bluuebunny/crossref_metadata_2025 huggingface dataset:
SNAIL gene inhibited by hypoxia-inducible factor 1α (HIF-1α) in epithelial ovarian cancer
Authors: Zhang Pengnan , Liu Yanmei , Feng Youji , Gao Shujun
Published: April 2016

The aim of this study was to investigate the relationship between HIF-1α and SNAIL gene expression in the epithelial ovarian cancer (EOC) cell line. EOC cells were treated with hypoxia, hypoxia combined with rapamycin, and control. The expression of HIF-1α and E-cad were assessed by reverse transcription–polymerase chain reaction (RT-PCR) and western blotting. The gene expression of SNAIL was studied by RT-PCR and real-time PCR. RNA interference technology was used to determine the relationship between HIF-1α and SNAIL. The present study indicated that the HIF-1α protein was expressed and increased in EOC cell line. SNAIL mRNA was found to increase and E-cad expression decreased with the time of hypoxia prolonged. Hypoxia increased invasion abilities of EOC cell line, but compared with cells exposed to hypoxia, the change of invasive ability of cells with rapamycin had no effect. The expression of HIF-1α protein and SNAIL mRNA could be inhibited gradually by rapamycin. siRNA of HIF-1α could suppress the expression of SNAIL while siRNA of SNAIL had no influence on HIF-1α protein expression. HIF-1α may be the upstream of the SNAIL gene in EOC. Our data suggested that HIF-1α might be an upregulator of the SNAIL gene and HIF-1α-SNAIL-E-cad pathway may play an important role in EOC invasion and metastasis.
Obesity and kidney disease: Beyond the hyperfiltration
Authors: Mascali A , Franzese O , Nisticò S , Campia U , Lauro D , Cardillo C , Di Daniele N , Tesauro M
Published: April 2016

In industrialized countries, overweight and obesity account for approximately 13.8% and 24.9% of the kidney disease observed in men and women, respectively. Moreover, obesity-associated glomerulopathy is now considered as “an emerging epidemic.” Kidney function can be negatively impacted by obesity through several mechanisms, either direct or indirect. While it is well established that obesity represents the leading risk factor for type 2 diabetes and hypertension, awareness that obesity is associated with direct kidney damage independently of hypertension and diabetes is still not widespread. In this paper we will discuss the emerging role of adipose tissue, particularly in the visceral depot, in obesity-induced chronic kidney damage.
Management of Current Psychiatric Disorders
Authors: Oude Engberink Agnés , Carbonnel François , David Michel , Norton Joanna , Bourrel Gérard , Boulenger Jean-Philippe , Capdevielle Delphine
Published: April 2016

Objective:

Describe and analyse the experience of family physicians in managing current psychiatric disorders to obtain a better understanding of the underlying reasons of under-detection and inadequate prescribing identified in studies.

Methods:

A qualitative study using in-depth interviews. Sample of 15 practicing family physicians, recruited by telephone from a precedent cohort (Sesame1) with a maximum variation: sex, age, single or group practice, urban or rural. Qualitative method is inspired by the completed grounded theory of a verbatim semiopragmatic analysis from 2 experts in this approach.

Results:

Family physicians found that current psychiatric disorders were related to psychological symptoms in reaction to life events. Their role was to make patients aware of a psychiatric symptom rather than establish a diagnosis. Their management responsibility was considered in contrasting ways: it was claimed or endured. They defined their position as facilitating compliance to psychiatrist consultations, while assuring a complementary psychotherapeutic approach. Prescribing medication was not a priority for them.

Conclusions:

The identified under-detection is essentially due to inherent frontline conditions and complexity of clinical forms. The family physician role, facilitating compliance to psychiatrist consultations while assuring a support psychotherapy is the main result of this study. More studies should be conducted to define more accurately the clinical reality, management and course of current psychiatric disorders in primary care.
Developments in cutting tool technology in improving machinability of Ti6Al4V alloy: A review
Authors: Saini Abhineet , Pabla BS , Dhami SS
Published: April 2016

Ti6Al4V is the most widely used titanium alloy and is a demanding material in applications requiring high specific strength and corrosion resistance, that is, aerospace, automobile and biomedical industries. However, the poor machinability of this alloy, resulting from its low thermal conductivity, high hardness at elevated temperatures, high chemical reactivity with the cutting tool and low elastic modulus, restricts its usage. As a result, the tool life in machining of Ti6Al4V is substantially less than conventional materials such as steel and aluminium. This work reviews the various techniques employed in improving the machinability of Ti6Al4V alloy, from the perspective of cutting tool technology. The focus is onto the parameters affecting tool life in machining of Ti6Al4V alloy with some trending techniques and their feasibility, considering the economics to develop the best techno-economic method.
Recognizing the Presidents
Authors: Roediger Henry L. , DeSoto K. Andrew
Published: April 2016

Studies over the past 40 years have shown that Americans can recall about half the U.S. presidents. Do people know the presidents even though they are unable to access them for recall? We investigated this question using the powerful cues of a recognition test. Specifically, we tested the ability of 326 online subjects to recognize U.S. presidents when presented with their full names among various types of lures. The hit rate for presidential recognition was .88, well above the proportion produced in free recall but far from perfect. Presidents Franklin Pierce and Chester Arthur were recognized less than 60% of the time. Interestingly, four nonpresidents were falsely recognized at relatively high rates, and Alexander Hamilton was more frequently identified as president than were several actual presidents. Even on a recognition test, knowledge of American presidents is imperfect and prone to error. The false alarm data support the theory that false fame can arise from contextual familiarity.
Undecided life: Standards, subjects, and sovereignty in compensating victims of the war on terror
Authors: Allen Matthew , Brown Steven D.
Published: April 2016

In this article we examine the relationship between standards and subjectivity in the context of compensating the victims of terrorism. We do so by drawing on a corpus of data that features survivor and bereaved accounts of two 21st-century terrorist attacks. We investigate the distressing period in which compensation claims remained undecided, in some cases for over seven years after the attacks, and how the process of assessment acts as a “technology of desubjectification.” To articulate this we turn to Giorgio Agamben’s notion of “undecidability” in which the ambiguity between life and law is used by governing authorities to suspend and blur key distinctions such as what lies inside or outside the juridical order. In particular we aim to clarify that, in the context of claiming compensation for an act of terrorism, being undecided is a means by which the state maintains claimants within a “holding category” of victimhood that prevents their recognition as a political subject. We conclude with some reflection on how technologies of desubjectification operate within an “age of austerity.” Critical psychology needs to update its neo-Foucauldian understanding of subjectivity to include the production of “cranked subjects.”
Barriers to Asthma Management as Identified by School Nurses
Authors: Quaranta Judith E. , Spencer Gale A.
Published: April 2016

Asthma rates are increasing in children. School nurses have opportunities to care for children with asthma but need to overcome barriers impacting their ability to manage asthma in the school setting. This study (a) assessed barriers present in the school setting, (b) determined the impact of barriers on performance of asthma management behaviors, and (c) determined the impact of barriers on importance ratings of asthma management behaviors, asthma self-efficacy, and asthma attitudes ( N = 537). Results revealed 72% of the nurses reported at least one barrier. As numbers of barriers increased, performance of asthma management behaviors decreased. Significant relationships were found between specific asthma management behaviors and specific barriers. No significant relationships were found between barriers and asthma self-efficacy, asthma attitude, or importance ratings of asthma management behaviors. Removing barriers may allow the nurse to perform at greatest effectiveness, enhancing the positive outcomes that result from appropriate asthma management.
Political Socialization and Voting
Authors: Gidengil Elisabeth , Wass Hanna , Valaste Maria
Published: April 2016

Status transmission theory represents an important challenge to social learning theory, but its generalizability may be limited to countries where there is a strong intergenerational correlation in educational attainment. Based on a unique data set that matches register data from the 1999 Finnish parliamentary elections with individual-level data provided by Statistics Finland for a sample of eighteen- to thirty-year-olds and their parents, we assess these two explanations for unequal turnout. We first show that parental education does affect the turnout of young adults, as predicted by status transmission theory. However, parental voting rather than the transmission of education from parent to child appears to be the more important mediating factor. We then go on to demonstrate that there is a strong association between parental voting and the turnout of their adult children that is independent of the effects of parental education. More detailed tests of a number of implications derived from social learning theory reinforce our conclusion that the theory offers a superior explanation in countries where there is not a strong parent–child link in educational attainment.
Contrasting Lay Theories of Polyculturalism and Multiculturalism
Authors: Bernardo Allan B. I. , Salanga Maria Guadalupe C. , Tjipto Susana , Hutapea Bonar , Yeung Susanna S. , Khan Aqeel
Published: April 2016

Multiculturalism and polyculturalism are two lay theories of culture that have been associated with some similar intergroup attitudes and behaviors. But other than the studies of Rosenthal and Levy in the United States, there have been no studies that directly distinguish between these two lay theories. In this study, we use confirmatory factor analysis procedures to show that multiculturalism and polyculturalism represent two distinct latent constructs among our 1,730 participants in six Asian cultural groups (China, Hong Kong, Indonesia, Macau, Malaysia, the Philippines). Moreover, we show that essentializing race is associated with endorsement of multiculturalism (but not polyculturalism) in five cultural groups (except Hong Kong). The results provide strong cross-cultural empirical evidence for the distinction between the two lay theories and, more importantly, point to aspects of the lay theory of multiculturalism that relate to why it is sometimes associated with stronger stereotyping and prejudice toward minority cultural groups.
Collaboration reconfigured: The evolving landscape of entertainment TV markets between Taiwan and Mainland China
Authors: Zhao Elaine Jing
Published: April 2016

This article examines the evolving landscape of variety show markets in Taiwan and Mainland China. It begins with an overview of the role of Taiwan in the initial development of variety show production in Mainland China. It then analyses the factors behind Taiwan’s declining position in distribution to the Mainland and its weakened role as a knowledge broker, which parallels the evolution of Mainland productions from copycats to licenced format trade and adaptation and subsequently original programming concepts. Following this is an analysis of recent movements of Taiwanese talent and capital to the Mainland and, increasingly, to online platforms. While digital technologies and platforms present new collaboration opportunities, and format trade facilitates production, this article points to potentially intensified tensions arising from cross-strait cultural production that often intends to address multiple audiences with hybrid content.
Comparative cultural economy and game industries in Asia
Authors: Fung Anthony YH
Published: April 2016

This article examines the development of different models of Asian game industries. In Asia, globalization has meant the penetration of Western ideas and the cultural homogenization of culture. However, nowadays, the game industry in Asia has demonstrated new collaboration models in which game industries are dependent on Western cultural industries in alternative ways. There are also new economies that are independent of the Western cultural economy in terms of production, distribution, marketing, value chains, workforce, regulations, and more importantly, the notion of creativity. Based on interviews and empirical studies that were conducted in China, Japan, Korea, and SE Asian countries from 2012 to 2014, this analysis reveals a few alternative routes of collaboration and non-collaboration that contrast the type of cultural economy found in the United States and the United Kingdom.
‘Spectacularly exposed and vulnerable’ – how Irish equality legislation subverted the personal and professional security of lesbian, gay and bisexual teachers
Authors: Fahie Declan
Published: April 2016

International studies have consistently highlighted the challenges experienced by lesbian, gay and bisexual (LGB) teachers from around the world as they negotiate their personal and professional identities within the context of an often hostile work environment, In Ireland, the education system remains heavily influenced by denominational mores, particularly those of the Roman Catholic Church. Unsurprisingly, with the declaration by the Roman Catholic Church that homosexuality was ‘intrinsically disordered’ ( Catechism of the Roman Catholic Church, Libreria Edittrice Vaticana, 2003), LGB teachers’ professional identity is often (in)formed by fear as well as perceived, or actual, harassment, bullying and overt discrimination. This study represents the first in-depth examination of the apparent contradiction between EU law (Employment Equality Directive 2000/78/EC – European Union, 2000) and the derogation afforded organizations with denominational ethos in Irish equality legislation which explicitly permitted discrimination in order to protect that ethos from being ‘undermined’ (Section 37(1), Employment Equality Acts, 1998–2011). Drawing on semi-structured, in-depth interviews with 23, LGB Irish primary school teachers, the research reveals the tensions which exist between the competing (and legitimate) rights of faith organizations to protect their values against those of LGB workers ‘ to working conditions which respect his or her health, safety and dignity’ (Article 31, EU Charter of Fundamental Rights, 2000).
Distinguished Scholar Invited Essay
Authors: Latham Gary P. , Seijts Gerard H.
Published: April 2016

This article reviews goal-setting theory in terms of the causal relationships it specifies, the boundary conditions within which the causal relationships occur, and the mediators that explain the causal relationships. Three types of goals are described: performance, behavioral, and learning. Emphasis in the article is placed on findings regarding the beneficial effect of setting a specific, difficult learning goal.
Fundamental Movement Skills and Health-Related Outcomes: A Narrative Review of Longitudinal and Intervention Studies Targeting Typically Developing Children
Authors: Bremer Emily , Cairney John
Published: April 2016

Many children with typical development are highly sedentary, overweight/obese, and are deemed not ready for school at kindergarten entry. All of these concerns can be related to a lack of movement skill proficiency in this population. The purpose of this narrative review was to synthesize the literature examining the impact of movement skills on 5 areas of overall health: physical activity, physical fitness, body composition, self-beliefs, and executive functioning. To gain an understanding of these relationships, only studies employing an experimental or observational longitudinal design were reviewed. Although the results were limited in the number of studies available, there is evidence that movement skill may have a positive influence on these broad domains of health both naturally over the course of development and through intervention. We recommend that a universal approach to movement skill development is warranted, given the range of benefits that stem from developing proficiency in these skills.
The Structure of Literary Taste: Class, Gender and Reading in the UK
Authors: Atkinson Will
Published: April 2016

In Distinction, Bourdieu indicated that literary taste was just as homologous with social class as tastes in music, food or art, even if it received comparatively little attention. Recent scholarship across various nations aiming to test, update and refine Bourdieu’s thesis has generally confirmed a relationship between cultural capital and reading habits, but neglect of Bourdieu’s multidimensional view of class, as well as reliance on rather undifferentiated genre categories, has tended to limit the conclusions. On top of that, gender is often flagged as far more important to the structuring of literary taste than Bourdieu ever supposed. This article seeks to overcome the limitations of extant research and clarify the relationship between class and gender in structuring literary taste, and thus symbolic domination, by exploring data relating to reading preferences in the 2012 British Cohort Study using a Bourdieusian class scheme.
Entrapment of the Superficial Peroneal Nerve Following a Distal Fibula Fracture
Authors: Corey Robert M. , Salazar Dane H.
Published: April 2016

Although peripheral nerve injury may result from fractures involving the long bones, bony entrapment of peripheral nerves is infrequently encountered. This report demonstrates a rare case of superficial peroneal nerve entrapment between 2 fracture ends of the distal fibula following a closed ankle fracture resulting from a supination-external rotation mechanism.

Levels of Evidence: Therapeutic, Level IV: Case report
Considerations of Administrative Licensure, Provider Type, and Leadership Quality
Authors: Hackmann Donald G.
Published: April 2016

This article reviews U.S. administrative licensure regulations, focusing on type of school leader licensure, provider types, and leadership quality. Licensure obtained through university-based and alternative routes is examined. Due to limited research on alternative school administrative licensure, regulations in medicine, psychology, engineering, law, and teaching are reviewed, as well as research on their effectiveness, to identify policies potentially relevant to school leadership. Licensure regulations are uniform in medicine, psychology, and engineering, with some variation in law, and licensure options vary greatly in teaching and school administration. The article concludes with recommendations for research, policy, and practice in school administrative licensure.
The role of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukemia
Authors: Benjamin Jonathan E. , Stein Anthony S.
Published: April 2016

Adults with relapsed/refractory B-acute lymphoblastic leukemia (ALL) have a complete remission (CR) rate of 20–45% and median overall survival of 3–9 months, depending on the duration of the first remission and number of lines of salvage therapy. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative option for adult patients with relapsed/refractory ALL, and achievement of CR is a crucial step before alloHSCT. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct with dual specificity for CD19 and CD3, simultaneously binding CD3-positive cytotoxic T cells and CD19-positive B cells, resulting in T-cell-mediated serial lysis of normal and malignant B cells. It recently gained accelerated approval by the US Food and Drug Administration (FDA) for the treatment of relapsed/refractory Philadelphia chromosome-negative ALL, based on a large phase II trial of 189 adults with relapsed/refractory B-ALL, which showed a CR/CRh (CR with partial hematologic recovery) of 43% after two cycles of treatment. Toxicities include cytokine-release syndrome (CRS) and neurologic events (encephalopathy, aphasia, and seizure). CRS can be alleviated by step-up dosing and dexamethasone, without affecting the cytotoxic effect of blinatumomab. The cause of neurologic toxicity is unclear but is also observed with other T-cell therapies and may relate to variable expression of CD19 within the brain. This review encompasses the preclinical rationale of using the BITE® class of compounds (blinatumomab being the only one that is FDA approved), with clinical data using blinatumomab in the relapsed/refractory setting (pediatrics and adults), the minimal residual disease setting (adults), as well as Philadelphia chromosome-positive ALL. The review also examines the main adverse events: their prevention, recognition, and management; possible mechanisms of resistance; causes of relapse. It also summarizes future trials evaluating the drug earlier in the treatment course to improve activity.
‘A difficult trip, I think’: The end days of the probation service in England and Wales?
Authors: Mair George
Published: April 2016

The probation service has been a key part of the criminal justice process for more than 100 years. It deals with more offenders than the prison service; it is more successful than prison in terms of reconviction rates, and it is considerably cheaper than prison. Its advantages as a court sentence seem to be only too clear. Yet, prison remains the gold standard for punishment in England and Wales while the probation service is facing a bleak future. How has it come about that the existence of probation is now under serious threat? That a vital public service is faced with extinction? This article explores the issues that have led to the possibility that probation’s days are numbered.
Brain Inflammation in an Infant With Hemimegalencephaly, Escalating Seizures, and Epileptic Encephalopathy
Authors: Kim Se Hee , Millichap John J. , Koh Sookyong
Published: April 2016

Hemimegalencephaly, a congenital brain malformation typically characterized by enlargement of one hemisphere, is frequently associated with intractable epilepsy. The authors report a case of a 12-month-old girl with hemimegalencephaly who underwent semiurgent hemispherectomy because of rapidly escalating seizures, arrested development, and associated encephalopathy. The brain tissue was examined and evaluated for neuroinflammation. Immunohistochemical analysis of the brain tissue revealed the presence of abundant activated CD68-positive microglia and reactive astrogliosis. Detection of active inflammatory changes in the brain of a patient with hemimegalencephaly complicated by intractable epilepsy suggests a potential role of ongoing brain inflammation in seizure exacerbation and epileptic encephalopathy.
Expression and functional analysis of the Wnt/beta-catenin induced mir-135a-2 locus in embryonic forebrain development
Authors: Caronia-Brown Giuliana , Anderegg Angela , Awatramani Rajeshwar
Published: April 2016

Background

Brain size and patterning are dependent on dosage-sensitive morphogen signaling pathways – yet how these pathways are calibrated remains enigmatic. Recent studies point to a new role for microRNAs in tempering the spatio-temporal range of morphogen functions during development. Here, we investigated the role of miR-135a, derived from the mir-135a-2 locus, in embryonic forebrain development.

Method

1. We characterized the expression of miR-135a, and its host gene Rmst, by in situ hybridization (ish). 2. We conditionally ablated, or activated, beta-catenin in the dorsal forebrain to determine if this pathway was necessary and/or sufficient for Rmst/miR-135a expression. 3. We performed bioinformatics analysis to unveil the most predicted pathways targeted by miR-135a. 4. We performed gain and loss of function experiments on mir-135a-2 and analyzed by ish the expression of key markers of cortical hem, choroid plexus, neocortex and hippocampus.

Results

1. miR-135a, embedded in the host long non-coding transcript Rmst, is robustly expressed, and functional, in the medial wall of the embryonic dorsal forebrain, a Wnt and TGFβ/BMP-rich domain. 2. Canonical Wnt/beta-catenin signaling is critical for the expression of Rmst and miR-135a, and the cortical hem determinant Lmx1a. 3. Bioinformatics analyses reveal that the Wnt and TGFβ/BMP cascades are among the top predicted pathways targeted by miR-135a. 4. Analysis of mir-135a-2 null embryos showed that dorsal forebrain development appeared normal. In contrast, modest mir-135a-2 overexpression, in the early dorsal forebrain, resulted in a phenotype resembling that of mutants with Wnt and TGFβ/BMP deficits - a smaller cortical hem and hippocampus primordium associated with a shorter neocortex as well as a less convoluted choroid plexus. Interestingly, late overexpression of mir-135a-2 revealed no change.

Conclusions

All together, our data suggests the existence of a Wnt/miR-135a auto-regulatory loop, which could serve to limit the extent, the duration and/or intensity of the Wnt and, possibly, the TGFβ/BMP pathways.
A note on the paper ‘Fixed point theorems for cyclic weak contractions in compact metric spaces’
Authors: Kadelburg Zoran , Radenović Stojan , Vujaković Jelena
Published: April 2016

We show that the result on cyclic weak contractions of Harjani et al. (J. Nonlinear Sci. Appl. 6:279-284, 2013) holds without the assumption of compactness of the underlying space, and also without the assumption of continuity of the given mapping.
Cancer and Fertility Program Improves Patient Satisfaction With Information Received
Authors: Kelvin Joanne F. , Thom Bridgette , Benedict Catherine , Carter Jeanne , Corcoran Stacie , Dickler Maura N. , Goodman Karyn A. , Margolies Allison , Matasar Matthew J. , Noy Ariela , Goldfarb Shari B.
Published: April 2016

Purpose

A cancer and fertility program was established at a large cancer center to support clinicians in discussing treatment-related fertility risks and fertility preservation (FP) options with patients and in referring patients to reproductive specialists. The program provides resources, clinician education, and fertility clinical nurse specialist consultation. This study evaluated the program’s impact on patient satisfaction with information received.

Patients and Methods

Retrospective cross-sectional surveys assessed satisfaction before (cohort 1 [C1]) and after (cohort 2 [C2]) program initiation. Questionnaires were investigator-designed, gender-specific, and anonymous.

Results

Most C1 (150 males, 271 females) and C2 (120 males, 320 females) respondents were 2 years postdiagnosis; the most frequently reported cancers were testicular, breast, and lymphoma. A significant difference in satisfaction with the amount of information received was seen between C1 and C2. For males, satisfaction with information on fertility risks was high in both cohorts but significantly greater in C2 for information on sperm banking (χ2 = 9.3, P = .01) and finding a sperm bank (χ2 = 13.3, P = .001). For females, satisfaction with information was significantly greater in C2 for information on fertility risks (χ2 = 62.1, P < .001), FP options (χ2 = 71.9, P < .001), help with decision making (χ2 = 80.2, P < .001), and finding a reproductive endocrinologist (χ2 = 60.5, P < .001). Among patients who received and read information materials, 96% of males and 99% of females found them helpful. Among C2 females, fertility clinical nurse specialist consultation was associated with significantly greater satisfaction with information on FP options (χ2 = 11.2, P = .004), help with decision making (χ2 = 10.4, P = .006), and finding a reproductive endocrinologist (χ2 = 22.6, P < .001), with 10% reporting lack of knowledge as a reason for not pursuing FP.

Conclusion

Improvements in patient satisfaction with information received demonstrate the potential for fertility programs in cancer care settings to improve the quality of clinician-patient discussions about fertility.
A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive Local Therapy
Authors: McKay Rana R. , Zurita Amado J. , Werner Lillian , Bruce Justine Y. , Carducci Michael A. , Stein Mark N. , Heath Elisabeth I. , Hussain Arif , Tran Hai T. , Sweeney Christopher J. , Ross Robert W. , Kantoff Philip W. , Slovin Susan F. , Taplin Mary-Ellen
Published: April 2016

Purpose

Patients with recurrent prostate cancer after local treatment make up a heterogeneous population for whom androgen deprivation therapy (ADT) is the usual treatment. The purpose of this randomized phase II trial was to investigate the efficacy and toxicity of short-course ADT with or without bevacizumab in men with hormone-sensitive prostate cancer.

Patients and Methods

Eligible patients had an increasing prostate-specific antigen (PSA) of ≤ 50 ng/mL and PSA doubling time of less than 18 months. Patients had either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases). Patients were randomly assigned 2:1 to a luteinizing hormone-releasing hormone agonist, bicalutamide and bevacizumab or ADT alone, for 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of more than 0.2 ng/mL for prostatectomy patients or PSA of more than 2.0 ng/mL for primary radiation therapy patients.

Results

Sixty-six patients received ADT + bevacizumab and 36 received ADT alone. Patients receiving ADT + bevacizumab had a statistically significant improvement in RFS compared with patients treated with ADT alone (13.3 months for ADT + bevacizumab v 10.2 months for ADT alone; hazard ratio, 0.47; 95% CI, 0.29 to 0.77; log-rank P = .002). Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36%).

Conclusion

ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor–targeting therapy with ADT in hormone-sensitive prostate cancer.
Prepregnancy Adverse Lipid Profile and Subsequent Risk of Gestational Diabetes
Authors: Han Emily S. , Krauss Ronald M. , Xu Fei , Sridhar Sneha B. , Ferrara Assiamira , Quesenberry Charles P. , Hedderson Monique M.
Published: April 2016

Context:

Lower low-density lipoprotein (LDL) peak diameter and a predominance of small, dense LDL are associated with type 2 diabetes, but it is unclear whether they are a risk factor for gestational diabetes mellitus (GDM).

Objective:

To evaluate whether prepregnancy lipid profile predicts the development of GDM during pregnancy.

Design:

A nested case-control study among women who participated in a multiphasic health exam, where blood was collected and stored between 1984 and 1996, and who then had a subsequent pregnancy between 1984 and 2009.

Setting:

Kaiser Permanente Northern California.

Participants:

Cases were 254 women who developed GDM. Two controls were selected for each case and matched for year of blood draw, age at baseline, age at pregnancy, and number of intervening pregnancies.

Main Outcome Measures:

Prepregnancy LDL peak diameter and prepregnancy lipid subfraction concentrations grouped according to size, and the odds of developing GDM.

Results:

Women in the lowest quartiles of LDL peak diameter and high-density lipoprotein had increased odds of GDM compared with women in the highest quartiles (odds ratio [95% CI], 2.60 [1.37–4.94] and 1.98 [1.01–3.86], respectively), in multivariable adjusted models. Being in the highest quartile of small and very small LDL subfractions also increased the odds of GDM (2.61 [1.35–5.03] and 2.44 [1.22–4.85], respectively).

Conclusions:

Lower LDL peak diameter size and high-density lipoprotein levels and higher levels of small and very small LDL subfraction groups were present years before pregnancy in women who developed GDM. A prepregnancy atherogenic lipid profile may help identify women at risk of GDM to target for prevention.
Feliform carnivores have a distinguished constitutive innate immune response
Authors: Heinrich Sonja K. , Wachter Bettina , Aschenborn Ortwin H. K. , Thalwitzer Susanne , Melzheimer Jörg , Hofer Heribert , Czirják Gábor Á.
Published: April 2016

Determining the immunological phenotype of endangered and threatened populations is important to identify those vulnerable to novel pathogens. Among mammals, members of the order Carnivora are particularly threatened by diseases. We therefore examined the constitutive innate immune system, the first line of protection against invading microbes, of six free-ranging carnivore species; the black-backed jackal (Canis mesomelas), the brown hyena (Hyena brunnea), the caracal (Caracal caracal), the cheetah (Acinonyx jubatus), the leopard (Panthera pardus) and the lion (Panthera leo) using a bacterial killing assay. The differences in immune responses amongst the six species were independent of their foraging behaviour, body mass or social organisation but reflected their phylogenetic relatedness. The bacterial killing capacity of black-backed jackals, a member of the suborder Caniformia, followed the pattern established for a wide variety of vertebrates. In contrast, the five representatives of the suborder Feliformia demonstrated a killing capacity at least an order of magnitude higher than any species reported previously, with a particularly high capacity in caracals and cheetahs. Our results suggest that the immunocompetence of threatened felids such as the cheetah has been underestimated and its assessment ought to consider both innate and adaptive components of the immune system.
Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism
Authors: Kettunen Kaisa M. , Karikoski Riitta , Hämäläinen Riikka H. , Toivonen Teija T. , Antonenkov Vasily D. , Kulesskaya Natalia , Voikar Vootele , Hölttä-Vuori Maarit , Ikonen Elina , Sainio Kirsi , Jalanko Anu , Karlberg Susann , Karlberg Niklas , Lipsanen-Nyman Marita , Toppari Jorma , Jauhiainen Matti , Hiltunen J. Kalervo , Jalanko Hannu , Lehesjoki Anna-Elina
Published: April 2016

Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37−/−) model for MUL. Trim37−/− mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37−/− mice as compared with wild-type. Both male and female Trim37−/− mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37−/− mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37−/− mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37−/− mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37−/− mice. The most consistently seen phenotypes in Trim37−/− mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37−/− mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis.
An interview with Abigail Tucker
Authors: Vicente Catarina
Published: April 2016

Abigail Tucker is a professor at King's College London, UK and her lab works on various aspects of craniofacial development – from basic, evolutionary and clinical biology perspectives. This year, Abigail will be awarded the first Cheryll Tickle Medal by the British Society for Developmental Biology (BSDB). We chatted with Abigail about her research, her commitment to public engagement and the challenges and rewards of working with emerging model systems.
An interview with Cheryll Tickle
Authors: Vicente Catarina
Published: April 2016

Cheryll Tickle is an Emeritus Professor at the University of Bath, UK. She dedicated her long research career mainly to the study of limb development in the chick, and has received numerous awards for her contributions to science, including being elected a Fellow of The Royal Society and receiving a CBE from the Queen. This year the British Society for Developmental Biology (BSDB) has created a new award in her honour, the Cheryll Tickle Medal, to be awarded to a mid-career, female scientist for outstanding achievements in the field. We asked Cheryll what this award means to her and how science has changed during her career.
Vimentin filaments regulate integrin–ligand interactions by binding to the cytoplasmic tail of integrin β3
Authors: Kim Jiyoon , Yang Chansik , Kim Eun Jin , Jang Jungim , Kim Se-Jong , Kang So Min , Kim Moon Gyo , Jung Hosung , Park Dongeun , Kim Chungho
Published: April 2016

Vimentin, an intermediate filament protein induced during epithelial-to-mesenchymal transition, is known to regulate cell migration and invasion. However, it is still unclear how vimentin controls such behaviors. In this study, we aimed to find a new integrin regulator by investigating the H-Ras-mediated integrin suppression mechanism. Through a proteomic screen using the integrin β3 cytoplasmic tail protein, we found that vimentin might work as an effector of H-Ras signaling. H-Ras converted filamentous vimentin into aggregates near the nucleus, where no integrin binding can occur. In addition, an increase in the amount of vimentin filaments accessible to the integrin β3 tail enhanced talin-induced integrin binding to its ligands by inducing integrin clustering. In contrast, the vimentin head domain, which was found to bind directly to the integrin β3 tail and compete with endogenous vimentin filaments for integrin binding, induced nuclear accumulation of vimentin filaments and reduced the amount of integrin–ligand binding. Finally, we found that expression of the vimentin head domain can reduce cell migration and metastasis. From these data, we suggest that filamentous vimentin underneath the plasma membrane is involved in increasing integrin adhesiveness, and thus regulation of the vimentin–integrin interaction might control cell adhesion.
FRMD4A–cytohesin signaling modulates the cellular release of tau
Authors: Yan Xu , Nykänen Niko-Petteri , Brunello Cecilia A. , Haapasalo Annakaisa , Hiltunen Mikko , Uronen Riikka-Liisa , Huttunen Henri J.
Published: April 2016

One of the defining pathological features of Alzheimer's disease is the intraneuronal accumulation of tau (also known as MAPT) protein. Tau is also secreted from neurons in response to various stimuli and accumulates in the cerebrospinal fluid of Alzheimer's disease patients. Tau pathology might spread from cell to cell through a mechanism involving secretion and uptake. Here, we developed an assay to follow cellular release and uptake of tau dimers. Individual silencing of ten common late-onset Alzheimer's disease risk genes in HEK293T cells expressing the tau reporters suggested that FRMD4A is functionally linked to tau secretion. FRMD4A depletion by using RNA interference (RNAi) reduced and overexpression increased tau secretion. The activity of cytohesins, interactors of FRMD4A and guanine-nucleotide-exchange factors of Arf6, was necessary for FRMD4A-induced tau secretion. Increased Arf6 and cell polarity signaling through Par6 and atypical protein kinase Cζ (aPKCζ) stimulated tau secretion. In mature cortical neurons, FRMD4A RNAi or inhibition of cytohesins strongly upregulated secretion of endogenous tau. These results suggest that FRMD4A, a genetic risk factor for late-onset Alzheimer's disease, regulates tau secretion by activating cytohesin–Arf6 signaling. We conclude that genetic risk factors of Alzheimer's disease might modulate disease progression by altering tau secretion.
Microtubule bundling plays a role in ethylene-mediated cortical microtubule reorientation in etiolated Arabidopsis hypocotyls
Authors: Ma Qianqian , Sun Jingbo , Mao Tonglin
Published: April 2016

The gaseous hormone ethylene is known to regulate plant growth under etiolated conditions (the ‘triple response’). Although organization of cortical microtubules is essential for cell elongation, the underlying mechanisms that regulate microtubule organization by hormone signaling, including ethylene, are ambiguous. In the present study, we demonstrate that ethylene signaling participates in regulation of cortical microtubule reorientation. In particular, regulation of microtubule bundling is important for this process in etiolated hypocotyls. Time-lapse analysis indicated that selective stabilization of microtubule-bundling structures formed in various arrays is related to ethylene-mediated microtubule orientation. Bundling events and bundle growth lifetimes were significantly increased in oblique and longitudinal arrays, but decreased in transverse arrays in wild-type cells in response to ethylene. However, the effects of ethylene on microtubule bundling were partially suppressed in a microtubule-bundling protein WDL5 knockout mutant (wdl5-1). This study suggests that modulation of microtubule bundles that have formed in certain orientations plays a role in reorienting microtubule arrays in response to ethylene-mediated etiolated hypocotyl cell elongation.
Haematophagy is costly: respiratory patterns and metabolism during feeding inRhodnius prolixus
Authors: Leis Miguel , Pereira Marcos H. , Casas Jérôme , Menu Fédéric , Lazzari Claudio R.
Published: April 2016

Feeding on the blood of vertebrates is a risky task for haematophagous insects and it can be reasonably assumed that it should also be costly in terms of energetic expenditure. Blood circulates inside vessels and it must be pumped through narrow tubular stylets to be ingested. We analysed the respiratory pattern and the energetic cost of taking a blood meal in Rhodnius prolixus using flow-through and stop-flow respirometry, for measuring carbon dioxide emission, oxygen consumption and water loss before and during feeding. We observed an increase of up to 17-fold in the metabolic rate during feeding and a change in the respiratory pattern, which switched from discontinuous cyclic during resting, to continuous when the insects started to feed, remaining this condition unchanged for several hours. The energetic cost of taking a meal was significantly higher when bugs fed on a living host, compared to feeding on an artificial feeder. No differences were observed between feeding on blood or on saline solution in vitro, revealing that the responsible for such difference in the energetic cost was the substrate for feeding (vessels vs. membrane) and not the nature of the fluid. Water loss significantly increased during feeding, but did not vary with the feeding method or the type of food. The mean respiratory quotient (RQ) in resting bugs was 0.83, decreasing during feeding to 0.52. These data constitute the first metabolic measures of an insect during blood feeding and provide the first insights on the energetic expenditure associated to haematophagy.
Whiteflies stabilize their take-off with closed wings
Authors: Ribak Gal , Dafni Eyal , Gerling Dan
Published: April 2016

The transition from ground to air in flying animals is often assisted by the legs pushing against the ground as the wings start to flap. Here, we show that when tiny whiteflies (Bemisia tabaci, body length ca. 1 mm) perform take-off jumps with closed wings, the abrupt push against the ground sends the insect into the air rotating forward in the sagittal (pitch) plane. However, in the air, B. tabaci can recover from this rotation remarkably fast (less than 11 ms), even before spreading its wings and flapping. The timing of body rotation in air, a simplified biomechanical model, and take-off in insects with removed wings all suggest that the wings, resting backwards alongside the body, stabilize motion through air to prevent somersaulting. The increased aerodynamic force at the posterior tip of the body results in a pitching moment that stops body rotation. Wing deployment increases the pitching moment further, returning the body to a suitable angle for flight. This inherent stabilizing mechanism is made possible by the wing shape and size, in which half of the wing area is located behind the posterior tip of the abdomen.
Effect of magnetic pulses on Caribbean spiny lobsters: implications for magnetoreception
Authors: Ernst David A. , Lohmann Kenneth J.
Published: April 2016

The Caribbean spiny lobster, Panulirus argus, is a migratory crustacean that uses Earth's magnetic field as a navigational cue, but how lobsters detect magnetic fields is not known. Magnetic material thought to be magnetite has previously been detected in spiny lobsters, but its role in magnetoreception, if any, remains unclear. As a first step toward investigating whether lobsters might have magnetite-based magnetoreceptors, we subjected lobsters to strong, pulsed magnetic fields capable of reversing the magnetic dipole moment of biogenic magnetite crystals. Lobsters were subjected to a single pulse directed from posterior to anterior and either: (1) parallel to the horizontal component of the geomagnetic field (i.e., toward magnetic north); or (2) antiparallel to the horizontal field (i.e., toward magnetic south). An additional control group was handled but not subjected to a magnetic pulse. After treatment, each lobster was tethered in a water-filled arena located within 200 m of the capture location and allowed to walk in any direction. Control lobsters walked in seemingly random directions and were not significantly oriented as a group. In contrast, the two groups exposed to pulsed fields were significantly oriented in approximately opposite directions. Lobsters subjected to a magnetic pulse applied parallel to the geomagnetic horizontal component walked westward; those subjected to a pulse directed antiparallel to the geomagnetic horizontal component oriented approximately northeast. The finding that a magnetic pulse alters subsequent orientation behavior is consistent with the hypothesis that magnetoreception in spiny lobsters is based at least partly on magnetite-based magnetoreceptors.