Deep-water channel-lobe transition zone dynamics: Processes and depositional architecture, an example from the Karoo Basin, South Africa

Submarine channel-lobe transition zones separate well-defined channels from well-defined lobes and form morphologically complicated areas, commonly located at breaks in slope. These areas play a vital role in the transfer of sediment through deep-water systems. Extensive outcrop exposures in the Karoo Basin, South Africa, permit investigation of the depositional architecture and evolution of entirely exhumed dip transects of a channel-lobe transition zone for the first time. Furthermore, the excellent paleogeographic constraint allows correlation to genetically related updip channel-levee systems and downdip lobe deposits over 40 km, with strike control over 20 km. Unlike the single time slice afforded by modern systems, the Karoo example uniquely allows study of the temporal shifting of the channel-lobe transition zone and transfer into the stratigraphic record. Key lateral changes along the base of slope include the variation from an interfingering levee-lobe transition zone to a bypass-dominated channel-lobe transition zone over a width of 14 km. Key recognition criteria for channel-lobe transition zones in the ancient record include combinations of scours and megaflutes, composite erosional surfaces, mudstone clast/coarse-grained sediment lags, and remnants of depositional bed forms, such as sediment waves. Documented here in a single channel-lobe transition zone, these features are arranged in a zone of juxtaposed remnant erosional and depositional features. The zone reaches 6 km in length, formed by at least four stages of expansion/contraction or migration. Strike variations and changes in the dimensions of the channel-lobe transition zone through time are interpreted to be the result of physiographic changes and variations in flow dynamics across the base of slope. The dynamic nature of channel-lobe transition zones results in complicated and composite stratigraphy, with preservation potential generally low but increasing distally and laterally away from the mouth of the feeder channel system. Here, we present the first generic model to account for dynamic channel-lobe transition zone development, encompassing distinctive recognition criteria, fluctuations in the morphology and position of the zone, and the complex transfer into the sedimentary record

Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity

The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

Appetite and Energy Intake Responses to Acute Energy Deficits in Females versus Males.

Purpose: To explore whether compensatory responses to acute energy deficits induced by exercise or diet differ by sex. Methods: In experiment one, twelve healthy women completed three 9 h trials (control, exercise-induced (Ex-Def) and food restriction induced energy deficit (Food-Def)) with identical energy deficits being imposed in the Ex-Def (90 min run, ~70% of VO2 max) and Food-Def trials. In experiment two, 10 men and 10 women completed two 7 h trials (control and exercise). Sixty min of running (~70% of VO2 max) was performed at the beginning of the exercise trial. Participants rested throughout the remainder of the exercise trial and during the control trial. Appetite ratings, plasma concentrations of gut hormones and ad libitum energy intake were assessed during main trials. Results: In experiment one, an energy deficit of ~3500 kJ induced via food restriction increased appetite and food intake. These changes corresponded with heightened concentrations of plasma acylated ghrelin and lower peptide YY3-36. None of these compensatory responses were apparent when an equivalent energy deficit was induced by exercise. In experiment two, appetite ratings and plasma acylated ghrelin concentrations were lower in exercise than control but energy intake did not differ between trials. The appetite, acylated ghrelin and energy intake response to exercise did not differ between men and women. Conclusions: Women exhibit compensatory appetite, gut hormone and food intake responses to acute energy restriction but not in response to an acute bout of exercise. Additionally, men and women appear to exhibit similar acylated ghrelin and PYY3-36 responses to exercise-induced energy deficits. These findings advance understanding regarding the interaction between exercise and energy homeostasis in women

Distinct Genetic Architectures for Male and Female Inflorescence Traits of Maize

We compared the genetic architecture of thirteen maize morphological traits in a large population of recombinant inbred lines. Four traits from the male inflorescence (tassel) and three traits from the female inflorescence (ear) were measured and studied using linkage and genome-wide association analyses and compared to three flowering and three leaf traits previously studied in the same population. Inflorescence loci have larger effects than flowering and leaf loci, and ear effects are larger than tassel effects. Ear trait models also have lower predictive ability than tassel, flowering, or leaf trait models. Pleiotropic loci were identified that control elongation of ear and tassel, consistent with their common developmental origin. For these pleiotropic loci, the ear effects are larger than tassel effects even though the same causal polymorphisms are likely involved. This implies that the observed differences in genetic architecture are not due to distinct features of the underlying polymorphisms. Our results support the hypothesis that genetic architecture is a function of trait stability over evolutionary time, since the traits that changed most during the relatively recent domestication of maize have the largest effects

Developmental features of cotton fibre middle lamellae in relation to cell adhesion and cell detachment in cultivars with distinct fibre qualities.

Background: Cotton fibre quality traits such as fibre length, strength, and degree of maturation are determined by genotype and environment during the sequential phases of cotton fibre development (cell elongation, transition to secondary cell wall construction and cellulose deposition). The cotton fibre middle lamella (CFML) is crucial for both cell adhesion and detachment processes occurring during fibre development. To explore the relationship between fibre quality and the pace at which cotton fibres develop, a structural and compositional analysis of the CFML was carried out in several cultivars with different fibre properties belonging to four commercial species: Gossypium hirsutum, G. barbadense, G. herbaceum and G. arboreum. Results: Cotton fibre cell adhesion, through the cotton fibre middle lamella (CFML), is a developmentally regulated process determined by genotype. The CFML is composed of de-esterified homogalacturonan, xyloglucan and arabinan in all four fibre-producing cotton species: G. hirsutum, G. barbadense, G. herbaceum and G. arboreum. Conspicuous paired cell wall bulges are a feature of the CFML of two G. hirsutum cultivars from the onset of fibre cell wall detachment to the start of secondary cell wall deposition. Xyloglucan is abundant in the cell wall bulges and in later stages pectic arabinan is absent from these regions. Conclusions: The CFML of cotton fibres is re-structured during the transition phase. Paired cell wall bulges, rich in xyloglucan, are significantly more evident in the G. hirsutum cultivars than in other cotton species

Metabolic recovery of Arabidopsis thaliana roots following cessation of oxidative stress

To cope with the various environmental stresses resulting in reactive oxygen species (ROS) production plant metabolism is known to be altered specifically under different stresses. After overcoming the stress the metabolism should be reconfigured to recover basal operation however knowledge concerning how this is achieved is cursory. To investigate the metabolic recovery of roots following oxidative stress, changes in metabolite abundance and carbon flow were analysed. Arabidopsis roots were treated by menadione to elicit oxidative stress. Roots were fed with 13C labelled glucose and the redistribution of isotope was determined in order to study carbon flow. The label redistribution through many pathways such as glycolysis, the tricarboxylic acid (TCA) cycle and amino acid metabolism were reduced under oxidative stress. After menadione removal many of the stress-related changes reverted back to basal levels. Decreases in amounts of hexose phosphates, malate, 2-oxoglutarate, glutamate and aspartate were fully recovered or even increased to above the control level. However, some metabolites such as pentose phosphates and citrate did not recover but maintained their levels or even increased further. The alteration in label redistribution largely correlated with that in metabolite abundance. Glycolytic carbon flow reverted to the control level only 18 h after menadione removal although the TCA cycle and some amino acids such as aspartate and glutamate took longer to recover. Taken together, plant root metabolism was demonstrated to be able to overcome menadione-induced oxidative stress with the differential time period required by independent pathways suggestive of the involvement of pathway specific regulatory processes

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS