Possibilities and Pitfalls of Social Media for Translational Medicine

We live in an age where the sharing of scientific findings and ideas is no longer confined to people with access to academic libraries or scientific journals. Social media have permitted for knowledge and ideas to be shared with an unprecedented speed and magnitude. This has made it possible for research findings to have a greater impact and to be rapidly implemented in society. However, the spread of unfiltered, unreferenced, and non-peer-reviewed articles through social media comes with dangers as well. In this perspective article, we aim to address both the possibilities and pitfalls of social media for translational medicine. We describe how social media can be used for patient engagement, publicity, transparency, sharing of knowledge, and implementing findings in society. Moreover, we warn about the potential pitfalls of social media, which can cause research to be misinterpreted and false beliefs to be spread. We conclude by giving advice on how social media can be harnessed to combat the pitfalls and provide a new avenue for community engagement in translational medicine

Translational Medicine in the Era of Social Media: A Survey of Scientific and Clinical Communities

Background: The integration of new scientific discoveries into clinical practice costs considerable time and resources. With the increased use of social media for scientific communication, new opportunities arise to "bridge the gap" in translational medicine. The present study aimed to investigate how medical professionals access scientific information and understand their view on the role of social media in translational medicine. Methods: A questionnaire regarding (i) the use of social media for scientific updates, (ii) the opportunities and challenges of social media for translational medicine, (iii) social media function Chatbot, and (iv) participant demographics was developed. The survey link was posted online from February, 2018, until April, 2018. Results: A total of 555 professionals responded to the survey. Respondents identified themselves predominantly as researcher/scientists (27%) or medical/biomedical students (15%). The majority of participants was employed at a university or research institute (59%), and most practiced either in Europe (48%) or in Asia (37%). Seventy-eight percent of respondents reported receiving most of scientific news and updates via non-social media options, such as journal websites and newspapers. Fifty-one percent of respondents believed that social media could contribute to closing the gap between scientific discovery and translation to medical application. The most crucial opportunity created by social media was found to be "connecting the right scientist to the right clinician." Participants rated "the translation of scientific finding to clinical practice is too fast before the safety is properly demonstrated" as the most crucial challenge. Half of the respondents were aware of their institutions policy on the professional use of social media. Only 2% of respondents had previously used Chatbot. Conclusions: Overall, medical professionals were positive about the idea that social media could contribute to the progress of translational medicine. However, it is clear that they are still being cautious about using social media for professional purposes. To fully harness the potential of social media on translational medicine, the medical community needs to be provided with educational programs, guidelines, and support infrastructure within social media.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Epstein-Barr virus encoded nuclear protein EBNA-3 binds a novel human uridine kinase/uracil phosphoribosyltransferase

BACKGROUND: Epstein-Barr virus (EBV) infects resting B-lymphocytes and transforms them into immortal proliferating lymphoblastoid cell lines (LCLs) in vitro. The transformed immunoblasts may grow up as immunoblastic lymphomas in immuno-suppressed hosts. RESULTS: In order to identify cellular protein targets that may be involved in Epstein-Barr virus mediated B-cell transformation, human LCL cDNA library was screened with one of the transformation associated nuclear antigens, EBNA-3 (also called EBNA-3A), using the yeast two-hybrid system. A clone encoding a fragment of a novel human protein was isolated (clone 538). The interaction was confirmed using in vitro binding assays. A full-length cDNA clone (F538) was isolated. Sequence alignment with known proteins and 3D structure predictions suggest that F538 is a novel human uridine kinase/uracil phosphoribosyltransferase. The GFP-F538 fluorescent fusion protein showed a preferentially cytoplasmic distribution but translocated to the nucleus upon co-expression of EBNA-3. A naturally occurring splice variant of F538, that lacks the C-terminal uracil phosphoribosyltransferase part but maintain uridine kinase domain, did not translocate to the nucleus in the presence of EBNA3. Antibody that was raised against the bacterially produced GST-538 protein showed cytoplasmic staining in EBV negative Burkitt lymphomas but gave a predominantly nuclear staining in EBV positive LCL-s and stable transfected cells expressing EBNA-3. CONCLUSION: We suggest that EBNA-3 by direct protein-potein interaction induces the nuclear accumulation of a novel enzyme, that is part of the ribonucleotide salvage pathway. Increased intranuclear levels of UK/UPRT may contribute to the metabolic build-up that is needed for blast transformation and rapid proliferation

MICA-129 dimorphism and soluble MICA are associated with the progression of multiple myeloma

Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms. Soluble MICA (sMICA) is overexpressed in the serum of MM patients, and its levels correlate with tumor progression. Interestingly, a methionine (Met) to valine (Val) substitution at position 129 of the α2 heavy chain domain classifies the MICA alleles into strong (MICA-129Met) and weak (MICA-129Val) binders to NKG2D receptor. We addressed whether the genetic polymorphisms in the MICA-129 alleles could affect MICA release during MM progression. The frequencies of Val/Val, Val/Met, and Met/Met MICA-129 genotypes in a cohort of 137 MM patients were 36, 43, and 22%, respectively. Interestingly, patients characterized by a Val/Val genotype exhibited the highest levels of sMICA in the sera. In addition, analysis of the frequencies of MICA-129 genotypes among different MM disease states revealed that Val/Val patients had a significant higher frequency of relapse. Interestingly, NKG2D was downmodulated in NK cells derived from MICA-129Met/Met MM patients. Results obtained by structural modeling analysis suggested that the Met to Val dimorphism could affect the capacity of MICA to form an optimal template for NKG2D recognition. In conclusion, our findings indicate that the MICA-129Val/Val variant is associated with significantly higher levels of sMICA and the progression of MM, strongly suggesting that the usage of soluble MICA as prognostic marker has to be definitely combined with the patient MICA genotype

Contribution of Herpesvirus Specific CD8 T Cells to Anti-Viral T Cell Response in Humans

Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza) pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR), proliferation (Ki-67/Bcl-2low) and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV). CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza) were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-γ during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response

Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study was supported by a Grant core funding from the Agency for Science Technology and Research (A*STAR, Singapore) and a Singapore Translational Research Investigator Award (NRMC/StaR/013/2012) to AB as well as NIHR Biomedical Centre, Oxford, WT 091663MA, NIAID1U19AI082630-01, Oxford Martin School funding and an NIHR Senior Investigator award to PK

Regulation of the pro-apoptotic protein Bim by T cell receptor triggering in human T cells

Bim is a significant pro-apoptotic member of Bcl-2 family of proteins; it is proved to be an important regulator of apoptosis: over the years it has been shown to play a pivotal role for the development and maintenance of homeostasis in many cellular systems and tissues. The Bcl-2 family of proteins is a group of key regulators of the mitochondrial, or intrinsic, pathway of apoptosis. It contains anti-apoptotic proteins, which promote cell survival, and pro-apoptotic ones, which induce cell death through the release of apoptotic factors from mitochondria. Proteins of the subfamily of BH-3 only proteins, which includes Bim, are important regulators of this process. Bim, as well as Bid were shown to bind the majority of anti-apoptotic and proapoptotic Bcl-2 family members and are believed to induce oligomerization of Bax and Bak proteins, which results in the outer membrane permeabilization and release of pro-apoptotic factors initiating cell death. In spite of its importance for different aspects of T-cell biology, regulation of Bim expression and activity by T-cell receptor (TCR) triggering is poorly understood. The focus of this work was to analyze how different modes of TCR-triggering affect Bim expression in human T-cells at different stages of their differentiation with particular emphasis on effector CD8+ cytotoxic T-lymphocytes (CTLs). We showed that expression of Bim is upregulated in activated antigen-specific human CTLs upon polyclonal or specific TCR triggering. Both activation of protein kinase C and induction of calcium influx appear to be necessary and sufficient for Bim upregulation after TCR-ligation. We also showed that Bim expression is differentially regulated by MHC:peptide ligands of different agonistic potency. Ligands which failed to induce Bim expression, failed to induce apoptosis, while induction of Bim accompanied by inefficient upregulation of Bcl-XL was associated with death receptor-independent activation induced cell death (AICD) triggered by partially agonistic ligands in specific CTLs. Cyclosporine A blocked Bim upregulation and rescued CTLs from death receptor independent AICD while rapamycin did not exhibit these activities, in accordance with known effects of the drugs on T-cell deletion in transplant recipients. These results defined a new pathway of Bim regulation, strongly implicated Bim as a mediator of AICD and suggested that Bim upregulation can be targeted to influence the outcome of specific immune responses. We also investigated in more detail the regulation of altered peptide ligands (APL) activity by immunologic help. We analyzed the capacity of exogenous IL-2 and IL-15, which are physiologically produced by cells of the adaptive and innate immune system, respectively, to modulate proliferation, responsiveness to repeated stimulation and apoptotic programs triggered in specific CTL by either fully or partially agonistic peptide ligands. We show that signals induced by the lymphokines synergize with weak TCR signaling induced by partially agonistic APL, converting many of these peptides from inhibitory to stimulatory ligands. Some APL partially suppress the responsiveness of specific CTL to secondary stimulation, while this inhibitory effect is diminished if APLstimulated cells are cultured in the presence of either of the lymphokines. We also demonstrate that IL-2 and IL-15 suppress up-regulation of Bim and induction of a death receptor-independent apoptotic program triggered by partially agonistic APL. Our results suggest that under conditions of insufficient immunologic help, partially agonistic APL may actively suppress specific CTL responses and become especially advantageous for immune escape of tumors or viruses. We analyzed the expression of Bim in total peripheral blood lymphocytes (PBLs) and different subpopulations of ex vivo isolated human T-lymphocytes from healthy donors or patients with infectious mononucleosis. We showed that the majority of freshly isolated PBLs express relatively low levels of Bim, which are not modulated by TCRcrosslinking. However, TCR triggering induced significant Bim upregulation in some PBL samples. Longitudinal analysis demonstrated that responsiveness to TCR triggering, as revealed by Bim upregulation, varies over time in PBLs isolated from the same individual. Memory or naive T-cells enriched on the basis of CD45RO or CD45RA expression did not differ in their capacity to upregulate Bim in response to receptor crosslinking and were comparable, in this respect, to freshly isolated total lymphocytes. In contrast, lymphocytes isolated from patients with acute stage IM containing characteristic massive expansions of antigenspecific effector CD8+ T-cells expressed increased levels of Bim, which could not be accounted for by increased proportion of CD8+ cells. Moreover, lymphocytes from at least half of the analyzed IM patients exhibited strong upregulation of all major Bim isoforms in response to TCR triggering. These results support the notion that the activity of Bim in human CD8+ T-cells is regulated at the level of protein expression and the regulation of Bim promoter changes along with the process of Tlymphocyte differentiation enabling them to respond to TCR triggering by Bim upregulation. Our data support an important role of Bim in the regulation of T-cell homeostasis and T-cell mediated immunity and suggest that interference with TCR induced Bim upregulation may affect the outcome of natural immune responses, vaccination, autoimmunity and development of transplant tolerance

Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

10.1155/2016/6958293Mediators of Inflammation20161-1

Potential Use of Salivary Markers for Longitudinal Monitoring of Inflammatory Immune Responses to Vaccination

Vaccination, designed to trigger a protective immune response against infection, is a trigger for mild inflammatory responses. Vaccination studies can address the question of inflammation initiation, levels, and resolution as well as its regulation for respective studied pathogens. Such studies largely based on analyzing the blood components including specific antibodies and cytokines were usually constrained by number of participants and volume of collected blood sample. Hence, blood-based studies may not be able to cover the full dynamic range of inflammation responses induced by vaccination. In this review, the potential of using saliva in addition to blood for studying the kinetics of inflammatory response studies was assessed. Saliva sampling is noninvasive and has a great potential to be used for studies aimed at analysing the magnitude, time course, and variance in immune responses, including inflammation after vaccination. Based on a literature survey of inflammatory biomarkers that can be determined in saliva and an analysis of how these biomarkers could help to understand the mechanisms and dynamics of immune reactivity and inflammation, we propose that the saliva-based approach might have potential to add substantial value to clinical studies, particularly in vulnerable populations such as infants, toddlers, and ill individuals

Role of Cellular Immunity in Cow's Milk Allergy: Pathogenesis, Tolerance Induction, and Beyond

Food allergy is an aberrant immune-mediated reaction against harmless food substances, such as cow's milk proteins. Due to its very early introduction, cow's milk allergy is one of the earliest and most common food allergies. For this reason cow's milk allergy can be recognized as one of the first indications of an aberrant inflammatory response in early life. Classically, cow's milk allergy, as is true for most other allergies as well, is primarily associated with abnormal humoral immune responses, that is, elevation of specific immunoglobulin E levels. There is growing evidence indicating that cellular components of both innate and adaptive immunity play significant roles during the pathogenesis of cow's milk allergy. This is true for the initiation of the allergic phenotype (stimulation and skewing towards sensitization), development and outgrowth of the allergic disease. This review discusses findings pertaining to roles of cellular immunity in allergic inflammation, and tolerance induction against cow's milk proteins. In addition, a possible interaction between immune mechanisms underlying cow's milk allergy and other types of inflammation (infections and noncommunicable diseases) is discussed