Alpha-1 Adrenergic Receptors in the Medial Preoptic Area are Involved in the Induction of Sleep

This paper reviews the recent studies that led to the conclusion that the noradrenergic neurons projecting to the medial preoptic area (mPOA) are hypnogenic and that they mediate this action through α₁ adrenergic receptors. Microinjection of noradrenaline (NA) into the mPOA induced arousal. Studies using α₂ adrenergic drugs showed that the arousal induced by intrapreoptic injection of NA was due to its action on presynaptic α₂ adrenergic receptors. A combination of lesion and chemical stimulation techniques demonstrated that when NA acted on the postsynaptic α₁ receptors in the mPOA, it induced sleep. Intrapreoptic injection of α₁ agonist, methoxamine could induce sleep, when the hypothermia, which was simultaneously produced, was behaviorally compensated for by the animal. Increased arousal produced by the destruction of noradrenergic fibers in the mPOA further confirmed the hypnogenic role of these fibers.     

DNA probes for the rapid identification of medically important Candida species using a multianalyte profiling system

Recently, a new flow cytometric technology to detect multiple DNA target sequences in a single microtiter well plate was developed [multianalyte profiling (MAP) System, Luminex Corp., Austin, TX]. DNA probes, directed to the internal transcribed spacer 2 region of ribosomal DNA, were therefore designed to detect and differentiate PCR amplicons from six medically important Candida species using this system. Each probe was covalently linked to one of 100 available microsphere (bead) sets. Biotinylated PCR amplicons were then hybridized to the complementary probe on each bead set. Bound amplicons were detected fluorometrically using a streptavidin-linked reporter dye, R-phycoerythrin. Specific hybridization was noted for all six Candida species probes (mean sample-to-background ratio+/-standard error: Candida albicans, 58.7+/-1.2; Candida tropicalis, 53.2+/-3.8; Candida glabrata, 46.9+/-2.1; Candida parapsilosis, 59.9+/-1.6; Candida krusei, 54.7+/-3.7 vs. 0.9+/-0.03 for all heterologous Candida species DNA targets and vs. 1.0+/-0.1 for samples containing water instead of DNA; P < 0.001). The limit of test sensitivity was 0.5 pg of DNA. A sample could be processed and analyzed within 1 h post-PCR amplification. Therefore, the multianalyte profiling system was rapid, sensitive and specific for the detection and differentiation of the most medically important species of Candida.     

Herders of Indian and European cattle share their predominant allele for lactase persistence

Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region--part of an enhancer--approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same>1 Mb extended haplotype in both populations.     

A new model of the distal convoluted tubule

The Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney is a key determinant of Na(+) balance. Disturbances in NCC function are characterized by disordered volume and blood pressure regulation. However, many details concerning the mechanisms of NCC regulation remain controversial or undefined. This is partially due to the lack of a mammalian cell model of the DCT that is amenable to functional assessment of NCC activity. Previously reported investigations of NCC regulation in mammalian cells have either not attempted measurements of NCC function or have required perturbation of the critical without a lysine kinase (WNK)/STE20/SPS-1-related proline/alanine-rich kinase regulatory pathway before functional assessment. Here, we present a new mammalian model of the DCT, the mouse DCT15 (mDCT15) cell line. These cells display native NCC function as measured by thiazide-sensitive, Cl(-)-dependent (22)Na(+) uptake and allow for the separate assessment of NCC surface expression and activity. Knockdown by short interfering RNA confirmed that this function was dependent on NCC protein. Similar to the mammalian DCT, these cells express many of the known regulators of NCC and display significant baseline activity and dimerization of NCC. As described in previous models, NCC activity is inhibited by appropriate concentrations of thiazides, and phorbol esters strongly suppress function. Importantly, they display release of WNK4 inhibition of NCC by small hairpin RNA knockdown. We feel that this new model represents a critical tool for the study of NCC physiology. The work that can be accomplished in such a system represents a significant step forward toward unraveling the complex regulation of NCC.     

Comparison of two ferns (Adiantum capillus-veneris Linn. and Microsorium punctatum (Linn.) Copel) for their Cr accumulation potential and antioxidant responses

Study was undertaken to compare Cr accumulation in two ferns (Adiantum capillus-veneris Linn. and Microsorium punctatum (Linn.) Copel) and the role of antioxidants were also investigated towards metal tolerance in order to assess the use of ferns in phytomediation/ phytostabilization. Different concentrations (0, 50, 100, 150 microg g(-1) dw) of Cr were added to fern planted in pot containing 1 kg soil. In both the ferns, Cr accumulation increased with increase in metal concentration and maximum accumulation of 800.5 microg g(-1) (fronds) and 1457.4 microg g(-1) (roots) in M. punctatum and 660.8 microg g(-1) (fronds) and 1259.6 microg g(-1) (roots) in A. capillus-veneris was recorded. The increase in the levels of malondialdehyde, antioxidants and antioxidant enzymes (superoxide dismutase, glutathione peroxidase) in A. capillus-veneris was less pronounced than M. punctatum under Cr exposure as compared to their respective controls. In view of less decrease in chlorophyll content and antioxidants along with higher accumulation of Cr in the fronds M. punctatum, is indicative of its higher tolerance towards Cr. However, bioaccumulation factor (concentration of Cr in fronds/concentration of Cr in the soil) of both the ferns was recorded > 1 which qualifies the plants as potential Cr hyperaccumulator and suitable for phytoremediaton.     

Reported infections after human tissue transplantation before and after new food and drug administration (FDA) regulations, United States, 2001 through June, 2010

Processors distributed about 1.5?million human tissue allografts in the U.S. in 2007. The potential for transmitting infections through allografts concerns clinicians and patients. In 2005, FDA implemented Current Good Tissue Practice (CGTP) rules requiring tissue establishments to report to FDA certain serious infections after allograft transplantations. We describe infection reports following tissue transplants received by FDA from 2005 through June, 2010, and compare reporting before and after implementation of CGTP rules. We identified reports received by FDA from January 2001 through June, 2010, for infections in human tissue recipients, examining the reports by tissue type, organism, time to onset, severity, and reporter characteristics. Among 562 reports, 83 (20.8/year) were received from 2001?C2004, before the CGTP rules, 43 in the 2005 transition year, and 436 (96.9/year) from 2006 through June, 2010, after the rules. Tissue processors accounted for 84.2% of reports submitted after the rules, compared to 26.5% previously. Bacterial infections were the most commonly reported organisms before (64.6%) and after (62.2%) the new rules. Afterward, 2.5% (11) of reports described deaths, and 33.7% (147) involved hospitalizations. Before the rules, 13% (11) described deaths, and another 72% involved hospitalizations. Reports received by the FDA quadrupled since 2005, suggesting that CGTP regulations have contributed to increased reporting and improved tissue safety surveillance. However, these data do not confirm that the reported infections were caused by suspect tissues; most reports may represent routine post-surgical infections not actually due to allografts.     

Mining and gene ontology based annotation of SSR markers from expressed sequence tags of Humulus lupulus

Humulus lupulus is commonly known as hops, a member of the family moraceae. Currently many projects are underway leading to the accumulation of voluminous genomic and expressed sequence tag sequences in public databases. The genetically characterized domains in these databases are limited due to non-availability of reliable molecular markers. The large data of EST sequences are available in hops. The simple sequence repeat markers extracted from EST data are used as molecular markers for genetic characterization, in the present study. 25,495 EST sequences were examined and assembled to get full-length sequences. Maximum frequency distribution was shown by mononucleotide SSR motifs i.e. 60.44% in contig and 62.16% in singleton where as minimum frequency are observed for hexanucleotide SSR in contig (0.09%) and pentanucleotide SSR in singletons (0.12%). Maximum trinucleotide motifs code for Glutamic acid (GAA) while AT/TA were the most frequent repeat of dinucleotide SSRs. Flanking primer pairs were designed in-silico for the SSR containing sequences. Functional categorization of SSRs containing sequences was done through gene ontology terms like biological process, cellular component and molecular function.     

Characteristics of consultants who hold distinction awards in England and Wales: database analysis with particular reference to sex and ethnicity

Objective To determine whether women, ethnic minorities, and particular specialties are discriminated against in the receipt of NHS distinction awards.Design Analysis of database of consultants eligible for distinction awards.Setting England and Wales, 2002.Main outcome measures Holding of B, A, and Aplus distinction awards, analysed for all awards, irrespective of when made, and for awards made in the last five years studied.Results Women and doctors from ethnic minorities were substantially under-represented among award holders when no account was taken of potential confounding factors. Differences diminished after multivariate analysis, but some remained significant. For example, the adjusted odds ratio of women holding awards compared with men was 0.69 (95% confidence interval 0.59 to 0.82) for any award and 1.37 (0.86 to 2.20) for Aplus awards; the odds ratio for any award for non-white doctors trained abroad compared with white doctors trained in the United Kingdom was 0.45 (0.37 to 0.56). In the last five years studied the adjusted ratio of women to men was 0.94 (0.79 to 1.10) for B awards and 1.54 (0.85 to 2.83) for Aplus awards. The adjusted ratio for non-white British trained consultants was 0.86 (0.62 to 1.17) for B awards and 1.20 (0.37 to 3.87) for Aplus awards; for non-white consultants trained abroad it was 0.68 (0.54 to 0.85) for B awards and 0.69 (0.15 to 3.10) for Aplus awards; and for white consultants trained abroad it was 0.70 (0.54 to 0.91) for B awards and 0.90 (0.38 to 2.15) for Aplus awards.Conclusion Historical under-representation in award holding by women and doctors from ethnic minorities was partly explained by time spent as a consultant. Recent awards showed no under-representation of women and no appreciable under-representation of ethnic minorities overall. However, doctors who trained abroad—both white and non-white—remained under-represented for B awards.     

Maternal footprints of Southeast Asians in North India

We have analyzed 7,137 samples from 125 different caste, tribal and religious groups of India and 99 samples from three populations of Nepal for the length variation in the COII/tRNA(Lys) region of mtDNA. Samples showing length variation were subjected to detailed phylogenetic analysis based on HVS-I and informative coding region sequence variation. The overall frequencies of the 9-bp deletion and insertion variants in South Asia were 1.9 and 0.6%, respectively. We have also defined a novel deep-rooting haplogroup M43 and identified the rare haplogroup H14 in Indian populations carrying the 9-bp deletion by complete mtDNA sequencing. Moreover, we redefined haplogroup M6 and dissected it into two well-defined subclades. The presence of haplogroups F1 and B5a in Uttar Pradesh suggests minor maternal contribution from Southeast Asia to Northern India. The occurrence of haplogroup F1 in the Nepalese sample implies that Nepal might have served as a bridge for the flow of eastern lineages to India. The presence of R6 in the Nepalese, on the other hand, suggests that the gene flow between India and Nepal has been reciprocal.