Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3α-hydroxysteroid dehydrogenase

Rat liver 3α-hydroxysteroid dehydrogenase cDNA was previously cloned by us. In this study, we used the rat cDNA as the probe to screen a human liver lambda gt11 cDNA library. A total of four different cDNAs were identified and sequenced. The sequence of one of the cDNAs is identical to that of the human chlordecone reductase cDNA except that our clone contains a much longer 5′-coding sequence than previously reported. The other three cDNAs display high degrees of sequence homology to those of both rat 3α-hydroxysteroid dehydrogenase and human chlordecone reductase. Because 3α-hydroxysteroid dehydrogenase and human chlordecone reductase belong to the aldo-keto reductase superfamily, we named these human clones HAKRa to HAKRd. Northern blot analysis showed that the liver expresses the highest levels of all four clones. Expression of all four clones was also detected in the brain, kidney, lung, and testis, whereas the placenta expressed only the messenger RNA for HAKRb. Genomic blot analysis using HAKRb as the probe detected multiple DNA fragments hybridized to the probe and a high degree of restriction fragment length polymorphism, suggesting the complexity of this supergene family.     

Reproductive parameters of the Taiwan monkey (Macaca cyclopis)

The following parameters of the Taiwan monkey,Macaca cyclopis, are presented and compared with other species ofMacaca: the menstrual cycle, sexual skin and vaginal desquamation changes during the menstrual cycle, time of ovulation, gestation period, breeding season, body weight of the newborn, age and body weight at menarche, body weight at first conception, spermatozoa count in the ejaculate, and the body weight at sexual maturity of the male.The many similarities in reproductive biology ofMacaca cyclopis, the rhesus monkey (Macaca mulatta), and the cynomolgus monkey (Macaca irus) include sexual skin and vaginal desquamation changes during the menstrual cycle, time of ovulation, gestation period, and placental sign. Body weight ofM. cyclopis is lower thanM. mulatta at birth, at menarche and at the first conception in females and at sexual maturation in males, is heavier thanM. irus at birth and is not different fromM. radiata at birth. No difference in menstrual cycle ofM. cyclopis was observed in animals housed in air-conditioned rooms compared to those housed in nonair-conditioned rooms. Summer amenorrhea was not observed inM. cyclopis but a high incidence of low vaginal desquamation was noted to occur in summer months. The mode of length of the menstrual cycle ofM. cyclopis is shorter thanM. mulatta and other species ofMacaca. The breeding season ofM. cyclopis in the wild extends from the end of September to January. In laboratory conditions their fertile period extends throughout the year.This study was supported in part by the National Council on Science Development, Republic of China, and in part by the Damon Runyon Memorial Fund for Cancer Research, U. S. A. (DRG-841 B and C). The paper was presented at the ICLA Asian Pacific Meeting on Laboratory Animals held at Tokyo and Inuyama, Japan, on September 20–25, 1971.     

High frequency of nonclassical steroid 21-hydroxylase deficiency.

Nonclassical steroid 21-hydroxylase deficiency is an autosomal recessive disorder that is defined by clinical and hormonal criteria that distinguishes it from the classical 21-hydroxylase deficiency. No estimates of the gene frequency of nonclassical 21-hydroxylase deficiency, also called attenuated, late-onset, acquired, and cryptic adrenal hyperplasia, have been published thus far. Here, we have used HLA-B genotype data in families containing multiple members affected with nonclassical 21-hydroxylase deficiency together with the results of quantitative hormonal tests to arrive at estimates of gene and disease frequencies for this disorder. We found nonclassical 21-hydroxylase deficiency to be a far more common disorder than classical 21-hydroxylase deficiency, which occurs in 1/8,000 births. The prevalence of the disease in Ashkenazi Jews was 3.7%; in Hispanics, 1.9%; in Yugoslavs, 1.6%; in Italians, 0.3%; and in the diverse Caucasian population, 0.1%. The gene for nonclassical 21-hydroxylase deficiency is in genetic linkage disequilibrium with HLA-B14 in Ashkenazi Jews, Hispanics, and Italians, but not in Yugoslavs or in a diverse, non-Jewish, Caucasian group. The penetrance of nonclassical 21-hydroxylase deficiency gene in the HLA-B14 containing haplotypes was incomplete. Thus, nonclassical 21-hydroxylase deficiency is probably the most frequent autosomal recessive genetic disorder in man and is especially frequent in Ashkenazi Jews, Hispanics, Italians, and Yugoslavs.     

Tempo and mode of concerted evolution in the L1 repeat family of mice

A 300-bp DNA sequence has been determined for 30 (10 from each of three species of mice) random isolates of a subset of the long interspersed repeat family L1. From these data we conclude that members of the L1 family are evolving in concert at the DNA sequence level in Mus domesticus, Mus caroli, and Mus platythrix. The mechanism responsible for this phenomenon may be either duplicative transposition, gene conversion, or a combination of the two. The amount of intraspecies divergence averages 4.4%, although between species base substitutions accumulate at the rate of approximately 0.85%/Myr to a maximum divergence of 9.1% between M. platythrix and both M. domesticus and M. caroli. Parsimony analysis reveals that the M. platythrix L1 family has evolved into a distinct clade in the 10-12 Myr since M. platythrix last shared a common ancestor with M. domesticus and M. caroli. The parsimony tree also provides a means to derive the average half-life of L1 sequences in the genome. The rates of gain and loss of individual copies of L1 were estimated to be approximately equal, such that approximately one-half of them turn over every 3.3 Myr.      

Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease

Modifications occurring on autoantigens during cell death have been proposed to have a role in the initiation of autoimmune diseases. Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most prominent. During apoptosis, 70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with the complex. Autoantibodies preferentially recognizing the apoptotic form of 70K have been described previously, and an apoptosis-specific epitope on 70K has been identified. This study shows that 29 of 53 (54%) MCTD sera preferentially recognize the apoptotic form of 70K over intact 70K. Moreover, we show that antibodies directed to an apoptosis-specific epitope on 70K are more specifically associated with MCTD than other anti-70K antibodies, suggesting that apoptotic 70K is a better antigen for the detection of these antibodies in MCTD patients. Longitudinal analysis of 12 MCTD patients showed in several patients that early sera are relatively enriched with antibodies recognizing an apoptosis-specific epitope, and that the levels of these apoptosis-specific antibodies decrease in time. These findings indicate that the early detection of apoptotic 70K is of considerable interest for anti-U1 snRNP-positive patients.     

Multi-agent modelling of climate outlooks and food security on a community garden scheme in Limpopo, South Africa

Seasonal climate outlooks provide one tool to help decision-makers allocate resources in anticipation of poor, fair or good seasons. The aim of the 'Climate Outlooks and Agent-Based Simulation of Adaptation in South Africa' project has been to investigate whether individuals, who adapt gradually to annual climate variability, are better equipped to respond to longer-term climate variability and change in a sustainable manner. Seasonal climate outlooks provide information on expected annual rainfall and thus can be used to adjust seasonal agricultural strategies to respond to expected climate conditions. A case study of smallholder farmers in a village in Vhembe district, Limpopo Province, South Africa has been used to examine how such climate outlooks might influence agricultural strategies and how this climate information can be improved to be more useful to farmers. Empirical field data has been collected using surveys, participatory approaches and computer-based knowledge elicitation tools to investigate the drivers of decision-making with a focus on the role of climate, market and livelihood needs. This data is used in an agent-based social simulation which incorporates household agents with varying adaptation options which result in differing impacts on crop yields and thus food security, as a result of using or ignoring the seasonal outlook. Key variables are the skill of the forecast, the social communication of the forecast and the range of available household and community-based risk coping strategies. This research provides a novel approach for exploring adaptation within the context of climate change.     

Effects of thymoquinone on liver miRNAs and oxidative stress in Ehrlich acid mouse solid tumor model

We investigated the effects of thymoquinone (TQ) on the expression of liver microRNAs (miRNAs), liver histopathology and oxidative stress in Ehrlich acid solid tumor model induced mice. We used 24 male BALB/c mice divided randomly into three groups. Control (C) group mice were injected intraperitoneally (i.p.) with 0.5 ml saline for four weeks. Tumor (T) group mice were injected i.p. with 0.5 ml saline for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck to induce solid tumor formation. TQ (T + Tq) group mice injected i.p. with 10 mg/kg TQ for four weeks, then Ehrlich acid tumor cells were injected subcutaneously into the neck of the mice in this group to induce solid tumor formation. At the end of the study, liver from all groups were removed for histopathological and miRNAs analysis, and oxidative stress measurement. We found that the expression of miR-206b-3p was up-regulated and the oxidative stress and necrosis increased in the liver tissue of mice with Ehrlich acid solid tumor. TQ application decreased the oxidative stress, prevented necrosis, increased regeneration and down-regulated the expression of miR-206b-3p in the liver tissue.     

Are Lepidoptera an effective ‘umbrella group‘ for biodiversity conservation?

Lepidoptera have attracted more attention than other insects in the development of insect conservation, commonly as charismatic flagship species. Wider benefits of conservation studies on single species include developing and clarifying their role as putative umbrella taxa whereby their protection also confers protection on coexisting organisms which are not as well documented. Examples are given of such umbrella Lepidoptera from the Australian region, and the values of documenting and defining changes in lepidopteran assemblages (for example, through analysis of light-trap catches of moths) as correlates of environmental change are outlined. Selection of optimal groups depends on documenting responses of both species and higher taxa to changes in vegetation or microclimate in particular. Potent umbrella taxa manifest many of the features of indicator and flagship taxa.     

Mismatch Correction Acts as a Barrier to Homeologous Recombination in Saccharomyces Cerevisiae

A homeologous mitotic recombination assay was used to test the role of Saccharomyces cerevisiae mismatch repair genes PMS1, MSH2 and MSH3 on recombination fidelity. A homeologous gene pair consisting of S. cerevisiae SPT15 and its S. pombe homolog were present as a direct repeat on chromosome V, with the exogenous S. pombe sequences inserted either upstream or downstream of the endogenous S. cerevisiae gene. Each gene carried a different inactivating mutation, rendering the starting strain Spt15(-). Recombinants that regenerated SPT15 function were scored after nonselective growth of the cells. In strains wild type for mismatch repair, homeologous recombination was depressed 150- to 180-fold relative to homologous controls, indicating that recombination between diverged sequences is inhibited. In one orientation of the homeologous gene pair, msh2 or msh3 mutations resulted in 17- and 9.6-fold elevations in recombination and the msh2 msh3 double mutant exhibited an 43-fold increase, implying that each MSH gene can function independently in trans to prevent homeologous recombination. Homologous recombination was not significantly affected by the msh mutations. In the other orientation, only msh2 strains were elevated (12-fold) for homeologous recombination. A mutation in MSH3 did not affect the rate of recombination in this orientation. Surprisingly, a pms1 deletion mutant did not exhibit elevated homeologous recombination.