AB0 blood group incompatibility and inbreeding effects: Evidence for an interaction

Summary It is known that consanguinity reduces the chances of maternal-foetal incompatibility but it is not known whether inbreeding influences the expression of the effects of such incompatibility. This paper investigates and finds evidence for an interaction between inbreeding and AB0 blood group incompatibility on the expression of neonatal mortality, sibship precocious mortality, neonatal jaundice, asphyxia, and sex ratio, through screening of 3923 consecutive newborns. Inbreeding and incompatibility individually showed variable effects on the above parameters, but their interaction was such that, in the presence of inbreeding, incompatibility reduced the incidence/relative risk of all the above factors. Such a uniform negative interaction was presumed to be due to homozygosity of some pleiotropic genes caused by inbreeding.     

Alteration of the acyl chain composition of free fatty acids,acyl coenzyme A and other liPids by dietary polyunsaturated fats

Dietary alterations were used to demonstrate selective handling of fatty acids during their redistributionin vivo. Differences in the mol Per cent of individual acyl chains in the non-esterified fatty acid, acyl-coenzyme A and PhosPholiPid fractions reflected a result of relative Precursor abundance combined with enzymic selectivities. Selective distributions were observed in the utilization of individual acyl chains between 16:0 and 18:0, 18:1 and 18:2, and among 20:3, 20:4 and 20:5, 22:6 by ligase(s), hydrolase(s) and acyl-transferases. The variations in the mol Per cent of linoleate Present in the acyl-coenzyme A fraction of liver relative to that in the non-esterified fatty acids suggested anin vivo regulation of the level of linoleoyl-coenzyme A that influenced the synthesis of both arachidonoyl-coenzyme A and lipids. The greater abundance of eicosaPentaenoic acid in the free fatty acid fraction relative to that in the acyl-coenzyme A fraction may increase the ability of dietary 20: 5n-3 to be an effective inhibitor of the synthesis of Prostaglandins derived from 20:4n-6.     

Changes in photoelectron transport activity in cyanophage N-1-infected cells ofNostoc muscorum

Cyanophage N-1-infectedNostoc muscorum cells were unable to carry out oxygen evolution and photosystem-II-dependent electron transport (H₂ODCPIP). This was associated with preferential degradation of phycobiliproteins. Such cells also exhibited decreased rate of ferredoxin:NADP⁺ oxidoreductase activity. However, Ca²⁺-dependent ATPase activity was maintained at a higher level (80%). The results suggested that virus development proceeds in the absence of photosystem-II activity, and the energy is provided by cyclic photophosphorylation aside from that possibly obtained via degradation of carbohydrate reserves.     

Age-related alterations in oxidatively damaged proteins of mouse skeletal muscle mitochondrial electron transport chain complexes

Age-associated mitochondrial dysfunction is a major source of reactive oxygen species (ROS) and oxidative modification to proteins. Mitochondrial electron transport chain (ETC) complexes I and III are the sites of ROS production and we hypothesize that proteins of the ETC complexes are primary targets of ROS-mediated modification which impairs their structure and function. The pectoralis, primarily an aerobic red muscle, and quadriceps, primarily an anaerobic white muscle, have different rates of respiration and oxygen-carrying capacity, and hence, different rates of ROS production. This raises the question of whether these muscles exhibit different levels of oxidative protein modification. Our studies reveal that the pectoralis shows a dramatic age-related decline in almost all complex activities that correlates with increased oxidative modification. Similar complex proteins were modified in the quadriceps, at a significantly lower level with less change in enzyme and ETC coupling function. We postulate that mitochondrial ROS causes damage to specific ETC subunits which increases with age and leads to further mitochondrial dysfunction. We conclude that physiological characteristics of the pectoralis vs quadriceps may play a role in age-associated rate of mitochondrial dysfunction and in the decline in tissue function.     

Development of a fluorescent transgenic zebrafish biosensor for sensing aquatic heavy metal pollution

We report a transgenic zebrafish (Danio rerio) designed to respond to heavy metals using a metal-responsive promoter linked to a fluorescent reporter gene (DsRed2). The metallothionein MT-Ia1 promoter containing metal-responsive elements was derived from the Asian green mussel, Perna viridis. The promoter is known to be induced by a broad spectrum of heavy metals. The promoter-reporter cassette cloned into the Tol2 transposon vector was microinjected into zebrafish embryos that were then reared to maturity. A transgene integration rate of 28 % was observed. The confirmed transgenics were mated with wild-type counterparts, and pools of F₁ embryos were exposed to sub-lethal doses of Cd²⁺, Cu²⁺, Hg²⁺, Pb²⁺ and Zn²⁺. The red fluorescence response of zebrafish embryos was observed 8 h post- exposure to these sub-lethal doses of heavy metals using a fluorescence microscope. Reporter expression estimated by real-time PCR revealed eightfold, sixfold and twofold increase on exposure to highest concentrations of Hg²⁺, Cd²⁺ and Cu²⁺, while Pb²⁺ and Zn²⁺ had no effect. This biosensor could be a first-level screening method for confirming aquatic heavy metal bio-toxicity to eukaryotes.     

Molecular insight into the genesis of ranked caste populations of western India based upon polymorphisms across non-recombinant and recombinant regions in genome

Background  

Large-scale trade and cultural contacts between coastal populations of western India and Western-Eurasians paved for extensive immigration and genesis of wide spectrum of admixed gene pool. To trace admixture and genesis of caste populations of western India, we have examined polymorphisms across non-recombining 20 Y-SNPs, 20 Y-STRs, 18 mtDNA diagnostic sites, HVS-1 plus HVS-2 regions; and recombining 15 highly polymorphic autosomal STRs in four predominant caste populations- upper-ranking Desasth-brahmin and Chitpavan-brahmin; a middle-ranking Kshtriya Maratha; and a lower-rank peasant Dhangar.     

Exact Tests using Two Correlated Binomial Variables in Contemporary Cancer Clinical Trials

New therapy strategies for the treatment of cancer are rapidly emerging because of recent technology advances in genetics and molecular biology. Although newer targeted therapies can improve survival without measurable changes in tumor size, clinical trial conduct has remained nearly unchanged. When potentially efficacious therapies are tested, current clinical trial design and analysis methods may not be suitable for detecting therapeutic effects. We propose an exact method with respect to testing cytostatic cancer treatment using correlated bivariate binomial random variables to simultaneously assess two primary outcomes. The method is easy to implement. It does not increase the sample size over that of the univariate exact test and in most cases reduces the sample size required. Sample size calculations are provided for selected designs.     

Controlling cancer through the autotaxin-lysophosphatidic acid receptor axis

LPA (lysophosphatidic acid, 1-acyl-2-hydroxy-sn-glycero-3-phosphate), is a growth factor-like lipid mediator that regulates many cellular functions, many of which are unique to malignantly transformed cells. The simple chemical structure of LPA and its profound effects in cancer cells has attracted the attention of the cancer therapeutics field and drives the development of therapeutics based on the LPA scaffold. In biological fluids, LPA is generated by ATX (autotaxin), a lysophospholipase D that cleaves the choline/serine headgroup from lysophosphatidylcholine and lysophosphatidylserine to generate LPA. In the present article, we review some of the key findings that make the ATX-LPA signalling axis an emerging target for cancer therapy.