MicroRNA-214 controls skin and hair follicle development by modulating the activity of the Wnt pathway

Skin development is governed by complex programs of gene activation and silencing, including microRNA-dependent modulation of gene expression. Here, we show that miR-214 regulates skin morphogenesis and hair follicle (HF) cycling by targeting β-catenin, a key component of the Wnt signaling pathway. miR-214 exhibits differential expression patterns in the skin epithelium, and its inducible overexpression in keratinocytes inhibited proliferation, which resulted in formation of fewer HFs with decreased hair bulb size and thinner hair production. The inhibitory effects of miR-214 on HF development and cycling were associated with altered activities of multiple signaling pathways, including decreased expression of key Wnt signaling mediators β-catenin and Lef-1, and were rescued by treatment with pharmacological Wnt activators. Finally, we identify β-catenin as one of the conserved miR-214 targets in keratinocytes. These data provide an important foundation for further analyses of miR-214 as a key regulator of Wnt pathway activity and stem cell functions during normal tissue homeostasis, regeneration, and aging.     

Feedback inhibition of ENaC: Acute and chronic mechanisms

Intracellular [Na⁺] ([Na⁺]_i) modulates the activity of the epithelial Na channel (ENaC) to help prevent cell swelling and regulate epithelial Na⁺ transport, but the underlying mechanisms remain unclear. We show here that short-term (60–80 min) incubation of ENaC-expressing oocytes in high Na⁺ results in a 75% decrease in channel activity. When the β subunit was truncated, corresponding to a gain-of-function mutation found in Liddle''s syndrome, the same maneuver reduced activity by 45% despite a larger increase in [Na⁺]_i. In both cases the inhibition occurred with little to no change in cell-surface expression of γENaC. Long-term incubation (18 hours) in high Na⁺ reduced activity by 92% and 75% in wild-type channels and Liddle''s mutant, respectively, with concomitant 70% and 52% decreases in cell-surface γENaC. In the presence of Brefeldin A to inhibit forward protein trafficking, high-Na⁺ incubation decreased wt ENaC activity by 52% and 88% after 4 and 8 hour incubations, respectively. Cleaved γENaC at the cell surface had lifetimes at the surface of 6 hrs in low Na⁺ and 4 hrs in high Na⁺, suggesting that [Na⁺]_i increased the rate of retrieval of cleaved γ ENaC by 50%. This implies that enhanced retrieval of ENaC channels at the cell surface accounts for part, but not all, of the downregulation of ENaC activity shown with chronic increases in [Na⁺]_i.     

Pyrolysis of groundnut de-oiled cake and characterization of the liquid product

Renewable biomass is considered as an important energy resource all over the world and for an agriculture based economy like that of India, the future prospects of being able to convert widely available biomass materials into various forms of fuel is most attractive. In this study, pyrolysis of groundnut de-oiled cake was investigated with an aim of studying the physical and chemical characteristics of the bio-fuel produced and to determine its feasibility as a commercial fuel. Thermal pyrolysis of groundnut de-oiled cake was done in a semi-batch reactor at a temperature range of 200-500 °C and at a heating rate of 20 °C/min. The chemical analysis of the bio-fuel showed the presence of functional groups such as alkanes, alkenes, alkynes, aldehydes, ketones, carboxylic acids, esters, amines, nitriles, nitro compounds and aromatics rings. The physical properties of the bio-fuel obtained were close to that of diesel and petrol.     

Decreased sensory responses in osteocalcin null mutant mice imply neuropeptide function

Osteocalcin, the most abundant member of the family of extracellular mineral binding gamma-carboxyglutamic acid proteins is synthesized primarily by osteoblasts. Its affinity for calcium ions is believed to limit bone mineralization. Several of the numerous hormones that regulate synthesis of osteocalcin, including glucocorticoids and parathyroid hormone, are also affected by stressful stimuli that require energy for an appropriate response. Based on our observations of OC responding to stressful sensory stimuli, the expression of OC in mouse and rat sensory ganglia was confirmed. It was thus hypothesized that the behavioral responses of the OC knockout mouse to stressful sensory stimuli would be abnormal. To test this hypothesis, behaviors related to sensory aspects of the stress response were quantified in nine groups of mice, aged 4-14 months, comparing knockout with their wild-type counterparts in six distinctly different behavioral tests. Resulting data indicated the following statistically significant differences: open field grooming frequency following saline injection, wild-type > knockout; paw stimulation with Von Frey fibers, knockout < wild-type; balance beam, knockout mobility < WT; thermal sensitivity to heat (tail flick), knockout < wild-type; and cold, knockout < wild-type. Insignificant differences in hanging wire test indicate that these responses are unrelated to reduced muscle strength. Each of these disparate environmental stimuli provided data indicating alterations of responses in knockout mice that suggest participation of osteocalcin in transmission of information about those sensory stimuli.     

Opioid Peptides: An Overview of Functional Significance

International Journal of Peptide Research and Therapeutics - Bioactive peptides have been reported to exhibit opioid-like activity and are termed as opioid peptides. Either these are produced...     

In vitro mesenchymal-epithelial transition in NIH3T3 fibroblasts results in onset of low-dose radiation hypersensitivity coupled with attenuated connexin-43 response

Background

Mesenchymal-to-epithelial transition (MET) is associated with altered cell adhesion patterns. Independent studies showed that cellular adhesion regulates low-dose hyper-radiosensitivity (HRS), a phenomenon reported widely in tumour cells. Therefore, present study aimed to investigate whether MET and associated cellular adhesion alterations affect cellular radiosensitivity.

Biophysical insight into the heparin‐peptide interaction and its modulation by a small molecule

The heparin‐protein interaction plays a vital role in numerous physiological and pathological processes. Not only is the binding mechanism of these interactions poorly understood, studies concerning their therapeutic targeting are also limited. Here, we have studied the interaction of the heparin interacting peptide (HIP) from Tat (which plays important role in HIV infections) with heparin. Isothermal titration calorimetry binding exhibits distinct biphasic isotherm with two different affinities in the HIP‐heparin complex formation. Overall, the binding was mainly driven by the nonionic interactions with a small contribution from ionic interactions. The stoichiometric analysis suggested that the minimal site for a single HIP molecule is a chain of 4 to 5 saccharide molecules, also supported by docking studies. The investigation was also focused on exploiting the possibility of using a small molecule as an inhibitor of the HIP‐heparin complex. Quinacrine, because of its ability to mimic the HIP interactions with heparin, was shown to successfully modulate the HIP‐heparin interactions. This result demonstrates the feasibility of inhibiting the disease relevant heparin‐protein interactions by a small molecule, which could be an effective strategy for the development of future therapeutic agents.     

Biochemical and physiological characterization of a halotolerant Dunaliella salina isolated from hypersaline Sambhar Lake,India

The objective of the present study was to characterize intrinsic physiological and biochemical properties of the wall‐less unicellular cholorophyte Dunaliella salina isolated from a hypersaline Sambhar Lake. The strain grew optimally at 0.5 M NaCl and 16:8 h L:D photoperiod along with maintaining low level of intracellular Na⁺ even at higher salinity, emphasizing special features of its cell membranes. It was observed that the cells experienced stress beyond 2 M NaCl as evidenced by increased intracellular reactive oxygen species and antioxidative enzymes, nevertheless proline and malondialdehyde content declined sharply accompanied by higher neutral lipid accumulation. Salinity exceeding 2 M resulted decrease in photosynthetic quantum yield (Fv/Fm) and enhanced glycerol synthesis accompanied by leakage. Super oxide dismutase seemed to play a pivotal role in antioxidative defense as eight isoforms were expressed differentially while catalase and glutathione peroxidase showing no significant change in their expression at higher salinity. The ability of D. salina to grow in range of salinities by sustaining healthy photosynthetic apparatus along with accumulation of valuable products made this alga an ideal organism that can be exploited as resource for biofuel and commercial products.     

Structure of Phosphorylated SF1 Bound to U2AF65 in an Essential Splicing Factor Complex

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Highlights? Splicing factor SF1 phosphorylation on a conserved SPSP motif is required in vivo ? SPSP phosphorylation (P) induces local folding within an SF1/U2AF⁶⁵ interface ? Phosphorylation promotes an acutely bent (P)SF1/U2AF⁶⁵/RNA conformation