Rates of decay for the survival probability of a mutant gene II The multitype case

This paper extends the results of [1] to the multitype case. For a multitype branching process that is slightly supercritical, approximations for the survival probability in terms of the maximal eigenvalue of the mean matrix and a generalized variance ² are developed. Our results improve upon those of Hoppe [5] and Eshel [3] that seek to validate a conjecture of Ewens [4].Research supported in part by NSF grant DMS 9007182     

Spotted in the News: Using Media Reports to Examine Leopard Distribution,Depredation, and Management Practices outside Protected Areas in Southern India

There is increasing evidence of large carnivore presence outside protected areas, globally. Although this spells conservation success through population recoveries, it makes carnivore persistence in human-use landscapes tenuous. The widespread distribution of leopards in certain regions of India typifies this problem. We obtained information on leopard-human interactions at a regional scale in Karnataka State, India, based on systematic surveys of local media reports. We applied an innovative occupancy modelling approach to map their distribution patterns and identify hotspots of livestock/human depredation. We also evaluated management responses like removals of ‘problem’ leopards through capture and translocations. Leopards occupied around 84,000 km² or 47% of the State’s geographic area, outside designated national parks and wildlife sanctuaries. Their presence was facilitated by extent of vegetative cover- including irrigated croplands, rocky escarpments, and prey base in the form of feral and free-ranging dogs. Higher probabilities of livestock/human attacks by leopards were associated with similar ecological features as well as with capture/removals of leopards. Of the 56 cases of leopard removals reported, 91% did not involve human attacks, but followed livestock predation or only leopard sightings. The lack of knowledge on leopard ecology in human-use areas has resulted in unscientific interventions, which could aggravate the problem rather than mitigating it. Our results establish the presence of resident, breeding leopards in human-use areas. We therefore propose a shift in management focus, from current reactive practices like removal and translocation of leopards, to proactive measures that ensure safety of human lives and livelihoods.     

Plasmid-Encoded Sequestration of Copper by Pseudomonas pickettii Strain US321

Pseudomonas pickettii strain US321 appeared to elicit a copper resistance mechanism upon exposure to copper. The bacterial colonies turned blue in the presence of this metal in a chemically defined medium, suggesting accumulation of copper. Prolonged exposure to copper resulted in the characteristic “copper sink” morphology of the colonies. Atomic absorption spectrophotometric analysis confirmed that this organism can accumulate copper. The strain US321 exhibited a high-molecular-weight plasmid, pUS321. The plasmid-cured strain, PC25, is highly sensitive to copper owing to a poor copper management. A plasmid-encoded sequestration mechanism operating in the strain US321 is suggested. Received: 3 September 1996 / Accepted: 12 December 1996     

Alcohol Consumption Practices among Married Women of Reproductive Age in Nepal: A Population Based Household Survey

BackgroundAlcohol chemically known as ethanol, causes several health, economic and social consequences across the world. Literatures suggest potential harm of alcohol drinking by pregnant women especially to the fetus and the mother. Despite anumber of significant public health problems related to alcohol consumption, this area has been ignored in Nepal and information at the national level is limited. Thus this study aimed at finding the prevalence of alcohol consumption among married women of reproductive age.MethodsA nationally representative household survey was carried out from April to August 2013 by taking 16 districts across all 15 eco administrative regions. From the selected districts, 86 village development committees and 14 municipalities were selected as primary sampling units using probability proportionate to size, followed by random selection of 3 wards from each primary sampling unit. Finally, 30 households within each ward were selected using systematic random sampling, and one married women of reproductive age from each household. A total of 9000 married women of reproductive age were interviewed using a semi-structured questionnaire, on alcohol consumption practices including environmental factors and socio demographic characteristics and were included in the analysis.ResultsNational prevalence of alcohol consumption ever among married women of reproductive age was 24.7% (95% CI:21.7–28.0), last 12 months 17.9% (95% CI:15.3–20.7) and last 30 days (current drinking) 11.8% (95% CI:9.8–14.1). There was substantial variation among the districts ranging from 2% to 60%. Multivariable analysis suggests women with no education or within formal education, dalit and janajatis ethnicity, whose husbands drink alcohol, who brew alcohol at home and women from mountains were significantly at higher risk of consuming alcohol. Among the women who drank alcohol in last 12 months, a substantial proportion of them drank home brewed alcoholic beverages (95.9%, 95% CI:94.3–97.4).ConclusionAlcohol consumption was common practice among married women of reproductive age in Nepal with variation among the subgroups of population. Thus, further investigation and behavior change communication interventions to reduce alcohol consumption especially among the women with higher risk of drinking is essential.     

TCR and IL-7 Signaling Are Altered in the Absence of Functional GTPase of the Immune Associated Nucleotide Binding Protein 5 (GIMAP5)

GTPase of the immune associated nucleotide binding protein (GIMAP) family of proteins are expressed essentially in cells of the hematopoietic system. Mutation in the founding member of this gene family, Gimap5, results in the lymphopenic phenotype in Bio-Breeding diabetes prone rats. In mice, deletion of functional Gimap5 gene affects the survival and renewal of hematopoietic stem cells in addition to the defects observed in T cells. Here we show that T cells from OTII TCR-transgenic Gimap5^sph/sph mice do not proliferate in response to its cognate antigen. Furthermore, T cells from Gimap5 mutant rats and mice show decreased phosphorylation of STAT5 following stimulation with IL-7. Our results suggest that functional Gimap5 is required for optimal signaling through TCR and IL-7R in T cells.     

Alterations in atrial natriuretic peptide and its receptors in streptozotocin-induced diabetic rat kidneys

In this study the effect of diabetes mellitus on atrial natriuretic peptide (ANP) receptors in streptozotocin- (STZ-) induced diabetic rat kidneys was studied. Moreover, plasma ANP concentration was evaluated in diabetic and control rats by using radioimmunoassay. In addition, the expression of ANP in the kidneys of control and diabetic rats was evaluated by immunohistochemistry. Body-weight loss and increased glucose levels were used as indices of diabetes mellitus in the STZ-induced rats. There was a significant loss in the body weight of the diabetic rats compared to controls. The efficacy of STZ administration was confirmed by rising blood glucose levels, which were significantly higher in diabetic rats compared to controls. Plasma ANP concentration was significantly greater in the diabetic rats in comparison with controls. Moreover, our immunohistochemical results show that the expression of ANP in diabetic rats was higher than that in age-matched controls. ANP was observed in the cells lining the proximal convoluted tubules in the cortex. The distribution and levels of ANP receptors in the kidneys of diabetic rats and age-matched controls were investigated using quantitative receptor autoradiography. Our results demonstrate significant decrease in ANP receptors in the kidneys of the diabetic rats compared to controls. The significant decrease was found in the juxtaglomerular medulla, inner medulla, and the papillae. The decrease in ANP receptors observed in the diabetic kidneys could have pathological consequences resulting in renal resistance to ANP in diabetes.     

Improved retention of idarubicin after intravenous injection obtained for cholesterol-free liposomes

To date there has been a focus on the application of sterically stabilized liposomes, composed of saturated diacylphospholipid, polyethylene glycol (PEG) conjugated lipids (5-10 mole%) and cholesterol (CH) (>30 mole%), for the systemic delivery of drugs. However, we are now exploring the utility of liposome formulations composed of diacylphospholipid conjugated PEG mixtures prepared in the absence of added cholesterol, with the primary objective of developing formulations that retain encapsulated drug better than comparable formulations prepared with cholesterol. In this report the stability of cholesterol-free distearoylphosphatidylcholine (DSPC):distearoylphosphatidylethanolamine (DSPE)-PEG(2000) (95:5 mol/mol) liposomes was characterized in comparison to cholesterol-containing formulations DSPC:CH (55:45 mol/mol) and DSPC:CH:DSPE-PEG(2000) (50:45:5 mol/mol/mol), in vivo. Circulation longevity of these formulations was determined in consideration of variables that included varying phospholipid acyl chain length, PEG content and molecular weight. The application of cholesterol-free liposomes as carriers for the hydrophobic anthracycline antibiotic, idarubicin (IDA), was assessed. IDA was encapsulated using a transmembrane pH gradient driven process. To determine stability in vivo, pharmacokinetic studies were performed using 'empty' and drug-loaded [(3)H]cholesteryl hexadecyl ether radiolabeled liposomes administered intravenously to Balb/c mice. Inclusion of 5 mole% of DSPE-PEG(2000) or 45 mole% cholesterol to DSPC liposomes increased the mean plasma area under the curve (AUC(0-24h)) 19-fold and 10-fold, respectively. Cryo-transmission electron micrographs of IDA loaded liposomes indicated that the drug formed a precipitate within liposomes. The mean AUC(0-4h) for free IDA was 0.030 micromole h/ml as compared to 1.38 micromole h/ml determined for the DSPC:DSPE-PEG(2000) formulation, a 45-fold increase, demonstrating that IDA was retained better in cholesterol-free compared to cholesterol-containing liposomes.     

Formation of transition metal-doxorubicin complexes inside liposomes

Doxorubicin complexation with the transition metal manganese (Mn²⁺) has been characterized, differentiating between the formation of a doxorubicin-metal complex and doxorubicin fibrous-bundle aggregates typically generated following ion gradient-based loading procedures that rely on liposome encapsulated citrate or sulfate salts. The physical and chemical characteristics of the encapsulated drug were assessed using cryo-electron microscopy, circular dichroism (CD) and absorbance spectrophotometric analysis. In addition, in vitro and in vivo drug loading and release characteristics of the liposomal formulations were investigated. Finally, the internal pH after drug loading was measured with the aim of linking formation of the Mn²⁺ complex to the presence or absence of a transmembrane pH gradient. Doxorubicin was encapsulated into either 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/cholesterol (Chol) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/Chol liposomes, where the entrapped salts were citrate, MnSO₄ or MnCl₂. In response to a pH gradient or a Mn²⁺ ion gradient, doxorubicin accumulated inside to achieve a drug-to-lipid ratio of approximately 0.2:1 (wt/wt). Absorbance and CD spectra of doxorubicin in the presence of Mn²⁺ suggested that there are two distinct structures captured within the liposomes. In the absence of added ionophore A23187, drug loading is initiated on the basis of an established pH gradient; however, efficient drug uptake is not dependent on maintenance of the pH gradient. Drug release from DMPC/Chol is comparable regardless of whether doxorubicin is entrapped as a citrate-based aggregate or a Mn²⁺ complex. However, in vivo drug release from DSPC/Chol liposomes indicate less than 5% or greater than 50% drug loss over a 24-h time course when the drug was encapsulated as an aggregate or a Mn²⁺ complex, respectively. These studies define a method for entrapping drugs possessing coordination sites capable of complexing transition metals and suggest that drug release is dependent on lipid composition, internal pH, as well as the nature of the crystalline precipitate, which forms following encapsulation.     

Correlations between the benzene character of acenes or helicenes and simple molecular descriptors

Aromatic stabilities of acenes and helicenes, which are responsible for their biological, environmental and cancerous behavior have been modeled using a newly introduced Sadhana (Sd) and A indices. The results are compared with those obtained from PI (Padmakar-Ivan) index. The regression analysis has shown that excellent results are obtained by considering acenes and helicenes as separate classes of isomeric benzenoid hydrocarbons and that A index is better index than both PI and Sd indices.     

Book review of evolutionary genetics: Concepts,analysis, and practice

Recent technological advances have expanded and increased the resolution of studies in evolutionary biology, creating a need for a modern textbook that highlights the latest developments in the field. Evolutionary Genetics: Concepts, Analysis, and Practice, by Glenn‐Peter Sætre and Mark Ravinet (2019), as well as the book's accompanying online tutorials, provide a clear, up‐to‐date, and enjoyable introduction to evolutionary biology and genetics that explains fundamental evolutionary concepts, illustrates recent exciting findings, and offers hands‐on experience in analysing and interpreting genomic data. The book's accessible nature and emphasis on developing practical skills make it a valuable resource for undergraduate courses on evolutionary biology.