The molecular basis of cytochrome oxidase deficiency in childhood

The mitochondrial respiratory chain and oxidative phosphorylation system (complexes I-V) produce ATP by aerobic metabolism. Complex IV or cytochrome c oxidase (COX) catalyses transfer of electrons from reduced cytochrome c to molecular oxygen, coupled with proton pumping across the inner mitochondrial membrane. Human COX has 13 polypeptide subunits. Three subunits (I, II and III) constitute the enzyme's catalytic core and are encoded on the mitochondrial genome. The remaining subunits are nuclear-encoded. COX deficiency, either total or partial, is the most commonly recognised respiratory chain defect in childhood. This may be an isolated defect, or combined with deficiencies of other respiratory chain components. Clinical presentations are heterogeneous but most patients with COX deficiency remain uncharacterised at the molecular level. COX subunit expression patterns were analysed in 5 patients with known mitochondrial DNA (mtDNA) mutations and 36 uncharacterised patients. A specific pattern of COX subunit loss was identified in COX deficiency secondary to mtDNA mutations. This suggested that immunohistochemistry using monoclonal antibodies may distinguish between mtDNA defects and nuclear defects in COX deficiency. Subsequent sequence analysis, targeted by immunohistochemistry findings, led to identification of a missense mutation of COX subunit II that causes defective assembly and myopathy. Characterisation of this mutation provided information about assembly of the metal centres of COX. Thus identification of naturally occurring COX mutations allows insight into structure-function relationships within the enzyme. The majority of children with COX deficiency did not have selective loss of mtDNA- encoded subunits, suggesting that nuclear gene defects account for many cases of childhood-onset COX deficiency. One nuclear gene SURF1 is responsible for COX assembly or maintenance. Four patients had homozygous SURF1 mutations, associated with reduced expression of both mtDNA- and nuclear-encoded COX subunits. Studying patterns of subunit expression in COX-deficient patients is fundamental to understanding the pathogenesis of respiratory chain enzyme deficiencies

Anti-Ulcer Effects of Piper Betel, Solanum Nigrum and Zingibercassumunar on Ulceration Induced by Selected Ulcerogens Inrats

Piper betel, Solanum nigrum and Zingiber cassumunar have been used among Malay community in traditional medicine for curing many diseases. These plants are believed to protect the mucosal lining of the stomach from ulcerogens. This study was conducted to investigate the antiulcerogenic properties of ethanol extracts of these plants. One hundred and forty four Sprague Dawley rats were used in this study. The rats were divided into two major groups, the control and treatment group. There were 6 groups of control rats (normal saline (Al); ethanol (Bl); aspirin (Cl); acetic acid (Dl); indomethacin (El); and cimetidine (Fl)). All control groups received distilled water ad libitum 7 days and fasted 24 hours prior forced fed either with normal saline, ethanol, aspirin, acetic acid, indomethacin and cimetidine accordingly. Treated groups were given 2mg / lOOg body weight per day of Piper betel, Solanum nigrum and Zingiber cassumunar extract for 7 days, fasted 24 hours prior force fed with either normal saline (Group A2, A3, A4); ethanol (Group B2, B3, B4); aspirin (Group C2, C3, C4); acetic acid (Group D2, D3, D4); indomethacin (Group E2, E3, E4) or cimetidine (Group F2, F3, F4) accordingly. They were 18 groups all together. They were then fasted again for 24 hours before sacrificed. Macroscopically, the stomachs of rats treated with all plant extracts of all ulcerogen groups (B2, B3, B4; C2, C3, C4; D2, D3, D4; E2, E3, E4; F2, F3, F4) showed a reduced ulcers with significant different (p < 0.05) when compared to B1, C1, Dl and El control groups. Even though treated groups showed some edema and small ulcers, they gave less lesion score when compared to B1, Cl, Dl and El control group. Histological findings showed reduced damage and inflammation score without erosion of mucosal layer in groups treated with Piper betel, Solanum nigrum and Zingiber cassumunar when compared to B1, C1, Dl and El groups. Even though there was slight epithelial disruptions, minimal inflammatory reactions and presence of red blood cells, the damage and inflammation score were less and significantly reduced (p < 0.05) when compared to control groups. This present study suggests that Piper betel, Solanum nigrum and Zingiber cassumunar have some beneficial properties implying that they may have some protective mechanisms to protect stomach from ulcerogens

The Shahbagh Movement of 2013 and its Impacts on the Politics of Bangladesh: A Modest Review

A hotchpotch political system exists in Bangladesh. Ruling party in the name of strengthening democratic system corners the opposition and politicizes all machineries of the government including the judiciary. Awami League led 14-party alliance due to her failure found her self alienated from the people in the second half of 4th year in office. In order to restore government’s declining support government played a drama with regard to the verdict of alleged war criminal Abdul Kader Mollah and gave birth to the so called Shahbagh movement. The first couples of weak Shahbagh gathering died down the failure of government, and ongoing opposition movement faced huge set back. But anti-Islamic blog writings by the organizers of Shabagh created another movement of religious masses. Uncensored support for and protection of these bloggers, and brutal massacre against the religious people washed away AL led government’s deeming chance of gaining power back. In this article the researcher analyses the genesis, working, success and failure of Shahbagh movement with an insight view, and at the end its consequence on AL led 14-party alliance government in electoral politics. Keywords: Shahbagh Gathering, War Crime, Anti-Islamic language, Bloggers and Online Network Activist, Hepajat-e-Isla

Leigh syndrome: One disorder, more than 75 monogenic causes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137543/1/ana24551_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137543/2/ana24551.pd

Transcriptomic analyses reveal neuronal specificity of Leigh syndrome associated genes

Leigh syndrome is a rare inherited, complex, neurometabolic disorder with genetic and clinical heterogeneity. Features present in affected patients range from classical stepwise developmental regression to ataxia, seizures, tremor, and occasionally psychiatric manifestations. Currently, more than 100 monogenic causes of Leigh syndrome have been identified, yet, the pathophysiology remains unknown. Here, we sought to determine the cellular specificity within the brain of all genes currently associated with Leigh syndrome. Further, we aimed to investigate potential genetic commonalities between Leigh syndrome and other disorders with overlapping clinical features. Enrichment of our target genes within the brain was evaluated with co-expression (CoExp) network analyses constructed using existing UK Brain Expression Consortium data. To determine the cellular specificity of the Leigh associated genes, we employed expression weighted cell type enrichment (EWCE) analysis of single cell RNA-Seq data. Finally, CoExp network modules demonstrating enrichment of Leigh syndrome associated genes were then utilised for synaptic gene ontology analysis and heritability analysis. CoExp network analyses revealed that Leigh syndrome associated genes exhibit the highest levels of expression in brain regions most affected on MRI in affected patients. EWCE revealed significant enrichment of target genes in hippocampal and somatosensory pyramidal neurons and interneurons of the brain. Analysis of CoExp modules enriched with our target genes revealed preferential association with pre-synaptic structures. Heritability studies suggested some common enrichment between Leigh syndrome and Parkinson disease and epilepsy. Our findings suggest a primary mitochondrial dysfunction as the underlying basis of Leigh syndrome with associated genes primarily expressed in neuronal cells

PHYTOCHEMICAL SCREENING OF INFLORESCENCE OF PIPER BETLE

Objective: The objective of the current study is to determine the phytoconstituents present in the Inflorescence of Piper betle (IPB). Methods: Phytochemical screening was performed to analyse the phytoconstituents present in IPB and the same was identified by TLC. The phytoconstituents were also estimated quantitatively. Results: Phytochemical screening showed the presence of alkaloids, flavonoids, saponins, tannins and polyphenols. TLC results indicated and confirmed the presence of alkaloids, polyphenols, flavonoids and tannins. On quantification IPB was found to contain 4.2±1.661 mg/ml and 1.523±0.156 mg/ml of flavonoids and tannins respectively. Conclusion: The present study suggests that Inflorescence of Piper betle can be a good source of secondary metabolites

Anti-Inflammatory and Antinociceptive Properties of three Local Channa Species Crude Extracts

Water extract and aqueous portion of chloroform:methanol extract of Channu striatus (haruan), Channa micropeltes (toman) and Channa luciw (bujuk) wcre tested for its anti-inflammatory and antinociceptive properties. The anti-inflammatory activity of the extracts was investigated by three chemical mediators induced rat paw edema (acute inflammation) and cotton pellet granuloma in rats (chronic inflammatory modulation testing). The antinociceptive or analgesic properties were investigated by abdominal constriction test and hot plate test. The results showed that the percentage edema inhibition increased with increased in time interval and was found to be maximal at 4 hours after prostaglandin D2 injection. The effects of 60 mgkg body weight aqueous portion of chloroform:methanol extract of Channa lucius and Channa micropeltes, piroxicam (10 mg/kg) and water extract of Channa striatus (60 mg/kg) exhibited 85.4%, 79.8%, 84.3% and 78.7% edema inhibition at 4 hours respectively. However, all three local Channa spp. extracts did not show significant inhibition (p>0.05) on histamine and bradykinin induced paw edema. In the cotton pellet induced granuloma, the percentage inhibition of anti- transudative was significantly different (p<0.05) by the water extract of Channa striatus (38.1%) and Channa micropelfes (30.3%) compared to the water extract of Channa lucius (10.8%) in inhibiting wet weight of the cotton pelletinduced granuloma formation in rats. Piroxicam showed significant inhibition (p<0.05) by 30.92% and mefenamic acid (13.28%) in inhibiting wet weight granuloma. The water extract of Channa striatus and Channa micropelfes exhibited anti-transudative activity but Channa lucius was devoid of this property. Both extracts of three local Channa spp. did not show anti-proliferative activity. The aqueous portion of chloroform:methanol extract of Channa striatus (60 mglkg) and mefenamic acid (10 mg/kg) increased the serum albumin levels at 24.83 * 4.09 g/dL and 24.83 * 4.30 g/dL respectively. The water extract of Channa striatus (30 mglkg) and the aqueous portion of chloroform:methanol extract Channa lucius (1 5 mg/kg) produced antinociceptive effect on acetic acid induced abdominal constriction test. However both extracts of three local Channa spp. failed to exhibit antinociceptive effect on hot plate test. As a reference drug, the administration of morphine (0.6 mg/kg) caused significant inhibition (p<0.05) by 99.3% in acetic acid induced abdominal constriction and 5 mg/kg of morphine produced significant increased the latency time in hot plate test when compared to control and both extracts of three local Channa spp. In conclusion, this study showed that Channa striatus extracts has more potent the anti-inflammatory and antinociceptive activities compared to the other closely related snakehead fish Channa micropelfes and Channa lucius. The extracts from Channa striafus have the potential being the antiinflammatory and antinociceptive agents

Phytochemical screening and antioxidant activities of Erythroxylum cuneatum leaf extracts

Objectives: Erythroxylum cuneatum is a plant that belongs to the family of Erythroxylaceae. It is locally known as “Chinta mula” and found around Southeast Asia. This study identified the active phytochemicals and antioxidant properties in various extracts derived from dried leaves of Erythroxylum cuneatum. Methods: The tests of phytochemical screening included extracts of ethanol, acetone, hexane and aqueous. The antioxidant activity was determined by measuring total phenolic content, 2,2- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and hydrogen peroxide scavenging activity. Results: The phytochemical screening of Erythroxylum cuneatum dried leaves revealed the presence of phenolic compounds namely flavonoids, tannins and total phenols. Alkaloids and saponins were also detected. The antioxidant activity of the examined extracts varies depending on the solvent used. Generally, acetone extract showed highest total phenolic content with a value of 2228 µg GAE/g and highest DPPH radical scavenging activity with IC50 of 1020.00 µg/ml compared to the standard ascorbic acid of 304.44 µg/ml. Ethanol extract exhibited high hydrogen peroxide activity with IC50 of 83.09 µg/ml. Conclusion: This study showed that acetone extract contains highest phenolic compounds and both ethanol and acetone extracts are a potential source of natural antioxidants