bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise Behaviors and Health Conditions of Runners After Childbirth
Authors: Blyholder Liga , Chumanov Elizabeth , Carr Kathleen , Heiderscheit Bryan
Published: October 2016

Background:

With a recent increase in running popularity, more women choose to run during and after pregnancy. Little research has examined exercise behaviors and postpartum health conditions of runners.

Hypothesis:

Antenatal and postpartum exercise is beneficial in reducing certain postpartum health conditions.

Study Design:

Cross-sectional study.

Level of Evidence:

Level 5.

Methods:

A self-administered, online survey was developed that consisted of questions regarding antenatal and postpartum exercise behaviors, maternal history, and postpartum health conditions. The survey was completed by 507 postpartum women who were running a minimum of once per week.

Results:

Seventy-two percent of participants ran regularly during pregnancy, with 38% reporting running in the third trimester. Women with musculoskeletal pain during pregnancy were more likely to experience pain on return to running postpartum (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.64-5.88). A birth spacing of <2 years or a vaginal-assisted delivery increased the odds of postpartum stress urinary incontinence (OR, 1.71; 95% CI, 1.00-2.91 and OR, 2.08; 95% CI, 1.24-3.47, respectively), while Caesarean section delivery decreased the odds (OR, 0.58; 95% CI, 0.35-0.96). Multiparous women and those who reported a Caesarean section delivery were more likely to report abdominal separation (OR, 2.11; 95% CI, 1.08-4.26 and OR, 2.20; 95% CI, 1.05-4.70, respectively). Antenatal weight training decreased the odds of postpartum pain (OR, 0.52; 95% CI, 0.28-0.94), stress urinary incontinence (OR, 0.46; 95% CI, 0.21-0.98), and abdominal separation (OR, 0.51; 95% CI, 0.26-0.96).

Conclusion:

Musculoskeletal pain, stress urinary incontinence, and abdominal separation are prevalent conditions among postpartum runners and are more likely to occur with specific maternal history characteristics. Antenatal weight training may reduce the odds of each of these conditions.

Clinical Relevance:

Strengthening exercises during pregnancy may prevent weakening and dysfunction of the abdominal and pelvic floor muscles, decreasing the odds of pain, stress urinary incontinence, and abdominal separation after pregnancy.
A Novel Neuroscience Intermediate-Level Care Unit Model
Authors: Quimby Alexandra E. , Shamy Michel C. F. , Rothwell Deanna M. , Liu Erin Y. , Dowlatshahi Dar , Stotts Grant
Published: October 2016

Background and Purpose:

Neurointensive care units have been shown to improve patient outcomes across a variety of neurological and neurosurgical conditions. However, the efficacy of less resource-intensive intermediate-level care units to deliver similar care has not been well studied. The purpose of this study is to evaluate the impact of neurocritical specialist comanagement on patient flow and safety in a neuroscience intermediate-level care unit.

Methods:

Our intervention consisted of the addition of a physician with critical care experience as well as training in neurology, anesthesiology, or intensive care to a neuroscience intermediate-level care unit to comanage patients alongside neurology and neurosurgery staff during weekday daytime hours. A retrospective analysis was performed on prospectively collected data pertaining to all patients admitted to the unit over a 3-year period, 1 year before our intervention and 2 years after. Patient statistics including wait times to admission, length of stay (LOS), and mortality were reviewed.

Results:

Following the intervention, there were significant reductions in wait times to unit admission from both the emergency department and postanesthetic care unit, as well as reductions in the average LOS. No significant safety concerns were identified.

Conclusion:

This study has demonstrated that the optimization of a neuroscience intermediate-level care unit involving comanagement of patients by a neurocritical specialist can reduce wait times to admission and lengths of stay, with preserved safety outcomes.
Intra-pericardial recurrent thymoma presenting with compression of the pulmonary trunk
Authors: Yamada Shunsuke , Masuda Daisuke , Takeichi Haruka , Nakamura Yusuke , Iwazaki Masayuki
Published: October 2016

A patient who had a second recurrent intra-pericardial thymoma is presented. The tumor was expanding in the pericardial space and compressed the pulmonary trunk. The obstruction of the pulmonary trunk could have resulted in a fatal outcome. Surgical management was required, and complete surgical resection and mediastinal adjuvant radiation therapy were effective in this patient’s management.
Percutaneous balloon atrial septostomy on top of venoarterial extracorporeal membrane oxygenation results in safe and effective left heart decompression
Authors: Baruteau Alban-Elouen , Barnetche Thomas , Morin Luc , Jalal Zakaria , Boscamp Nicholas S , Le Bret Emmanuel , Thambo Jean-Benoit , Vincent Julie A , Fraisse Alain , Torres Alejandro J
Published: October 2016

Background:

Transcatheter techniques are emerging for left atrial (LA) decompression under venoarterial extracorporeal membrane oxygenation (VA-ECMO). We aimed to assess whether balloon atrioseptostomy (BAS) is a safe and efficient strategy.

Methods:

All patients who underwent percutaneous static BAS under VA-ECMO at four tertiary institutions were retrospectively reviewed.

Results:

From 2000 to 2014, BAS was performed in 64 patients (32 adults and 32 children). Indications for ECMO support included acute myocarditis (31.3%) and non-myocarditis cardiac disease, mostly end-stage dilated cardiomyopathy (32.8%). BAS was required because of pulmonary oedema/haemorrhage and left ventricular (LV) distension. The mean balloon diameter was 21.8 ± 8.4mm. Adequate LA decompression was achieved in all patients. Mean LA pressure fell from 24.2 ± 6.9 mmHg to 7.8 ± 2.6 mmHg ( p < 0.001). The left-to-right atrial pressure gradient fell from 17.2 ± 7.1 mmHg to 0.09 ± 0.5 mmHg ( p < 0.001). Echocardiography showed an unrestrictive left-to-right atrial shunting in all patients. Improvement of day 1 chest X-ray was observed in 76.6% of patients, clinical status in 98.4% of patients and pulmonary haemorrhage in 14 out of 14 patients. Complications occurred in 9.4% of patients, representing pericardial effusion, fast atrial fibrillation, ventricular fibrillation requiring defibrillation, transient complete heart block and femoral venous dissection requiring covered stent placement. In the 37 (57.8%) patients who were successfully decannulated, the median ECMO duration was 9 (range: 4–24) days. After a median follow-up of 12.3 (range: 0.1–142) months, 35.9% patients died, 17.2% received a LV assist device as a bridge to transplantation, 31.2% were transplanted and 56.2% were home discharged and alive.

Conclusions:

Percutaneous BAS may be a safe and efficient strategy for discharging the LA in both adults and children supported by VA-ECMO.
Current tools available for the diagnosis of drug-resistant tuberculosis
Authors: Gilpin Christopher , Korobitsyn A. , Weyer K.
Published: October 2016

Drug-resistant tuberculosis (DR-TB) poses a major threat to control of tuberculosis worldwide. Diagnosis and treatment of DR-TB are considerably more difficult than for drug-susceptible tuberculosis (TB) and require higher level infrastructure and proficiency from laboratory specialists and clinicians. The World Health Organization (WHO) End TB Strategy calls for early diagnosis and initiation of appropriate treatment of all persons of all ages with any form of drug-susceptible TB or DR-TB. This requires ensuring access to WHO-recommended rapid diagnostics and universal drug susceptibility testing (DST) for all persons with signs and symptoms of TB. There are a number of laboratory tools available for diagnosis of DR-TB, including phenotypic culture-based DST as well as molecular methods. Optimal and complementary use of the available diagnostic tools at the different levels of the tiered network of TB laboratories, as well as correct interpretation of the diagnostic results provided by them is critical for accurate and timely diagnosis of DR-TB thus enabling effective treatment and care of patients.
A Study on Attributes of Customer Patronage toward Choosing a Fast Food Retail Outlet
Authors: Kotni V.V. Devi Prasad
Published: October 2016

QSR … the buzzword all over the world. Quick service restaurants (QSRs) are the fast food retail outlets which provide fast food in no time. The leading QSRs are McDonald, KFC, Pizza Hut, Dominos Pizza, Subway etc. Almost every major city in India and all over the world is having most of these fast food restaurants. The customers are visiting these outlets either to spent leisure time or they do not have time to go for home made meals. In such a situation it is very difficult to know what exactly the customer wants. The fast food business in India and the rest of the world is getting increasingly more complex and competitive. Keeping this market situation in view, primary objective of this study is to identify the attributes of customer patronage for choosing a particular fast food outlet for fast food consumption. The study also offers recommendations to the fast food retailers based on the most expected attributes by the fast food consumers.
Exploring the Linkage between Awareness and Perception of High-performance Work Practices with Employee Well-being at Workplace: A New Dimension for HRM
Authors: Garg Naval , Lal Bhajan
Published: October 2016

The present study is an attempt to examine critical perspective of high-performance work system in Indian settings. As per critical perspective, high-performance work practices (HPWPs) may lead to increase in job demands and pressure, which, in turn, may result into poor employee attitudes and well-being. The article seeks to examine the perspective by exploring the direct linkage between HPWPs and employee well-being. Employee well-being is studied through three constructs, namely, employee commitment, job satisfaction, and work–life balance satisfaction. Data reveal direct statistical relationship between awareness and perception of employees with all three constructs of employee well-being. Thus the article statistically discards critical perspective and approves mutual gain perspective of high performance practices. Further managerial implications and theoretical contribution of the article is also discussed.
Emotional Intelligence of Entrepreneurs and their Decision-making Style: Role of Vision
Authors: Dua Yesha Seth
Published: October 2016

The paper discusses the relationship between emotional intelligence and decision-making styles (Intuitive, Decision making through thorough analysis, Consultative, Based on Market demand) of Entrepreneurs in the Indian manufacturing Industry. Past literature supports the importance of vision for decisions to be advantageous to the company. The present paper is an effort towards this direction, of understanding the role played by Top management teams Vision, between (Emotional Intelligence) EI and Decision making style (DMS). The sample consisted of 4 Indian medium-sized manufacturing companies. Emotional Intelligence was measured by an EI questionnaire by Esther Orioli, Cooper & Sawaf, and Decision-making styles questionnaire for measuring decision-making style of Indian entrepreneurs. Test of Cronbach’s alpha for all the variables were above 0.8, indicated that reliability for these questionnaires were accepted. The analysis is done using Structural Equation modeling. The results emphasize on the importance of emotional intelligence of entrepreneurs on their decision making style and the mediating role of Vision between emotional intelligence and Decision making style. Analyzing the data revealed that there is a significant positive relationship between EI and Decision making style (DMS) through TMT Vision. The study supports the past theory of interdependence of emotion and cognition in Decision making process.
Does CRR and Repo Change Affect Corporate Output?
Authors: Ahmad Moid U.
Published: October 2016

Bank financing is an imperative component of financing the companies. When banks are short on liquidity, this financing activity also tends to go slow. Banks liquidity is dependent upon the policy enforced by the central bank which uses cash reserve ratio (CRR) and Repo rates very frequently to this effect. Since bank credit is dependent on its liquidity position, any change in key policy rates will affect the corporate funding. This is the basic hypothesis which is being tested in this research. The objective of the article is to understand the effect of two important policy rates, Repo and CRR, on corporate output through aggregate sales of the listed companies. The objective was achieved by building a VAR system and doing the required analysis using quarterly data for the time period 2000–2015. One of the important findings was that lag effect is very critical to understand this relationship between policy rates and corporate output and while formulating policies, this should be an important variable to be considered.
Acute Ultrasonography Investigation to Predict Reruptures and Outcomes in Patients With an Achilles Tendon Rupture
Authors: Westin Olof , Nilsson Helander Katarina , Grävare Silbernagel Karin , Möller Michael , Kälebo Peter , Karlsson Jón
Published: October 2016

Background:

The optimal treatment for acute Achilles tendon ruptures is still an ongoing debate. Acute ultrasonography (US) investigation to measure the diastasis between the tendon ends has previously been used to classify acute Achilles tendon ruptures; however, no study has used US to predict reruptures and functional outcomes.

Purpose:

To investigate whether acute US can be used to predict the risk of reruptures and outcomes after treatment of an acute Achilles tendon rupture.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

Forty-five patients (37 men, 8 women) with a mean age of 39 ± 9.2 years (range, 23-59 years) from a cohort of 97 patients participating in a randomized controlled study comparing surgical and nonsurgical treatment were included. US was performed within 72 hours from the index injury. Diastasis between the tendon ends was documented. Reruptures were documented, and the patients’ functional outcomes were measured 12 months after injury.

Results:

Patients with a diastasis of >10 mm treated nonsurgically had a higher degree of rerupture. In the nonsurgically treated group, 3 of 4 patients with a diastasis of >10 mm suffered from rerupture ( P < .001). Moreover, in the nonsurgical group, there was significantly worse outcomes in patients with a diastasis of >5 mm in terms of patient-reported outcomes using the Achilles tendon Total Rupture Score (ATRS) ( P = .004) and heel-rise height at 12 months ( P = .048) compared with the group with a lesser degree of tendon separation.

Conclusion:

US may be a useful tool to predict the risk of rerupture and greater degree of functional deficit. It may be an important measure in a clinical treatment algorithm for deciding whether a patient will benefit from surgical intervention after an acute Achilles tendon rupture.
Aging and Spectro-Temporal Integration of Speech
Authors: Grose John H. , Porter Heather L. , Buss Emily
Published: October 2016

The purpose of this study was to determine the effects of age on the spectro-temporal integration of speech. The hypothesis was that the integration of speech fragments distributed over frequency, time, and ear of presentation is reduced in older listeners—even for those with good audiometric hearing. Younger, middle-aged, and older listeners (10 per group) with good audiometric hearing participated. They were each tested under seven conditions that encompassed combinations of spectral, temporal, and binaural integration. Sentences were filtered into two bands centered at 500 Hz and 2500 Hz, with criterion bandwidth tailored for each participant. In some conditions, the speech bands were individually square wave interrupted at a rate of 10 Hz. Configurations of uninterrupted, synchronously interrupted, and asynchronously interrupted frequency bands were constructed that constituted speech fragments distributed across frequency, time, and ear of presentation. The over-arching finding was that, for most configurations, performance was not differentially affected by listener age. Although speech intelligibility varied across condition, there was no evidence of performance deficits in older listeners in any condition. This study indicates that age, per se, does not necessarily undermine the ability to integrate fragments of speech dispersed across frequency and time.
Advancing Community Health Workers Through Higher Education: Lessons Learned From a Basic Certificate Program Implementation
Authors: Haywood Marlon , Garman Andy , Johnson Tricia , Christopher Beth-Anne M. , Walker Roy
Published: October 2016

The Affordable Healthcare Act has, among other changes, created greater incentives to reduce health disparities in low-income communities across the country, which heightened the importance and expectations of community health workers (CHWs) as part of the clinical care team. These heightened expectations have begun to transition what has historically been a paraprofessional role into one that involves more clearly defined competencies and development needs. In an effort to meet these needs in the city of Chicago, a CHW basic certificate program was developed and launched at Malcolm X college (one of the seven city Colleges of Chicago), in collaboration with several community partners. This article presents the experience of this program, the challenges faced in its implementation, and lessons from this experience that may be relevant to others involved in the professional preparation of CHWs.
Capnography Prevents Hypoxia during Sedation for Dental Treatment: A Randomized Controlled Trial
Authors: Takaya K. , Higuchi H. , Ishii-Maruhama M. , Yabuki-Kawase A. , Honda Y. , Tomoyasu Y. , Maeda S. , Miyawaki T.
Published: October 2016

Intravenous sedation is useful for dental treatment in patients with intellectual disabilities. However, it is often necessary to manage such patients with deep sedation because their cooperation cannot be obtained. During deep sedation, undetected hypoventilation can lead to severe complications, such as hypoxia. Recently, capnographic monitoring has been advocated as a useful technique for preventing hypoxia during sedation. This randomized control trial evaluated whether the use of capnography reduces the incidence of hypoxia during the deep sedation of patients for dental treatment. This study involved patients with intellectual disabilities who underwent dental treatment under sedation. The subjects were randomized to the intervention group (I-group) or control group (C-group). All of the patients underwent routine monitoring, as well as bispectral index (BIS) and capnographic monitoring; however, only an independent observer had access to the patients’ capnographic data during the dental procedures. Sedation was maintained at a BIS of 50 to 70 by administration of propofol. In the I-group, the independent observer signaled to the dental anesthesiologist if the capnogram indicated that the patient had been suffering from alveolar hypoventilation or apnea for >15 s. In the C-group, the observer signaled to the dental anesthesiologist if the capnogram indicated that the patient had been suffering from alveolar hypoventilation or apnea for >60 s. In both groups, the dental anesthesiologists responded to the signals using appropriate airway management strategies. The primary endpoint of this study was the incidence of hypoxia during dental treatment, which was defined as oxygen saturation of <95%. Hypoxemic episodes occurred in 13.4% and 34.8% of cases in the I-group and C-group, respectively. The incidence of hypoxia was significantly lower in the I-group. These results suggest that capnographic monitoring during deep sedation for dental treatment prevents hypoxemic episodes by allowing the early detection of hypoventilation.

Knowledge Transfer Statement: This is the first randomized controlled trial to examine whether the use of capnography reduces the incidence of hypoxia during deep sedation for dental treatment. The findings of this study can be used by clinicians to aid decision-making regarding dental sedation standards at individual clinics. Moreover, they can be used as high-level evidence during the production or updating of clinical guidelines for dental sedation by leading associations.
My Pilgrimage in Mission
Authors: Richard Wesley
Published: October 2016

This personal account chronicles the journey of one expatriate family that tested the viability of the migration evangelism model set forth in 1961 by Mennonite theologian John Howard Yoder. Reflecting on nearly two decades of cultural identification and church involvement as self-supporting English teachers in Japan, the author identifies ways in which their tentmaking status impacted nearly every aspect of their lives, from their legal status in the country to their relationships with other Mennonite missionaries. The article concludes that the experiment was financially successful, replicable, and led to long-term commitment, providing a satisfying, practical, and compelling paradigm for overseas missions.
The very long-term risk and predictors of recurrent ischaemic events after a stroke at a young age: The FUTURE study
Authors: Arntz Renate M , van Alebeek Mayte E , Synhaeve Nathalie E , van Pamelen Jeske , Maaijwee Noortje AMM , Schoonderwaldt Hennie , van der Vlugt Maureen J , van Dijk Ewoud J , Rutten-Jacobs Loes CA , de Leeuw Frank-Erik
Published: October 2016

Introduction

Patients who suffer a stroke at a young age, remain at a substantial risk of developing recurrent vascular events and information on very long-term prognosis and its risk factors is indispensable. Our aim is to investigate this very long-term risk and associated risk factors up to 35 years after stroke.

Patients and methods

Prospective cohort study among 656 patients with a first-ever ischaemic stroke or transient ischaemic stroke (TIA), aged 18–50, who visited our hospital (1980–2010). Outcomes assessed at follow-up (2014–2015) included TIA or ischaemic stroke and other arterial events, whichever occurred first. Kaplan–Meier analysis quantified cumulative risks. A prediction model was constructed to assess risk factors independently associated with any ischaemic event using Cox proportional hazard analyses followed by bootstrap validation procedure to avoid overestimation.

Results

Mean follow-up was 12.4 (SD 8.2) years (8105 person-years). Twenty-five years cumulative risk was 45.4% (95%CI: 39.4–51.5) for any ischaemic event, 30.1% (95%CI: 24.8–35.4) for cerebral ischaemia and 27.0% (95%CI: 21.1–33.0) for other arterial events. Risk factors retained in the prediction model were smoking (HR 1.35, 95%CI: 1.04–1.74), poor kidney function (HR 2.10, 95%CI: 1.32–3.35), history of peripheral arterial disease (HR 2.10, 95%CI: 1.08–3.76) and cardiac disease (HR 1.84, 95%CI: 1.06–3.18) (C-statistic 0.59 (95%CI: 0.55–0.64)).

Discussion and conclusion

Young stroke patients remain at a substantial risk for recurrent events; almost 1 of 2 develops a recurrent ischaemic event and 1 of 3 develops a recurrent stroke or TIA during 25 years of follow-up. Risk factors independently associated with recurrent events were poor kidney function, smoking, history of peripheral arterial disease and cardiac disease.
Theophylline as an add-on to thrombolytic therapy in acute ischaemic stroke (TEA-Stroke): A randomized, double-blinded, placebo-controlled, two-centre phase II study
Authors: Modrau Boris , Hjort Niels , Østergaard Leif , Mouridsen Kim , Andersen Grethe , Bach Flemming Winther
Published: October 2016

Introduction

Early reperfusion of brain tissue at risk of injury (penumbra salvage) is crucial in treating acute ischaemic stroke. Neuroprotective agents may extend the time window for the reperfusion. The vasoactive agent theophylline redistributes the perfusion to ischaemic brain tissue and thus reduces brain damage, brain tissue oedema and mortality in animal stroke models. Furthermore, treatment with theophylline has been shown to result in considerable and rapid clinical improvement, albeit only temporary, in some stroke patients. We hypothesize that treatment with theophylline will improve the collateral supply in acute ischaemic brain tissue and thus facilitate reperfusion despite proximal vessel occlusion. The primary study objective is to evaluate whether theophylline is safe and efficient in acute ischaemic stroke patients as an add-on to thrombolytic therapy.

Methods

The TEA-Stroke Trial is a two-centre, proof of concept phase II clinical study with a randomized, double-blinded, placebo-controlled design. One hundred and twenty patients with acute ischaemic stroke and significant perfusion–diffusion mismatch, as determined by magnetic resonance imaging, are randomized 1:1 to either theophylline or placebo as an add-on to standard thrombolytic therapy.

Study outcome

The dual primary outcome measures include penumbra salvage (penumbral tissue not developing into infarcted tissue) and clinical improvement at the 24-h follow-up.

Discussion

Results from studies of theophylline in stroke animal models, clinical case series and randomized clinical trials are controversial. A Cochrane analysis from 2004 concluded that there was not enough evidence to assess whether theophylline is safe and improves outcomes in patients with acute ischaemic stroke. The TEA-Stroke Trial will clarify whether theophylline as an add-on to standard thrombolytic therapy improves penumbra salvage with a reduced risk of reperfusion damage, reduced final infarct size, and improved clinical outcome.
A novel mutation in the N-terminal domain of Drosophila BubR1 affects the spindle assembly checkpoint function of BubR1
Authors: Duranteau Marie , Montagne Jean-Jacques , Rahmani Zohra
Published: October 2016

The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate segregation of chromosomes into two daughter cells. BubR1, a key component of the SAC, also plays a role in the mitotic timing since depletion of BubR1 leads to accelerated mitosis. We previously found that mutation of the KEN1-box domain of Drosophila BubR1 (bubR1-KEN1 mutant) affects the binding of BubR1 to Cdc20, the activating co-factor of the APC/C, and does not accelerate the mitotic timing despite resulting in a defective SAC, which was unlike what was reported in mammalian cells. Here, we show that a mutation in a novel Drosophila short sequence (bubR1-KAN mutant) leads to an accelerated mitotic timing as well as SAC failure. Moreover, our data indicate that the level of Fzy, the Drosophila homolog of Cdc20, recruited to kinetochores is diminished in bubR1-KEN1 mutant cells and further diminished in bubR1-KAN mutant cells. Altogether, our data show that this newly identified Drosophila BubR1 KAN motif is required for a functional SAC and suggest that it may play an important role on Cdc20/Fzy kinetochore recruitment.
Escargot controls the sequential specification of two tracheal tip cell types by suppressing FGF signaling in Drosophila
Authors: Miao Guangxia , Hayashi Shigeo
Published: October 2016

Extrinsic branching factors promote the elongation and migration of tubular organs. In the Drosophila tracheal system, Branchless (Drosophila FGF) stimulates the branching program by specifying tip cells that acquire motility and lead branch migration to a specific destination. Tip cells have two alternative cell fates: the terminal cell (TC), which produces long cytoplasmic extensions with intracellular lumen, and the fusion cell (FC), which mediates branch connections to form tubular networks. How Branchless controls this specification of cells with distinct shapes and behaviors is unknown. Here we report that this cell type diversification involves the modulation of FGF signaling by the zinc-finger protein Escargot (Esg), which is expressed in the FC and is essential for its specification. The dorsal branch begins elongation with a pair of tip cells with high FGF signaling. When the branch tip reaches its final destination, one of the tip cells becomes an FC and expresses Esg. FCs and TCs differ in their response to FGF: TCs are attracted by FGF, whereas FCs are repelled. Esg suppresses ERK signaling in FCs to control this differential migratory behavior.
DUX4 induces a transcriptome more characteristic of a less-differentiated cell state and inhibits myogenesis
Authors: Knopp Paul , Krom Yvonne D. , Banerji Christopher R. S. , Panamarova Maryna , Moyle Louise A. , den Hamer Bianca , van der Maarel Silvère M. , Zammit Peter S.
Published: October 2016

Skeletal muscle wasting in facioscapulohumeral muscular dystrophy (FSHD) results in substantial morbidity. On a disease-permissive chromosome 4qA haplotype, genomic and/or epigenetic changes at the D4Z4 macrosatellite repeat allows transcription of the DUX4 retrogene. Analysing transgenic mice carrying a human D4Z4 genomic locus from an FSHD-affected individual showed that DUX4 was transiently induced in myoblasts during skeletal muscle regeneration. Centromeric to the D4Z4 repeats is an inverted D4Z4 unit encoding DUX4c. Expression of DUX4, DUX4c and DUX4 constructs, including constitutively active, dominant-negative and truncated versions, revealed that DUX4 activates target genes to inhibit proliferation and differentiation of satellite cells, but that it also downregulates target genes to suppress myogenic differentiation. These transcriptional changes elicited by DUX4 in mouse have significant overlap with genes regulated by DUX4 in man. Comparison of DUX4 and DUX4c transcriptional perturbations revealed that DUX4 regulates genes involved in cell proliferation, whereas DUX4c regulates genes engaged in angiogenesis and muscle development, with both DUX4 and DUX4c modifing genes involved in urogenital development. Transcriptomic analysis showed that DUX4 operates through both target gene activation and repression to orchestrate a transcriptome characteristic of a less-differentiated cell state.
Essential role of the Dishevelled DEP domain in a Wnt-dependent human-cell-based complementation assay
Authors: Gammons Melissa V. , Rutherford Trevor J. , Steinhart Zachary , Angers Stephane , Bienz Mariann
Published: October 2016

Dishevelled (DVL) assembles Wnt signalosomes through dynamic head-to-tail polymerisation by means of its DIX domain. It thus transduces Wnt signals to cytoplasmic effectors including β-catenin, to control cell fates during normal development, tissue homeostasis and also in cancer. To date, most functional studies of Dishevelled relied on its Wnt-independent signalling activity resulting from overexpression, which is sufficient to trigger polymerisation, bypassing the requirement for Wnt signals. Here, we generate a human cell line devoid of endogenous Dishevelled (DVL1– DVL3), which lacks Wnt signal transduction to β-catenin. However, Wnt responses can be restored by DVL2 stably re-expressed at near-endogenous levels. Using this assay to test mutant DVL2, we show that its DEP domain is essential, whereas its PDZ domain is dispensable, for signalling to β-catenin. Our results imply two mutually exclusive functions of the DEP domain in Wnt signal transduction – binding to Frizzled to recruit Dishevelled to the receptor complex, and dimerising to cross-link DIX domain polymers for signalosome assembly. Our assay avoids the caveats associated with overexpressing Dishevelled, and provides a powerful tool for rigorous functional tests of this pivotal human signalling protein.
Bumble bees regulate their intake of the essential protein and lipid pollen macronutrients
Authors: Vaudo A. D. , Stabler D. , Patch H. M. , Tooker J. F. , Grozinger C. M. , Wright G. A.
Published: October 2016

Bee population declines are linked to reduction of nutritional resources due to land-use intensification, yet we know little about the specific nutritional needs of many bee species. Pollen provides bees their primary source of protein and lipids, but nutritional quality varies widely among host-plant species. Therefore, bees may be adapted to assess resource quality and adjust their foraging behavior to balance nutrition from multiple food sources. We tested the ability of two bumble bee species, Bombus terrestris and B. impatiens, to regulate protein and lipid intake. We restricted B. terrestris adults to single synthetic diets varying in protein:lipid ratios (P:L). The bees overate protein on low fat diets and overate lipid on high fat diets to reach their targets of lipid and protein respectively. The bees survived best on a 10:1 P:L diet; the risk of dying increased as a function of dietary lipid when bees ate diets with lipid contents greater than 5:1 P:L. Hypothesizing that P:L intake target of adult worker bumble bees was between 25:1-5:1, we presented workers from both species unbalanced but complementary paired diets to determine if they self-select their diet to reach a specific intake target. Bees consumed similar amounts of proteins and lipids in each treatment and averaged a 14:1 P:L for B. terrestris and 12:1 P:L for B. impatiens. These results demonstrate that adult worker bumble bees likely select foods that provide them with a specific ratio of P:L. These P:L intake targets could affect pollen foraging in the field and help explain patterns of host-plant species choice by bumble bees.
Dopaminergic inhibition of gonadotropin-releasing hormone neurons in the cichlid fish,Astatotilapia burtoni
Authors: Bryant Astra S. , Greenwood Anna K. , Juntti Scott A. , Byrne Allie E. , Fernald Russell D.
Published: October 2016

Dopamine regulates reproduction in part by modulating neuronal activity within the hypothalamic-pituitary-gonadal (HPG) axis. Previous studies suggested numerous mechanisms by which dopamine exerts inhibitory control over the HPG axis, ultimately changing the levels of sex steroids that regulate reproductive behaviors. However, it is not known whether these mechanisms are conserved across vertebrate species. In particular, it is unknown whether mechanisms underlying dopaminergic control of reproduction are shared between mammals and teleost fish. In mammals, dopamine directly inhibits GnRH1 hypothalamic neurons, the gatekeepers for activation of the HPG axis. Here, we demonstrate, for the first time in teleost fish, dopaminergic control of GnRH1 neurons via direct dopamine receptor type-2 (D2R) mediated inhibition within the hypothalamus. These results suggest that direct dopaminergic control of GnRH1 neurons via interactions in the hypothalamus is not exclusive to tetrapod reproductive control, but is likely conserved across vertebrate species.
Hemolymph circulation in insect flight appendages: physiology of the wing heart and circulatory flow in the wings of the mosquito,Anopheles gambiae
Authors: Chintapalli Ravi Theja V. , Hillyer Julián F.
Published: October 2016

The wings of insects are composed of membranes supported by interconnected veins. Within these veins are epithelial cells, nerves and tracheae, and their maintenance requires the flow of hemolymph. For this purpose, insects employ accessory pulsatile organs (auxiliary hearts) that circulate hemolymph throughout the wings. Here, we used correlative approaches to determine the functional mechanics of hemolymph circulation in the wings of the malaria mosquito, Anopheles gambiae. Examination of sectioned tissues and intravital videos showed that the wing heart is located underneath the scutellum and is separate from the dorsal vessel. It is composed of a single pulsatile diaphragm (indicating that it is unpaired) that contracts at 3 Hz and circulates hemolymph throughout both wings. The wing heart contracts significantly faster than the dorsal vessel, and there is no correlation between the contractions of these two pulsatile organs. The wing heart functions by aspirating hemolymph out of the posterior wing veins, which forces hemolymph into the wings via anterior veins. By tracking the movement of fluorescent microspheres, we show that the flow diameter of the wing circulatory circuit is less than 1 µm, and we present a spatial map detailing the flow of hemolymph across all the wing veins, including the costa, sub-costa, ambient costa, radius, media, cubitus anterior, anal vein, and crossveins. We also quantified the movement of hemolymph within the radius and within the ambient costa, and show that hemolymph velocity and maximum acceleration are higher when hemolymph is exiting the wing.
The roles of tissue nitrate reductase activity and myoglobin in securing nitric oxide availability in deeply hypoxic crucian carp
Authors: Hansen Marie N. , Lundberg Jon O. , Filice Mariacristina , Fago Angela , Christensen Nanna M. G. , Jensen Frank B.
Published: October 2016

In mammals, treatment with low doses of nitrite have cytoprotective effects in ischemia/reperfusion events, due to nitric oxide formation and S-nitrosation of proteins. Interestingly, anoxia-tolerant lower vertebrates possess an intrinsic ability to increase intracellular [nitrite] during anoxia in tissues with high myoglobin and mitochondria contents, such as the heart. Here we test the hypothesis that red and white skeletal muscle develops different nitrite levels in crucian carp exposed to deep hypoxia and whether this correlates with myoglobin concentration. We also tested if liver, muscle, and heart tissue possess nitrate reductase activity that supply nitrite to the tissues during severe hypoxia. Crucian carp exposed to deep hypoxia (1<Po2<3mmHg) for one day increased nitrite in red musculature to more than double the value in normoxic fish, while nitrite was unchanged in white musculature. There was a highly significant positive correlation between tissue concentrations of nitrite and nitros(yl)ated compounds. Myoglobin levels were 7 times higher in red than white musculature, but there was no clear correlation between [nitrite] and [Mb]. Finally, we found a low but significant nitrate reductase activity in liver and white muscle, but not in cardiomyocytes. Nitrate reduction was inhibited by allopurinol, showing that it was partly catalyzed by xanthine oxidoreductase.
CRISPR/Cas9 with single guide RNA expression driven by small tRNA promoters showed reduced editing efficiency compared to a U6 promoter
Authors: Wei Yuda , Qiu Yan , Chen Yanhao , Liu Gaigai , Zhang Yongxian , Xu Luwei , Ding Qiurong
Published: October 2016

Multiplex genome engineering in vivo with CRISPR/Cas9 shows great promise as a potential therapeutic approach. The ability to incorporate multiple single guide RNA (sgRNA) cassettes together with Cas9 gene expression in one AAV vector could greatly enhance the efficiency. In a recent Method article, Mefferd and coworkers indicated that small tRNA promoters could be used to drive sgRNA expression to facilitate the construction of a more effective AAV vector. In contrast, we found that when targeting endogenous genomic loci, CRISPR/Cas9 with tRNA promoter-driven sgRNA expression showed much reduced genome editing activity, compared with significant cleavage with U6 promoter-driven sgRNA expression. Though the underlying mechanisms are still under investigation, our study suggests that the CRISPR/Cas9 system with tRNA promoter-driven sgRNA expression needs to be reevaluated before it can be used for therapeutic genome editing.
Quantifying RNA binding sites transcriptome-wide using DO-RIP-seq
Authors: Nicholson Cindo O. , Friedersdorf Matthew , Keene Jack D.
Published: October 2016

RNA-binding proteins (RBPs) and noncoding RNAs orchestrate post-transcriptional processes through the recognition of specific sites on targeted transcripts. Thus, understanding the connection between binding to specific sites and active regulation of the whole transcript is essential. Many immunoprecipitation techniques have been developed that identify either whole transcripts or binding sites of RBPs on each transcript using cell lysates. However, none of these methods simultaneously measures the strength of each binding site and quantifies binding to whole transcripts. In this study, we compare current procedures and present digestion optimized (DO)-RIP-seq, a simple method that locates and quantifies RBP binding sites using a continuous metric. We have used the RBP HuR/ELAVL1 to demonstrate that DO-RIP-seq can quantify HuR binding sites with high coverage across the entire human transcriptome, thereby generating metrics of relative RNA binding strength. We demonstrate that this quantitative enrichment of binding sites is proportional to the relative in vitro binding strength for these sites. In addition, we used DO-RIP-seq to quantify and compare HuR's binding to whole transcripts, thus allowing for seamless integration of binding site data with whole-transcript measurements. Finally, we demonstrate that DO-RIP-seq is useful for identifying functional mRNA target sets and binding sites where combinatorial interactions between HuR and AGO-microRNAs regulate the fate of the transcripts. Our data indicate that DO-RIP-seq will be useful for quantifying RBP binding events that regulate dynamic biological processes.
Sequence-selective recognition of double-stranded RNA and enhanced cellular uptake of cationic nucleobase and backbone-modified peptide nucleic acids
Authors: Hnedzko Dziyana , McGee Dennis W. , Karamitas Yannis A. , Rozners Eriks
Published: October 2016

Sequence-selective recognition of complex RNAs in live cells could find broad applications in biology, biomedical research, and biotechnology. However, specific recognition of structured RNA is challenging, and generally applicable and effective methods are lacking. Recently, we found that peptide nucleic acids (PNAs) were unusually well-suited ligands for recognition of double-stranded RNAs. Herein, we report that 2-aminopyridine (M) modified PNAs and their conjugates with lysine and arginine tripeptides form strong (Ka = 9.4 to 17 × 107 M−1) and sequence-selective triple helices with RNA hairpins at physiological pH and salt concentration. The affinity of PNA–peptide conjugates for the matched RNA hairpins was unusually high compared to the much lower affinity for DNA hairpins of the same sequence (Ka = 0.05 to 1.1 × 107 M−1). The binding of double-stranded RNA by M-modified PNA–peptide conjugates was a relatively fast process (kon = 2.9 × 104 M−1 sec−1) compared to the notoriously slow triple helix formation by oligodeoxynucleotides (kon ∼ 103 M−1 sec−1). M-modified PNA–peptide conjugates were not cytotoxic and were efficiently delivered in the cytosol of HEK293 cells at 10 µM. Surprisingly, M-modified PNAs without peptide conjugation were also taken up by HEK293 cells, which, to the best of our knowledge, is the first example of heterocyclic base modification that enhances the cellular uptake of PNA. Our results suggest that M-modified PNA–peptide conjugates are promising probes for sequence-selective recognition of double-stranded RNA in live cells and other biological systems.
Investigation of operation factors in the self-balancing device of the washing machine in resonance zone
Authors: Alekhin Sergey N. , Petrosov Sergey P. , Alekhin Alexey S.
Published: October 2016

The paper objective is to solve the issues related to the increase of reliability, profitability, and safety of modern washing machines on the basis of decrease in dynamic loads under whizzing. The principles of forming operation factors in the liquid self-balancing device (SBD) with the displaced fluid (on which design a number of patents are received) when passing a resonance zone under whizzing are considered. A comparative analysis of the SBD function implementation for the conditions of forming an adequate force response to the force input for two earlier established most rational conditions: for the force generated by resonance, and if reached the maximum unbalanced force, is carried out. The dependences of the SBD internal capacity traverse on the design factors of the SBD and the cleaning unit suspension system, and also on the operation parameters of the extraction process, are obtained. The research results are submitted in diagrams. The results analysis allows drawing the conclusions on the obtained data application perspectiveness to ensure maximum efficiency of the process of balancing irregular masses of textiles in the drum during the whizzing cycle.
Wear-resistance of high entropy cutting-tool materials
Authors: Ryzhkin Anatoly A. , Bokov Anatoly I. , Oleynikova Yulia A.
Published: October 2016

The work objective is to study the wear resistance of the experimental hard alloys (EHA) and complex alloyed high-speed steels (HSS) under cutting, as well as to establish the interconnection between their tribological characteristics and the entropy values (thermal EMF). The experimental studies on the EHA wear are carried out under the longitudinal turning, and HSS - under the friction conditions and drilling operations. Molybdenum, iron, titanium and copper mono carbide alloys are inserted into the cobalt bonds. It is shown that in this case, both entropy and wear-resistance increase (up to 2.5-3 times) as compared to the VK8 base alloy. At the same time the optimum machining spectrum extends. The functional relation between entropy and thermal EMF of the HSS is established, and it is shown that the minimum values of the thermal EMF correspond to the high entropy values. The HSS wear rate under friction is lower and the guaranteed life of drills is higher in steels with a high entropy value. The results obtained should be applied to the forming operations for the cutting-tool materials (CTM) of the maximum wear-resistance, and when developing new CTM.
Integral equation for numerical solution of stationary quantum-mechanical problems
Authors: Knyazev Sergey Yu.
Published: October 2016

The work objective is to describe the numerical solution method for the stationary Schrödinger equation based on the application of the integral equation identical to the Schrödinger equation. The structure of this integral equation is close to the structure of the Fredholm equation of second kind and allows obtaining the problem numerical solution. The method under study allows finding the energy eigenvalues and eigensolutions to the quantum-mechanical problems of various dimensions. The test results of the solving problems method for one-dimensional and two-dimensional quantum oscillators are obtained. The found numerical values of eigenenergy and eigenfunctions of the oscillator are compared to the known analytical solutions, and then the error of result is evaluated. The highest accuracy of the solution is obtained for the first energy levels. The numerical solution error increases with the number of the energy eigenvalue. For the subsequent energy level, the error increases almost by an order of magnitude. The solution error for the fourth energy level is less than 2% if the integration domain contains 500 elements. If the energy level is degenerate, it is possible to obtain all eigenfunctions corresponding to the given level. For this purpose, various auxiliary functions the symmetry of which is coherent with the eigenfunction symmetry are used.