Selective Cu2+ binding, redox silencing, and cytoprotective effects of the small heat shock proteins alphaA- and alphaB-crystallin

Oxidative stress and Cu²⁺ have been implicated in several neurodegenerative diseases and in cataract. Oxidative stress, as well as Cu²⁺, is also known to induce the expression of the small heat shock proteins α-crystallins. However, the role of α-crystallins in oxidative stress and in Cu²⁺-mediated processes is not clearly understood. We demonstrate using fluorescence and isothermal titration calorimetry that α-crystallins (αA- and αB-crystallin and its phosphorylation mimic, 3DαB-crystallin) bind Cu²⁺ with close to picomolar range affinity. The presence of other tested divalent cations such as Zn²⁺, Mg²⁺, and Ca²⁺ does not affect Cu²⁺ binding, indicating selectivity of the Cu²⁺-binding site(s) in α-crystallins. Cu²⁺ binding induces structural changes and increase in the hydrodynamic radii of α-crystallins. Cu²⁺ binding increases the stability of α-crystallins towards guanidinium chloride-induced unfolding. Chaperone activity of αA-crystallin increases significantly upon Cu²⁺ binding. α-Crystallins rescue amyloid beta peptide, Aβ_1-40, from Cu²⁺-induced aggregation in vitro. α-Crystallins inhibit Cu²⁺-induced oxidation of ascorbate and, hence, prevent the generation of reactive oxygen species. Interestingly, α-synuclein, a Cu²⁺-binding protein, does not inhibit this oxidation process significantly. We find that the Cu²⁺-sequestering (or redox-silencing) property of α-crystallins confers cytoprotection. To the best of our knowledge, this is the first study to reveal high affinity (close to picomolar) for Cu²⁺ binding and redox silencing of Cu²⁺ by any heat shock protein. Thus, our study ascribes a novel functional role to α-crystallins in Cu²⁺ homeostasis and helps in understanding their protective role in neurodegenerative diseases and cataract.     

Soil-transmitted helminths in relation to hemoglobin status among school children of the Kashmir Valley

Soil-transmitted helminths (STHs) remain a major threat to the health of children throughout the world, mostly in developing nations. The aim of the present study was to determine any relationship between STHs and hemoglobin status in school children of Kashmir Valley (India). Stool and blood samples were collected from 382 male and female school children in the age group of 5-15 yr from all 6 school districts of the Kashmir Valley. Finger-prick blood samples were used to collect the hemoglobin, which was then measured on-site by Sahli's acid hematin method; stool samples were processed using both simple smear and zinc sulphate concentration methods. Of the 382 children surveyed, 299 (78.27%) were infected with Ascaris lumbricoides, Trichuris trichiura, or both. Children infected by STHs were found to have lower mean values of hemoglobin than uninfected children. The present study reveals that STHs are abundant among school children of Kashmir Valley, creating a negative effect on the hemoglobin values and indicating the necessity of implementing control measures.     

Dual regulation of the cardiac L-type calcium channel in L6 cells by protein kinase C

The role of protein kinase C (PKC) in the regulation of cardiac L-type Ca²⁺ channel activity (LCC) was investigated in L6 rat neonatal myoblasts. Depolarization of fura-2 loaded cells with 140 mM KCl activated a Ba²⁺ influx pathway that was blocked by nifedipine and stimulated by (−) Bay K 8644. At least two splice variants of the α_1C subunit of the cardiac LCC were identified by PCR; the α_1S subunit of the skeletal muscle LCC was not detected. Peptides that specifically inhibit translocation of the novel, Ca²⁺-independent δ and PKC isozymes reduced Ba²⁺ influx by 27% and 19%, respectively, whereas a corresponding peptide directed against translocation of classical PKC α had no effect. Ingenol 3,20-dibenzoate, an agent reported to selectively activate novel PKCs, increased Ba²⁺ uptake by 31% while ethanol, a PKC agonist, enhanced uptake by 38%. In contrast, selective activation of classical PKCs with thymeleatoxin or an agonist peptide reduced Ba²⁺ influx by 23–33%. Ba²⁺ influx was reduced by 30–40% when cells were treated with either a PKC inhibitor (Gö 6983, bisindolylmaleimide) or the PKC activator phorbol-12-myristate-13-acetate. We propose that novel, Ca²⁺-insensitive PKC(s) enhance cardiac Ca²⁺ channel activity in L6 cells under basal conditions while activation of the classical, Ca²⁺-sensitive PKC(s) inhibits channel activity. These findings provide the first evidence that different PKC isozymes exert class-specific opposing effects on cardiac L-type Ca²⁺ channel activity in L6 myoblasts.     

Culture-Based Strategies for Reduction of Protease Activity in Filtrates from Aspergillus niger NRRL-3

Summary While Aspergillus strains are also being considered as potential hosts for production of extracellular heterologous proteins, the proteases produced by the host are highly problematic in that they typically modify and degrade the recombinant proteins. Culture-based approaches for minimization of protease activity in culture supernatants of Aspergillus niger NRRL-3 included reduction or elimination of peptide nitrogen in the medium, preferential use of a defined salts medium rather than a non-peptide nitrogen medium containing yeast-nitrogen base, supplementation of the medium with carboxymethylcellulose and cultivation at pH 6.5 rather than 7.5. In general, increased proteolytic activity was observed after maximum biomass was observed and biomass was declining suggesting the majority of protease activity was released by cell lysis. Carboxymethylcellulose shifted mycelial morphology from pelleted to filamentous. Mycelium lysis in the centre of pellets, with resultant release of intracellular proteases, would explain why filamentous cultures exhibited much lower proteolytic activity than pelleted cultures.     

Encapsulating Trogtalite CoSe2 Nanobuds into BCN Nanotubes as High Storage Capacity Sodium Ion Battery Anodes

Trogtalite CoSe₂ nanobuds encapsulated into boron and nitrogen codoped graphene (BCN) nanotubes (CoSe₂@BCN‐750) are synthesized via a concurrent thermal decomposition and selenization processes. The CoSe₂@BCN‐750 nanotubes deliver an excellent storage capacity of 580 mA h g^?1 at current density of 100 mA g^?1 at 100th cycle, as the anode of a sodium ion battery. The CoSe₂@BCN‐750 nanotubes exhibit a significant rate capability (100–2000 mA g^?1 current density) and high stability (almost 98% storage retention after 4000 cycles at large current density of 8000 mA g^?1). The reasons for these excellent storage properties are illuminated by theoretical calculations of the relevant models, and various possible Na⁺ ion storage sites are identified through first‐principles calculations. These results demonstrate that the insertion of heteroatoms, B–C, N–C as well as CoSe₂, into BCN tubes, enables the observed excellent adsorption energy of Na⁺ ions in high energy storage devices, which supports the experimental results.     

Splenic peliosis – a potentially fatal condition which can mimick malignancy

Isolated splenic peliosis is an extremely rare occurrence, and this disease often manifests itself with spontaneous haemoperitoneum.We report a case where an otherwise healthy patient was found to have splenomegaly on clinical examination. On computerised tomography, a diagnosis of splenic malignancy was made, and the patient underwent a splenectomy. Histological examination gave the diagnosis of splenic peliosis, which had not been considered prior to the operation. In retrospect, splenectomy was the most prudent course of action, as the risk of spontaneous haemorrhage and fatality was eliminated. This case emphasises the need to retain an index of suspicion for this condition, even in otherwise healthy patients, and is a reminder of the usefulness of total splenectomy in the current era of minimally invasive diagnostic techniques.     

Historical demographic profiles and genetic variation of the East African Butana and Kenana indigenous dairy zebu cattle

Butana and Kenana breeds from Sudan are part of the East African zebu Bos indicus type of cattle. Unlike other indigenous zebu cattle in Africa, they are unique due to their reputation for high milk production and are regarded as dairy cattle, the only ones of their kind on the African continent. In this study, we sequenced the complete mitochondrial DNA (mtDNA) D‐loop of 70 animals to understand the maternal genetic variation, demographic profiles and history of the two breeds in relation to the history of cattle pastoralism on the African continent. Only taurine mtDNA sequences were identified. We found very high mtDNA diversity but low level of maternal genetic structure within and between the two breeds. Bayesian coalescent‐based analysis revealed different historical and demographic profiles for the two breeds, with an earlier population expansion in the Butana vis a vis the Kenana. The maternal ancestral populations of the two breeds may have diverged prior to their introduction into the African continent, with first the arrival of the ancestral Butana population. We also reveal distinct demographic history between the two breeds with the Butana showing a decline in its effective population size (N_e) in the recent past ~590 years. Our results provide new insights on the early history of cattle pastoralism in Sudan indicative of a large ancient effective population size.     

On the Importance of Hysteresis in Numerical Modeling of Surfactant-Induced Unsaturated Flow

It is known that surfactants can induce flow in unsaturated porous media due to the dependence of capillary pressure on surface tension. A commonly observed feature in systems with surfactant-induced flow is a transient wetting/drying/wetting sequence associated with the propagation of a surfactant solute front under monotonic flow conditions. Previous efforts to model surfactant-induced flow in relatively complex (e.g., two-dimensional systems) have not successfully incorporated hysteretic moisture retention properties. In this research, hysteretic, two-dimensional simulations of surfactant-induced flow were performed to assess the potential importance of considering hysteresis in such simulations. Hysteretic simulation results were compared to experimental data and to non-hysteretic simulations. The results suggest that the inclusion of hysteresis in numerical simulations can improve the match between simulated and experimental results in systems with surfactant-induced unsaturated flow. Furthermore, the inclusion of hysteresis in numerical simulations played a significant role in predicting the distribution of the contaminant and correct pressure head/moisture condition at the end of the experiment.