Investigation of Membrane Receptors’ Oligomers Using Fluorescence Resonance Energy Transfer and Multiphoton Microscopy in Living Cells

Investigating quaternary structure (oligomerization) of macromolecules (such as proteins and nucleic acids) in living systems (in vivo) has been a great challenge in biophysics, due to molecular diffusion, fluctuations in several biochemical parameters such as pH, quenching of fluorescence by oxygen (when fluorescence methods are used), etc. We studied oligomerization of membrane receptors in living cells by means of Fluorescence (Förster) Resonance Energy Transfer (FRET) using fluorescent markers and two photon excitation fluorescence micro-spectroscopy. Using suitable FRET models, we determined the stoichiometry and quaternary structure of various macromolecular complexes. The proteins of interest for this work are : (1) sigma-1 receptor and (2) rhodopsin, are described as below. (1) Sigma-1 receptors are molecular chaperone proteins, which also regulate ion channels. S1R seems to be involved in substance abuse, as well as several diseases such as Alzheimer’s. We studied S1R in the presence and absence of its ligands haloperidol (an antagonist) and pentazocine +/- (an agonist), and found that at low concentration they reside as a mixture of monomers and dimers and that they may form higher order oligomers at higher concentrations. (2) Rhodopsin is a prototypical G protein coupled receptor (GPCR) and is directly involved in vision. GPCRs form a large family of receptors that participate in cell signaling by responding to external stimuli such as drugs, thus being a major drug target (more than 40% drugs target GPCRs). Their oligomerization has been largely controversial. Understanding this may help to understand the functional role of GPCRs oligomerization, and may lead to the discovery of more drugs targeting GPCR oligomers. It may also contribute toward finding a cure for Retinitis Pigmentosa, which is caused by a mutation (G188R) in rhodopsin, a disease which causes blindness and has no cure so far. Comparing healthy rhodopsin’s oligomeric structure with that of the mutant may give clues to find the cure

A retrospective analysis comparing functional and radiological outcomes after treatment of unstable distal radius fractures using volar locked plate versus percutaneous fixation

Background: Distal radius fractures are one of the most routinely encountered injuries in an orthopaedic setting. Despite the wide variety of treatment options available there is still debate about the optimal way to treat these fractures. The aim was to evaluate and compare functional and radiological outcomes of unstable distal radius fractures treated by either by using volar locking compression plating (VLP) or by using percutaneous fixation augmented by Kirschner (K) wires (EF).Methods: A retrospective analysis was carried out on all cases of acute unstable unilateral fracture distal radius who were admitted between January 2015 and December 2017 and were treated either by VLP or EF. QuickDASH score and PRWE were documented at every follow up in OPD at 6 weeks, 6 months and 1 year post-op along with serial X-rays at immediate post-op and 01 year which were then compared.Results: A total of 122 cases of fracture distal radius were selected for study which fulfilled the inclusion criteria out of which 49 were treated by VLP and 73 by EF. There was no statistical difference in QuickDASH, PRWE scores or wrist ROM between two groups at1 year follow up. However VLP group was better in maintaining palmar tilt, radial length and inclination at the end of 1 year.Conclusions: Both VLP and EF show comparable and predictable good outcomes in treating unstable distal radius fractures when measured in terms of ROM and clinically validated patient outcome scores at 01 year follow up with similar rate of complications.

MSEA: Modified Symmetric Encryption Algorithm

In this article, a new symmetric block cipher named MSEA is proposed. MSEA is based on ARX cryptographic design technique. MSEA is simple in nature due to the use of combinations of elementary operations like modular addition, bit-wise rotation and bit-wise XOR. In MSEA, plain text block, secret key, and number of encryption rounds are variable in size, while the size of cipher text is double of size of plain text. Data-dependant rotation is the most vital feature of MSEA through which the unpredictability of encrypted text is increasing. Key formation and encryption/decryption schemes of MSEA are significantly fast

Public health insurance coverage in India before and after PM-JAY:Repeated cross-sectional analysis of nationally representative survey data

Introduction:The provision of non-contributory public health insurance (NPHI) to marginalised populations is a critical step along the path to universal health coverage. We aimed to assess the extent to which Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana (PM-JAY) - potentially, the world's largest NPHI programme - has succeeded in raising health insurance coverage of the poorest two-fifths of the population of India. Methods:We used nationally representative data from the National Family Health Survey on 633 699 and 601 509 households in 2015-2016 (pre-PM-JAY) and 2019-2021 (mostly, post PM-JAY), respectively. We stratified by urban/rural and estimated NPHI coverage nationally, and by state, district and socioeconomic categories. We decomposed coverage variance between states, districts, and households and measured socioeconomic inequality in coverage. For Uttar Pradesh, we tested whether coverage increased most in districts where PM-JAY had been implemented before the second survey and whether coverage increased most for targeted poorer households in these districts. Results:We estimated that NPHI coverage increased by 11.7 percentage points (pp) (95% CI 11.0% to 12.4%) and 8.0 pp (95% CI 7.3% to 8.7%) in rural and urban India, respectively. In rural areas, coverage increased most for targeted households and pro-rich inequality decreased. Geographical inequalities in coverage narrowed. Coverage did not increase more in states that implemented PM-JAY. In Uttar Pradesh, the coverage increase was larger by 3.4 pp (95% CI 0.9% to 6.0%) and 4.2 pp (95% CI 1.2% to 7.1%) in rural and urban areas, respectively, in districts exposed to PM-JAY and the increase was 3.5 pp (95% CI 0.9% to 6.1%) larger for targeted households in these districts. Conclusion:The introduction of PM-JAY coincided with increased public health insurance coverage and decreased inequality in coverage. But the gains cannot all be plausibly attributed to PM-JAY, and they are insufficient to reach the goal of universal coverage of the poor.</p

Mining of diverse short non-coding RNAs from transcriptome of milk somatic cells of Murrah buffalo

The non-coding RNAs (ncRNA) are known to regulate expression of genes at the transcription, translation and processing levels. The present study was conducted to identify diverse short ncRNAs from milk somatic cells of lactating Murrah buffaloes. Elucidating the molecular drivers of lactation in dairy animals will help understand the process of lactation, eventually leading to improvement in milk production and quality. In order to discover the ncRNA, the transcriptome data of 12 samples of somatic cells from buffalo milk were analyzed. A web based pipeline, exceRpt was used to perform the analysis. The most abundant short ncRNA molecules discovered in buffalo milk were the miRNAs, followed by snRNAs. Least number of rRNAs was discovered in the investigated samples. The total number of rRNAs, tRNAs, snRNAs, snoRNAs and miRNAs were 12, 23, 72, 51 and 229 respectively, in the entire dataset. On matching with miRBase v22.1, a total of 1724, 897, 211 and 4 miRNAs were observed to be common to human, bovine, caprine and ovine genomes. The results provide information on the bioavailability of short ncRNAs in buffalo milk somatic cells, most of which are largely uncharacterized. The generated information is a step towards developing a database for ncRNAs in buffalo species

Quantum Griffiths phase in disordered Mn1-xFexSi

We show the presence of magnetic rare regions consistent with the quantum Griffiths phase in Fe-doped MnSi using detailed heat capacity, magnetization, and muon spin relaxation (μSR) measurements down to millikelvin temperatures. The slow dynamics of these rare regions at low temperatures leads to the non-Fermi-liquid behavior in heat capacity and magnetization. The μSR and magnetization results further indicate that the dynamics freezes into a cluster-glass state below Tf ∼ 1.25 K. The results are in agreement with theoretical models proposed in the literature for metallic systems with Heisenberg symmetry that exhibit the quantum Griffiths phase in the presence of strong disorder

Telemedicine across the globe-position paper from the COVID-19 pandemic health system resilience PROGRAM (REPROGRAM) international consortium (Part 1)

Coronavirus disease 2019 (COVID-19) has accelerated the adoption of telemedicine globally. The current consortium critically examines the telemedicine frameworks, identifies gaps in its implementation and investigates the changes in telemedicine framework/s during COVID-19 across the globe. Streamlining of global public health preparedness framework that is interoperable and allow for collaboration and sharing of resources, in which telemedicine is an integral part of the public health response during outbreaks such as COVID-19, should be pursued. With adequate reinforcement, telemedicine has the potential to act as the “safety-net” of our public health response to an outbreak. Our focus on telemedicine must shift to the developing and under-developing nations, which carry a disproportionate burden of vulnerable communities who are at risk due to COVID-19

Razvoj radiomarkiranog β-humanog koriogonadotropina

-human chorionic gonadotropin (-hCG) was successively labeled with [67Ga] gallium chloride after conjugation with freshly prepared diethylenetriaminepentaacetic acid dianhydride (ccDTPA). After solid phase purification of the radiolabeled hormone, high performance liquid chromatography showed radiochemical purity higher than 95 % under optimized conditions (specific activity = 2223 TBq mM1, labeling efficiency 80 %). Preliminary in vivo studies (ID g1, %) in male wild-type rats showed marked gonadal uptake of the tracer after 240 minutes in agreement with the biodistribution studies and reported -hCG receptors. Target to blood ratios were 5.1 and 15.2 after 3 and 24 hours, respectively, while target to muscle ratios were 35 and 40 after 3 and 24 hours, respectively.Beta-humani korionski gonadotropin (beta-hCG) uspješno je markiran s [67Ga] galijevim kloridom nakon konjugacije sa svježe priređenim dianhidridom dietilentriaminpentaoctene kiseline (ccDTPA). Nakon čišćenja radiomarkiranog hormona na čvrstoj fazi, radiokemijska čistoća bila je prema HPLC veća od 95 % (specifična aktivnost = 22-23 TBq mM-1, učinkovitost markiranja 80 %). Preliminarni in vivo pokusi (ID g-1, %) na mužjacima divljeg tipa štakora pokazali su da obilježeni hormon značajno ulazi u gonade nakon 240 minuta, što je u suglasnosti s ispitivanjima biodistribucije i podacima o receptorima za beta-hCG. Omjer koncentracija u gonadama i krvi bio je 5,1, odnosno 15,2 nakon 3, odnosno 24 sata, dok je omjer koncentracija u gonadama i mišićima bio 35, odnosno 40 nakon 3, odnosno 24 sata