Soluble Nogo Receptor Down-regulates Expression of Neuronal Nogo-A to Enhance Axonal Regeneration

Nogo-A, a member of the reticulon family, is present in neurons and oligodendrocytes. Nogo-A in central nervous system (CNS) myelin prevents axonal regeneration through interaction with Nogo receptor 1, but the function of Nogo-A in neurons is less known. We found that after axonal injury, Nogo-A is increased in dorsal root ganglion (DRG) neurons unable to regenerate following a dorsal root injury or a sciatic nerve ligation-cut injury and that exposure in vitro to CNS myelin dramatically enhanced neuronal Nogo-A mRNA and protein through activation of RhoA while inhibiting neurite growth. Knocking down neuronal Nogo-A by small interfering RNA results in a marked increase of neurite outgrowth. We constructed a nonreplicating herpes simplex virus vector (QHNgSR) to express a truncated soluble fragment of Nogo receptor 1 (NgSR). NgSR released from QHNgSR prevented myelin inhibition of neurite extension by hippocampal and DRG neurons in vitro. NgSR prevents RhoA activation by myelin and decreases neuronal Nogo-A. Subcutaneous inoculation of QHNgSR to transduce DRG neurons resulted in improved regeneration of myelinated fibers in both the dorsal root and the spinal dorsal root entry zone, with concomitant improvement in sensory behavior. The results indicate that neuronal Nogo-A is an important intermediate in neurite growth dynamics and its expression is regulated by signals related to axonal injury and regeneration, that CNS myelin appears to activate signaling events that mimic axonal injury, and that NgSR released from QHNgSR may be used to improve recovery after injury.     

A Disease-causing Mutation in the Active Site of Serine Palmitoyltransferase Causes Catalytic Promiscuity

The autosomal dominant peripheral sensory neuropathy HSAN1 results from mutations in the LCB1 subunit of serine palmitoyltransferase (SPT). Serum from patients and transgenic mice expressing a disease-causing mutation (C133W) contain elevated levels of 1-deoxysphinganine (1-deoxySa), which presumably arise from inappropriate condensation of alanine with palmitoyl-CoA. Mutant heterodimeric SPT is catalytically inactive. However, mutant heterotrimeric SPT has ∼10–20% of wild-type activity and supports growth of yeast cells lacking endogenous SPT. In addition, long chain base profiling revealed the synthesis of significantly more 1-deoxySa in yeast and mammalian cells expressing the heterotrimeric mutant enzyme than in cells expressing wild-type enzyme. Wild-type and mutant enzymes had similar affinities for serine. Surprisingly, the enzymes also had similar affinities for alanine, indicating that the major affect of the C133W mutation is to enhance activation of alanine for condensation with the acyl-CoA substrate. In vivo synthesis of 1-deoxySa by the mutant enzyme was proportional to the ratio of alanine to serine in the growth media, suggesting that this ratio can be used to modulate the relative synthesis of sphinganine and 1-deoxySa. By expressing SPT as a single-chain fusion protein to ensure stoichiometric expression of all three subunits, we showed that GADD153, a marker for endoplasmic reticulum stress, was significantly elevated in cells expressing mutant heterotrimers. GADD153 was also elevated in cells treated with 1-deoxySa. Taken together, these data indicate that the HSAN1 mutations perturb the active site of SPT resulting in a gain of function that is responsible for the HSAN1 phenotype.     

Clinical application prospects and transformation value of dental follicle stem cells in oral and neurological diseases

Since dental pulp stem cells (DPSCs) were first reported, six types of dental SCs (DSCs) have been isolated and identified. DSCs originating from the craniofacial neural crest exhibit dental-like tissue differentiation potential and neuro-ectodermal features. As a member of DSCs, dental follicle SCs (DFSCs) are the only cell type obtained at the early developing stage of the tooth prior to eruption. Dental follicle tissue has the distinct advantage of large tissue volume compared with other dental tissues, which is a prerequisite for obtaining a sufficient number of cells to meet the needs of clinical applications. Furthermore, DFSCs exhibit a significantly higher cell proliferation rate, higher colony-formation capacity, and more primitive and better anti-inflammatory effects than other DSCs. In this respect, DFSCs have the potential to be of great clinical significance and translational value in oral and neurological diseases, with natural advantages based on their origin. Lastly, cryopreservation preserves the biological properties of DFSCs and enables them to be used as off-shelf products for clinical applications. This review summarizes and comments on the properties, application potential, and clinical transformation value of DFSCs, thereby inspiring novel perspectives in the future treatment of oral and neurological diseases.     

Bone marrow mesenchymal stem cell treatment improves post-stroke cerebral function recovery by regulating gut microbiota in rats

Early intervention with bone marrow mesenchymal stem cells to change the form and function of the gut microbiota may help rats regain neurological function after a stroke.     

Effects of methamidophos on sediment processing and body mass of Capitella sp. Y from Estero del Yugo, Mazatlán, Mexico

The cosmopolitan species-complex Capitella, a deposit-feeding polychaete, is widely used as an indicator of organic pollution and plays an important role in sewage waste cycling in marine and estuarine ecosystems. The organophosphorous insecticide methamidophos is currently employed in agriculture fields to control insect infestations. Its occurrence could pose a hazard to infauna. A bioassay to investigate the effects of exposing Capitella sp. Y to sediment spiked with methamidophos (0.008, 0.016, 0.032, 0.064, 0.130 and 0.260 mg/g dry wt sediment) is described. Increasing methamidophos concentrations significantly reduced faecal pellet production and body mass. Some specimens exhibited morphological abnormalities and behaviour changes, which could be attributed to toxic effects of methamidophos not severe enough to stop feeding activity. Results using Capitella sp. Y suggest that methamidophos could affect the rate of sediment processing by polychaetes or other benthic invertebrates in zones subjected to the influence of such insecticide.     

High temperature acclimation alters upper thermal limits and growth performance of Indian major carp,rohu, Labeo rohita (Hamilton, 1822)

Increase in water temperature due to anthropogenic and climatic changes is expected to affect physiological functions of fish. In this study, we determined high temperature tolerance (CTmax) of a common aquacultured Indian major carp, rohu, Labeo rohita fingerlings (15.96 ± 0.72 g BW, 11.56 ± 0.42 cm TL) followed by acclimatization at three temperatures (30, 33, 36 °C). To determine the CTmax, we analyzed the major hemato-biochemical indices - hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC), blood glucose levels, and erythrocytic nuclear abnormalities (ENAs) and erythrocytic cellular abnormalities (ECAs) of peripheral erythrocytes in the fish sampled at the start and end point at each acclimated temperature. Significantly decreased CTmax of the fish was found at 36 °C compared to 30 °C and 33 °C. The fish in the highest (36 °C) temperature were found with significantly lower Hb and RBC content and significantly higher WBC and blood glucose levels than that of the fishes in the lowest (30 °C) temperature both at the start and end points. The highest frequencies of ENAs and ECAs were found in the highest (36 °C) temperature group compared to the lowest (30 °C) temperature group at both the points. We also evaluated growth performance of the rohu fingerlings reared in the three temperatures for 60 days. The growth parameters - final weight gain, percent weight gain and specific growth rate were the highest at 33 °C and the lowest at 36 °C. The present study revealed that the highest temperature (36 °C) tested here may be hazardous to rohu and the temperature should be kept below 36 °C in the aquaculture setting to avoid physiological damage and growth and production loss to the fish.     

The dazzling rise of neurofilaments: Physiological functions and roles as biomarkers

In the last two years, neurofilaments (NFs) have become one of the most blazing topics in clinical neuroscience. NFs are major cytoskeletal constituents of neurons, can be detected in body fluids, and have recently emerged as universal biomarkers of neuronal injury and neurological diseases. This review will examine the evolving landscape of NFs, from their specific cellular functions within neurons to their broad clinical value as biomarkers. Particular attention will be given to the dynamic nature of the NF network and its novel roles in microtubule regulation, neurotransmission, and nanomedicine. Building from the initial evidence of causative mutations in NF genes in Charcot–Marie–Tooth diseases, the latest advances at the frontiers of basic and clinical sciences have expanded the scope and relevance of NFs for human health remarkably and have poised to fuel innovation in cell biology and neuroscience.     

X-ray irradiation of excised embryos of mesta (Hibiscus cannabinus L. and H. sabdariffa L.)

Summary Excised embryos of Hibiscus spp. were treated with 1 kR to 6 kR of X-ray. Results indicate that germination was unaffected at this level of employed doses in both species, which in turn implies that the factors responsible for inhibition of germination are not present in the embryo. LD₅₀ values differed between varieties and species. Early varieties of both species were more sensitive to radiation than late varieties. Strikingly similar effects were observed for the varieties with smaller embryos over those with larger ones. Allopolyploid H. sabdariffa (2n=72) was more susceptible than diploid H. cannabinus (2n=36).Differences in mutation frequency exist between species with different levels of ploidy and between varieties within the same species. Most of the HC mesta varieties yielded higher mutation frequencies than those of HS mesta. Optimal dose for triggering mutations in all varieties (except the chlorophyll mutation variety of HC mesta) of the two species lies within a narrow range of 1 kR to 2 kR. Cent per cent seedling abnormalities is concomitant to LD₅₀; nevertheless, optimum dose for mutation frequency is independent of LD₅₀. Hence, the response should be viewed in terms of respective genotype. The advantages of the embryo irradiation technique are mentioned.     

14th International Workshop on Ataxia-Telangiectasia ATW2012

The fourteenth international Ataxia-Telangiectasia Workshop 2012 (ATW2012) (www.atw2012.com) on ataxia-telangiectasia (AT) and the role of the ataxia telangiectasia mutated (ATM) gene in DNA repair, neurological disease, cancer and related topics was held from February 07 to 11, 2012 in Delhi, India. The international ATW2012 meeting reported the latest advances in ATM research as well as potential therapeutic treatments for A-T. The meeting was attended by a productive mix of scientists, ranging from those prominent in the initial characterization of the underlying genetic defect to young scientists just entering the field. In broad terms, three main themes were discussed at the meeting: first, a wealth of new details emerged on DNA damage signaling/repair mechanisms for which ATM is a critical element; secondly, important functions for ATM in previously unrelated cellular pathways were identified; and thirdly, new physiological effects and potential therapeutic treatments related to A-T were presented. This report summarizes below a sampling of the many interesting results from the meeting.