人体肠道病毒组学研究进展

人体微生物组计划开展近10年来,大量的研究显示人体微生物通过各种方式深刻地影响着人体健康。人体肠道内丰富多样的病毒构成了肠道病毒组,是人体微生物组的重要组成部分,和人体健康密切相关。本文综述了近些年国际上人体肠道病毒组研究的最新进展,分别从人体肠道病毒组的组成特征、肠道病毒组-细菌组-人体间的相互作用及其对人体健康的影响、病毒组研究的技术策略及挑战等方面进行了论述,探讨了肠道病毒组在人体疾病预防和治疗领域应用的可行性。     

In vitro cultivation of human renal cell cancer

Summary A technique for initiating and propagating epithelial cell cultures of human renal cell cancer and adjacent nontumor kidney is described. Seventy-five percent of the tumors and 79% of the adjacent kidney specimens cultured with this method have shown initial outgrowth and have been subcultured at least once. Two renal cell cancer cultures initiated by this method have now been in continuous culture more than 6 months, have been subcultured 27 and 19 times, and now appear to be stable lines. The ability to establish long-term in vitro cultures of human renal cell cancers will facilitate studies concerning the immunoreactivity, cholesterol metabolism, the isolation of renal-cell-cancer-specific antigens, and in vitro chemotherapy testing and will further our understanding of the basic biology of human renal cell cancer. American Cancer Society Clinical Fellow 1975–1976. Supported in part by Grants CA 13095-03 and CA 15551-03 from the National Cancer Institute.     

Bio-therapeutics from human milk: prospects and perspectives

Human milk is elixir for neonates and is a rich source of nutrients and beneficial microbiota required for infant growth and development. Its benefits prompted research into probing the milk components and their use as prophylactic or therapeutic agents. Culture-independent estimation of milk microbiome and high-resolution identification of milk components provide information, but a holistic purview of these research domains is lacking. Here, we review the current research on bio-therapeutic components of milk and simplified future directions for its efficient usage. Publicly available databases such as PubMed and Google scholar were searched for keywords such as probiotics and prebiotics related to human milk, microbiome and milk oligosaccharides. This was further manually curated for inclusion and exclusion criteria relevant to human milk and clinical efficacy. The literature was classified into subgroups and then discussed in detail to facilitate understanding. Although milk research is still in infancy, it is clear that human milk has many functions including protection of infants by passive immunization through secreted antibodies, and transfer of immune regulators, cytokines and bioactive peptides. Unbiased estimates show that the human milk carries a complex community of microbiota which serves as the initial inoculum for establishment of infant gut. Our search effectively screened for evidence that shows that milk also harbours many types of prebiotics such as human milk oligosaccharides which encourage growth of beneficial probiotics. The milk also trains the naive immune system of the infant by supplying immune cells and stimulatory factors, thereby strengthening mucosal and systemic immune system. Our systematic review would improve understanding of human milk and the inherent complexity and diversity of human milk. The interrelated functional role of human milk components especially the oligosaccharides and microbiome has been discussed which plays important role in human health.     

AMP-deaminase from human term placenta

AMP-deaminase from human term placenta was chromatographed on a phosphocellulose column and physico-chemical and immunological properties of the purified enzyme were investigated. At physiological pH7.0, in the absence of regulatory ligands (control conditions) studied AMP-deaminase manifested sigmoid-shaped substrate saturation kinetics, with half-saturation parameter (S_0.5) value of about 7 mM. Addition of important allosteric effectors (ATP, ADP or orthophosphate) modified kinetic properties of studied AMP-deaminase, influencing mainly the value of S_0.5 parameter. Micromolar concentrations of stearylo-CoA inhibited potently the enzyme making it no longer sensitive towards 1 mM ATP-induced activation. SDS-PAGE electrophoresis of the purified enzyme revealed presence of 68 kDa protein fragment, reacting with anti-(human) liver AMP-deaminase antibodies. Experimental results presented indicate that liver type of AMP-deaminase is an enzyme form present in human term placenta.     

Virtual human hand: model and kinematics

The human hand plays an important role in daily life. It is the interface between the human and the exterior world by positioning, orienting, touching and grasping objects. The human hand has multiple degrees of freedom (DOFs) to enable mobility and dexterity. A virtual human hand model can be inserted into CAD (Computer Aided Design) models to assess the manipulation capabilities in the early design stage to reduce design time and cost. Joystick assessment is one of the important design cases. This study is a first step towards a comprehensive hand simulation tool to simulate the manipulation and grasping of objects. This paper presents a novel 25 DOFs' hand skeletal model based on hand anatomy and hand kinematics: (1) joint range of motion, (2) Denavit–Hartenberg method to define the joint relationship and (3) finger workspace determination. Novelty for this hand model includes arching the palm with the four DOFs added in the carpometacarpal and wrist joints for the ring and small fingers.     

Allometry of human fertility and energy use

The flux of energy and materials constrains all organisms, and allometric relationships between rates of energy consumption and other biological rates are manifest at many levels of biological organization. Although human ecology is unusual in many respects, human populations also face energetic constraints. Here we present a model relating fertility rates to per capita energy consumption rates in contemporary human nations. Fertility declines as energy consumption increases with a scaling exponent of ?1/3 as predicted by allometric theory. The decline may be explained by parental trade‐offs between the number of children and the energetic investment in each child. We hypothesize that the ?1/3 exponent results from the scaling properties of the networked infrastructure that delivers energy to consumers. This allometric analysis of human fertility offers a framework for understanding the demographic transition to smaller family sizes, with implications for human population growth, resource use and sustainability.     

Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells

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Immunodiffusion test for diagnosing human pythiosis

An immunodiffusion test was developed for diagnosing subcutaneous and systemic pythiosis in humans. When culture filtrate antigen (CFA) from P. insidiosum was reacted against patient and rabbit antisera, 1–5 precipitin bands occured both in patient and rabbit antisera, and a line of identity also occured between patient and rabbit sera. When control P. insidiosum CFA was reacted with 30 apparently normal persons, 20 Thalassemia patients, 2 candidosis and 5 aspergillosis patients, no precipitin bands were found. P. insidiosum CFA also tested with rabbit antibodies to B. dermatitidis, C. immitis, H. capsulatum, P. brasiliensis, C. albicans, M. furfur and A. fumigatus revealed no cross reactions. This test is practical, sensitive and specific.     

Efficacy of alcohol-based hand sanitizers against human norovirus using RNase-RT-qPCR with validation by human intestinal enteroid replication

Successful human norovirus (HuNoV) cultivation in stem cell-derived human intestinal enteroids (HIE) was recently reported. The purpose of this study was to evaluate the anti-HuNoV efficacy of two alcohol-based commercial hand sanitizers and 60% ethanol by suspension assay using RNase-RT-qPCR, with subsequent validation of efficacy by HuNoV cultivation using the HIE model. In suspension, when evaluated by RNase-RT-qPCR, 60% ethanol resulted in less than one log₁₀ reduction in HuNoV genome equivalent copies (GEC) regardless of contact time (30 or 60s) or soil load. The two commercial products outperformed 60% ethanol regardless of contact time or soil load, providing 2·2–3·2 log₁₀ HuNoV GEC reductions by suspension assay. Product B could not be validated in the HIE model due to cytotoxicity. Following a 60s exposure, viral replication in the HIE model increased 1·9 ± 0·2 log₁₀ HuNoV GEC for the neutralization (positive) control and increased 0·9 ± 0·2 log₁₀ HuNoV GEC in challenged HIE after treatment with 60% ethanol. No HuNoV replication in HIE was observed after a 60 s exposure to Product A.     

In vitro cultivation of human renal cell cancer

Summary Two cell lines derived from primary human renal-cell cancers (RCC) have been established and characterized. Cell line 786-O has been in culture for longer than 1 year and has been subcultured more than 50 times. It has a doubling time of 45 hr and a hypertriploid karyotype and possesses a Y chromosome. Cell line 769-P also has been in culture for longer than 1 year. It has been subcultured 50 times and has a doubling time of 35 hr and a hypodiploid karyotype. Cells from both lines are epithelial, and they produce tumors in the cheek pouches of immunosuppressed hamsters. Neither cell line is contaminated withMycoplasma. Cells of the two lines can be distinguished from HeLa cells both by their karyotypes and by the mobility patterns of their isoenzymes of glucose-6-phosphate dehydrogenase. American Cancer Society Clinical Faculty Fellow, 1977–1980. Supported in part by Grants CA 13095-03 and CA 15551-03 from the National Cancer Institute.     

Geographic views of human development

Human development can be divided into three stages: human ancestors (Lower Palaeolithic), early human races (Middle Palaeolithic) and modern humans (Upper Palaeolithic). Regional differentiation has been detected in the Lower Palaeolithic and is strongly developed in the Middle Palaeolithic but continues into the Upper Palaeolithic less marked. Clearly mixture at all levels accounts for this. Early humans absorbed the pre-existing regionalizations even as they further differentiated. Modern humans resulted from Upper Palaeolithic people spreading across the world and again absorbing the previous differentiations.     

Composition of the peptide fraction in human blood plasma: database of circulating human peptides

A database was established from human hemofiltrate (HF) that consisted of a mass database and a sequence database, with the aim of analyzing the composition of the peptide fraction in human blood. To establish a mass database, all 480 fractions of a peptide bank generated from HF were analyzed by MALDI-TOF mass spectrometry. Using this method, over 20 000 molecular masses representing native, circulating peptides were detected. Estimation of repeatedly detected masses suggests that approximately 5000 different peptides were recorded. More than 95% of the detected masses are smaller than 15 000, indicating that HF predominantly contains peptides. The sequence database contains over 340 entries from 75 different protein and peptide precursors. 55% of the entries are fragments from plasma proteins (fibrinogen A 13%, albumin 10%, β2-microglobulin 8.5%, cystatin C 7%, and fibrinogen B 6%). Seven percent of the entries represent peptide hormones, growth factors and cytokines. Thirty-three percent belong to protein families such as complement factors, enzymes, enzyme inhibitors and transport proteins. Five percent represent novel peptides of which some show homology to known peptide and protein families. The coexistence of processed peptide fragments, biologically active peptides and peptide precursors suggests that HF reflects the peptide composition of plasma. Interestingly, protein modules such as EGF domains (meprin Aα-fragments), somatomedin-B domains (vitronectin fragments), thyroglobulin domains (insulin like growth factor-binding proteins), and Kazal-type inhibitor domains were identified. Alignment of sequenced fragments to their precursor proteins and the analysis of their cleavage sites revealed that there are different processing pathways of plasma proteins in vivo.     

Skin equivalent produced with human collagen

Summary Several studies have recently been conducted on cultured skin equivalent (SE), prepared using human keratinocytes seeded on various types of dermal equivalents (DE). We previously showed the advantages of our anchorage method in preventing the severe surface reduction of DE due to fibroblast contractile properties in vitro. A new anchored human SE was established in our laboratory in order to obtain a bioengineered tissue that would possess the appropriate histological and biological properties. In order to compare the effects of different collagen origins on the evolution of SE in vitro, human keratinocytes were seeded on three types of anchored DE. A comparative study was carried out between bovine SE (bSE), human SE (hSE), and human skin equivalent containing additional dermal matrix components (hSE +). Immunohistological analysis showed that hSE and hSE+ presented good structural organization, including the deposition of several basement membrane constituents. Higher amounts of transglutaminase, ceramides, and keratin 1 were detected in the epidermal layers of all SE when cultured at the air-liquid interface. However, a 92 kDa gelatinase activity was higher in bovine skin equivalent (bSE) compared to hSE cultures. The use of human collagens comparatively to bovine collagen as SE matricial component delayed the degradation of the dermal layer in culture.     

On the origin of human tumors

Summary A proposal is made to extend the commitment theory of cellular aging to the process of tumorigenesis. Indirect data are cited in support of a scheme whereby human tumors arise from a small number of unique cells which are termed “uncommitted.” The process of tumorigenesis as described is both multistep and reversible.     

Purification techniques for human interferons

This article outlines the development and general status of present purification methods for human interferons. The isolation of each interferon species from natural sources is extremely difficult because of molecular characteristics, high losses of activity and the small amount of interferon protein present in production media. Few of the highly sophisticated methods meet the requirements for scale-up or give acceptable recoveries for a production process. The adaptation of purification procedures to the different interferon species is described, such as initial concentration, the extraction of beta interferon (IFN-β) by aqueous two-phase systems and the final purification of alpha interferon (IFN-α) and beta interferon to homogeneity. H.p.l.c. techniques are discussed in more detail together with problems in the purification of beta interferon and gamma interferon (IFN-γ). The range of interferon expression and excretion in recombinant microbial and animal cells is reviewed and different approaches for the solubilization and purification of intracellular recombinant interferons are described, which are covered mainly in patent applications.     

古人类对赭石的利用行为在其演化中的意义

长期以来赭石利用行为被视为人类行为现代性的标志之一,受到国内外考古学界的普遍关注。本文回溯和梳理了全球背景下赭石利用的起源、发展及其与人类演化史的关系。在现代人广泛分布于全球之后,赭石利用行为更加丰富和多样化地出现在各地,然而现有考古证据表明该行为并不是解剖学意义上的现代人突变性的发明。赭石利用不能被单纯地定义为现代人行为,而应是有着长久演化积累的现代性行为之一。在长期传播与演化过程中,赭石的功能从意识形态、艺术表达等逐渐扩展到作为矿物成分被用于实际生产生活。赭石的利用历史可追溯到中更新世中期,但其广泛分布仍与晚更新世以来现代人的广泛扩散直接相关,对于理解现代人的意识形态、社会组织方式以及艺术表达、精神文化发展都具有重要的意义。国内目前所发表的相关考古学证据相对较少,以下马碑遗址为代表的材料,也恰处于现代人在全球广泛扩散的窗口期,并伴有进步的细小石器镶嵌使用的证据,成为认识东亚现代人行为的关键性考古证据。