Melatonin synthesis in the human pineal gland

Poster presentation: The mammalian pineal organ is a peripheral oscillator, depending on afferent information from the so-called master clock in the suprachiasmatic nuclei of the hypothalamus. One of the best studied outputs of the pineal gland is the small and hydrophobic molecule melatonin. In all vertebrates, melatonin is synthesized rhythmically with high levels at night, signalling the body the duration of the dark period. Changes or disruptions of melatonin rhythms in humans are related to a number of pathophysiological disorders, like Alzheimer's disease, seasonal affective disorder or the Smith-Magenis-Syndrome. To use melatonin in preventive or curative interferences with the human circadian system, a complete understanding of the generation of the rhythmic melatonin signal in the human pineal gland is essential. Melatonin biosynthesis is best studied in the rodent pineal gland, where the activity of the penultimate and rate-limiting enzyme, the arylalkylamine N-acetyltransferase (AA-NAT), is regulated on the transcriptional level, whereas the regulatory role of the ultimate enzymatic step, achieved by the hydroxyindole O-methyltransferase (HIOMT), is still under debate. In rodents, Aa-nat mRNA is about 100-fold elevated during the night in response to adrenergic stimulation of the cAMP-signalling pathway, with AA-NAT protein levels closely following this dynamics. In contrast, in all ungulates studied so far (cow, sheep), a post-transcriptional regulation of the AA-NAT is central to determine rhythmic melatonin synthesis. AA-NAT mRNA levels are constantly elevated, and lead to a constitutive up-regulation of AA-NAT protein, which is, however, rapidly degraded via proteasomal proteolysis during the day. AA-NAT proteolysis is only terminated upon the nocturnal increase in cAMP levels. Similar to ungulates, a post-transcriptional control of this enzyme seems evident in the pineal gland of the primate Macaca mulatta. Studies on the molecular basis of melatonin synthesis in the human being are sparse and almost exclusively based on phenomenological data, derived from non-invasive investigations. Yet the molecular mechanisms underlying the generation of the hormonal message of darkness can currently only be deciphered using autoptic material. We therefore analyzed in human post-mortem pineal tissue Aa-nat and Hiomt mRNA levels, AA-NAT and HIOMT enzyme activity, and melatonin levels for the first time simultaneously within tissue samples of the same specimen. Here presented data show the feasibility of this approach. Our results depict a clear diurnal rhythm in AA-NAT activity and melatonin content, despite constant values for Aa-nat and Hiomt mRNA, and for HIOMT activity. Notably, the here elevated AA-NAT activity during the dusk period does not correspond to a simultaneous elevation in melatonin content. It is currently unclear whether this finding may suggest a more important role of the ultimate enzyme in melatonin synthesis, the HIOMT, for rate-limiting the melatonin rhythm, as reported recently for the rodent pineal gland. Thus, our data support for the first time experimentally that post-transcriptional mechanisms are responsible for the generation of rhythmic melatonin synthesis in the human pineal gland

Effective genes for resistance to stripe rust and virulence of Puccinia striiformis f. sp. tritici in Pakistan

Virulence patterns of wheat stripe rust were studied under the field conditions across four environmentally different locations: Quaid-i-Azam University (Islamabad), Pirsabak (NWFP), Faisalabad (Punjab) and Sakrand (Sindh) by planting trap nursery of tester lines and Pakistan varieties. The results revealed that stripe rust resistance genes Yr3, Yr5, Yr10, Yr15, Yr26, YrSP and YrCV were resistant, while Yr18 showed moderate susceptibility at all locations. Genes YrA-, Yr2, Yr6, Yr7, Yr8, Yr9, Yr17, Yr27 and gene combinations Opata (Yr27+Yr18) and Super Kauz (Yr9, Yr27, Yr18) were found susceptible. Among the fifty-one (51) commercial varieties; Barani70, Marvi2000, Iqbal2000, GA2000 and Seher2006 were found resistant. The genes found effective against stripe rust under natural conditions may be deployed singly or in combination to develop high yielding resistant wheat varieties in Pakistan.Key words: Near-isogenic lines, Puccinia striiformis f. sp. tritici, stripe rust, Triticum aestivum, virulence, Yr genes

Cost-effectiveness of community-based strategies for blood pressure control in a low-income developing country: findings from a cluster-randomized, factorial-controlled trial.

BACKGROUND: Evidence on economically efficient strategies to lower blood pressure (BP) from low- and middle-income countries remains scarce. The Control of Blood Pressure and Risk Attenuation (COBRA) trial randomized 1341 hypertensive subjects in 12 randomly selected communities in Karachi, Pakistan, to 3 intervention programs: (1) combined home health education (HHE) plus trained general practitioner (GP); (2) HHE only; and (3) trained GP only. The comparator was no intervention (or usual care). The reduction in BP was most pronounced in the combined group. The present study examined the cost-effectiveness of these strategies. METHODS AND RESULTS: Total costs were assessed at baseline and 2 years to estimate incremental cost-effectiveness ratios based on (1) intervention cost; (2) cost of physician consultation, medications, diagnostics, changes in lifestyle, and productivity loss; and (3) change in systolic BP. Precision of the incremental cost-effectiveness ratio estimates was assessed by 1000 bootstrapping replications. Bayesian probabilistic sensitivity analysis was also performed. The annual costs per participant associated with the combined HHE plus trained GP, HHE alone, and trained GP alone were $3.99,$3.34, and $0.65, respectively. HHE plus trained GP was the most cost-effective intervention, with an incremental cost-effectiveness ratio of$23 (95 confidence interval, 6-99) per mm Hg reduction in systolic BP compared with usual care, and remained so in 97.7 of 1000 bootstrapped replications. CONCLUSIONS: The combined intervention of HHE plus trained GP is potentially affordable and more cost-effective for BP control than usual care or either strategy alone in some communities in Pakistan, and possibly other countries in Indochina with similar healthcare infrastructure

Observation of a Cooperative Radiation Force in the Presence of Disorder

Cooperative scattering of light by an extended object such as an atomic ensemble or a dielectric sphere is fundamentally different from scattering from many point-like scatterers such as single atoms. Homogeneous distributions tend to scatter cooperatively, whereas fluctuations of the density distribution increase the disorder and suppress cooperativity. In an atomic cloud, the amount of disorder can be tuned via the optical thickness, and its role can be studied via the radiation force exerted by the light on the atomic cloud. Monitoring cold $^{87}\text{Rb}$ atoms released from a magneto-optical trap, we present the first experimental signatures of radiation force reduction due to cooperative scattering. The results are in agreement with an analytical expression interpolating between the disorder and the cooperativity-dominated regimes

Cooperative Scattering by Cold Atoms

We have studied the interplay between disorder and cooperative scattering for single scattering limit in the presence of a driving laser. Analytical results have been derived and we have observed cooperative scattering effects in a variety of experiments, ranging from thermal atoms in an optical dipole trap, atoms released from a dark MOT and atoms in a BEC, consistent with our theoretical predictions.Comment: submitted for special issue of PQE 201

Cohomological finiteness conditions for a class of metabelian groups

We consider a class of metabelian groups first studied by Baumslag and Stammbach and we show that these groups are consistent with the Bieri-Groves conjecture which relates cohomological finiteness conditions to the Bieri-Neumann-Strebel sigma invariant.Comment: 10 pages Accepted for publication in the Bulletin of the London Mathematical Societ

Cytological, Phenological and Molecular Characterization of B (S)-Genome Synthetic Hexaploids (2n = 6x = 42; AABBSS)

The B(S) genome diploids (2n = 2x = 14) are a unique reservoir of genetic diversity that can provide wheat breeders a rich source of allelic variation for stress traits that limit productivity. Restricted in practical use essentially due to their complex chromosomal behavior, these diploids have been in limited practical usage. The classic utilization example has been the suppression activity of the Ph locus and role in alien genetic transfer aspects that has been a standard in cytogenetic manipulation studies. For applied efforts focusing on Aegilops speltoides researchers in CIMMYT initiated an ambitious program to make AABBBB(SS) synthetics and made progress by generating over 50 such synthetics. Of these 20 were available for this study in which phenology and powdery mildew screening were evaluated. Four of these 20 synthetics appeared to be useful sources for further exploitation in breeding. These were entries 6, 9, 10 and 11 suited for exploitation in pre-breeding, with positive phenological characters particularly high thousand-kernel weight and are cytologically near euploid at 2n = 6x = 42. The subtle hyper (43) and hypoploid number would not negate their applied use potential. Preference however goes to genotypes 9 and 11

Complication rates in managing hepatic trauma: a cross-sectional study stratifying their outcomes

Background: Liver trauma is the most commonly observed injured organ in abdominal trauma. The objectives of this study was to determine and evaluate the rates of complication in the management of liver traumaMethods: This cross-sectional observational study using non-probability convenient sampling technique was done at surgical unit of Liaquat University of Medical and Health Sciences, Jamshoro, for 06 months. After ethical approval from Institute’s Institutional Review Board (IRB), patients presenting to surgical emergency of the hospital between ages 16 to 60 years having blunt or penetrating liver trauma within 04 hours of incident, either road traffic accident, sustaining a fall, sporting injury, knife or stab wound were include while patients of liver trauma conservatively managed or had severe co-morbid, not fit for anesthesia, with multiple organs lesions (polytrauma) and all hepatic injury patients that were hemo-dynamically stable were excluded. SPSS version 23 was used for data analysis keeping p-value <0.05 as significant.Results: Among 136 patients with mean age 32.33±11.23 years, 120(88.2%) were males. 122(89.7%) of the patients were admitted due to liver trauma of blunt variety while 14(10%) with penetrating liver injury. Overall mean duration of hospital stay was 13.1±4.58 days. 41(30%) patients reported intra-abdominal sepsis, followed by recurrent hemorrhage in 33(24%) of patients while in 22(16%) of patients, biliary leakage was observed. An insignificant difference persisted in either surgical intervention in terms of the complication rates.Conclusions: Higher complication rates were observed in patients with peri-hepatic packing, however outcome of both surgical techniques in terms of complication rates were found to be insignificant. Further studies are needed to shed light upon the findings or this study

Evaluation of seedling resistance and marker assisted selection for leaf rust (Puccinia triticina) resistance in Pakistani wheat landraces, cultivars and advanced lines

Leaf rust is amongst major biotic constraints of wheat (Triticum aestivum L.) having ability to cause substantial yield reductions worldwide. A continuous exploration for novel sources of resistance is pre-requisite for its management. Objectives of study were to conduct resistance evaluation of 112 Pakistani landraces and 48 advanced lines/ cultivars at seedling stage with total 10 virulent pathotypes of leaf rust, 3 from Pakistan and 7 from U.S.A and to detect closely linked markers for Lr10, 16, 34 and 67 genes through marker-assisted selection (MAS). Findings revealed most of Pakistani landraces showed lack of resistance at seedling stage. Only 7 accessions of landraces and 11 advanced lines were found highly resistant against all pathotypes of Pakistan. Similarly, 10 advanced lines exhibited high resistance while variability in resistance was recorded for landraces against all pathotypes tested from USA. Marker-assisted selection revealed Lr genes i.e. Lr10, Lr16, Lr34 and Lr67 were present at various frequencies. Highest frequency was observed for Lr34 followed by Lr16 & Lr67 while lowest was recorded for Lr10. These genetic resources and lines identified effective against Pakistan and USA pathotypes are potential sources for improvement of leaf rust (LR) resistance and can be utilized as valuable material for breeding resistant wheat cultivars.Campus Ic