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71.
Transforming growth factor-β (TGF-β) has diverse and multiple roles throughout the body. This review focuses on the evidence
supporting its functions in the central nervous system, with a particular emphasis on its purported role in cerebral ischemia.
Numerous studies have documented that TGF-β1 levels are enhanced in the brain following cerebral ischemia. As evidence that
such an upregulation is beneficial, agonist studies have demonstrated that TGF-β1 reduces neuronal cell death and infarct
size following middle cerebral artery occlusion (MCAO), while conversely, antagonist studies have shown increased neuronal
cell death and infarct size after MCAO. These studies suggest that TGF-β1 has a neuroprotective role in cerebral ischemia.
Recent work with adenoviral-mediated overexpression of TGF-β1 in vivo in mice has further implicated a neuroprotective role
for TGF-β1 in cerebral ischemia, as evidenced by a reduction in neuronal cell death, infarct size, and neurological outcome.
Additionally, numerous in vitro studies have documented the neuroprotective ability of TGF-β1 in neurons from a variety of
species, including rats, mice, chicks, and humans. Of significant interest, TGF-β1 was shown to be protective against a wide
variety of death-inducing agents/insults, including hypoxia/ischemia, glutamate excitotoxicity, β-amyloid, oxidative damage,
and human immunodeficiency virus. The mechanism of TGF-β1-mediated neuroprotection remains to be resolved, but early evidence
suggests that TGF-β1 regulates the expression and ratio of apoptotic (Bad) and antiapoptotic proteins (Bcl-2, Bcl-x1), creating an environment favorable for cell survival of death-inducing insults. Taken as a whole, these results suggest
that TGF-β1 is an important neuroprotective factor that can reduce damage from a wide-array of death-inducing agents/insults
in vitro, as well as exert protection of the brain during cerebral ischemia.
The authors’ research is supported by research grants (HD-28964 and AG-17186 to DWB) from the National Institutes of Health,
NICHD, and NIA. 相似文献
72.
Duda Teresa Venkataraman Venkateswar Krishnan Anuradha Sharma Rameshwar K. 《Molecular and cellular biochemistry》1998,189(1-2):63-70
At present there are two recognized members of the ROS-GC subfamily of membrane guanylate cyclases. They are ROS-GC1 and ROS-GC2. A distinctive feature of this family is that its members are not switched on by the extracellular peptide hormones; instead, they are modulated by intracellular Ca2+ signals, consistent to their linkage with phototransduction. An intriguing feature of ROS-GC1, which distinguishes it from ROS-GC2, is that it has two Ca2+ switches. One switch inhibits the enzyme at micromolar concentrations of Ca2+, as in phototransduction; the other, stimulates. The stimulatory switch, most likely, is linked to retinal synaptic activity. Thus, ROS-GC1 is linked to both phototransduction and the synaptic activity. The present study describes (1) the almost complete structural identity of 18.5 kb ROS-GC1 gene; (2) its structural organization: the gene is composed of 20 exons and 19 introns with classical GT/AG boundaries; (3) the activity of the ROS-GC1 promoter assayed through luciferase reporter in COS cells; and (4) induction of the gene by phorbol ester, a protein kinase C (PKC) activator. The co-presence of PKC and ROS-GC1 in photoreceptors suggests that regulation of the ROS-GC1 gene by PKC might be a physiologically relevant phenomenon. 相似文献
73.
Screening and selection of media components for lactic acid production using Plackett–Burman design 总被引:2,自引:0,他引:2
S. Krishnan S. G. Prapulla D. Rajalakshmi M. C. Misra N. G. Karanth 《Bioprocess and biosystems engineering》1998,19(1):61-65
Plackett–Burman design was used to efficiently select important media components influencing lactic acid production in a two step screening procedure. A total of 36 screening experiments were conducted for studying the effect of various media components such as carbon and nitrogen (simple and complex) sources, minerals/buffering agents and a specific inducer for the production of lactic acid by Lactobacillus plantarum NCIM 2084. The eleven ingredients chosen after the first screening experiments were further screened by a Plackett-Burman design consisting of 12 experiments. Liquefied starch, wheat bran extract, ammonium nitrate, manganese sulphate and sodium acetate were chosen as promising ingredients for further optimisation studies. The highest yield of 41.9?g/l of lactic acid was obtained at the end of 24 hours of fermentation which corresponded to 90% conversion, on the basis of sugar supplied. 相似文献
74.
Gururaja P. Pazhani Sushanta K. Bhowmik Santanu Ghosh Sucharita Guin Sanjucta Dutta Krishnan Rajendran Dhira Rani Saha Ranjan K. Nandy Mihir K. Bhattacharya Asish K. Mukhopadhyay Thandavarayan Ramamurthy 《PLoS neglected tropical diseases》2014,8(5)
A total of 178 strains of V. parahaemolyticus isolated from 13,607 acute diarrheal patients admitted in the Infectious Diseases Hospital, Kolkata has been examined for serovar prevalence, antimicrobial susceptibility and genetic traits with reference to virulence, and clonal lineages. Clinical symptoms and stool characteristics of V. parahaemolyticus infected patients were analyzed for their specific traits. The frequency of pandemic strains was 68%, as confirmed by group-specific PCR (GS-PCR). However, the prevalence of non-pandemic strains was comparatively low (32%). Serovars O3:K6 (19.7%), O1:K25 (18.5%), O1:KUT (11.2%) were more commonly found and other serovars such as O3:KUT (6.7%), O4:K8 (6.7%), and O2:K3 (4.5%) were newly detected in this region. The virulence gene tdh was most frequently detected in GS-PCR positive strains. There was no association between strain features and stool characteristics or clinical outcomes with reference to serovar, pandemic/non-pandemic or virulence profiles. Ampicillin and streptomycin resistance was constant throughout the study period and the MIC of ampicillin among selected strains ranged from 24 to >256 µg/ml. Susceptibility of these strains to ampicillin increased several fold in the presence of carbonyl cyanide-m-chlorophenyldrazone. The newly reported ESBL encoding gene from VPA0477 was found in all the strains, including the susceptible ones for ampicillin. However, none of the strains exhibited the β-lactamase as a phenotypic marker. In the analysis of pulsed-field gel electrophoresis (PFGE), the pandemic strains formed two different clades, with one containing the newly emerged pandemic strains in this region. 相似文献
75.
76.
Lujan HL Krishnan S Dicarlo SE 《American journal of physiology. Regulatory, integrative and comparative physiology》2011,301(3):R775-R782
The response to myocardial ischemia is complex and involves the cardio-cardiac sympathetic reflex. Specifically, cardiac spinal (sympathetic) afferents are excited by ischemic metabolites and elicit an excitatory sympathetic reflex, which plays a major role in the genesis of ventricular arrhythmias. For example, brief myocardial ischemia leads to ATP release, which activates cardiac spinal afferents through stimulation of P2 receptors. Clinical work with patients and preclinical work with animals document that disruption of this reflex protects against ischemia-induced ventricular arrhythmias. However, the role of afferent signals in the initiation of sustained ventricular tachycardia has not been investigated. Therefore, we tested the hypothesis that cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in adult (12-15 wk of age), conscious, male Sprague-Dawley rats. To test this hypothesis, the susceptibility to ventricular tachyarrhythmias produced by occlusion of the left main coronary artery was determined in two groups of conscious rats: 1) deafferentation (bilateral excision of the T1-T5 dorsal root ganglia) and 2) control (sham deafferentation). The ventricular arrhythmia threshold (VAT) was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Results document a significantly higher VAT in the deafferentation group (7.0 ± 0.7 min) relative to control (4.3 ± 0.3 min) rats. The decreased susceptibility to tachyarrhythmias with deafferentation was associated with a reduced cardiac metabolic demand (lower rate-pressure product and ST segment elevation) during ischemia. 相似文献
77.
Agency,intimacy, and rape jokes: an ethnographic study of young women and sexual risk in Chennai 下载免费PDF全文
Sneha Krishnan 《The journal of the Royal Anthropological Institute》2016,22(1):67-83
In this article, I examine the circulation of jokes about sexual violence among young middle‐class women in the South Indian city of Chennai. Drawing on ethnographic research with undergraduate students in this city, I locate the rape joke in an ambivalent discourse of risk that conflates the possibility of sexual assault with the perceived ‘risks’ of women's sexual autonomy. In this context, I argue that humour about sexual violence functions as a form of lateral agency, facilitating a break from the task of reproducing middle‐class respectability. 相似文献
78.
Nazia Khatoon Rajan Kumar Pandey Rupal Ojha Veeranarayanan Surya Aathmanathan Muthukalingan Krishnan 《Journal of biomolecular structure & dynamics》2019,37(9):2381-2393
Visceral leishmaniasis (VL) is a deadly parasitic infection which affects poorest to poor population living in the endemic countries. Increasing resistant to existing drugs, disease burden and a significant number of deaths, necessitates the need for an effective vaccine to prevent the VL infection. This study employed a combinatorial approach to develop a multi-epitope subunit vaccine by exploiting Leishmania donovani membrane proteins. Cytotoxic T- and helper T-lymphocyte binding epitopes along with suitable adjuvant and linkers were joined together in a sequential manner to design the subunit vaccine. The occurrence of B-cell and IFN-γ inducing epitopes approves the ability of subunit vaccine to develop humoral and cell-mediated immune response. Physiochemical parameters of vaccine protein were also assessed followed by homology modeling, model refinement and validation. Moreover, disulfide engineering was performed for the increasing stability of the designed vaccine and molecular dynamics simulation was performed for the comparative stability purposes and to conform the geometric conformations. Further, molecular docking and molecular dynamics simulation study of a mutated and non-mutated subunit vaccine against TLR-4 immune receptor were performed and respective complex stability was determined. In silico cloning ensures the expression of designed vaccine in pET28a(+) expression vector. This study offers a cost-effective and time-saving way to design a novel immunogenic vaccine that could be used to prevent VL infection.
Communicated by Ramaswamy H. Sarma 相似文献
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