A biophysical characterization of the folded domains of KCTD12: insights into interaction with the GABAB2 receptor

Recent investigations have shown that members of the KCTD family play important roles in fundamental biological processes. Despite their roles, very limited information is available on their structures and molecular organization. By combining different experimental and theoretical techniques, we have here characterized the two folded domains of KCTD12, an integral component and modulator of the GABA_B2 receptor. Secondary prediction methods and CD spectroscopy have shown that the N‐terminal domain KCTD12_BTB assumes an α/β structure, whereas the C‐terminal domain KCTD12_H1 is predominantly characterized by a β‐structure. Binding assays indicate that the two domains independently expressed show a good affinity for each other. This suggests that the overall protein is likely endowed with a rather compact structure with two interacting structured domains joint by a long disordered region. Notably, both KCTD12_BTB and KCTD12_H1 are tetrameric when individually expressed. This finding could modify the traditional view that ascribes only to POZ/BTB domain a specific oligomerization role. The first quantification of the affinity of KCTD12_POZ/BTB for the C‐terminal region of GABA_B2 shows that it falls in the low micromolar range. Interestingly, we also demonstrate that a GABA_B2‐related peptide is able to bind KCTD12_BTB with a very high affinity. This peptide may represent a useful tool for modulating KCTD12/GABA_B2 interaction in vitro and may also constitute the starting point for the development of peptidomimetic compounds with a potential for therapeutic applications. Copyright © 2013 John Wiley & Sons, Ltd.     

Speciation of antimony in natural waters : the determination of Sb(III) and Sb(V) by continuous flow hydride generation-atomic absorption spectrometry

Abstract

A new procedure for the speciation of dissolved antimony is described. This makes use of complexation with citrate to prevent, preferentially, the formation of hydride from Sb(V) and allow the selective determination of Sb(III) to be made by continuous flow hydride generation - atomic absorption spectrometry. When the citric acid (12% m/V) is replaced by potassium iodide (3% m/V), total antimony is determined and the concentration of Sb(V) can be obtained by difference. The determination of the antimony species is dominated in this new procedure by the complexation of Sb(V) with citrate and the effect of pH is limited to a minor, re-inforcing role. This permits acidification to be made with hydrochloric acid. The principal interfering species in the determination of total antimony and Sb(III) is Fe³⁺, with Fe²⁺, Cu²⁺ and Ni²⁺ showing lesser effects on Sb(III). The technique is applied successfully to synthetic mixtures and to natural waters from the environment of a disused antimony mine.

The characteristic concentration obtained for antimony was 0.7 ng mL^–1 and the detection limit 1 ng mL^–1.     

Foraging area fidelity for Kemp's ridleys in the Gulf of Mexico

For many marine species, locations of key foraging areas are not well defined. We used satellite telemetry and switching state‐space modeling (SSM) to identify distinct foraging areas used by Kemp's ridley turtles (Lepidochelys kempii) tagged after nesting during 1998–2011 at Padre Island National Seashore, Texas, USA (PAIS; N = 22), and Rancho Nuevo, Tamaulipas, Mexico (RN; N = 9). Overall, turtles traveled a mean distance of 793.1 km (±347.8 SD) to foraging sites, where 24 of 31 turtles showed foraging area fidelity (FAF) over time (N = 22 in USA, N = 2 in Mexico). Multiple turtles foraged along their migratory route, prior to arrival at their “final” foraging sites. We identified new foraging “hotspots” where adult female Kemp's ridley turtles spent 44% of their time during tracking (i.e., 2641/6009 tracking days in foraging mode). Nearshore Gulf of Mexico waters served as foraging habitat for all turtles tracked in this study; final foraging sites were located in water <68 m deep and a mean distance of 33.2 km (±25.3 SD) from the nearest mainland coast. Distance to release site, distance to mainland shore, annual mean sea surface temperature, bathymetry, and net primary production were significant predictors of sites where turtles spent large numbers of days in foraging mode. Spatial similarity of particular foraging sites selected by different turtles over the 13‐year tracking period indicates that these areas represent critical foraging habitat, particularly in waters off Louisiana. Furthermore, the wide distribution of foraging sites indicates that a foraging corridor exists for Kemp's ridleys in the Gulf. Our results highlight the need for further study of environmental and bathymetric components of foraging sites and prey resources contained therein, as well as international cooperation to protect essential at‐sea foraging habitats for this imperiled species.     

Cyanobacterial bioactive metabolites—A review of their chemistry and biology

Cyanobacterial blooms occur when algal densities exceed baseline population concentrations. Cyanobacteria can produce a large number of secondary metabolites. Odorous metabolites affect the smell and flavor of aquatic animals, whereas bioactive metabolites cause a range of lethal and sub-lethal effects in plants, invertebrates, and vertebrates, including humans. Herein, the bioactivity, chemistry, origin, and biosynthesis of these cyanobacterial secondary metabolites were reviewed. With recent revision of cyanobacterial taxonomy by Anagnostidis and Komárek as part of the Süβwasserflora von Mitteleuropa volumes 19(1–3), names of many cyanobacteria that produce bioactive compounds have changed, thereby confusing readers. The original and new nomenclature are included in this review to clarify the origins of cyanobacterial bioactive compounds.Due to structural similarity, the 157 known bioactive classes produced by cyanobacteria have been condensed to 55 classes. This review will provide a basis for more formal procedures to adopt a logical naming system. This review is needed for efficient management of water resources to understand, identify, and manage cyanobacterial harmful algal bloom impacts.     

Identification of Cognitive Dysfunction in Patients with T2DM Using Whole Brain Functional Connectivity

Majority of type 2 diabetes mellitus (T2DM) patients are highly susceptible to several forms of cognitive impairments, particularly dementia. However, the underlying neural mechanism of these cognitive impairments remains unclear. We aimed to investigate the correlation between whole brain resting state functional connections (RSFCs) and the cognitive status in 95 patients with T2DM. We constructed an elastic net model to estimate the Montreal Cognitive Assessment (MoCA) scores, which served as an index of the cognitive status of the patients, and to select the RSFCs for further prediction. Subsequently, we utilized a machine learning technique to evaluate the discriminative ability of the connectivity pattern associated with the selected RSFCs. The estimated and chronological MoCA scores were significantly correlated with R = 0.81 and the mean absolute error (MAE) = 1.20. Additionally, cognitive impairments of patients with T2DM can be identified using the RSFC pattern with classification accuracy of 90.54% and the area under the receiver operating characteristic (ROC) curve (AUC) of 0.9737. This connectivity pattern not only included the connections between regions within the default mode network (DMN), but also the functional connectivity between the task-positive networks and the DMN, as well as those within the task-positive networks. The results suggest that an RSFC pattern could be regarded as a potential biomarker to identify the cognitive status of patients with T2DM.     

Quantifying and Understanding Voltage Losses Due to Nonradiative Recombination in Bulk Heterojunction Organic Solar Cells with Low Energetic Offsets

Open‐circuit voltage (V_OC) losses in organic photovoltaics (OPVs) inhibit devices from reaching V_OC values comparable to the bandgap of the donor–acceptor blend. Specifically, nonradiative recombination losses (?V_nr) are much greater in OPVs than in silicon or perovskite solar cells, yet the origins of this are not fully understood. To understand what makes a system have high or low loss, an investigation of the nonradiative recombination losses in a total of nine blend systems is carried out. An apparent relationship is observed between the relative domain purity of six blends and the degree of nonradiative recombination loss, where films exhibiting relatively less pure domains show lower ?V_nr than films with higher domain purity. Additionally, it is shown that when paired with a fullerene acceptor, polymer donors which have bulky backbone units to inhibit close π–π stacking exhibit lower nonradiative recombination losses than in blends where the polymer can pack more closely. This work reports a strategy that ensures ?V_nr can be measured accurately and reports key observations on the relationship between ?V_nr and properties of the donor/acceptor interface.     

An Air‐Stable and Dendrite‐Free Li Anode for Highly Stable All‐Solid‐State Sulfide‐Based Li Batteries

Li metal is a promising anode material for all‐solid‐state batteries, owing to its high specific capacity and low electrochemical potential. However, direct contact of Li metal with most solid‐state electrolytes induces severe side reactions that can lead to dendrite formation and short circuits. Moreover, Li metal is unstable when exposed to air, leading to stringent processing requirements. Herein, it is reported that the Li₃PS₄/Li interface in all‐solid‐state batteries can be stabilized by an air‐stable Li_xSiS_y protection layer that is formed in situ on the surface of Li metal through a solution‐based method. Highly stable Li cycling for over 2000 h in symmetrical cells and a lifetime of over 100 cycles can be achieved for an all‐solid‐state LiCoO₂/Li₃PS₄/Li cell. Synchrotron‐based high energy X‐ray photoelectron spectroscopy in‐depth analysis demonstrates the distribution of different components within the protection layer. The in situ formation of an electronically insulating Li_xSiS_y protection layer with highly ionic conductivity provides an effective way to prevent Li dendrite formation in high‐energy all‐solid‐state Li metal batteries.