Effects of flanking sequences and cellular context on subcellular behavior and pathology of mutant HTT

Huntington’s disease (HD) is caused by an expansion of a poly glutamine (polyQ) stretch in the huntingtin protein (HTT) that is necessary to cause pathology and formation of HTT aggregates. Here we ask whether expanded polyQ is sufficient to cause pathology and aggregate formation. By addressing the sufficiency question, one can identify cellular processes and structural parameters that influence HD pathology and HTT subcellular behavior (i.e. aggregation state and subcellular location). Using Drosophila, we compare the effects of expressing mutant full-length human HTT (fl-mHTT) to the effects of mutant human HTTexon1 and to two commonly used synthetic fragments, HTT171 and shortstop (HTT118). Expanded polyQ alone is not sufficient to cause inclusion formation since full-length HTT and HTTex1 with expanded polyQ are both toxic although full-length HTT remains diffuse while HTTex1 forms inclusions. Further, inclusions are not sufficient to cause pathology since HTT171-120Q forms inclusions but is benign and co-expression of HTT171-120Q with non-aggregating pathogenic fl-mHTT recruits fl-mHTT to aggregates and rescues its pathogenicity. Additionally, the influence of sequences outside the expanded polyQ domain is revealed by finding that small modifications to the HTT118 or HTT171 fragments can dramatically alter their subcellular behavior and pathogenicity. Finally, mutant HTT subcellular behavior is strongly modified by different cell and tissue environments (e.g. fl-mHTT appears as diffuse nuclear in one tissue and diffuse cytoplasmic in another but toxic in both). These observations underscore the importance of cellular and structural context for the interpretation and comparison of experiments using different fragments and tissues to report the effects of expanded polyQ

Melanosis and quality attributes of chill stored farm raised whiteleg shrimp (Litopenaeus vannamei)

Loss of market value of shrimp is mainly due to the formation of black spot called melanosis. A study was conducted for 14 days to determine the extent of melanosis and quality changes during that period of freshly har-vested whiteleg shrimp (Litopenaeus vannamei) under chilled storage (2?). Among quality parameters, total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBAR-S), were varied from 13.17 mg % to 44.50 mg % and 0.04to 2.57 mg malondehaldehyde/kg of fat respectively whereas melanosis score and metric chroma (C) exhibited significant increases during chilled storage (P<0.05). There was a slight increase in moisture, crude fat and pH from 73.96 % to 74.57 %, 1.05 % to 1.14 % and 6.52 to 7.60 respectively at 14th day of storage. Loss of protein from 22.51 % to 21.28 % may be due to decrease in available amino acids during chilled storage and total plate count (TPC) showed gradual increase of bacterial load up to 1.73*107 log CFU/g at the end of chilled storage. The sensory analysis by panellists indicated, the acceptability of white leg shrimp was up to 6 days in chilled condition and formation of black spot is one of the major parameter for rejection by the panellists

Transcriptome response and spatial pattern of gene expression in the primate subventricular zone neurogenic niche after cerebral ischemia

The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys. Transcriptomics shows that in ischemic SVZa, 541 genes were upregulated and 488 genes were down-regulated. The transcription data encompassing the upregulated genes revealed a profile typical for quiescent stem cells and astrocytes. In the primate brain the SVZ is morphologically subdivided in distinct and separate ependymal and subependymal regions. The subependymal contains predominantly neural stem cells (NSC) and differentiated progenitors. To determine in which SVZa region ischemia had evoked transcriptional upregulation, sections through control and ischemic SVZa were analyzed by high-throughput in situ hybridization for a total of 150 upregulated genes shown in the www.monkey-niche.org image database. The majority of the differentially expressed genes mapped to the subependymal layers on the striatal or callosal aspect of the SVZa. Moreover, a substantial number of upregulated genes was expressed in the ependymal layer, implicating a contribution of the ependyma to stem cell biology. The transcriptome analysis yielded several novel gene markers for primate SVZa including the apelin receptor that is strongly expressed in the primate SVZa niche upon ischemic insult

Effects of flanking sequences and cellular context on subcellular behavior and pathology of mutant HTT

Huntington’s disease (HD) is caused by an expansion of a poly glutamine (polyQ) stretch in the huntingtin protein (HTT) that is necessary to cause pathology and formation of HTT aggregates. Here we ask whether expanded polyQ is sufficient to cause pathology and aggregate formation. By addressing the sufficiency question, one can identify cellular processes and structural parameters that influence HD pathology and HTT subcellular behavior (i.e. aggregation state and subcellular location). Using Drosophila, we compare the effects of expressing mutant full-length human HTT (fl-mHTT) to the effects of mutant human HTTexon1 and to two commonly used synthetic fragments, HTT171 and shortstop (HTT118). Expanded polyQ alone is not sufficient to cause inclusion formation since full-length HTT and HTTex1 with expanded polyQ are both toxic although full-length HTT remains diffuse while HTTex1 forms inclusions. Further, inclusions are not sufficient to cause pathology since HTT171-120Q forms inclusions but is benign and co-expression of HTT171-120Q with non-aggregating pathogenic fl-mHTT recruits fl-mHTT to aggregates and rescues its pathogenicity. Additionally, the influence of sequences outside the expanded polyQ domain is revealed by finding that small modifications to the HTT118 or HTT171 fragments can dramatically alter their subcellular behavior and pathogenicity. Finally, mutant HTT subcellular behavior is strongly modified by different cell and tissue environments (e.g. fl-mHTT appears as diffuse nuclear in one tissue and diffuse cytoplasmic in another but toxic in both). These observations underscore the importance of cellular and structural context for the interpretation and comparison of experiments using different fragments and tissues to report the effects of expanded polyQ

Haofa dog – An indigenous canine germplasm from Manipur, India

A study on Haofa dog was carried out at its breeding tract in Ukhrul and Kamjong districts of Manipur to find out its origin, distribution and phenotypic characteristics. A total of 100 adult Haofa dogs (50 male and 50 female) were recorded for studying physical characters and body measurement. Further, 69 number of observation were also recorded for studying body weights of adult male and female. In addition, 100 Haofa owners were interviewed to study the reproductive characteristics, management practices followed and their utility, etc. The study revealed that Haofa were of medium size with a compact body, broad chest, straight top line and slightly tucked up abdomen. The coat colour is usually black with grey skin while some dogs have black coat colour with white markings in ventral parts and tips of legs. The head of a Haofa dog is medium in size with a slightly trapezoid shape, while the forehead is usually prominent with the straight nasal bridge. Eyes are oval shaped with golden colour. Ears are erect and usually cropped at an early age. The dogs have short coats and their tails are usually semi-curved and docked usually at a young age. The adult body weight and average litter size at birth ranges from 22-31 kg and 3-8, respectively. Haofa is morphologically different from the other exotic breeds, crossbreeds or local dogs found in the state. Hence, it deserves to be recognized as a distinct breed of dog

Letter to the Editor - Amphotericin B Induced Ventricular Arrhythmia and Its Relation to Central Venous Line

Sir, A 40-year-old man, weighing 81 kg, with no previous history of heart disease presented with complaint of fever since 25 days. Ultrasonography and computed tomography of abdomen showed altered echotexture and multiple splenic hypodense lesions. Aspiration and culture showed the growth of Candida tropicalis and a rising serological titre from 1:256 to 1:1024. The patient was started on intravenous amphotericin B 8 mg (0.1 mg/kg body weight) over three hours after a test dose of 1 mg. After a cumulative dose of 28 mg, he developed a life-threatening ventricular tachycardia which was DC-verted to normal sinus rhythm

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Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer’s disease from bioptic olfactory mucosa

Alzheimer's disease (AD) pathology precedes the onset of clinical symptoms by several decades. Thus, biomarkers are required to identify prodromal disease stages to allow for the early and effective treatment. The methoxy-X04-derivative BSC4090 is a fluorescent ligand which was designed to target neurofibrillary tangles in AD. BSC4090 staining was previously detected in post-mortem brains and olfactory mucosa derived from AD patients. We tested BSC4090 as a potential diagnostic marker of prodromal and early AD using olfactory mucosa biopsies from 12 individuals with AD, 13 with mild cognitive impairment (MCI), and 10 cognitively normal (CN) controls. Receiver-operating curve analysis revealed areas under the curve of 0.78 for AD versus CN and of 0.86 for MCI due to AD versus MCI of other causes. BSC4090 labeling correlated significantly with cerebrospinal fluid levels of tau protein phosphorylated at T181. Using NMR spectroscopy, we find that BSC4090 binds to fibrillar and pre-fibrillar but not to monomeric tau. Thus, BSC4090 may be an interesting candidate to detect AD at the early disease stages