Driver Preference for Automatic or Manual Transmission Systems for Vehicles: A Case Study in Ghana

Systems in vehicles are being modified due to current technological trends. One of the commonest modified systems in vehicles was the transmission system. This study presented    views of drivers on preference for automatic or manual transmission vehicles in Ghana.   In all, data was collected from 1260 drivers selected randomly through survey, in-depth interviews and six focus group discussions. The study indicated that manual transmission vehicles were more in Ghana with the automatic now gaining relative patronage. However, automatic transmission vehicles were preferred by females than males. The first three factors that determined preference for automatic transmission were shifting quality, easy to use and power (engine) performance. However, for manual transmission vehicles repairability (easily reparable), reliability and better fuel economy were the first three factors that determined driver’s choice for such vehicles. The results further showed that most respondents believed that manual transmission vehicles had strong advantages over the automatic ones. The study concludes that more people prefer manual transmission vehicles than the automatic ones although the automatic ones are now gaining popularity. Key words:Automatic transmission, Manual Transmission, Vehicles, Preference, Ghan

LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Persistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation. Originally published in British Journal of Cancer 2009 Vol. 110, No.

Antimicrobial peptide gramicidin S is accumulated in granules of producer cells for storage of bacterial phosphagens

Many antimicrobial peptides are synthesized non-ribosomally in bacteria, but little is known about their subcellular route of biosynthesis, their mode of intracellular accumulation, or their role in the physiology of the producer cells. Here, we present a comprehensive view on the biosynthesis of gramicidin S (GS) in Aneurinibacillus migulanus, having observed a peripheral membrane localization of its synthetases. The peptide gets accumulated in nano-globules, which mature by fusion into larger granules and end up within vacuolar structures. These granules serve as energy storage devices, as they contain GS molecules that are non-covalently attached to alkyl phosphates and protect them from dephosphorylation and premature release of energy. This finding of a fundamentally new type of high-energy phosphate storage mechanism can explain the curious role of GS biosynthesis in the physiology of the bacterial producer cells. The unknown role of the GrsT protein, which is part of the non-ribosomal GS synthetase operon, can thus be assumed to be responsible for the biosynthesis of alkyl phosphates. GS binding to alkyl phosphates may suggest its general affinity to phosphagens such as ATP and GTP, which can represent the important intracellular targets in pathogenic bacteria

S-Glutathionylation at Cys328 and Cys542 Impairs STAT3 Phosphorylation.

STAT3 is a latent transcription factor that promotes cell survival and proliferation and is often constitutively active in cancers. Although many reports provide evidence that STAT3 is a direct target of oxidative stress, its redox regulation is poorly understood. Under oxidative conditions STAT3 activity can be modulated by S-glutathionylation, a reversible redox modification of cysteine residues. This suggests the possible cross-talk between phosphorylation and glutathionylation and points out that STAT3 is susceptible to redox regulation. Recently, we reported that decreasing the GSH content in different cell lines induces inhibition of STAT3 activity through the reversible oxidation of thiol groups. In the present work, we demonstrate that GSH/diamide treatment induces S-glutathionylation of STAT3 in the recombinant purified form. This effect was completely reversed by treatment with the reducing agent dithiothreitol, indicating that S-glutathionylation of STAT3 was related to formation of protein-mixed disulfides. Moreover, addition of the bulky negatively charged GSH moiety impairs JAK2-mediated STAT3 phosphorylation, very likely interfering with tyrosine accessibility and thus affecting protein structure and function. Mass mapping analysis identifies two glutathionylated cysteine residues, Cys328 and Cys542, within the DNA-binding domain and the linker domain, respectively. Site direct mutagenesis and in vitro kinase assay confirm the importance of both cysteine residues in the complex redox regulatory mechanism of STAT3. Cells expressing mutant were resistant in this regard. The data presented herein confirmed the occurrence of a redox-dependent regulation of STAT3, identified the more redox-sensitive cysteines within STAT3 structure, and may have important implications for development of new drugs

Salmonella in commercial swine from weaning through slaughter

Sixty swine on each of four farms in Iowa and on four farms in North Carolina were monitored for Salmonella, from weaning through kill. 1\vo farms in each state used ali-in-allout (AIAO) management, while two were continuous flow. All pigs were individually identified, in North Carolina with ear tags and in Iowa with implanted microchips. Feces for culture and serum for Danish mixELISA were collected at weaning and approximately every eight weeks, with the fourth collection coming within 48 hours of slaughter. At slaughter, carcasses were swabbed using the FSIS method. Ileocecal lymph nodes, cecum, and/or colon were collected

Necdin, a Negative Growth Regulator, Is a Novel STAT3 Target Gene Down-Regulated in Human Cancer

Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized. We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. Among these genes we identified Necdin, a negative growth regulator, as a novel STAT3 target gene, whose expression is down-regulated at the mRNA and protein levels when STAT3 is constitutively active. This repression is STAT3 dependent, since inhibition of STAT3 using siRNA restores Necdin expression. A STAT3 DNA-binding site was identified in the Necdin promoter and both EMSA and chromatin immunoprecipitation confirm binding of STAT3 to this region. Necdin expression has previously been shown to be down-regulated in a melanoma and a drug-resistant ovarian cancer cell line. Further analysis of Necdin expression demonstrated repression in a STAT3-dependent manner in human melanoma, prostate and breast cancer cell lines. These results suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis. STAT3 may exert its oncogenic effect by up-regulating transcription of genes involved in promoting growth and proliferation, but also by down-regulating expression of negative regulators of the same cellular processes, such as Necdin

Effects of some methodologic factors on detection of Salmonella in swine feces

Bacteriologic culture of feces for Salmonella continues to be a central component of epidemiologic studies. We conducted a series of experiments on fecal samples collected from commercial swine farms to evaluate the effects of several methodologic factors on detection of Salmonella. Factors examined included fecal sample storage (no storage, 4C, -15C) and fecal sample weight. In addition we compared the standard method (Method I) used in our laboratory [JOg feces/buffered peptone water pre-enrichment/selective enrichment in Rappaport Vassiliadis (RV) broth] with another method (Method 2) used by ourselves and others in the USA (=I g sample/primary enrichments in tetrathionate and Hajna GN broths/secondary enrichment in RV broth). Inunediate processing of samples yielded the best recovery of Salmonella, although storage at 4C for 6 days did not significantly reduce detection. Freezing of fecal samples resulted in significant reduction of detection. The weight of feces sampled had a marked linear effect on the detection of Salmonella using method I. Direct comparison of Method I and Method 2 indicated comparable results, with Method I tending to yield higher detection of Salmonella. However, when conducted on samples of equal weight, Method 2 had significantly better detection than Method I. The choice of methods can markedly affect the results of fecal sample culture. The preferred methodology for epidemiologic studies will be determined by many factors including logistics and cost. Our data highlight the imperfect sensitivity of culture methods, and the need for researchers to consider the sensitivity of their bacteriologic methods in the design and interpretation of field studies based on fecal culture