Population‐level influence of a recurring disease on a long‐lived wildlife host

Despite a heightened interest regarding the role of infectious diseases in wildlife conservation, few studies have explicitly addressed the impacts of chronic, persistent diseases on long‐term host population dynamics. Using mycoplasmal upper respiratory tract disease (URTD) within natural gopher tortoise Gopherus polyphemus populations as a model system, we investigated the influence of chronic recurring disease epizootics on host population dynamics and persistence using matrix population models and Markov chain models for temporally autocorrelated environments. By treating epizootics as a form of environmental stochasticity, we evaluated host population dynamics across varying levels of outbreak duration (ρ), outbreak recurrence (f), and disease‐induced mortality (μ). Baseline results indicated a declining growth rate (λ) for populations under unexposed or enzootic conditions (λ_Enzootic= 0.903, 95% CI: 0.765–1.04), and a median time to quasi‐extinction of 29 years (range: 28–30 years). Under recurring epizootics, stochastic growth rates overlapped with baseline growth rates, and ranged between 0.838–0.902. Median quasi‐extinction times under recurring epizootics also overlapped for most scenarios with those of baseline conditions, and ranged between 18–29 years, with both metrics decreasing as a function of f and μ. Overall, baseline (enzootic) conditions had a greater impact on λ than epizootic conditions, and demographic vital rates were proportionately more influential on λ than disease‐ or outbreak‐associated parameters. Lower‐level elasticities revealed that, among disease‐ and outbreak‐associated parameters, increases in μ, force of infection (φ), and f negatively influenced λ. The impact of disease on host population dynamics depended primarily on how often a population underwent an epizootic state, rather than how long the epizootic persisted within the exposed population. The modeling framework presented in this paper could be widely applied to a range of wildlife disease systems in which hosts suffer from persistent recurring diseases.     

AVPR1A and SLC6A4 polymorphisms in choral singers and non-musicians: a gene association study

Amateur choral singing is a common pastime and worthy of study, possibly conferring benefits to health and social behaviour. Participants might be expected to possess musical ability and share some behavioural characteristics. Polymorphisms in genes concerned with serotonergic neurotransmission are associated with both behaviour and musical aptitude. Those investigated previously include the variable number tandem repeats RS1, RS3 and AVR in the AVPR1A (arginine vasopressin receptor 1a) gene and STin2 in the SLC6A4 (solute carrier family 6 [neurotransmitter transporter, serotonin], member 4) gene, as well as the SLC6A4 promoter region polymorphism, 5-HTTLPR. We conducted a genetic association study on 523 participants to establish whether alleles at these polymorphisms occur more commonly in choral singers than in those not regularly participating in organised musical activity (non-musicians). We also analysed tagging single nucleotide polymorphisms (SNPs) for AVPR1A and SLC6A4 to determine whether other variants in these genes were associated with singer/non-musician status. At the STin2 polymorphism, overall association with singer/non-musician status was evident at P = 0.006. The 9-repeat (P = 0.04) and 12-repeat (P = 0.04) alleles were more common in singers and the 10-repeat allele less so (P = 0.009). Odds ratios were 0.73 (95% CI 0.57-0.94) for the 10-repeat allele and 2.47 (95% CI 0.88-6.94) for the rarer 9-repeat allele. No overall association was detected at P<0.05 between any other polymorphism and singer/non-musician status. Our null findings with respect to RS3, RS1 and AVR, polymorphisms associated with musical ability by other authors, suggest that choir membership may depend partly on factors other than musical ability. In a related musical project involving one participating choir, a new 40-part unaccompanied choral work, "Allele", was composed and broadcast on national radio. In the piece, each singer's part incorporated their personal RS3 genotype.     

Arabidopsis nonhost resistance gene PSS1 confers immunity against an oomycete and a fungal pathogen but not a bacterial pathogen that cause diseases in soybean

ABSTRACT: BACKGROUND: Nonhost resistance (NHR) provides immunity to all members of a plant species against all isolates of a microorganism that is pathogenic to other plant species. Three Arabidopsis thaliana PEN (penetration deficient) genes, PEN1, 2 and 3 have been shown to provide NHR against the barley pathogen Blumeria graminis f. sp. hordei at the prehaustorial level. Arabidopsis pen1-1 mutant lacking the PEN1 gene is penetrated by the hemibiotrophic oomycete pathogen Phytophthora sojae, the causal organism of the root and stem rot disease in soybean. We investigated if there is any novel nonhost resistance mechanism in Arabidopsis against the soybean pathogen, P. sojae. RESULTS: The P. sojae susceptible (pss) 1 mutant was identified by screening a mutant population created in the Arabidopsis pen1-1 mutant that lacks penetration resistance against the non adapted barley biotrophic fungal pathogen, Blumeria graminis f. sp. hordei. Segregation data suggested that PEN1 is not epistatic to PSS1. Responses of pss1 and pen1-1 to P. sojae invasion were distinct and suggest that PSS1 may act at both pre- and post-haustorial levels, while PEN1 acts at the pre-haustorial level against this soybean pathogen. Therefore, PSS1 encodes a new form of nonhost resistance. The pss1 mutant is also infected by the necrotrophic fungal pathogen, Fusarium virguliforme, which causes sudden death syndrome in soybean. Thus, a common NHR mechanism is operative in Arabidopsis against both hemibiotrophic oomycetes and necrotrophic fungal pathogens that are pathogenic to soybean. However, PSS1 does not play any role in immunity against the bacterial pathogen, Pseudomonas syringae pv. glycinea, that causes bacterial blight in soybean. We mapped PSS1 to a region very close to the southern telomere of chromosome 3 that carries no known disease resistance genes. CONCLUSIONS: The study revealed that Arabidopsis PSS1 is a novel nonhost resistance gene that confers a new form of nonhost resistance against both a hemibiotrophic oomycete pathogen, P. sojae and a necrotrophic fungal pathogen, F. virguliforme that cause diseases in soybean. However, this gene does not play any role in the immunity of Arabidopsis to the bacterial pathogen, P. syringae pv. glycinea, which causes bacterial blight in soybean. Identification and further characterization of the PSS1 gene would provide further insights into a new form of nonhost resistance in Arabidopsis, which could be utilized in improving resistance of soybean to two serious pathogens.     

Survival and population growth of a long-lived threatened snake species, Drymarchon couperi (Eastern Indigo Snake)

Demographic data provide a basis for understanding the life history and ecology of species, factors which are vital for informing conservation efforts; however, little is known regarding the population ecology of most snake species, including the threatened Eastern Indigo Snake (Drymarchon couperi). We used 11 years (1999–2009) of capture-mark-recapture (CMR) and 2.5 years (2003–2005) of radiotelemetry data from southeastern Georgia, USA, in a CMR modeling framework to estimate apparent survival, capture and transition probabilities, and evaluate factors influencing these parameters. The model-averaged estimate of overall apparent annual survival probability was 0.700 (±0.030 SE) and is comparable to that obtained from known fate analysis (radiotelemetry) at the same site. Body size positively influenced survival, regardless of sex. Capture probability differed seasonally by sex, suggesting lower capture probability for females in fall and males in winter. There was no evidence for effect of precipitation or site-specific differences in survival. Model averaged estimate of annual adult survival estimated using multistate CMR models was 0.738 ± 0.030 and 0.515 ± 0.189 for subadults. We estimated population growth rate (λ) and elasticity (proportional sensitivity) of λ to vital rates using a stage-structured matrix population model. Population growth rate ranged from 0.96 to 1.03 depending on the value of the probability of transitioning from subadult to adult stage. The λ was proportionally most sensitive to changes in adult survival rate, followed by subadult survival. Our results suggest that protecting adult snakes and their habitats would result in the highest likelihood of long-term population stability and growth.     

Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7 cells

Tamoxifen (Tam) is most widely used selective estrogen receptor modulator (SERM) for treatment of hormone-responsive breast cancer. Despite being regularly used in clinical therapy for breast cancer since 1971, the mechanism of Tam action remains largely unclear. In order to gain insights into Tam-mediated antibreast cancer actions, we applied 2DE and MS based proteomics approach to identify target proteins of Tam. We identified E6-associated protein, i.e. E6AP (UBE3A) among others to be regulated by Tam that otherwise is upregulated in breast tumors. We confirmed our 2DE finding by immunoblotting and further show that Tam leads to inhibition of E6AP expression presumably by promoting its autoubiquitination, which is coupled with nuclear export and subsequent proteasome-mediated degradation. Furthermore, we show that Tam- and siE6AP-mediated inhibition of E6AP leads to enhanced G0-G1 growth arrest and apoptosis, which is also evident from significant upregulation of cytochrome-c, Bax, p21, and PARP cleavage. Taken together, our data suggest that, Tam-targeted E6AP inhibition is in fact required for Tam-mediated antibreast cancer actions. Thus, E6AP may be a therapeutic target in breast cancer.     

Recognition pliability is coupled to structural heterogeneity: a calmodulin intrinsically disordered binding region complex

Protein interactions within regulatory networks should adapt in a spatiotemporal-dependent dynamic environment, in order to process and respond to diverse and versatile cellular signals. However, the principles governing recognition pliability in protein complexes are not well understood. We have investigated a region of the intrinsically disordered protein myelin basic protein (MBP(145-165)) that interacts with calmodulin, but that also promiscuously binds other biomolecules (membranes, modifying enzymes). To characterize this interaction, we implemented an NMR spectroscopic approach that calculates, for each conformation of the complex, the maximum occurrence based on recorded pseudocontact shifts and residual dipolar couplings. We found that the MBP(145-165)-calmodulin interaction is characterized by structural heterogeneity. Quantitative comparative analysis indicated that distinct conformational landscapes of structural heterogeneity are sampled for different calmodulin-target complexes. Such structural heterogeneity in protein complexes could potentially explain the way that transient and promiscuous protein interactions are optimized and tuned in complex regulatory networks.     

Comparative organic growth factor requirements of nine Candida species

Nine Candida species isolated from fleshy fruits have been examined for their organic growth factor requirements. Complete or partial deficiencies for thiamine, biotin, pyridoxine, inositol, pantothenic acid, ascorbic acid and xanthine have been reported in C. catenuclta, C. curiosa, C. curvata, C. humicola, C. rhagii, C. steatolytica and C. tropicalis. Only two species, namely, C. fragicola and C. ishiwadea were prototrophic for the growth factors. Concentrations of essential growth factors higher than the optimum have been found inhibitory for the growth of yeasts.     

Double-minute chromatin bodies in HL-60 leukemia cells sensitive and resistant to differentiation inducing agents

We studied the chromosome characteristics of HL-60 promyelocytic leukemia cells sensitive and resistant to differentiation inducing agents (DI). The karyotypic analysis of sensitive (HL-60 S) and resistant (HL-60 R) cells revealed the presence of identical chromosome abnormalities such as loss of chromosomes 5, 9, 10, 14, 16, 17 and X; and gain of chromosome 18. HL-60 S and HL-60 R cells also share five common markers. The difference between the two cell lines consisted essentially of the loss of an unidentifiable chromosome segment in the HL-60 R cell line. In addition, the two sublines showed marked differences in the content of double-minute chromatin bodies (DM), which were abundant in HL-60 S but rarely found in HL-60 R cells. Contrary to a previous report by others, there was no evidence of chromosome rearrangement of the DM as homogeneously stained regions (HSR) or abnormally banding regions (ABR) in the resistant HL-60 R cells. The presence of DM as an expression of gene amplification may be of relevance in the determination of susceptibility of HL-60 cells to DI.     

Fluorescence analysis of late DNA replication in mouse metaphase chromosomes using BUdR and 33258 Hoechst

A late replicating X or Y chromosome can be detected by 33258 Hoechst staining and fluorescence microscopy in a large proportion of female or male mouse embryo cells, respectively, which have been cultured in medium containing 5-bromodeoxyuridine (BUdR) for part of one DNA synthesis period, The observed distribution of late replicating chromosome regions also includes centromeric heterochromatin and some quinacrine positive bands.     

Coping with ethnicity in South Asia: Bangladesh,Punjab and Kashmir compared

In the anthropological and sociological studies of India the terms ‘tribe’ and ‘caste’, have been in use for almost two hundred years. The related notions of ‘tribalism’ and ‘casteism’ were brought in to replace a static (structural) by a dynamic (organizational, processual) approach. Since the 1970s, ‘ethnic group’ and ‘ethnicity’ have gained currency. After defining the terms, three cases of ethnicity are examined, namely East Bengali Muslim, Punjabi Sikh and Kashmiri Muslim. It is argued that, while the first is a success story, the second seems more like a retreat at present, and the third is at best nascent. The reasons for this difference are explored. Ethnicity, it is argued, is not only characterization of identity, but also a set of strategies to establish a new state. This objective is opposed by competing ethnic groups and the existing state. Ethnic movements therefore involve violence and their outcome is dependent upon a variety of factors and therefore contingent.