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.     

Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells

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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.     

Homogeneous antibodies directed against human cell surface antigens: I. The mouse spleen fragment culture response to T and B cell lines derived from the same individual

The use of the mouse spleen fragment culture system is extended to the production of antibodies to human lymphoblastoid cell lines. These antibodies were tested for reactivity against the immunizing cell line, and against a second cell line which had been derived from the same human blood sample. Many of the antibodies were found to discriminate between the 2 isogenic lines. These results demonstrate the potential of the mouse spleen fragment culture system to provide homogeneous reagents which detect distinguishing markers on closely related human cells.     

Brief communication: Evaluating grandmother effects

Women who have outlived child‐bearing have long been described as postreproductive. But contributions they make to the survival or fertility of their descendants enhance the reproduction of their genes. Consequently, natural selection affects this characteristic stage of human life history. Grandmother effects can be measured in data sets that include births and deaths over several generations, but unmeasured covariates complicate the task. Here we focus on two complications: cohort shifts in mortality and fertility, and maternal age at death. We use the Utah Population Database to show that longevity of grandmothers may be associated with fewer grandchildren, as reported by Madrigal and Melendez‐Obando (Am J Phys Anthropol 136 (2008) 223–229) for a Costa Rican sample, even when grandmother effects are actually positive. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.     

Efficient production of human tumour necrosis factor in Escherichia coli

Human tumour necrosis factor (TNF) cDNA was isolated from a cDNA library prepared using TNF mRNA from human alveolar macrophages. Using the cDNA, various expression plasmids were constructed and their TNF producibility was examined in Escherichia coli. The best transformants produced a TNF polypeptide in a yield of about 20% of cellular proteins. The purified TNF polypeptide was lacking a methionine residue at the N-terminus, and possessed the expected physical and chemical properties and the biological activities characteristic of TNF.     

Ethical Issues in the Use of Data from Testing of Human Subjects to Support Risk Assessment

The public understands and supports the ethical use of human subjects in medical research, recognizing the unique role for this type of study in the development of new drugs and therapeutic strategies for treatment of disease. The use of data from human subjects can also be of value in understanding the circumstances under which individuals exposed to chemicals in the food supply, in the workplace, or in the environment might experience toxicity, i.e., in support of risk assessment. However, questions have been raised as to whether this latter type of research is ethical, or can be performed in an ethical manner. Under what circumstances is it acceptable to intentionally expose human subjects to potentially toxic agents? This is an extremely important issue for the risk assessment community to address, because it affects in a fundamental way the types of information that will be available to conduct human health risk assessments. Four papers in this issue offer viewpoints on the value of human data, the circumstances under which human subjects might be exposed to toxic chemicals for research purposes, the ethical problems associated with this research, and the role of human vs. animal data in the development of toxicity values for human health risk assessment     

Adaptive sequence divergence forged new neurodevelopmental enhancers in humans

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The Ethical Conduct of Studies Involving Controlled Human Exposure to Environmental Pollutants

In recent years, the concern for human research subject protection has increased markedly in the United States. The nature of research subject participation in controlled-exposure environmental health research is such that the individual subject bears the risk of participation, while the benefits of such research accrue to society. Therefore, particular attention must be paid when designing studies to protect the health and safety of human research subject. This paper outlines principles for the appropriate selection of pollutants to which humans can be exposed, and the principles that should be used to protect the health and safety of human research subject.     

Maternal age effect on early human embryonic development and blastocyst formation

In humans, age-related decline in female fertility can be explained by a reduction in quality either of the older uterus or of the embryos arising from aging oocytes. The aim of this study was to examine the latter hypothesis, using in vitro fertilization (I.V.F.) and coculture of embryos until the blastocyst stage. We determined the blastocyst formation rate ([expanded blastocysts/blastocysts]*100) according to the patient's age the day of I.V.F. With increase in age, the number of retrieved oocytes decreased, without alteration of the cleavage rate. In patients above age 30 years, preimplantation development to blastocysts declined due to an increase in embryo arrest at the morula stage. If blastocyst stage was reached, a negative linear relationship between blastocyst expansion rate and patient age was observed. Drops in gamete production and embryo development with increasing age led to a drastic decrease in patients having at least one expanded blastocyst (<30 years, 82%; ≥40 years, 36%). A high delivery rate per oocyte retrieval (25.8%) was observed in patients above age 40 years after embryo transfer at the blastocyst stage. These results give a clear indication of decline in the quality of human embryos arising from aging oocytes. The origin of this alteration is discussed in terms of chromosome abnormalities, role of maternally-inherited products from the oocyte, timing of genomic activation, and temporal pattern of gene expression during initial development of the human embryo. © 1996 Wiley-Liss, Inc.     

Activation of human neutrophils with Helicobacter pylori and the role of Toll-like receptors 2 and 4 in the response

The innate immune response to Helicobacter pylori infection is beginning to be understood and recent works support a role for Toll-like receptors (TLRs). Our aim was to study the response of human neutrophils to H. pylori and to elucidate the role of TLR2 and TLR4. Neutrophils from healthy H. pylori-negative volunteers were cocultured with H. pylori 26695 strain. The release of IL-8, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-10 was measured. The role of TLR2 and TLR4 was investigated with blocking assays using monoclonal antibodies against TLRs. Neutrophils produced a significant increase of IL-8, IL-1beta and TNF-alpha after 3, 6 and 24 h of H. pylori challenge, respectively, whereas IL-10 increased after 24 h. Helicobacter pylori challenge increased TLR2 and TLR4 expression; and antibodies against TLR2 and TLR4 diminished significantly the H. pylori-induced production of IL-8 and IL-10. In human neutrophils, H. pylori induces an early inflammatory response, partially mediated via TLR2 and TLR4 activation.     

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。     

产生人抗体的转染色体动物研究进展

现已证明,应用抗体治疗疾病是一种非常成功的方法。单克隆抗体的生产使免疫治疗达到一个新水平,但鼠源单抗在治疗人体疾病方面有很多问题,而人源化抗体可以解决这些问题。目前抗体人源化已由鼠嵌合抗体发展到了转基因动物表达完全人抗体阶段,而人类人工染色体(HAC)载体的发展和微细胞介导的转染色体技术使得产生携带人类免疫球蛋白基因位点的转染色体动物成为可能。通过HAC将人的免疫球蛋白基因转入后,这类转染色体动物可以产生大量人源化多克隆抗体,这对预防及治疗疾病,甚至防御生物武器都有很重要的作用。转染色体技术可以使动物携带大而复杂的人类基因或基因簇,这些转基因动物有助于研究人类基因组在体内的功能作用,并用于各种疾病研究和生产药物蛋白。     

人类基因组中的反转录转座子

人类基因组中有35%以上的序列为转座子序列.反转录转座子是引起人类疾病的潜在病因.人类基因组中的主导转座子——L1反转录转座子内部有二个开放读框,其编码蛋白具有RNA结合蛋白、反转录酶和内切酶活性.L1可能通过靶引物反转录机制整合到染色体中;Alu等非自主性反转录转座子可能利用L1反转录酶的反式互补作用进行转座.     

A note on the KNM-ER 999 hominid femur

The KNM-ER 999 hominid femur, in light of improved knowledge of later Pleistocene human postcranial morphology and ongoing reassessments of the emergence of modern humans in Africa, appears morphologically aligned with early modern humans rather than with late archaic humans. This is reflected especially in its having a clear pilaster, a proximally positioned minimum diaphyseal breadth (thereby lacking a proximo-medial diaphyseal buttress) and an exceptionally high neck-shaft angle. In these features, and especially the fast, it shows affinities to the Levantine Qafzeh-Skhul early modern human sample. However, the uncertainty regarding its stratigraphic provenience (early Late Pleistocene versus early Holocene) makes its relevance to the emergence of modern humans in Africa tenuous.     

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.