Comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of three highly pathogenic human coronaviruses (MERS-CoV, SARS-CoV, and SARS-CoV-2).

The last two decades have witnessed the emergence of three deadly coronaviruses (CoVs) in humans: severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are still no reliable and efficient therapeutics to manage the devastating consequences of these CoVs. Of these, SARS-CoV-2, the cause of the currently ongoing coronavirus disease 2019 (COVID-19) pandemic, has posed great global health concerns. The COVID-19 pandemic has resulted in an unprecedented crisis with devastating socio-economic and health impacts worldwide. This highlights the fact that CoVs continue to evolve and have the genetic flexibility to become highly pathogenic in humans and other mammals. SARS-CoV-2 carries a high genetic homology to the previously identified CoV (SARS-CoV), and the immunological and pathogenic characteristics of SARS-CoV-2, SARS-CoV, and MERS contain key similarities and differences that can guide therapy and management. This review presents salient and updated information on comparative pathology, molecular pathogenicity, immunological features, and genetic characterization of SARS-CoV, MERS-CoV, and SARS-CoV-2; this can help in the design of more effective vaccines and therapeutics for countering these pathogenic CoVs.

Modulation of host epigenome by coronavirus infections and developing treatment modalities for COVID-19 beyond genetics.

The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak has resulted in coronavirus disease 2019 (COVID-19) pandemic worldwide, affecting millions of lives. Although vaccines are presently made available, and vaccination drive is in progress to immunize a larger population; still the risk of SARS-CoV-2 infection and related mortality is persistent amid threats of the third wave of the ongoing pandemic. In the scenario of unavailability of robust and efficient treatment modalities, it becomes essential to understand the mechanism of action of the virus and deeply study the molecular mechanisms (both at the virus level and the host level) underlying the infection processes. Recent studies have shown that coronaviruses (CoVs) cause-specific epigenetic changes in the host cells to create a conducive microenvironment for replicating, assembling, and spreading. Epigenetic mechanisms can contribute to various aspects of the SARS-CoV-2 multiplication cycle, like expressing cytokine genes, viral receptor ACE2, and implicating different histone modifications. For SARS-CoV-2 infection, viral proteins are physically associated with various host proteins resulting in numerous interactions between epigenetic enzymes (i.e., histone deacetylases, bromodomain-containing proteins). The involvement of epigenetic mechanisms in the virus life cycle and the host immune responses to control infection result in epigenetic factors recognized as emerging prognostic COVID-19 biomarkers and epigenetic modulators as robust therapeutic targets to curb COVID-19. Therefore, this narrative review aimed to summarize and discuss the various epigenetic mechanisms that control gene expression and how these mechanisms are altered in the host cells during coronavirus infection. We also discuss the opportunities to exploit these epigenetic changes as therapeutic targets for SARS-CoV-2 infection. Epigenetic alterations and regulation play a pivotal role at various levels of coronavirus infection: entry, replication/transcription, and the process of maturation of viral proteins. Coronaviruses modulate the host epigenome to escape the host immune mechanisms. Therefore, host epigenetic alterations induced by CoVs can be considered to develop targeted therapies for COVID-19.

Consecutive Hits of COVID-19 in India: The Mystery of Plummeting Cases and Current Scenario.

The novel coronavirus disease 2019 (COVID-19)-related pandemic has been in existence for almost 2 years now after its possible emergence from a wet market in the city of Wuhan of the Chinese mainland. Evidence of the emergence and transmission of this virus was attributed to bats and pangolins. The causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread globally, affecting humans considerably with its current death toll to be over 4.7 million out of more than 233 confirmed cases as of September 2021. The virus is constantly mutating and continuously trying to establish itself in humans by increasing its transmissibility and virulence through its numerous emerging variants. Several countries have been facing multiple waves of COVID-19 outbreaks one after the other, putting the medical and healthcare establishments under tremendous stress. Although very few drugs and vaccines have been approved for emergency use, their production capabilities need to meet the needs of a huge global population. Currently, not even a quarter of the world population is vaccinated. The situation in India has worsened during the ongoing second wave with the involvement of virus variants with a rapid and huge surge in COVID-19 cases, where the scarcity of hospital infrastructure, antiviral agents, and oxygen has led to increased deaths. Recently, increased surveillance and monitoring, strengthening of medical facilities, campaigns of awareness programs, progressive vaccination drive, and high collaborative efforts have led to limiting the surge of COVID-19 cases in India to a low level. This review outlines the global status of the pandemic with special reference to the Indian scenario.

Unified Explanation of the eejj, Diboson, and Dijet Resonances at the LHC.

We show that the excess events observed in a number of recent LHC resonance searches can be simultaneously explained within a nonsupersymmetric left-right inverse seesaw model for neutrino masses with W_{R} mass around 1.9 TeV. The minimal particle content that leads to gauge coupling unification in this model predicts g_{R}≃0.51 at the TeV scale, which is consistent with data. The extra color singlet, SU(2)-triplet fermions required for unification can be interpreted as the dark matter of the Universe. Future measurements of the ratio of same-sign to opposite-sign dilepton events can provide a way to distinguish this scenario from the canonical cases of type-I and inverse seesaw, i.e., provide a measure of the relative magnitudes of the Dirac and Majorana masses of the right-handed neutrinos in the SU(2)_{R} doublet of the left-right symmetric model.

A phase 3, randomized, double-blind study of single-dose fosaprepitant for prevention of cisplatin-induced nausea and vomiting: results of an Indian population subanalysis.

CONTEXT: Currently, there is limited data on the prevention of chemotherapy-induced nausea and vomiting (CINV) in Indian patients. AIMS: This post hoc study assessed the efficacy and safety of fosaprepitant compared with aprepitant for prevention of CINV in the Indian population. A subgroup analysis was performed from data collected in a phase 3 study of intravenous (IV) fosaprepitant or oral aprepitant, plus the 5-HT 3 antagonist ondansetron and the corticosteroid dexamethasone, in cisplatin-naοve patients with solid malignancies. MATERIALS AND METHODS: Patients scheduled to receive cisplatin (≥70 mg/m 2 ) were administered a single IV dose of fosaprepitant dimeglumine (150 mg) on day 1 or a 3-day dosing regimen of oral aprepitant (day 1:125 mg, days 2 and 3:80 mg) with standard doses of ondansetron and dexamethasone. Patients recorded nausea and/or vomiting episodes and their use of rescue medication and were monitored for adverse events (AEs) and tolerability. STATISTICAL ANALYSIS USED: Differences in response rates between fosaprepitant and aprepitant were calculated using the Miettinen and Nurminen method. RESULTS: In the Indian subpopulation (n = 372), efficacy was similar for patients in both the fosaprepitant or aprepitant groups; complete response in the overall, acute, and delayed phases and no vomiting in all phases were approximately 4 percentage points higher in the fosaprepitant group compared with the aprepitant group. Fosaprepitant was generally well-tolerated; common AEs were similar to oral aprepitant. CONCLUSIONS: IV fosaprepitant is as safe and effective as oral aprepitant in the Indian subpopulation and offers an alternative to the oral formulation.

B-L violating proton decay modes and new baryogenesis scenario in SO(10).

We show that grand unified theories based on SO(10) generate quite naturally baryon number violating dimension seven operators that violate B-L, and lead to novel nucleon decay modes such as n→e(-)K(+), e(-)π(+) and p→νπ(+). We find that in two-step breaking schemes of nonsupersymmetric SO(10), the partial lifetimes for these modes can be within reach of experiments. The interactions responsible for these decay modes also provide a new way to understand the origin of matter in the Universe via the decays of grand unified theory (GUT) scale scalar bosons of SO(10). Their (B-L)-violating nature guarantees that the GUT scale induced baryon asymmetry is not washed out by the electroweak sphaleron interactions. In minimal SO(10) models this asymmetry is closely tied to the masses of quarks, leptons and the neutrinos.

Studies on rheological and leaching characteristics of heavy metals through selective additive in high concentration ash slurry.

The generation and disposal level of thermal power plant ash in India is a challenging task. The conventional mode of dilute phase ash slurry (10-20% solids by weight) transport through pipelines being practiced in majority of these plants not only consumes huge amount of precious water and pumping energy but also causes serious environmental problem at the disposal site. The present study investigates the rheological and leaching characteristics of an Indian ash samples at high solids concentrations (>50% by weight) using sodium silicate as an additive. The flow behaviour of ash slurry in the concentration range of 50-60% by weight is described by a Bingham-plastic model. It was indicated that the addition of sodium silicate (0.2-0.6% of the total solids) could able to reduce both the slurry viscosity and the yield stress. The analysis of the ash samples for the presence of heavy metals such as Fe, Cd, Ni, Pb, Zn, Cu, Co, As and Hg were carried out following Hansen and Fisher procedure. The addition of sodium silicate affected the leaching characteristics of the ash samples over a period of 300 days resulting in the reduction of leaching of heavy metals.

Sneutrino dark matter in gauged inverse seesaw models for neutrinos.

Extending the minimal supersymmetric standard model to explain small neutrino masses via the inverse seesaw mechanism can lead to a new light supersymmetric scalar partner which can play the role of inelastic dark matter (IDM). It is a linear combination of the superpartners of the neutral fermions in the theory (the light left-handed neutrino and two heavy standard model singlet neutrinos) which can be very light with mass in ~5-20 GeV range, as suggested by some current direct detection experiments. The IDM in this class of models has keV-scale mass splitting, which is intimately connected to the small Majorana masses of neutrinos. We predict the differential scattering rate and annual modulation of the IDM signal which can be testable at future germanium- and xenon-based detectors.

Urine leakage in persons with spinal cord injury and using long-term Foley catheters: a simple solution.

STUDY DESIGN: To visualize residual urine in a bladder using a regular Foley catheter and then using a modified Foley catheter. OBJECTIVES: To determine whether a modified Foley catheter eliminates or reduces a catheter-associated deposition of residual urine around the balloon and whether this reduction eliminates catheter leakage. SETTINGS: A patient with chronic spinal cord injury using a Foley catheter and experiencing significant refractory urine leakage around the catheter. METHODS: The design of a Foley catheter and the way it drains lead to the constant presence of small amounts of residual urine at the base, surrounding the balloon. The Foley catheter was modified using a cook catheter punch to make two extra holes just below the balloon. RESULTS: A cystogram of an unmodified Foley catheter showed the presence of residual urine around the Foley balloon. A cystogram of a modified Foley catheter eliminated this residual urine around the balloon. After the modification there was no more leakage around the Foley catheter. CONCLUSION: Modification of the catheter, as described, eliminated the residual urine around the catheter balloon and eliminated clinical urine leakage around the Foley catheter.

Unified TeV scale picture of baryogenesis and dark matter.

We present a simple extension of the minimal supersymmetric standard model which provides a unified picture of cosmological baryon asymmetry and dark matter. Our model introduces a gauge singlet field N and a color triplet field X which couple to the right-handed quark fields. The out-of-equilibrium decay of the Majorana fermion N mediated by the exchange of the scalar field X generates adequate baryon asymmetry for MN approximately 100 GeV and MX approximately TeV. The scalar partner of N (denoted N1) is naturally the lightest SUSY particle as it has no gauge interactions and plays the role of dark matter. The model is experimentally testable in (i) neutron-antineutron oscillations with a transition time estimated to be around 10(10)sec, (ii) discovery of colored particles X at LHC with mass of order TeV, and (iii) direct dark matter detection with a predicted cross section in the observable range.

Reconciling the CAST and PVLAS results.

The PVLAS experiment has recently claimed evidence for an axionlike particle in the milli-electron-volt mass range with a coupling to two photons that appears to be in contradiction with the negative results of the CAST experiment searching for solar axions. The simple axion interpretation of these two experimental results is therefore untenable and it has posed a challenge for theory. We propose a possible way to reconcile these two results by postulating the existence of an ultralight pseudoscalar particle interacting with two photons and a scalar boson and the existence of a low scale phase transition in the theory.

Postsphaleron baryogenesis.

We present a new mechanism for generating the baryon asymmetry of the Universe directly in the decay of a singlet scalar field S(r) with a weak scale mass and a high dimensional baryon number-violating coupling. Unlike most currently popular models, this mechanism, which becomes effective after the electroweak phase transition, does not rely on the sphalerons for inducing a nonzero baryon number. CP asymmetry in S(r) decay arises through loop diagrams involving the exchange of W+/- gauge bosons and is suppressed by light quark masses, leading naturally to a value of eta(B) approximately 10(-10). The simplest realization of this idea which uses a six quark DeltaB=2 operator predicts colored scalars accessible to the CERN Large Hadron Collider and neutron-antineutron oscillation within reach of the next-generation experiments.

Observable N-N oscillation in high scale seesaw models.

We discuss a realistic high scale (nu(B-L) approximately 10(12) GeV) supersymmetric seesaw model based on the gauge group SU(2)L x SU(2)R x SU(4)c where neutron-antineutron oscillation can be in the observable range. This is contrary to the naive dimensional arguments which say that tau(N-N) is proportional to nu(B-L)5 and should therefore be unobservable for seesaw scale nu(B-L) > or = 10(5) GeV. Two reasons for this enhancement are (i) accidental symmetries which keep some of the diquark Higgs masses at the weak scale and (ii) a new supersymmetric contribution from a lower dimensional operator. The net result is that tau(N-N) is proportional to nu(B-L)2 nu(wk)3 rather than nu(B-L)5. The model also can explain the origin of matter via the leptogenesis mechanism and predicts light diquark states which can be produced at LHC.

Suppressing proton decay in the minimal SO(10) model.

We show that in a class of minimal supersymmetric SO(10) models which have been found to be quite successful in predicting neutrino mixings, all proton decay modes can be suppressed by a particular choice of Yukawa textures. The required texture not only fits all lepton and quark masses as well as Cabibbo-Kobayashi-Maskawa parameters, but it also predicts neutrino mixing parameter U(e3) and Dirac CP phase sin(/delta(MNS)/ to be 0.07-0.09 and 0.3-0.7, respectively.

Geometric CP violation with extra dimensions.

We discuss how CP symmetry can be broken geometrically through orbifold projections in hidden extra dimensions in the context of brane-bulk models for particle unifications. The CP violation arises from a crash between the geometry of the compactification and the original higher dimensional CP definition. We present toy models to illustrate the idea and suggest ways to incorporate it into more realistic models.

History of trace gases in presolar diamonds inferred from ion-implantation experiments.

Diamond grains are the most abundant presolar grains found in primitive meteorites. They formed before the Solar System, and therefore provide a record of nuclear and chemical processes in stars and in the interstellar medium. Their origins are inferred from the unusual isotopic compositions of trace elements-mainly xenon-which suggest that they came from supernovae. But the exact nature of the sources has been enigmatic, as has the method by which noble gases were incorporated into the grains. One observation is that different isotopic components are released at different temperatures when the grains are heated, and it has been suggested that these components have different origins. Here we report results of a laboratory study that shows that ion implantation (previously suggested on other grounds) is a viable mechanism for trapping noble gases. Moreover, we find that ion implantation of a single isotopic composition can produce both low- and high-temperature release peaks from the same grains. We conclude that both isotopically normal and anomalous gases may have been implanted by multiple events separated in space and/or time, with thermal processing producing an apparent enrichment of the anomalous component in the high-temperature release peak. The previous assumption that the low- and high-temperature components were not correlated may therefore have led to an overestimate of the abundance of anomalous argon and krypton, while obscuring an enhancement of the light-in addition to the heavy-krypton isotopes.

Large extra dimensions, sterile neutrinos and solar neutrino data.

Solar, atmospheric, and LSND neutrino oscillation results require a light sterile neutrino, nu(B), which can exist in the bulk of extra dimensions. Solar nu(e), confined to the brane, can oscillate in the vacuum to the zero mode of nu(B) and via successive Mikheyev-Smirnov-Wolfenstein transitions to Kaluza-Klein states of nu(B). This new way to fit solar data is provided by both low and intermediate string scale models. From average rates seen in the three types of solar experiments, the Super-Kamiokande spectrum is predicted with 73% probability, but dips characteristic of the 0.06 mm extra dimension should be seen in the SNO spectrum.

Evaluation of cyfluthrin and fenfluthrin for their insecticidal activity against three vector mosquitoes.

The EC50/EC90 concentrations of cyfluthrin and fenfluthrin were tested for their activity against different developmental stages of three important vector mosquitoes viz., Anopheles stephensi Liston, Aedes aegypti (Linn.) and Culex quinquefasciatus Say. The EC90 concentrations of both cyfluthrin and fenfluthrin showed ovicidal effect on An. Stephensi and Ae. aegypti whereas EC90 of cyfluthrin checked the hatching of eggs completely in Cx. quinquefasciatus. Fenfluthrin at EC50 concentration reduced the percentage of hatching significantly (p < 0.05) only in An. stephensi. Both the compounds were more active against the fourth larval instars of all mosquito species and cyfluthrin in culicines (17.3% Ae. aegypti = 9.1%) and fenfluthrin in anophenlines (An. stephensi = 36.8%) brought about maximum inhibition in adult emergence. Various types/degrees of morphogenetic aberrations were induced in all mosquito species on treatment with these compounds. Cyfluthrin treated female mosquitoes showed reduced fecundity rates in An. stephensi (p < 0.05), Cx. quinquefasciatus (p < 0.001) and fenfluthrin treated in An. stephensi (p < 0.5) and Ae. aegypti (p < 0.05). The fertility rates of all the mosquito species were significantly reduced (p < 0.001) by both the compounds.