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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are associated with loss of nuclear transactive response DNA-binding protein 43 (TDP-43). Here we identify that TDP-43 regulates expression of the neuronal growth-associated factor stathmin-2. Lowered TDP-43 levels, which reduce its binding to sites within the first intron of stathmin-2 pre-messenger RNA, uncover a cryptic polyadenylation site whose utilization produces a truncated, non-functional mRNA. Reduced stathmin-2 expression is found in neurons trans-differentiated from patient fibroblasts expressing an ALS-causing TDP-43 mutation, in motor cortex and spinal motor neurons from patients with sporadic ALS and familial ALS with GGGGCC repeat expansion in the C9orf72 gene, and in induced pluripotent stem cell (iPSC)-derived motor neurons depleted of TDP-43. Remarkably, while reduction in TDP-43 is shown to inhibit axonal regeneration of iPSC-derived motor neurons, rescue of stathmin-2 expression restores axonal regenerative capacity. Thus, premature polyadenylation-mediated reduction in stathmin-2 is a hallmark of ALS-FTD that functionally links reduced nuclear TDP-43 function to enhanced neuronal vulnerability.

Total DNAs were extracted from different sections of deep sea sediment core sample collected from the Western Pacific “Warm Pool”. The bacterial 16S ribosomal DNA (rDNA) clone libraries were constructed and analyzed by PCR-restriction fragment length polymorphism (RFLP) and DNA sequencing. The bacterial communities in these samples and their relationship to environment were analyzed consequently. The results indicated that among eight main bacterial groups found in these sediments, members of the γ-Proteobacteria were most abundant in each section of sediment core sample and the genus Colwellia belonging to γ-Proteobacteria was dominant in this area. Members of the α-Proteobacteria were found commonly existing in these samples, while members belonging to β-Proteobacteria were seldom detected. The diversity of bacterial communities from different sections of sediment core sample was δ- and e-Proteobacteria and the bacterial group including generaCytopahga, Flexibacteria andBacteroides (CFB group). These bacteria all were inversely proportional to the depth of sediment. Phylogenetic analysis showed that there were 18%–30% and 15%–25% of total bacterial communities related to methane and sulfur metabolism respectively in each section of core sample, implicating that the metabolism of sulfur and methane played an important role in the substance and energy cycles of the Western Pacific “Warm Pool”.

An extracellular protease was purified from a deep-sea psychrophilic bacterium strain DY-A which was identified as a Pseudomonas species. The optimal growth and protease-producing temperatures of the strain were all 10 degrees C, and the protease was secreted only at temperatures under 20 degrees C. The enzyme was most active at 40 degrees C and at pH 10.0. It was inhibited by phenylmethyl sulfonylfluoride and diisopropyl fluorophosphate, indicating that it is a serine protease. Chelators such as EDTA, EGTA, 1,10-phenanthroline and 2,2'-bipyridyl produced a decrease of activity. The enzyme was sensitive to denaturing agents such as SDS, urea, and guanidine HCl and resistant to thiol-containing reducing agents such as dithiotreitol. The enzyme was active towards N-succinyl-Ala-Ala-Pro-Phe- p-nitroanilide and N-succinyl-Ala-Ala-Pro-Leu- p-nitroanilide. The native molecular mass of the enzyme determined by native PAGE and SDS-PAGE was 25 kDa.