The physiological ups and downs of thermal variability in temperate freshwater ecosystems

Freshwater fish face a variety of spatiotemporal thermal challenges throughout their life. On a broad scale, temperature is an important driver of physiological, behavioural and ecological patterns and ultimately affects populations and overall distribution. These broad patterns are partly underpinned by the small-scale local effects of temperature on individuals within the population. Climate change is increasing the range of daily thermal variation in most freshwater ecosystems, altering behaviour and performance of resident fishes. The aim of this review is understanding how daily thermal variation in temperate rivers affects individual fish physiology, behaviour and overall performance. The following are highlighted in this study: (a) the physical characteristics of rivers that can either buffer or exacerbate thermal variability, (b) the effects of thermal variability on growth and metabolism, (c) the approaches for quantifying thermal variation and thermal stress and (d) how fish may acclimatize or adapt to our changing climate.     

Neuronal Basis of Innate Olfactory Attraction to Ethanol in Drosophila

The decision to move towards a mating partner or a food source is essential for life. The mechanisms underlying these behaviors are not well understood. Here, we investigated the role of octopamine – the invertebrate analogue of noradrenaline – in innate olfactory attraction to ethanol. We confirmed that preference is caused via an olfactory stimulus by dissecting the function of the olfactory co-receptor Orco (formally known as OR83b). Orco function is not required for ethanol recognition per se, however it plays a role in context dependent recognition of ethanol. Odor-evoked ethanol preference requires the function of Tbh (Tyramine β hydroxalyse), the rate-limiting enzyme of octopamine synthesis. In addition, neuronal activity in a subset of octopaminergic neurons is necessary for olfactory ethanol preference. Notably, a specific neuronal activation pattern of tyraminergic/octopaminergic neurons elicit preference and is therefore sufficient to induce preference. In contrast, dopamine dependent increase in locomotor activity is not sufficient for olfactory ethanol preference. Consistent with the role of noradrenaline in mammalian drug induced rewards, we provide evidence that in adult Drosophila the octopaminergic neurotransmitter functions as a reinforcer and that the molecular dissection of the innate attraction to ethanol uncovers the basic properties of a response selection system.     

Donor–Acceptor Shape Matching Drives Performance in Photovoltaics

While the demonstrated power conversion efficiency of organic photovoltaics (OPVs) now exceeds 10%, new design rules are required to tailor interfaces at the molecular level for optimal exciton dissociation and charge transport in higher efficiency devices. We show that molecular shape‐complementarity between donors and acceptors can drive performance in OPV devices. Using core hole clock (CHC) X‐ray spectroscopy and density functional theory (DFT), we compare the electronic coupling, assembly, and charge transfer rates at the interface between C₆₀ acceptors and flat‐ or contorted‐hexabenzocorone (HBC) donors. The HBC donors have similar optoelectronic properties but differ in molecular contortion and shape matching to the fullerene acceptors. We show that shape‐complementarity drives self‐assembly of an intermixed morphology with a donor/acceptor (D/A) ball‐and‐socket interface, which enables faster electron transfer from HBC to C₆₀. The supramolecular assembly and faster electron transfer rates in the shape complementary heterojunction lead to a larger active volume and enhanced exciton dissociation rate. This work provides fundamental mechanistic insights on the improved efficiency of organic photovoltaic devices that incorporate these concave/convex D/A materials.     

The Structure of the T190M Mutant of Murine α-Dystroglycan at High Resolution: Insight into the Molecular Basis of a Primary Dystroglycanopathy

The severe dystroglycanopathy known as a form of limb-girdle muscular dystrophy (LGMD2P) is an autosomal recessive disease caused by the point mutation T192M in α-dystroglycan. Functional expression analysis in vitro and in vivo indicated that the mutation was responsible for a decrease in posttranslational glycosylation of dystroglycan, eventually interfering with its extracellular-matrix receptor function and laminin binding in skeletal muscle and brain. The X-ray crystal structure of the missense variant T190M of the murine N-terminal domain of α-dystroglycan (50-313) has been determined, and showed an overall topology (Ig-like domain followed by a basket-shaped domain reminiscent of the small subunit ribosomal protein S6) very similar to that of the wild-type structure. The crystallographic analysis revealed a change of the conformation assumed by the highly flexible loop encompassing residues 159–180. Moreover, a solvent shell reorganization around Met190 affects the interaction between the B1–B5 anti-parallel strands forming part of the floor of the basket-shaped domain, with likely repercussions on the folding stability of the protein domain(s) and on the overall molecular flexibility. Chemical denaturation and limited proteolysis experiments point to a decreased stability of the T190M variant with respect to its wild-type counterpart. This mutation may render the entire L-shaped protein architecture less flexible. The overall reduced flexibility and stability may affect the functional properties of α-dystroglycan via negatively influencing its binding behavior to factors needed for dystroglycan maturation, and may lay the molecular basis of the T190M-driven primary dystroglycanopathy.     

Escherichia coli Heat-Stable Enterotoxin Mediates Na+/H+ Exchanger 4 Inhibition Involving cAMP in T84 Human Intestinal Epithelial Cells

The enterotoxigenic Escherichia coli strains lead to diarrhoea in humans due to heat-labile and heat-stable (STa) enterotoxins. STa increases Cl^-release in intestinal cells, including the human colonic carcinoma T₈₄ cell line, involving increased cGMP and membrane alkalization due to reduced Na⁺/H⁺ exchangers (NHEs) activity. Since NHEs modulate intracellular pH (pH_i), and NHE1, NHE2, and NHE4 are expressed in T₈₄ cells, we characterized the STa role as modulator of these exchangers. pH_i was assayed by the NH₄Cl pulse technique and measured by fluorescence microscopy in BCECF–preloaded cells. pH_i recovery rate (dpHi/dt) was determined in the absence or presence of 0.25 μmol/L STa (30 minutes), 25 μmol/L HOE-694 (concentration inhibiting NHE1 and NHE2), 500 μmol/L sodium nitroprusside (SNP, spontaneous nitric oxide donor), 100 μmol/L dibutyryl cyclic GMP (db-cGMP), 100 nmol/L H89 (protein kinase A inhibitor), or 10 μmol/L forskolin (adenylyl cyclase activator). cGMP and cAMP were measured in cell extracts by radioimmunoassay, and buffering capacity (ßi) and H⁺ efflux (J _H ⁺) was determined. NHE4 protein abundance was determined by western blotting. STa and HOE-694 caused comparable reduction in dpHi/dt and J _H ⁺ (~63%), without altering basal pH_i (range 7.144–7.172). STa did not alter ßi value in a range of 1.6 pH_i units. The dpHi/dt and J _H ⁺ was almost abolished (~94% inhibition) by STa + HOE-694. STa effect was unaltered by db-cGMP or SNP. However, STa and forskolin increased cAMP level. STa–decreased dpHi/dt and J _H ⁺ was mimicked by forskolin, and STa + HOE-694 effect was abolished by H89. Thus, incubation of T₈₄ cells with STa results in reduced NHE4 activity leading to a lower capacity of pH_i recovery requiring cAMP, but not cGMP. STa effect results in a causal phenomenon (STa/increased cAMP/increased PKA activity/reduced NHE4 activity) ending with intracellular acidification that could have consequences in the gastrointestinal cells function promoting human diarrhoea.     

Synthesis and biological activity of -tyrosine-based PPARγ agonists with reduced molecular weight

A series of PPARγ agonists were synthesized from -tyrosine that incorporated low molecular weight N-substituents. The most potent analogue, pyrrole (Scheme 1 and Scheme 2), demonstrated a K_i of 6.9 nM and an EC₅₀ of 4.7 nM in PPARγ binding and functional assays, respectively. Pyrrole (Scheme 1 and Scheme 2), which is readily synthesized from -tyrosine methyl ester in four steps, also demonstrated in vivo activity in a rodent model of Type 2 diabetes.