The Path from Skin to Brain: Generation of Functional Neurons from Fibroblasts

Cell fate reprogramming makes possible the generation of new cell types from healthy adult cells to replace those lost or damaged in disease. Additionally, reprogramming patient cells into specific cell types allows for drug screening and the development of new therapeutic tools. Generation of new neurons is of particular interest because of the potential to treat diseases of the nervous system, such as neurodegenerative disorders and spinal cord injuries, with cell replacement therapy. Recent advances in cell fate reprogramming have led to the development of novel methods for the direct conversion of fibroblasts into neurons and neural stem cells. This review will highlight the advantages of these new methods over neuronal induction from embryonic stem cells and induced pluripotent stem cells, as well as outline the limitations and the potential for future applications.     

Morphological indicators of salinity stress and their relation with osmolyte associated redox regulation in mango cultivars

Soil salinization is a global issue impeding horticulture production and is approaching an alarming status due to climate change and urbanization. Breeding salt-tolerant rootstock varieties is an ideal strategy to mitigate stress due to salinity in mango and other perennial fruit species. Stress combating strategies employed by seedlings of 7 mango were studied under saline conditions (200 mM NaCl, EC: > 4.0 dSm⁻¹, pH 8.5) in pot experiments. Significantly high accumulation of proline (19.07 µg g⁻¹ FW in Bappakai), glycine betaine (55.11 µg g⁻¹ FW in 13–1), and total sugars (17.33 mg g⁻¹ FW in Kurukkan) were found to be the common mechanism employed by the tolerant cultivars to counter the osmotic stress, under suboptimal conditions. Non-enzymatic antioxidants viz., tannins (17.18 mg g⁻¹), phenols (18.68 mg g⁻¹), and anthocyanins (1.59 mg g⁻¹) were increased in seedling of "13–1", the salt-resistant cultivar from Israel. Reactive oxygen species (ROS) regulation by increased activity of superoxide dismutase and catalase in the two polyembryonic cultivars of Indian origin (Kurukkan and Nekkare) suggests their potential use as rootstocks to combat oxidative stress. The tolerance index of various cultivars was calculated by averaging the scores of morphological stress indicators, and its correlation with studied parameters suggests that salinity resilience is more tightly linked to enhanced catalase accumulation (r² = 0.8361) that is reduced ionic stress. This evidence assign the role of osmotic stress alleviation and redox regulation in salt tolerance mechanism operational in native Indian cultivars, Nekkare and Kurukkan at par with known salt tolerant rootstocks.

     

Air-borne fungi at Doha, Qatar

Thirty-five genera and 73 species, were identifiedfrom 312 daily exposures set up during theperiod March 1997–March 1998. The total fungalcatch exhibited two peaks in July and December1997 and a trough in February 1998. Cladosporium (6 spp. 40.1% of total fungi),Alternaria (4 spp., 21%) andUlocladium (4 spp., 9.2%) were the maincomponents of air-borne fungi, and thecommonest species were Cladosporium.sphaerospermum (29.7%), C.cladosporioides (6.9%), Alternaria.alternata (13.9%) and U. atrum (5%).The predominance of these dark-coloured fungiin air is discussed and is attributed to one orboth of two hypotheses. Aspergillus (9spp., 4.3%) and Penicillium (8 spp.,3.95%) came next and were represented mainlyby A.niger (1.3%) andP. chrysogenum (2.4%).Spore showers of C.cladosporioides, C. sphaerospermum, Penicillium chrysogenum and Myrotheciumverrucaria were noticed with no regularseasonal pattern.The monthly number of species ranalmost parallel to the total count of fungi.The broadest species spectrum (25–29 spp.) wasrecorded in the summer months May–August 1997and the narrowest (11–12 spp.) in February andMarch 1998.The highest monthly wind velocity wasregularly associated with higher fungal colonycounts than in case of the lowest velocity. Onthe other hand, wind direction did not exhibitany regular correlation either with the colonycounts of fungi or with the wind velocity. Highwind velocity could bring more fungal spores tobe sedimented on the surface of exposed agar.Diurnal fluctuations of fungal spores offungi displayed one peak at 12 noon when thehighest temperature and wind velocity, and theleast relative humidity were recorded and onetrough at midnight.     

Coordinate activation of human platelet protease-activated receptor-1 and -4 in response to subnanomolar alpha-thrombin

We previously demonstrated that human platelets activated with SFLLRN release PAR-1 activation peptide, PAR-1-(1-41), even in the presence of hirudin. This observation suggests that during their activation, platelets generate a protease that activates PAR-1. In this study, PAR-1 and -4 activation peptides were detected 10 s after 相似文献   

Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study

Objective To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures.Design Cross sectional survey of people randomly selected from general practice registers. Invitation to provide a specimen collected at home.Setting England.Participants 19 773 men and women aged 16-39 years invited to participate in screening.Main outcome measures Coverage and uptake of screening; prevalence of chlamydia.Results Coverage of chlamydia screening was 73% and was lower in areas with a higher proportion of non-white residents. Uptake in 16-24 year olds was 31.5% and was lower in men, younger adults, and practices in disadvantaged areas. Overall prevalence of chlamydia was 2.8% (95%confidence interval 2.2% to 3.4%) in men and 3.6% (3.1% to 4.9%) in women, but it was higher in people younger than 25 years (men 5.1%; 4.0% to 6.3%; women 6.2%; 5.2% to 7.8%). Prevalence was higher in the subgroup of younger women who were harder to engage in screening. The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year.Conclusions Postal chlamydia screening was feasible, but coverage was incomplete and uptake was modest. Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health.     

Functional Overexpression and Purification of a Codon Optimized Synthetic Glucarpidase (Carboxypeptidase G2) in Escherichia coli

Glucarpidase (former name: carboxypeptidase G2, or CPG2) is a bacterial enzyme that is widely used in detoxification of the cytotoxic drug, methotrexate, and in Antibody Directed Enzyme Prodrug Therapy for cancer treatment. The glucarpidase gene of Pseudomonas sp. strain RS-16 was previously cloned in E coli, but expresses at a level that is approximately 100-fold lower than in the native strain. In this study, a synthetic gene coding for glucarpidase was codon-optimised and synthesized for maximum expression in E. coli using the vector pET28a. Our work indicated that the enzyme was expressed to ~60% of the total host protein and that purification of the recombinant His-tagged protein could be achieved in a single step by Ni²⁺ charged column chromatography. The synthetic recombinant glucarpidase expressed within this system was biologically active and zinc dependant. Our study showed that Mg²⁺ as well as Mn²⁺ ions inhibit the activity of the recombinant enzyme.     

Genome scale portrait of cAMP-receptor protein (CRP) regulons in mycobacteria points to their role in pathogenesis

cAMP Receptor Protein (CRP)/Fumarate Nitrate Reductase Regulator (FNR) family proteins are ubiquitous regulators of cell stress in eubacteria. These proteins are commonly associated with maintenance of intracellular oxygen levels, redox-state, oxidative and nitrosative stresses, and extreme temperature conditions by regulating expression of target genes that contain regulatory cognate DNA elements. We describe the use of informatics enabled comparative genomics to identify novel genes under the control of CRP regulator in Mycobacterium tuberculosis (M.tb). An inventory of CRP regulated genes and their operon context in important mycobacterial species such as M. leprae, M. avium subsp. paratuberculosis and M. smegmatis and several common genes within this genus including the important cellular functions, mainly, cell-wall biogenesis, cAMP signaling and metabolism associated with such regulons were identified. Our results provide a possible theoretical framework for better understanding of the stress response in mycobacteria. The conservation of the CRP regulated genes in pathogenic mycobacteria, as opposed to non-pathogenic ones, highlights the importance of CRP-regulated genes in pathogenesis.     

The environmental and genetic regulation of obake expressivity: morphogenetic fields as evolvable systems

The morphogenetic field, a fundamental concept of classical embryology, is once again being invoked to describe developmental processes. Because the evolution of adult structures requires the modification of development, the ways in which morphogenetic fields can change over time may yield insights into evolutionary possibilities. We considered how the duplication/multiplication of a morphogenetic field in fruit flies, caused by the previously described obake (obk) mutation, is regulated by genetic and environmental factors. Mutations of genes in the canonical antenna-producing imaginal disc pathway suppressed duplication as expected, although the results suggested that other pathways might also be involved. Overgrowth mutations, expected to increase duplication, actually suppressed it. Mutations in the heat-shock protein gene Hsp83 did not uniformly enhance obk expressivity as hypothesized. Using third chromosomes extracted from wild-derived lines, natural genetic variation for modifiers of obk function was found to be extensive. Larval crowding suppressed the obk phenotype, but there was no evidence of trade-offs between body or head size and arista number. Our results suggest that a complex interplay of genetic and environmental factors in the regulation of fields may be responsible for ample natural variation in the expressivity of adult phenotypes, affording multiple opportunities for selection and evolutionary modification.