bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring fatigue as a symptom in COPD
Authors: Antoniu Sabina Antonela , Ungureanu Didona
Published: March 2015

Fatigue is a symptom commonly diagnosed in cancers and in many other chronic debilitating diseases and is one of the main therapeutic targets for various pharmacologic and non-pharmacologic interventions. However, in chronic obstructive pulmonary disease (COPD), this symptom, which can be considered as the main extrapulmonary clinical feature of the disease, can impact significantly on the health-related quality of life of the patients. The aims of this review are to discuss the issues related to fatigue assessment in COPD and to highlight the importance of this symptom in this setting based on the data retrieved from articles published between 1987 through August 2014 available on MEDLINE database. Fatigue can be measured by various scales or questionnaires that are designed for generic purposes or for COPD-related purposes but is still underdiagnosed and undertreated. This is due to the fact that its clinical and prognostic relevance are not appropriately acknowledged. The early identification of fatigue clinical descriptors from patients’ reports could help with better management of this symptom.
Team Travel Effects and the College Football Betting Market
Authors: Coleman B. Jay
Published: March 2015

This research examines whether the college football betting line and over/under accurately assimilate travel effects on visiting teams, including time zones traversed; direction and distance traveled; and temperature, elevation, and aridity changes. We investigate the market’s accuracy at predicting winners, point differentials, and points scored and examine its market efficiency, that is, whether travel affects the chance the home team covers the spread or the chance that an “over” bet wins. The betting market is found to be an inaccurate and inefficient processor of travel effects, most consistently for late-season games involving an underdog with a 1-hr time deficit versus its opponent.
The Sunk-Cost Fallacy in the National Football League
Authors: Keefer Quinn A. W.
Published: March 2015

The National Football League (NFL) draft is used to examine the presence of the sunk-cost fallacy in teams’ playing time decisions. In the NFL, salary cap value represents a significant sunk cost to teams. We use the structure of the NFL draft to conduct a fuzzy regression discontinuity design. Optimal bandwidth local linear results suggest a 10% increase in salary cap value yields an additional 2.7 games started, for players selected near the cutoff between the first two rounds. Despite being no more productive, the first round selections receive a compensation premium, which leads to them starting significantly more games.
Biomedical Research Ethics Committees in Sub-Saharan Africa
Authors: Silaigwana Blessing , Wassenaar Douglas
Published: March 2015

Research Ethics Committees (RECs) are mandated to protect human participants by conducting ethical reviews of biomedical research. To date, there is a dearth of information on the structure, functioning, and outcomes of RECs in Africa. This article reviews empirical studies investigating African RECs, with the aim of providing an overview of what is known and identifying gaps in our knowledge. We conducted a literature search of the EBSCO, PubMed, and Google Scholar electronic databases. Twenty-three empirical studies reporting on the structure, functions, and outcomes of African RECs were included in our analysis. The review yielded limited systematic data on RECs in Africa. Available empirical evidence suggests that challenges hampering the effective functioning of RECs included lack of membership diversity, scarcity of resources, insufficient training of members, inadequate capacity to review and monitor studies, and lack of national ethics guidelines and accreditation. Relatively little data on the review outcomes of African RECs were described. There is an ongoing need for concerted efforts from various stakeholders to support capacity development and enhancement of African RECs.
Leading schools in communities of multiple deprivation
Authors: Lumby Jacky
Published: March 2015

This article explores how leadership and gender are constructed by women principals of schools located in communities of multiple deprivation in two provinces of South Africa. Analysis of interview data uncovers a hierarchy of goals related to establishing a school, recruiting and retaining learners, ensuring they are ready to learn, developing learning and enhancing their life chances. The pursuit of these goals entails actions which both challenge and sustain gender disadvantage and offer both gains and losses for learners. A highly complex relationship between the material conditions of the school community, gender construction, the South African context and the individual principal’s history and characteristics is suggested. The article concludes that principals are both bound by and challenge the constraints of gender. It also suggests that heroic Anglophone notions of principals turning around schools in communities of multiple deprivation is a process of misrecognition which conceals the reality of the lives and possibilities for both principals and learners in schools in such locations.
What is ‘policy’ and what is ‘policy response’? An illustrative study of the implementation of the Leadership Standards for Social Justice in Scotland
Authors: Ward SC , Bagley C , Lumby J , Hamilton T , Woods P , Roberts A
Published: March 2015

This article examines ‘policy’ and ‘policy response’ through documentary analysis and an illustrative study of policy implementation. Our approach is informed by Foucault’s (2009) theory that power relations in society are conditioned by a culturally generated set of ideas, and that these relations contain the space for both coercion and resistance. Our aim is to consider the potential for policy compliance and contestation by: (1) describing policy and policy response, drawing attention to the neoliberal hegemony that has come to dominate policy discourse globally; and (2) considering how social agents respond to a particular instance of policy. We provide documentary analysis of the interpolation of leadership into policy development in Scotland following the OECD (2007) report, and offer a small scale illustrative study of the implementation of the Leadership Standards for Social Justice in Scotland (GTCS, 2012). The head teachers in our study drew upon the discourse of marketization when describing their response to policy on social justice. We consider this finding in light of the argument that our interaction with policy has been conditioned through previous instances of neoliberal discourse formation (Ball, 2008). We conclude by considering the implications of the neoliberal hegemony for policy debate.
Type I IFN signaling on dendritic cells is required for NK cell-mediated anti-tumor immunity
Authors: Karimi Khalil , Karimi Yalda , Chan Jeffrey , Boudreau Jeanette E , Basset Jennifer , Chew Marianne V , Reid Sarah , Bramson Jonathan L , Wan Yonghong , Ashkar Ali A
Published: March 2015

NK cells play a vital role in innate anti-tumor immunity. Crosstalk between NK cells and dendritic cells (DCs) has come to the forefront in protection against tumors in the context of DC vaccines. We previously discovered that NK cell activation mediates the anti-tumor activity elicited by DC vaccines in response to melanoma tumor challenge in a murine lung metastasis model. In this study, we sought to explore the mechanism behind this NK–DC communication, specifically looking at the involvement of IL-15 and type I IFN signaling. Using DCs from IL-15–/– and IL-15Rα–/– mice, we found that the anti-tumor effect of the vaccine remained comparable with DCs from wild type mice. Moreover, DCs derived from IFN-α/βR–/– mice also maintained their anti-tumor effect. Interestingly, endogenous DCs were found to accumulate in the draining lymph nodes post-immunization and their depletion abolished the anti-tumor effect of the vaccine. Our findings suggest the important role that type I IFN signaling and endogenous DCs play in DC vaccine-mediated anti-tumor protection. Our data suggest that type I IFNs from vaccine DCs activate host DCs to provide NK cell-mediated anti-tumor immunity.
Benign prostatic hyperplasia
Authors: Cantlay Anna , Ni Raghallaigh Holly
Published: March 2015

Lower urinary tract symptoms (LUTS) are common and can affect up to 30% of men over the age of 65 years. The term LUTS encompasses storage, voiding and post-micturition symptoms; all of which can produce a significant impact on quality of life. There are many causes of LUTS. In addition to pathology within the urinary tract, LUTS can also be caused by medication, diabetes, heart failure, obstructive sleep apnoea and high levels of fluid intake. A common urological cause for symptoms is benign prostatic hyperplasia (BPH); a benign enlargement of the prostate gland that affects 30% of men between 50 and 60 years in age and up to 90% of men over the age of 85 years. This article aims to assist GPs to identify and understand the patient presenting with prostatic symptoms, and effectively manage BPH in a primary care setting.
Catheters and conveens
Authors: Smith Thomas J , Gietzmann William , Drinnan Nicholas , Sellaturay Senthy
Published: March 2015

Catheters and conveens are very common, with their long-term use being found in up to 9% of nursing home residents. GPs must understand the indications for urinary catheterisation and be aware of complications associated with catheter and conveen use. GPs must educate patients to care for them and understand when referral to urology is required.
Non-hormonal treatments for the menopause
Authors: McBride Kate Louise
Published: March 2015

The International Menopause Society defines menopause as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. It is recognised to have occurred after 12 consecutive months of amenorrhoea, for which there is no obvious physiological or pathological cause. This article will outline, and evaluate the evidence for, the range of non-hormonal options available for managing the menopause.
An outbreak of invasive group A streptococcal infection among elderly patients receiving care from a district nursing team, October 2013 – May 2014
Authors: Olufon Oluwakemi , Iyanger Nalini , Cleary Vivien , Lamagni Theresa
Published: March 2015

Between October 2013 and April 2014 five elderly patients living within a 2 square mile radius, were admitted to local hospitals with severe group A streptococcal cellulitis and septicaemia. Molecular typing confirmed four patients for whom typing results were available to have the same emm gene sequence type, emm st89. An outbreak investigation was launched and identified that each patient had received care interventions from a district nursing team at their home or local health clinic in the 7 days prior to onset of symptoms.
Mental health service utilization in sub-Saharan Africa: is public mental health literacy the problem? Setting the perspectives right
Authors: Atilola Olayinka
Published: March 2015

The severely constrained resources for mental health service in less-developed regions like sub-Saharan Africa underscore the need for good public mental health literacy as a potential additional mental health resource. Several studies examining the level of public knowledge about the nature and dynamics of mental illness in sub-Saharan Africa in the last decade had concluded that such knowledge was poor and had called for further public enlightenment. What was thought to be mental health ‘ignorance’ has also been blamed for poor mainstream service utilization. These views however assume that non-alignment of the views of community dwellers in sub-Saharan Africa with the biomedical understanding of mental illness connotes ‘ignorance’, and that correcting such ‘ignorance’ will translate to improvements in service utilization. Within the framework of contemporary thinking in mental health literacy, this paper argues that such assumptions are not culturally nuanced and may have overrated the usefulness of de-contextualized public engagement in enhancing mental health service utilization in the region. The paper concludes with a discourse on how to contextualize public mental health enlightenment in the region and the wider policy initiatives that can improve mental health service utilization.
Trust Me, I Am Your News Channel
Authors: Choi Yunmi , Axelrod Daniel , Kim Jihyun
Published: March 2015

This article compares how millennial generation members perceive the credibility of the news they consume from television (TV) channels, radio stations, newspapers, websites, and mobile devices such as tablets and smartphones. American and Korean college students prefer to access the news through mobile devices and computers. But unlike Americans, young Koreans think that journalism is most credible when it comes from a TV or a newspaper. Additionally, this study found that owning and using a smartphone, a different mobile device, or a computer to access news did not automatically make those platforms a young adult’s favorite ways to consume journalism.
Reference Values for the Marx Activity Rating Scale in a Young Athletic Population
Authors: Cameron Kenneth L. , Peck Karen Y. , Thompson Brandon S. , Svoboda Steven J. , Owens Brett D. , Marshall Stephen W.
Published: March 2015

Background:

Activity-related patient-reported outcome measures are an important component of assessment after knee ligament injury in young and physically active patients; however, normative data for most activity scales are limited.

Objective:

To present reference values by sex for the Marx Activity Rating Scale (MARS) within a young and physically active population while accounting for knee ligament injury history and sex.

Study Design:

Cross-sectional study.

Level of Evidence:

Level 2.

Methods:

All incoming freshman entering a US Service Academy in June of 2011 were recruited to participate in this study. MARS was administered to 1169 incoming freshmen (203 women) who consented to participate within the first week of matriculation. All subjects were deemed healthy and medically fit for military service on admission. Subjects also completed a baseline questionnaire that asked for basic demographic information and injury history. We calculated means with standard deviations, medians with interquartile ranges, and percentiles for ordinal and continuous variables, and frequencies and proportions for dichotomous variables. We also compared median scores by sex and history of knee ligament injury using the Kruskal-Wallis test. MARS was the primary outcome of interest.

Results:

The median MARS score was significantly higher for men when compared with women (χ2 = 13.22, df = 1, P < 0.001) with no prior history of knee ligament injury. In contrast, there was no significant difference in median MARS scores between men and women (χ2 = 0.47, df = 1, P = 0.493) who reported a history of injury. Overall, median MARS scores were significantly higher among those who reported a history of knee ligament injury when compared with those who did not (χ2 = 9.06, df = 1, P = 0.003).

Conclusion:

Assessing activity as a patient-reported outcome after knee ligament injury is important, and reference values for these instruments need to account for the influence of prior injury and sex.
The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients
Authors: Aghamohammadzadeh Nasser , Niafar Mitra , Dalir Abdolahinia Elham , Najafipour Farzad , Mohamadzadeh Gharebaghi Saeed , Adabi Khadijeh , Dalir Abdolahinia Elaheh , Ahadi Hamidreza
Published: March 2015

Background:

Pioglitazone is one of the antidiabetic agents used in the management of type 2 diabetes mellitus (DM). The effect of pioglitazone on blood glucose, lipid profile, liver enzymes and weight has been shown with conflicting results. In this study we aim to evaluate the effect of pioglitazone on the weight, lipid profile and liver enzymes in patients with DM.

Methods:

In this single-arm clinical trial, 110 poorly controlled diabetic type 2 patients (63.6% female with mean age of 54.26 ± 8.96 years) who were on maximal dosage of metformin and glibenclamide were enrolled. Patients were treated with pioglitazone for 3 months and laboratory. Fasting blood sugar (FBS), haemoglobin A1C (HbA1C), cholesterol, triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and weight changes were measured before and at the end of the study.

Results:

The levels of FBS ( p < 0.001), HbA1c ( p < 0.001), triglyceride ( p = 0.001), ALT ( p = 0.005) and ALK-P ( p = 0.001) were significantly decreased, but weight was significantly increased ( p < 0.001) after the intervention. There were no significant difference in cholesterol, LDL and HDL values before and after study.

Conclusion:

Although pioglitazone causes a significant decrease in FBS, HbA1C and triglyceride levels, it is associated with weight gain, which would limit its utility. IRCT registration code: IRCT201209276712N2
College Adjustment, Relationship Satisfaction, and Conflict Management
Authors: Roberson Patricia N. E. , Fish Jessica N. , Olmstead Spencer B. , Fincham Frank D.
Published: March 2015

Emerging adulthood is a period in the life course that consists of several developmental tasks, including occupational and relationship exploration. Consistent with the developmental tasks of this period, we tested a model of individual development. Using a sample of emerging adults in romantic relationships ( N = 267), we examined the longitudinal association between conflict management and relationship satisfaction and subsequent college adjustment using two cross-lag path analyses. In the first path analyses, results indicated conflict management and social adjustment are mutually influential over time. In this second path analyses, conflict management is related to academic adjustment through relationship satisfaction. Implications for romantic relationship education for emerging adults and future research are discussed.
Bivariate Trajectories of Substance Use and Antisocial Behavior
Authors: Trim Ryan S. , Worley Matthew J. , Wall Tamara L. , Hopfer Christian J. , Crowley Thomas J. , Hewitt John K. , Brown Sandra A.
Published: March 2015

Substance use and antisocial behavior (ASB) are complex and interrelated behaviors. This study identified model trajectory classes defined by concurrent substance use and ASB and examined trajectory associations with emerging adult outcomes. Participants from a high-risk sample of youth ( n = 536; 73% male) completed interviews at baseline (mean age = 16.1 years) and follow-up (mean age = 22.6 years). Latent class growth analyses identified five trajectory classes based on alcohol/drug use (AOD) and ASB, namely, dual chronic, increasing AOD/persistent ASB, persistent AOD/adolescent ASB, decreasing drugs/persistent ASB, and resolved. Many individuals (56%) exhibited elevated/increasing AOD, and most (91%) reported ASB decreases. Those associated with the dual chronic class had the highest rates of substance dependence, antisocial personality disorder, and negative psychosocial outcomes. There were no differences in adult role attainment across classes. Conjoint examination of these behaviors provides greater detail regarding clinical course and can inform secondary prevention and intervention efforts.
Peripherally Increased Artemin is a Key Regulator of TRPA1/V1 Expression in Primary Afferent Neurons
Authors: Ikeda-Miyagawa Yasuko , Kobayashi Kimiko , Yamanaka Hiroki , Okubo Masamichi , Wang Shenglan , Dai Yi , Yagi Hideshi , Hirose Munetaka , Noguchi Koichi
Published: March 2015

Background

Artemin, a member of the glial cell line-derived neurotrophic factor family, is known to have a variety of neuronal functions, and has been the subject of attention because it has interesting effects, including bi-directional results in modulation in neuropathic and inflammatory pain. It has been shown that the overexpression of artemin is associated with an increase in the expression of TRP family channels in primary afferents and subsequent hyperalgesia, and an increase in neuronal activity. The purpose of this study was to examine the peripheral synthesis of artemin in inflammatory and neuropathic pain models, and to demonstrate the effects of long-term or repeated application of artemin in vivo on pain behaviors and on the expression of TRP family channels. Further, the regulatory mechanisms of artemin on TRPV1/A1 were examined using cultured DRG neurons.

Results

We have demonstrated that artemin is locally elevated in skin over long periods of time, that artemin signals significantly increase in deep layers of the epidermis, and also that it is distributed over a broad area of the dermis. In contrast, NGF showed transient increases after peripheral inflammation. It was confirmed that the co-localization of TRPV1/A1 and GFRc3 was higher than that between TRPV1/A1 and TrkA. In the peripheral sciatic nerve trunk, the synthesis of artemin was found by RT-PCR and in situ hybridization to increase at a site distal to a nerve injury. We demonstrated that in vivo repeated artemin injections into the periphery changed the gene expression of TRPV1/A1 in DRG neurons without affecting GFRc3 expression. Repeated artemin injections also induced mechanical and heat hyperalgesia. Using primary cultured DRG neurons, we found that artemin application significantly increased TRPV1/A1 expression and Ca2+ influx. Artemin-induced p38 MAPK pathway regulated the TRPV1 channel expression, however TRPA1 upregulation by artemin is not mediated through p38 MAPK.

Conclusions

These data indicate the important roles of peripherally-derived artemin on the regulation of TRPV1/A1 in DRG neurons in pathological conditions such as inflammatory and neuropathic pain.
A [14C]iodoantipyrine Study of Inter-Regional Correlations of Neural Substrates Following Central Post-Stroke Pain in Rats
Authors: Lu Hsiang-Chin , Chang Wei-Jen , Kuan Yung-Hui , Huang Andrew Chih-Wei , Shyu Bai Chuang
Published: March 2015

Background

Central pain syndrome is characterized by a combination of abnormal pain sensations, and pain medications often provide little or no relief. Accumulating animal and clinical studies have shown that impairments of the spinothalamic tract (STT) and thalamocingulate pathway causes somatosensory dysfunction in central post-stroke pain (CPSP), but the involvement of other neuronal circuitries in CPSP has not yet been systematically examined. The aim of the present study was to evaluate changes in brain activity and neuronal circuitry using [14C]iodoantipyrine (IAP) in an animal model of CPSP.

Results

Rats were subjected to lateral thalamic hemorrhage to investigate the characteristics of CPSP. Thermal and mechanical hyperalgesia developed in rats that were subjected to thalamic hemorrhagic lesion. The medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), striatum, thalamus, hypothalamus, and amygdala were more active in the CPSP group compared with rats that were not subjected to lateral thalamic hemorrhage. The inter-regional correlation analysis showed that regional cerebral blood flow in the mPFC was highly correlated with the amygdala in the right brain, and the right brain showed complex connections among subregions of the ACC. Rats with CPSP exhibited strong activation of the thalamocingulate and mPFC-amygdala pathways.

Conclusions

These results corroborate previous findings that the STT and thalamocingulate pathway are involved in the pathophysiological mechanisms of CPSP symptoms. The mPFC, amygdala, and periaqueductal gray emerged as having important correlations in pain processing in CPSP. The present data provide a basis for a neural correlation hypothesis of CPSP, with implications for CPSP treatment.
MASTL promotes cyclin B1 destruction by enforcing Cdc20-independent binding of cyclin B1 to the APC/C
Authors: Voets Erik , Wolthuis Rob
Published: March 2015

When cells enter mitosis, the anaphase-promoting complex/cyclosome (APC/C) is activated by phosphorylation and binding of Cdc20. The RXXL destruction box (D-box) of cyclin B1 only binds Cdc20 after release of the spindle checkpoint in metaphase, initiating cyclin B1 ubiquitination upon chromosome bi-orientation. However, we found that cyclin B1, through Cdk1 and Cks, is targeted to the phosphorylated APC/CCdc20 at the start of prometaphase, when the spindle checkpoint is still active. Here, we show that MASTL is essential for cyclin B1 recruitment to the mitotic APC/C and that this occurs entirely independently of Cdc20. Importantly, MASTL-directed binding of cyclin B1 to spindle checkpoint-inhibited APC/CCdc20 critically supports efficient cyclin B1 destruction after checkpoint release. A high incidence of anaphase bridges observed in response to MASTL RNAi may result from cyclin B1 remaining after securin destruction, which is insufficient to keep MASTL-depleted cells in mitosis but delays the activation of separase.
RHAMM deficiency disrupts folliculogenesis resulting in female hypofertility
Authors: Li Huaibiao , Moll Jürgen , Winkler Anne , Frappart Lucien , Brunet Stéphane , Hamann Jana , Kroll Torsten , Verlhac Marie-Hélène , Heuer Heike , Herrlich Peter , Ploubidou Aspasia
Published: March 2015

The postnatal mammalian ovary contains the primary follicles, each comprising an immature oocyte surrounded by a layer of somatic granulosa cells. Oocytes reach meiotic and developmental competence via folliculogenesis. During this process, the granulosa cells proliferate massively around the oocyte, form an extensive extracellular matrix (ECM) and differentiate into cumulus cells. As the ECM component hyaluronic acid (HA) is thought to form the backbone of the oocyte-granulosa cell complex, we deleted the relevant domain of the Receptor for HA Mediated Motility (RHAMM) gene in the mouse. This resulted in folliculogenesis defects and female hypofertility, although HA-induced signalling was not affected. We report that wild-type RHAMM localises at the mitotic spindle of granulosa cells, surrounding the oocyte. Deletion of the RHAMM C-terminus in vivo abolishes its spindle association, resulting in impaired spindle orientation in the dividing granulosa cells, folliculogenesis defects and subsequent female hypofertility. These data reveal the first identified physiological function for RHAMM, during oogenesis, and the importance of this spindle-associated function for female fertility.
A single and rapid calcium wave at egg activation in Drosophila
Authors: York-Andersen Anna H. , Parton Richard M. , Bi Catherine J. , Bromley Claire L. , Davis Ilan , Weil Timothy T.
Published: March 2015

Activation is an essential process that accompanies fertilisation in all animals and heralds major cellular changes, most notably, resumption of the cell cycle. While activation involves wave-like oscillations in intracellular Ca2+ concentration in mammals, ascidians and polychaete worms and a single Ca2+ peak in fish and frogs, in insects, such as Drosophila, to date, it has not been shown what changes in intracellular Ca2+ levels occur. Here, we utilise ratiometric imaging of Ca2+ indicator dyes and genetically encoded Ca2+ indicator proteins to identify and characterise a single, rapid, transient wave of Ca2+ in the Drosophila egg at activation. Using genetic tools, physical manipulation and pharmacological treatments we demonstrate that the propagation of the Ca2+ wave requires an intact actin cytoskeleton and an increase in intracellular Ca2+ can be uncoupled from egg swelling, but not from progression of the cell cycle. We further show that mechanical pressure alone is not sufficient to initiate a Ca2+ wave. We also find that processing bodies, sites of mRNA decay and translational regulation, become dispersed following the Ca2+ transient. Based on this data we propose the following model for egg activation in Drosophila: exposure to lateral oviduct fluid initiates an increase in intracellular Ca2+ at the egg posterior via osmotic swelling, possibly through mechano-sensitive Ca2+ channels; a single Ca2+ wave then propagates in an actin dependent manner; this Ca2+ wave co-ordinates key developmental events including resumption of the cell cycle and initiation of translation of mRNAs such as bicoid.
The effect of water temperature on routine swimming behaviour of new born guppies (Poecilia reticulata)
Authors: Kent Maud , Ojanguren Alfredo F.
Published: March 2015

Guppies have successfully established populations in places with thermal regimes very different from the Tropical conditions in their native range. This indicates a remarkable capacity for thermal adaptation. Given their vulnerability to predation as juveniles, acute changes in temperature, which can alter predator-prey relationships, can impact juvenile survival and have amplified consequences at the population level. To understand how temperature may impact juvenile survival and gain insight into their success as an invasive species, we researched the effect of acute temperature changes on the routine swimming behaviour of juvenile guppies. Using a novel 3-dimensional tracking technique, we calculated 4 routine swimming parameters, speed, depth, and variation in speed or depth, at 6 different test temperatures (17, 20, 23, 26, 29, or 32°C). These temperatures cover their natural thermal range and also extended past it in order to include upper and lower thermal limits. Using model selection, we found that body length and temperature had a significant positive relationship with speed. Variation in speed decreased with rising temperatures and fish swam slightly closer to the bottom at higher temperatures. All juveniles increased variation in depth at higher temperatures, though larger individuals maintained slightly more consistent depths. Our results indicate that guppies have a large thermal range and show substantial plasticity in routine swimming behaviours, which may account for their success as an invasive species.
Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells
Authors: Wong Kimberly A. , Trembley Michael , Abd Wahab Syafiq , Viczian Andrea S.
Published: March 2015

Retina formation requires the correct spatiotemporal patterning of key regulatory factors. While it is known that repression of several signaling pathways lead to specification of retinal fates, addition of only Noggin, a known BMP antagonist, can convert pluripotent Xenopus laevis animal cap cells to functional retinal cells. The aim of this study is to determine the intracellular molecular events that occur during this conversion. Surprisingly, blocking BMP signaling alone failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells resulted in a concentration-dependent suppression of both Smad1 and Smad2 phosphorylation, which act downstream of BMP and Activin signaling, respectively. This caused a decrease in downstream targets: endothelial marker, xk81, and mesodermal marker, xbra. We treated pluripotent cells with dominant-negative receptors or the chemical inhibitors, dorsomorphin and SB431542, which each target either the BMP or Activin signaling pathway. We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT) assay; in which treated pluripotent cells were transplanted into the eye field of host embryos. We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone. In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542. Future studies could translate these findings to a mammalian culture assay, in order to more efficiently produce retinal cells in culture.
The dual structural roles of the membrane distal region of α integrin cytoplasmic tail in integrin inside-out activation
Authors: Liu Jiafu , Wang Zhengli , Thinn Aye Myat Myat , Ma Yan-Qing , Zhu Jieqing
Published: March 2015

Studies on the mechanism of integrin inside-out activation have been focused on the role of β cytoplasmic tails that are relatively conserved and bear binding sites for the intracellular activators including talin and kindlin. Integrin α cytoplasmic tails share a conserved GFFKR motif at the membrane-proximal region forming specific interface with β membrane-proximal region that keeps integrin inactive. The α membrane-distal regions after the GFFKR motif are diverse both in length and sequence and their roles in integrin activation have not been well-defined. In this study, we report that the α cytoplasmic membrane-distal region contributes to maintaining integrin in the resting state and to integrin inside-out activation. Complete deletion of the α membrane-distal region diminished talin and kindlin mediated integrin ligand binding and conformational change. A proper length and amino acids of α membrane-distal region is important for integrin inside-out activation. Our data establish an essential role of the α integrin cytoplasmic membrane-distal region in integrin activation and provide new insights into how talin and kindlin induce the high affinity integrin conformation that is required for fully functional integrins.
VGLUT1/VGAT co-expression sustains glutamate-gaba co-release and is regulated by activity
Authors: Fattorini Giorgia , Antonucci Flavia , Menna Elisabetta , Matteoli Michela , Conti Fiorenzo
Published: March 2015

In adult neocortex, VGLUT1, the main glutamate vesicular transporter, and VGAT, the GABA vesicular transporter, are co-expressed in a subset of axon terminals forming both symmetric and asymmetric synapses, where they are sorted to the same vesicles. However, the functional consequence of this co-localization in cortical neurons has not been clarified. Here, we tested the hypothesis that cortical axon terminals co-expressing VGLUT1 and VGAT can evoke simultaneously monosynaptic glutamate and GABA responses and investigated whether the amount of terminals co-expressing VGLUT1 and VGAT is affected by perturbations of excitation-inhibition balance. In rat primary cortical neurons, we found that a proportion of synaptic and autaptic responses were indeed sensitive to consecutive application of selective glutamate and GABAA receptor blockers. These “mixed” synapses exhibited paired-pulse depression. Notably, reducing the activity of the neuronal network by glutamate receptor antagonists decreased the amount of “mixed” synapses, whereas reducing spontaneous inhibition by bicuculline increased them. These synapses may contribute to homeostatic regulation of excitation/inhibition balance.
Emerging roles of protocadherins: from self-avoidance to enhancement of motility
Authors: Hayashi Shuichi , Takeichi Masatoshi
Published: March 2015

Protocadherins are a group of transmembrane proteins belonging to the cadherin superfamily that are subgrouped into ‘clustered’ and ‘non-clustered’ protocadherins. Although cadherin superfamily members are known to regulate various forms of cell–cell interactions, including cell–cell adhesion, the functions of protocadherins have long been elusive. Recent studies are, however, uncovering their unique roles. The clustered protocadherins regulate neuronal survival, as well as dendrite self-avoidance. Combinatorial expression of clustered protocadherin isoforms creates a great diversity of adhesive specificity for cells, and this process is likely to underlie the dendritic self-avoidance. Non-clustered protocadherins promote cell motility rather than the stabilization of cell adhesion, unlike the classic cadherins, and mediate dynamic cellular processes, such as growth cone migration. Protocadherin dysfunction in humans is implicated in neurological disorders, such as epilepsy and mental retardation. This Commentary provides an overview of recent findings regarding protocadherin functions, as well as a discussion of the molecular basis underlying these functions.
The adipocyte clock controls brown adipogenesis via TGF-β/BMP signaling pathway
Authors: Nam Deokhwa , Guo Bingyan , Chatterjee Somik , Chen Miao-Hsueh , Nelson David , Yechoor Vijay K. , Ma Ke
Published: March 2015

The molecular clock is intimately linked with metabolic regulation and brown adipose tissue plays a key role in energy homeostasis. However, whether the cell-intrinsic clock machinery participates in brown adipocyte development is unknown. Here we show that Bmal1, the essential clock transcription activator, inhibits brown adipogenesis to adversely impact brown fat formation and thermogenic capacity. Global ablation of Bmal1 in mice increases brown fat mass and cold tolerance, while adipocyte-selective inactivation of Bmal1 recapitulates these effects and demonstrates its cell-autonomous role in brown adipocyte formation. Further loss- and gain-of function studies in mesenchymal precursors and committed brown progenitors reveal that Bmal1 inhibits brown adipocyte lineage commitment and terminal differentiation. Mechanistically, Bmal1 inhibits brown adipogenesis through direct transcriptional control of key components of the TGF-β pathway together with reciprocally altered BMP signaling, and activation of TGF-β, or blockade of BMP pathways, suppresses enhanced differentiation in Bmal1-deficient brown adipocytes. Collectively, our study demonstrates a novel temporal regulatory mechanism in fine-tuning brown adipocyte lineage progression to impact brown fat formation and thermogenic regulation, which may be targeted therapeutically to combat obesity.
Unsteady turbulent boundary layers in swimming rainbow trout
Authors: Yanase Kazutaka , Saarenrinne Pentti
Published: March 2015

The boundary layers of rainbow trout, Oncorhynchus myskiss, swimming at 1.02±0.09 L s−1 (mean±s.d., N=4), were measured by the Particle Image Velocimetry (PIV) technique at a Reynolds number of 4×105. The boundary-layer profile showed unsteadiness, oscillating above and beneath the classical logarithmic law of the wall with body motion. Across the entire surface regions that were measured, local Reynolds numbers based on momentum thickness, which is the distance that is perpendicular to the fish surface through which the boundary-layer momentum flows at free-stream velocity, were greater than the critical value of 320 for laminar-to-turbulent transition.

The skin friction was dampened on the convex surface while the surface was moving towards a free-stream flow and increased on the concave surface while retreating. These observations contradict the result of a previous study using different species swimming by different methods. Boundary layer compression accompanied by an increase in local skin-friction was not observed. Thus, the overall results may not support absolutely the Bone-Lighthill boundary-layer thinning hypothesis that the undulatory motions of swimming fish cause a large increase in their friction drag because of the compression of the boundary layer. In some cases, marginal flow separation occurred on the convex surface in the relatively anterior surface region, but the separated flow reattached to the fish surface immediately downstream. Therefore, we believe that a severe impact due to induced drag components (i.e. pressure drag) on the swimming performance, an inevitable consequence of flow separation, was avoided.
Vision in avian emberizid foragers: maximizing both binocular vision and fronto-lateral visual acuity
Authors: Moore Bret A. , Pita Diana , Tyrrell Luke P. , Fernández-Juricic Esteban
Published: March 2015

Avian species vary in their visual system configuration, but previous studies have often compared single visual traits between 2-3 distantly related species. However, birds use different visual dimensions that cannot be maximized simultaneously to meet different perceptual demands, potentially leading to trade-offs between visual traits. We studied the degree of inter-specific variation in multiple visual traits related to foraging and anti-predator behaviors in nine species of closely related emberizid sparrows, controlling for phylogenetic effects. Emberizid sparrows maximize binocular vision, even seeing their bill tips, which may enhance the detection of prey and facilitate food handling. Sparrows have a single retinal center of acute vision (i.e., fovea) projecting fronto-laterally (but not into the binocular field). The foveal projection close to the edge of the binocular field may shorten the time to gather and process both monocular and binocular visual information from the foraging substrate. Contrary to previous work, we found that species with larger visual fields had higher visual acuity, which may compensate for larger blind spots (i.e., pectens) above the center of acute vision, enhancing predator detection. Finally, species with a steeper change in ganglion cell density across the retina had higher eye movement amplitude likely due to a more pronounced reduction in visual resolution away from the fovea, which would need to be moved around more frequently. The visual configuration of emberizid passive prey foragers is substantially different from that of previously studied avian groups (e.g., sit-and-wait and tactile foragers).
Expression and light-triggered movement of rhodopsins in the larval visual system of mosquitoes
Authors: Rocha Manuel , Kimler Kyle J. , Leming Matthew T. , Hu Xiaobang , Whaley Michelle A. , O'Tousa Joseph E.
Published: March 2015

During the larval stages, the visual system of the mosquito Aedes aegypti contains five stemmata, often referred to as larval ocelli, positioned laterally on each side of the larval head. The stemmata contain two photoreceptor types, distinguished by the expression of different rhodopsins. Aaop3 rhodopsin is expressed in the majority of the larval photoreceptors. There are two small clusters of photoreceptors located within the satellite and central stemmata that express Aaop7 rhodopsin instead of Aaop3. Electroretinogram analysis of transgenic Aaop7 Drosophila indicates that Aaop3 and Aaop7, both classified as long-wavelength rhodopsins, possess similar but not identical spectral properties. Light triggers an extensive translocation of Aaop3 from the photosensitive rhabdoms to the cytoplasmic compartment, while light-driven translocation of Aaop7 is limited. The results suggest that these photoreceptor cell types play distinct roles in larval vision. An additional component of the larval visual system is the adult compound eye, which initiates development at the anterior face of the larval stemmata during the 1st instar stage. The photoreceptors of the developing compound eye show rhodopsin expression during the 4th larval instar stage, consistent with indications from previous reports that the adult compound eye contributes to larval and pupal visual capabilities.
Effect of light intensity on flight control and temporal properties of photoreceptors in bumblebees
Authors: Reber Therese , Vähäkainu Antti , Baird Emily , Weckström Matti , Warrant Eric , Dacke Marie
Published: March 2015

To control flight, insects rely on the pattern of visual motion generated on the retina as they move through the environment. When light levels fall, vision becomes less reliable and flight control thus becomes more challenging. Here, we investigated the effect of light intensity on flight control by filming the trajectories of free-flying bumblebees (Bombus terrestris, Linnaeus, 1758) in an experimental tunnel at different light levels. As light levels fell, flight speed decreased and the flight trajectories became more tortuous but the bees were still remarkably good at centring their flight about the tunnel's midline. To investigate if this robust flight performance can be explained by visual adaptations in the bumblebee retina, we also examined the response speed of the green sensitive photoreceptors at the same light intensities. We found that the response speed of the photoreceptors significantly decreased as light levels fell. This indicates that bumblebees have both behavioural (reduction in flight speed) and retinal (reduction in response speed of the photoreceptors) adaptations to allow them to fly in dim light. However, the more tortuous flight paths recorded in dim light suggest that these adaptations do not support flight with the same precision during the twilight hours of the day.
Paracellular pathway remodeling enhances sodium secretion by teleost fish in hypersaline environments
Authors: Cozzi Regina R.F. , Robertson George N. , Spieker Melanie , Claus Lauren N. , Zaparilla Gabriella M.M. , Garrow Kelly L. , Marshall William S.
Published: March 2015

In vertebrate salt-secreting epithelia, Na+ moves passively down an electrochemical gradient via a paracellular pathway. We assessed how this pathway is modified to allow Na+ secretion in hypersaline environments. Mummichogs (Fundulus heteroclitus) acclimated to hypersaline (2SW, 64 ‰) for 30 days developed invasive projections of accessory cells with increased area of tight junction, detected by punctate distribution of CFTR immunofluorescence and TEM of opercular epithelia (OE), a gill-like tissue rich in ionocytes. CFTR distribution was not explained by membrane raft organization, as chlorpromazine (50 μM) and filipin (1.5 μM) did not affect OE electrophysiology. Isolated OE bathed in SW on the mucosal side had a transepithelial potential (Vt) of +40.1+0.9 mV (n=24), sufficient for passive Na+ secretion (Nernst equilibrium voltage≡ENa=+24.11 mV). OE from fish acclimated to 2SW bathed in 2SW had higher Vt of +45.1+1.2 mV (n=24), sufficient for passive Na+ secretion (ENa=+40.74 mV), but with diminished net driving force. Bumetanide block of Cl− secretion reduced Vt by 45% and 29% in SW and 2SW, respectively, a decrease in the driving force for Na+ extrusion. Estimates of shunt conductance from epithelial conductance (Gt ) vs. short-circuit current (Isc) plots (extrapolation to zero Isc) suggested a reduction in total epithelial shunt conductance in 2SW acclimated fish. In contrast, the morphological elaboration of tight junctions, an increase in accessory cell-ionocyte contact points, suggests an increase local paracellular conductance, compensating for the diminished net driving force for Na+ and allowing salt secretion even in extreme salinities.
Regulation of the rplY gene encoding 5S rRNA binding protein L25 in Escherichia coli and related bacteria
Authors: Aseev Leonid V. , Bylinkina Natalia S. , Boni Irina V.
Published: March 2015

Ribosomal protein (r-protein) L25 is one of the three r-proteins (L25, L5, L18) that interact with 5S rRNA in eubacteria. Specific binding of L25 with a certain domain of 5S r-RNA, a so-called loop E, has been studied in detail, but information about regulation of L25 synthesis has remained totally lacking. In contrast to the rplE (L5) and rplR (L18) genes that belong to the polycistronic spc-operon and are regulated at the translation level by r-protein S8, the rplY (L25) gene forms an independent transcription unit. The main goal of this work was to study the regulation of the rplY expression in vivo. We show that the rplY promoter is down-regulated by ppGpp and its cofactor DksA in response to amino acid starvation. At the level of translation, the rplY expression is subjected to the negative feedback control. The 5′-untranslated region of the rplY mRNA comprises specific sequence/structure features, including an atypical SD-like sequence, which are highly conserved in a subset of gamma-proteobacterial families. Despite the lack of a canonical SD element, the rplY’-‘lacZ single-copy reporter showed unusually high translation efficiency. Expression of the rplY gene in trans decreased the translation yield, indicating the mechanism of autogenous repression. Site-directed mutagenesis of the rplY 5′ UTR revealed an important role of the conserved elements in the translation control. Thus, the rplY expression regulation represents one more example of regulatory pathways that control ribosome biogenesis in Escherichia coli and related bacteria.