Low-temperature thermochronology and thermokinematic modeling of deformation, exhumation, and development of topography in the central Southern Alps, New Zealand

Apatite and zircon (U-Th)/He and fission track ages were obtained from ridge transects across the central Southern Alps, New Zealand. Interpretation of local profiles is difficult because relationships between ages and topography or local faults are complex and the data contain large uncertainties, with poor reproducibility between sample duplicates. Data do form regional patterns, however, consistent with theoretical systematics and corroborating previous observations: young Neogene ages occur immediately southeast of the Alpine Fault (the main plate boundary structure on which rocks are exhumed); partially reset ages occur in the central Southern Alps; and older Mesozoic ages occur further toward the southeast. Zircon apparent ages are older than apatite apparent ages for the equivalent method. Three-dimensional thermokinematic modeling of plate convergence incorporates advection of the upper Pacific plate along a low-angle detachment then up an Alpine Fault ramp, adopting a generally accepted tectonic scenario for the Southern Alps. The modeling incorporates heat flow, evolving topography, and the detailed kinetics of different thermochronometric systems and explains both complex local variations and regional patterns. Inclusion of the effects of radiation damage on He diffusion in detrital apatite is shown to have dramatic effects on results. Geometric and velocity parameters are tuned to fit model ages to observed data. Best fit is achieved at 9 mm a−1 plate convergence, with Pacific plate delamination on a gentle 10°SE dipping detachment and more rapid uplift on a 45–60° dipping Alpine Fault ramp from 15 km depth. Thermokinematic modeling suggests dip-slip motion on reverse faults within the Southern Alps should be highest ∼22 km from the Alpine Fault and much lower toward the southeast

Biopharmaceutics

Biopharmaceutics, in connection with pharmacokinetics, is the field that investigates and describes everything that happens with a medicinal product and the active substance between the moment of administration, the moment it exerts its action and the moment it is eliminated from the body. Biopharmaceutics connects the physico-chemical properties of an active substance and its dosage form, especially through the drug release characteristics, with its fate and action in the living organism. Actually biopharmaceutics describes how medicine formulation technologies can affect pharmacokinetics and pharmacodynamics. The route of administration, the way the active substance is released from the dosage form, and the way the body handles (absorbs, distributes, metabolises and excretes) the active substance, together determine its (duration of) action, its efficacy and the occurrence of adverse effects. This chapter explains general principles of biopharmaceutics and its relation to pharmacokinetics in the light of their implications on the design of medicines. It describes the general biopharmaceutical principles that are relevant to the major routes of administration: parenteral, oromucosal, oral, rectal, dermal, nasal, pulmonary and ocular. Topics discussed include solubility and dissolution, bioavailability, partition coefficient and pH partition theory, the biopharmaceutical classification system (BCS), excipient-, food-, drug- and herb-drug interactions, first-pass effects and drug metabolism, bioequivalence and new developments in the field of advanced drug delivery systems.</p

Climatic control on seasonal variations in mountain glacier surface velocity

Accurate measurements of ice flow are essential to predict future changes in glaciers and ice caps. Glacier displacement can in principle be measured on the large scale by cross-correlation of satellite images. At weekly to monthly scales, the expected displacement is often of the same order as the noise for the commonly used satellite images, complicating the retrieval of accurate glacier velocity. Assessments of velocity changes on short timescales and over complex areas such as mountain ranges are therefore still lacking but are essential to better understand how glacier dynamics are driven by internal and external factors. In this study, we take advantage of the wide availability and redundancy of satellite imagery over the western Pamirs to retrieve glacier velocity changes over 10 d intervals for 7 years and for a wide range of glacier geometry and dynamics. Our results reveal strong seasonal trends. In spring/summer, we observe velocity increases of up to 300 % compared to a slow winter period. These accelerations clearly migrate upglacier throughout the melt season, which we link to changes in subglacial hydrology efficiency. In autumn, we observe glacier accelerations that have rarely been observed before. These episodes are primarily confined to the upper ablation zone with a clear downglacier migration. We suggest that they result from glacier instabilities caused by sudden subglacial pressurization in response to (1) supraglacial pond drainage and/or (2) gradual closure of the hydrological system. Our 10 d resolved measurements allow us to characterize the short-term response of glaciers to changing meteorological and climatic conditions

Antarctic Peninsula glaciation patterns set by landscape evolution and dynamic topography

The dimensions of past ice sheets provide a record of palaeoclimate but depend on underlying topography, which evolves over geological timescales by tectonic uplift and erosional downcutting. Erosion during the Pleistocene epoch (2,580 to 11.650 thousand years ago) reduced glacier extent in some locations even as climate cooled, but whether other non-climatic influences impacted the glacial–geological record is poorly known. The Antarctic Peninsula provides an opportunity to examine this issue because of its long glacial history and preservation of remnants of a low-relief pre-glacial land surface. Here we reconstructed both palaeo-surface topography and long-wavelength variations of surface uplift for the Antarctic Peninsula by using inverse analysis that assimilates local topographic remnants with the branching structures of entire modern drainage networks. We found that the Antarctic Peninsula rose tectonically by up to 1.5 km due to dynamical support from the mantle. Glaciological models using the current climate and our palaeotopography show greatly reduced ice extent in the northern Antarctic Peninsula compared with modern, indicating that the onset of glaciation identified at offshore sites reflects tectonic uplift of the topography rather than climatic cooling. In the southern Antarctic Peninsula, however, we suggest the low-relief pre-glacial landscape supported a considerably greater ice volume than the modern mountainous topography, illustrating the influence of erosional sculpting on glaciation patterns

The proline-rich motif of the proDer p 3 allergen propeptide is crucial for protease-protease interaction.

The majority of proteases are synthesized in an inactive form, termed zymogen, which consists of a propeptide and a protease domain. The propeptide is commonly involved in the correct folding and specific inhibition of the enzyme. The propeptide of the house dust mite allergen Der p 3, NPILPASPNAT, contains a proline-rich motif (PRM), which is unusual for a trypsin-like protease. By truncating the propeptide or replacing one or all of the prolines in the non-glycosylated zymogen with alanine(s), we demonstrated that the full-length propeptide is not required for correct folding and thermal stability and that the PRM is important for the resistance of proDer p 3 to undesired proteolysis when the protein is expressed in Pichia pastoris. Additionally, we followed the maturation time course of proDer p 3 by coupling a quenched-flow assay to mass spectrometry analysis. This approach allowed to monitor the evolution of the different species and to determine the steady-state kinetic parameters for activation of the zymogen by the major allergen Der p 1. This experiment demonstrated that prolines 5 and 8 are crucial for proDer p 3-Der p 1 interaction and for activation of the zymogen.Peer reviewe

Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue

International audienceLHX4 is a LIM homeodomain transcription factor involved in the early steps of pituitary ontogenesis. To date, 8 heterozygous LHX4 mutations have been reported as responsible of combined pituitary hormone deficiency (CPHD) in Humans. We identified 4 new LHX4 heterozygous allelic variants in patients with congenital hypopituitarism: W204X, delK242, N271S and Q346R. Our objective was to determine the role of LHX4 variants in patients' phenotypes. Heterologous HEK293T cells were transfected with plasmids encoding for wild-type or mutant LHX4. Protein expression was analysed by Western Blot, and DNA binding by electro-mobility shift assay experiments. Target promoters of LHX4 were cotransfected with wild type or mutant LHX4 to test the transactivating abilities of each variant. Our results show that the W204X mutation was associated with early GH and TSH deficiencies and later onset ACTH deficiency. It led to a truncated protein unable to bind to alpha-Gsu promoter binding consensus sequence. W204X was not able to activate target promoters in vitro. Cotransfection experiments did not favour a dominant negative effect. In contrast, all other mutants were able to bind the promoters and led to an activation similar as that observed with wild type LHX4, suggesting that they were likely polymorphisms. To conclude, our study underlines the need for functional in vitro studies to ascertain the role of rare allelic variants of LHX4 in disease phenotypes. It supports the causative role of the W204X mutation in CPHD and adds up childhood onset ACTH deficiency to the clinical spectrum of the various phenotypes related to LHX4 mutations

Expanding the utilization of sustainable plant products in aquafeeds: a review

Continued growth and intensification of aquaculture production depends upon the development of sustainable protein sources to replace fish meal in aquafeeds. This document reviews various plant feedstuffs, which currently are or potentially may be incorporated into aquafeeds to support the sustainable production of various fish species in aquaculture. The plant feedstuffs considered include oilseeds, legumes and cereal grains, which traditionally have been used as protein or energy concentrates as well as novel products developed through various processing technologies. The nutritional composition of these various feedstuffs are considered along with the presence of any bioactive compounds that may positively or negatively affect the target organism. Lipid composition of these feedstuffs is not specifically considered although it is recognized that incorporating lipid supplements in aquafeeds to achieve proper fatty acid profiles to meet the metabolic requirements of fish and maximize human health benefits are important aspects. Specific strategies and techniques to optimize the nutritional composition of plant feedstuffs and limit potentially adverse effects of bioactive compounds are also described. Such information will provide a foundation for developing strategic research plans for increasing the use of plant feedstuffs in aquaculture to reduce dependence of animal feedstuffs and thereby enhance the sustainability of aquaculture