Characterization of the mouse ClC-K1/Barttin chloride channel

Several Cl⁻ channels have been described in the native renal tubule, but their correspondence with ClC-K1 and ClC-K2 channels (orthologs of human ClC-Ka and ClC-Kb), which play a major role in transcellular Cl⁻ absorption in the kidney, has yet to be established. This is partly because investigation of heterologous expression has involved rat or human ClC-K models, whereas characterization of the native renal tubule has been done in mice. Here, we investigate the electrophysiological properties of mouse ClC-K1 channels heterologously expressed in Xenopus laevis oocytes and in HEK293 cells with or without their accessory Barttin subunit. Current amplitudes and plasma membrane insertion of mouse ClC-K1 were enhanced by Barttin. External basic pH or elevated calcium stimulated currents followed the anion permeability sequence Cl⁻ > Br⁻ > NO₃⁻ > I⁻. Single-channel recordings revealed a unit conductance of ~ 40 pS. Channel activity in cell-attached patches increased with membrane depolarization (voltage for half-maximal activation: ~ − 65 mV). Insertion of the V166E mutation, which introduces a glutamate in mouse ClC-K1, which is crucial for channel gating, reduced the unit conductance to ~ 20 pS. This mutation shifted the depolarizing voltage for half-maximal channel activation to ~ + 25 mV. The unit conductance and voltage dependence of wild-type and V166E ClC-K1 were not affected by Barttin. Owing to their strikingly similar properties, we propose that the ClC-K1/Barttin complex is the molecular substrate of a chloride channel previously detected in the mouse thick ascending limb (Paulais et al., J Membr. Biol, 1990, 113:253–260).     

Interpreting skeletal growth in the past from a functional and physiological perspective

The study of juvenile skeletal remains can yield important insights into the health, behavior, and biological relationships of past populations. However, most studies of past skeletal growth have been limited to relatively simple metrics. Considering additional skeletal parameters and taking a broader physiological perspective can provide a more complete assessment of growth patterns and environmental and genetic effects on those patterns. We review here some alternative approaches to ontogenetic studies of archaeological and paleontological skeletal material, including analyses of body size (stature and body mass) and cortical bone structure of long bone diaphyses and the mandibular corpus. Together such analyses can shed new light on both systemic and localized influences on bone growth, and the metabolic and mechanical factors underlying variation in growth. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Effects of experimental calcium availability,egg parameters and laying order on Great Tit Parus major eggshell pigmentation patterns

Many bird species lay eggs speckled with protoporphyrin‐based spots, however, for most of them the function of eggshell spotting is unknown. A plausible hypothesis is that protoporphyrin might have a structural function in strengthening the eggshell and is therefore deposited when calcium is scarce. In this study, we experimentally provided Great Tit Parus major females with supplemental calcium to examine its effect on the protoporphyrin‐based maculation of their eggs. In addition, we studied variation in eggshell pigmentation patterns in relation to other egg parameters and laying order. Calcium‐supplemented females laid larger eggs but shell thickness was not significantly affected by the treatment. Calcium supplementation may reduce the time and energy females devote to searching for calcium‐rich material, so that they can collect more nutrients and so lay larger eggs. Furthermore, pigment darkness was associated with egg volume and shape, which suggests that female quality and environmental food availability may also influence the shell pigmentation pattern. Within clutches, later‐laid eggs had larger and darker spots that were distributed more unevenly on the shell surface. This within‐clutch pattern could be explained by the increase in egg volume and egg shape and a decline in shell thickness with egg‐laying order, which characteristics were all related to shell‐spotting pattern. Eggs with a coronal ring had thinner shells, but pigment intensity and spot size were not related to shell thickness. Thus, our results suggest that concentrated spotting distribution may have a mechanical function, supporting the structural‐function hypothesis.     

Multispectral image analysis for algal biomass quantification

This article reports a novel multispectral image processing technique for rapid, noninvasive quantification of biomass concentration in attached and suspended algae cultures. Monitoring the biomass concentration is critical for efficient production of biofuel feedstocks, food supplements, and bioactive chemicals. Particularly, noninvasive and rapid detection techniques can significantly aid in providing delay‐free process control feedback in large‐scale cultivation platforms. In this technique, three‐band spectral images of Anabaena variabilis cultures were acquired and separated into their red, green, and blue components. A correlation between the magnitude of the green component and the areal biomass concentration was generated. The correlation predicted the biomass concentrations of independently prepared attached and suspended cultures with errors of 7 and 15%, respectively, and the effect of varying lighting conditions and background color were investigated. This method can provide necessary feedback for dilution and harvesting strategies to maximize photosynthetic conversion efficiency in large‐scale operation. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:808–816, 2013     

In Situ Measurement of Solid Electrolyte Interphase Evolution on Silicon Anodes Using Atomic Force Microscopy

In situ measurements of the growth of solid electrolyte interphase (SEI) layer on silicon and the lithiation‐induced volume changes in silicon in lithium ion half‐cells are reported. Thin film amorphous silicon electrodes are fabricated in a configuration that allows unambiguous separation of the total thickness change into contribution from SEI thickness and silicon volume change. Electrodes are assembled into a custom‐designed electrochemical cell, which is integrated with an atomic force microscope. The electrodes are subjected to constant potential lithiation/delithiation at a sequence of potential values and the thickness measurements are made at each potential after equilibrium is reached. Experiments are carried out with two electrolytes—1.2 m lithium hexafluoro‐phosphate (LiPF₆) in ethylene carbonate (EC) and 1.2 m LiPF₆ in propylene carbonate (PC)—to investigate the influence of electrolyte composition on SEI evolution. It is observed that SEI formation occurs predominantly during the first lithiation and the maximum SEI thickness is ≈17 and 10 nm respectively for EC and PC electrolytes. This study also presents the measured Si expansion ratio versus equilibrium potential and charge capacity versus equilibrium potential; both relationships display hysteresis, which is explained in terms of the stress–potential coupling in silicon.     

Lysosomal membrane permeabilization is involved in oxidative stress-induced apoptotic cell death in LAMP2-deficient iPSCs-derived cerebral cortical neurons

Patients with Danon disease may suffer from severe cardiomyopathy, skeletal muscle dysfunction as well as varying degrees of mental retardation, in which the primary deficiency of lysosomal membrane-associated protein-2 (LAMP2) is considerably associated. Owing to the scarcity of human neurons, the pathological role of LAMP2 deficiency in neural injury of humans remains largely elusive. However, the application of induced pluripotent stem cells (iPSCs) may shed light on overcoming such scarcity.In this study, we obtained iPSCs derived from a patient carrying a mutated LAMP2 gene that is associated with Danon disease. By differentiating such LAMP2-deficient iPSCs into cerebral cortical neurons and with the aid of various biochemical assays, we demonstrated that the LAMP2-deficient neurons are more susceptible to mild oxidative stress-induced injury.The data from MTT assay and apoptotic analysis demonstrated that there was no notable difference in cellular viability between the normal and LAMP2-deficient neurons under non-stressed condition. When exposed to mild oxidative stress (10 μM H₂O₂), the LAMP2-deficient neurons exhibited a significant increase in apoptosis. Surprisingly, we did not observe any aberrant accumulation of autophagic materials in the LAMP2-deficient neurons under such stress condition.Our results from cellular fractionation and inhibitor blockade experiments further revealed that oxidative stress-induced apoptosis in the LAMP2-deficient cortical neurons was caused by increased abundance of cytosolic cathepsin L. These results suggest the involvement of lysosomal membrane permeabilization in the LAMP2 deficiency associated neural injury.     

The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice

There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd.     

宝石能谱CT评估冠状动脉介入治疗术后支架内成像质量的研究

目的:探讨宝石能谱CT用于冠状动脉支架内成像质量评估的应用价值。方法:回顾分析56例冠状动脉支架植入后患者,按照支架厚度及直径分成四组。采用宝石能谱CT对冠状动脉成像及同时进行冠状动脉造影患者的影像学资料,通过分析宝石能谱CT的冠状动脉的成像质量,与冠状动脉造影进行对比,得出宝石能谱CT用于冠状动脉介入治疗术后支架内成像质量评估的价值。结果:宝石能谱CT显示支架内再狭窄的敏感度为100%,特异度为98.6%,阴性预测值为100%。直径≥3 mm的支架内成像质量优于直径3 mm的支架。但支架直径和厚度对宝石能谱CT支架内成像质量的可评估率没有差异。结论:宝石能谱CT均能提供优秀的冠状动脉支架内成像质量,采用宝石能谱CT替代冠状动脉造影术可对冠脉支架术后支架内影像进行评估。     

Room Temperature Processed Highly Efficient Large‐Area Polymer Solar Cells Achieved with Molecular Engineering of Copolymers

The room temperature (RT) processability of the photoactive layers in polymer solar cells (PSCs) from halogen‐free solvent along with their highly reproducible power conversion efficiencies (PCEs) and intrinsic thickness tolerance are extremely desirable for the large‐area roll‐to‐roll (R2R) production. However, most of the photoactive materials in PSCs require elevated processing temperatures due to their strong aggregation, which are unfavorable for the industrial R2R manufacturing of PSCs. These limiting factors for the commercialization of PSCs are alleviated by synthesizing random terpolymers with components of (2‐decyltetradecyl)thiophen‐2‐yl)naphtho[1,2‐c:5,6‐c′]bis[1,2,5]thiadiazole and bithiophene substituted with methyl thiophene‐3‐carboxylate (MTC). In contrast to the temperature‐dependent PNTz4T polymer, the resulting random terpolymers (PNTz4T‐MTC) show better solubility, slightly reduced crystallinity and aggregation, and weaker intermolecular interaction, thus enabling PNTz4T‐MTC to be processed at RT from a halogen‐free solvent. Particularly, the PNTz4T‐5MTC‐based photoactive layer exhibits an excellent PCE of 9.66%, which is among the highest reported PCEs for RT and ecofriendly halogen‐free solvent processed fullerene‐based PSCs, and a thickness tolerance with a PCE exceeding 8% from 100 to 520 nm. Finally, large‐area modules fabricated with the PNTz4T and PNTz4T‐5MTC polymer have shown 4.29% and 6.61% PCE respectively, with an area as high as 54.45 cm² in air.