Unquestionable Role Research Articles

Applications of in Silico Methods for Design and Development of Drugs Targeting Protein-Protein Interactions.

Identification of Protein-Protein Interactions (PPIs) is a major challenge in modern molecular biology and biochemistry research, due to the unquestionable role of proteins in cells, biological process and pathological states. Over the past decade, the PPIs have evolved from being considered a highly challenging field of research to being investigated and examined as targets for pharmacological intervention. Comprehension of protein interactions is crucial to known how proteins come together to build signalling pathways, to carry out their functions, or to cause diseases, when deregulated. Multiplicity and great amount of PPIs structures offer a huge number of new and potential targets for the treatment of different diseases. Computational techniques are becoming predominant in PPIs studies for their effectiveness, flexibility, accuracy and cost. As a matter of fact, there are effective in silico approaches which are able to identify PPIs and PPI site. Such methods for computational target prediction have been developed through molecular descriptors and data-mining procedures. In this review, we present different types of interactions between protein-protein and the application of in silico methods for design and development of drugs targeting PPIs. We described computational approaches for the identification of possible targets on protein surface and to detect of stimulator/ inhibitor molecules. A deeper study of the most recent bioinformatics methodologies for PPIs studies is vital for a better understanding of protein complexes and for discover new potential PPI modulators in therapeutic intervention.

The Use of Humor in Palliative Care: A Systematic Literature Review.

Humor has its own place in the context of medicine. Nevertheless, its acceptance by terminal stage patients and health-care professionals has not been studied in depth and is not free from controversy. To understand the significance, appropriateness, and pertinence of the use of humor in palliative care and to analyze its applicability. A narrative systematic review was undertaken and included in PROSPERO. Online searches were carried out on PUBMED, PSYCINFO, EBSCO (CINHAL), EMBASE, SCIELO, SCOPUS, TESEO, WEB of SCIENCE, and COCHRANE between their launch date and December 31, 2015, complemented with manual searches with queries to experts. A total of 156 studies were identified, which were then filtered in pairs by means of an established hierarchy, selecting studies that discussed the use of humor specifically in palliative care from all perspectives and designs, and finally published in Spanish, English, French, or Portuguese. Critical reading of all the selected studies took place, with no exclusions due to quality evaluation. Thirty-four studies were included. Five main topics were identified: (1) definition of humor, (2) use and functions of humor in palliative care, (3) how to use humor, (4) when not to use humor, and (5) humor before and after the diagnosis of terminal illness. Humor plays an unquestionable role in palliative care, but its use needs training and appropriate use.

Ischemia-reperfusion injury in stroke: impact of the brain barriers and brain immune privilege on neutrophil function.

Reperfusion injury following ischemic stroke is a complex pathophysiological process involving numerous mechanisms ranging from the release of excitatory amino acids and ion disequilibrium to the induction of apoptosis and necrosis, to oxidative stress and inflammation. The migration of neutrophils into the brain parenchyma and release of their abundant proteases are generally considered the main cause of neuronal cell death and acute reperfusion injury following ischemic stroke. Recent findings in experimental and human stroke have challenged this view, as the majority of neutrophils were rather found to accumulate within the neurovascular unit (NVU) and the subarachnoid space (SAS) where they remain separated from the brain parenchyma by the glia limitans. The brain parenchyma is an immune-privileged site that is not readily accessible to immune cells and does not elicit stereotypic adaptive or innate immune responses. Understanding brain immune privilege requires intimate knowledge of its unique anatomy in which the brain barriers, that include the glia limitans, establish compartments that differ remarkably with regard to their accessibility to the immune system. We here propose that the brain immune privilege also extends to an ischemic insult, where the brain parenchyma does not evoke a rapid infiltration of neutrophils as observed in ischemic events in peripheral organs. Rather, neutrophil accumulation in the NVU and SAS could have a potential impact on cerebrospinal fluid (CSF) drainage from the central nervous system (CNS) and thus on edema formation and reperfusion injury after ischemic stroke. Integrating the anatomical and functional implications of the brain immune privilege with the unquestionable role of neutrophils in reperfusion injury is a prerequisite to exploit appropriate strategies for therapeutic interventions aiming to reduce neuronal cell death after ischemic stroke.

Chrzest i Eucharystia w praktyce ekumenicznej Kościoła katolickiego i luterańskiego

In the constant ecumenical quest, there is a tendency nowadays to reach the most basic levels of church life in order to put the ecumenical rules into practice. The time has come to concentrate our attention on this very level of church life. It is here, in the pastoral work, where we approach couples and families of different confessions. The issue arises now with redoubled strength because of great migrations of people on the European continent. The problem of mixed couples is, among other problems, a challenge in solving the question of baptism and taking Communion. That is why, the everyday life of believers opens on newer and newer experiences, also in the field of ecumenism. Analysing some texts concerning the issue of ecumenical dialogue dealing with baptism and Eucharist, we can find a confirmation of the thesis that it is the parish which should be the unquestionable role model of ecumenical movement.

Low Incidence along with Low mRNA Levels of EGFRvIII in Prostate and Colorectal Cancers Compared to Glioblastoma.

Background: The presence as well as the potential role of EGFRvIII in tumors other than glioblastoma still remains a controversial subject with many contradictory data published. Previous analyses, however, did not consider the level of EGFRvIII mRNA expression in different tumor types. Methods: Appropriately designed protocol for Real-time quantitative reverse-transcription PCR (Real-time qRT-PCR) was applied to analyze EGFRvIII and EGFRWT mRNA expression in 155 tumor specimens. Additionally, Western Blot (WB) analysis was performed for selected samples. Stable cell lines showing EGFRvIII expression (CAS-1 and DK-MG) were analyzed by means of WB, immunocytochemistry (ICC) and fluorescence in situ hybridization (FISH). Results: Our analyses revealed EGFRvIII expression in 27.59% of glioblastomas (8/29), 8.11% of colorectal cancers (3/37), 6.52% of prostate cancers (3/46) and none of breast cancers (0/43). Despite the average relative expression of EGFRvIII varying greatly among tumors of different tissues (approximately 800-fold) or even within the same tissue group (up to 8000-fold for GB), even the marginal expression of EGFRvIII mRNA can be detrimental to cancer progression, as determined by the analysis of stable cell lines endogenously expressing the oncogene.Conclusion: EGFRvIII plays an unquestionable role in glioblastomas with high expression of this oncogene. Our data suggests that EGFRvIII importance should not be underestimated even in tumors with relatively low expression of this oncogene.

Predicting Protein-Protein Interactions from the Molecular to the Proteome Level.

Identification of protein-protein interactions (PPIs) is at the center of molecular biology considering the unquestionable role of proteins in cells. Combinatorial interactions result in a repertoire of multiple functions; hence, knowledge of PPI and binding regions naturally serve to functional proteomics and drug discovery. Given experimental limitations to find all interactions in a proteome, computational prediction/modeling of protein interactions is a prerequisite to proceed on the way to complete interactions at the proteome level. This review aims to provide a background on PPIs and their types. Computational methods for PPI predictions can use a variety of biological data including sequence-, evolution-, expression-, and structure-based data. Physical and statistical modeling are commonly used to integrate these data and infer PPI predictions. We review and list the state-of-the-art methods, servers, databases, and tools for protein-protein interaction prediction.

Nie(kwestionowana) rola pedeutologii w kształceniu przyszłych nauczycieli religii

Preliminarytraining of religion teachers includes different areas of theological, humanist, pedagogical and catechetic education. To be qualified to teach religion, theology students are required to gain knowledge in pedagogy, didactics, psychology and to develop their practical skills and social competences. Among these general issues, knowledge of the teaching profession is worth particular attention.

Migrant Labour and Industrial Work Environment: A Relationship Vital to National development

The present paper focuses on the work environment, which is the core of employment relationship, faced by the migrant labourers that work in the industrial units of Ludhiana, also known as ‘Manchester of India’. Despite their unquestionable vital role in the economic growth of the city, especially the secondary sector, many of the migrant labourersinhospitable work environment as they are made to work for more than the stipulated time, not paid for the overtime work, not provided with safe work environment, face health issues due hazardous work, do not get work according to choice, employed as temporary labour, and discriminated during the routine work and at the time of payment of wages. Though dissatisfied with the workplace, these labourers are change averse for they put up with the existing work conditions and prefer to get employed again at the same place of work. This clearly points to the fact that these labourers are helpless, neglected, exploited and discriminated to which they wilfully accept for being financially depressed. There is a dire need to preserve the interests of the migrants to ensure aflourishing homogeneoussocial and economic environment.

Contextual influences on nurses' decision-making in cases of physical restraint.

In order to fully understand nurses' ethical decision-making in cases of physical restraint in acute older people care, contextual influences on the process of decision-making should be clarified. What is the influence of context on nurses' decision-making process in cases of physical restraint, and what is the impact of context on the prioritizing of ethical values when making a decision on physical restraint? A qualitative descriptive study inspired by the Grounded Theory approach was carried out. In total, 21 in-depth interviews were carried out with nurses working on acute geriatric wards in Flanders, Belgium. The research protocol was approved by the Ethics Committee of the Faculty of Medicine, Leuven. Relationships with nursing colleagues and the patient's family form an inter-personal network. Nurses also point to the importance of the procedural-legal context as expressed in an institutional ethics policy and procedures, or through legal requirements concerning physical restraint. Furthermore, the architectural structure of a ward, the availability of materials and alternatives for restraint use can be decisive in nurses' decision-making. All interviewed nurses highlighted the unquestionable role of the practical context of care. Context can have a guiding, supportive, or decisive role in decision-making concerning the application of physical restraint. The discussion focuses on the role of the inter-personal network of nurses on the process of decision-making. An institutional ethics policy and a value-supportive care environment can support nurses in their challenge to take ethically sound decisions.

Assessments of empathy in medical school admissions: what additional evidence is needed?

The Association for the Study of Medical Education (ASME) sponsored a symposium on the theme of Examining the Evidence with Regard to Character, Personality and Values in Medical School Selection which was held on October 14, 2013 at the University of Sheffield Medical School in the United Kingdom. I was invited to speak about credibility issues related to personality assessments in health profession educations. To my pleasant surprise, I found the European audience receptive (more than their counterparts in the United States) to the idea of using personality assessments in admission decisions. There seems to be a hesitation among leaders in medical education in the United States to use personality assessments for selection purposes. They argue that convincing evidence is needed to support using personality assessments in medical school admission. In my presentation, I provided evidence to refute the argument against using personality assessments in admission decisions. Because of our extensive research at Jefferson Medical College on the topic of empathy in medical education and patient care, I placed the emphasis on credibility of evidence for using assessments of empathy, as a personality attribute, in the selection of applicants and professional development of students in any academic health profession institution. The editor of this journal who has a keen interest in medical education issues attended the symposium and suggested that I write an opinion piece about the issue for international audience of the journal. This editorial is based, in part, on my presentation at that symposium. Why is personality relevant to medical school admissions? There is a consensus among behavioral and social scholars that personality plays an unquestionable role in human behavior. In the practice of medicine, the importance of personality in professional assessments has been acknowledged in a paradigm of physician performance.1,2 There is a large volume of research in medical education about the contribution of personality to academic achievement, clinical competence, and specialty interest of doctors-in-training and in-practice.3 The notion that personality is a contributing factor to academic achievement, clinical competence, career choice, and professional behavior implies that personality should be considered as a pertinent measure not only for the assessment of professional development of doctors-in-training, but more importantly as an additional requirement for the admission of qualified applicants to medical schools.

Legal, Safety and Practical Regenerative Braking Control Challenges

The aim of this paper is to describe at a system-level, the development of combined regenerative and friction braking technology with emphasis on control strategies and system complexity. The subject of the study has resulted from prior and current involvement of the Control Theory and Applications Centre (CTAC) and MIRA in research and development activities related to control systems for hybrid/electric vehicles. Regenerative braking plays an unquestionable role in the economic success of hybrid/electric vehicles. Current developments in regenerative braking technology are focused on increasing the regenerative braking operating region beyond the limits of vehicle stability which requires sophisticated control strategies that are suitable for safe vehicle operation. For realisation of continual economic viability with further improvement of the technology, advancement should be focused not only on the development of control strategies but also on the minimum increase of vehicle complexity and thereby minimal additional final cost of the vehicle, that is, by utilisation of standard vehicle components (e.g. driveline components and four-channel anti-lock braking system).

Association of Cytokine Gene Polymorphisms with Oral Lichen Planus in Malayalam-Speaking Ethnicity from South India (Kerala)

Oral lichen planus (OLP) is a chronic mucocutaneous condition that affects the oral mucous membrane as well as skin. It is a chronic cell-mediated autoimmune condition where the T-cell-mediated immune response plays an important part in the pathogenesis by causing damage to basal keratinocytes in oral mucosa. Cytokine gene polymorphisms have an unquestionable role in the orchestration of the immune response, leading to different functional scenarios, which in turn influence the outcome of the disease establishment and evolution. The purpose of this study was to understand the role of these cytokine gene polymorphisms in the tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 genes with OLP in 101 individuals of Malayalam-speaking ethnicity from South India (Kerala). We further investigated the role of these polymorphisms in patients suffering from OLP with other comorbid factors. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism. The results demonstrate that the A allele in the TNF-α -308 polymorphism could play an important role in the susceptibility to OLP. IL-1β +3954 in OLP was associated with other comorbid factors in both allelic and genotypic combinations. However, when patients suffering from OLP were stratified to understand the involvement of other comorbid factors, we observed that the T and C alleles were independent risk factors for chronic periodontitits and diabetes mellitus. On the other hand, IL-6 -597 did not show any disease association with OLP in the study population. This study indicates that proinflammatory cytokines are an important factor in understanding the disease burden of OLP and their comorbid factors.

The Power of Rumours in the Making of History: The Case of the Adana Incident of 1909 in the Ottoman Empire

The Adana Incident of 1909 is one of the local events of the Armeno-Muslim relations during the final decades of the history of the Ottoman Empire. A good amount of works has been hitherto done by the historians of the Middle East about the communal conflict in Adana in April 1909. Historians have so far heavily focused on the political, economic and social dimensions and/or reasons of the conflict. In spite of the proliferation of writings, however, very few have touched upon the power of rumours in the escalation of violence between the two communities. Indeed, my work on the archival sources of the incident have produced enormous documentation which indicate that the rumours circulated around the city had played unquestionable role in building distrust between the peoples and led to the rise of numerous conspiracy theories. According to one rumour the Armenians were organizing themselves against the Muslims in order to separate from the Empire. Another rumour was that a group of Armenian rebels were about to attack Muslim villages around the city, which stirred up the fears of Muslims. There were also rumours circulating among the Muslim community that Armenians had dug up an underground tunnel in order to reach the weapons depot, which was to aid them in their quest for independence. One major rumour was that Armenians placed human faeces at the door of the Great Mosque. Indeed it was through such rumours that suspicions were piqued and people sought to acquire weapons as a means of protecting themselves. Thus when the killings began on April 14, 1909 in Adana, people attacked each other under the influence of the psychology built by such rumours. Therefore I am of the opinion that it is important to deal with rumour and its affinity to communal violence in history. In this paper an attempt will be made to analyse the role of rumours in the events that unfolded in Adana in April 1909.

Why ordinary people comply with environmental laws: A structural model on normative and attitudinal determinants of illegal anti-ecological behaviour

Purpose. The aim of this study is to propose and test a comprehensive model of compliance with environmental law (EL). The legal and psychosocial peculiarities of environmental transgressions suggest that the nature and relative impact of the determinants of ordinary people's compliance with EL may differ from those involved in compliance with ordinary laws. Method. A total of 439 university students of Law, Psychology, Pedagogy, and Speech Therapy majors, aged between 18 and 58, took part in the study. Participants answered a questionnaire assessing illegal anti-ecological behaviour (IAEB), legal-sanction-related variables, injunctive and prescriptive social norms, personal norms, and sustainability attitudes. The data from all participants were processed using structural equation analysis to test the hypothesized model. Results. The main antecedents of IAEB are personal norms and, to a lesser extent, sustainability attitudes and descriptive social norms. Personal norms on IAEB are influenced by injunctive social norms and also by sustainability attitudes. Legal-sanction-related variables affect personal norms and IAEB, but only by indirectly influencing social norms. Conclusions. Although legal-sanction-related variables and norms have been traditionally used to explain illegal behaviour, the legal and psychosocial peculiarities of IAEB are reflected in the process of compliance with environmental protection laws. Results allow for a refinement of the relationship between personal and social norms, showing that the main determinants of IAEB is personal norm, but that descriptive social norms also directly affect behaviour, and that sustainability attitudes play an unquestionable role in compliance with ELs.

Avaliação das Alterações Hemodinâmicas em Pacientes com Diagnóstico de Doença de Buerger

Buerger's disease or thromboangiitis obliterans (TAO) is a vascular disease characterized by vascular and segmental occlusion of small and medium-sized arteries of the extremities, caused by an inflammatory and thrombotic phenomena. The aim of this study was to evaluate functionally the hemodynamic consequences of this disease and its main arterial vascular changes. A retrospective clinical study was conducted with a sample of 100 patients diagnosed with TAO, who underwent to follow-up appointments every two years for peripheral arterial doppler, plethysmography and ankle-brachial index (ABI) at the Department of Angiology and Vascular Surgery of the Hospital de São João in Porto. To conduct the study, the last hemodynamic evaluation of each patient was selected between 2004 and 2010. It was observed that tobacco has an unquestionable role in TAO, both in the rate of limb amputations (p = 0.006) and ABI values, with significant differences between non-smokers and groups of former and current smokers. Monophasic flow patterns are associated with low resistance spectrum and lower ABI values when compared to biphasic and triphasic flow patterns (p < 0.001). Normal ABI have a lower prevalence of collateral arteries associated in the right (p = 0.005) and left limbs (p = 0.032). The clinical manifestations of peripheral vascular disease characteristic of TAO were reflected hemodynamically with monophasic low-resistance patterns associated with altered ABI values. Tobacco has an important role in the vascular blood flow, determinating high rates of amputation and low ABI values.

Potentiating exercise training with resveratrol

Potentiating exercise training with resveratrol

Who Trusts Berlusconi? An Econometric Analysis of the Role of Television in the Political Arena

SummaryThe objective of this paper is to improve our understanding on how the former Italian prime minister formed and kept his exceptional political consensus despite the never‐ending series of scandals in which he has been involved. Specifically, we carry out an empirical assessment of the relationship between trust in television and trust towards the prime minister. Many Italian commentators argue that television does not exert any particular bias on public opinion. If the assumption of television's irrelevance were true, one could reasonably expect to find no significant relationship between trust in TV and trust in Mr Berlusconi as prime minister. Contrary to this hypothesis, our empirical analysis shows that trust in television was the strongest predictor of trust in the Italian prime minister in Spring 2011, thus suggesting that Mr Berlusconi's media empire played a key role in the building of his political consensus.This result is based on probit and ordered logit estimates and is robust to different specifications. However, there are three reasons for which this finding could be interpreted as the fruit of a spurious correlation. First, it is difficult to distinguish the effect of trust in television from that of other phenomena that potentially influence trust in the prime minister. To deal with this problem, we include in the main equation a wide set of individual and household control variables. Second, individual effects, such as individuals' exogenous shocks, may be correlated with trust both towards television and the prime minister, thus creating a common bias. Third, as we explain in the paper, it is reasonable to assume the existence of reverse causality. To deal with the last two problems, we turn to instrumental variables (IV) estimates. When we address endogeneity in IV estimates, trust in television remains the best (most significant and strongest) predictor of trust in the prime minister. By contrast, we find that the dependent variable is significantly and negatively correlated with educational qualification, trust in the judicial system and with a measure of tolerance towards immigrants.Even if these results pass robustness checks and hold in IV estimates, it must be remarked that the cross‐sectional design of the research dictates extreme caution in the interpretation of correlations as causal relationships. Nonetheless, the paper contributes to the literature by carrying out the first econometric investigation into the role of television in individuals' political opinions, with a focus on trust towards the Italian prime minister. The relationship between television and political attitudes and beliefs is an important topic for economics, in view of the unquestionable role that political institutions, particularly the government and the prime minister, play in a country's economic performance.

Application of spectroscopic techniques: ICP-OES, LA-ICP-MS and chemometric methods for studying the relationships between trace elements in clinical samples from patients with atherosclerosis obliterans

The study was aimed to evaluate the influence of the vascular disease, atherosclerotic obliterans (AO), on the location and concentration of elements in the arterial wall and serum. Use of a modern method for studying element’s concentration and distribution in samples of clinical material, i.e. laser ablation inductively coupled plasma mass spectrometry, is presented. Elements are not equally distributed between the inner (intima) and the outer (media + adventitia) layer of the arterial wall. Among the studied elements, calcium was found to have an unquestionable role in the calcification of the wall. Increased concentration of calcium found in the inner part of the atherosclerotic arterial wall and in the plaque, as compared to the control arterial wall samples, demonstrates the unquestionable role of this element in the calcification of the wall observed in AO. Applied chemometric methods were useful for demonstrating the differences in the element’s concentration in blood serum and the arterial wall samples between AO and the control group. FigureImage of the ruptured atherosclerotic plaque done while surgery

Water deficit affects photosynthetic induction in Bauhinia forficata Link (Fabaceae) and Esenbeckia leiocarpa Engl. (Rutaceae) growing in understorey and gap conditions

In tropical forests, light is considered the most limiting resource for plant growth and reproduction. Besides light, water deficit leads invariably to a decrease in photosynthesis. Thus, despite of the unquestionable role of light in CO2 assimilation (A), it is expected that water deficit affects and limits the light utilization by plants. In this study, we investigated how water deficit influenced the photosynthetic induction of the early successional tree Bauhinia forficata (Fabaceae) and the late successional Esenbeckia leiocarpa (Rutaceae) in the understorey and in the forest gap. Field measurements were carried out in June and August 2006 in plants of approximately two-years-old. In August, the plants were subjected to a period of 45 d without rain characterizing a water deficit situation. Leaf water potential was significantly lower in August, both in forest gap and understorey (-2.5 and -3.8 MPa, respectively), than in June (-0.6 and -1.6 MPa, respectively). In June, both species presented a rapid increase in A after a saturating light pulse under gap conditions. However, in the understorey the increase in A was slower in B. forficata than in E. leiocarpa. In August water deficit limited the increase in Amax in both species, indicating that potential utilization of increasing irradiance was reduced by water deficit conditions. The constrain in Amax was less pronounced in the understorey where plants at least reached the irradiance compensation point, whereas carbon gain by photosynthesis of the plants grown in the gap did not compensate the carbon loss by respiration.

Littoral invertebrates associated with aquatic plants and bioassessment of ecological status in Lake Bracciano (Central Italy)

Lake Bracciano is a large and deep volcanic lake which plays an unquestionable role for drawing water source and for fishing and recreational activities. The existence of a project aimed at increasing the amount of water drawn from the lake suggested the advisability of undertaking an ecological analysis of the invertebrate community associated with aquatic plants in order to obtain a detailed knowledge of its composition, biodiversity and quantitative structure, and to provide a set of basic and essential information for defining the ecological status in the littoral zone and for future bioassessments in the lake ecosystem. A good water quality, approaching oligotrophy, was evidenced both from data on aquatic vegetation, which showed the extensive colonization of Charales (down to a depth of about 20 m), and from faunal parameters such as high species richness and diversity values, presence and abundance of bioindicator taxa (mainly cladocerans and gastropods), abundances of total fauna. Nevertheless, a considerable disappearance of the reed thicket due to the intense shore management for recreational purposes have negatively influenced the colonization of the more shallow and productive waters, so evidencing a negative trend of the littoral quality.