Kin selection is implicated in partial sib-mating populations with constant viability differences before mating

The change in the frequency of a rare mutant allele under constant sex-differentiated viability selection in an infinite, partial full-sib mating population is studied. The diplo-diploid and haplo-diploid polygynous models are considered with a Poisson distribution for the number of offspring produced by every mated female. Reproduction is followed by weak selection among the offspring and then mating to form the next generation. It is shown that the rate of change with respect to the frequency of the mutant allele and the intensity of selection can be expressed in terms of costs or benefits of substituting the mutant type for the wild type, which correspond to average excesses in viability in females and males, multiplied by coefficients of relatedness to the individuals affected by such a substitution and reproductive values associated to the sexes of these individuals. This reveals hidden interactions between mated individuals and between males for mating, the former having positive effects on the reproductive success of related individuals and the latter having negative effects. Such interactions are the result of reproductive constraints when a fixed proportion of females must mate with a male sib and all females are fertilized as long as one mate is available. However, they affect the change in allele frequency because there is inbreeding or relatedness between mates and more generally relatedness between interacting individuals. Surprisingly, the effects of these interactions cancel out in a diploid population when the number of offspring is large enough so that the possibility for a female to have no male sib to mate with can be neglected and the viability differences are the same in both sexes.     

DNA sequence conservation between the Bacillus anthracis pXO2 plasmid and genomic sequence from closely related bacteria

Background  

Complete sequencing and annotation of the 96.2 kb Bacillus anthracis plasmid, pXO2, predicted 85 open reading frames (ORFs). Bacillus cereus and Bacillus thuringiensis isolates that ranged in genomic similarity to B. anthracis, as determined by amplified fragment length polymorphism (AFLP) analysis, were examined by PCR for the presence of sequences similar to 47 pXO2 ORFs.     

7-Methoxyfuro[2,3-c]pyridine-4-carboxamides as PDE4 inhibitors: a potential treatment for asthma

The synthesis and pharmacological profile of a novel series of 7-methoxy-furo[2,3-c]pyridine-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4).     

UDP-Glucose: (1,3)-beta-Glucan Synthase from Daucus carota L. : Characterization, Photoaffinity Labeling, and Solubilization

The membrane-bound UDP-glucose-β-(1,3)-glucan synthase from Daucus carota L. was characterized and a solubilization procedure was developed. The enzyme exhibited maximal activity in the presence of 0.75 millimolar Ca²⁺, 0.5 millimolar EGTA, and 5 millimolar cellobiose at pH 7.5 and 30°C at 1 millimolar UDPG. Reaction products were confirmed to be (1,3)-linked glucan. Polypeptides of 150, 57, and 43 kilodaltons were labeled with the photoactivatible affinity label 5-azido-uridine 5′-β-[³²P] diphosphateglucose. Labeling of the 150 and 57 kilodalton polypeptides was completely protected against by 1 millimolar non-radioactive UDPG suggesting that one or both of these polypeptides may represent the UDPG binding subunit of glucan synthase. Carrot glucan synthase was solubilized with the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) in the absence of divalent cations and chelators; however, the percentage of enzyme which could be solubilized showed variability with membrane source. With microsomal membranes, up to 80% of the enzyme was released with 0.7% CHAPS. Solubilized enzyme was stable for at least 9 hours at 4°C. When more highly purified membrane fractions were isolated from sucrose step gradients a slightly different picture emerged. Activity from the 20/30% interface (Golgi and tonoplast enriched) was readily solubilized and expressed. Activity from the 30/40% interface (plasma membrane enriched) was also solubilized; however, it was necessary to add heat inactivated microsomes to assay mixtures for full activity to be expressed. A requirement for endogenous activators is suggested.     

Comparison of immunodeficiency and AIDS defining conditions in HIV negative and HIV positive men with haemophilia A.

OBJECTIVE--To investigate the hypothesis that high usage of clotting factor concentrate, rather than HIV infection, is the cause of immunodeficiency and AIDS in men with haemophilia. DESIGN--A comparison of AIDS defining conditions and CD4 counts in HIV positive and HIV negative patients with haemophilia matched for usage of clotting factor concentrate. SETTING--A comprehensive care haemophilia centre. SUBJECTS--17 HIV positive and 17 HIV negative male patients with haemophilia A (age range 12-60 at beginning of study period) who had received similar amounts of clotting factor concentrate yearly over the years 1980-90. MAIN OUTCOME MEASURES--Clinical events listed as AIDS defining in the Centers for Disease Control AIDS definition; CD4 lymphocyte counts; death. RESULTS--Of 108 HIV positive male patients with haemophilia A, only 17 could be matched to an HIV negative patient. This was due to the much higher average usage of factor VIII in the HIV positive group. Between 1980 and 1990, 16 clinical events occurred in nine of the 17 HIV positive patients. No event occurred in the 17 HIV negative patients. In each pair the mean CD4 count during follow up was, on average, 0.5 x 10(9)/l lower in the HIV positive patient. CONCLUSION--These data reject the hypothesis that high usage of clotting factor concentrate, rather than HIV infection, is the cause of immunodeficiency and AIDS in men with haemophilia.     

Viral Hepatitis: Problems of Incidence and Control in Military Personnel

(A) Hepatitis B virus (HBV) is now the major cause of infectious viral hepatitis in U.S. military personnel and probably also in the civilian population over 15 years of age. (B) The incidence of icteric, viral hepatitis is much higher in U.S. military personnel than in comparable age groups in the civilian population. The 17-to 20-year-old enlisted men show the highest rates. (C) In parts of the world (e.g., U.S.A., Germany) where most of the inapparent infection is caused by the adw subtype of HBV, most of the acute clinical disease is caused by the ayw subtype. In the U.S.A. and Germany, 95% or more of HB_s Ag isolates from U.S. military personnel with acute hepatitis is ayw. (D) It may be many years before one can expect to have sufficient data for a decision as to the possible availability of an effective HBV vaccine. Accordingly, a decision is urgently needed regarding either the immediate use of the best practically available hepatitis immune gamma globulin, that can be prepared by modern techniques, for the prevention of hepatitis in U.S. military personnel or postponement of such use until an adequate and properly controlled trial can be carried out in active duty military personnel in an area of high incidence.     

Fixation probability for a beneficial allele and a mutant strategy in a linear game under weak selection in a finite island model

The effect of population structure on the probability of fixation of a newly introduced mutant under weak selection is studied using a coalescent approach. Wright's island model in a framework of a finite number of demes is assumed and two selection regimes are considered: a beneficial allele model and a linear game among offspring. A first-order approximation of the fixation probability for a single mutant with respect to the intensity of selection is deduced. The approximation requires the calculation of expected coalescence times, under neutrality, for lineages starting from two or three sampled individuals. The results are obtained in a general setting without assumptions on the number of demes, the deme size or the migration rate, which allows for simultaneous coalescence or migration events in the genealogy of the sampled individuals. Comparisons are made with limit cases as the deme size or the number of demes goes to infinity or the migration rate goes to zero for which a diffusion approximation approach is possible. Conditions for selection to favor a mutant strategy replacing a resident strategy in the context of a linear game in a finite island population are addressed.     

Depot-specific effects of fatty acids on lipid accumulation in children's adipocytes

Circulating concentrations of fatty acids are elevated in obesity, although their effect on regional fat deposition is relatively unexplored. With the increasing prevalence of childhood obesity, we aimed to investigate whether saturated and unsaturated fatty acids lead to differential lipid accumulation (LA) in children's subcutaneous and visceral adipocytes. To examine this, subcutaneous and peri-nephric pre-adipocytes, isolated from fat biopsies from 6 pre-pubertal children, were differentiated in vitro before being exposed to palmitate and/or oleate for 24 h. Lipid accumulation was then quantified by nile red staining. Palmitate significantly increased LA in visceral adipocytes at all doses > or =188 microM (e.g. Palmitate 750 microM: +30.0%[8.2]; p<0.01), whilst only a dose of 375 microM led to a significant, but smaller, increase in LA in subcutaneous adipocytes (Palmitate 375 micro: +13.0%[4.3]; p=0.02). In contrast, oleate significantly increased LA in subcutaneous (Oleate 1000 microM: +36.3%[14.0]; p=0.01), but not visceral (Oleate 1000 microM: +16.2%[9.6]; p=0.25) adipocytes. These data suggest that saturated and unsaturated fatty acids may exert depot-specific effects on lipid accumulation.     

Novel nucleotide triphosphates as potent P2Y2 agonists

The synthesis and P2Y2 activities of a novel series of nucleoside triphosphates are described. Many of these compounds were potent agonists of the P2Y2 receptor.     

A transferable plasticity region in Campylobacter coli allows isolates of an otherwise non‐glycolytic food‐borne pathogen to catabolize glucose

Thermophilic Campylobacter species colonize the intestine of agricultural and domestic animals commensally but cause severe gastroenteritis in humans. In contrast to other enteropathogenic bacteria, Campylobacter has been considered to be non‐glycolytic, a metabolic property originally used for their taxonomic classification. Contrary to this dogma, we demonstrate that several Campylobacter coli strains are able to utilize glucose as a growth substrate. Isotopologue profiling experiments with ¹³C‐labeled glucose suggested that these strains catabolize glucose via the pentose phosphate and Entner‐Doudoroff (ED) pathways and use glucose efficiently for de novo synthesis of amino acids and cell surface carbohydrates. Whole genome sequencing of glycolytic C. coli isolates identified a genomic island located within a ribosomal RNA gene cluster that encodes for all ED pathway enzymes and a glucose permease. We could show in vitro that a non‐glycolytic C. coli strain could acquire glycolytic activity through natural transformation with chromosomal DNA of C. coli and C. jejuni subsp. doylei strains possessing the ED pathway encoding plasticity region. These results reveal for the first time the ability of a Campylobacter species to catabolize glucose and provide new insights into how genetic macrodiversity through intra‐ and interspecies gene transfer expand the metabolic capacity of this food‐borne pathogen.