérie
Published: December 2018

Cells respond to protein-damaging insults by activating heat shock factors (HSFs), key transcription factors of proteostasis. Abnormal HSF protein levels occur in cancer and neurodegenerative disorders, highlighting the importance of the tight control of HSF expression. HSF2 is a short-lived protein, but it is abundant in the prenatal brain cortex and required for brain development. Here, we reveal that HSF2 is acetylated and co-localized with the lysine-acetyl transferases CBP and EP300 in human brain organoids. Using unbiased, biochemical, cell-imaging, and in silico approaches, we show that CBP/EP300 acetylates HSF2 at specific lysine residues, which promotes HSF2 stabilization, whereas the lysine deacetylase HDAC1 catalyzes its proteasomal degradation. The CBP KIX domain and KlX-recognizing motifs in HSF2 are critical for its interaction with acetylating enzymes. The functional importance of acetylated HSF2 is evidenced in Rubinstein-Taybi syndrome (RSTS), characterized by mutated CBP or EP300. We show that RSTS patient cells exhibit decreased HSF2 levels and impaired heat shock response. The dysregulated HSF pathway in RSTS opens new avenues for understanding the molecular basis of this multifaceted pathology.
Evaluating a Primary Healthcare Centre's Preparedness for Disasters Using the Hospital Safety Index: Lessons Learned from the 2014 Floods in Obrenovac, Serbia
Authors: Lapčević Zoran , Mandić-Rajčević Stefan , Lepić Milan , Jovanović Mića
Published: December 2018

Various organizations have endeavored to develop assessment methods for the identification and management of weaknesses in hospital disaster preparedness. Although the largest number of patients receive their regular care at the primary level, there is no internationally validated tool for the rapid safety assessment of primary health care centers (PHC). Flooding accounts for almost 50% of all disasters related to weather, and climate models consider these events as highly probable in the future. In May 2014, heavy rain caused floods affecting around 1.6 million people in Serbia, leaving the municipality of Obrenovac most severely impacted. This paper aims at assessing the safety of PHC Obrenovac using the Hospital Safety Index (HSI), evaluating the usefulness of HSI for safety assessment of PHCs, and drawing lessons from the 2014 floods. PHC Obrenovac had an overall safety index of 0.82, with structural, nonstructural safety, and disaster management indices of 0.95, 0.74, and 0.75, respectively, implying it is likely to function in disasters. A detailed analysis of individual HSI items underlined the necessary improvements in the field of emergency power and water supply, telecommunication, and emergency medical supplies, which rendered the PHC non-functional during the 2014 floods. Most items were considered of same relevance for primary healthcare centers as for hospitals, excluding some items in the medical equipment, patient care, and support services. Fine-tuning the HSI to primary healthcare settings, officially translating it into different languages, facilitating scoring and analysis could result in a valid safety evaluation tool of primary healthcare facilities.
σ54 (σL) plays a central role in carbon metabolism in the industrially relevant Clostridium beijerinckii
Authors: Hocq Rémi , Bouilloux-Lafont Maxime , Lopes Ferreira Nicolas , Wasels François
Published: December 2018

Microbial production of butanol and isopropanol, two high value-added chemicals, is naturally occurring in the solventogenic Clostridium beijerinckii DSM 6423. Despite its ancient discovery, the precise mechanisms controlling alcohol synthesis in this microorganism are poorly understood. In this work, an allyl alcohol tolerant strain obtained by random mutagenesis was characterized. This strain, designated as the AA mutant, shows a dominant production of acids, a severely diminished butanol synthesis capacity, and produces acetone instead of isopropanol. Interestingly, this solvent-deficient strain was also found to have a limited consumption of two carbohydrates and to be still able to form spores, highlighting its particular phenotype. Sequencing of the AA mutant revealed point mutations in several genes including CIBE_0767 (sigL), which encodes the σ54 sigma factor. Complementation with the wild-type sigL gene fully restored solvent production and sugar assimilation, demonstrating that σ54 plays a central role in regulating these pathways in C. beijerinckii DSM 6423. Genomic comparison with other strains further revealed that these functions are probably conserved among the C. beijerinckii strains. The importance of σ54 in C. beijerinckii was further assessed by the characterization of a sigL deletion mutant of the model strain NCIMB 8052 obtained with a CRISPR/Cas9 tool. The resulting mutant exhibited phenotypic traits similar to the AA strain, and was subsequently complemented with the sigL gene from either the wild type or the AA strains. The results of this experiment confirmed the crucial role of σ54 in the regulation of both solventogenesis and sugar consumption pathways in C. beijerinckii.
Unification of miRNA and isomiR research: the mirGFF3 format and the mirtop API
Authors: Desvignes Thomas , Loher Phillipe , Eilbeck Karen , Ma Jeffery , Urgese Gianvito , Fromm Bastian , Sydes Jason , Aparicio-Puerta Ernesto , Barrera Victor , Espin Roderic , Londin Eric , Telonis Aristeidis G , Ficarra Elisa , Friedlander Marc R , Postlethwait John H , Rigoutsos Isidore , Hackenberg Michael , Vlachos Ioannis S , Halushka Marc K. , Pantano Lorena
Published: December 2018

Background: MicroRNAs (miRNAs) are small RNA molecules (~22 nucleotide long) involved in post-transcriptional gene regulation. Advances in high-throughput sequencing technologies led to the discovery of isomiRs, which are miRNA sequence variants. While many miRNA-seq analysis tools exist, a lack of consensus on miRNA/isomiR analyses exists, and the resulting diversity of output formats hinders accurate comparisons between tools and precludes data sharing and the development of common downstream analysis methods.
Findings: To overcome this situation, we present here a community-based project, miRTOP (miRNA Transcriptomic Open Project) working towards the optimization of miRNA analyses. The aim of miRTOP is to promote the development of downstream analysis tools that are compatible with any existing detection and quantification tool. Based on the existing GFF3 format, we first created a new standard format, mirGFF3, for the output of miRNA/isomiR detection and quantification results from small RNA-seq data. Additionally, we developed a command line Python tool, mirtop, to manage the mirGFF3 format. Currently, mirtop can convert into mirGFF3 the outputs of commonly used pipelines, such as seqbuster, miRge2.0, isomiR-SEA, sRNAbench, and Prost!, as well as BAM files. Its open architecture enables any tool or pipeline to output results in mirGFF3.
Conclusions: Collectively a comprehensive isomiR categorization system, along with the accompanying mirGFF3 and mirtop API provide a complete solution for the standardization of miRNA and isomiR analysis, enabling data sharing, reporting, comparative analyses, and benchmarking, while promoting the development of common miRNA methods focusing on downstream steps to miRNA detection, annotation, and quantification.
Measurements of Subthreshold and Fast Population Neuronal Activity with Genetically Encoded Calcium Indicator GCaMP-6f
Authors: Li Pinggan , Geng Xinling , Jiang Huiyi , Caccavano Adam , Vicini Stefano , Wu Jian-young
Published: December 2018

GCaMP-6f is among the best calcium indicators and has been widely used for monitoring neuronal activity in the brain. Applications are at cellular level (calcium transients of action potentials) or population activity (fluorimetry) during network events. Two important issues remain less explored: 1) Is GCaMP-6f signal sensitive enough for detecting subthreshold activity, similar to the sensitivity of local field potential (LFP)? 2) Is the GCaMP-6f signal fast enough for detecting network oscillations seen in LFP? Here the two issues are explored in a number of network events including hippocampus sharp waves (SWs), carbachol induced theta oscillations, interictal-like spikes and neuronal response evoked by high frequency stimuli. SWs are a typical network event with the majority of neurons receiving subthreshold excitatory or inhibitory synaptic input without firing action potentials. The excitatory/inhibitory post synaptic potentials (EPSP/IPSP) in the neuropil become detectable in local field potential (LFP) signals. We compare simultaneously recorded LFP and optical recording of GCaMP-6f fluorescent signals in Thy1-GCaMP-6f mice hippocampal slices. We found that the occurrence of SWs produces a clear population GCaMP-6f signal of 0.3% dF/F. This population GCaMP-6f signal correlated well with the LFP, albeit a delay of ~50 ms was observed. The population GCaMP-6f signal follows well with the 20 Hz population activity evoked by electric stimuli, while activity up to 40 Hz was detected with reduced amplitude. GCaMP-6f and LFP signals showed a large amplitude discrepancy. The amplitude of GCaMP increased ~1000 times from SW to carbachol induced theta burst, while the LFP changed less than 10 times. Our results suggested that population GCaMP-6f signals may become a sensitive tool for detecting network activity, especially for that with low LFP amplitude during elevated spiking rate but asynchronized events. GCaMP signal is fast enough for monitoring theta and beta oscillations (<25Hz) in the neuronal population. Faster calcium indicators (e.g., GCaMP-7) may improve the frequency response property for detecting gamma band oscillations. In addition, population GCaMP recordings are non-contact and free from stimulation artifacts. These features may be useful for high throughput recordings and applications sensitive to stimulus artifact, e.g., monitoring response during continuous stimulations.
TOMVi: A Tool for Overviewing Metadata Visualization
Authors: Kyoui Daisuke , Yamamoto Hiroyuki , Mikami Natsumi , Ishii Ryota , Tanaka Hiroki , Fukuda Naruki , Kawarai Taketo , Ogihara Hirokazu
Published: December 2018

DNA sequencing technology has been improved drastically in the recent decades, which allows comprehensively analyze microbial community and gene expression. Simultaneously with the improvements, many tools and software for much amount of sequence data have been released. These analysis tools/software can produce statistic information. However, to interpret and to find the relationships and/or associations between the information and the experimental condition may be a complex task, especially for non-bioinformaticians. In this article, an open source software TOMVi (Tool for Overviewing Metadata Visualization) which visualized similarity and relationships between the samples corresponding to the experimental conditions was introduced. TOMVi allows researcher to interactively manipulate the composition data in each sample toward to each experimental condition such as location, time-series and others with graphical user interface (GUI), and to visualize the existence and behavior of each OTU. The figure illustrated by this tool can provide an intuitive suggestion but not always correct as statistically, and will be helpful to decide further analyzing tactics. The TOMVi is available at http://github.com/Daisuke-Kyoui/tomvi.
Feedback between a retinoid-related nuclear receptor and the let-7 microRNAs controls the pace and number of molting cycles in C. elegans
Authors: Patel Ruhi , Galagali Himani , Kim John K. , Frand Alison R.
Published: December 2018

Animal development requires coordination among cyclic processes, sequential cell fate specifications, and once-a-lifetime morphogenic events, but the underlying mechanisms are not well understood. C. elegans undergo four molts at regular 8–10 h intervals. The pace of the cycle is governed by PERIOD/lin-42 and other as-yet unknown factors. Cessation of the cycle in young adults is controlled by the let-7 family of microRNAs and downstream transcription factors in the heterochronic pathway. Here, we characterize a negative feedback loop between NHR-23, the worm homolog of mammalian retinoid-related orphan receptors (RORs), and the let-7 family of microRNAs that regulates both the frequency and finite number of molts. The molting cycle is decelerated in nhr-23 knockdowns, accelerated in let-7(-) mutants, and similar to wild type animals in let-7(-) nhr-23(-) double mutants. NHR-23 binds response elements (ROREs) in the let-7 promoter and activates transcription. In turn, let-7 dampens nhr-23 expression across development via a complementary let-7 binding site (LCS) in the nhr-23 3′ UTR. The molecular interactions between NHR-23 and let-7 hold true for other let-7 family microRNAs. Either derepression of nhr-23 transcripts by LCS deletion or high gene dosage of nhr-23 leads to protracted behavioral quiescence and extra molts in adults. NHR-23 and let-7 also co-regulate scores of genes required for execution of the molts, including lin-42. In addition, ROREs and LCSs isolated from mammalian ROR and let-7 genes function in C. elegans, suggesting conservation of this feedback mechanism. We propose that this feedback loop unites the molting timer and the heterochronic gene regulatory network possibly by functioning as a cycle counter.
Where does time go when you blink?
Authors: Grossman Shany , Guata Chen , Pesin Slav , Malach Rafael , Landau Ayelet N
Published: December 2018

Retinal input is frequently lost due to eye blinks, yet humans rarely notice these gaps in visual input. While previous studies focused on the psychophysical and neural correlates of diminished awareness to blinks, the impact of blinks on the perceived time of concurrent events is unknown. Here, we investigated whether the subjective sense of time is altered by spontaneous eye blinks, and how this link may inform mechanisms of time perception. We found that participants significantly underestimated the duration of a visual stimulus when a blink occurred during the stimulus. Importantly, this effect was not present when durations of an auditory stimulus were judged. These results point to a link between spontaneous blinks, previously demonstrated to induce suppression of activity in early visual cortex, and a compression of subjective time. The findings suggest that ongoing encoding within modality-specific sensory cortices, independent of conscious awareness, inform the subjective sense of time.
The role of Selenoprotein N in the differentiation of erythroid progenitors during stress erythropoiesis
Authors: Paulson Robert F , Nettleford Shaneice K , Liao Chang , Chen Yuanting , Hao Siyang , Blatzinger Mereille , Thami-Braye Melanie , Lescure Alain , Prabhu K. Sandeep
Published: December 2018

Low serum Se is independently associated with anemia in elderly population, dialysis patients, sickle-cells patients, and hypothyroidism patients. Previous work from our laboratory showed that dietary Se deficiency in mice showed mild anemia indicating activation of stress- erythropoietic mechanisms. Unlike steady state erythropoiesis that is primarily responsible for homeostasis to produce new erythrocytes at a constant rate, stress erythropoiesis predominates when the bone marrow cannot generate sufficient erythrocytes. During such a process, short-term reconstituting hematopoietic stem cells (CD34+Kit+Sca1+Linneg) migrate to the spleen leading to the proliferation and differentiation of stress-erythroid progenitors (SEPs). These cells lead to stress burst forming unit- erythroid cells (BFU-E) followed by terminal differentiation to erythrocytes. Recent studies demonstrate deficits in selenoproteins block the expansion and development of stress BFU-E with defects in terminal differentiation. Analysis of selenoprotein expression showed that selenoprotein W (SelenoW) was highly expressed in developing SEPs. CRISPR-Cas9 knockout of SelenoW blocked the proliferation of immature SEPs in murine and human stress erythropoiesis cultures demonstrating a central role for SelenoW in stress erythropoiesis. Using the two-culture system to generate SEPs, selenoprotein N (SelenoN) expression increased as the progenitors transition from self-renewing progenitors to form committed erythroid progenitors. SelenoN-/- mice showed significantly slower erythroid recovery following phenylhydrazine (PHZ)-induced acute hemolytic anemia. As in the muscle satellite cells where SelenoN regulates cellular Ca2+ signaling, SelenoN may also regulate Ca2+ signaling in SEPs to modulate pathways of differentiation. In summary, these data suggest that multiple selenoproteins, including SelenoN and SelenoW, coordinately regulate stress erythropoiesis.
Sharing cells with Wolbachia: the transovarian vertical transmission of Culex pipiens densovirus
Authors: Altinli Mine , Soms Julien , Ravallec Marc , Justy Fabienne , Bonneau Manon , Weill Mylene , Gosselin‐Grenet Anne‐Sophie , Sicard Mathieu
Published: December 2018

Culex pipiens densovirus (CpDV), a single stranded DNA virus, has been isolated from Culex pipiens mosquitoes but differs from other mosquito densoviruses in terms of genome structure and sequence identity. Its transmission from host to host, the nature of its interactions with both its host and host's endosymbiotic bacteria Wolbachia are not known. Here, we report the presence of CpDV in the ovaries and eggs of Cx. pipiens mosquitoes in close encounters with Wolbachia. In the ovaries, CpDV amount significantly differed between mosquito lines harbouring different strains of Wolbachia and these differences were not linked to variations in Wolbachia densities. CpDV was vertically transmitted in all laboratory lines to 17%–20% of the offspring. For some females, however, the vertical transmission reached 90%. Antibiotic treatment that cured the host from Wolbachia significantly decreased both CpDV quantity and vertical transmission suggesting an impact of host microbiota, including Wolbachia, on CpDV transmission. Overall our results show that CpDV is transmitted vertically via transovarian path along with Wolbachia with which it shares the same cells. Our results are primordial to understand the dynamics of densovirus infection, their persistence and spread in populations considering their potential use in the regulation of mosquito vector populations.
Transcriptomic responses of the marine cyanobacterium Prochlorococcus to viral lysis products
Authors: Fang Xiaoting , Liu Yaxin , Zhao Yao , Chen Yue , Liu Riyue , Qin Qi‐Long , Li Gang , Zhang Yu‐Zhong , Chan Wan , Hess Wolfgang R. , Zeng Qinglu
Published: December 2018

Viral infection of marine phytoplankton releases a variety of dissolved organic matter (DOM). The impact of viral DOM (vDOM) on the uninfected co‐occurring phytoplankton remains largely unknown. Here, we conducted transcriptomic analyses to study the effects of vDOM on the cyanobacterium Prochlorococcus, which is the most abundant photosynthetic organism on Earth. Using Prochlorococcus MIT9313, we showed that its growth was not affected by vDOM, but many tRNAs increased in abundance. We tested tRNA‐gly and found that its abundance increased upon addition of glycine. The decreased transcript abundances of N metabolism genes also suggested that Prochlorococcus responded to organic N compounds in vDOM. Addition of vDOM to Prochlorococcus reduced the maximum photochemical efficiency of photosystem II and CO2 fixation while increasing its respiration rate, consistent with differentially abundant transcripts related to photosynthesis and respiration. One of the highest positive fold‐changes was observed for the 6S RNA, a noncoding RNA functioning as a global transcriptional regulator in bacteria. The high level of 6S RNA might be responsible for some of the observed transcriptional responses. Taken together, our results revealed the transcriptional regulation of Prochlorococcus in response to viral lysis products and suggested its metabolic potential to utilize organic N compounds.
Developing and maintaining collaborative practice: Exploring perspectives from dietetics and speech pathology about ‘what works well’
Authors: Croker Anne , Brown Leanne , Little Alexandra , Squires Kelly , Crowley Elesa
Published: December 2018

Aim

The aim was to support rich collaborative practice between two professions who frequently work together across both ordered and organic modes of collaboration.

Methods

This study uses a qualitative research approach of collaborative dialogical inquiry to explore the question ‘From the perspective of dietitians and speech pathologists, “what works well” for developing and maintaining collaborative practice?’ We deliberately chose a context where collaborative practice is evident, University Department of Rural Health (UONDRH). Participants in the research were academics and clinicians from dietetics and speech pathology. Data were sourced from our research reflections and focus group transcriptions. Analysis was dialogical and iterative.

Results

Beyond shared purpose, knowledge of roles and good communication, the notions of curiosity, willingness and momentum were at the core of ‘what works well’ for collaborative practice between dietitians and speech pathologists. Participant perspectives related to collaborative practice between these professions and beyond to other professions, and involved collaborative practice within and across healthcare organisations and a university setting.

Conclusions

Our interpreted themes of curiosity, willingness and momentum for developing and maintaining collaborative practice highlight the importance of paying attention to the less visible and difficult to measure aspects of patient‐centred care. Questions for reflection are suggested to inform the ongoing process of developing and maintaining our and others’ collaborative practice.
Diet shift in bank voles induced by competition from grey‐sided voles?
Authors: MAGNUSSON Magnus , SAMELIUS Gustaf , HÖRNFELDT Birger , ECKE Frauke
Published: December 2018

Grey‐sided voles (Myodes rufocanus) and bank voles (Myodes glareolus) co‐exist in boreal forests in northern Scandinavia. Previous studies suggest that the 2 species interact interspecifically, the grey‐sided vole being the dominant species. We tested the hypothesis that bank voles shift their diet due to competition with the dominant grey‐sided vole by studying stable isotope ratios in both species. Muscle samples were taken from voles in patches of old forest occupied by only bank voles and patches of old forest occupied by both grey‐sided voles and bank voles. We found that: (i) stable isotope ratios of bank voles differed in areas with and without grey‐sided voles; and that (ii) the stable isotope ratios of bank voles were more similar to those of grey‐sided voles in areas where grey‐sided voles were absent. Our data suggests that grey‐sided voles forced bank voles to change their diet due to interspecific competition.