Considerations for measuring genetic variation and population structure with multilocus fingerprinting

Multilocus DNA fingerprinting provides a cost-effective means to rapidly assay genetic variation at many loci. While this makes the technique particularly attractive for studies of evolution and conservation biology, fingerprint data can be difficult to interpret. Measurement errors inherent with the technique force investigators to group similar-sized alleles (bands) into discrete bins before estimating genetic parameters. If too little error is accounted for in this process homologous alleles will not be grouped in a common bin, whereas overestimated error can produce bins with homoplasic alleles. We used simulations and empirical data for two frog species ( Rana luteiventris and Hyla regilla ) to demonstrate that mean band-sharing ( S¯_xy ) and heterozygosity ( H ¯_E) are a function of both bin width and band profile complexity (i.e. number and distribution of bands). These estimators are also sensitive to the number of lanes included in the analysis when bin width is wide and a floating bin algorithm is employed. Multilocus estimates of H ¯_E were highly correlated with S¯_xy and thus provide no additional information about genetic variation. Estimates of population subdivision ( F ^ and Φ^_ST) appeared robust to changes in bin size. We also examined the issue of statistical independence for band-sharing data when comparisons are made among all samples. This analysis indicated that the covariance between band-sharing statistics was very small and not statistically different from zero. We recommend that sensitivity analyses for bin size be used to improve confidence in the biological interpretation of multilocus fingerprints, and that the covariance structure for band-sharing statistics be examined.     

Effectiveness of Lethal,Directed Wolf-Depredation Control in Minnesota

Abstract: Wolf (Canis lupus) depredations on livestock in Minnesota, USA, are an economic problem for many livestock producers, and depredating wolves are lethally controlled. We sought to determine the effectiveness of lethal control through the analysis of data from 923 government-verified wolf depredations from 1979 to 1998. We analyzed the data by 1) assessing the correlations between the number of wolves killed in response to depredations with number of depredations the following year at state and local levels, and 2) the time to the next depredation. No analysis indicated that trapping wolves substantially reduced the following year's depredations at state or local levels. However, more specific analyses indicated that in certain situations, killing wolves was more effective than no action (i.e., not trapping). For example, trapping and killing adult males decreased the re-depredation risk. At sheep farms, killing wolves was generally effective. Attempting to trap, regardless of the results, seemed more effective at reducing depredations than not trapping, suggesting that mere human activity near depredation sites might deter future depredations. (JOURNAL OF WILDLIFE MANAGEMENT 72(3):778–784; 2008)     

Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation

Introduction  

In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation.     

Homology modeling and molecular dynamics study of West Nile virus NS3 protease: a molecular basis for the catalytic activity increased by the NS2B cofactor

The West Nile virus (WNV) NS3 serine protease, which plays an important role in assembly of infective virion, is an attractive target for anti-WNV drug development. Cofactors NS2B and NS4A increase the catalytic activity of NS3 in dengue virus and Hepatitis C virus, respectively. Recent studies on the WNV-NS3 characterize the catalytically active form of NS3 by tethering the 40-residue cofactor NS2B. It is suggested that NS2B is essential for the NS3 activity in WNV, while there is no information of the WNV-NS3-related crystal structure. To understand the role of NS2B/substrate in the NS3 catalytic activity, we built a series of models: WNV-NS3 and WNV-NS3-NS2B and WNV-NS3-NS2B-substrate using homology modeling and molecular modeling techniques. Molecular dynamics (MD) simulations were performed for 2.75 ns on each model, to investigate the structural stabilization and catalytic triad motion of the WNV NS3 protease with and without NS2B/substrate. The simulations show that the NS3 rearrangement occurs upon the NS2B binding, resulting in the stable D75-OD1...H51-NH hydrogen bonding. After the substrate binds to the NS3-NS2B active site, the NS3 protease becomes more stable, and the catalytic triad is formed. These results provide a structural basis for the activation and stabilization of the enzyme by its cofactor and substrate.     

Quencher-free molecular beacon: Enhancement of the signal-to-background ratio with graphene oxide

We report the highly improved version of quencher-free molecular beacon (QF-MB) system by using graphene oxide (GO) as an external quencher. This QF-MB/GO system provided a higher S/B ratio (31.0) relative to that (2.2) of the same system in the absence of GO, while retaining a high selectivity for fully matched over single-base-mismatched targets.     

Parathyroid responsiveness to hypocalcemic and hypercalcemic stimuli in adult growth hormone deficiency after growth hormone replacement

Adult growth hormone deficiency (AGHD) is associated with osteoporosis. Previous reports have suggested that alterations in parathyroid gland responsiveness to changes in calcium concentration may play a role in the genesis of osteoporosis in untreated AGHD patients. We investigated the endogenous parathyroid hormone [PTH-(1-84)] response to hypocalcemic and hypercalcemic stimuli induced by sodium EDTA and calcium gluconate infusion, respectively, and to PTH-(1-34) infusion in AGHD patients before and during GH replacement (GHR). We have demonstrated that the maximum PTH-(1-84) stimulation and suppression occurred at significantly higher calcium concentrations and in response to smaller changes in calcium concentrations after GHR. The calcemic response to the effects of PTH-(1-34) infusion significantly increased after GHR. The calcium set point (the calcium concentration at which the rate of PTH secretion is one-half of its maximal value) significantly increased in all groups after 3 mo on GHR, and it increased further at 12 mo. Our results suggest increased parathyroid gland sensitivity to smaller changes in serum calcium and increased end-organ sensitivity to the effects of PTH in AGHD patients after GHR. These findings may help us to understand the mechanisms underlying the genesis of osteoporosis in AGHD patients.     

Structural basis of triclosan resistance

Triclosan (5-chloro-2-(2,4-dichloro-phenoxy)-phenol, TCL) is a well known inhibitor against enoyl-acyl carrier protein reductase (ENR), an enzyme critical for cell-wall synthesis of bacteria. The inhibitory concentration at 50% inhibition (IC(50)) of TCL against the Escherichia coli ENR is 150nM for wild type (WT), 380, 470 and 68,500nM for Ala, Ser and Val mutants, respectively. To understand this high TCL resistance in the G93V mutant, we obtained the crystal structures of mutated ENRs complexed with TCL and NAD(+). The X-ray structural analysis along with the ab initio calculations and molecular dynamics simulations explains the serious consequence in the G93V mutant complex. The major interactions around TCL due to the aromatic(cation)-aromatic and hydrogen bonding interactions are found to be conserved both in WT and mutant complexes. Thus, the overall structural change of protein is minimal except that a flexible α-helical turn around TCL is slightly pushed away due to the presence of the bulky valine group. However, TCL shows substantial edge-to-face aromatic (π)-interactions with both the flexible R192-F203 region and the residues in the close vicinity of G93. The weakening of some edge-to-face aromatic interactions around TCL in the G93V mutant results in serious resistance to TCL. This understanding is beneficial to design new generation of antibiotics which will effectively act on the mutant ENRs.     

Wolf Use of Summer Territory in Northeastern Minnesota

ABSTRACT Movements of wolves (Canis lupus) during summer 2003 and 2004 in the Superior National Forest were based around homesites but included extensive use of territories. Away from homesites, wolves used different areas daily, exhibiting rotational use. Mean daily range overlap was 22% (SE = 0.02) and that of breeding wolves was significantly greater than for nonbreeders ( = 25% and 16%, respectively). Rotational use may improve hunting success. Managers seeking to remove entire packs must maintain control long enough to ensure that all pack members are targeted.     

The English national risk-reduction programme for preservation of sight in diabetes

This paper discusses the new national guidelines for a systematic screening programme to detect sight-threatening diabetic retinopathy in the population of people with diabetes in England. A review of the literature examines the evidence base to support screening interventions and effective management and treatments in diabetic retinopathy. The current evidence supports the establishment of a digital retinal photography system using pupil dilation. A Policy Advisory Group has been formulated by the National Screening Committee to guide the meeting of this target in England. A conclusion is made that with increased effort and organisation, health care professionals can ensure that the screening programme is successfully implemented and rates of visual impairment and blindness caused by diabetic retinopathy can be reduced significantly. (Mol Cell Biochem 261: 183–185, 2004)     

The English national risk-reduction programme for preservation of sight in diabetes

This paper discusses the new national guidelines for a systematic screening programme to detect sight-threatening diabetic retinopathy in the population of people with diabetes in England. A review of the literature examines the evidence base to support screening interventions and effective management and treatments in diabetic retinopathy. The current evidence supports the establishment of a digital retinal photography system using pupil dilation. A Policy Advisory Group has been formulated by the National Screening Committee to guide the meeting of this target in England. A conclusion is made that with increased effort and organisation, health care professionals can ensure that the screening programme is successfully implemented and rates of visual impairment and blindness caused by diabetic retinopathy can be reduced significantly.