Human Biological Functions Research Articles

Two combinatorial optimization problems for SNP discovery using base-specific cleavage and mass spectrometry

BackgroundThe discovery of single-nucleotide polymorphisms (SNPs) has important implications in a variety of genetic studies on human diseases and biological functions. One valuable approach proposed for SNP discovery is based on base-specific cleavage and mass spectrometry. However, it is still very challenging to achieve the full potential of this SNP discovery approach.ResultsIn this study, we formulate two new combinatorial optimization problems. While both problems are aimed at reconstructing the sample sequence that would attain the minimum number of SNPs, they search over different candidate sequence spaces. The first problem, denoted as , limits its search to sequences whose in silico predicted mass spectra have all their signals contained in the measured mass spectra. In contrast, the second problem, denoted as , limits its search to sequences whose in silico predicted mass spectra instead contain all the signals of the measured mass spectra. We present an exact dynamic programming algorithm for solving the problem and also show that the problem is NP-hard by a reduction from a restricted variation of the 3-partition problem.ConclusionsWe believe that an efficient solution to either problem above could offer a seamless integration of information in four complementary base-specific cleavage reactions, thereby improving the capability of the underlying biotechnology for sensitive and accurate SNP discovery.

RFID technology for human implant devices

Abstract This article presents an overview on Radio Frequency Identification (RFID) technology for human implants and investigates the technological feasibility of such implants for locating and tracking persons or for remotely controlling human biological functions. Published results on the miniaturization of implantable passive RFID devices are reported as well as a discussion on the choice of the transmission frequency in wireless communication between a passive RFID device implanted inside human body and an off-body interrogator. The two techniques (i.e., inductive coupling and electromagnetic coupling) currently used for wirelessly supplying power to and read data from a passive implantable RFID device are described and some documented biomedical and therapeutic applications of human RFID-implant devices are finally reported.

Exponential growth combined with exponential decline explains lifetime performance evolution in individual and human species

The physiological parameters characterizing human capacities (the ability to move, reproduce or perform tasks) evolve with ageing: performance is limited at birth, increases to a maximum and then decreases back to zero at the day of death. Physical and intellectual skills follow such a pattern. Here, we investigate the development of sport and chess performances during the lifetime at two different scales: the individual athletes’ careers and the world record by age class in 25 Olympic sports events and in grandmaster chess players. For all data sets, a biphasic development of growth and decline is described by a simple model that accounts for 91.7% of the variance at the individual level and 98.5% of the variance at the species one. The age of performance peak is computed at 26.1 years old for the events studied (26.0 years old for track and field, 21.0 years old for swimming and 31.4 years old for chess). The two processes (growth and decline) are exponential and start at age zero. Both were previously demonstrated to happen in other human and non-human biological functions that evolve with age. They occur at the individual and species levels with a similar pattern, suggesting a scale invariance property.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-011-9274-9) contains supplementary material, which is available to authorised users.

Genomics of Long-Range Regulatory Elements

Transcriptional regulation of gene expression plays a significant role in establishing the diversity of human cell types and biological functions from a common set of genes. The components of regulatory control in the human genome include cis-acting elements that act across immense genomic distances to influence the spatial and temporal distribution of gene expression. Here we review the established categories of distant-acting regulatory elements, discussing the classical and contemporary evidence of their regulatory potential and clinical importance. Current efforts to identify regulatory sequences throughout the genome and elucidate their biological significance depend heavily on advances in sequence conservation-based analyses and on increasingly large-scale efforts applying transgenic technologies in model organisms. We discuss the advantages and limitations of sequence conservation as a predictor of regulatory function and present complementary emerging technologies now being applied to annotate regulatory elements in vertebrate genomes.

Discoveries of Rhythms in Human Biological Functions: A Historical Review

Discoveries of Rhythms in Human Biological Functions: A Historical Review

Biomarkers by gender

Regressions were determined for age-related human biological functions containing information for both genders. Their intercept T0 on the age axis (x) was used as a measure of the aging rate. The peak of the frequency distribution of T0 was consistent with earlier estimates. The frequency distribution of the ratio R of T0(women)/T0(men) peaked at unity. However, when the T0-values were divided into two groups, namely those relating to functions involving musculature vs. the rest, respectively, the ratio of R for musculature was <1 and that for the latter significantly >1. This suggests that men are the stronger gender when musculature is involved, but, more broadly, women are “biologically stronger”.

The APOBEC-2 crystal structure and functional implications for the deaminase AID.

APOBEC-2 (APO2) belongs to the family of apolipoprotein B messenger RNA-editing enzyme catalytic (APOBEC) polypeptides, which deaminates mRNA and single-stranded DNA. Different APOBEC members use the same deamination activity to achieve diverse human biological functions. Deamination by an APOBEC protein called activation-induced cytidine deaminase (AID) is critical for generating high-affinity antibodies, and deamination by APOBEC-3 proteins can inhibit retrotransposons and the replication of retroviruses such as human immunodeficiency virus and hepatitis B virus. Here we report the crystal structure of APO2. APO2 forms a rod-shaped tetramer that differs markedly from the square-shaped tetramer of the free nucleotide cytidine deaminase, with which APOBEC proteins share considerable sequence homology. In APO2, two long alpha-helices of a monomer structure prevent the formation of a square-shaped tetramer and facilitate formation of the rod-shaped tetramer via head-to-head interactions of two APO2 dimers. Extensive sequence homology among APOBEC family members allows us to test APO2 structure-based predictions using AID. We show that AID deamination activity is impaired by mutations predicted to interfere with oligomerization and substrate access. The structure suggests how mutations in patients with hyper-IgM-2 syndrome inactivate AID, resulting in defective antibody maturation.

A Note on Age-Related Biomarkers

Forty-eight randomly selected age-related human biological functions were analyzed in order to establish whether or not their (linear) regressions were modified by age-related standard errors. Possible reasons for this are advanced. Statistically significant multiple regressions were obtained in 25%, and 21% of the functions yielded statistically significant changes in the correlations between data and age when partial correlation coefficients were calculated. The conclusion is that age-related data need to be subjected to the above tests in order to minimize confounding factors.

Biorepair mechanisms and longevity.

The purpose of the study was to find out whether a link could be established between hypothetical biological repair mechanisms, their decay, and longevity. Human biological functions (biomarkers) can be classified accordingly as their generally linear age-related decline starts at birth or in adulthood ( approximately 1% per annum), or occurs at a rate of less than approximately 0.5% per annum Sums of exponentially declining functions representing the decline of repair mechanisms are fitted to the averages of each of the above groups. The time constants of the mechanisms are lowest for those ceasing normal function at the age of approximately 35-40 years, i.e., approximately at twice the maximal age at which puberty is reached. An extrapolation of the overall loss of the mechanisms, postulated to account for the declining biomarkers, is, at present, such as to reach zero in the twelfth decade of life.

Studies on human neutrophil biological functions by means of formyl-peptide receptor agonists and antagonists.

Phagocytes are activated by several extracellular signals, including formyl-peptides derived from bacterial proteins or disrupted cells. The most intensely studied member of the formylpeptide family is the synthetic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), whose specific receptors have been identified on neutrophil plasma membrane and subsequently cloned. The fMLP-receptor interaction activates multiple transduction pathways responsible for various neutrophil functions such as adhesion, chemotaxis, exocytosis of secretory granules and superoxide anion production, which represent the physiological response to bacterial infection and tissue damage. An unresolved question is whether signaling requirements are identical or specific for each physiological function. The development of fMLP receptor agonists and antagonists has led to an improvement of our knowledge about the above issue. Of particular interest is the possibility that receptorial antagonists, able to transiently inhibit neutrophil responses to formylpeptides, could be therapeutic agents in the treatment of inflammation-related diseases. Aim of this review is, i) to summarise the current understanding of the series of events that begins at the level of formylpeptide-receptor interaction and is responsible for the activation of transduction pathways, which finally determine neutrophil response; ii) to define the state of art regarding the synthesis as well as the biological actions of fMLP receptor agonists and antagonists.

How the United Nations mortality tables hang together

The mortality statistics of 80 member states of the United Nations were used to calculate Gompertz constants. When compared with a model based on the cumulant of failures of 46 human biological functions, they were found to form essentially one set, their slopes spreading out from a constant value like spokes from the axle of a wheel. Data for the longest lived regions agree with a prediction based on the above model, and those for less long lived regions are consistent with such a model having a constant normal cumulant average but increased S.D.s. Several different approaches support the view that the data are based on a probabilistic life-span.

Human biological decline and mortality rates

Intercepts on the x (age)-axis of 107 normalized declining human biological functions were determined and assembled in 3 histograms, being placed in increasing order within each decade (10 year period). The histograms were classed accordingly as they contained properties associated with dividing cells, sensory properties and non-dividing cells respectively. Their cumulants were determined, multiple regressions calculated and compared with current death-rates for women and men respectively, for 10 amongst the longest living populations in the World. An alternative verification based on risk theory led to an estimate of an optimal life expectancy of 96 years. The survival curve turns out to be of the form N(t)/N(0)=− exp ∫ t ∫ t″ exp [−{(t′−μ)/σ} 2] dt′· dt″ where the inner integral represents the cumulant dimension ( t′) and the outer one age ( t″). The premises underlying this study are compatible with the notion of a probable life-span, rather than a fixed one.

Have human biological functions evolved in support of a life-span?

Published data on age-related human biological functions are surveyed. For the many showing a linear decrease, regressions were calculated, or existing functions extrapolated, to yiled an intercept on the abscissa. The values of ×(0), the age at which a function ceases, provide a tentative means of comparison. The distribution of ×(0) is skewed because of the apparent longevity of nervous and cerebral functions. The database is sufficiently large to enable one to distinguish those biological functions which appear to have immediate survival value from those which do not. Such an approach may link biomarkers to estimates of the life-span of species.

Changes in fibronectin levels in the blood of patients with viral hepatitis A and B

Currently, the attention of researchers is attracted by fibronectin protein, which is present in all human organs, tissues and biological fluids, performing adhesive and opsonic functions. Fibronectin is most closely related to the liver: firstly, liver cells - hepatocytes - are the main site of blood fibronectin synthesis; secondly, numerous experimental and clinical studies have revealed a direct functional relationship between fibronectin levels and the uptake capacity of RES, in particular the relationship with the function of endothelial kupffer cells.