bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Femtosecond Laser-Enabled Descemetorhexis and Manual Descemetorhexis in Descemet Membrane Endothelial Keratoplasty
Authors: Einan-Lifshitz Adi , Sorkin Nir , Boutin Tanguy , Showail Mahmood , Borovik Armand , Alobthani Murad , Chan Clara C. , Rootman David S.
Published: April 2017

Purpose:

To introduce a novel method to perform descemetorhexis in Descemet membrane endothelial keratoplasty (DMEK) using the femtosecond laser and to compare it with Descemet membrane endothelial keratoplasty performed with manual descemetorhexis (M-DMEK).

Methods:

A retrospective medical chart review of 2 groups of patients who underwent DMEK surgery combined with cataract surgery secondary to Fuchs corneal endothelial dystrophy and cataract: 17 patients underwent femtosecond laser-enabled descemetorhexis Descemet membrane endothelial keratoplasty (FE-DMEK) and 89 patients underwent DMEK surgery with M-DMEK. Best spectacle-corrected visual acuity, endothelial cell density (ECD), graft detachment rate, and complications were compared.

Results:

Average age of the 106 patients (64 women and 42 men) was 68 ± 11 years. Postoperative best spectacle-corrected visual acuity was 0.19 ± 0.13 logarithm of the minimum angle of resolution in the FE-DMEK group and 0.35 ± 0.48 logarithm of the minimum angle of resolution in the M-DMEK group (P = 0.218). One day after surgery, there were no significant graft detachments in the FE-DMEK group, compared with 20% graft detachment rate in the M-DMEK group (P = 0.041). Rebubbling was performed in 17% of eyes in the M-DMEK group compared with none in the FE-DMEK group (P = 0.066). The mean endothelial cell count in the FE-DMEK and M-DMEK groups at 6 months after surgery were 2105 ± 285 cells per square millimeter (24% cells loss) and 1990 ± 600 cells per square millimeter (29% cells loss), respectively (P = 0.579).

Conclusions:

FE-DMEK shows efficacy similar to that of M-DMEK with apparently less graft detachment and reduced need for rebubbling.
Solitary Iris Plasmacytoma With Anterior Chamber Crystalline Deposits
Authors: Stacey Andrew W. , Lavric Alenka , Thaung Caroline , Siddiq Samreen , Sagoo Mandeep S.
Published: April 2017

Purpose:

To report a case of solitary iris plasmacytoma successfully treated with ruthenium plaque radiotherapy.

Methods:

A 44-year-old white woman presented with pain in the right eye and raised intraocular pressure. Her medical history included breast cancer treated 11 years earlier with lumpectomy, lymph node clearance, chemotherapy, and radiotherapy. On examination, the right iris had a tan-colored mass with crystalline deposits visible on the mass surface and on the corneal endothelium. The fundus and left eye were normal. An anterior segment ultrasound scan showed a mass with mixed internal echogenicity and internal blood flow.

Results:

An iris biopsy showed an infiltrate of plasma cells. Immunohistochemistry for kappa and lambda light chains demonstrated lambda light chain restriction. Systemic hematologic investigations including complete blood count, serum paraproteins, bone marrow biopsy, and full-body magnetic resonance image were normal. The monoclonal plasma cell infiltrate was consistent with a solitary iris plasmacytoma. The mass was treated with ruthenium plaque radiotherapy. After 4 years of follow-up, the mass remained regressed, and no systemic myeloma has developed.

Conclusions:

Iris plasmacytoma is rare and should prompt systemic evaluation to rule out multiple myeloma. Solitary iris plasmacytoma can be successfully treated with plaque radiotherapy.
Virologic Failure of High-Dose Raltegravir With Concomitant Rifampin
Authors: Miller Misty M. , Kinney Karen K. , Liedtke Michelle D.
Published: April 2017

Treating mycobacterial infections and HIV concurrently typically presents difficulties due to drug-to-drug interactions between rifampin and many antiretrovirals. We present a case of raltegravir failure during concomitant rifampin use, despite documented administration of recommended increased dose of raltegravir.
Septic Arthritis Secondary to Neisseria gonorrheae Without Genital Symptoms and After Presumed Prolonged Carriage
Authors: Suady Barake Suhaireirene R. , Winn Richard E. , Crist Christopher J. , McKenzie Paula , Emrick Alanna L. , Ismail Amr M.
Published: April 2017

Septic arthritis remains an uncommon but not rare occurrence, with the potential for catastrophic morbidity if not recognized and treated early with appropriate antimicrobial agents. The role of Neisseria gonorrheae is well established in the differential diagnosis of septic arthritis in the young, sexually active population and particularly in monoarticular presentations. Gonococcal septic arthritis occurring without genital symptoms is not emphasized, although it has been described previously. The length of time from exposure to N. gonorrheae to the development of pyogenic arthritis is variable but usually is within 3 weeks. We report 4 cases of septic arthritis due to N. gonorrheae occurring in our hospital within 18 months (approximately 5.3% of septic arthritis), with prolonged intervals from initial exposure and with minimal to no genital symptoms.
Addressing the Challenges of Chagas Disease
Authors: Edwards Morven S. , Stimpert Kelly K. , Montgomery Susan P.
Published: April 2017

Chagas disease is an emerging health concern in the United States. US health care providers have an unparalleled opportunity to respond to the challenges this infection poses and to provide state-of-the-art care for patients with Chagas disease. Most of the approximately 300,000 persons with Trypanosoma cruzi infection living in the United States have chronic, asymptomatic infection acquired in endemic regions in Latin America. Congenital infection is often asymptomatic and, even when symptomatic, has no features that distinguish it from other congenitally transmitted infections. Health care providers and the public have limited awareness of this infection. Recognizing risk groups and performing targeted diagnostic testing for at-risk infants, children, and adults are a health priority because early treatment can effect cure and avert the life-threatening cardiac manifestations of Chagas disease. Two medications for treatment, benznidazole and nifurtimox, are available through the Centers for Disease Control and Prevention. Although challenges exist, informed health care providers can greatly reduce the effects of Chagas disease in the United States.
Molecular diagnosis of familial hypercholesterolaemia
Authors: Graham Colin A. , Latten Mark J. , Hart Padraig J.
Published: April 2017

Purpose of review

Familial hypercholesterolaemia is a hereditary disorder of lipoprotein metabolism which causes a lifelong increase in LDL-C levels resulting in premature coronary heart disease. The present review looks at some of the recent literature on how molecular methods can be used to assist in the definitive diagnosis of familial hypercholesterolaemia in a range of patient groups.

Recent findings

Several recent studies have shown that the prevalence of clinical familial hypercholesterolaemia is higher than previously thought at 1/200 to 1/300, and that 2–5% of patients presenting with early myocardial infarction can be found to have a familial hypercholesterolaemia mutation. The present review then examines different approaches to molecular testing for familial hypercholesterolaemia including point mutation panels versus next-generation sequencing gene panels, and the range of genes tested by some of those panels. Finally, we review the recent evidence for polygenic hypercholesterolaemia within clinically defined familial hypercholesterolaemia patient populations.

To identify patients with familial hypercholesterolaemia within clinically selected patient groups efficiently, a clinical scoring system should be combined with a molecular testing approach for mutations and for polygenic LDL-C single-nucleotide polymorphisms. Alternatively, a population screening methodology may be appropriate, using mutation testing at an early age before significant atherosclerosis has begun. The precise molecular testing method chosen may depend on the clinical presentation of the patient, and/or the population from which they arise.
Functional Impairment in Older Adults With Bipolar Disorder
Authors: Comes Mercè , Rosa Adriane , Reinares Maria , Torrent Carla , Vieta Eduard
Published: April 2017

Data describing bipolar disorder in older adults people are scarce, particularly with regard to functional status. This observational, comparative study assessed psychosocial functioning in 33 euthymic older adults with bipolar disorder compared with 30 healthy controls. In addition, we evaluated the association between clinical variables and poor functioning in the patient group. The mean age of the group was 68.70 years. Patients with bipolar disorder experienced poorer psychosocial functioning (19.15 ± 11.36) than healthy controls (5.17 ± 3.72; p = 0.0001), as assessed using the Functioning Assessment Short Test. Significant differences between the groups were found for specific domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, and interpersonal relationships (p = 0.0001, respectively). The largest variation was observed in overall functioning (Cohen’s d = 0.63). The number of previous hospitalizations was strongly associated with poor overall functioning (F = 7.217, p = 0.002). Older patients with bipolar disorder had a greater functional impairment than the healthy control group. Implementation of novel rehabilitation models is critical to help patients manage their illness.
Playing and Never Testing: Human Immunodeficiency Virus and Sexually Transmitted Infection Testing Among App-Using MSM in Southeast Asia
Authors: Weiss Kevin M. , Jonas Kai J. , Guadamuz Thomas E.
Published: April 2017

Little is known about mobile application (app)-based behavior of men who have sex with men (MSM) in Thailand. A cross-sectional online assessment of app users in Bangkok found that more than a quarter have never tested for human immunodeficiency virus (HIV) and 1 in 3 never tested for sexually transmitted infections (STI). STI testing patterns and HIV testing frequency were highly associated with each other in multinomial logistic regression. In the midst of an escalating epidemic where HIV incidence among MSM is highest in Asia, apps can serve to engage those least likely to be reached by traditional methods of recruitment and outreach in Thailand.
Human Papillomavirus Vaccination Among Young Men Who Have Sex With Men and Transgender Women in 2 US Cities, 2012–2014
Authors: Gorbach Pamina M. , Cook Ryan , Gratzer Beau , Collins Thomas , Parrish Adam , Moore Janell , Kerndt Peter R. , Crosby Richard A. , Markowitz Lauri E. , Meites Elissa
Published: April 2017

Background

Since 2011, in the United States, quadrivalent human papillomavirus (HPV) vaccine has been recommended for boys aged 11 to 12 years, men through age 21, and men who have sex with men (MSM) through age 26. We assessed HPV vaccination coverage and factors associated with vaccination among young MSM (YMSM) and transgender women (TGW) in 2 cities.

Methods

During 2012–2014, 808 YMSM and TGW aged 18 to 26 years reported vaccination status in a self-administered computerized questionnaire at 3 sexually transmitted disease (STD) clinics in Los Angeles and Chicago. Associations with HPV vaccination were assessed using bivariate and multivariable models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results

Few of the diverse participants (Hispanic/Latino, 38.0%; white, 27.0%; and black/African American, 17.9%) reported receiving 1 or more HPV vaccine doses (n = 111 [13.7%]) and even fewer reported 3 doses (n = 37 [4.6%]). A multivariable model found associations between vaccination and having a 4-year college degree or higher (aOR, 2.83; CI, 1.55–5.17) and self-reported STDs (aOR, 1.21; CI, 1.03–1.42). In a model including recommendation variables, the strongest predictor of vaccination was a health care provider recommendation (aOR, 11.85; CI, 6.70–20.98).

Conclusions

Human papillomavirus vaccination coverage was low among YMSM and TGW in this 2–US city study. Our findings suggest further efforts are needed to reach YMSM seeking care in STD clinics, increase strong recommendations from health care providers, and integrate HPV vaccination with other clinical services such as STD testing.
Coping With Staff Burnout and Work-Related Posttraumatic Stress in Intensive Care*
Authors: Colville Gillian A. , Smith Jared G. , Brierley Joe , Citron Kim , Nguru Noreen M. , Shaunak Priyanka D. , Tam Olivia , Perkins-Porras Linda
Published: April 2017

Objectives:

To examine the associations with symptoms of 1) burnout and 2) work-related posttraumatic stress, in adult and pediatric intensive care staff, focusing on the particular contributions of resilience and coping strategies.

Design:

Point prevalence cross-sectional study.

Setting:

Three adult ICUs and four PICUs.

Subjects:

Three hundred seventy-seven ICU staff.

Interventions:

None.

Measurements and Main Results:

Brief Resilience Scale, abbreviated Maslach Burnout Inventory, Trauma Screening Questionnaire, and Hospital Anxiety and Depression Scale. Prevalence of burnout (defined as high emotional exhaustion or high depersonalization) was 37%. Prevalence of clinically significant posttraumatic stress symptoms was 13%. There was a degree of overlap between burnout and other measures of distress, most notably for anxiety (odds ratio, 10.56; 95% CI, 4.12–27.02; p < 0.001). Hierarchical logistic regression demonstrated that self-reported resilience was strongly associated with decreased likelihood of meeting criteria for both forms of work-related distress (burnout: odds ratio, 0.52; 95% CI, 0.36–0.74; p < 0.001 and posttraumatic stress: odds ratio, 0.28; 95% CI, 0.16–0.46; p < 0.001) and that physicians were twice as likely as nurses to be at risk of reporting burnout (odds ratio, 2.11; 95% CI, 1.18–3.78; p = 0.012). After controlling for resilience, profession, and setting, the following coping strategies were independently associated with outcomes: attending debriefing reduced risk of burnout (odds ratio, 0.45; 95% CI, 0.21–0.95; p = 0.036), whereas the odds of posttraumatic stress were less if staff used talking to seniors (odds ratio, 0.43; 95% CI, 0.20–0.92; p = 0.029) or hobbies (odds ratio, 0.46; 95% CI, 0.23–0.93; p = 0.030) to cope with stress at work. Venting emotion (odds ratio, 1.92; 95% CI, 1.12–3.31; p = 0.018) and using alcohol (odds ratio, 2.30; 95% CI, 1.26–4.20; p = 0.006) were associated with a doubling in risk of reporting burnout.

Conclusions:

The use of particular coping strategies was systematically associated with symptoms of burnout and work-related posttraumatic stress in this group of intensive care staff, even after controlling for resilience and other factors. More research on how best to promote adaptive coping is needed in these challenging settings.
An International Survey of Corticosteroid Use for the Management of Low Cardiac Output Syndrome*
Authors: Flores Saul , FitzGerald Michael R. , Iliopoulos Ilias , Daily Joshua A. , Rodriguez Marco , Nelson David P. , Wong Hector R. , Menon Kusum , Cooper David S.
Published: April 2017

Objective:

Limited evidence exists on use of corticosteroids in low cardiac output syndrome following cardiac surgery. We sought to determine physicians’ practices and beliefs with regard to corticosteroids therapy for low cardiac output syndrome.

Design:

Multinational internet-based survey.

Setting:

Pediatric Cardiac Intensive Care Society member database.

Subjects:

Pediatric cardiac intensive care physicians.

Interventions:

None.

Measurements and Main Results:

We received 188 responses from 85 centers throughout the world including 57 U.S. congenital heart centers, eight Canadian centers, and 20 international centers. The majority of respondents (51%) reported performing at least 200 bypass cases per year and had separate dedicated cardiac ICUs (57%). Most physicians (89%) rarely or never prescribe corticosteroids for mild low cardiac output syndrome (single vasoactive agent and mildly decreased perfusion), whereas 94% of those surveyed sometimes or always administer corticosteroids to patients with severe low cardiac output syndrome (two or more vasoactive agents and persistent hypotension). Hydrocortisone was the most commonly used corticosteroids (88%), but there was no consensus on dosage used. There was a variable approach to cortisol level measurement and cortisol stimulation testing to inform therapy with corticosteroids. A majority of respondents (75%) stated that they would be willing to randomize patients with severe low cardiac output syndrome into a trial of corticosteroids efficacy.

Conclusions:

Our survey demonstrates considerable practice variability with regard to the type of patients in whom corticosteroids are administered, adrenal axis testing is performed, and dosage of hydrocortisone used. The majority of physicians, however, stated their willingness to randomize patients with severe low cardiac output syndrome in a corticosteroids trial. This survey identified multiple areas for future research on use of corticosteroids for low cardiac output syndrome.
A Novel Weaning Protocol for High-Flow Nasal Cannula in the PICU
Authors: Betters Kristina A. , Hebbar Kiran B. , McCracken Courtney , Heitz David , Sparacino Stephanie , Petrillo Toni
Published: April 2017

Objective:

High-flow nasal cannula use in the PICU continues to increase; however, a protocol for weaning patients has yet to be published. This study aimed to create an efficient and safe protocol for weaning high-flow nasal cannula.

Design:

A Respiratory Assessment Score was created using two validated scoring systems. A protocol was established for set “holidays” off high-flow nasal cannula, where nasal cannula flow was reduced to age-based low-flow nasal cannula rates if Respiratory Assessment Scores met certain criteria.

Setting:

The PICU at Children’s Healthcare of Atlanta at Egleston, a quaternary level hospital affiliated with Emory University.

Patients:

Patients treated in the PICU with high-flow nasal cannula from August 2013 to March 2014. Exclusions included apnea, heliox therapy, oxygen saturations less than 92% with a Fio
2 greater than 50%, admitted to PICU less than 6 hours, progression to intubation prior to scoring, or those ordered by physician to not receive holidays based on clinical status.

Interventions:

Patients who qualified for a “holiday” based on Respiratory Assessment Score were trialed off high-flow nasal cannula and rescored afterwards to assess tolerance.

Measurements and Main Results:

One hundred thirty-three patients were treated with high-flow nasal cannula, with the most common diagnosis being bronchiolitis (43%). Of these 133 patients, 119 (89.5%) successfully weaned to low-flow nasal cannula within four holiday attempts. Eighty-three patients (70%) weaned with only one attempt. Fourteen patients (10.5%) failed to wean. Reasons for failure were reintubation, increasing flow on high-flow nasal cannula, too high of Respiratory Assessment Score to meet weaning criteria, or slow weaning after failed attempts. Holidays did not precipitate clinical deterioration or lead to immediate intubation.

Conclusions:

Our study suggests that a high-flow nasal cannula “holiday” protocol is a safe and effective way to successfully wean PICU patients off high-flow nasal cannula. Additional investigation including validation of the scoring system used is warranted.
Vision Loss and Symmetric Basal Ganglia Lesions in Leber Hereditary Optic Neuropathy
Authors: Mercuri Matthew A. , White Halina , Oliveira Cristiano
Published: April 2017

A 30-year-old woman with progressive vision loss was found to have asymptomatic, bilateral, and symmetric basal ganglia lesions on MRI and was later diagnosed with Leber hereditary optic neuropathy (LHON). The rare occurrence of basal ganglia changes on MRI in patients with LHON is discussed.
Interpreting differentiation landscapes in the light of long-term linked selection
Authors: Burri Reto
Published: April 2017

Identifying genomic regions underlying adaptation in extant lineages is key to understand the trajectories along which biodiversity evolves. However, this task is complicated by evolutionary processes that obscure and mimic footprints of positive selection. Particularly the long-term effects of linked selection remain underappreciated and difficult to account for. Based on patterns emerging from recent research on the evolution of differentiation across the speciation continuum, I illustrate how long-term linked selection affects the distribution of differentiation along genomes. I then argue that a comparative population genomics framework that exploits emergent features of long-term linked selection can help overcome shortcomings of traditional genome scans for adaptive evolution, but needs to account for the temporal dynamics of differentiation landscapes.
Secondary osteons scale allometrically in mammalian humerus and femur
Authors: Felder A. A. , Phillips C. , Cornish H. , Cooke M. , Hutchinson J. R. , Doube M.
Published: May 2017

Intra-cortical bone remodelling is a cell-driven process that replaces existing bone tissue with new bone tissue in the bone cortex, leaving behind histological features called secondary osteons. While the scaling of bone dimensions on a macroscopic scale is well known, less is known about how the spatial dimensions of secondary osteons vary in relation to the adult body size of the species. We measured the cross-sectional area of individual intact secondary osteons and their central Haversian canals in transverse sections from 40 stylopodal bones of 39 mammalian species. Scaling analysis of our data shows that mean osteonal resorption area (negative allometry, exponent 0.23,R20.54,p< 0.005) and Haversian canal area (negative allometry, exponent 0.34,R20.45,p< 0.005) are significantly related to body mass, independent of phylogeny. This study is the most comprehensive of its kind to date, and allows us to describe overall trends in the scaling behaviour of secondary osteon dimensions, supporting the inference that osteonal resorption area may be limited by the need to avoid fracture in smaller mammalian species, but the need to maintain osteocyte viability in larger mammalian species.
10-Month-Old Infants Are Sensitive to the Time Course of Perceived Actions: Evidence From a Study Combining Eye-tracking and EEG
Authors: Bache Cathleen , Springer Anne , Noack Hannes , Stadler Waltraud , Kopp Franziska , Lindenberger Ulman , Werkle-Bergner Markus
Published: April 2017

Research has shown that infants are able to track a moving target efficiently – even if it is transiently occluded from sight. This basic ability allows prediction of when and where events happen in everyday life. Yet, it is unclear whether, and how, infants internally represent thetime courseof ongoing movements to derive predictions. In this study, 10-month-old crawlers observed the video of a same-aged crawling baby that was transiently occluded and reappeared in either a temporallycontinuousor non-continuous manner (i.e.,delayedby 500 ms vs.forwardedby 500 ms relative to the real-time movement). Eye movement and rhythmic neural brain activity (EEG) were measured simultaneously. Eye movement analyses showed that infants were sensitive to slight temporal shifts in movement continuation after occlusion. Furthermore, brain activity related to sensorimotor rather than mnemonic processing differed between observation of continuous and non-continuous movements. Early sensitivity to an action’s timing may hence be explained within the internal real-time simulation account of action observation. Overall, the results support the hypothesis that 10-month-old infants are well prepared for internal representation of the time course of observed movements that are within the infants’ current motor repertoire.
A heuristic method to identify runs of homozygosity associated with reduced performance in livestock
Authors: Howard J.T. , Tiezzi F. , Huang Y. , Gray K.A. , Maltecca C.
Published: April 2017

While for the most part genome-wide metrics are currently employed in managing livestock inbreeding, genomic data offer, in principle, the ability to identify functional inbreeding. Here we present a heuristic method to identify haplotypes contained within a run of homozygosity (ROH) associated with reduced performance. Results are presented for simulated and swine data. The algorithm comprises 3 steps. Step 1 scans the genome based on marker windows of decreasing size and identifies ROH genotypes associated with an unfavorable phenotype. Within this stage, multiple aggregation steps reduce the haplotype to the smallest possible length. In step 2, the resulting regions are formally tested for significance with the use of a linear mixed model. Lastly, step 3 removes nested windows. The effect of the unfavorable haplotypes identified and their associated haplotype probabilities for a progeny of a given mating pair or an individual can be used to generate an inbreeding load matrix (ILM). Diagonals ofILMcharacterize the functional inbreeding load of individual (IIL). We estimated the accuracy of predicting the phenotype based on ILL. We further compared the significance of the regression coefficient for IIL on phenotypes to genome-wide inbreeding metrics. We tested the algorithm using simulated scenarios (n =12) combining different levels of linkage disequilibrium (LD) and number of loci impacting a quantitative trait. Additionally, we investigated 9 traits from two maternal purebred swine lines. In simulated data, as the LD in the population increased the algorithm identified a greater proportion of the true unfavorable ROH effects. For example, the proportion of highly unfavorable true ROH effects identified raised from 32 to 41 % for the low to the high LD scenario. In both simulated and real data the haplotypes identified were contained within a much larger ROH (9.12-12.1 Mb). The IIL prediction accuracy was greater than zero across all scenarios for simulated data (high LD scenario mean (95% confidence interval): 0.49 (0.47-0.52)) and for nearly all swine traits (mean ± SD: 0.17±0.10). On average across simulated and swine datasets the IIL regression coefficient was more closely related to progeny performance than any genome-wide inbreeding metric. A heuristic method was developed that identified ROH genotypes with reduced performance and characterized the combined effects of ROH genotypes within and across individuals.
Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function
Authors: Rengachari Srinivasan , Groiss Silvia , Devos Juliette , Caron Elise , Grandvaux Nathalie , Panne Daniel
Published: April 2017

Cytokine signalling is mediated by the activation of distinct sets of structurally homologous JAK and STAT signalling molecules, which control nuclear gene expression and cell fate. A significant expansion in the gene regulatory repertoire controlled by JAK/STAT signalling has arisen by the selective interaction of STATs with IRF transcription factors. Type I interferons (IFN), the major antiviral cytokines, trigger the formation of the ISGF3 complex containing STAT1, STAT2 and IRF9. ISGF3 regulates the expression of IFN–stimulated genes (ISGs). ISGF3 assembly depends on selective interaction between IRF9, through its IRF–association domain (IAD), with the coiled–coil domain (CCD) of STAT2. Here, we report the crystal structures of the IRF9–IAD alone and in a complex with STAT2–CCD. Despite similarity in the overall structure among respective paralogs, the surface features of the IRF9–IAD and STAT2– CCD have diverged to enable specific interaction between these family members, thus enabling ISGF3 formation and expression of ISGs.
Coalescent models for populations with time-varying population sizes and arbitrary offspring distributions
Authors: Fraser Christophe , Li Lucy M
Published: April 2017

The coalescent has been used to infer from gene genealogies the population dynamics of biological systems, such as the prevalence of an infectious disease. The offspring distribution affects the relationship between population dynamics and the genealogy, and for infectious diseases, the offspring distribution is often highly overdispersed. Here, we provide a general formula for the coalescent rate for populations with time-varying sizes and any offspring distribution. The formula is valid in the same large population limit as Kingman’s original derivation. By relating our derivation to existing formulations of the coalescent, we show that differences in the coalescent rate derived for many population models may be explained by differences in the offspring distribution. The coalescent derivations presented here could be used to quantify the overdispersion in the offspring distribution of infectious diseases, which is useful for accurate modelling disease outbreaks.
Induction of Reproductive Behaviors by Exogenous Hormones in Captive Southern Rocky Mountain Boreal Toads,Anaxyrus boreas boreas
Authors: Calatayud Natalie Emma , Mullen Amanda Kathryn , Langhorne Cecilia Jane
Published: April 2017

Loss of reproductive viability, physiologically and/or behaviorally, can have profound effects on the fitness of a captive population and conservation efforts. The southern rocky mountain (SRM) population of the boreal toad has declined over the past 35 years, making captive breeding necessary to protect and augment the species in the wild. In recent years, a notable reduction in the incidence of amplexus and viable offspring from the captive breeding population has been observed. Hormone treatment protocols to stimulate gamete release in males and females are established in this species andin vitrofertilization has been performed successfully. However, successful hormone stimulation of reproductive behaviors and natural fertilization has not been well documented. During the breeding season of 2012, 24 males and 24 female toads were selected from a population of over 600 captive animals. Both sexes were treated with Human chorionic gonadotropin (hCG) and Gonadotropin Releasing Hormone (GnRH) or phosphate buffered saline (PBS). Females were primed twice with 3.7IU/g hCG and then injected with an ovulatory dose (OvD) of 13.5 IU/ g BW (Body weight) hCG and 0.4 μg/ g BW GnRH. Males were injected a single time with 10 IU/g BW hCG and 0.4 μg/ g BW GnRH, 12 h after females received their OvD. In 2013, knowing the approximate time when females oviposited after hormone treatments, we tested the best time to induce amplexus and spermiation. Males were divided into 4 groups and injected at 4 different times: (a) 12 h before females OvD; (b) at the same time as OvD; (c) 12 h after OvD; (d) control injected with PBS. Results from 2012 indicated that oviposition was solely dependent on females receiving hormone treatments not males. However, in 2013 we found that the duration of amplexus significantly influenced oviposition (P>0.05), and males injected 12 h prior to females spent more time in amplexus than males injected at the same time or 12 h after the females received hormones. Promoting reproductive behaviors and synchronizing gamete deposition continues to be imprecise and may require more than exogenous hormones. The complexity of promoting breeding behaviors may require a closer assessment of the captive environment.
Visual Response Properties in the Three Layer Turtle Visual Cortex
Authors: Hoseini Mahmood S. , Pobst Jeff , Wright Nathaniel C. , Clawson Wesley , Shew Woodrow , Wessel Ralf
Published: April 2017

Turtle dorsal cortex provides us with unique insights into cortical processing. It is known to share many features with the mammalian hippocampus and olfactory cortex as well as geniculo-cortical areas in stem amniotes from which mammals evolved. To this end, we have used data from extracellular recordings from microelectrode arrays to study spatial and temporal patterns of responses to visual stimuli as seen in both local field potential and action potentials. We discovered surprisingly large receptive fields, responsiveness to a broad range of stimuli, and high correlation between distant neural ensembles across recording array. Moreover, we found significant response variability regarding latency and strength in the presence of adaptation to both ongoing and visually evoked activity.
Mid-infrared free-electron laser-evoked discharge of crayfish compound eyes
Authors: Shishikura Fumio , Zen Heishun , Hayakawa Ken , Komatsuzaki Yoshimasa , Hayakawa Yashushi , Sakai Takeshi , Kii Toshiteru , Ohgaki Hideaki
Published: April 2017

Light perception is an intriguing subject, and it has been demonstrated that some animals can perceive wavelengths beyond human vision. However, it is still controversial whether animals can see mid-infrared radiation. A combination of two free-electron laser (FEL) facilities, LEBRA-FEL (Nihon University) and KU-FEL (Kyoto University), can provide light sources with high peak power and spatially coherent monochromatic wavelengths that are continuously tuneable from 400 nm to 20 μm. We show that the crayfish (Procambarus clarkii) compound eye responds to pulsed mid-infrared FELs (1 Hz for KU-FEL; 2 Hz for LEBRA-FEL) from 3 to 17 μm. Our finding provides insight into the animal’s visual sensing of mid-infrared radiation, and that the sensing does not depend on thermal effects. Although the behavioural reason for vision in this wavelength range and the mechanism are still under investigation, understanding this type of visual sensing may lead to applications other than photophysical applications.
Myotis rufonigerGenome Sequence and Analyses:M. rufoniger’s Genomic Feature and the Decreasing Effective Population Size ofMyotisBats
Authors: Bhak Youngjune , Jeon Yeonsu , Jeon Sungwon , Chung Oksung , Jho Sungwoong , Jun JeHoon , Kim Hak-Min , Cho Yongsoo , Yoon Changhan , Lee Seungwoo , Kang Jung-Hoon , Lim Jong-Deock , An Junghwa , Cho Yun Sung , Ryu Doug-Young , Bhak Jong
Published: April 2017

Myotis rufonigeris a vesper bat in the genusMyotis. Here we report the whole genome sequence and analyses of theM. rufoniger. We generated 124 Gb of short-read DNA sequences with an estimated genome size of 1.88 Gb at a sequencing depth of 66× fold. The sequences were aligned toM. brandtiibat reference genome at a mapping rate of 96.50% covering 95.71% coding sequence region at 10× coverage. The divergence time ofMyotisbat family is estimated to be 11.5 million years, and the divergence time betweenM. rufonigerand its closest speciesM. davidiiis estimated to be 10.4 million years. We found 1,239 function-alteringM. rufonigerspecific amino acid sequences from 929 genes compared to otherMyotisbat and mammalian genomes. The functional enrichment test of the 929 genes detected amino acid changes in melanin associatedDCT,SLC45A2,TYRP1, andOCA2genes possibly responsible for theM. rufoniger’s red fur color and a general coloration inMyotis.N6AMT1gene, associated with arsenic resistance, showed a high degree of function alteration inM. rufoniger. We further confirmed thatM. rufonigeralso has bat-specific sequences withinFSHB,GHR,IGF1R,TP53, MDM2,SLC45A2,RGS7BP,RHO,OPN1SW, andCNGB3genes that have already been published to be related to bat’s reproduction, lifespan, flight, low vision, and echolocation. Additionally, our demographic history analysis found that the effective population size ofMyotisclade has been consistently decreasing since ∼30k years ago.M. rufoniger’s effective population size was the lowest inMyotisbats, confirming its relatively low genetic diversity.
Functional diversity among sensory neurons from efficient coding principles
Authors: Gjorgjieva Julijana , Meister Markus , Sompolinsky Haim
Published: April 2017

In many sensory systems the neural signal is coded by the coordinated response of heterogeneous populations of neurons. What computational benefit does this diversity confer on information processing? We derive an efficient coding framework assuming that neurons have evolved to communicate signals optimally given natural stimulus statistics and metabolic constraints. Incorporating nonlinearities and realistic noise, we study optimal population coding of the same sensory variable using two measures: maximizing the mutual information between stimuli and responses, and minimizing the error incurred by the optimal linear decoder of responses. Our theory is applied to a commonly observed splitting of sensory neurons into ON and OFF that signal stimulus increases or decreases, and to populations of monotonically increasing responses of the same type, ON. Depending on the optimality measure, we make different predictions about how to optimally split a population into ON and OFF, and how to allocate the firing thresholds of individual neurons given realistic stimulus distributions and noise, which accord with certain biases observed experimentally.
wft4galaxy: A Workflow Tester for Galaxy
Authors: Piras Marco Enrico , Pireddu Luca , Zanetti Gianluigi
Published: April 2017

Motivation

Workflow managers for scientific analysis provide a high-level programming platform facilitating standardization, automation, collaboration and access to sophisticated computing resources. The Galaxy workflow manager provides a prime example of this type of platform. As compositions of simpler tools, workflows effectively comprise specialized computer programs implementing often very complex analysis procedures. To date, no simple way exists to automatically test Galaxy workflows and ensure their correctness has appeared in the literature.

Results

Withwft4galaxywe offer a tool to bring automated testing to Galaxy workflows, making it feasible to bring continuous integration to their development and ensuring that defects are detected promptly.wft4galaxycan be easily installed as a regular Python program or launched directly as a Docker container – the latter reducing installation effort to a minimum.

Availability

wft4galaxyis available online athttps://github.com/phnmnl/wft4galaxyunder the Academic Free License v3.0.

Supplementary information

Supplementary information is available athttp://wft4galaxy.readthedocs.io.
Real-time observation of light-controlled transcription in living cells
Authors: Rademacher Anne , Erdel Fabian , Trojanowski Jorge , Rippe Karsten
Published: April 2017

Gene expression is a tightly controlled process that is coordinated in space and time. To dissect its dynamic regulation with high temporal resolution, we introduce an optogenetic tool termed BLInCR (Blue Light-Induced Chromatin Recruitment) that combines rapid and reversible light-dependent recruitment of effector proteins with a real-time readout for transcription. We used BLInCR to control the activity of a reporter gene cluster in the human osteosarcoma cell line U2OS by reversibly recruiting the viral transactivator VP16. RNA production was detectable ∼2 minutes after VP16 recruitment and readily decreased when VP16 dissociated from the cluster in the absence of light. Quantitative assessment of the activation process revealed biphasic activation kinetics with a pronounced early phase in cells treated with the histone deacetylase inhibitor SAHA. Comparison with kinetic models for transcription activation suggests that the gene cluster undergoes a maturation process when activated. BLInCR will facilitate the study of transcription dynamics in living cells.
N-(3-oxododecanoyl)-L-homoserine lactone interactions in the breast tumor microenvironment: implications for breast cancer viability and proliferationin vitro
Authors: Balhouse Brittany N. , Patterson Logan , Schmelz Eva M. , Slade Daniel J. , Verbridge Scott S.
Published: April 2017

It is well documented that the tumor microenvironment profoundly impacts the etiology and progression of breast cancer, yet the contribution of the resident microbiome within breast tissue remains poorly understood. Tumor microenvironmental conditions, such as hypoxia and dense tumor stroma, predispose progressive phenotypes and therapy resistance, however the role of bacteria in this interplay remains uncharacterized. We hypothesized that the effect of individual bacterial secreted molecules on breast cancer viability and proliferation would be modulated by these tumor-relevant stressors differentially for cells at varying stages of progression. To test this, we incubated human breast adenocarcinoma cells (MDA-MB-231,MCF-DCIS.com) and non-malignant breast epithelial cells (MCF-10A) with N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), a quorum-sensing molecule fromPseudomonas aeruginosathat regulates bacterial stress responses. This molecule was selected becausePseudomonaswas recently characterized as a significant fraction of the breast tissue microbiome and OdDHL is documented to impact mammalian cell viability. After OdDHL treatment, we demonstrated the greatest decrease in viability with the more malignant MDAMB-231 cells and an intermediateMCF-DCIS.com(ductal carcinomain situ) response. The responses were also culture condition (i.e. microenvironment) dependent. These results contrast the MCF-10A response, which demonstrated no change in viability in any culture condition. We further determined that the observed trends in breast cancer viability were due to modulation of proliferation for both cell types, as well as the induction of necrosis for MDA-MB-231 cells in all conditions. Our results provide evidence that bacterial quorum-sensing molecules interact with the host tissue environment to modulate breast cancer viability and proliferation, and that the effect of OdDHL is dependent on both cell type as well as microenvironment. Understanding the interactions between bacterial signaling molecules and the host tissue environment will allow for future studies that determine the contribution of bacteria to the onset, progression, and therapy response of breast cancer.
MicroRNA regulation of the MRN complex impacts DNA damage, cellular senescence and angiogenic signaling
Authors: Espinosa-Diez Cristina , Wilson RaeAnna , Chatterjee Namita , Hudson Clayton , Ruhl Rebecca , Hipfinger Christina , Helms Erin , Khan Omar F. , Anderson Daniel G. , Anand Sudarshan
Published: April 2017

MicroRNAs contribute to biological robustness by buffering cellular processes from external perturbations. Here we report an unexpected link between DNA damage response and angiogenic signaling that is buffered by two distinct microRNAs. We demonstrate that genotoxic stress-induced miR-494 and miR-99b inhibit the DNA repair machinery by targeting the MRE11a-RAD50-NBN (MRN) complex. Functionally, gain and loss of function experiments show that miR-494 and miR-99b affect telomerase activity, activate p21 and Rb pathways and diminish angiogenic sproutingin vitroandin vivo. Genetic and pharmacological disruption of VEGFR-2 signaling and the MRN complex reveal a surprising co-dependency of these pathways in regulating endothelial senescence and proliferation. Vascular-targeted delivery of miR-494 decreases both growth factor-induced and tumor angiogenesis in mouse models. Mechanistically, disruption of the MRN complex induced CD44, a known driver of senescence and regulator of VEGF signaling in addition to suppressing IL-13 a stimulator of VEGF signaling. Our work identifies a putative miR-facilitated mechanism by which endothelial cells can be insulated against VEGF signaling to facilitate the onset of senescence and highlight the potential of targeting DNA repair to disrupt pathological angiogenesis.
A horizontally transferred autonomous Helitron became a full polydnavirus segment inCotesia vestalis
Authors: Heringer Pedro , Dias Guilherme B. , Kuhn Gustavo C. S.
Published: May 2017

Bracoviruses associate symbiotically with thousands of parasitoid wasp species in the family Braconidae, working as virulence gene vectors, and allowing the development of wasp larvae within hosts. These viruses are composed by multiple DNA circles that are packaged into infective particles and injected together with wasp's eggs during parasitization. One of the viral segments ofCotesia vestalisbracovirus contains a gene that has been previously described as a helicase of unknown origin. Here we demonstrate that this gene is a Rep/Helicase from an intact Helitron transposable element that covers the viral segment almost entirely. We also provide evidence that this element underwent at least two horizontal transfers, which appear to have occurred consecutively: first from a Drosophila host ancestor to the genome of the parasitoid waspCotesia vestalisand its bracovirus, and then fromC. vestalisto a lepidopteran host (Bombyx mori). Our results reinforce the idea of parasitoid wasps as frequent agents of horizontal transfers in eukaryotes. Additionally, this Helitron-bracovirus segment is the first example of a transposable element that effectively became a whole viral circle.
Caterpillars lack a resident gut microbiome
Authors: Hammer Tobin J. , Janzen Daniel H. , Hallwachs Winnifred , Jaffe Samuel L. , Fierer Noah
Published: May 2017

Many animals are inhabited by microbial symbionts that influence their hosts’ development, physiology, ecological interactions, and evolutionary diversification. However, firm evidence for the existence and functional importance of resident microbiomes in larval Lepidoptera (caterpillars) is lacking, despite the fact that these insects are enormously diverse, major agricultural pests, and dominant herbivores in many ecosystems. Using 16S rRNA gene sequencing and quantitative PCR, we characterized the gut microbiomes of wild leaf-feeding caterpillars in the United States and Costa Rica, representing 124 species from 16 families. Compared with other insects and vertebrates assayed using the same methods, the microbes we detected in caterpillar guts were unusually low-density and highly variable among individuals. Furthermore, the abundance and composition of leaf-associated microbes were reflected in the feces of caterpillars consuming the same plants. Thus, microbes ingested with food are present (though possibly dead or dormant) in the caterpillar gut, but host-specific, resident symbionts are largely absent. To test whether transient microbes might still contribute to feeding and development, we conducted an experiment on field-collected caterpillars of the model speciesManduca sexta. Antibiotic suppression of gut bacterial activity did not significantly affect caterpillar weight gain, development, or survival. The high pH, simple gut structure, and fast transit times that typify caterpillar digestive physiology may prevent microbial colonization. Moreover, host-encoded digestive and detoxification mechanisms likely render microbes unnecessary for caterpillar herbivory. Caterpillars illustrate the potential ecological and evolutionary benefits of independence from symbionts, a lifestyle which may be widespread among animals.
When “N of 2” is not enough: integrating statistical and functional data in gene discovery
Authors: Cassa Christopher A. , Akle Sebastian , Jordan Daniel M. , Rosenfeld Jill A.
Published: May 2017

The expanding use of genomic sequencing promises to improve clinical diagnostics and to drive the discovery of new disease genes. Candidate genes are increasingly being identified through recurrent cases (e.g., two or more independent cases [“N of 2”] in which variants are present in the same gene). These second case hits provide statistical evidence of an association, which may then be combined with functional validation or familial segregation studies to bolster the evidence that a gene is truly causal. Here, we discuss how to integrate different forms of functional evidence with human genetics case and segregation data to improve the significance of new disease–gene associations.