TIM3 is a context-dependent coregulator of cytotoxic T cell function

Cytotoxic T lymphocytes (CTLs) are essential effectors in the antiviral and antitumour immune response and attractive targets in cancer immunotherapy. Although CTLs can directly recognise and kill tumour cells, CTLs become suppressed in the tumour microenvironment. This project investigated the inhibitory receptor T cell immunoglobulin and mucin domain 3 (TIM3). TIM3 is expressed on T cells after chronic antigen exposure and marks the most exhausted tumour infiltrating CTLs in multiple solid tumours. However, it is unclear whether TIM3 directly regulates CTL function. In addition, despite its predominantly inhibitory role in vivo, TIM3 can promote cellular activation in T and non-T cells, and the roles of putative ligands in TIM3 function are disputed. Therefore, we aimed to determine the effect of TIM3 on direct CTL antitumour function and how the TIM3 ligands Galectin9 (GAL9) and CEACAM1 regulate its function. We employed three-dimensional (3D) tumour spheroids that effectively induce CTL suppression similar to the in vivo tumour microenvironment in comparison to conventional two-dimensional (2D) tumour cell culture. In the 3D spheroid model, TIM3 significantly inhibited CTL cytotoxicity and cytoskeletal polarisation as a key mechanism of effective cytolysis in murine and human CTLs. In contrast, in the 2D tumour model, TIM3 stimulated CTL cytotoxicity, cytoskeletal polarisation, and secretion of the immune-stimulatory cytokine interferon γ (IFNγ). Expression of GAL9 and CEACAM1 in trans on tumour cells further suppressed the CTL killing ability in the 3D spheroid model and enhanced costimulatory function in 2D. CEACAM1 in cis neutralised TIM3 functions in both 3D and 2D. We suggest that TIM3 functions as a context-dependent coregulatory receptor, as supported by the engagement of its ligands GAL9 and CEACAM1. In a largely stimulatory signalling context of a CTL, TIM3 functions as a costimulator, and in a more inhibitory context, TIM3 functions as a coinhibitor

Amman’s Facades Lost between Identity and Veracity; Factors Impacting Facades’ Design

Today`s building façades continuously lose connection to their local identities and contextual surroundings, more attention is required when designing façades in order to come up with designs that synergize with  their unique surroundings. This does not imply that building façades should be approached in a typical traditional manner, but rather that their design should be a result of different factors, interacting and overlapping, and in respect to the physical and non-physical context.  Façades should be designed in respect to high performance, aesthetics and efficient constructability for example, and this in return indicates that variations in façade designs are a positive indication that buildings are responding to their built and natural contexts. Architects and designers should respond to side effects of globalization resulting in the spreading of out of context styles, unresponsive and kitschy, in order to save the visual interest in the city and the beyond  physical meaning of architecture. It is advised here that architects and designers articulate the very meaning of modernity within local architecture and environment. This article tries to discuss various factors impacting façade design generally, relating discussions to the current situation Amman, the metropolis, and its buildings are undergoing. Keywords: Façade design, contemporary façade, local identity, Amman

Regional Planning in Jordan, the Status Quo - Regional Planning in the Jordan Rift Valley

This paper is intended to examine and research a new way of planning on the Jordanian ground, regional planning, a planning approach proven to be highly effective globally on multiple levels but unfortunately not widely practiced in the Arab World. This research paper tries to examine how the area of the Jordan Valley is being administered regionally, and attempts to breakdown and discuss the different elements of this process in a critical manner. Outcomes of the reserch indicate mainly that although this planning approach is implicated to a certain degree; still it is seen as being more sectoral in nature. Keywords: Jordan Rift Valley, Regional Planning, Dead Sea, Master Plan, Sustainability

Efficient and Strategic Resource Allocation for Sustainable Development in Jordan

This research addresses a modern-day major topic; sustainability, and although it is in fact a very vast and wide topic and on every tongue at current times, some aspects of it seem to be left with little exploration in comparison to the other aspects, such as resource allocation. Mainly, this research will go into the importance of resource allocation for sustainable development, with emphasis on infrastructure, financial, human and information resources, and it will address topic related questions, questions like: how much effect has resource allocation on sustainable place promotion? And is it possible to allocate resources on the basis of any priority structure? And most of all, what can we do in Jordan to improve allocation of resources to achieve the desired integrated and long term development. The results basically highlight incorporating the public for achieving equitable resource allocation, and its dependence on concepts of having a priority system not hierarchy for the process of allocation, planning with objectives and introducing new adaptable global concepts to alleviate the current resource allocation condition in Jordan.This research basically recommends that resources should be allocated according to the priorities and objectives concept, objectives that are predetermined and integrated with a holistic vision of how development should be in a certain area, facilitated by a proper national agenda. Also, these priorities and objectives should always be determined according to the locals in the concerned area, and in a way that is environmentally considerate, socially integrated and economically strengthening. Keywords: External and Internal Resources, Decentralization, Community Involvement, Resource Allocation According to Priorities, Accountability, Equally Shared benefits

Effects of precompetition state anxiety interventions on performance time and accuracy among amateur soccer players: Revisiting the matching hypothesis

In this study, we tested the matching ypothesis, which contends that administration of a cognitive or somatic anxiety intervention should be matched to a participant's dominant anxiety response. Sixty-one male soccer players (mean age 31.6 years, s=6.3) were assigned to one of four groups based on their responses to the Competitive State Anxiety Inventory-2, which was modified to include a directional scale. Interventions were randomly administered in a counterbalanced order 10 min before each performance trial on a soccer skill test. The dominantly cognitive anxious group (n=17), the dominantly somatic anxious group (n=17), and the non-anxious control intervention group (n=14) completed a baseline performance trial. The second and third trials were completed with random administration of brief cognitive and somatic interventions. The non-anxious control group (n=13) completed three trials with no intervention. A mixed-model, GroupTreatment multivariate analysis of variance indicated significant (P0.05), or performance time or accuracy (P>0.05). The present findings do not provide support for the matching hypothesis for state anxiety intensity and direction, or for performance

Implementing the Five-A Model of technical refinement: Key roles of the sport psychologist

There is increasing evidence for the significant contribution provided by sport psychologists within applied coaching environments. However, this rarely considers their skills/knowledge being applied when refining athletes’ already learned and well-established motor skills. Therefore, this paper focuses on how a sport psychologist might assist a coach and athlete to implement long-term permanent and pressure proof refinements. It highlights key contributions at each stage of the Five-A Model—designed to deliver these important outcomes—providing both psychomotor and psychosocial input to the support delivery. By employing these recommendations, sport psychologists can make multiple positive contributions to completion of this challenging task

In Vitro Interaction of Lithium on Phospholipids in Human Erythrocytes

Lithium salts are used in the treatment of mania and as prophylaxis against manic depressive disorder. The aim of these studies was the in vitro investigation of the effect of lithium on phospholipids of human erythrocyte membranes. Erythrocytes were treated with lithium for 1 h. Phospholipids phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylocholine (PC) were separated from erythrocyte ghosts and determined by HPLC. Blood samples from healthy adults were investigated. A very strong decrease in PC content in erythrocyte membranes due to lithium in vitro treatment was found, as well as a statistically significant increase in PI content

Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2

The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19

Interactive effects of video, priming, and music on emotions and the needs underlying intrinsic motivation

Objectives: Emotions can enhance motivation towards a particular goal (Brehm, 1999), while activation of human motivation does not necessarily involve conscious processes (Bargh, 1990). The main purpose of the present study was to explore the impact of video, priming, and music on a range of emotion- and motivation-related variables, while the secondary purpose was to conduct a cross-cultural comparison. Design: A randomized controlled design was employed to address the interactive effects of video, priming, and music on emotions and motivation with reference to the circumplex theory of emotion. Methods: Participants comprised a convenience sample of 210 volunteers (English, n = 128; M = 20.0, SD = 4.7 years; Male, n = 65; Female, n = 63; Greek, n = 82, M = 23.3, SD = 2.4 years; Male, n = 59; Female, n = 23). A control condition and five experimental conditions were presented to participants in a counterbalanced order. The needs underlying intrinsic motivation were accessed using the Activity Feeling-state Scales (AFS; Reeve & Sickenius, 1994), while emotional states were assessed using adjectives from the Circumplex Model of Affect (Russell, 1980). Results: Findings showed that music had positive effects on emotional states and the psychological needs underlying intrinsic motivation. They also highlighted the positive effects of priming as a psychological intervention – particularly when presented through video and coupled with music. Conclusions: The study presents the state-of-the-art for the use of video, priming, and music in sport and includes recommendations for sport psychology practitioners and researchers