bluuebunny/crossref_metadata_2025 huggingface dataset:
Is willpower important in acts of leadership?
Authors: Karp Tom
Published: March 2014

In this article, we explore the phenomenon of willpower in acts of leadership, a capacity that has been largely overlooked by leadership research. It is argued that leadership is a social process where someone assumes leadership by taking and earning a right to lead, and we investigate whether willpower is important for leadership. We do this by conducting three studies. Even though the research is still in need of further work, the conclusions from these studies combined indicate that willpower may be an important capacity in acts of leadership. We also find that willpower is a process phenomenon to which certain generic principles apply, and we suggest a set of strategies for this available to leaders, and to others who want to better use and develop their willpower. We also think that some of the recommendations provided are of interest to other than leaders, given the suggested importance of willpower.
Leadership and the Australian Greens
Authors: Cunningham Christine , Jackson Stewart
Published: March 2014

This paper examines the inherent tension between a Green political party’s genesis and official ideology and the conventional forms and practices of party leadership enacted in the vast bulk of other parties, regardless of their place on the ideological spectrum. A rich picture is painted of this ongoing struggle through a case study of the Australian Greens with vivid descriptions presented on organisational leadership issues by Australian state and federal Green members of parliaments. What emerges from the data is the Australian Green MPs’ conundrum in retaining an egalitarian and participatory democracy ethos while seeking to expand their existing frame of leadership to being both more pragmatic and oriented towards active involvement in government.
Emotional responses of leaders to passive versus active members
Authors: Schneider Andreas , Gardner William L , Hinojosa Amanda , Marin Alejandra
Published: March 2014

In our investigation of emotion management in organizations, we shift the focus from leadership to followership. To maintain their leadership identity in leader–member relationships, leaders have to elicit emotions that are contingent on the identity of the member. As such, members play a key role in defining leadership. We apply the symbolic interactionist approach of affect control theory and its operationalization in computer simulations to investigate the emotion management of leaders. To do so, we determine which emotions are most normative for leaders to show during their interactions with members that assume identities as passive followers versus active colleagues. The results reveal that the identity of a passive follower elicits emotions that are relatively negative (e.g. defiant, mad, shocked, alarmed, anxious) from leaders, whereas the active colleague identity generates comparatively positive emotions (e.g. pleased, delighted, glad, amused, thankful, relaxed, serene).
Paradoxes of authentic leadership: Leader identity struggles
Authors: Nyberg Daniel , Sveningsson Stefan
Published: March 2014

Using in-depth interview material, this article explores the socially constructed and locally mediated nature of authentic leadership. The findings illustrate an irony of authentic leadership: while leaders claim that it is their true and natural selves that make them good leaders; simultaneously, they must restrain their claimed authenticity in order to be perceived as good leaders. This generates tensions that undermine the construction of a more stable and coherent leader identity. The study finds that in order to resolve these tensions, the managers develop metaphorical selves—Mother Teresa, messiah and coach—as a way of trying to accommodate conflicting identity claims while remaining true to the idea of themselves as authentic leaders exercising good leadership. These findings contribute to a constructed, situational and contested notion of leadership by showing how authenticity is an existential project of ‘essentialising’ fragmented and conflicting selves.
Leadership and moral neutralisation
Authors: Kvalnes Øyvind
Published: March 2014

This paper explores how moral neutralisation techniques can be employed by business leaders in their moral reasoning. It presents results from leadership training with participants from a Norwegian financial institution. Each participant faced the challenge of being a reference person for an employee who had created social unrest at work. The option of lying about the problems to get rid of the employee initially appeared to conflict with the participants’ moral convictions. Nevertheless, some of them managed to overcome the dissonance by applying moral neutralisation techniques. Focus on moral reasoning of this kind among business leaders is shown to be part of a more general shift in attention from moral character to circumstances in explanations of and countermeasures against moral wrongdoing.
Women’s participation in entrepreneurial and political leadership: The importance of culturally endorsed implicit leadership theories
Authors: Bullough Amanda , de Luque Mary Sully
Published: March 2014

This paper explores how globally endorsed leadership behaviors affect women’s involvement in leadership by empirically examining the impact of Project GLOBE’s culturally endorsed implicit leadership theories on a sample of female business and political leaders. The study examines two continuous dependent variables provided by the World Bank: Female Seats in National Parliaments (%) and Self-employed Females (% of Total Self-employment). Regression analysis was used to test the viability of the culturally endorsed implicit leadership theories as possible predictors of women’s participation in leadership. The results indicate that charismatic leadership and self-protective leadership are predictors of women’s leadership participation but in different ways; the former has a positive effect for participation in both leadership (political and business) contexts, and the latter has a negative effect only on political leadership participation.
Cloning International Law: The Science and Science Fiction of Human Cloning and Stem-Cell Patenting
Authors: Lavi Shai
Published: March 2014

The article offers a critical appraisal of the rise of international governance in the field of genetics and reproductive technologies as “legal cloning.” It critically explores two of the dominant approaches to the homogenization of international law: the instrumentalist approach promoted by legal realists (law and science) and the deterministic approach advanced by legal surrealists (law and science fiction). As an alternative to both, the article offers an account of bio-technology’s modus operandi, and its power to “clone,” namely, to reduce human diversity – whether genetic, moral, or legal – not to identity but to a controlled and standardized uniformity. By examining three case studies of international law and transnational law – the UN declaration on human cloning, the recent restriction of the patenting of human embryonic stem cell research by the CJEU – along with Aldous Huxley’s classic novel Brave New World, the article unveils three different ways in which cloning operates in international law: international law versus cloning, international law as cloning, and the cloning of international law.
Children’s Transitional Rights
Authors: Dailey Anne C.
Published: March 2014

This article reflects upon the contribution that psychoanalysis can make to our understanding of children’s rights in a liberal legal system. The question of children’s rights has been richly debated over the past half century. Some commentators believe children’s rights would undermine parental authority; others argue that rights would diminish children’s welfare claims. But a major obstacle to children’s rights is our liberal legal system itself. We presume children lack the autonomy that liberalism sets as a precondition to possessing rights. Yet psychoanalytic theory supports the notion of “transitional rights” grounded in children’s special status as children. Unlike liberalism’s baseline rejection of children’s rights, which assumes children’s lack of adult decision-making skills, a psychoanalytic account of children’s transitional rights focuses on the skills and capacities that children have rather than the adult capacities they lack. It captures the emotionally-laden, developmentally-anchored, interpersonally-derived psychological experience of what it means to become a mature, autonomous, rights-bearing adult. The psychoanalytic ideas relevant here concern intrinsic capacities such as attachment, internalization, and fantasy, and the interplay of these capacities with early cognitive and reality-based thinking. To the extent this account of children’s intrinsic experience reveals the importance of early emotional relationships for the unfolding of mature autonomy, we discover the affirmative, constitutive, protective – even Romantic – role of transitional rights in a liberal system of justice.
Stochastic activity networks for performance evaluation of fault-tolerant systems
Authors: Maza Samia
Published: March 2014

The need for high-performance, productive and dependable industrial systems guided engineers to design complex operational architectures. Many features and subsystems are added to the process to produce a fault-tolerant system. All of these subsystems will interact with each other to improve the whole system’s performances. Each feature/component has its own dynamic and performances, and the interactions between them may induce a difficulty to control and evaluate the system’s behavior. This article proposes the use of an integrated modeling approach for fault-tolerant systems based on stochastic activity networks. It shows how to use this approach to evaluate some system’s performance parameters such as the reliability, availability and maintenance cost.
Life probability distribution model of mechanical components with the number of load application as life parameter
Authors: Wang Zheng , Wang A-na
Published: March 2014

With the number of load application as the life parameter, the method for modeling the life probability distribution of mechanical components is studied. First, the failure behavior of mechanical components is analyzed, and the method for describing the failure behavior of mechanical components is developed with the stress–strength interference theory. Then, based on the failure behavior, the life probability density function, life cumulative distribution function, reliability, failure rate, and mean life of component with the number of load application as the life parameter, which can embody the effect of parameters including stress, strength and its degradation, and so on, are derived, respectively. Finally, for the cases of different parameters of stress and strength, the life probabilistic distribution characteristic, reliability, failure rate, mean life, and reliable life of components are studied. The result shows that the life probabilistic distribution characteristic of components is dependent on the specific value of parameters describing the failure behavior. With the method and model proposed in this article, as long as the parameters of strength, stress, strength degradation, and so on are known, the life probabilistic distribution functions of components can be calculated, the rules that the reliability and failure rate of component change as the number of load application can be obtained, and the mean life and reliable life of components can be determined.
Salmonella enterica serovar Typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes
Authors: Knetter Susan M , Bearson Shawn MD , Huang Ting-Hua , Kurkiewicz Dason , Schroyen Martine , Nettleton Dan , Berman Daniel , Cohen Valerie , Lunney Joan K , Ramer-Tait Amanda E , Wannemuehler Michael J , Tuggle Christopher K
Published: March 2014

Foodborne salmonellosis costs the US $2.7 billion/year, including $100.0 million in annual losses to pork producers. Pigs colonized with Salmonella are usually asymptomatic with varied severity and duration of fecal shedding. Thus, understanding the responses that result in less shedding may provide a mechanism for control. Fifty-four pigs were inoculated with Salmonella enterica serovar Typhimurium (ST) and clinical signs, fecal ST shedding, growth performance, peripheral cytokines and whole blood gene expression were measured. Persistently shedding (PS) pigs had longer pyrexia and elevated serum IL-1β, TNF-α and IFN-γ compared with low shedding (LS) pigs, while LS pigs had brief pyrexia, less shedding that decreased more rapidly and greater serum CXCL8 than PS pigs. The PS pigs up-regulated genes involved with the STAT1, IFNB1 and IFN-γ networks on d 2, while up-regulation of genes involved in immune response regulation were only detected in LS pigs. This is the first study to examine host responses to ST infection at a clinical, performance, cytokine and transcriptomic level. The results indicated that pigs with different shedding outcomes developed distinct immune responses within the first 2 d of ST infection, and elucidated alternative mechanisms that could be targeted to reduce Salmonella shedding and spread.
Management of iatrogenic ureteral injury
Authors: Burks Frank N. , Santucci Richard A.
Published: March 2014

Iatrogenic injury to the ureter is a potentially devastating complication of modern surgery. The ureters are most often injured in gynecologic, colorectal, and vascular pelvic surgery. There is also potential for considerable ureteral injury during endoscopic procedures for ureteric pathology such as tumor or lithiasis. While maneuvers such as perioperative stenting have been touted as a means to avoid ureteral injury, these techniques have not been adopted universally, and the available literature does not make a case for their routine use. Distal ureteral injuries are best managed with ureteroneocystostomy with or without a vesico-psoas hitch. Mid-ureteral and proximal ureteral injuries can potentially be managed with ureteroureterostomy. If the distal segment is unsuitable for anastomosis then a number of techniques are available for repair including a Boari tubularized bladder flap, transureteroureterostomy, or renal autotransplantation. In rare cases renal autotransplantation or ureteral substitution with gastrointestinal segments may be warranted to re-establish urinary tract continuity. Laparoscopic and minimally invasive techniques have been employed to remedy iatrogenic ureteral injuries.
Design of the Glucose Rate Increase Detector
Authors: Harvey Rebecca A. , Dassau Eyal , Zisser Howard , Seborg Dale E. , Doyle Francis J.
Published: March 2014

Background:

The Glucose Rate Increase Detector (GRID), a module of the Health Monitoring System (HMS), has been designed to operate in parallel to the glucose controller to detect meal events and safely trigger a meal bolus.

Methods:

The GRID algorithm was tuned on clinical data with 40-70 g CHO meals and tested on simulation data with 50-100 g CHO meals. Active closed- and open-loop protocols were executed in silico with various treatments, including automatic boluses based on a 75 g CHO meal and boluses based on simulated user input of meal size. An optional function was used to reduce the recommended bolus using recent insulin and glucose history.

Results:

For closed-loop control of a 3-meal scenario (50, 75, and 100 g CHO), the GRID improved median time in the 80-180 mg/dL range by 17% and in the >180 range by 14% over unannounced meals, using an automatic bolus for a 75 g CHO meal at detection. Under open-loop control of a 75 g CHO meal, the GRID shifted the median glucose peak down by 73 mg/dL and earlier by 120 min and reduced the time >180 mg/dL by 57% over a missed-meal bolus scenario, using a full meal bolus at detection.

Conclusions:

The GRID improved closed-loop control in the presence of large meals, without increasing late postprandial hypoglycemia. Users of basal-bolus therapy could also benefit from GRID as a safety alert for missed meal corrections.
What Are the Next Steps in Continuous Glucose Monitoring?
Authors: Lodwig Volker , Kulzer Bernhard , Schnell Oliver , Heinemann Lutz
Published: March 2014

The development of glucose sensors for continuous glucose monitoring (CGM) is likely still in its early days. A number of novel approaches—along with many attempts to improve current CGM systems—are in development. The next generation of glucose sensors (NGGS) will also enable, for example, reliable glucose measurement in the low glycemic range. NGGS systems represent an important step forward for closed-loop systems. This commentary discusses a number of aspects that are relevant in this context.
Current Trends in Continuous Glucose Monitoring
Authors: Lodwig Volker , Kulzer Bernhard , Schnell Oliver , Heinemann Lutz
Published: March 2014

The market introduction of systems for continuous glucose monitoring (CGM) some 15 years ago did not immediately revolutionize the treatment of diabetes; however, for a given group of patients, it would almost be inconceivable nowadays to imagine life without CGM. One day the development of insulin pumps together with CGM could culminate in an artificial pancreas system. The performance of the glucose sensors used for glucose measurement in the interstitial fluid in the subcutaneous tissue and the algorithms employed to analyze these data have improved so much over the past decade that current CGM systems by far outperform those of the first generations. This commentary discusses a number of aspects about what we have learned since CGM systems entered the market and what current trends exist in their usage. Some of these are major hurdles facing a more widespread usage of CGM.
DialBetics
Authors: Waki Kayo , Fujita Hideo , Uchimura Yuji , Omae Koji , Aramaki Eiji , Kato Shigeko , Lee Hanae , Kobayashi Haruka , Kadowaki Takashi , Ohe Kazuhiko
Published: March 2014

Background:

Numerous diabetes-management systems and programs for improving glycemic control to meet guideline targets have been proposed, using IT technology. But all of them allow only limited—or no—real-time interaction between patients and the system in terms of system response to patient input; few studies have effectively assessed the systems’ usability and feasibility to determine how well patients understand and can adopt the technology involved.

Method:

DialBetics is composed of 4 modules: (1) data transmission module, (2) evaluation module, (3) communication module, and (4) dietary evaluation module. A 3-month randomized study was designed to assess the safety and usability of a remote health-data monitoring system, and especially its impact on modifying patient lifestyles to improve diabetes self-management and, thus, clinical outcomes. Fifty-four type 2 diabetes patients were randomly divided into 2 groups, 27 in the DialBetics group and 27 in the non-DialBetics control group.

Results:

HbA1c and fasting blood sugar (FBS) values declined significantly in the DialBetics group: HbA1c decreased an average of 0.4% (from 7.1 ± 1.0% to 6.7 ± 0.7%) compared with an average increase of 0.1% in the non-DialBetics group (from 7.0 ± 0.9% to 7.1 ± 1.1%) ( P = .015); The DialBetics group FBS decreased an average of 5.5 mg/dl compared with a non-DialBetics group average increase of 16.9 mg/dl ( P = .019). BMI improvement—although not statistically significant because of the small sample size—was greater in the DialBetics group.

Conclusions:

DialBetics was shown to be a feasible and an effective tool for improving HbA1c by providing patients with real-time support based on their measurements and inputs.
The AAA (appraisals, attributions, adaptation) model of job stress
Authors: Mackey Jeremy D. , Perrewé Pamela L.
Published: March 2014

The AAA model is presented as an integrative conceptualization of workplace stress that combines research from multiple models and theories to account for the numerous complexities that employees experience when cognitively evaluating organizational demands. The proposed model examines the effects of employees’ organizational stressors on the cognitive appraisal process and describes how employees’ emotions and self-regulation affect individual coping behaviors, adaptation, and learning from stressful experiences. Practitioner applications, theoretical contributions, and directions for future research are presented.
Clinical features of constipation in general practice in Italy
Authors: Cottone Carmelo , Tosetti Cesare , Disclafani Giuseppe , Ubaldi Enzo , Cogliandro Rosanna , Stanghellini Vincenzo
Published: March 2014

Background

Definition and diagnosis of constipation remain challenging, partly due to different perceptions of the disease by doctors and patients.

Aim

To evaluate prevalence and features of constipation among individuals seen in general practice, by comparing different diagnostic instruments.

Methods

Standardized questionnaires and the Bristol stool form scale were distributed to all subjects attending 10 general practitioners for any reason in a 2‐week period. The questionnaires investigated constipation defined according to: (1) self‐perception (yes/no); (2) a visual analogue scale; (3) Rome III Criteria.

Results

The prevalence of constipation in 1306 subjects (790 female, 516 male) resulted: (1) 34% self‐reported; (2) 28% by visual analogue scale; (3) 24% by Rome Criteria. Constipation was more frequent in females. A high frequency of symptoms of obstructed defecations was observed with differences among patients with self‐reported constipation with or without Bristol stool type 1–2.

Conclusions

Prevalence of constipation among individuals attending their GP ranges between 24 and 34%, according to the different definitions adopted. Symptoms of obstructed defecations are frequent. The combination of self‐evaluation and the Bristol stool type scale is potentially useful to identify subgroups of patients with different clinical features in general practice.
Interactions Between Monoamine Oxidase A and Punitive Discipline in African American and Caucasian Men’s Antisocial Behavior
Authors: Choe Daniel Ewon , Shaw Daniel S. , Hyde Luke W. , Forbes Erika E.
Published: March 2014

Although previous studies have shown that interactions between monoamine oxidase A ( MAOA) genotype and childhood maltreatment predict Caucasian boys’ antisocial behavior, the generalizability of this gene-environment interaction to more diverse populations and more common parenting behaviors, such as punitive discipline in early childhood, is not clearly understood. Among 189 low-income men (44% African American, 56% Caucasian) who underwent rigorous assessments of family behavior and social context longitudinally across 20 years, those men with the low activity MAOA allele who experienced more punitive discipline at ages 1.5, 2, and 5 years showed more antisocial behavior from ages 15 through 20 years. Effects of punitive discipline on antisocial behavior differed by caregiver and age at which it occurred, suggesting sensitive periods throughout early childhood in which low MAOA activity elevated boys’ vulnerability to harsh parenting and risk for antisocial behavior. This genetic vulnerability to punitive discipline—and not just extreme, maltreatment experiences—may generalize to other male populations at risk for antisocial behavior.
A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3
Authors: Steward-Tharp Scott M. , Laurence Arian , Kanno Yuka , Kotlyar Alex , Villarino Alejandro V. , Sciume Giuseppe , Kuchen Stefan , Resch Wolfgang , Wohlfert Elizabeth A. , Jiang Kan , Hirahara Kiyoshi , Vahedi Golnaz , Sun Hong-wei , Feigenbaum Lionel , Milner Joshua D. , Holland Steven M. , Casellas Rafael , Powrie Fiona , O'Shea John J.
Published: March 2014

Key Points

Mice that express a mutation in STAT3 phenocopy patients with HIES. Bone marrow transplantation does not fully correct the susceptibility of these animals to bacterial infection.
Multiple roles of the coagulation protease cascade during virus infection
Authors: Antoniak Silvio , Mackman Nigel
Published: March 2014

The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.
Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma
Authors: Iqbal Javeed , Wright George , Wang Chao , Rosenwald Andreas , Gascoyne Randy D. , Weisenburger Dennis D. , Greiner Timothy C. , Smith Lynette , Guo Shuangping , Wilcox Ryan A. , Teh Bin Tean , Lim Soon Thye , Tan Soon Yong , Rimsza Lisa M. , Jaffe Elaine S. , Campo Elias , Martinez Antonio , Delabie Jan , Braziel Rita M. , Cook James R. , Tubbs Raymond R. , Ott German , Geissinger Eva , Gaulard Philippe , Piccaluga Pier Paolo , Pileri Stefano A. , Au Wing Y. , Nakamura Shigeo , Seto Masao , Berger Francoise , de Leval Laurence , Connors Joseph M. , Armitage James , Vose Julie , Chan Wing C. , Staudt Louis M.
Published: March 2014

Key Points

Diagnostic signatures for PTCL subtypes and 2 novel subgroups with distinct oncogenic pathway and prognostic importance in PTCL-NOS were identified. Demonstrated that ALK(–) ALCL is a distinct molecular entity and the tumor microenvironment has prognostic significance in AITL patients.
Deregulated cell death and lymphocyte homeostasis cause premature lethality in mice lacking the BH3-only proteins Bim and Bmf
Authors: Labi Verena , Woess Claudia , Tuzlak Selma , Erlacher Miriam , Bouillet Philippe , Strasser Andreas , Tzankov Alexandar , Villunger Andreas
Published: March 2014

Key Points

BH3-only proteins Bim and Bmf jointly coregulate developmental cell death. Bim and Bmf act as a barrier against autoimmunity and malignant disease.
Targeting MUC1-C is synergistic with bortezomib in downregulating TIGAR and inducing ROS-mediated myeloma cell death
Authors: Yin Li , Kufe Turner , Avigan David , Kufe Donald
Published: March 2014

Key Points

Targeting the MUC1-C oncoprotein in MM cells potentiates BTZ-induced downregulation of TIGAR and thereby ROS-mediated death. Targeting MUC1-C is effective in resensitizing BTZ-resistant MM cells to BTZ and thus represents a potential strategy for combination treatment.
Regulation of tight junction gene expression in the kidney of calbindin-D9k and/or -D28k knockout mice after consumption of a calcium- or a calcium/vitamin D-deficient diet
Authors: Hwang Inho , Hong Eui-Ju , Yang Hyun , Kang Hong-Seok , Ahn Changhwan , An Beum-Soo , Jeung Eui-Bae
Published: March 2014

Background

Calciotropic hormones were thought to facilitate calcium transfer through active transcellular or passive paracellular pathway for calcium homeostasis. While calcium transport proteins such as CaBP-28 k, TRPV5, NCX1, PMCA1b are involved in calcium reabsorption of the renal tubule using transcellular transport, tight junction proteins are known as critically related to calcium absorption through paracellular pathway. The regulation of each pathway for calcium transport was well studied but the correlation was not. It is expected that present study will provide new information about the link between transcellular and paracellular pathway within renal tubules.

Results

Transcripts and proteins of tight junction related genes (occludin, ZO-1, and claudins) were examined in CaBP-9 k-and/or-28 k-deficient mice as well as the effect of dietary calcium and/or vitamin D supplementation. With a normal diet, the transcriptional and translational expressions of most tight junction proteins in the kidney was not significantly changed but with a calcium- and vitamin D-deficient diet, and they were significantly increased in the kidney of the CaBP-28 k and CaBP-9 k/28 k double KO (DKO) mice. In these genotypes, the increase of tight junction related transcripts and proteins are referred to as an evidence explaining correlation between transcellular transport and paracellular pathway.

Conclusions

These findings are particularly interesting in evidences that insufficient transcellular calcium transports are compensated by paracellular pathway in calcium or calcium/vitamin D deficient condition, and that both transcellular and paracellular pathways functionally cooperate for calcium reabsorption in the kidney.
Natural polymorphisms and unusual mutations in HIV-1 protease with potential antiretroviral resistance: a bioinformatic analysis
Authors: Mata-Munguía Carlos , Escoto-Delgadillo Martha , Torres-Mendoza Blanca , Flores-Soto Mario , Vázquez-Torres Mildred , Gálvez-Gastelum Francisco , Viniegra-Osorio Arturo , Castillero-Manzano Marcelo , Vázquez-Valls Eduardo
Published: March 2014

Background

The correlations of genotypic and phenotypic tests with treatment, clinical history and the significance of mutations in viruses of HIV-infected patients are used to establish resistance mutations to protease inhibitors (PIs). Emerging mutations in human immunodeficiency virus type 1 (HIV-1) protease confer resistance to PIs by inducing structural changes at the ligand interaction site. The aim of this study was to establish anin silicostructural relationship between natural HIV-1 polymorphisms and unusual HIV-1 mutations that confer resistance to PIs.

Results

Protease sequences isolated from 151 Mexican HIV-1 patients that were naïve to, or subjected to antiretroviral therapy, were examined. We identified 41 unrelated resistance mutations with a prevalence greater than 1%. Among these mutations, nine exhibited positive selection, three were natural polymorphisms (L63S/V/H) in a codon associated with drug resistance, and six were unusual mutations (L5F, D29V, L63R/G, P79LandT91V). TheD29Vmutation, with a prevalence of 1.32% in the studied population, was only found in patients treated with antiretroviral drugs. Usingin silicomodelling, we observed that D29V formed unstable protease complexes when were docked with lopinavir, saquinavir, darunavir, tipranavir, indinavir and atazanavir.

Conclusions

The structural correlation of natural polymorphisms and unusual mutations with drug resistance is useful for the identification of HIV-1 variants with potential resistance to PIs. The D29V mutation likely confers a selection advantage in viruses; however,in silico, presence of this mutation results in unstable enzyme/PI complexes, that possibly induce resistance to PIs.
Genomic convergence and network analysis approach to identify candidate genes in Alzheimer's disease
Authors: Talwar Puneet , Silla Yumnam , Grover Sandeep , Gupta Meenal , Agarwal Rachna , Kushwaha Suman , Kukreti Ritushree
Published: March 2014

Background

Alzheimer’s disease (AD) is one of the leading genetically complex and heterogeneous disorder that is influenced by both genetic and environmental factors. The underlying risk factors remain largely unclear for this heterogeneous disorder. In recent years, high throughput methodologies, such as genome-wide linkage analysis (GWL), genome-wide association (GWA) studies, and genome-wide expression profiling (GWE), have led to the identification of several candidate genes associated with AD. However, due to lack of consistency within their findings, an integrative approach is warranted. Here, we have designed a rank based gene prioritization approach involving convergent analysis of multi-dimensional data and protein-protein interaction (PPI) network modelling.

Results

Our approach employs integration of three different AD datasets- GWL,GWA and GWE to identify overlapping candidate genes ranked using a novel cumulative rank score (SR) based method followed by prioritization using clusters derived from PPI network. SR for each gene is calculated by addition of rank assigned to individual gene based on either p value or score in three datasets. This analysis yielded 108 plausible AD genes. Network modelling by creating PPI using proteins encoded by these genes and their direct interactors resulted in a layered network of 640 proteins. Clustering of these proteins further helped us in identifying 6 significant clusters with 7 proteins (EGFR, ACTB, CDC2, IRAK1, APOE, ABCA1 and AMPH) forming the central hub nodes. Functional annotation of 108 genes revealed their role in several biological activities such as neurogenesis, regulation of MAP kinase activity, response to calcium ion, endocytosis paralleling the AD specific attributes. Finally, 3 potential biochemical biomarkers were found from the overlap of 108 AD proteins with proteins from CSF and plasma proteome. EGFR and ACTB were found to be the two most significant AD risk genes.

Conclusions

With the assumption that common genetic signals obtained from different methodological platforms might serve as robust AD risk markers than candidates identified using single dimension approach, here we demonstrated an integrated genomic convergence approach for disease candidate gene prioritization from heterogeneous data sources linked to AD.
Comparative transcriptomics of Atlantic Salmo salar, chum Oncorhynchus keta and pink salmon O. gorbuscha during infections with salmon lice Lepeophtheirus salmonis
Authors: Sutherland Ben JG , Koczka Kim W , Yasuike Motoshige , Jantzen Stuart G , Yazawa Ryosuke , Koop Ben F , Jones Simon RM
Published: March 2014

Background

Salmon species vary in susceptibility to infections with the salmon louse (Lepeophtheirus salmonis). Comparing mechanisms underlying responses in susceptible and resistant species is important for estimating impacts of infections on wild salmon, selective breeding of farmed salmon, and expanding our knowledge of fish immune responses to ectoparasites. Herein we report three L. salmonis experimental infection trials of co-habited Atlantic Salmo salar, chum Oncorhynchus keta and pink salmon O. gorbuscha, profiling hematocrit, blood cortisol concentrations, and transcriptomic responses of the anterior kidney and skin to the infection.

Results

In all trials, infection densities (lice per host weight (g)) were consistently highest on chum salmon, followed by Atlantic salmon, and lowest in pink salmon. At 43 days post-exposure, all lice had developed to motile stages, and infection density was uniformly low among species. Hematocrit was reduced in infected Atlantic and chum salmon, and cortisol was elevated in infected chum salmon. Systemic transcriptomic responses were profiled in all species and large differences in response functions were identified between Atlantic and Pacific (chum and pink) salmon. Pink and chum salmon up-regulated acute phase response genes, including complement and coagulation components, and down-regulated antiviral immune genes. The pink salmon response involved the largest and most diverse iron sequestration and homeostasis mechanisms. Pattern recognition receptors were up-regulated in all species but the active components were often species-specific. C-type lectin domain family 4 member M and acidic mammalian chitinase were specifically up-regulated in the resistant pink salmon.

Conclusions

Experimental exposures consistently indicated increased susceptibility in chum and Atlantic salmon, and resistance in pink salmon, with differences in infection density occurring within the first three days of infection. Transcriptomic analysis suggested candidate resistance functions including local inflammation with cytokines, specific innate pattern recognition receptors, and iron homeostasis. Suppressed antiviral immunity in both susceptible and resistant species indicates the importance of future work investigating co-infections of viral pathogens and lice.
Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer
Authors: Leite Marcelo Sobral , Giacomin Letícia Carlos , Piranda Diogo Nascimento , Festa-Vasconcellos Juliana Simões , Indio-do-Brasil Vanessa , Koifman Sérgio , de Moura-Neto Rodrigo Soares , de Carvalho Marcelo Alex , Vianna-Jorge Rosane
Published: March 2014

Background

The epidermal growth factor receptor (EGFR) is differently expressed in breast cancer, and its presence may favor cancer progression. We hypothesized that twoEGFRfunctional polymorphisms, a (CA)n repeat in intron 1, and a single nucleotide polymorphism,R497K, may affectEGFRexpression and breast cancer clinical profile.

Methods

The study population consisted of 508 Brazilian women with unilateral breast cancer, and no distant metastases. Patients were genotyped for the(CA)nandR497Kpolymorphisms, and the associations between(CA)npolymorphism and EGFR transcript levels (n = 129), or between either polymorphism and histopathological features (n = 505) were evaluated. The REMARK criteria of tumor marker evaluation were followed.

Results

(CA)n lengths ranged from 14 to 24 repeats, comprehending 11 alleles and 37 genotypes. The most frequent allele was(CA)16(0.43; 95% CI = 0.40–0.46), which was set as the cut-off length to define theShortallele. Variant(CA)ngenotypes had no significant effect in tumoralEGFRmRNA levels, but patients with two(CA)n Longalleles showed lower chances of being negative for progesterone receptor (ORadjusted = 0.42; 95% CI = 0.19–0.91). The evaluation ofR497Kpolymorphism indicated a frequency of 0.21 (95% CI = 0.19 – 0.24) for the variant (Lys) allele. Patients with variantR497Kgenotypes presented lower proportion of worse lymph node status (pN2 or pN3) when compared to the reference genotypeArg/Arg(ORadjusted = 0.32; 95% CI = 0.17–0.59), which resulted in lower tumor staging (ORadjusted = 0.34; 95% CI = 0.19-0.63), and lower estimated recurrence risk (OR = 0.50; 95% CI = 0.30-0.81). The combined presence of bothEGFRpolymorphisms (Lysallele of R497K andLong/Long (CA)n) resulted in lower TNM status (ORadjusted = 0.22; 95% CI = 0.07-0.75) and lower ERR (OR = 0.25; 95% CI = 0.09-0.71). When tumors were stratified according to biological classification, the favorable effects of variantEGFRpolymorphisms were preserved for luminal A tumors, but not for other subtypes.

Conclusions

The data suggest that the presence of the variant forms ofEGFRpolymorphisms may lead to better prognosis in breast cancer, especially in patients with luminal A tumors.
Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness
Authors: Jami Mohammad-Saeid , Hou Jinxuan , Liu Miao , Varney Michelle L , Hassan Hesham , Dong Jixin , Geng Liying , Wang Jing , Yu Fang , Huang Xin , Peng Hong , Fu Kai , Li Yan , Singh Rakesh K , Ding Shi-Jian
Published: March 2014

Background

KIAA1199is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

Methods

We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosisin vitro. We studied the effects of KIAA1199 knockdownin vivoin two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer.

Results

KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferationin vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility.

Conclusions

Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it may represent a novel target for biomarker development and a novel therapeutic target for breast cancer.
Study of zeolite influence on analytical characteristics of urea biosensor based on ion-selective field-effect transistors
Authors: Shelyakina Margaryta K , Soldatkin Oleksandr O , Arkhypova Valentyna M , Kasap Berna O , Akata Burcu , Dzyadevych Sergei V
Published: March 2014

A possibility of the creation of potentiometric biosensor by adsorption of enzyme urease on zeolite was investigated. Several variants of zeolites (nano beta, calcinated nano beta, silicalite, and nano L) were chosen for experiments. The surface of pH-sensitive field-effect transistors was modified with particles of zeolites, and then the enzyme was adsorbed. As a control, we used the method of enzyme immobilization in glutaraldehyde vapour (without zeolites). It was shown that all used zeolites can serve as adsorbents (with different effectiveness). The biosensors obtained by urease adsorption on zeolites were characterized by good analytical parameters (signal reproducibility, linear range, detection limit and the minimal drift factor of a baseline). In this work, it was shown that modification of the surface of pH-sensitive field-effect transistors with zeolites can improve some characteristics of biosensors.
Separated boundary value problems for second-order impulsive q-integro-difference equations
Authors: Thaiprayoon Chatthai , Tariboon Jessada , Ntouyas Sotiris K
Published: March 2014

This article studies the existence and uniqueness of solutions for a boundary value problem of nonlinear second-order impulsive

q
k

-integro-difference equations with separated boundary conditions. Several new results are obtained by applying a variety of fixed point theorems. Some examples are presented to illustrate the results.

MSC:26A33, 39A13, 34A37.
Tolerance of pentose utilising yeast to hydrogen peroxide-induced oxidative stress
Authors: Spencer Jennifer , Phister Trevor G , Smart Katherine A , Greetham Darren
Published: March 2014

Background

Bioethanol fermentations follow traditional beverage fermentations where the yeast is exposed to adverse conditions such as oxidative stress. Lignocellulosic bioethanol fermentations involve the conversion of pentose and hexose sugars into ethanol. Environmental stress conditions such as osmotic stress and ethanol stress may affect the fermentation performance; however, oxidative stress as a consequence of metabolic output can also occur. However, the effect of oxidative stress on yeast with pentose utilising capabilities has yet to be investigated.

Results

Assaying for the effect of hydrogen peroxide-induced oxidative stress on Candida, Pichia and Scheffersomyces spp. has demonstrated that these yeast tolerate hydrogen peroxide-induced oxidative stress in a manner consistent with that demonstrated by Saccharomyces cerevisiae. Pichia guillermondii appears to be more tolerant to hydrogen peroxide-induced oxidative stress when compared to Candida shehatae, Candida succiphila or Scheffersomyces stipitis.

Conclusions

Sensitivity to hydrogen peroxide-induced oxidative stress increased in the presence of minimal media; however, addition of amino acids and nucleobases was observed to increase tolerance. In particular adenine increased tolerance and methionine reduced tolerance to hydrogen peroxide-induced oxidative stress.
RNF168-mediated H2A neddylation antagonizes its ubiquitination and regulates DNA damage repair
Authors: Li Tingting , Guan Junhong , Huang Ziji , Hu Xiang , Zheng Xiaofeng
Published: March 2014

NEDD8 is an important regulatory factor in many biological processes. However, the substrates of neddylation and the relation between ubiquitin and NEDD8 pathways are remained largely unknown. Here, we showed that NEDD8 is covalently conjugated to H2A, and neddylation of H2A antagonizes its ubiquitination. NEDD8 suppresses H2A ubiquitination and decrease of the free NEDD8 level promotes H2A ubiquitination. We further found that E3 ligase RNF168 promotes both H2A ubiquitination and neddylation. Interestingly, RNF168 is a substrate of NEDD8 and neddylation of RNF168 is necessary for its E3 ubiquitin activity. Inhibition of RNF168 neddylation impairs the interaction between RNF168 and its E2 Ubc13. Moreover, in response to DNA damage, the level of H2A neddylation decreased with the increase of H2A ubiquitination, which facilitates DNA damage repair. And at the late stage of damage repair, H2A neddylation increased gradually while ubiquitination decreased to the basal levels. Mechanistically, NEDD8 negatively regulates DNA damage repair process by suppressing the ubiquitination of H2A and γH2AX, which further blocks the recruitment of damage-response protein BRCA1. Our findings elucidate the relation of H2A ubiquitination and neddylation, and suggest a novel modulate approach of DNA damage repair through neddylation pathway.
High resolution live cell imaging reveals novel cyclin A2 degradation foci involving autophagy
Authors: Loukil Abdelhalim , Zonca Manuela , Rebouissou Cosette , Baldin Véronique , Coux Olivier , Biard-Piechaczyk Martine , Blanchard Jean-Marie , Peter Marion
Published: March 2014

Cyclin A2 is a key actor in cell cycle regulation. Its degradation in mid-mitosis relies on the ubiquitin-proteasome system (UPS). Using high resolution microscopic imaging, we find that cyclin A2 persists beyond metaphase. Indeed, we identify a novel cyclin A2-containing compartment that forms dynamic foci. FRET and FLIM analyses show that cyclin A2 ubiquitylation takes place predominantly in these foci before spreading throughout the cell. Moreover, inhibition of autophagy in proliferating cells induce a stabilisation of a cyclin A2 subset, while induction of autophagy accelerates cyclin A2 degradation, thus showing that autophagy is a novel regulator of cyclin A2 degradation.