The proteostasis network and its decline in ageing

Ageing is a major risk factor for the development of many diseases, prominently including neurodegenerative disorders such as Alzheimer disease and Parkinson disease. A hallmark of many age-related diseases is the dysfunction in protein homeostasis (proteostasis), leading to the accumulation of protein aggregates. In healthy cells, a complex proteostasis network, comprising molecular chaperones and proteolytic machineries and their regulators, operates to ensure the maintenance of proteostasis. These factors coordinate protein synthesis with polypeptide folding, the conservation of protein conformation and protein degradation. However, sustaining proteome balance is a challenging task in the face of various external and endogenous stresses that accumulate during ageing. These stresses lead to the decline of proteostasis network capacity and proteome integrity. The resulting accumulation of misfolded and aggregated proteins affects, in particular, postmitotic cell types such as neurons, manifesting in disease. Recent analyses of proteome-wide changes that occur during ageing inform strategies to improve proteostasis. The possibilities of pharmacological augmentation of the capacity of proteostasis networks hold great promise for delaying the onset of age-related pathologies associated with proteome deterioration and for extending healthspan

Determination of Ionospheric Current Systems by Measuring the Phase Shift on Amateur Satellite Frequencies

We investigate the possibility of measuring and using the phase delay of radio frequency transmissions in the amateur satellite band as a method to determine the distribution of currents systems in the ionosphere. The amateur satellite transmissions at 7MHz, 14M Hz, and 144M Hz are low enough for Faraday rotation to cause a significant phase delay on the propagating signals in addition to the phase delay produced by the total electron content (TEC) in the ionosphere. The ionosphere in the E and F regions is modeled as an equivalent thin planar shell of collision free cold plasma 100 km in thickness located in an altitude range of 100 � 200 km. The earth\u27s magnetic field is superposed with a weaker magnetic field due to a narrow Gaussian strip of current representing an ionospheric electrojet. The prole of the current system is obtained by numerically optimizing the Appleton-Hartree dispersion relation for rays of simulated radio frequency (RF) signals that propagate through the ionosphere shell. The optimization procedure is performed with a differential evolution algorithm. From the optimization procedure, we obtain the ionosphere total electron content (TEC) and the strength, prole, and orientation of the ionospheric current system

Acylation and alkylation of 1, 3-dimethoxybenzene in polyphosphoric acid

Products of the reaction of 3-halo- and 3-ethoxypropionic acids with 1,3-dimethoxybenzene (4) in polyphosphoric acid have been shown to be 2',4'-dimethoxy-3-(2,4-dimethoxyphenyl)-propiophenone (6) and 1,5-bis[3-(2,4-dimethoxyphenyl)-3-keto-propyl]-2,4-dimethoxybenzene (15) and these have been prepared by unambiguous syntheses. 2',4'-Dimethoxy-3-ethoxypropiophenone (3a) and 2',3,4'- trimethoxypropiophenone (3d) have been synthesized by the reaction of 3-chloro-2',4'-dimethoxypropiophenone (3c) with ethanol and methanol respectively

Correlation between neuroimaging (CT scan) and neurological presentation in antepartum and postpartum eclampsia

Background: Eclampsia is a pregnancy related condition with high mortality and morbidity along with perinatal mortality and morbidity. The following study is designed to correlate the neurological presentation with neuroimaging (CT scan brain) in antepartum and postpartum eclampsia patients, which will guide in proper management of the patients.Methods: A prospective study conducted over a period of one year. 100 patients were included in all. The neurological presentation and neuroimaging findings were correlated in all antepartum and postpartum eclampsia patients who met the study criteria. The comparison was done using chi-square test and unpaired student ‘t’ test. Sensitivity, specificity, positive predictive value and negative predictive value were calculated to find the accuracy of neurological presentation in determining the diagnosis and kappa agreement.Results: Out of the 100 patients studied, 52 had significant CT scan findings. Of these 52, 35 women had neurological signs and symptoms, and 17 cases did not have neurological signs and symptoms (p=0.003). The sensitivity, specificity, positive predictive value and negative predictive value were found to be 67.31%, 62.5%, 66.04% and 63.83% respectively and the diagnostic accuracy was found to be 65%.Conclusions: Evaluation of neurological signs and symptoms in women with eclampsia is an important assessment which helps for the further management. Neuroimaging has limited role in uncomplicated cases. Neuroimaging is indicated in atypical presentation, fatal cases and those resistant to standard anti-eclamptic therapy, where the signs and symptoms fail to predict the likelihood diagnosis

A study on association of thrombocytopenia with pregnancy induced hypertension

Background: Hypertension is common complication of pregnancy and contributes significantly to maternal and perinatal morbidity and mortality. With incidence of 5-7% of all pregnancy. Platelet count is the most simple and economical method of prediction of PIH, way before the derangements in PT, PTT and TT occur. This study sought the importance of platelet count as the most consistent and reliable method in predicting the severity of PIH. The aim and objectives of the study was to correlate severity of PIH with degree of thrombocytopenia and the degree of thrombocytopenia with fetal and maternal outcome.Methods: Prospective observational study was done during November 2014 to June 2015. A total of 100 cases were included in this period that was diagnosed as PIH. Investigations like platelet count, LFT, RFT, PT were done. Observations were tabulated, analyzed and conclusions were drawn.Results: 66% of all the cases had severe preeclampsia and 56% had thrombocytopenia. There was very high significant relationship between the degree of thrombocytopenia with the severity of the PIH (at p <0.001). 12% of the fetuses had IUD, 10% had IUGR, 4% died after birth and 2% had severe birth asphyxia. 5 % of the mothers had DIC, 3 % showing HELLP syndrome, and 1% died.Conclusions: Thrombocytopenia is the most common complications of PIH and at times is life threatening. Therefore, platelet count can be used as an early, simple, and rapid test to assess the severity of pre eclampsia and prevent progression to HELLP syndrome and DIC

Structural flexibility of multifunctional HABP1 may be important for regulating its binding to different ligands

Hyaluronan-binding protein 1 (HABP1)/p32/gC1qR was characterized as a highly acidic and oligomeric protein, which binds to different ligands like hyaluronan, C1q, and mannosylated albumin. It exists as trimer in high ionic and reducing conditions as shown by crystal structure. In the present study, we have examined the structural changes of HABP1 under a wide range of ionic environments. HABP1 exhibits structural plasticity, which is influenced by the ionic environment under in vitro conditions near physiological pH. At low ionic strength HABP1 exists in a highly expanded and loosely held trimeric structure, similar to that of the molten globule-like state, whereas the presence of salt stabilizes the trimeric structure in a more compact fashion. It is likely that the combination of the high net charge asymmetrically distributed along the faces of the molecule and the relatively low intrinsic hydrophobicity of HABP1 result in its expanded structure at neutral pH. Thus, the addition of counter ions in the molecular environment minimizes the intramolecular electrostatic repulsion in HABP1 leading to its stable and compact conformations, which reflect in its differential binding toward different ligands. Whereas the binding of HABP1 toward HA is enhanced on increasing the ionic strength, no significant effect was observed with the two other ligands, C1q and mannosylated albumin. Thus, although HA interacts only with compact HABP1, C1q and mannosylated albumin can bind to loosely held oligomeric HABP1 as well. In other words, structural changes in HABP1 mediated by changes in the ionic environment are responsible for recognizing different ligands

Disulfide bond formation through Cys186 facilitates functionally relevant dimerization of trimeric hyaluronan-binding protein 1 (HABP1)/p32/gC1qR

Hyaluronan-binding protein 1 (HABP1), a ubiquitous multifunctional protein, interacts with hyaluronan, globular head of complement component 1q (gC1q), and clustered mannose and has been shown to be involved in cell signalling. In vitro, this recombinant protein isolated from human fibroblast exists in different oligomeric forms, as is evident from the results of various independent techniques in near-physiological conditions. As shown by size-exclusion chromatography under various conditions and glutaraldehyde cross-linking, HABP1 exists as a noncovalently associated trimer in equilibrium with a small fraction of a covalently linked dimer of trimers, i.e. a hexamer. The formation of a covalently-linked hexamer of HABP1 through Cys186 as a dimer of trimers is achieved by thiol group oxidation, which can be blocked by modification of Cys186. The gradual structural transition caused by cysteine-mediated disulfide linkage is evident as the fluorescence intensity increases with increasing Hg2+ concentration until all the HABP1 trimer is converted into hexamer. In order to understand the functional implication of these transitions, we examined the affinity of the hexamer for different ligands. The hexamer shows enhanced affinity for hyaluronan, gC1q, and mannosylated BSA compared with the trimeric form. Our data, analyzed with reference to the HABP1/p32 crystal structure, suggest that the oligomerization state and the compactness of its structure are factors that regulate its function

PENBANDINGAN TEKANAN DARAH SEBELUM DAN SESUDAH EKSTRAKSI GIGI PADA PASIEN MIDDLE AGE & ELDERLY DI RUMAH SAKIT GIGI DAN MULUT (RSGM) UNIVERSITAS SYIAH KUALA

ABSTRAKNama: Ika Kasturi M Prodi: Program Studi Pendidikan Dokter GigiFakultas : Kedokteran GigiJudul:Perbandingan Tekanan Darah Sebelum dan Sesudah Ekstraksi Pada Pasien Middle Age & Elderly di Rumah Sakit Gigi dan Mulut Universitas syiah kuala (RSGM Unsyiah)Kelompok umur Usia Pertengahan dan Menua yang melakukan pencabutan gigi di Rumah Sakit Gigi dan Mulut Universitas syiah kuala (RSGM Unsyiah) menjadi hal yang harus diperhatikan ketika melakukan tindakan ekstraksi gigi menyangkut tekanan darah yang dipengaruhi oleh efek agen eksogen adrenalin yang terdapat pada anastesi. Hal itu berdasarkan penelitian Ogunlewe et al. Yang dilakukan di nigeria. Tujuan penelitian adalah untuk mengetahui perbandingan tekanan darah pada pasien Middle Age & Elderly di Rumah Sakit Gigi dan Mulut Unsyiah (RSGM Unsyiah). Penelitian ini mengunakan uji statistik t berpasangan, setiap objek penelitian mendapatkan dua kali perlakuan berbeda yang terdiri dari 23 orang, yang menjadi subjek penelitian adalah pasien yang datang RSGM Unsyiah. Hasil penelitian ini menunjukan bahwa tekanan darah sistolik mengalami perubahan yang signifikan akan tetapi untuk tekanan darah diastol perubahan tidak terjadi perubahan yang signifikan. hasil penelitian ini disimpulkan bahwa faktor agen eksogen adrenalin yang terdapat di anastesi tidak mempengaruhi tekanan darah dengan signifikan, sehingga hal ini tidak membahayakan dengan cacatan operator harus memperhatikan hal-hal yang menjadi faktor predisposisi.Kata kunci : tekanan darah, pasien Middle Age & Elderly, pencabutan gigiABSTRACTNama: Ika Kasturi MProdi: Program Studi Kedokteran GigiFakultas : Kedokteran GigiJudul:Perbandingan Tekanan Darah Sebelum dan Sesudah Ekstraksi Pada Pasien Middle Age & Elderly di Rumah Sakit Gigi Universitas syiah kuala (RSGM Unsyiah)Middle age group age & Elderly who perform tooth extractions in Hospital Dental University syiah kuala (the Hospital Unsyiah) into things that must be considered when taking action regarding tooth extraction blood pressure is influenced by the effects of exogenous agents adrenaline contained in anesthesia. It was based on research Ogunlewe et al. Conducted in nigeria. The research objective is to determine the ratio of blood pressure in patients Middle age and Elderly in Hospital Dental Unsyiah (RSGM Unsyiah). This study uses statistical paired t test, each object of research to get twice the different treatment which consists of 23 people, which is the subject of the study were patients who come Unsyiah the Hospital. Results of this study showed that systolic blood pressure is a significant change but for diastolic blood pressure changes were not significant changes. Based on the results of this study concluded that factors exogenous agents adrenaline contained in anesthesia did not affect blood pressuresignificantly, so it is not harmful to the remarks operator must pay attention to things being a predisposing factor.Keyword : Blood pressure, Middle age group age & Elderly, tooth exractio

Transformations in Early Historic and Early Medieval India: Excavations at Paithan, Maharashtra 1996-1999.

Transformations in Early Historic and Early Medieval India: Excavations at Paithan, Maharashtra 1996-1999 (Delhi: Archaeological Survery of India and British Association for South Asian Studies, 2015)