Potential role of NGF,BDNF, and their receptors in oligodendrocytes differentiation from neural stem cell: An in vitro study

Neural stem cells (NSCs) or neuronal progenitor cells are cells capable of differentiating into oligodendrocytes, myelin-forming cells that have the potential of remyelination. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are two neurotrophic factors that have been studied to stimulate NSC differentiation thus playing a role in multiple sclerosis pathogenesis and several other demyelinating disorders. While several studies have demonstrated the proliferative and protective capabilities of these neurotrophic factors, their cellular and molecular functions are still not well understood. Thus, in the present study, we focus on understanding the role of these neurotrophins (BDNF and NGF) in oligodendrogenesis from NSCs. Both neurotrophic factors have been shown to promote NSC proliferation and NSC differentiation particularly into oligodendroglial lineage in a dose-dependent fashion. Further, to establish the role of these neurotrophins in NSC differentiation, we have employed pharmacological inhibitors for TrkA and TrkB receptors in NSCs. The use of these inhibitors suppressed NSC differentiation into oligodendrocytes along with the downregulation of phosphorylated ERK suggesting active involvement of ERK in the functioning of these neurotrophins. The morphometric analysis also revealed the important role of both neurotrophins in oligodendrocytes development. These findings highlight the importance of neurotrophic factors in stimulating NSC differentiation and may pave a role for future studies to develop neurotrophic factor replacement therapies to achieve remyelination.     

Long-term continuous corticosterone treatment decreases VEGF receptor-2 expression in frontal cortex

Objective

Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated.

Material and Methods

We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects.

Results

We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects.

Conclusions

The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.     

Biological observations on the bristly catshark Bythaelurus hispidus from deep waters off the south‐west coast of India

Biological data are presented for the poorly known bristly catshark Bythaelurus hispidus based on specimens collected from the by‐catch of the commercial deep‐sea shrimp trawl fishery operating in the Arabian Sea at depths of 200–500 m off the south‐west coast of India. One hundred and sixty‐two individuals, which ranged from 120 to 366 mm total length (L_T), were collected for this study. Size‐at‐maturity (L₅₀) for females and males was estimated at 252 and 235 mm L_T, respectively. The reproductive mode of B. hispidus was aplacental viviparity, which is the rarest reproductive mode within the Scyliorhinidae and is considered to be the most advanced of the three reproductive modes occurring within this family. Dietary analysis of stomach contents revealed B. hispidus feeds on a variety of prey, primarily fishes.     

Effects of Cellular Activation on Anti-HIV-1 Restriction Factor Expression Profile in Primary Cells

Expression of cell-intrinsic antiviral factors suppresses HIV-1 replication. We hypothesized that cellular activation modulates host restriction and susceptibility to HIV-1 infection. We measured the gene expression of 34 antiviral factors in healthy peripheral blood mononuclear cells (PBMC). Cellular activation induced expression of interferon-stimulated gene 15 (ISG15), tripartite motif 5α (TRIM5α), bone marrow stromal cell antigen 2 (BST-2)/tetherin, and certain apolipoprotein B mRNA editing enzyme 3 (APOBEC3) family members. Expression of RTF1, RNA polymerase II-associated factor 1 (PAF1), TRIM11, TRIM26, and BST-2/tetherin correlated with decreased HIV-1 infectivity. This report demonstrates synchronous effects of activation-induced antiviral genes on HIV-1 infectivity, providing candidates for pharmacological manipulation.     

Smurf E3 ubiquitin ligases at the cross roads of oncogenesis and tumor suppression

Smad ubiquitin regulatory factors (Smurfs) belong to the HECT- family of E3 ubiquitin ligases and comprise mainly of two members, Smurf1 and Smurf2. Initially, Smurfs have been implicated in determining the competence of cells to respond to TGF-β/BMP signaling pathway. Nevertheless, the intrinsic catalytic activity has extended the repertoire of Smurf substrates beyond the TGF-β/BMP super family expanding its realm further to epigenetic modifications of histones governing the chromatin landscape. Through regulation of a large number of proteins in multiple cellular compartments, Smurfs regulate diverse cellular processes, including cell-cycle progression, cell proliferation, differentiation, DNA damage response, maintenance of genomic stability, and metastasis. As the genomic ablation of Smurfs leads to global changes in histone modifications and predisposition to a wide spectrum of tumors, Smurfs are also considered to have a novel tumor suppressor function. This review focuses on regulation network and biological functions of Smurfs in connection with its role in cancer progression. By providing a portrait of their protein targets, we intend to link the substrate specificity of Smurfs with their contribution to tumorigenesis. Since the regulation and biological functions of Smurfs are quite complex, understanding the oncogenic potential of these E3 ubiquitin ligases may facilitate the development of mechanism-based drugs in cancer treatment.     

Landings of whale sharks Rhincodon typus Smith, 1828 in Indian waters since protection in 2001 through the Indian Wildlife (Protection) Act, 1972

Since 28^th May 2001, Whale shark Rhincodon typus Smith, 1828 have received the highest protected status for an animal in India through the Indian Wildlife (Protection) Act, 1972 Schedule-1. However, landings have still been recorded off the Indian coast since 2001, mostly as incidental bycatch in commercial fishing operations, and other sightings have also been reported. In the 1990’s, a targeted whale shark fishery existed off the Gujarat coast following increased demand for the flesh in some other Asian countries. Since the ban, landings of whale sharks have decreased substantially with only 79 recorded between 2001 and 2011. Landings were recorded in each year and in each month of the year with the highest landings in January and February. Between 2001 and 2011, the smallest specimen reported from Indian waters was a 94 cm TL individual and the largest was a 13.7 m TL individual, with most individuals recorded in the 4–6 m TL size class. Small juveniles of less than 3 m TL are rarely recorded in the literature and appear to be rarely observed globally. Between 2006 and 2011, seven juveniles of less than 3 m TL were recorded from two landing sites. Despite the continued landing of whale sharks along the Indian coasts since 2001, the protection of this species appears to have substantially reduced the catches with only incidental landings and strandings now evident. The protection status of whale sharks in India is generally well understood by fishers, but still there is need for further education regarding the current national legislation and vulnerability of the species.     

Guanidinium chloride-induced spectral perturbations of 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid confound interpretation of data on molten globule states

We describe limitations in the use of 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid (bis-ANS) to examine unfolding intermediates associated with guanidinium chloride (GuHCl)-induced protein denaturation. Several studies have used alterations in fluorescence emission of bis-ANS to quantify the population of “molten globule” states. Our findings indicate that the observed changes in bis-ANS spectroscopic properties could originate from the interactions of bis-ANS and GuHCl and the aggregation of the dye at higher GuHCl concentrations. We posit that in the absence of additional complementary structural or spectroscopic measurements, the use of bis-ANS emission alone to monitor protein conformations can be misleading.