Miracle-dz/UniFAR-FTUs huggingface dataset:
Larval Echinococcus multilocularis infection reduces dextran sulphate sodium‐induced colitis in mice by attenuating T helper type 1/type 17‐mediated immune reactions

The tumour‐like growth of larval Echinococcus multilocularis tissue (causing alveolar echinococcosis, AE) is directly linked to the nature/orientation of the periparasitic host immune‐mediated processes. Parasite‐mediated immune suppression is a hallmark triggering infection outcome in both chronic human and murine AE. So far, little is known about secondary systemic immune effects of this pathogen on other concomitant diseases, e.g. endogenous gut inflammation. We examined the influence of E. multilocularis infection on murine dextran sodium sulphate (DSS) ‐induced colitis. At 3 months after E. multilocularis infection (chronic stage), the mice were challenged with 3% DSS in the drinking water for 5 days plus subsequently with tap water (alone) for another 4 days. After necropsy, fixed tissues/organs were sectioned and stained with haematoxylin & eosin for assessing inflammatory reactions. Cytokine levels were measured by flow cytometry and quantitative RT‐PCR. Colitis severity was assessed (by board‐certified veterinary pathologists) regarding (i) colon length, (ii) weight loss and (iii) a semi‐quantitative score of morphological changes. The histopathological analysis of the colon showed a significant reduction of DSS‐induced gut inflammation by concomitant E. multilocularis infection, which correlated with down‐regulation of T helper type 1 (Th1)/Th17 T‐cell responses in the colon tissue. Echinococcus multilocularis infection markedly reduced the severity of DSS‐induced gut inflammation upon down‐regulation of Th1/Th17 cytokine expression and attenuation of CD11b+ cell activation. In conclusion, E. multilocularis infection remarkably reduces DSS‐induced colitis in mice by attenuating Th1/Th17‐mediated immune reactions.
Endocarditis infecciosa sobre válvula tricúspide sin factores predisponentes asociados: a propósito de un caso

Summary Infective endocarditis on a normal triscuspid valve in children without pathology constitute a rare disease with a difficult diagnosis but with an increasing incidence in the last decades. A clinical case of an eleven year old child without predisposing factors for endocarditis, in whom the diagnosis of Staphylococcus aureus infective ebdocarditis on tricuspid valve complicated with pulmonary septic emboli is presented. Conservative surgical treatment in the active phase of the disease was necessary because of the recurrent episodes of pulmonary emboli clinically evident and because of the ecocardiographic features suggesting high probability of new embolic events and failure of the antibiotic treatment.
Price modeling of imported natural gas in Turkey

The Turkish manufacturing sector has become the dynamo of the economy, driven by imported natural gas. However, the country's dependency on imported energy has also increased vulnerability of the country to the specter of unexpected supply shocks, and hence the long-term sustainability of industrialization. Thanks to long-term contracts which provide relatively cheap imports of natural gas, Turkey has sufficient “breathing space” to develop alternative energy sources. In the meantime, the country must adopt a rational pricing policy for imported natural gas to ensure allocative efficiency. Accordingly, this paper offers an econometric “gas-price-growth” model which reveals that long-run equilibrium relationship exists between each pair of variables such as natural gas prices, crude oil prices, taxes on gas and real exchange rates. Rapid changes in capital markets and possible risks associated with high inflation may increase future prices of natural gas in Turkey. Furthermore, this study revealed the exis.
Piecing together the family portrait of TCR‐CD3 complexes

The pre‐T‐cell receptor (TCR)‐, αβTCR‐, and γδTCR‐CD3 complexes are members of a family of modular biosensors that are responsible for driving T‐cell development, activation, and effector functions. They inform essential checkpoint decisions by relaying key information from their ligand‐binding modules (TCRs) to their signaling modules (CD3γε + CD3δε and CD3ζζ) and on to the intracellular signaling apparatus. Their actions shape the T‐cell repertoire, as well as T‐cell‐mediated immunity; yet, the mechanisms that underlie their activity remain an enigma. As with any molecular machine, understanding how they function depends upon understanding how their parts fit and work together. In the 30 years since the initial biochemical and genetic characterizations of the αβTCR, the structure and function of the individual components of these family members have been extensively characterized. Cumulatively, this information has allowed us to piece together a portrait of the αβTCR‐CD3 complex and outline the form of the remaining family members. Here we review the known structural and functional characteristics of the components of these TCR‐CD3 complex family members. We then discuss how these data have informed our understanding of the architecture of the αβTCR‐CD3 complex as well as their implications for the other family members. The intent is to provide a framework for considering: (i) how these thematically similar complexes diverge to execute their specific functions and (ii) how our knowledge of the form and function of these distinct family members can cross‐inform our understanding of the other family members.
RNA‐based mechanisms regulating host–virus interactions

RNA interference (RNAi) is an ancient process by which non‐coding RNAs regulate gene expression in a sequence‐specific manner. The core components of RNAi are small regulatory RNAs, approximately 21–30 nucleotides in length, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). The past two decades have seen considerable progress in our understanding of the molecular mechanisms underlying the biogenesis of siRNAs and miRNAs. Recent advances have also revealed the crucial regulatory roles played by small RNAs in such diverse processes as development, homeostasis, innate immunity, and oncogenesis. Accumulating evidence indicates that RNAi initially evolved as a host defense mechanism against viruses and transposons. The ability of the host small RNA biogenesis machinery to recognize viral double‐stranded RNA replication intermediates and transposon transcripts is critical to this process, as is small RNA‐guided targeting of RNAs via complementary base pairing. Collectively, these properties confer unparalleled specificity and precision to RNAi‐mediated gene silencing as an effective antiviral mechanism.
Increasing multicultural competence

This is a highly practical handbook aimed specifically at medical and health care professionals. The book begins with an overview of the main issues of counselling and communication looking also at the importance of self-care from both a personal and organizational perspective. Basic counselling and communication skills are followed by their application to specialised settings including sexual health, child health, infertility and rehabilitation.
The effectiveness of manipulation of the subtalar joint combined with static stretching of the triceps surae muscles compared to manipulation alone in the treatment of Plantar Fasciitis

Plantar Fasciitis (PF) is a common injury, and one which is known to be stubborn to many forms of treatment. The purpose of this investigation was to determine the effectiveness of manipulation of the subtalar joint combined with static stretching of the Triceps Surae muscles compared to manipulation alone in the treatment of PF. Studies have shown chiropractic manipulation to be effective in treating this overuse injury, and gastro-soleus stretching is a treatment advocated by many authors, but which has not yet been investigated in combination with manipulation. This study consisted of 40 patients who were randomly divided into two equal groups. Group One received manipulation to restrictions in the subtalar joint, and Group Two received subtalar manipulation in addition to two static stretched of the gastro-soleus muscles.
Interferon induction and function at the mucosal surface

Interferons (IFNs) are produced in response to virus infection and induce an antiviral state in virtually all cell types. In addition to upregulating the transcription of genes that inhibit virus replication, type I (or ‐α/β) IFNs also act to orchestrate the adaptive immune response to virus infection. Recently a new family of antiviral cytokines, the type III (or ‐λ) IFNs, has been identified that activate the same antiviral pathways via a distinct receptor. Although the identical transcription factor, IFN‐stimulated gene factor 3 is activated by either IFN‐α/β or IFN‐λ signaling, differences in the induction and action of these two cytokine families are beginning to be appreciated. In this article, we review this emerging body of literature on the differing roles these cytokines play in host defense of the mucosal surface. Although many viruses enter the body through the respiratory and gastrointestinal tracts, we have focused the discussion on influenza A virus, respiratory syncytial virus, and rotavirus, three ubiquitous human pathogens that target the epithelial lining and are associated with a major disease burden.
Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma

Adoptive T‐cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo‐engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody‐derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T‐cell therapy by modulating the tumor stroma by a CAR T‐cell‐secreted transgenic cytokine like interleukin‐12 (IL‐12). The basic process is that CAR T cells, when activated by their CAR, deposit IL‐12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine‐mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials.
Transplantation tolerance: from theory to clinic

Tolerance induction and alloreactivity can be applied to the clinic for the transplantation of solid organs and in the treatment of human cancers respectively. Hematopoietic chimerism, the stable coexistence of host and donor blood cells, guarantees that a solid organ from the same donor will be tolerated without a requirement for maintenance immunosuppression, and it also serves as a platform for the adoptive immunotherapy of hematologic malignancies using donor lymphocyte infusions. This review focuses on clinically relevant methods for inducing hematopoietic chimerism and transplantation tolerance, with a special emphasis on reduced intensity transplantation conditioning and high dose, post‐transplantation cyclophosphamide to prevent graft rejection and graft‐versus‐host disease (GVHD). Reduced intensity transplantation regimens permit a transient cooperation between donor and host immune systems to eradicate malignancy without producing GVHD. Their favorable toxicity profile also enables the application of allogeneic stem cell transplantation to treat non‐malignant disorders of hematopoiesis and to induce tolerance for solid organ transplantation.
The importance of regulatory T‐cell heterogeneity in maintaining self‐tolerance

CD4+ Forkhead box protein 3 (Foxp3)+ regulatory T cells (Tregs) are the major cell type that mediates dominant tolerance in the periphery. Over the past decade, extensive study of Tregs has revealed that these cells express substantial heterogeneity to maintain tolerance and regulate immune responses. Tregs possess heterogeneity with respect to their origin and processes for development, functional activity, migratory pattern, and activation status. Some of the same environmental cues and molecular pathways utilized to generate specialized T‐effector cells are also integrated by Tregs to colocalize and fine‐tune suppressive mechanisms to optimally regulate and restrain distinctive self and antigen‐specific T‐cell responses. Here, we review our current understanding and significance of Treg heterogeneity in maintaining peripheral immune tolerance. We also highlight recent work from our laboratory that has studied the extent phenotypically distinct Treg subsets are related to each other and expand in an ordered fashion to give rise to highly activated short‐lived Klrg1+ suppressor cells to optimize immune regulation and maintain homeostasis of the Treg compartment.
Cellular and molecular mechanisms underlying NOD2 risk‐associated polymorphisms in Crohn's disease

The discovery that polymorphisms in the NOD2 (nucleotide‐binding oligomerization domain containing 2) gene are associated with a greatly increased risk for the development of Crohn's disease has provided a means to achieve a deeper understanding of the dysregulation of mucosal immune responses to the commensal intestinal organisms that is thought to underlie this disease. NOD2 is a NOD‐like receptor (NLR) family member that senses and responds to bacterial wall peptides; thus, the most widely held view of the relation of the NOD2 polymorphisms with Crohn's disease is that these polymorphisms lead to deficient immune responses to gut bacteria, and these, in turn, lead to quantitative or qualitative changes in the bacterial population in the gut lumen or lamina propria that cause inflammation at this site. Initially, this view was based mainly on the observation that defective NOD2 function can result in reduced α‐defensin production by intestinal Paneth cells and that such impairment leads to loss of host defense against gut bacteria. In this review, we reconsider this possibility and marshal evidence that it is not in fact likely to be a prime element of Crohn's disease causation. More recently, evidence has been accumulating that the NOD2 dysfunction leads to Crohn's inflammation by inducing changes in the gut microbiome that influence immune effector or regulatory function. We review the strengths and weaknesses of this emerging hypothesis. Finally, we consider the possibility that NOD2 dysfunction can lead to inflammation because of a second and somewhat overlooked aspect of its function, that as an immunoregulator of innate immune responses. In particular, we review the body of evidence that NOD2 stimulation activates a cross‐tolerance response that downregulates and thus prevents excessive TLR responses that cause Crohn's inflammation.
Identification of biomarkers for diagnosis of thyroid cancer and exploration of their functional role in cancerdevelopment

Sī doktora darba ietvaros tika identificēts multipleks biomerķieru modelis vairogdziedzera vēža pacientiem, kam nepieciesams apstiprinājums FNAB. Kā arī sajā darbā autors pēta TFF3, vienu no daudzsolosākiem vairogdziedzera vēža biomarķieriem, funkcijas vairogdziedzera vēzī un demonstrē, ka tas var funkcionēt gan kā tumor suppresors, gan onkogēns atkarībā no sūnu konteksta. Sī darba ietvaros tika arī sistemātiski pētīts vēža asociēto autoantivielu repertuārs vairogdziedzera vēža pacientos. Kopumā sis darbs sniedz dziļāku izpratni par molekulārām izmaiņām, kas noved pie vairogdziedzera vēža attīstības un identificē potenciālos biomarķierus diagnostikas testa attīstīsanai un signālceļus terapijas attīstīsanai vairogdziedzera vēža pacientos.
Peripheral T‐cell and NK cell lymphoproliferative disorders: cell of origin, clinical and pathological implications

T‐cell lymphoproliferative disorders are a heterogeneous group of neoplasms with distinct clinical‐biological properties. The normal cellular counterpart of these processes has been postulated based on functional and immunophenotypic analyses. However, T lymphocytes have been proven to be remarkably capable of modulating their properties, adapting their function in relationship with multiple stimuli and to the microenvironment. This impressive plasticity is determined by the equilibrium among a pool of transcription factors and by DNA chromatin regulators. It is now proven that the acquisition of specific genomic defects leads to the enforcement/activation of distinct pathways, which ultimately alter the preferential activation of defined regulators, forcing the neoplastic cells to acquire features and phenotypes distant from their original fate. Thus, dissecting the landscape of the genetic defects and their functional consequences in T‐cell neoplasms is critical not only to pinpoint the origin of these tumors but also to define innovative mechanisms to re‐adjust an unbalanced state to which the tumor cells have become addicted and make them vulnerable to therapies and targetable by the immune system. In our review, we briefly describe the pathological and clinical aspects of the T‐cell lymphoma subtypes as well as NK‐cell lymphomas and then focus on the current understanding of their pathogenesis and the implications on diagnosis and treatment.
Atherosclerosis Complicating Chronic Hypertension

The accelerating effect of hypertension on atherogenesis in the aorta and iliofemoral and coronary arteries is presented here as a graded function of elevated intraarterial pressure. Predilection of the abdominal aorta and iliofemoral arteries for atherosclerosis can be explained on the basis of pressure augmentation by reflected pressure pulse waves and the increase in hydrostatic pressure that is produced by standing. Wave reflection is intensified by vasoconstriction, which is a characteristic not only of hypertension but also occurs with upright posture. Standing also raises the hydrostatic pressure of blood in vessels below heart level. Coronary atherosclerosis seems likely to relate to the fact that the coronary vessels are located in an area of high pressure in the arterial system and that their intramyocardial branches are normally completely occluded during systole — a condition which could be accompanied by subtle differences in the pressure-volume characteristics of the epicardial vessels.Evidence is presented from actuarial statistics, epidemiologic studies, and laboratory experiments to indicate that the level of arterial pressure has a measurable effect on the metabolism of arterial smooth muscle cells. Thus arterial pressure is viewed as having a metabolic determinant role in addition to its vital role in the circulation of blood.
Fatores de risco cardiovascular em adolescentes de município do sul do Brasil: prevalência e associações com variáveis sociodemográficas

OBJETIVO: Determinar a prevalencia de fatores de risco cardiovascular e analisar sua associacao com variaveis sociodemograficas em adolescentes do municipio de Tres de Maio/RS. METODOS: Estudo transversal de base escolar com amostra probabilistica, estratificada por sexo e nivel economico, composta por 660 adolescentes de 14 a 19 anos, 343 mocas (52%). Foram investigadas as prevalencias dos fatores de risco comportamentais (sedentarismo, dieta aterogenica, tabagismo) e biologicos (excesso de peso, excesso de adiposidade abdominal, pre-hipertensao/hipertensao arterial, hiperglicemia e dislipidemias) e sua associacao com variaveis sociodemograficas (sexo, idade e nivel economico). As associacoes foram testadas por meio do teste qui-quadrado e razao de prevalencia (intervalo de confianca de 95%) entre os fatores de risco e as variaveis sociodemograficas. RESULTADOS: Os fatores de risco mais prevalentes foram: dieta aterogenica (98,3%), sedentarismo (61,2%), excesso de adiposidade abdominal (32,6%), baixos niveis de lipoproteina de alta densidade (25,9%) e colesterol total elevado (20,3%). Foram encontradas associacoes significativas entre sexo feminino, sedentarismo [razao de prevalencia (RP) = 1,33 (1,17 - 1,50)], excesso de adiposidade abdominal [RP = 2,44 (1,89 - 3,16)] e colesterol total elevado [RP = 1,89 (1,36 - 2,62)]; e, entre o sexo masculino, baixos niveis de lipoproteina de alta densidade [RP = 2,22 (1,67 - 2,94)] e pre-hipertensao/hipertensao arterial [RP = 4,87 (1,67 - 14,23)]. Verificou-se tambem,associacao entre a idade de 17 a 19 anos e o tabagismo [RP = 1,84 (1,05 - 3,22)] e pre-hipertensao/hipertensao arterial [RP = 3,36 (1,43 - 7,90)]. O nivel economico nao foi associado aos fatores de risco cardiovascular na amostra estudada. CONCLUSAO: Os resultados indicam a necessidade de intervencoes que promovam um estilo de vida saudavel, com enfase a adocao de habitos alimentares adequados e ao aumento dos niveis de atividade fisica.
A bird's eye view of NK cell receptor interactions with their MHC class I ligands

The surveillance of target cells by natural killer (NK) cells utilizes an ensemble of inhibitory and activating receptors, many of which interact with major histocompatibility complex (MHC) class I molecules. NK cell recognition of MHC class I proteins is important developmentally for the acquisition of full NK cell effector capacity and during target cell recognition, where the engagement of inhibitory receptors and MHC class I molecules attenuates NK cell activation. Human NK cells have evolved two broad strategies for recognition of human leukocyte antigen (HLA) class I molecules: (i) direct recognition of polymorphic classical HLA class I proteins by diverse receptor families such as the killer cell immunoglobulin‐like receptors (KIRs), and (ii) indirect recognition of conserved sets of HLA class I‐derived peptides displayed on the non‐classical HLA‐E for recognition by CD94‐NKG2 receptors. In this review, we assess the structural basis for the interaction between these NK receptors and their HLA class I ligands and, using the suite of published KIR and CD94‐NKG2 ternary complexes, highlight the features that allow NK cells to orchestrate the recognition of a range of different HLA class I proteins.
Structure of serum amyloid A suggests a mechanism for selective lipoprotein binding and functions: SAA as a hub in macromolecular interaction networks

Serum amyloid A is a major acute‐phase plasma protein that modulates innate immunity and cholesterol homeostasis. We combine sequence analysis with x‐ray crystal structures to postulate that SAA acts as an intrinsically disordered hub mediating interactions among proteins, lipids and proteoglycans. A structural model of lipoprotein‐bound SAA monomer is proposed wherein two α‐helices from the N‐domain form a concave hydrophobic surface that binds lipoproteins. A C‐domain, connected to the N‐domain via a flexible linker, binds polar/charged ligands including cell receptors, bridging them with lipoproteins and rerouting cholesterol transport. Our model is supported by the SAA cleavage in the interdomain linker to generate the 1–76 fragment deposited in reactive amyloidosis. This model sheds new light on functions of this enigmatic protein.