Science Collected Works - Research Publications

Permanent URI for this collection

Search Results

Now showing 1 - 10 of 138
  • Item
    Thumbnail Image
    Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities
    Barkauskaite, E ; Brassington, A ; Tan, ES ; Warwicker, J ; Dunstan, MS ; Banos, B ; Lafite, P ; Ahel, M ; Mitchison, TJ ; Ahel, I ; Leys, D (NATURE PUBLISHING GROUP, 2013-08-01)
    Poly-ADP-ribosylation is a post-translational modification that regulates processes involved in genome stability. Breakdown of the poly(ADP-ribose) (PAR) polymer is catalysed by poly(ADP-ribose) glycohydrolase (PARG), whose endo-glycohydrolase activity generates PAR fragments. Here we present the crystal structure of PARG incorporating the PAR substrate. The two terminal ADP-ribose units of the polymeric substrate are bound in exo-mode. Biochemical and modelling studies reveal that PARG acts predominantly as an exo-glycohydrolase. This preference is linked to Phe902 (human numbering), which is responsible for low-affinity binding of the substrate in endo-mode. Our data reveal the mechanism of poly-ADP-ribosylation reversal, with ADP-ribose as the dominant product, and suggest that the release of apoptotic PAR fragments occurs at unusual PAR/PARG ratios.
  • Item
    Thumbnail Image
    The transcriptional regulator CprK detects chlorination by combining direct and indirect readout mechanisms
    Kemp, LR ; Dunstan, MS ; Fisher, K ; Warwicker, J ; Leys, D (ROYAL SOC, 2013-04-19)
    The transcriptional regulator CprK controls the expression of the reductive dehalogenase CprA in organohalide-respiring bacteria. Desulfitobacterium hafniense CprA catalyses the reductive dechlorination of the terminal electron acceptor o-chlorophenol acetic acid, generating the phenol acetic acid product. It has been shown that CprK has ability to distinguish between the chlorinated CprA substrate and the de-halogenated end product, with an estimated an estimated 10(4)-fold difference in affinity. Using a green fluorescent protein GFPUV-based transcriptional reporter system, we establish that CprK can sense o-chlorophenol acetic acid at the nanomolar level, whereas phenol acetic acid leads to transcriptional activation only when approaching micromolar levels. A structure-activity relationship study, using a range of o-chlorophenol acetic-acid-related compounds and key CprK mutants, combined with pKa calculations on the effector binding site, suggests that the sensitive detection of chlorination is achieved through a combination of direct and indirect readout mechanisms. Both the physical presence of the bulky chloride substituent as well as the accompanying electronic effects lowering the inherent phenol pKa are required for high affinity. Indeed, transcriptional activation by CprK appears strictly dependent on establishing a phenolate-K133 salt bridge interaction, rather than on the presence of a halogen atom per se. As K133 is strictly conserved within the CprK family, our data suggest that physiological function and future applications in biosensing are probably restricted to phenolic compounds.
  • Item
    Thumbnail Image
    NUMT Confounding Biases Mitochondrial Heteroplasmy Calls in Favor of the Reference Allele
    Maude, H ; Davidson, M ; Charitakis, N ; Diaz, L ; Bowers, WHT ; Gradovich, E ; Andrew, T ; Huntley, D (FRONTIERS MEDIA SA, 2019-09-25)
    Homology between mitochondrial DNA (mtDNA) and nuclear DNA of mitochondrial origin (nuMTs) causes confounding when aligning short sequence reads to the reference human genome, as the true sequence origin cannot be determined. Using a systematic in silico approach, we here report the impact of all potential mitochondrial variants on alignment accuracy and variant calling. A total of 49,707 possible mutations were introduced across the 16,569 bp reference mitochondrial genome (16,569 × 3 alternative alleles), one variant at-at-time. The resulting in silico fragmentation and alignment to the entire reference genome (GRCh38) revealed preferential mapping of mutated mitochondrial fragments to nuclear loci, as variants increased loci similarity to nuMTs, for a total of 807, 362, and 41 variants at 333, 144, and 27 positions when using 100, 150, and 300 bp single-end fragments. We subsequently modeled these affected variants at 50% heteroplasmy and carried out variant calling, observing bias in the reported allele frequencies in favor of the reference allele. Four variants (chrM:6023A, chrM:4456T, chrM:5147A, and chrM:7521A) including a possible hypertension factor, chrM:4456T, caused 100% loss of coverage at the mutated position (with all 100 bp single-end fragments aligning to homologous, nuclear positions instead of chrM), rendering these variants undetectable when aligning to the entire reference genome. Furthermore, four mitochondrial variants reported to be pathogenic were found to cause significant loss of coverage and select haplogroup-defining SNPs were shown to exacerbate the loss of coverage caused by surrounding variants. Increased fragment length and use of paired-end reads both improved alignment accuracy.
  • Item
    Thumbnail Image
    YCu(TeO3)2(NO3)(H2O)3: a novel layered tellurite.
    Mills, SJ ; Dunstan, MA ; Christy, AG (International Union of Crystallography (IUCr), 2016-08-01)
    A new hydrated yttrium copper tellurite nitrate, yttrium(III) copper(II) bis-[trioxidotellurate(IV)] nitrate trihydrate, has been synthesized hydro-thermally in a Teflon-lined autoclave and structurally determined using synchrotron radiation. The new phase is the first example containing yttrium, copper and tellurium in one structure. Its crystal structure is unique, with relatively strongly bound layers extending parallel to (020), defined by YO8, CuO4 and TeO3 polyhedra, while the NO3 (-) anions and one third of the water mol-ecules lie between those layers. The structural unit consists of [Cu2(TeO3)4](4-) loop-branched chains of {Cu⋯Te⋯Cu⋯Te} squares running parallel to [001], which are linked further into layers only through Y(O,H2O)8 polyhedra. Weak 'secondary' Te bonds and O-H⋯O hydrogen-bonding inter-actions, involving water mol-ecules and layer O atoms, link the layers and inter-layer species. IR spectroscopic data are also presented.
  • Item
    Thumbnail Image
    Biogeography of functional trait diversity in the Taiwanese reef fish fauna
    Denis, V ; Chen, J-W ; Chen, Q ; Hsieh, YE ; Lin, YV ; Wang, C-W ; Wang, H-Y ; Sturaro, N (WILEY, 2019-01-01)
    The richness of Taiwanese reef fish species is inversely correlated to latitude as a direct consequence of the abiotic environment and its effects on benthic habitats. However, to date, no studies have investigated the variations in the diversity of traits (FD) linked with the role of these fishes in the ecosystem. FD is usually considered more sensitive than species richness in detecting early changes in response to disturbances, and therefore could serve as an indicator of ecological resilience to environmental changes. Here, we aim to characterize FD in the Taiwanese reef fish fauna and to document its regional variations. Six traits were used to categorize the 1,484 reef fish species occurring in four environmentally contrasted regions around Taiwan. The number of unique trait combinations (FEs), their richness (FRic), their redundancy (FR), their over-redundancy (FOR), and their vulnerability (FV) were compared among these regions. Overall, 416 FEs were identified. Their number decreased from south to north in step with regional species richness but FRic remained similar among regions. FR and FOR were higher to the south. At the local scale, variations in FEs and FRic are in concordance with the worldwide pattern of FD. High-latitude, impoverished fish assemblages, offer a range of trait combinations similar to diversified tropical assemblages. Increasing diversity in the latter mainly contributes to raising FR and supports already over-redundant entities. High vulnerability makes many combinations highly sensitive to species loss, and was higher at intermediate latitudes when using a fine resolution in trait categories. It suggests that the loss of FEs may first be characterized by an increase in their vulnerability, a pattern that could have been overlooked in previous global scale analyses. Overall, this study provides new insights into reef fish trait biogeography with potential ramifications for ecosystem functioning.
  • Item
    Thumbnail Image
    Reduction of hydroelastic response of a flexible floating structure by an annular flexible permeable membrane
    Selvan, SA ; Behera, H ; Sahoo, T (Springer, 2019-10-01)
    In the present study, hydroelastic response mitigation of a very large floating circular structure by an annular flexible permeable membrane is studied under the assumption of the linearized theory of water waves and small amplitude structural response. The very large floating structure is modeled based on small amplitude plate theory, while the flexible annular membrane is modeled using the two-dimensional string equation. Darcy’s law is used to model wave past the permeable annular membrane. To keep the structures in position, both the floating structures are assumed to be moored on the circular boundaries. The velocity potentials are expanded in terms of the Fourier–Bessel series in the open water, membrane-, and plate-covered regions. The solution of the physical problem is obtained using the matched eigenfunction expansion method along with the orthogonality of the vertical eigenfunctions in the open water region. On the other hand, orthogonal mode–coupling relation, satisfied by the vertical eigenfunctions in the floating flexible plate-covered region, is used when there is no spacing between the outer and the inner structures. The wave forces exerted on the inner and outer structures, deflection of the plate, and flow distribution around the inner plate are analyzed using numerical computations to understand the hydroelastic response of the inner elastic plate in the presence of the outer porous membrane. The effects of various wave and structural parameters such as wavenumber, porous-effect parameter, tensile force, width of the outer membrane, spring constants associated with the mooring joints, and the spacing between the structures are examined. The study reveals that the porous-effect parameter and the width of the annular membrane play an important role in reducing the wave forces on the inner plate. Moreover, due to the reflection and dissipation of a major part of the wave energy concentrating near the free surface, the inner floating structure experiences negligible wave loads in the case of deep water.
  • Item
    Thumbnail Image
    Correction: HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse.
    Lim, SL ; Qu, ZP ; Kortschak, RD ; Lawrence, DM ; Geoghegan, J ; Hempfling, A-L ; Bergmann, M ; Goodnow, CC ; Ormandy, CJ ; Wong, L ; Mann, J ; Scott, HS ; Jamsai, D ; Adelson, DL ; O'Bryan, MK (Public Library of Science (PLoS), 2015-12)
  • Item
    Thumbnail Image
    Monitoring vaginal electrical resistance, follicular waves, and hormonal profile during oestrous cycle in the transition period in Bangladeshi sheep
    Talukder, MRI ; Hasan, M ; Rosy, TA ; Bari, FY ; Juyena, NS (WALTER DE GRUYTER GMBH, 2018-12-01)
    INTRODUCTION: The ovarian follicular dynamics, vaginal electrical resistance (VER), progesterone (P4) and oestrogen (E2) profiles were investigated during the oestrous cycle in four indigenous ewes. MATERIAL AND METHODS: Daily VER values were recorded with a heat detector. The follicles were observed and measured by trans-rectal ultrasonography. Blood was collected daily for hormonal profiles. RESULTS: A significant variation in VER values (P < 0.05) in oestrus by ewes and position in the sequence of cycles was observed. Trans-rectal ultrasonography of ovaries revealed the presence of 2-4 waves of follicular growth. Study of hormonal profiles by ELISA revealed a positive correlation between E2 concentration and development of follicles and a negative correlation between P4 concentration and their development. The concentrations of oestradiol increased in oestrus and then decreased to a basal level. Follicular growth was accompanied by a rise in the concentration of serum oestradiol. Inversely, when follicles received the stimulation for ovulation, concentration of progesterone started to fall, but after ovulation, it climbed back to its peak and remained at this state until next ovulatory follicle reached its maximum diameter. CONCLUSION: This study could help to set up a manipulative reproductive technique for improving genetic values in indigenous sheep.
  • Item
    Thumbnail Image
    Productive, reproductive, and estrus characteristics of different breeds of buffalo cows in Bangladesh
    Harun-Or-Rashid, M ; Sarkar, AK ; Hasan, MMI ; Hasan, M ; Juyena, NS (NETWORK VETERINARIANS BANGLADESH, 2019-12-01)
    OBJECTIVE: The objective of this research work is to know the productive and reproductive performances and problems of local, crossbred, Nilli, and Murrah buffalo cows in selected study areas in Bangladesh. METHODOLOGY: A total of 1,241 local, crossbred, Nilli, and Murrah buffalo cows were surveyed in the selected areas with a pre-set questionnaire. Among 1,241 buffalo cows, 112 buffalo cows were randomly selected at day 0 of the estrus cycle for studying ovarian features. RESULTS: Results showed that the average age, body condition score, and body weight were significantly (p < 0.05) different among the studied breeds. Milk production in Murrah and lactation length in Nilli cows were significantly (p < 0.05) higher than indigenous, crossbred, Nilli, and indigenous, crossbred, Murrah buffalo cows, respectively. Results also illustrated that sexual maturity, estrus cycle length, insemination time after the onset of estrus, and gestation length insignificantly (p > 0.05) varied among the surveyed breed. But, the fallout of the study denoted that estrus duration, first calving age, parity number, number of service per conception, calving interval, and voluntary waiting period varied significantly (p < 0.05) in different breeds. Ovarian physiological characteristics such as vaginal electrical resistance, average number of follicles in two ovaries, and largest follicular diameter, estrogen, and progesterone at day 0 of the estrus cycle of local, crossbred, Nilli, and Murrah buffalo cows showed insignificantly (p > 0.05) differences. CONCLUSION: The study will help the veterinarian and researcher to identify the constraints for the reproductive efficiency of buffalo in Bangladesh.
  • Item
    Thumbnail Image
    Pleistocene climatic changes drive diversification across a tropical savanna
    Potter, S ; Xue, AT ; Bragg, JG ; Rosauer, DF ; Roycroft, EJ ; Moritz, C (WILEY, 2018-01-01)
    Spatial responses of species to past climate change depend on both intrinsic traits (climatic niche breadth, dispersal rates) and the scale of climatic fluctuations across the landscape. New capabilities in generating and analysing population genomic data, along with spatial modelling, have unleashed our capacity to infer how past climate changes have shaped populations, and by extension, complex communities. Combining these approaches, we uncover lineage diversity across four codistributed lizards from the Australian Monsoonal Tropics and explore how varying climatic tolerances interact with regional climate history to generate common vs. disparate responses to late Pleistocene change. We find more divergent spatial structuring and temporal demographic responses in the drier Kimberley region compared to the more mesic and consistently suitable Top End. We hypothesize that, in general, the effects of species' traits on sensitivity to climate fluctuation will be more evident in climatically marginal regions. If true, this points to the need in climatically marginal areas to craft more species-(or trait)-specific strategies for persistence under future climate change.