Cellular Prion Protein (PrPC): Identification and Characterization of Novel Interacting Partners

The cellular prion protein (PrPC) is highly conserved throughout the evolution of mammals. (What does this sentence mean? What do you mean by ``conserved´´? This protein was higly conserved during the evolution of mammals [pantera et al. 2009; Jiayu et al.2009] and the gene tree deduced from the PrP sequences largely agrees with the species tree, indicating that no major deviations occurred in the evolution of the prion gene in different placental lineages [Teun van Rheede et al. 2003].) However, the cellular function of this ubiquitous protein is still not clear. The accumulation of misfolded and aggregated forms of PrPC (known as PrPSc) causes transmissible neurodegenerative diseases. Despite increasing knowledge concerning the PrPSc, very little is known about the physiological characteristics of PrPC and its interaction with other cellular proteins. The present study was undertaken to identify proteins interacting with PrPC that could provide new insights into its physiological functions and pathological role. Human PrPC was expressed in prion protein-deficient murine hippocampus (HpL3-4) neuronal cells. The PrPC along with its interacting proteins were affinity purified using STrEP-Tactin chromatography, in-gel digested and then identified by Q-TOF MS/MS analysis. Forty three proteins appeared to interact with PrPC in this neuronal cell line. Of these, fifteen were already known for their interaction with PrPC or PrPSc, while twenty eight new proteins were identified. All 43 (known and new) proteins which we identified as interacting partners) were structural constituents of the cytoskeleton. Some are involved in cell growth, some in metabolism and some in energy pathways. In addition, proteins that are important for cell homeostasis, cell communication, signal transduction, stress response and protein folding were also among the newly identified interacting partners of PrPC. Interactions of two novel interacting partners of the GTPase family (Rab7a and Arf1) which have a suggested role in vesicle trafficking as well as the cytoskeleton associated protein alpha-tubulin 1 were further investigated using confocal laser scanning microscopy and reverse co-immunoprecipitation. Both reverse immunoprecipitation and immunofluorescence results confirmed potential interactions of Rab7a, Arf1 and alpha-tubulin 1 with the PrPC. We used siRNA against the Rab7a gene to decrease the expression of Rab7a protein ( knockdown ), in PrPC expressing HpL3-4 and SH-SHY5Y cells. This depleted Rab7a expression led to the enhanced accumulation of PrPC in Rab9 positive endosomal compartments. The PrPC which accumulated within these Rab9 positive late endosomes remained sensitive to proteinase K digestion. Furthermore, Arf1 deactivation by brefeldin A treatment down regulated PrPC expression and redistributed PrPC into the cytosolic ,whereas nocodazole treatment increased PrPC expression and redistributed PrPC into the cytosol. The work described demonstrated for the first time that Rab7a and Arf1 may interact with PrPC and may possibly be involved in the cellular trafficking and distribution of PrPC into microtubules. These results highlight the pivotal involvement of endosomal compartments in the trafficking and regulation of PrPC

Risk factors for depression among married women belonging to higher and lower socioeconomic status in Karachi, Pakistan

OBJECTIVES: To determine the risk factors for depression among married women belonging to low and high socioeconomic status in Karachi.METHODS: The study design was cross-sectional. The data was collected from 128 adult married women during July to September 2005. The women were selected from different socioeconomic classes from five hospitals/institutes in Karachi. The Centre for Epidemiology Studies-Depression (CES-D) scale was used to screen the subjects for depression and a structured questionnaire was used to identify the factors for depression.RESULT: According to the CES-D scale, 65% of the study population was found to be depressed. Among the women from high socioeconomic status, social conditions were identified as a significant factor for causing depression, whereas social relations, specifically relationship problems with husband, were the major factor for depression among women belonging to the low socioeconomic status.CONCLUSION: The prevalence of depression among married women living in Karachi is high. However, underlying factors for causing depression vary among women belonging to low and high socioeconomic status

Prion Protein Strain Diversity and Disease Pathology

The infectious agents, prions, are composed mainly of conformational isomers of the cellular prion protein (PrPc) in its abnormal accumulated scrapie forms (PrPSc). The distinct prion isolates or strains have been associated with different PrPSc prion protein conformations and patterns of glycosylation and are associated with disease progression and severity. In humans, sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form and has been divided into six subtypes, based on PrPSc electrophoretic mobility and allelic variation at codon 129, among which sCJD MM1 and sCJD VV2 are the two most commonly occurring subtypes with known clinical manifestations. The strain-specific response of PrPSc suggests both the molecular classification and the pathogenesis of prion diseases along with posttranslational modification of PrP in humans and animals

Pharmacognostic Studies of Some Indigenous Medicinal Plants of Pakistan

Medicinal plants constitute an effective source of traditional and modern medicines. The plant is a biosynthetic laboratory, not only for chemical compounds but also a multitude of the compounds. The present research work was confined to study the macro, microscopic features and analysis of powdered drug of Acacia modesta Wall., Acacia nilotica (L.) Delile, Berberis lycium Royle and Zanthoxylum alatum D. C. Prod. These studies were carried out in Botany laboratory of University of Arid Agriculture, Rawalpindi during 2004. These species are used as miswak (tooth brush) by local people of Pakistan in different areas. Anatomical features such as, fibres, parenchyma cells, vessels and pith were identified during microscopic studies. Powdered miswak of Acacia modesta Wall., Berberis lycium Royle and Zanthoxylum alatum D. C. Prod. were soluble in sulphuric acid only while insoluble in other solvents i.e., hydrochloric acid, acetic acid, benzene and water. Powdered miswak of Acacia nilotica was insoluble in these solvents. Powdered drug of these species did not retain their original colour in cold and hot tests and on dry filter paper, when mixed in various solvents

Magnetic resonance spectroscopy in focal brain lesions

OBJECTIVE: To describe the spectrum of Magnetic Resonance spectroscopy in focal brain lesions and determine its diagnostic accuracy using histopathology as gold standard in differentiating neoplastic and non-neoplastic focal brain lesions. METHODS: The study was conducted in Department of Radiology, Aga Khan University Hospital, Karachi from Dec 2006 till Jan 2009. Fifty three patients found to have focal brain lesions on magnetic resonance imaging (MRI) were included in the study. Magnetic Resonance spectroscopy (MRS) was performed in these focal lesions. These lesions were deemed neoplastic and non-neoplastic on MR Spectrum findings. Correlation of all these findings was done with histopathology obtained in all these patients. Sensitivity, specificity, positive, negative predictive values and diagnostic accuracy of MR Spectroscopy was calculated. Percentage agreement between spectroscopy and histopathology was also calculated using kappa statistics. RESULTS: Increase Choline/creatine and Choline/NAA ratio noted in neoplastic lesions compared to nonneoplastic lesion with significant p-value. MR Spectroscopy has a sensitivity of 93.02%, specificity of 70%, positive predictive value of 93.02%, negative predictive value of 70% and diagnostic accuracy of 88.67% in differentiating neoplastic and non-neoplastic brain lesions. Kappa statistics shows a good agreement between MR Spectroscopy and histopathology (k = 0.630). CONCLUSION: Magnetic Resonance spectroscopy (MRS) is non-invasive sensitive, however, relatively nonspecific modality in differentiating neoplastic and non-neoplastic brain lesions. This modality should be considered as an adjunct to conventional imaging rather than replacement for histopathological evaluation

BRICS: Is the Group Really Creating Impact?

In 2001, Jim O'Neill coined the acronym for Brazil, Russia, India and China as the largest emerging markets economies. He expected them to grow faster than the developed countries and to play an increasingly important role in the world. In 2009, BRIC countries held their first summit which in its 3rd summit turned into BRICS with the addition of South Africa. The BRICS now represent 3 billion people and a combined GDP of $16 trillion. The group is the third giant after the EU and the US. Analysts predict that the BRICS will overtake US in terms of GDP this year and the G7 by 2030. In the summit in July 2014, BRICS leaders have approved creating the BRICS New Development Bank which would fund long-term investment in infrastructure and more sustainable development. The economics projections show that till 2040, the BRICS is expected to rule the world market

Coinfection with Lichtheimia corymbifera and Aspergillus flavus in an Immune-Competent Patient Mimicking as Pulmonary-Renal Syndrome

Lichtheimia corymbifera and Aspergillus flavus pulmonary coinfection has been rarely reported in immune-competent patients. We report case of a young male who presented with clinical features of pulmonary-renal syndrome and was later diagnosed to have bilateral polymicrobial fungal lung infection

Accuracy of magnetic resonance imaging in pretreatment lymph node assessment for gynecological malignancies

Objective: To determine the accuracy of magnetic resonance imaging (MRI) in detection of metastasis in pelvic and para-aortic lymph nodes from different gynecological malignancies.MATERIALS AND Methods: This retrospective cross sectional analytic study was conducted at the Department of Diagnostic Radiology, Aga Khan University Hospital Karachi Pakistan from January 2011 to December 2012. A sample of 48 women, age range between 20-79 years, fulfilling inclusion criteria were included. All patients had histopathologically proven gynecological malignancies in the cervix, endometrium or ovary and presented for a pretreatment MRI to our radiology department.Results: MRI was 100% sensitive and had a 100% positive predictive value to detect lymph node metastasis in lymph nodes with spiculated margins and 100% sensitive with a 75% positive predictive value to detect lymph node metastasis in a lymph node with lobulated margins. The sensitivity and positive predictive value of MRI to detect heterogeneous nodal enhancement were 100% and 75% respectively.CONCLUSIONS: Our study results reinforce that MRI should be used as a modality of choice in the pretreatment assessment of lymph nodes in proven gynaecological malignancies in order to determine the line of patient management, distinguishing surgical from non-surgical cases

Triphasic computed tomography (CT) scan in focal tumoral liver lesions

OBJECTIVE: To assess the diagnostic accuracy of triphasic spiral CT in differentiating benign from malignant focal tumoral liver lesions. METHODS: The study was conducted in Department of Radiology of Aga Khan University Hospital and Sind Institute of Urology and Transplantation, Karachi from Feb 2006 to Feb 2007. By convenient sampling, 45 patients found to have focal tumoral liver lesions were recruited for one year period and their triphasic CT scans findings were evaluated and later correlated with histopathology. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of triphasic CT scan were calculated. RESULTS: Among 45 patients, 136 liver lesions (11 benign and 125 malignant) were detected with the help of different enhancement patterns. Out of these, 37(82.2%) patients had malignant while 8 (17.8%) had benign lesions. On later histopathological examination, 35 (77.8%) of the total 45 cases had malignant lesions while 10 (22.2%) were diagnosed as benign lesions. Based on these results, it could be assessed that triphasic CT Scan has a sensitivity of 100%, specificity of 80%, positive predictive value of 94.5%, negative predictive value of 100% and diagnostic accuracy of 95.5% in differentiating benign from malignant liver lesions. CONCLUSION: Triphasic CT Scan is a good non-invasive tool in characterizing and differentiating benign from malignant liver lesions