Trade-related Infections: Global Traffic and Microbial Travel

Science is only beginning to understand the interplay between global trade and human infectious diseases. The reported frequency of the emergence of new human pathogens has been increasing, coincident with the burgeoning of global trade. This report examines the phenomenon of trade related infections which are infections whose emergence, or dissemination and transmission may be driven by global trade in commodities, or whose occurrence cause major economic impact through trade disruption. Through four case studies, the interplay between global trade and the emergence and dissemination of new human infections is described. The examples are drawn from three distinct types of emergent infections: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and the trade in blood clotting derivatives, enteric disease and fresh produce, and prion infections and beef. The observations from these studies are then placed in the global policy framework for the control of infectious diseases and the regulation of trade. This framework is embodied in the World Health Organization and the World Trade Organization. While increasing discourse is occurring between the sectors of health and trade at the level of international organizations, such discourse at the national and local level is largely absent. A more complete evidence base for policy decision making is sorely needed to foster a global trading system which also maintains the public safety from emergent infectious diseases.     

Morphofunctional Organization of Lymphoepithelial Organs of the Human Pharynx

We present the current concepts of morphofunctional organization of the lymphoepithelial organs in the human pharynx based on the published data and authors" results. Functional compartmentation of palatine and pharyngeal tonsils is considered, which reflects cooperative cell interactions in the immune response; B- and T-areas have been structurally isolated and functionally substantiated. A special attention is paid to the fine structure of cryptal epithelium and its interactions with lymphoid cells infiltrating the epithelial sheet: lymphoepithelial symbiosis. Attention is also paid to structural homology of the lymphoepithelial compartment of palatine tonsils and thymus. The problem concerns the place of lymphoepithelial organs in hierarchy of the immune system as secondary organs with their own immunoregulatory area and having the functions of a regional center controlling the mucosal immunity.     

Identification of a Novel Human Polyomavirus in Organs of the Gastrointestinal Tract

Polyomaviruses are small, non-enveloped viruses with a circular double-stranded DNA genome. Using a generic polyomavirus PCR targeting the VP1 major structural protein gene, a novel polyomavirus was initially identified in resected human liver tissue and provisionally named Human Polyomavirus 12 (HPyV12). Its 5033 bp genome is predicted to encode large and small T antigens and the 3 structural proteins VP1, VP2 and VP3. Phylogenetic analyses did not reveal a close relationship to any known human or animal polyomavirus. Investigation of organs, body fluids and excretions of diseased individuals and healthy subjects with both HPyV12-specific nested PCR and quantitative real-time PCR revealed additional virus-positive samples of resected liver, cecum and rectum tissues and a positive fecal sample. A capsomer-based IgG ELISA was established using the major capsid protein VP1 of HPyV12. Seroprevalences of 23% and 17%, respectively, were determined in sera from healthy adults and adolescents and a pediatric group of children. These data indicate that the virus naturally infects humans and that primary infection may already occur in childhood.     

Dendrochronology and Human Dimensions Issues in Global Change

This introduction briefly outlines the context for global change, the origin of this volume and presents a brief summary of its contents.     

The Traffic in Brides

Petr Lom's film, Bride Kidnapping in Kyrgyzstan , offers viewers a striking visual narration of the deeply routinized practices of bride capture in contemporary Central Asia. In this review, I offer historical context eschewed by the film, observing how, contrary to popular belief, bride kidnapping increased under Russian imperial supervision. It later dwindled in the activist Soviet period, but rose again in the relative anarchy of the postsocialist landscape. What the film invites but does not explicitly entertain is a complex arithmetic of culturally coded understandings of volition, personal property, and alliance.     

The Evolution of Complex Organs

The origin of complex biological structures has long been a subject of interest and debate. Two centuries ago, natural explanations for their occurrence were considered inconceivable. However, 150 years of scientific investigation have yielded a conceptual framework, abundant data, and a range of analytical tools capable of addressing this question. This article reviews the various direct and indirect evolutionary processes that contribute to the origins of complex organs. The evolution of eyes is used as a case study to illustrate these concepts, and several of the most common misconceptions about complex organ evolution are discussed.

Neuropilin-1 Expression Characterizes T Follicular Helper (Tfh) Cells Activated during B Cell Differentiation in Human Secondary Lymphoid Organs

T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. Tfh cells regulate the differentiation and survival of activated B cells outside and inside germinal centers (GC) of secondary lymphoid organs. They act through cognate contacts with antigen-presenting B cells, but there is no current marker to specifically identify those Tfh cells which productively interact with B cells. Here we show that neuropilin 1 (Nrp1), a cell surface receptor, is selectively expressed by a subset of Tfh cells in human secondary lymphoid organs. Nrp1 expression on Tfh cells correlates with B cell differentiation in vivo and in vitro, is transient, and can be induced upon co-culture with autologous memory B cells in a cell contact-dependent manner. Comparative analysis of ex vivo Nrp1⁺ and Nrp1^- Tfh cells reveals gene expression modulation during activation. Finally, Nrp1 is expressed by malignant Tfh-like cells in a severe case of angioimmunoblastic T-cell lymphoma (AITL) associated with elevated terminal B cell differentiation. Thus, Nrp1 is a specific marker of Tfh cells cognate activation in humans, which may prove useful as a prognostic factor and a therapeutic target in neoplastic diseases associated with Tfh cells activity.     

全球人冠状病毒抗体领域研发现状与发展趋势

抗体在疾病的诊断、治疗和预防方面发挥着重要作用。随着2019新型冠状病毒(SARSCoV-2)感染引起的肺炎不断传播,如何研发针对该病毒的抗体迫在眉睫。基于IncoPat数据库的专利信息和Cortellis数据库的药物信息,采用定量分析与定性调研相结合的方法,从申请趋势、技术分布、国家/地区分布、机构分布以及市场现状等维度对人冠状病毒抗体领域的专利进行态势分析。结果表明美国是专利技术拥有量最大的国家,中国是专利保护的重点国家。中国科学院等3家国内机构进入全球前十位。人冠状病毒抗体产品研发主要以SARS和MERS为主,部分MERS抗体已进入临床阶段。研究结果为2019冠状病毒病(COVID-19)的相关抗体研发提供数据参考与决策支撑。     

The Pathology of Severe Dengue in Multiple Organs of Human Fatal Cases: Histopathology,Ultrastructure and Virus Replication

Dengue is a public health problem, with several gaps in understanding its pathogenesis. Studies based on human fatal cases are extremely important and may clarify some of these gaps. In this work, we analyzed lesions in different organs of four dengue fatal cases, occurred in Brazil. Tissues were prepared for visualization in optical and electron microscopy, with damages quantification. As expected, we observed in all studied organ lesions characteristic of severe dengue, such as hemorrhage and edema, although other injuries were also detected. Cases presented necrotic areas in the liver and diffuse macro and microsteatosis, which were more accentuated in case 1, who also had obesity. The lung was the most affected organ, with hyaline membrane formation associated with mononuclear infiltrates in patients with pre-existing diseases such as diabetes and obesity (cases 1 and 2, respectively). These cases had also extensive acute tubular necrosis in the kidney. Infection induced destruction of cardiac fibers in most cases, with absence of nucleus and loss of striations, suggesting myocarditis. Spleens revealed significant destruction of the germinal centers and atrophy of lymphoid follicles, which may be associated to decrease of T cell number. Circulatory disturbs were reinforced by the presence of megakaryocytes in alveolar spaces, thrombus formation in glomerular capillaries and loss of endothelium in several tissues. Besides histopathological and ultrastructural observations, virus replication were investigated by detection of dengue antigens, especially the non-structural 3 protein (NS3), and confirmed by the presence of virus RNA negative strand (in situ hybridization), with second staining for identification of some cells. Results showed that dengue had broader tropism comparing to what was described before in literature, replicating in hepatocytes, type II pneumocytes and cardiac fibers, as well as in resident and circulating monocytes/macrophages and endothelial cells.     

Analysis of the Temporal Relationship between Human Immunodeficiency Virus Type 1 Quasispecies in Sequential Blood Samples and Various Organs Obtained at Autopsy

We studied the temporal relationship between human immunodeficiency type 1 (HIV-1) quasispecies in tissues and in peripheral blood mononuclear cells (PBMC) of infected individuals. Sequential PBMC and tissue samples from various organs obtained at autopsy from three patients who died of AIDS-related complications were available for analysis. Biological HIV-1 clones were isolated from PBMC samples, and cellular tropism and syncytium-inducing (SI) capacity were determined. Genomic DNA was isolated from 1 cm³ of organ tissue, and proviral DNA was amplified by means of PCR and cloned with the PGEM-T vector system. A 185-bp region encompassing the third variable domain of the virus envelope, known to influence HIV-1 biological properties, was sequenced. HIV-1 could be amplified from all PBMC and organ samples, except from liver tissue for two patients. Both SI and non-syncytium-inducing (NSI) genotypes could be detected in the different tissues. Tissue-specific quasispecies were observed in brain, lung, and testis. Lymphoid tissues, such as bone marrow, lymph node, and spleen, harbored several different variants similar to those detected in blood in the last PBMC samples. In general, only tissues in which macrophages are likely to be the main target cell for HIV-1 harbored NSI HIV-1 sequences that clustered separately. Both SI and NSI sequences that clustered with sequences from late-stage PBMC were present in other tissues, which may indicate that the presence of HIV-1 in those tissues is secondary to lymphocyte infiltration rather than to tissue tropism of HIV-1 itself. These data suggest that the viral reservoir may be limited, which will have important implications for the success of HIV-1 eradication.     

Global Profiling of Carbohydrate Active Enzymes in Human Gut Microbiome

Motivation

Carbohydrate Active enzyme (CAZyme) families, encoded by human gut microflora, play a crucial role in breakdown of complex dietary carbohydrates into components that can be absorbed by our intestinal epithelium. Since nutritional wellbeing of an individual is dependent on the nutrient harvesting capability of the gut microbiome, it is important to understand how CAZyme repertoire in the gut is influenced by factors like age, geography and food habits.

Results

This study reports a comprehensive in-silico analysis of CAZyme profiles in the gut microbiomes of 448 individuals belonging to different geographies, using similarity searches of the corresponding gut metagenomic contigs against the carbohydrate active enzymes database. The study identifies a core group of 89 CAZyme families that are present across 85% of the gut microbiomes. The study detects several geography/age-specific trends in gut CAZyme repertoires of the individuals. Notably, a group of CAZymes having a positive correlation with BMI has been identified. Further this group of BMI-associated CAZymes is observed to be specifically abundant in the Firmicutes phyla. One of the major findings from this study is identification of three distinct groups of individuals, referred to as ''CAZotypes'', having similar CAZyme profiles. Distinct taxonomic drivers for these CAZotypes as well as the probable dietary basis for such trends have also been elucidated. The results of this study provide a global view of CAZyme profiles across individuals of various geographies and age-groups. These results re-iterate the need of a more precise understanding of the role of carbohydrate active enzymes in human nutrition.