Relative Antiviral Resistance Induced in Homologous and Heterologous Cells by Cross-Reacting Interferons

Human cells incubated with human interferon become more resistant to vesicular stomatitis virus (VSV) than to Semliki Forest virus (SFV); monkey cells treated with monkey interferon become more resistant to SFV than to VSV. However, monkey cells incubated with human interferon developed relative antiviral activity identical to that induced by homologous interferon, and human cells developed characteristic human interferon-induced relative antiviral activity when exposed to monkey interferon. Therefore, cross-reacting interferons induce the relative antiviral activity characteristic of the interferon-treated cell rather than the cell of the interferon's origin. This relationship supports the hypothesis that interferon is not itself antiviral but rather induces cells to develop their own antiviral activity.     

The Case for Conserving Disability

It is commonly believed that disability disqualifies people from full participation in or recognition by society. This view is rooted in eugenic logic, which tells us that our world would be a better place if disability could be eliminated. In opposition to this position, I argue that that disability is inherent in the human condition and consider the bioethical question of why we might want to conserve rather than eliminate disability from our shared world. To do so, I draw together an eclectic, rather than systematic, configuration of counter-eugenic arguments for conserving disability. The idea of preserving intact, keeping alive, and even encouraging to flourish denoted by conserve suggests that disabilities would be better understood as benefits rather than deficits. I present, then, a reading of disability as a potentially generative resource rather than unequivocally restrictive liability. In other words, what I consider here is the cultural and material contributions disability offers to the world.     

The evolution of premature reproductive senescence and menopause in human females

Reproductive senescence in human females takes place long before other body functions senesce. This fact presents an evolutionary dilemma since continued reproduction should generally be favored by natural selection. Two commonly proposed hypotheses to account for human menopause are (a) a recent increase in the human lifespan and (b) a switch to investment in close kin rather than direct reproduction. No support is found for the proposition that human lifespans have only recently increased. Data from Ache hunter-gatherers are used to test the kin selection hypothesis. Ache data do not support the proposition that females can gain greater fitness benefits in old age by helping kin rather than continuing to reproduce. Nevertheless, one crucial parameter in the model, when adjusted to the highest value within the measured 95% confidence interval, would lead to the evolution of reproductive senescence at about 53 years of age. Further investigation is necessary to determine whether the kin selection hypothesis of menopause can account for its current maintenance in most populations.     

Selenocysteine's mechanism of incorporation and evolution revealed in cDNAs of three glutathione peroxidases

The nonsense codon, UGA, has for the first time recently been shown to encode selenocysteine in two proteins, mouse glutathione peroxidase (GSH-Px) (EC 1.11.1.9) and bacterial formate dehydrogenase. A co-translational rather than post-translational selenium-incorporation mechanism has been implicated. Furthermore, high expression levels of GSH-Px have suggested that suppression of termination is efficient and specific. We have isolated and characterized pituitary, kidney and placenta cDNAs for bovine, human and mouse GSH-Px respectively. It is demonstrated that this novel suppression event occurs in diverse tissues, in at least three mammalian species and at the translational step. Surprisingly, GSH-Px is shown to be extramitochondrially encoded, indicating a cytosolic suppression event rather than one utilizing the mitochondria's well-documented extended codon-reading ability. Sequence analysis reveals that a simple proximal contextual pattern responsible for readthrough does not exist. Analysis of predicted secondary structures of mRNAs, however, has revealed a conformation which may be unique to selenocysteine proteins and may prove useful as a tool for artificial incorporation of selenocysteines. A human intron for GSH-Px from an unspliced mRNA has been isolated whose position indicates an ancient, divergent evolutionary relationship with thioredoxin-S2, rather than an independent convergent one.     

Meta-vinculin distribution in adult human tissues and cultured cells

Meta-vinculin distribution in adult human tissue was studied by immunoblotting technique. Meta-vinculin was found in smooth (aorta wall and myometrium) and cardiac muscle, rather than in skeletal muscle, liver, kidney and cultured cells - macrophages, foreskin fibroblasts, peripheral blood lymphocytes and vascular endothelial cells. In the primary culture of smooth muscle cells from human aorta the meta-vinculin/vinculin ratio was reduced, and on the onset of cell division meta-vinculin could hardly be detected. Subcultured smooth muscle cells from human aorta did not contain meta-vinculin. The data show that the presence of meta-vinculin is characteristic of 'contractile' smooth muscle cells rather than of proliferating in vitro.     

陕西洛南人牙化石及其地质时代

在陕西省洛南县洛河左岸洞穴中,发现一古人类上臼齿,其特点与郧县人牙化石很相似。与人牙化石共存的有大熊猫和獏。后二者比华南洞穴中常见的同类化石明显小,比广西柳城巨猿洞中的小型者要大。从化石特点分析,洛南人牙化石及其所在沉积层的时代为中更新世早期(也有早更新世晚期的可能)。     

Tuberculin response of lymphocytes from human skin test nonreactors; evidence for in vitro primary sensitization of T lymphocytes.

Tuberculin-purified protein derivative (PPD) is a B-lymphocyte mitogen in a variety of experimental animals. Although peripheral blood mononuclear cells (PB MNC) from healthy human tuberculin responders consistently responded to PPD by increased incorporation of [³H]thymidine, cell fractionation studies showed this to be due to T-lymphocyte rather than B-cell blastogenesis. Moreover, utilizing thymidine suicide experiments, the T-lymphocyte response could be categorized as antigenic rather than nonspecific mitogenic reactivity. Kinetic studies revealed a delayed peak of PPD-induced thymidine incorporation in PB MNC from tuberculin skin test-negative as compared to skin test-positive donors. This suggested in vitro primary sensitization of T lymphocytes to PPD, which was corroborated in experiments demonstrating tuberculin reactivity of human umbilical-cord blood lymphocytes.     

A comparison of the effects of prednisolone and methylprednisolone on human lymphoblastoid cells.

Methylprednisolone is more effective than prednisolone in mediating long-term cytolysis and immediate inhibition of nucleoside uptake in human lymphoblastoid cells. This suggests that methylation of prednisolone makes it more potent by aiding interaction with a cellular target rather than increasing its stability.     

Ontology for genome comparison and genomic rearrangements

We present an ontology for describing genomes, genome comparisons, their evolution and biological function. This ontology will support the development of novel genome comparison algorithms and aid the community in discussing genomic evolution. It provides a framework for communication about comparative genomics, and a basis upon which further automated analysis can be built. The nomenclature defined by the ontology will foster clearer communication between biologists, and also standardize terms used by data publishers in the results of analysis programs. The overriding aim of this ontology is the facilitation of consistent annotation of genomes through computational methods, rather than human annotators. To this end, the ontology includes definitions that support computer analysis and automated transfer of annotations between genomes, rather than relying upon human mediation.     

Resolving head rotation for human bipedalism

Alignment of the body to the gravitational vertical is considered to be the key to human bipedalism. However, changes to the semicircular canals during human evolution suggest that the sense of head rotation that they provide is important for modern human bipedal locomotion. When walking, the canals signal a mix of head rotations associated with path turns, balance perturbations, and other body movements. It is uncertain how the brain uses this information. Here, we show dual roles for the semicircular canals in balance control and navigation control. We electrically evoke a head-fixed virtual rotation signal from semicircular canal nerves as subjects walk in the dark with their head held in different orientations. Depending on head orientation, we can either steer walking by "remote control" or produce balance disturbances. This shows that the brain resolves the canal signal according to head posture into Earth-referenced orthogonal components and uses rotations in vertical planes to control balance and rotations in the horizontal plane to navigate. Because the semicircular canals are concerned with movement rather than detecting vertical alignment, this result shows the importance of movement control and agility rather than precise vertical alignment of the body for human bipedalism.     

Correlated dynamics in egocentric communication networks

We investigate the communication sequences of millions of people through two different channels and analyse the fine grained temporal structure of correlated event trains induced by single individuals. By focusing on correlations between the heterogeneous dynamics and the topology of egocentric networks we find that the bursty trains usually evolve for pairs of individuals rather than for the ego and his/her several neighbours, thus burstiness is a property of the links rather than of the nodes. We compare the directional balance of calls and short messages within bursty trains to the average on the actual link and show that for the trains of voice calls the imbalance is significantly enhanced, while for short messages the balance within the trains increases. These effects can be partly traced back to the technological constraints (for short messages) and partly to the human behavioural features (voice calls). We define a model that is able to reproduce the empirical results and may help us to understand better the mechanisms driving technology mediated human communication dynamics.     

Mapping the human genome: some thoughts for those who say "There should be a law on it

... It appears from this discussion that the most effective method of regulating the problems that may arise from the human genome project is to concentrate, not on the research involved in the project, but rather on the uses that may be made of the information gained from it. Furthermore, there is already a good deal of legislation and administrative machinery that is directly or incidentally relevant to the matters in question. This should obviously be used as much as possible, rather than new legislation, to reduce bureaucracy, overlapping provisions and costs.     

Defining the role of essential genes in human disease

A greater understanding of the causes of human disease can come from identifying characteristics that are specific to disease genes. However, a full understanding of the contribution of essential genes to human disease is lacking, due to the premise that these genes tend to cause developmental abnormalities rather than adult disease. We tested the hypothesis that human orthologs of mouse essential genes are associated with a variety of human diseases, rather than only those related to miscarriage and birth defects. We segregated human disease genes according to whether the knockout phenotype of their mouse ortholog was lethal or viable, defining those with orthologs producing lethal knockouts as essential disease genes. We show that the human orthologs of mouse essential genes are associated with a wide spectrum of diseases affecting diverse physiological systems. Notably, human disease genes with essential mouse orthologs are over-represented among disease genes associated with cancer, suggesting links between adult cellular abnormalities and developmental functions. The proteins encoded by essential genes are highly connected in protein-protein interaction networks, which we find correlates with an over-representation of nuclear proteins amongst essential disease genes. Disease genes associated with essential orthologs also are more likely than those with non-essential orthologs to contribute to disease through an autosomal dominant inheritance pattern, suggesting that these diseases may actually result from semi-dominant mutant alleles. Overall, we have described attributes found in disease genes according to the essentiality status of their mouse orthologs. These findings demonstrate that disease genes do occupy highly connected positions in protein-protein interaction networks, and that due to the complexity of disease-associated alleles, essential genes cannot be ignored as candidates for causing diverse human diseases.     

Identification of plasma inactive renin as prorenin with a site-directed antibody

A sequence-specific antibody that recognizes a portion of the prosegment of human renin precursor was raised and used to provide direct evidence that plasma inactive renin contains the prosequence of renal renin and is therefore probably prorenin rather than an inactivated form of previously active renin. The information may help not only to resolve a major controversy concerning the nature of inactive renin in human plasma but also to elucidate its exact physiological role.     

Infection of brain-derived cells with the human immunodeficiency virus.

A malignant glioma cell line was infected with the human T-lymphotropic virus type IIIB isolate of the human immunodeficiency virus. Infection appeared to be latent rather than productive. Through contact with monocytic or lymphoid cells, the virus present in the glioma cells could be transmitted and gave rise to a fully productive infection.     

Silver staining studies on the short arm variant of human chromosome 17

Summary The absence of silver grain precipitation on human chromosome 17, consistently observed in four patients displaying the 17p variant, supports the hypothesis that the 17p variant is a structural heteromorphism rather than translocated satellite material.     

Glycosylphosphatidylinositol-anchored CD4/Thy-1 chimeric molecules serve as human immunodeficiency virus receptors in human, but not mouse, cells and are modulated by gangliosides.

Human and mouse cell lines that expressed a CD4/Thy-1 fusion protein on the cell surface were constructed and tested for the capacity to be infected with human immunodeficiency virus. The human cell lines, in contrast to the mouse line, were infectable. The CD4/Thy-1 fusion, which is anchored to the membrane by a glycosylphosphatidylinositol tail rather than a peptide linkage, can therefore serve as a human immunodeficiency virus receptor. In addition, this molecule, like CD4, is down-modulated in its cell surface expression by exogenous gangliosides.     

Measuring genetic admixture in human populations: The gila river story

Admixture between human populations is the norm rather than the exception. Many groups practice deme exogamy, so that all marriages include one spouse from an outside group. Typically, that group is a nearby population, but in many areas, especially since the advent of post-agricultural times, human movement has been greater and matings have occurred between ever more disparate groups. Because evolution is a response to local conditions, and occurs in the context of the overall genetic variability of local groups, admixture may be an important factor in human evolution and adaptation. To understand the potential impact of admixture on human evolution, it is important to know the effect of admixture on the geographic distribution of human variation.     

Immunopathogenesis of Pneumocystis carinii pneumonia

Pneumocystis carinii pneumonia (PCP) is a life-threatening infection that occurs in immunocompromised individuals, particularly those with advanced human immunodeficiency virus (HIV) infection. Interestingly, morbidity and mortality is related to the underlying cause of immunosuppression, with AIDS patients faring better than oncology patients for example. In addition, the prognosis of PCP has been correlated with markers of inflammation rather than with organism numbers. There is now increasing evidence that lung damage occurring during PCP is a result of the type and extent of the host inflammatory response to P. carinii rather than a result of direct damage by the organism. This review will discuss the experimental and clinical data demonstrating how the host-mediated inflammatory response to infection with P. carinii determines the ultimate outcome of PCP. A better understanding of the pathophysiology of PCP should lead to the development of improved therapies for the treatment of PCP.     

Evolutionary dynamics of the T-cell receptor VB gene family as inferred from the human and mouse genomic sequences

The diversity of T-cell receptors is generated primarily by the variable-region gene families, each of which is composed of a large number of member genes. The entire genomic sequence of the variable region (VB) of the T- cell receptor beta chain from humans and mice has become available. To understand the evolutionary dynamics of the VB gene family, we conducted a phylogenetic analysis of all VB genes from humans and mice, as well as a detailed analysis of internal DNA duplications in the human genomic VB region. The phylogenetic tree obtained shows that human and mouse VB genes intermingle extensively rather than forming two separate clusters and that many gene duplications occurred both before and after the divergence between primates and rodents. Analyzing the genomic maps of transposable elements (e.g., LINEs and SINEs) and relic VB genes in the VB gene region, we present evidence that a 20-kb VB region duplicated tandemly four times in the human lineage during the last 32 Myr, and 6 out of the 15 VB genes in this region have become nonfunctional during this period. Our results show that the VB gene family is subject to evolution by a birth-and-death process rather than to concerted evolution.