Demographic history of India and mtDNA-sequence diversity.

The demographic history of India was examined by comparing mtDNA sequences obtained from members of three culturally divergent Indian subpopulations (endogamous caste groups). While an inferred tree revealed some clustering according to caste affiliation, there was no clear separation into three genetically distinct groups along caste lines. Comparison of pairwise nucleotide difference distributions, however, did indicate a difference in growth patterns between two of the castes. The Brahmin population appears to have undergone either a rapid expansion or steady growth. The low-ranking Mukri caste, however, may have either maintained a roughly constant population size or undergone multiple bottlenecks during that period. Comparison of the Indian sequences to those obtained from other populations, using a tree, revealed that the Indian sequences, along with all other non-African samples, form a starlike cluster. This cluster may represent a major expansion, possibly originating in southern Asia, taking place at some point after modern humans initially left Africa.     

FUBP3 regulates chronic myeloid leukaemia progression through PRC2 complex regulated PAK1‐ERK signalling

The development of resistance and heterogeneity in differential response towards tyrosine kinase inhibitors (TKI) in chronic myeloid leukaemia (CML) treatment has led to the exploration of factors independent of the Philadelphia chromosome. Among these are the association of deletions of genes on derivative (der) 9 chromosome with adverse outcomes in CML patients. However, the functional role of genes near the breakpoint on der (9) in CML prognosis and progression remains largely unexplored. Copy number variation and mRNA expression were evaluated for five genes located near the breakpoint on der (9). Our data showed a significant association between microdeletions of the FUBP3 gene and its reduced expression with poor prognostic markers and adverse response outcomes in CML patients. Further investigation using K562 cells showed that the decrease in FUBP3 protein was associated with an increase in proliferation and survival due to activation of the MAPK–ERK pathway. We have established a novel direct interaction of FUBP3 protein and PRC2 complex in the regulation of ERK signalling via PAK1. Our findings demonstrate the role of the FUBP3 gene located on der (9) in poor response and progression in CML with the identification of additional druggable targets such as PAK1 in improving response outcomes in CML patients.     

Variation in bark thickness in a tropical forest community of Western Ghats in India

1. We examined the relation between bark thickness and girth in a large sample of trees from evergreen and semi-evergreen rain forest.
2. There is a significant tendency for bark thickness to increase with tree girth. Removing this tendency, we find a significant trend for species from more disturbed habitats to possess thicker bark.
3. Species from more disturbed habitats also have a greater propensity for secreting gums and resins.
4. Nine of the 29 species occurring in more than one habitat type and with a sample size of at least 11 individuals show a tendency for possession of a thicker bark by individuals in the more disturbed habitats.
5. We conclude that bark thickness and occurrence of gums and resins are physiognomic–structural attributes of value in characterizing tree communities created by different levels of disturbance.     

Lentiviral mediated transgenesis by in vivo manipulation of spermatogonial stem cells

This report describes a technique for the generation of transgenic mice by in vivo manipulation of spermatogonial stem cells with a high rate of success. Spermatogonial stem cells (SSCs) in pre-pubescent animals were infected in vivo with recombinant lentiviruses expressing EGFP-f and mated with normal females. All male pre-founder mice produced transgenic pups with an overall success rate of over 60%. The transgene was heritable and the pre-founder mice could be used in multiple mating experiments. This technology could be used to perform overexpression/knockdown screens in vivo using bar-coded lentiviruses, thus permitting the design of genetic screens in the mouse. Further, this technology could be adapted to other laboratory animals resulting in the generation of model systems that closely approximate human development and disease.     

Links between Schwann cells and melanocytes in development and disease

Melanocytes are pigment‐producing cells that reside in the skin, eyes, ears, heart, and central nervous system meninges of mammals. Schwann cells are glial cells, which closely associate with peripheral nerves, myelinating, and sheathing them. Melanocytes and Schwann cells both arise from the neural crest during development, and some melanocytes arise directly from Schwann cell precursors lining developing spinal nerves. In this review, we explore the connections between melanocytes and Schwann cells in development and transformation.     

Manganese increases high mannose glycoform on monoclonal antibody expressed in CHO when glucose is absent or limiting: Implications for use of alternate sugars

Alternate sugars such as galactose and fructose are metabolized at a slower rate than glucose and result in lower accumulation of lactate. While low lactate accumulation is desirable, we report that complete substitution of glucose with these sugars results in an increase in M5 high mannose glycans. Surprisingly, this increase is much higher when the culture is supplemented with manganese: for example, when cells are cultured with galactose, M5 high mannose glycan content increased from 5% at 1 nM Mn²⁺ in the basal medium to 32% with 16 µM Mn²⁺ supplementation. When galactose is supplemented with glucose maintained at low concentrations, a small reduction in high mannose glycans is seen. In control cultures with glucose, the high mannose content was however <2% in this range of Mn²⁺ concentration. By varying Mn²⁺ and glucose supplementation levels, with or without galactose, we systematically demonstrate that Mn²⁺ concentration and glucose availability, together, significantly affect the high mannose glycan content. To our knowledge, this is the first report that shows that the effect of Mn²⁺ on high mannose glycan content depends on glucose availability. At each Mn²⁺ supplementation level evaluated, galactosylation percentages were highest for cultures where galactose was supplemented with glucose at non‐limiting concentration. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:460–467, 2015