BACKGROUND: The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate.

OBJECTIVE: This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone (V-SVZ).

METHODS: A literature search was conducted using Pubmed including the keywords “ventricular-subventricular zone,” “neural stem cell,” “heterogeneity,” “identity” and/or “single cell” to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche(s).

RESULTS: This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including flow cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type.

CONCLUSIONS: Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including how these cells may be redirected after injury or genetic manipulation.

BACKGROUND: Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein–protein interactions in elucidating the mechanisms of leukemia fusion proteins.

OBJECTIVE: In this review, we aim to summarize these new developments while also providing a historic overview of the related early studies.

METHODS: A total of 218 publications were reviewed in this article, a majority of which were published after 2004. We also downloaded 3D structures of AML1-ETO domains from Protein Data Bank and provided a systematic summary of their structures.

RESULTS: By reviewing the literature, we summarized early and recent findings on AML1-ETO, including its protein–protein interactions, transcriptional and leukemogenic mechanisms, as well as the recently reported involvement of ETO family corepressors in regulating the function of E2A-Pbx1.

CONCLUSION: While the recent development in genomic and structural studies has clearly demonstrated that the fusion proteins function by directly regulating transcription, a further understanding of the underlying mechanisms, including crosstalk with other transcription factors and cofactors, and the protein–protein interactions in the context of native proteins, may be necessary for the development of highly targeted drugs for leukemia therapy.

BACKGROUND: Bone marrow mesenchymal stromal cells (BM-MSCs) are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abnormalities is controversial. In this study, we attempted to review the cytogenetic profiles of MSCs in patients with leukemia, and verify whether these profiles were related to different ex vivo culture conditions or to chronic or acute disease states. This information could be useful in clarifying the origin of MSCs and developing clinical applications for this cell type.

METHODS: A systematic literature search was performed using the PubMed search engine. Studies published over the past 15 years, i.e., between 1995 and January 2015, were considered for review. The following keywords were used: “cytogenetic,” “leukemia,” “bone marrow,” and “mesenchymal stromal cells.”

RESULTS: Some studies demonstrated that BM-MSCs are cytogenetically normal, whereas others provided evidence of aberrations in these cells.

CONCLUSIONS: Studying cytogenetic changes of MSCs in a variety of leukemias will help researchers understand the nature of these tumors and ensure the safety of human stem cells in clinical applications.

BACKGROUND: Epigenomic reconfiguration, including changes in DNA methylation and histone modifications, is crucial for the differentiation of embryonic stem cells (ESCs) into somatic cells. However, the extent to which the epigenome is reconfigured and the interplay between components of the epigenome during cellular differentiation remain poorly defined.

METHODS: We systematically analyzed and compared DNA methylation, various histone modification, and transcriptome profiles in ESCs with those of two distinct types of somatic cells from human and mouse.

RESULTS: We found that global DNA methylation levels are lower in somatic cells compared to ESCs in both species. We also found that 80% of regions with histone modification occupancy differ between human ESCs and the two human somatic cell types. Approximately 70% of the reconfigurations in DNA methylation and histone modifications are locus- and cell type-specific. Intriguingly, the loss of DNA methylation is accompanied by the gain of different histone modifications in a locus- and cell type-specific manner. Further examination of transcriptional changes associated with epigenetic reconfiguration at promoter regions revealed an epigenetic switching for gene regulation—a transition from stable gene silencing mediated by DNA methylation in ESCs to flexible gene repression facilitated by repressive histone modifications in somatic cells.

CONCLUSIONS: Our findings demonstrate that the epigenome is reconfigured in a locus- and cell type-specific manner and epigenetic switching is common during cellular differentiation in both human and mouse.

BACKGROUND: Lipases differ from one another with respect to certain properties, and such differences can be very important for various industrial applications. Considering the rapidly developing nature of the relevant industries, there is a need for new lipases with characteristics differing from those of existing enzymes.

METHODS: In this study, a bacterium was isolated from both the surface mucus layer and gills of rainbow trout (Oncorhynchus mykiss) from Giresun, Turkey. The bacterial species was identified based on its morphological and physiochemical properties, and on its 16S rDNA sequence. The qualitative activity of the bacterial lipase was determined on Rhodamine B and Tween-20 agar plates. The lipase was partially purified from the supernatant of bacterial cultures, and then characterized.

RESULTS: The bacterial strain was identified as Acinetobacter sp. strain SU15. The enzyme from Asp-SU15 exhibits maximum activity toward p-nitrophenyl dodecanoate (C₁₂) at 40°C and pH 8.0. The specific activity of the lipase was calculated to be 10.059 U·L^–1. The molecular mass of the enzyme was determined to be ~62 kDa via SDS-PAGE. However, native-PAGE indicated that the enzyme forms very large active aggregates, with molecular masses exceeding 250 kDa. The catalytic activity of the enzyme is enhanced in the presence of Co²⁺, Ca²⁺, and methanol, but is partially inhibited by Ni²⁺, ethyl acetate, and butanol.

CONCLUSIONS: Further research could examine possible industrial applications for the lipase from Asp-SU15.

BACKGROUND: Aquatic invertebrates are playing an important role in assessment of the water contaminants and also serve as a major component of food chain. Freshwater mussels are considered to be the good bioindicator species of aquatic environment and widely used to determine the metals load.

METHODS: Proximate composition and elemental analysis were carried out in edible (foot, mantle) and non-edible portion (gills) of freshwater mussels (Anodonta anatina) harvested from various site of Chashma Lake, River Indus Pakistan.

RESULTS: The nutritional components were varied among the studied portion and muscular foot found to be the best part for consumption. Protein and fat contents were significantly higher in foot (15.90±0.88%, 1.19±0.26%) as compared to mantle (10.78±2.24%, 0.27±0.09%) and gills (6.44±1.22%, 0.53±0.15%) respectively. For the macro minerals mantle had high concentration of Ca (46838±984 mg/kg), Na (2706±343 mg/kg), P (6921±1063 mg/kg) and Mn (7207±1046 mg/kg) as compared to foot.

CONCLUSIONS: Heavy metals (Cd, Cu, Cr) concentration in edible portions were lower than the permissible limit by WHO whereas the concentration of Pb was slightly higher than the recommended value that might be the risk for the consumers. Being filter feeder gills accumulated the high concentration of all the metals and found to be the key portion for biomonitoring studies. Freshwater mussels of Chashma Lake Indus River are the rich source of protein and all the other micro and macro minerals therefore could be used as an excellent source of food.