bluuebunny/crossref_metadata_2025 huggingface dataset:
Suicidal Behavior Among Hospitalized Adults With Inflammatory Bowel Disease: A United States Nationwide Analysis
Authors: Marchioni Beery Renée M , Barnes Edward L , Nadkarni Ashwini , Korzenik Joshua R
Published: December 2017

Background

Suicidal behavior in inflammatory bowel disease (IBD) has been minimally explored. We aimed to determine United States (US) nationally representative prevalence estimates of suicidal ideation (SI) and suicide/self-inflicted injury (S/SII) among hospitalized adults with IBD and to examine trends in suicidal behavior over time.

Methods

A retrospective cross-sectional study using National (Nationwide) Inpatient Sample data (2006–2011) identified adults with Crohn’s disease (CD) or ulcerative colitis (UC), SI or S/SII, and multiple comorbid risk factors for suicidal behavior.

Results

We identified 331,777 (estimated 1.64 million) IBD-related hospitalizations (64% CD, 36% UC) and 39,787,239 (estimated 196.08 million) hospitalizations among the general US population. Among IBD-related hospitalizations, 2502 discharges were associated with SI (prevalence 0.76%) and 1104 with S/SII (prevalence 0.33%). Both were significantly greater in CD versus UC (P < 0.001). Relative to the general US population, IBD patients were significantly less likely to demonstrate suicidal behavior: (SI:0.33% versus 0.59%, P < 0.001) (S/SII:0.75% versus 1.04%, P < 0.001). Multivariable logistic regression revealed that IBD was associated with decreased odds of SI (adjusted odds ratio [aOR] 0.62, 95%CI 0.60–0.65) and S/SII (aOR 0.43, 95%CI 0.40–0.45) relative to the general population, and suicidal behavior was lower in IBD compared to disease-related controls with rheumatoid arthritis and systemic lupus erythematosus. Similar increasing trends in suicidal behavior were observed in IBD and non-IBD populations (2006–2011).

Conclusion

In this large US database, SI or S/SII occurred in over 1% of the IBD population and was increased in CD versus UC.

10.1093/ibd/izx005_video1 izx005.video1 5732754099001
Integrating population genomics and biophysical models towards evolutionary-based fisheries management
Authors: Baltazar-Soares Miguel , Hinrichsen Hans-Harald , Eizaguirre Christophe
Published: December 2017

Overfishing and rapid environmental shifts pose severe challenges to the resilience and viability of marine fish populations. To develop and implement measures that enhance species’ adaptive potential to cope with those pressures while, at the same time, ensuring sustainable exploitation rates is part of the central goal of fisheries management. Here, we argue that a combination of biophysical modelling and population genomic assessments offer ideal management tools to define stocks, their physical connectivity and ultimately, their short-term adaptive potential. To date, biophysical modelling has often been confined to fisheries ecology whereas evolutionary hypotheses remain rarely considered. When identified, connectivity patterns are seldom explored to understand the evolution and distribution of adaptive genetic variation, a proxy for species’ evolutionary potential. Here, we describe a framework that expands on the conventional seascape genetics approach by using biophysical modelling and population genomics. The goals are to identify connectivity patterns and selective pressures, as well as putative adaptive variants directly responding to the selective pressures and, ultimately, link both to define testable hypotheses over species response to shifting ecological conditions and overexploitation.
Extreme Values of the Riemann Zeta Function on the 1-Line
Authors: Aistleitner Christoph , Mahatab Kamalakshya , Munsch Marc
Published: December 2017

We prove that there are arbitrarily large values of t such that $|\zeta (1+it)| \geq e^{\gamma } (\log _{2} t +\log _{3} t) + \mathcal{O}(1)$. This essentially matches the prediction for the optimal lower bound in a conjecture of Granville and Soundararajan. Our proof uses a new variant of the “long resonator” method. While earlier implementations of this method crucially relied on a “sparsification” technique to control the mean-square of the resonator function, in the present paper we exploit certain self-similarity properties of a specially designed resonator function.
Employment Tribunal Fees and the Rule of Law: R (Unison) v Lord Chancellor in the Supreme Court
Authors: Ford Michael
Published: December 2017

In R (UNISON) v Lord Chancellor (Equality and Human Rights Commission Intervening) the Supreme Court held that fees for bringing claims in the employment tribunal were unlawful both under common law and as a matter of EU law. The judgment has very significant implications for any system in which the enforcement of employment or social rights is left to individual claimants, the paradigmatic model adopted in the UK. Recent government policy has ignored the public function of individual tribunal claims in delivering employment rights at the systemic level, exemplified by the theoretical assumptions and justifications which lay behind the introduction of fees. The Supreme Court’s analysis of the rule of law and the common law right of access to justice is in sharp conflict with these policies. I discuss the difference between the common law principles and the parallel principles in EU law and under Article 6 of the ECHR. The article explores the consequences of the judgment for cases rejected, dismissed or not brought owing to fees, and its longer-term implications for impediments to access to courts and tribunals, all the more important with Brexit on the horizon. The judgment represents an important triumph of the rule of law over the increased marketisation of legal rights.
Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit
Authors: Wiens Jenna , Snyder Graham M , Finlayson Samuel , Mahoney Monica V , Celi Leo Anthony
Published: December 2017

Background

The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU).

Methods

Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission.

Results

Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile. The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes.

Conclusions

The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.
QTL Analysis for Downy Mildew Resistance in Cucumber Inbred Line PI 197088
Authors: Li Lixia , He Huiqiang , Zou Zhirong , Li Yuhong
Published: December 2017

Downy mildew (DM), caused by Pseudoperonospora cubensis, is one of the major foliar diseases prevailing in cucumber-growing areas. The mechanism of DM resistance in cucumber, particularly the plant introduction (PI) 197088 from India, is presently unclear. Quantitative trait locus (QTL) mapping is an efficient approach to studying DM resistance genes in cucumber. In this study, we performed QTL mapping for DM resistance in PI 197088 with 183 F2-derived F3 (F2:3) families from the cross between PI 197088 (DM resistant) and Changchunmici (DM susceptible). A linkage map was constructed using 141 simple sequence repeat markers. Phenotypic data were collected from seven independent experiments. In total, five QTL were detected on chromosomes 1, 3, 4, and 5 with DM resistance contributed by PI 197088. The QTL on chromosome 4, dm4.1, was reproducibly detected in all indoor experiments, which could explain 27% of the phenotypic variance detected. Additionally, dm1.1 and dm5.2 showed moderate effects, while dm3.1 and dm5.1 were minor-effect QTL. This study revealed the unique genetic architecture of DM resistance in PI 197088, which may provide important guidance for efficient use in cucumber breeding for DM resistance.
THE INTEGRATIVE SURGICAL THEATER
Authors: Ehlers Justis P. , Uchida Atsuro , Srivastava Sunil K.
Published: December 2017

Purpose:

To evaluate the feasibility of integrating intraoperative optical coherence tomography (OCT) with a digital visualization platform for vitreoretinal surgery.

Methods:

The DISCOVER study is a prospective study examining microscope-integrated intraoperative OCT across multiple prototypes and platforms. For this assessment, a microscope-integrated OCT platform was combined with a three-dimensional (3D) surgical visualization system to allow for digital display of the OCT data stream on the large immersive display. Intraoperative OCT scans were obtained at various surgical milestones that were directly overlaid to the surgical view in a 55-inch passive 3D 4K high-definition display. Surgeon feedback was obtained related to system performance and integration into the surgical procedures through a prespecified surgeon questionnaire.

Results:

Seven eyes of seven subjects were identified. Clinical diagnosis included epiretinal membrane (n = 3), macular hole (2), symptomatic vitreous opacity (1), and proliferative vitreoretinopathy (1). Optical coherence tomography images were successfully obtained and displayed on the 4K screen in all cases. Intraoperative OCT images facilitated identification of subtle retinal alterations. Surgeons reported that the 4K screen seemed to provide improved visualization of the OCT data stream compared with the semitransparent ocular view. Surgeons were able to examine the OCT data on the 4K screen without reverting to the external display system of the microscope. The system provided a uniform surgical visualization experience for both the surgeon and the assistant. In addition, the digital platform allowed all surgical personnel to simultaneously view both the OCT and the surgical field. All eyes underwent uneventful vitrectomy without reverting to the conventional microscope. No intraoperative adverse events occurred.

Conclusion:

Integration of OCT into the digital visualization system may enable unique opportunities for surgeon feedback of intraoperative diagnostics. The overlay of the OCT data onto the 4K monitor seemed to provide excellent visualization of OCT details. Further research is needed to compare the conventional microscope–based approach to the digital 3D screen approach in regards to intraoperative OCT.
Defining the Process of a Cardiovascular Risk Assessment Program: Lessons Learned From Cardiac Assessment of Elite Soccer Players in the United Kingdom
Authors: Speers Christopher , Seth Ajai Narain , Patel Kiran Chhaganbhai , Rakhit Dhrubo Jyoti , Gillett Mark James
Published: December 2017

Objective:

Retrospectively analyze the cardiac assessment process for elite soccer players, and provide team physicians with a systematic guide to managing longitudinal cardiac risk.

Design:

Descriptive Epidemiology Study.

Setting:

Cardiac assessments incorporating clinical examination, 12-lead ECG, echocardiography, and health questionnaire.

Participants:

Soccer players at 5 professional clubs in England, the United Kingdom.

Intervention:

Data was retrospectively collected, inspected, and analyzed to determine their clinical management and subsequent follow-up.

Results:

Over 2 years, 265 soccer players, aged 13 to 37 years with 66% of white European ethnicity, were included in the cohort. Eleven percent had “not-normal” assessments, of these assessments, 83% were considered gray screens, falling into three broad categories: structural cardiac features (including valvular abnormalities), functional cardiac features, and electrocardiogram changes. After cardiology consultation, all assessments were grouped into low, enhanced and high-risk categories for ongoing longitudinal risk management. Overall clear-cut pathology was identified in 2%.

Conclusions:

Cardiovascular assessment is a vital tool in identifying athletes at risk of sudden cardiac death to mitigate their risk through surveillance, intervention, or participation restriction. The decision whether a player is fit to play or not requires a robust risk assessment followed by input from a multidisciplinary team that includes both the team physician and cardiologist. This educational article proposes a clinical management pathway to aid clinicians with this process.

Clinical Relevance:

Sudden cardiac death is the important medical cause of death during exercise. The team physician should assume responsibility for the management of the longitudinal risk of their players' cardiac assessments in conjunction with sports cardiologist.
Ehlers-Danlos Syndrome Type IVB and Tracheobronchomegaly
Authors: Girit Saniye , Senol Ebru , Cag Yakup , Karatas Ozge , Baysal Tamer
Published: December 2017

Tracheobronchomegaly (TBM) is a rare disease of unknown etiology, characterized by dilatation of the trachea and main bronchi. Despite its rarity, TBM has been reported to accompany several conditions, particularly Ehlers-Danlos syndrome. Herein, we report on a 15-year-old patient who was diagnosed with TBM on the basis of radiologic and endoscopic findings and with Ehlers-Danlos syndrome type IVB presenting with marfanoid features, severe kyphoscoliosis, increased skin elasticity, and ongoing hypotonia since the neonatal period.
Screening, Brief Intervention, and Referral to Treatment in the Emergency Department
Authors: Pringle Janice L. , Kelley David K. , Kearney Shannon M. , Aldridge Arnie , Dowd William , Johnjulio William , Venkat Arvind , Madden Michael , Lovelace John
Published: December 2017

Background:

There is increasing interest in deploying screening, brief intervention, and referral to treatment (SBIRT) practices in emergency departments (ED) to intervene with patients at risk for substance use disorders. However, the current literature is inconclusive on whether SBIRT practices are effective in reducing costs and utilization.

Objective:

This study sought to evaluate the health care costs and health care utilization associated with SBIRT services in the ED.

Research Design:

This study analyzed downstream health care utilization and costs for patients who were exposed to SBIRT services within an Allegheny County, Pennsylvania, ED through a program titled Safe Landing compared with 3 control groups of ED patients (intervention hospital preintervention, and preintervention and postintervention time period at a comparable, nonintervention hospital).

Subjects:

The subjects were patients who received ED SBIRT services from January 1 to December 31 in 2012 as part of the Safe Landing program. One control group received ED services at the same hospital during a previous year. Two other control groups were patients who received ED services at another comparable hospital.

Measures:

Measures include total health care costs, 30-day ED visits, 1-year ED visits, inpatient claims, and behavioral health claims.

Results:

Results found that patients who received SBIRT services experienced a 21% reduction in health care costs and a significant reduction in 1-year ED visits (decrease of 3.3 percentage points).

Conclusions:

This study provides further support that SBIRT programs are cost-effective and cost-beneficial approaches to substance use disorders management, important factors as policy advocates continue to disseminate SBIRT practices throughout the health care system.
Intersecting Evidence-Based Practice With a Lean Improvement Model
Authors: Halm Margo A. , Alway Ann , Bunn Sandra , Dunn Nancy , Hirschkorn Michelle , Ramos Becky , St. Pierre Jeanne
Published: December 2017

In our journey from Magnet designation to a Lean hospital, a team of advanced practice nurses, a nurse scientist, and Lean specialists developed a crosswalk of evidence-based practice (EBP) with Lean to explicitly embed the use of evidence in our organization's 4-step problem-solving method. Once finalized, the blended Lean-EBP model now guides improvement work as highlighted in the example of updating our practice for frequency of changing peripheral intravenous catheters.
Tamoxifen-Prefabricated Beige Adipose Tissue Improves Fat Graft Survival in Mice
Authors: Cai Junrong , Li Bin , Wang Jing , Liu Kaiyang , Zhang Yuteng , Liao Yunjun , Lu Feng
Published: December 2017

Background:

Fat grafting has become an important tool for breast reconstruction in breast cancer patients. Tamoxifen, the hormone therapy agent most frequently used for breast cancer, can affect adipose metabolism and cause browning of adipose tissue. This study hypothesized that tamoxifen could increase fat graft survival by altering adipose metabolism.

Methods:

C57/BL6 mice were divided into three groups receiving different treatments before and after fat grafting. The tamoxifen/grafting/tamoxifen group was pretreated with daily tamoxifen for 8 weeks, received fat grafting, and was treated with daily tamoxifen. The graft/tamoxifen group was pretreated with daily phosphate-buffered saline for 8 weeks, received fat grafting, and was treated with daily tamoxifen. The control group was pretreated with daily phosphate-buffered saline for 8 weeks, received fat grafting, and was treated with daily phosphate-buffered saline. The inguinal fat used for transplantation and the transferred fat at weeks 4 and 12 after transplantation were harvested and analyzed.

Results:

Tamoxifen-pretreated inguinal fat showed beige fat features, with smaller adipocyte size, up-regulated uncoupling protein 1 expression, and improved vascularization. The retention rate of transferred fat was significantly higher in the tamoxifen/grafting/tamoxifen group than in the control group (69 ± 12 percent versus 36 ± 13 percent; p < 0.05), but fat grafts in the graft/tamoxifen group had a retention rate similar to that in the control group (31 ± 12 percent versus 36 ± 13 percent; p > 0.05). Improved angiogenesis and increased vascular endothelial growth factor expression were found in the tamoxifen/grafting/tamoxifen group but not in the graft/tamoxifen group.

Conclusions:

Tamoxifen treatment before fat grafting resulted in prefabricated vascularized beige fat with small adipocytes, which greatly improve fat graft survival. However, tamoxifen after fat grafting did not affect fat graft evolution.
Glycemic variability is associated with myocardial damage in nondiabetic patients with ST-elevation myocardial infarction
Authors: Oka Satoshi , Deyama Juntaro , Umetani Ken , Harama Tomoko , Shimizu Takuya , Makino Aritaka , Sano Keita , Nakamura Masahiko
Published: December 2017

Background

Glycemic variability (GV) induces coronary microcirculatory disturbance and myocardial damage in diabetic patients with acute myocardial infarction. However, in nondiabetic acute myocardial infarction patients, the relationship between GV and myocardial damage remains unclear.

Patients and methods

We investigated GV with a continuous glucose monitoring system in nondiabetic ST-segment elevation myocardial infarction patients treated with emergent percutaneous coronary intervention. GV was expressed as the mean amplitude of glycemic excursions (MAGE). Myocardial damage was estimated by myocardial blush grade and ST-segment resolution (STRes). STRes was defined as complete (>70%), partial (30–70%), or none (<30%).

Results

Consecutive patients (n=73) were enrolled and classified into a lower or higher MAGE group on the basis of the median MAGE. The higher MAGE group showed lower levels of myocardial blush grade (2.41±0.76 vs. 1.72±0.85, P=0.001) and STRes (complete: 56.8 vs. 33.3%, P=0.044; partial: 32.4 vs. 36.1%, P=0.741; none: 10.8 vs. 30.6%, P=0.037).

Conclusion

GV was associated with myocardial damage after percutaneous coronary intervention in nondiabetic ST-segment elevation myocardial infarction patients.
Feeding strategies in arthropods from the Rhynie and Windyfield cherts: ecological diversification in an early non-marine biota
Authors: Haug Carolin
Published: December 2017

The key to understanding fossil ecosystems is to understand the life habits of long extinct organisms. Yet, as direct observations are no longer possible, morphological details are usually the only available data source. One important aspect of lifestyle is feeding strategies, which can be inferred from morphological structures in comparison with those of extant relatives. The Lower Devonian Rhynie and Windyfield cherts preserve even minute structures to a high degree of detail, which allows investigation of the functional morphology of structures possibly involved in feeding. In this contribution, the feeding structures of different arthropods from the Rhynie and Windyfield cherts are described and the corresponding feeding strategies of the animals are discussed. This overview illustrates that in this early non-marine biota, a wide range of feeding strategies already existed.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
Fungi and fungal interactions in the Rhynie chert: a review of the evidence, with the description ofPerexiflasca taylorianagen. et sp. nov.†
Authors: Krings Michael , Harper Carla J. , Taylor Edith L.
Published: December 2017

The Lower Devonian Rhynie chert is one of the most important rock deposits yielding comprehensive information on early continental plant, animal and microbial life. Fungi are especially abundant among the microbial remains, and include representatives of all major fungal lineages except Basidiomycota. This paper surveys the evidence assembled to date of fungal hyphae, mycelial cords and reproductive units (e.g. spores, sporangia, sporocarps), and presents examples of fungal associations and interactions with land plants, other fungi, algae, cyanobacteria and animals from the Rhynie chert. Moreover, a small, chytrid-like organism that occurs singly, in chain-like, linear arrangements, planar assemblages and three-dimensional aggregates of less than 10 toindividuals in degrading land plant tissue in the Rhynie chert is formally described, and the namePerexiflasca taylorianaproposed for the organism.Perexiflasca taylorianaprobably colonized senescent or atrophied plant parts and participated in the process of biological degradation. The fungal fossils described to date from the Rhynie chert constitute the largest body of structurally preserved evidence of fungi and fungal interactions from any rock deposit, and strongly suggest that fungi played important roles in the functioning of the Early Devonian Rhynie ecosystem.

This article is part of a discussion meeting issue ‘The Rhynie cherts: our earliest terrestrial ecosystem revisited’.
Ex vivolive cell tracking in kidney organoids using light sheet fluorescence microscopy
Authors: Held Marie , Santeramo Ilaria , Wilm Bettina , Murray Patricia , Lévy Raphaël
Published: December 2017

Screening cells for their differentiation potential requires a combination of tissue culture models and imaging methods that allow for long-term tracking of the location and function of cells. Embryonic kidney re-aggregationin vitroassays have been established which allow for the monitoring of organotypic cell behaviour in re-aggregated and chimeric renal organoids. However, evaluation of cell integration is hampered by the high photonic load of standard fluorescence microscopy which poses challenges for imaging three-dimensional systems in real-time over a time course. Therefore, we employed light sheet microscopy, a technique that vastly reduces photobleaching and phototoxic effects. We have also developed a new method for culturing the re-aggregates which involves immersed culture, generating organoids which more closely reflect developmentin vivo. To facilitate imaging from various angles, we embedded the organoids in a freely rotatable hydrogel cylinder. Endpoint fixing and staining were performed to provide additional biomolecular information. We succeeded in imaging labelled cells within re-aggregated kidney organoids over 15 hours and tracking their fate while simultaneously monitoring the development of organotypic morphological structures. Our results show that Wt1-expressing embryonic kidney cells obtained from transgenic mice could integrate into re-aggregated chimeric kidney organoids and contribute to developing nephrons. Furthermore, the nascent proximal tubules that formed in the re-aggregated tissues using the new culture method displayed secretory function, as evidenced by their ability to secrete an organic anion mimic into the tubular lumen.
Sex-specific gene and pathway modeling of inherited glioma risk
Authors: Ostrom Quinn T. , Coleman Warren , Huang William , Rubin Joshua B. , Lathia Justin D. , Berens Michael E. , Speyer Gil , Liao Peter , Wrensch Margaret R. , Eckel-Passow Jeanette E , Armstrong Georgina , Rice Terri , Wiencke John K. , McCoy Lucie S. , Hansen Helen M. , Amos Christopher I. , Bernstein Jonine L. , Claus Elizabeth B. , Il’yasova Dora , Johansen Christoffer , Lachance Daniel H. , Lai Rose K. , Merrell Ryan T. , Olson Sara H. , Sadetzki Siegel , Schildkraut Joellen M. , Shete Sanjay , Houlston Richard S. , Jenkins Robert B. , Andersson Ulrika , Rajaraman Preetha , Chanock Stephen J. , Linet Martha S. , Wang Zhaoming , Yeager Meredith , Melin Beatrice , Bondy Melissa L. , Barnholtz-Sloan Jill S.
Published: December 2017

Background

Genome-wide association studies (GWAS) have identified 25 risk variants for glioma, which explain ~30% of heritable risk. Most glioma histologies occur with significantly higher incidence in males. A sex-stratified analysis ide7ntified sex-specific glioma risk variants, and further analyses using gene- and pathway-based approaches may further elucidate risk variation by sex.

Methods

Results from the Glioma International Case-Control Study were used as a testing set, and results from three GWAS were combined via meta-analysis and used as a validation set. Using summary statistics for autosomal SNPs found to be nominally significant (p<0.01) in a previous meta-analysis and X chromosome SNPs with nominally significant association (p<0.01), three algorithms (Pascal, BimBam, and GATES) were used to generate gene-scores, and Pascal was used to generate pathway scores. Results were considered significant when p<3.3x10−6in ⅔ algorithms.

Results

25 genes within five regions and 19 genes within six regions reached the set significance threshold in at least 2/3 algorithms in males and females, respectively.EGFRandRTEL1-TNFRSF6Bwere significantly associated with all glioma and glioblastoma in males only, and a female-specific association inTERT, all of which remained nominally significant after conditioning on known risk loci. There were nominal associations with the Telomeres, Telomerase, Cellular Aging, and Immortality pathway in both males and females.

Conclusions

These results suggest that there may be biologically relevant significant differences by sex in genetic risk for glioma. Additional gene- and pathway-based analyses may further elucidate the biological processes through which this risk is conferred.
Sex in the wild: how and why field-based studies contribute to solving the problem of sex
Authors: Neiman Maurine , Meirmans Patrick G. , Schwander Tanja , Meirmans Stephanie
Published: December 2017

Why and how sexual reproduction is maintained in natural populations, the so-called “queen of problems”, is a key unanswered question in evolutionary biology. Recent efforts to solve the problem of sex have often emphasized results generated from laboratory settings. Here, we use a survey of representative “sex in the wild” literature to review and synthesize the outcomes of empirical studies focused on natural populations. Especially notable results included relatively strong support for mechanisms involving niche differentiation and a near absence of attention to adaptive evolution. Support for a major role of parasites is largely confined to a single study system, and only three systems contribute most of the support for mutation accumulation hypotheses. This evidence for taxon specificity suggests that outcomes of particular studies should not be more broadly extrapolated without extreme caution. We conclude by suggesting steps forward, highlighting tests of niche differentiation mechanisms in both lab and nature and empirical evaluation of adaptive evolution-focused hypotheses in the wild. We also emphasize the value of leveraging the growing body of genomic resources for non-model taxa to address whether the clearance of harmful mutations and spread of beneficial variants in natural populations proceeds as expected under various hypotheses for sex.

Author contributions

SM and MN conceived the paper idea, SM, PM, MN, and TS designed the review strategy, reviewed and analysed the literature, and wrote the manuscript. All authors gave final approval for publication.

Data archival location

The results of our literature survey are provided as electronic supplementary material.
On how the dentate gyrus contributes to memory discrimination
Authors: van Dijk Milenna T. , Fenton Andre A.
Published: December 2017

The dentate gyrus (DG) is crucial for behaviorally discriminating similar spatial memories, predicting that dentate gyrus place cells change (“remap”) spatial tuning (“place fields”) for memory discrimination. This prediction was never tested, although DG place cells remap across similar environments without memory tasks. We confirm this prior finding, then demonstrate that DG place fields do not remap across spatial tasks that require DG-dependent memory discrimination. Instead of remapping, place-discriminating discharge is observed transiently amongst DG place cells, particularly where memory discrimination is most necessary. The DG network signals memory discrimination by expressing distinctive sub-second network patterns of co-firing amongst principal cells at memory discrimination sites. This is accompanied by increased coupling of discharge from excitatory principal cells and inhibitory interneurons. Instead of remapping, these findings identify that memory discrimination is signaled by sub-second patterns of correlated discharge within the dentate network.

eTOC blurb

van Dijk and Fenton report that dentate gyrus place cells signal memory discrimination not by remapping, but by variable sub-second patterns of coordinated place cell network discharge and enhanced discharge coupling between excitatory and inhibitory neurons, at sites of memory discrimination.

Highlights

Dentate gyrus-dependent memory discrimination does not require place cell remapping

Dentate neural correlates of pattern discrimination are transient, lasting seconds

Sub-second dentate network discharge correlations signal memory discrimination

Dentate excitatory-inhibitory coupling is increased at memory discrimination sites
Molecular insights intoVibrio cholerae’s intra-amoebal host-pathogen interactions
Authors: Van der Henst Charles , Clerc Stéphanie , Stutzmann Sandrine , Stoudmann Candice , Scrignari Tiziana , Maclachlan Catherine , Knott Graham , Blokesch Melanie
Published: December 2017

Vibrio cholerae, which causes the diarrheal disease cholera, is a species of bacteria commonly found in aquatic habitats. Within such environments, the bacterium must defend itself against predatory protozoan grazers. Amoebae are prominent grazers, withAcanthamoeba castellaniibeing one of the best-studied aquatic amoebae. We previously showed thatV. choleraeresists digestion byA. castellaniiand establishes a replication niche within the host’s osmoregulatory organelle. In this study, we deciphered the molecular mechanisms involved in the maintenance ofV. cholerae’s intra-amoebal replication niche and its ultimate escape from the succumbed host. We demonstrated that minor virulence features important for disease in mammals, such as extracellular enzymes and flagellum-based motility, play a key role role in the replication and transmission ofV. choleraein its aqueous environment. This work, therefore, describes new mechanisms that provide the pathogen with a fitness advantage in its primary habitat, which may have contributed to the emergence of these minor virulence factors in the speciesV. cholerae.
Coherent representations of subjective spatial position in primary visual cortex and hippocampus
Authors: Saleem Aman B. , Diamanti E. Mika , Fournier Julien , Harris Kenneth D. , Carandini Matteo
Published: December 2017

A major role of vision is to guide navigation, and navigation is strongly driven by vision1-4. Indeed, the brain’s visual and navigational systems are known to interact5, 6, and signals related to position in the environment have been suggested to appear as early as in visual cortex6, 7. To establish the nature of these signals we recorded in primary visual cortex (V1) and in the CA1 region of the hippocampus while mice traversed a corridor in virtual reality. The corridor contained identical visual landmarks in two positions, so that a purely visual neuron would respond similarly in those positions. Most V1 neurons, however, responded solely or more strongly to the landmarks in one position. This modulation of visual responses by spatial location was not explained by factors such as running speed. To assess whether the modulation is related to navigational signals and to the animal’s subjective estimate of position, we trained the mice to lick for a water reward upon reaching a reward zone in the corridor. Neuronal populations in both CA1 and V1 encoded the animal’s position along the corridor, and the errors in their representations were correlated. Moreover, both representations reflected the animal’s subjective estimate of position, inferred from the animal’s licks, better than its actual position. Indeed, when animals licked in a given location – whether correct or incorrect – neural populations in both V1 and CA1 placed the animal in the reward zone. We conclude that visual responses in V1 are tightly controlled by navigational signals, which are coherent with those encoded in hippocampus, and reflect the animal’s subjective position in the environment. The presence of such navigational signals as early as in a primary sensory area suggests that these signals permeate sensory processing in the cortex.
Statistical mechanics of cell decision-making: the cell migration force distribution
Authors: Hatzikirou Haralampos
Published: December 2017

Cell decision-making is the cellular process of responding to microenvironmental cues. This can be regarded as the regulation of cell’s intrinsic variables to extrinsic stimuli. Currently, little is known about the principles dictating cell decision-making. Regarding cells as Bayesian decision-makers under energetic constraints, I postulate the principle of least microenvironmental uncertainty (LEUP). This is translated into a free-energy principle and I develop a statistical mechanics theory for cell decision-making. I exhibit the potential of LEUP in the case of cell migration. In particular, I calculate the dependence of cell locomotion force on the steady state distribution of adhesion receptors. Finally, the associated migration velocity allows for the reproduction of the cell anomalous diffusion, as observed in cell culture experiments.
Topology independent structural matching discovers novel templates for protein interfaces
Authors: Mirabello Claudio , Wallner Björn
Published: December 2017

Motivation

Protein-protein interactions (PPI) are essential for the function of the cellular machinery. The rapid growth of protein-protein complexes with known 3D structures offers a unique opportunity to study PPI to gain crucial insights into protein function and the causes of many diseases. In particular, it would be extremely useful to compare interaction surfaces ofmonomers, as this would enable the pinpointing of potential interaction surfaces based solely on the monomer structure, without the need to predict the complete complex structure. While there are many structural alignment algorithms for individual proteins, very few have been developed for protein interfaces, and none that can align only the interface residues to other interfaces or surfaces of interacting monomer subunits in a topology independent (non-sequential) manner.

Results

We present InterComp, a method for topology and sequence-order independent structural comparisons. The method is general and can be applied to various structural comparison applications. By representing residues as independent points in space rather than as a sequence of residues, InterComp can can be applied to a wide range of problems including: interface-surface comparisons, interface-interface comparisons and even comparisons of small molecule ligands. We demonstrate a use-case by applying InterComp to find similar protein interfaces on the surface of proteins. We show that InterComp pinpoints the correct interface for almost half of the targets (283 of 586) when considering the top 10 hits, and for 24% of the top 1, even when no templates can be found with the already available sequence-order dependent methods like TM-align.

Availability

The program is available from:http://wallnerlab.org/InterComp

Contact

bjorn.wallner@liu.se

Supplementary information

Supplementary data included in the pdf.
Multiplexed targeted resequencing identifies coding and regulatory variation underlying phenotypic extremes of HDL-cholesterol in humans
Authors: Khetarpal Sumeet A. , Babb Paul L. , Zhao Wei , Hancock-Cerutti William F. , Brown Christopher D. , Rader Daniel J. , Voight Benjamin F.
Published: December 2017

Genome-wide association studies have uncovered common variants at many loci influencing human complex traits and diseases, such as high-density lipoprotein cholesterol (HDL-C). However, the contribution of the identified genes is difficult to ascertain from current efforts interrogating common variants with small effects. Thus, there is a pressing need for scalable, cost-effective strategies for uncovering causal variants, many of which may be rare and noncoding. Here, we used a multiplexed inversion probe (MIP) target capture approach to resequence both coding and regulatory regions at seven HDL-C associated loci in 797 individuals with extremely high HDL-C vs. 735 low-to-normal HDL-C controls. Our targets included protein-coding regions of GALNT2, APOA5, APOC3, SCARB1, CCDC92, ZNF664, CETP, and LIPG (>9 kb), and proximate noncoding regulatory features (>42 kb). Exome-wide genotyping in 1,114 of the 1,532 participants yielded a >90% genotyping concordance rate with MIP-identified variants in ~90% of participants. This approach rediscovered nearly all established GWAS associations in GALNT2, CETP, and LIPG loci with significant and concordant associations with HDL-C from our phenotypic-extremes design at 0.1% of the sample size of lipid GWAS studies. In addition, we identified a novel, rare, CETP noncoding variant enriched in the extreme high HDL-C group (P<0.01, Score Test). Our targeted resequencing of individuals at the HDL-C phenotypic extremes offers a novel, efficient, and cost-effective approach for identifying rare coding and noncoding variation differences in extreme phenotypes and supports the rationale for applying this methodology to uncover rare variation—particularly non-coding variation--underlying myriad complex traits.
Size Matters: Metastatic cluster size and stromal recruitment in the establishment of successful prostate cancer to bone metastases
Authors: Araujo Arturo , Cook Leah M. , Lynch Conor C. , Basanta David
Published: December 2017

Prostate cancer (PCa) impacts over 180,000 men every year in the US alone with 26,000 patients expected to succumb to the disease (cancer.gov). The primary cause of death is metastasis, with secondary lesions most commonly occurring in the skeleton. Prostate cancer to bone metastasis is an important yet poorly understood process that is difficult to explore with experimental techniques alone. To this end we have utilized a hybrid (discrete-continuum) cellular automata (HCA) model of normal bone matrix homeostasis that allowed us to investigate how metastatic PCa can disrupt the bone microenvironment. Our previously published results showed that PCa cells can recruit mesenchymal stem cells (MSCs) that give rise to bone building osteoblasts. MSCs are also thought to be complicit in the establishment of successful bone metastases (1). Here we have explored aspects of early metastatic colonization and shown that the size of PCa clusters needs to be within a specific range to become successfully established: sufficiently large to maximize success but not too large to risk failure through competition amongst cancer and stromal cells for scarce resources. Furthermore, we show that MSC recruitment can promote the establishment of a metastasis and compensate for relatively low numbers of PCa cells seeding the bone microenvironment. Combined, our results highlight the utility of computational models that capture the complex and dynamic dialogue between cells during the initiation of active metastases.
Copy number variation and neurodevelopmental problems in females and males in the general population
Authors: Martin Joanna , Tammimies Kristiina , Karlsson Robert , Lu Yi , Larsson Henrik , Lichtenstein Paul , Magnusson Patrik
Published: December 2017

Objective

Neurodevelopmental problems (NPs) are childhood phenotypes that are more common in males. Conversely, anxiety and depression (which are frequently comorbid with NPs) are more common in females. Rare copy number variants (CNVs) have been implicated in clinically-defined NPs. Here, we aimed to characterise the relationship between rare CNVs with NPs and anxiety/depression in a population sample of twin children. Additionally, we examined whether sex-specific CNV effects underlie the sex bias of these disorders.

Method

We analysed a sample of N=12,982 children, of whom 5.3% had narrowly-defined NPs (clinically-diagnosed), 20.9% had broadly-defined NPs (based on validated screening measures, but no diagnosis) and 3.0% had clinically-diagnosed anxiety or depression. Rare (<1% frequency) CNVs were categorised by size (medium: 100-500kb or large: >500kb), type (duplication or deletion) and putative relevance to NPs (affecting previously implicated loci or evolutionarily-constrained genes). We tested for associations between the different CNV categories with NPs and anxiety/depression, followed by examination of sex-specific effects.

Results

Medium deletions (OR(CI)=1.18(1.05-1.33),p=0.0053) and large duplications (OR(CI)=1.45(1.19-1.75),p=0.00017) were associated with broadly-defined NPs. Large deletions (OR(CI)=1.85(1.14-3.01),p=0.013) were associated with narrowly-defined NPs. The effect sizes increased for large NP-relevant CNVs (broadly-defined: OR(CI)=1.60(1.06-2.42),p=0.025; narrowly-defined: OR(CI)=3.64(2.16-6.13),p=1.2E-6). No sex differences in CNV burden were found in individuals with NPs (p>0.05). In individuals diagnosed with anxiety or depression, females were more likely to have large CNVs (OR(CI)=3.75(1.45-9.68),p=0.0064).

Conclusion

Rare CNVs are significantly associated with both narrowly- and broadly-defined NPs in a general population sample of children. Our results also suggest that large, rare CNVs may show sex-specific phenotypic effects.
Replay of Stimulus Specific Temporal Patterns during Associative Memory Formation
Authors: Michelmann Sebastian , Bowman Howard , Hanslmayr Simon
Published: December 2017

Forming a memory often entails the association of recent experience with present events. This recent experience is usually an information rich and dynamic representation of the world around us. We here show that associating a static cue with a previously shown dynamic stimulus, yields a detectable, dynamic representation of this stimulus in working memory. We further implicate this representation in the decrease of low-frequency power (∼4-30 Hz) in the ongoing electroencephalogram (EEG), which is a well-known correlate of successful memory formation. The maintenance of content specific patterns in desynchronizing brain oscillations was observed in two sensory domains, i.e. in a visual and in an auditory condition. Together with previous results, these data suggest a mechanism that generalizes across domains and processes, in which the decrease in oscillatory power allows for the dynamic representation of information in ongoing brain oscillations.
Human Herpes Virus 6 (HHV-6) - Pathogen or Passenger? A pilot study of clinical laboratory data and next generation sequencing
Authors: Sharp Colin , Golubchik Tanya , Gregory William F. , McNaughton Anna L. , Gow Nicholas , Selvaratnam Mathyruban , Mirea Alina , Foster Dona , Andersson Monique , Klenerman Paul , Jeffery Katie , Matthews Philippa C.
Published: December 2017

ABSTRACT

Background

Human herpes virus 6 (HHV-6) is a ubiquitous organism that can cause a variety of clinical syndromes ranging from short-lived rash and fever through to life-threatening encephalitis.

Objectives

We set out to generate observational data regarding the epidemiology of HHV-6 infection in clinical samples from a UK teaching hospital and to compare different diagnostic approaches.

Study design

First, we scrutinized HHV-6 detection in samples submitted to our hospital laboratory through routine diagnostic pathways. Second, we undertook a pilot study using Illumina next generation sequencing (NGS) to determine the frequency of HHV-6 in CSF and respiratory samples that were initially submitted to the laboratory for other diagnostic tests.

Results

Of 72 samples tested for HHV-6 by PCR at the request of a clinician, 24 (33%) were positive for HHV-6. The majority of these patients were under the care of the haematology team (30/41, 73%), and there was a borderline association between HHV-6 detection and both Graft versus Host Disease (GvHD) and Central nervous system (CNS) disease (p=0.05 in each case). We confirmed detection of HHV-6 DNA using NGS in 4/20 (20%) CSF and respiratory samples.

Conclusions

HHV-6 is common in clinical samples submitted from a high-risk haematology population, and enhanced screening of this group should be considered. NGS can be used to identify HHV-6 from a complex microbiomee, but further controls are required to define the sensitivity and specificity, and to correlate these results with clinical disease. Our results underpin ongoing efforts to develop NGS technology for viral diagnostics.