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    Insect Antennal Morphology: The Evolution of Diverse Solutions to Odorant Perception
    Elgar, MA ; Zhang, D ; Wang, Q ; Wittwer, B ; Hieu, TP ; Johnson, TL ; Freelance, CB ; Coquilleau, M (Yale University, 2018-12-01)
    Chemical communication involves the production, transmission, and perception of odors. Most adult insects rely on chemical signals and cues to locate food resources, oviposition sites or reproductive partners and, consequently, numerous odors provide a vital source of information. Insects detect these odors with receptors mostly located on the antennae, and the diverse shapes and sizes of these antennae (and sensilla) are both astonishing and puzzling: what selective pressures are responsible for these different solutions to the same problem - to perceive signals and cues? This review describes the selection pressures derived from chemical communication that are responsible for shaping the diversity of insect antennal morphology. In particular, we highlight new technologies and techniques that offer exciting opportunities for addressing this surprisingly neglected and yet crucial component of chemical communication.
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    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)
    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.
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    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.
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    YCu(TeO3)2(NO3)(H2O)3: a novel layered tellurite
    Mills, SJ ; Dunstan, MA ; Christy, AG (INT UNION CRYSTALLOGRAPHY, 2016-08)
    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.
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    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)
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    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)
    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.
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    Pleistocene climatic changes drive diversification across a tropical savanna
    Potter, S ; Xue, AT ; Bragg, JG ; Rosauer, DF ; Roycroft, EJ ; Moritz, C (WILEY, 2018-01)
    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.
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    Chemotherapy-related cardiotoxicity: are Australian practitioners missing the point?
    Conyers, R ; Costello, B ; La Gerche, A ; Tripaydonis, A ; Burns, C ; Ludlow, L ; Lange, P ; Ekert, P ; Mechinaud, F ; Cheung, M ; Martin, M ; Elliot, D (WILEY, 2017-10)
    BACKGROUND: It has long been established that cardiotoxicity occurs as a result of exposure to certain chemotherapeutics, particularly anthracyclines. Historically, clinicians equate cardiotoxicity with a poor prognosis, in a small percentage of patients and deem long-term surveillance as optional. Emerging evidence suggests that anthracycline cardiotoxicity (ACT) is a life-long risk with an incidence approaching 20%. AIMS: To elucidate the incidence of anthracycline cardiotoxicity within a current paediatric oncology survivor cohort. METHODS: Participants were identified through the Haematology-Oncology database at the Royal Children's Hospital, Melbourne. Patients were identified from a retrospective audit of outpatient attendances between January 2008 and December 2015. Patients with a cancer diagnosis exposed to anthracyclines were eligible for the study. Patient demographics and echocardiogram findings were recorded with patients subcategorised according to degree of ACT. More significant ACT defined as fractional shortening (FS) <24% and less significant if FS 24-28% or a decline in baseline ejection fraction of >10%. RESULTS: Two hundred and eighty-six of a total 481 identified patients were eligible for study inclusion. Twenty patients displayed significant ACT with FS <24%. Ten patients had a FS 24-28% and 25 patients with a decline in ejection fraction from baseline of >10%. Overall, 6.6% demonstrated significant cardiac complications, whilst 19.6 % demonstrated some degree of ACT and decline in myocardial function. When stratified for cumulative anthracycline dose, the incidence of severe cardiac dysfunction was 5.1% (<250 mg/m2 ) and 25% (>250 mg/m2 ) CONCLUSION: This study demonstrates, in keeping with modern literature, the higher incidence of anthracycline associated cardiac toxicity and a need for better surveillance and follow up.
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    Impaired bone and muscle development in young people treated with antiepileptic drugs
    Simm, PJ ; Seah, S ; Gorelik, A ; Gilbert, L ; Nuguid, J ; Werther, GA ; Mackay, MT ; Freeman, JL ; Petty, SJ ; Wark, JD (WILEY, 2017-11)
    OBJECTIVE: Antiepileptic drugs (AEDs) are associated with reduced bone density, balance impairment, and increased fracture risk in adults. However, pediatric data are limited. Therefore, we aimed to examine bone, muscle, and balance outcomes in young patients taking AEDs. METHODS: We undertook a case-control study utilizing an AED exposure-discordant matched-pair approach. Subjects were aged 5-18 years with at least 12 months of AED exposure. Pairs were twins, nontwin siblings and first cousins, sex- and age-matched (to within 2 years), allowing for greater power than with unrelated control subjects. Dual energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and muscle force/balance were tested, with questionnaires were administered for bone health and epilepsy details. RESULTS: Twenty-three pairs were recruited, (median age 12.9 years [subjects] and 13.5 years [controls])-7 twin, 14 sibling, and 2 cousin pairs. Those taking AEDs had an increased prevalence of fractures (15 fractures in 8 subjects, compared with 4 fractures in 3 controls, p < 0.01). Trabecular volumetric bone mineral density (vBMD) measured by pQCT at the 4% site (tibia) was reduced by 14% (p = 0.03) in subjects. Subjects exerted a decreased maximum force compared to body weight (Fmax total/g) at the tibia. There were no differences seen in either bone mineral parameters measured by DXA or balance measures. SIGNIFICANCE: Young people taking AEDs reported more fractures and had reductions in tibial vBMD and lower limb muscle force compared to their matched controls. These findings suggest that further exploration of bone health issues of young patients on AED therapy is required. Longitudinal studies are required to confirm these changes in the muscle-bone unit and to further explore the clinical outcomes.
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    Validation and application of a novel integrated genetic screening method to a cohort of 1,112 men with idiopathic azoospermia or severe oligozoospermia
    Oud, MS ; Ramos, L ; O'Bryan, MK ; McLachlan, RI ; Okutman, O ; Viville, S ; de Vries, PF ; Smeets, DFCM ; Lugtenberg, D ; Hehir-Kwa, JY ; Gilissen, C ; van de Vorst, M ; Vissers, LELM ; Hoischen, A ; Meijerink, AM ; Fleischer, K ; Veltman, JA ; Noordam, MJ (WILEY-HINDAWI, 2017-11)
    Microdeletions of the Y chromosome (YCMs), Klinefelter syndrome (47,XXY), and CFTR mutations are known genetic causes of severe male infertility, but the majority of cases remain idiopathic. Here, we describe a novel method using single molecule Molecular Inversion Probes (smMIPs), to screen infertile men for mutations and copy number variations affecting known disease genes. We designed a set of 4,525 smMIPs targeting the coding regions of causal (n = 6) and candidate (n = 101) male infertility genes. After extensive validation, we screened 1,112 idiopathic infertile men with non-obstructive azoospermia or severe oligozoospermia. In addition to five chromosome YCMs and six other sex chromosomal anomalies, we identified five patients with rare recessive mutations in CFTR as well as a patient with a rare heterozygous frameshift mutation in SYCP3 that may be of clinical relevance. This results in a genetic diagnosis in 11-17 patients (1%-1.5%), a yield that may increase significantly when more genes are confidently linked to male infertility. In conclusion, we developed a flexible and scalable method to reliably detect genetic causes of male infertility. The assay consolidates the detection of different types of genetic variation while increasing the diagnostic yield and detection precision at the same or lower price compared with currently used methods.