Resynchrony of postpartum dairy cows previously treated for anestrus

Cows that are diagnosed as anestrus (defined as >3 weeks postpartum, not detected in estrus by 1 week before commencement of seasonal breeding and without a palpable corpus luteum) have a lower probability of being inseminated, a lower conception rate to insemination and hence a lower probability of pregnancy within the breeding period. A current progesterone (P) and estradiol benzoate (EB) treatment for anestrus results in an 85% insemination rate, but only 57% of cows not conceiving to that first insemination are subsequently detected in estrus 14-28 days later. Resynchrony after an initial anestrous treatment has been used to increase the probability that cows not conceiving to first insemination will subsequently be detected in estrus. Anestrous cows (n=971) were initially treated with an intravaginal P-releasing device for 6 days and given 1 mg EB 1 day after device removal (day of EB treatment=Day 0). Cows detected in estrus between Days 0 and 3 were assigned randomly to be treated with reinsertion of a used P-releasing device for 8 days (commencing on Day 15), with 0.5 mg EB at reinsertion and again 1 day after removal (EB-RS), treatment as for EB-RS group but with substitution of 250 microg GnRH for EB at device reinsertion (GnRH-RS), or left as untreated controls (no-RS). Resynchrony treatments increased the proportion of non-pregnant cows detected in estrus from Days 14 to 28 compared to no-RS (79.1, 69.8, and 55.1% for EB-RS, GnRH-RS, and no-RS, respectively; P<0.05). Fewer cows were pregnant by Days 28 and 56 following GnRH-RS than EB-RS and no-RS. The final pregnancy rate was higher following EB-RS treatment than no-RS or GnRH-RS treatment (95.0, 88.3, and 88.6%; P<0.05). In conclusion, EB-RS enhanced reproductive performance of anestrous cows compared to no-RS.     

A Hybrid Discrete-Continuum Mathematical Model of Pattern Prediction in the Developing Retinal Vasculature

Pathological angiogenesis has been extensively explored by the mathematical modelling community over the past few decades, specifically in the contexts of tumour-induced vascularisation and wound healing. However, there have been relatively few attempts to model angiogenesis associated with normal development, despite the availability of animal models with experimentally accessible and highly ordered vascular topologies: for example, growth and development of the vascular plexus layers in the murine retina. The current study aims to address this issue through the development of a hybrid discrete-continuum mathematical model of the developing retinal vasculature in neonatal mice that is closely coupled with an ongoing experimental programme. The model of the functional vasculature is informed by a range of morphological and molecular data obtained over a period of several days, from 6?days prior to birth to approximately 8?days after birth.The spatio-temporal formation of the superficial retinal vascular plexus (RVP) in wild-type mice occurs in a well-defined sequence. Prior to birth, astrocytes migrate from the optic nerve over the surface of the inner retina in response to a chemotactic gradient of PDGF-A, formed at an earlier stage by migrating retinal ganglion cells (RGCs). Astrocytes express a variety of chemotactic and haptotactic proteins, including VEGF and fibronectin (respectively), which subsequently induce endothelial cell sprouting and modulate growth of the RVP. The developing RVP is not an inert structure; however, the vascular bed adapts and remodels in response to a wide variety of metabolic and biomolecular stimuli. The main focus of this investigation is to understand how these interacting cellular, molecular, and metabolic cues regulate RVP growth and formation.In an earlier one-dimensional continuum model of astrocyte and endothelial migration, we showed that the measured frontal velocities of the two cell types could be accurately reproduced by means of a system of five coupled partial differential equations (Aubert et?al. in Bull. Math. Biol. 73:2430-2451, 2011). However, this approach was unable to generate spatial information and structural detail for the entire retinal surface. Building upon this earlier work, a more realistic two-dimensional hybrid PDE-discrete model is derived here that tracks the migration of individual astrocytes and endothelial tip cells towards the outer retinal boundary. Blood perfusion is included throughout plexus development and the emergent retinal architectures adapt and remodel in response to various biological factors. The resulting in?silico RVP structures are compared with whole-mounted retinal vasculatures at various stages of development, and the agreement is found to be excellent. Having successfully benchmarked the model against wild-type data, the effect of transgenic over-expression of various genes is predicted, based on the ocular-specific expression of VEGF-A during murine development. These results can be used to help inform future experimental investigations of signalling pathways in ocular conditions characterised by aberrant angiogenesis.     

Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies

Angiogenesis, the growth of a network of blood vessels, is a crucial component of solid tumour growth, linking the relatively harmless avascular growth phase and the potentially fatal vascular growth phase. As a process, angiogenesis is a well-orchestrated sequence of events involving endothelial cell migration, proliferation; degradation of tissue; new capillary vessel (sprout) formation; loop formation (anastomosis) and, crucially, blood flow through the network. Once there is blood flow associated with the nascent network, the subsequent growth of the network evolves both temporally and spatially in response to the combined effects of angiogenic factors, migratory cues via the extracellular matrix and perfusion-related haemodynamic forces in a manner that may be described as both adaptive and dynamic. In this paper we present a mathematical model which simultaneously couples vessel growth with blood flow through the vessels--dynamic adaptive tumour-induced angiogenesis (DATIA). This new mathematical model presents a theoretical and computational investigation of the process and highlights a number of important new targets for therapeutic intervention. In contrast to earlier flow models, where the effects of perfusion (blood flow) were essentially evaluated a posteriori, i.e. after generating a hollow network, blood flow in the model described in this paper has a direct impact during capillary growth, with radial adaptations and network remodelling occurring as immediate consequences of primary anastomoses. Capillary network architectures resulting from the dynamically adaptive model are found to differ radically from those obtained using earlier models. The DATIA model is used to examine the effects of changing various physical and biological model parameters on the developing vascular architecture and the delivery of chemotherapeutic drugs to the tumour. Subsequent simulations of chemotherapeutic treatments under different parameter regimes lead to the identification of a number of new therapeutic targets for tumour management.     

Fluvially-deposited large wood and riparian plant diversity

Out-of-channel wood jams centred by fluvially-deposited large wood represent an important habitat for riparian plant species along large rivers dominated by exposed riverine sediments. Such wood jams often display distinct physical features associated with the jams, such as areas of scour immediately upstream, plumes of fine sediment downstream and abundant organic material deposited throughout the jam. This paper examines the relationship between physical characteristics of young wood jams (1–3 years since deposition) and riparian plant diversity along the braided River Tagliamento in Northeast Italy. Species richness of riparian plants was significantly positively correlated to the depth of scour features and amount of fine sediment around the wood jams, which facilitate improved access to the water table and increase available water in the sediments, respectively. Species diversity was significantly positively correlated to scour pool depth only. Scour depth was in turn influenced by wood jam size, indicating that larger jams may indirectly increase riparian plant diversity. Management and restoration of riparian zones containing exposed riverine sediments should allow for the formation of wood jams and their associated features where possible, in order to potentially increase localised biodiversity.     

Archaea S‐layer nanotube from a “black smoker” in complex with cyclo‐octasulfur (S8) rings

Elemental sulfur exists primarily as an ring and serves as terminal electron acceptor for a variety of sulfur‐fermenting bacteria. Hyperthermophilic archaea from black smoker vents are an exciting research tool to advance our knowledge of sulfur respiration under extreme conditions. Here, we use a hybrid method approach to demonstrate that the proteinaceous cavities of the S‐layer nanotube of the hyperthermophilic archaeon Staphylothermus marinus act as a storage reservoir for cyclo‐octasulfur . Fully atomistic molecular dynamics (MD) simulations were performed and the method of multiconfigurational thermodynamic integration was employed to compute the absolute free energy for transferring a ring of elemental sulfur from an aqueous bath into the largest hydrophobic cavity of a fragment of archaeal tetrabrachion. Comparisons with earlier MD studies of the free energy of hydration as a function of water occupancy in the same cavity of archaeal tetrabrachion show that the sulfur ring is energetically favored over water.     

Which morphological forms of the fungus Aureobasidium pullulans are responsible for pullulan production?

Attempts were made to clarify the precise location and possible site of production of the alpha-glucan pullulan in different morphological forms of the fungus Aureobasidium pullulans. Gold-conjugated pullulanase was used as the specific probe for this purpose. No cell wall pullulan-like material was detected by transmission electron microscopy (TEM) in any morphological form of this fungus, although intracellular electron transparent material bound this probe. When silver enhancement of this gold-conjugated pullulanase probe was used, the data strongly suggested that only swollen cells and chlamydospores, and neither hyphae nor unicellular blastospores, often held responsible for pullulan formation, appeared to produce pullulan-like material.     

A yeast gene for trehalose-6-phosphate synthase and its complementation of an Escherichia coli otsA mutant

Abstract A Saccharomyces cerevisiae gene for trehalose-6-phosphate synthase (TPS1) was sequenced. The gene appeared to code for a protein of 495 amino acid residues, giving the protein a molecular mass of 56 kDa. The TPS1 gene was able to restore both osmotolerance and trehalose accumulation during salt stress in an Escherichia coli strain mutated in the otsA gene encoding trehalose-6-phosphate synthase. Complementation studies with E. coli galU mutants showed that the TPS1-encoded trehalose-6-phosphate synthase is UDP-glucose-dependent. Sequence analysis and data base searches showed that TPS1 is allelic to GGS1, byp1, cif1 and fdp1 . A possible gene for trehalose-6-phosphate synthase in Methanobacterium thermoautotrophicum was identified.