Syn- and post-rift lower crustal flow under the Sunda Shelf, southern Vietnam: A role for climatically modulated erosion

Tectonic subsidence on rifted, passive continental margins are largely controlled by patterns of extension and the nature of strain partitioning in the lithosphere. The Sunda Shelf, adjacent to the SW South China Sea, is characterized by deep basins linked to regional Cenozoic extension associated with propagating seafloor spreading caused by slab pull from the south. Analysis of seismic reflection profiles and drilled sections crossing the Nam Con Son and Cuu Long basins highlight Oligocene extension, with most of the thinning concentrated in the ductile mid-lower crust. Upper crustal extension was modest and ductile flow is inferred to be directed northwestwards, towards the oceanic crust. Basin inversion occurred in the Mid Miocene, associated with the collision of the Dangerous Grounds Block and Borneo. Subsequent accelerated tectonic subsidence exceeded predictions from uniform extension models assumed to relate to extensional collapse after inversion. We correlate this to a period of faster erosion onshore driven by strong monsoon rains in Indochina and Peninsular Thailand at that time. Erosion of the onshore basement, inducing rock uplift and coupled with loading of the basins offshore, drives ductile mid-lower crustal flow, likely to the northeast under Indochina, and/or to the west where Plio-Pleistocene subsidence of the shelf is very slow. Significant sediment delivery from the Mekong River into the Cuu Long Basin began in the Late Miocene and migrated seawards as the basin filled. Mass balancing suggests that the basins of this part of the Sunda Shelf are filled through erosion of bedrock sources around the Gulf of Thailand. There is no need for sediment delivery from a major river draining the Tibetan Plateau to account for the deposited volumes

Reported Acquisition Practices of Australian Dog Owners

In Australia, the UK and the US dog ownership is prevalent with an estimated 40% ofAustralian households, 25% of UK households, and 50% of US households owning a dog. Onceacquired, a dog usually becomes a family companion so, unlike a faulty product, it can rarely bereturned or resold without some emotional impact on both the acquirer and the dog. Regarding thereality of dog relinquishment, there is a growing need for cross-disciplinary research that considershow dog owners are making their acquisition choices and, if prioritising different attributes, leads tomore optimal acquisition choices. This research collected data from 2840 dog owners via an onlinesurvey and examines how owners prioritised various attributes when acquiring their latest dog.The Pearson-Blotchky analysis of survey results show owners are split into two groups, with eachgroup prioritising different attributes or characteristics in their search for a new dog. The first groupare those dog owners who prioritised: the ability to rescue a dog, how compatible the dog wason the first meeting, and how compatible they believed the dog would be with their household.The second group are those owners who prioritised: a dog’s morphology, temperament predictability,and breeding practices. While each group prioritised different attributes, neither group madesubstantially more optimal acquisition choices in terms of overall satisfaction with the dog that theyultimately selected

Quantitative genetics of gastrointestinal strongyle burden and associated body condition in feral horses

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordVariability in host resistance or tolerance to parasites is nearly ubiquitous, and is of key significance in understanding the evolutionary processes shaping host-parasite interactions. While ample research has been conducted on the genetics of parasite burden in livestock, relatively little has been done in free-living populations. Here, we investigate the sources of (co)variation in strongyle nematode faecal egg count (FEC) and body condition in Sable Island horses, a feral population in which parasite burden has previously been shown to negatively correlate with body condition. We used the quantitative genetic “animal model” to understand the sources of (co)variation in these traits, and tested for impacts of an important spatial gradient in habitat quality on the parameter estimates. Although FEC is significantly heritable (h 2 = 0.43 ± 0.11), there was no evidence for significant additive genetic variation in body condition (h 2 = 0.04 ± 0.07), and therefore there was also no significant genetic covariance between the two traits. The negative phenotypic covariance between these traits therefore does not derive principally from additive genetic effects. We also found that both FEC and body condition increase from east to west across the island, which indicates that the longitudinal environmental gradient is not responsible for the negative phenotypic association observed between these traits. There was also little evidence to suggest that quantitative genetic parameters were biased when an individual’s location along the island’s environmental gradient was not incorporated into the analysis. This research provides new and important insights into the genetic basis and adaptive potential of parasite resistance in free-living animals, and highlights the importance of environmental heterogeneity in modulating host-parasite interactions in wild vertebrate systems.Natural Sciences and Engineering Research Council of CanadaCanada Foundation for InnovationRoyal Society International ExchangeRyan Dubé and Heather Ryan Veterinary and Research FundNSERC-CREATE Host-Parasite Interactions Training ProgramLeverhulme Trus

The discovery of a novel antibiotic for the treatment of Clostridium difficile infections: a story of an effective academic-industrial partnership

Academic drug discovery is playing an increasingly important role in the identification of new therapies for a wide range of diseases. There is no one model that guarantees success. We describe here a drug discovery story where chance, the ability to capitalise on chance, and the assembling of a range of expertise, have all played important roles in the discovery and subsequent development of an antibiotic chemotype based on the bis-benzimidazole scaffold, with potency against a number of current therapeutically challenging diseases. One compound in this class, SMT19969, has recently entered Phase 2 human clinical trials for the treatment of Clostridium difficile infections

Modulation of Global Low-Frequency Motions Underlies Allosteric Regulation: Demonstration in CRP/FNR Family Transcription Factors

Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distinct site. There is growing evidence that allosteric cooperativity can be communicated by modulation of protein dynamics without conformational change. The mechanisms, however, for communicating dynamic fluctuations between sites are debated. We provide a foundational theory for how allostery can occur as a function of low-frequency dynamics without a change in structure. We have generated coarse-grained models that describe the protein backbone motions of the CRP/FNR family transcription factors, CAP of Escherichia coli and GlxR of Corynebacterium glutamicum. The latter we demonstrate as a new exemplar for allostery without conformation change. We observe that binding the first molecule of cAMP ligand is correlated with modulation of the global normal modes and negative cooperativity for binding the second cAMP ligand without a change in mean structure. The theory makes key experimental predictions that are tested through an analysis of variant proteins by structural biology and isothermal calorimetry. Quantifying allostery as a free energy landscape revealed a protein ‘‘design space’’ that identified the inter- and intramolecular regulatory parameters that frame CRP/FNR family allostery. Furthermore, through analyzing CAP variants from diverse species, we demonstrate an evolutionary selection pressure to conserve residues crucial for allosteric control. This finding provides a link between the position of CRP/FNR transcription factors within the allosteric free energy landscapes and evolutionary selection pressures. Our study therefore reveals significant features of the mechanistic basis for allostery. Changes in low-frequency dynamics correlate with allosteric effects on ligand binding without the requirement for a defined spatial pathway. In addition to evolving suitable three-dimensional structures, CRP/FNR family transcription factors have been selected to occupy a dynamic space that fine-tunes biological activity and thus establishes the means to engineer allosteric mechanisms driven by low-frequency dynamics

The effects of childbirth on the pelvic-floor

Basically, vaginal delivery is associated with the risk of pelvic floor damage. The pelvic floor sequelae of childbirth includes anal incontinence, urinary incontinence and pelvic organ prolapse. Pathophysiology, incidence and risk factors for the development of the respective problems are reviewed. Where possible, recommendations for reducing the risk of pelvic floor damage are given