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Cutaneous mast cells (MCs) express Mas-related G protein-coupled receptor-X2 (MRGPRX2; mouse ortholog MrgprB2), which is activated by an ever-increasing number of cationic ligands. Antimicrobial host defense peptides (HDPs) generated by keratinocytes contribute to host defense likely by two mechanisms; one involving direct killing of microbes and the other via MC activation through MRGPRX2. However, its inappropriate activation may cause pseudoallergy and likely contribute to the pathogenesis of rosacea, atopic dermatitis, allergic contact dermatitis, urticaria and mastocytosis. Gain- and loss-of-function missense single nucleotide polymorphisms in MRGPRX2 have been identified. The ability of certain ligands to serve as balanced or G protein-biased agonists have been defined. Small molecule HDP mimetics have been developed that display both direct antimicrobial activity and activate MCs via MRGPRX2. In addition, antibodies and reagents have been generated that modulate MRGPRX2 expression and signaling. In this article, we provide a comprehensive update on MrgprB2 and MRGPRX2 biology. We propose that harnessing MRGPRX2’s host defense function by small molecule HDP mimetics may provide a novel approach for the treatment of antibiotic-resistant cutaneous infections. By contrast, MRGPRX2-specific antibodies and inhibitors could be utilized for the modulation of allergic and inflammatory diseases that are mediated via this receptor.

Mast cells are multifunctional immune cells that are found most abundantly at host-environment interfaces, such as the skin, respiratory tract, and oral/gastrointestinal mucosa. Not surprisingly, mast cells act as sentinel cells that sense microbial attacks and initiate a protective immune response and promote healing. Although mast cells share many features with other innate immune effector cells, such as neutrophils and macrophages, they uniquely interact closely with blood vessels and release an extensive set of mediators for the recruitment of innate and adaptive immune cells. A novel human G protein-coupled receptor (GPCR), known as Mas-related GPCR-X2 (MRGPRX2, mouse ortholog, MrgprB2), has recently been identified, which is expressed on mast cells but not neutrophils and macrophages. Interestingly, activation of MrgprB2 by bacteria-derived quorum-sensing peptides inhibits bacterial growth, prevents biofilm formation, and leads to the recruitment of neutrophils to effectively clear bacteria. Furthermore, host defense antimicrobial peptides and small-molecule peptide mimetics also activate mast cells via MRGPRX2/B2. MrgprB2-mediated activation of local mast cells also clears cutaneous bacterial infection, promotes healing, and protects against reinfection. In addition to their role in host defense, mast cells contribute to a number of chronic inflammatory diseases such as periodontitis, neurogenic inflammation, and inflammatory pain likely via the activation of MRGPRX2. In this review, we discuss the roles of MRGPRX2/B2 in the clearance of bacterial infection, wound healing, periodontal disease, neurogenic inflammation, and inflammatory pain. We propose that harnessing mast cells’ host defense and immunomodulatory properties via the activation of MRGPRX2 may lead to novel approaches for the treatment of drug-resistant bacterial infections. On the other hand, increased MRGPRX2 expression on mast cells and their inappropriate activation may contribute to periodontitis, neurogenic inflammation, and inflammatory pain. Thus, targeting MRGPRX2 could provide novel approaches to modulate these conditions.

There is a great deal of psychological pressure on medical students, which results in depression, addiction, and suicide. Resilience plays a significant role in coping with psychological distress. The study aimed to determine the resilience level of medical students in Kolkata and factors related to it.A cross-sectional study was conducted among undergraduate students of a medical college in the eastern part of India during October 2020. Resilience was assessed using the validated "Adult Resilience Measure-R." Data were collected on Google Forms and analyzed using SPSS (version 16.0). Logistic regression analysis was performed to find factors associated with low resilience.The study revealed that one-fourth (25.2%) of the participants had low-level resilience. Nearly half (44.9%) of them perceived their mental health status as having worsened during the lockdown. Students who did not enjoy staying at home during the lockdown and who spent10 h of their time with their family members had higher odds of low resilience. In multivariable analysis, not enjoying staying at home during the lockdown remained the only significant predictor of low resilience.Students should spend more time with their parents and family members and learn coping skills. Appropriate resilience training programs have to be integrated into the medical curriculum to help in coping with future challenges.

Performance of quantum teleportation is typically measured by the average fidelity, an overlap between the input and output states. Along with the first moment, we introduce the second moment of fidelity in CV teleportation, i.e., the fidelity deviation as the figures of merit to assess the protocol's efficiency. We show that CV states, both Gaussian and non Gaussian, can be better characterized by considering both average fidelity and fidelity deviation, which is not possible with only average fidelity. Moreover, we shed light on the performance of the teleportation protocol in two different input scenarios - one is when input states are sampled from constrained uniform distribution while the other one is Gaussian suppression of the input states which again lead to a different classification of CV states according to their performance. The entire analysis is carried out in noiseless and noisy scenarios with noise being incorporated in the measurement and the shared channels. We also report that one type of noise can make the protocol robust against the other one which leads to a `constructive effect' and identify the noise models which are responsible for decreasing average fidelity and increment in fidelity deviation., Comment: v1: 14 pages, 8 figures, v2: 15 pages, 8 figures, close to published version

We present a framework of a multimode dense coding network with multiple senders and a single receiver using continuous variable systems. The protocol is scalable to arbitrary numbers of modes with the encoding being displacements while the decoding involves homodyne measurements of the modes after they are combined in a pairwise manner by a sequence of beam splitters, thereby exhibiting its potentiality to implement in laboratories with currently available resources. We compute the closed form expression of the dense coding capacity for the cases of two and three senders that involve sharing of three- and four-mode states respectively. The dense coding capacity is calculated with the constraint of fixed average energy transmission when the modes of the sender are transferred to the receiver after the encoding operation. In both the cases, we demonstrate the quantum advantage of the protocol using paradigmatic classes of three- and four-mode states. The quantum advantage increases with the increase in the amount of energy that is allowed to be transmitted from the senders to the receiver., Comment: 10 pages, 3 figures

We systematically generalize the Grover algorithm in a density matrix formalism by exploiting the underlying two-dimensional subspace of the problem. Using this, we derive analytic expressions for the success probability after arbitrary iterations of the generalized Grover operator with two generic phase angles . We show for the phase matching condition with three iterations, success probability can be achieved only with knowledge about the lower bound , where λ is the ratio of marked to total number of states in the database. This result will improve the quantum search algorithm when applied to databases with unknown number of marked states in the specified regime of λ, at the cost of decreased efficiency in the smaller λ region.

Mesothelial to mesenchymal transition (MesoMT) is one of the crucial mechanisms underlying pleural fibrosis, which results in restrictive lung disease. DOCK2 (dedicator of cytokinesis 2) plays important roles in immune functions; however, its role in pleural fibrosis, particularly MesoMT, remains unknown. We found that amounts of DOCK2 and the MesoMT marker α-SMA (α-smooth muscle actin) were significantly elevated and colocalized in the thickened pleura of patients with nonspecific pleuritis, suggesting the involvement of DOCK2 in the pathogenesis of MesoMT and pleural fibrosis. Likewise, data from three different pleural fibrosis models (TGF-β [transforming growth factor-β], carbon black/bleomycin, and streptococcal empyema) consistently demonstrated DOCK2 upregulation and its colocalization with α-SMA in the pleura. In addition, induced DOCK2 colocalized with the mesothelial marker calretinin, implicating DOCK2 in the regulation of MesoMT. Our in vivo data also showed that DOCK2-knockout mice were protected from Streptococcus pneumoniae–induced pleural fibrosis, impaired lung compliance, and collagen deposition. To determine the involvement of DOCK2 in MesoMT, we treated primary human pleural mesothelial cells with the potent MesoMT inducer TGF-β. TGF-β significantly induced DOCK2 expression in a time-dependent manner, together with α-SMA, collagen 1, and fibronectin. Furthermore, DOCK2 knockdown significantly attenuated TGF-β–induced α-SMA, collagen 1, and fibronectin expression, suggesting the importance of DOCK2 in TGF-β–induced MesoMT. DOCK2 knockdown also inhibited TGF-β–induced Snail upregulation, which may account for its role in regulating MesoMT. Taken together, the current study provides evidence that DOCK2 contributes to the pathogenesis of pleural fibrosis by mediating MesoMT and deposition of neomatrix and may represent a novel target for its prevention or treatment.

Cathelicidin LL-37‒mediated activation of mast cells (MCs) has been implicated in the pathogenesis of rosacea, but the receptor involved and the mechanism of its activation and regulation remain unknown. We found that skin biopsies from patients with rosacea display higher frequencies of MCs expressing MRGPRX2 (mouse counterpart MrgprB2) than normal skin. Intradermal injection of LL-37 in wild-type mice resulted in MC recruitment, expression of inflammatory mediators, and development of rosacea-like inflammation. These responses were substantially reduced in MrgprB2

AG-30/5C is an angiogenic host defense peptide that activates human mast cells (MC) via an unknown mechanism. Using short hairpin RNA–silenced human MC line LAD2 and stably transfected RBL-2H3 cells, we demonstrate that AG-30/5C induces MC degranulation via Mas-related G protein–coupled receptor X2 (MRGPRX2). Most G protein–coupled receptors signal via parallel and independent pathways mediated by G proteins and β-arrestins. AG-30/5C and compound 48/80 induced similar maximal MC degranulation via MRGPRX2, which was abolished by pertussis toxin. However, compound 48/80 induced a robust β-arrestin activation as determined by transcriptional activation following arrestin translocation (Tango), but AG-30/5C did not. Overnight culture of MC with compound 48/80 resulted in reduced cell surface MRGPRX2 expression, and this was associated with a significant decrease in subsequent MC degranulation in response to compound 48/80 or AG-30/5C. However, AG-30/5C pretreatment had no effect on cell surface MRGPRX2 expression or degranulation in response to compound 48/80 or AG-30/5C. Icatibant, a bradykinin B2 receptor antagonist, promotes MC degranulation via MRGPRX2 and causes pseudoallergic drug reaction. Icatibant caused MC degranulation via a pertussis toxin–sensitive G protein but did not activate β-arrestin. A screen of the National Institutes of Health Clinical Collection library led to the identification of resveratrol as an inhibitor of MRGPRX2. Resveratrol inhibited compound 48/80–induced Tango and MC degranulation in response to compound 48/80, AG-30/5C, and Icatibant. This study demonstrates the novel finding that AG-30/5C and Icatibant serve as G protein–biased agonists for MRGPRX2, but compound 48/80 signals via both G protein and β-arrestin with distinct differences in receptor regulation.

Water pollution is one of the most aggravated problems threatening the sustainability of human race and other life forms due to the rapid pace of civilization and industrialization. A long history exists of release of hazardous pollutants into the water bodies due to selfish human activities since the Industrial Revolution, but no effort has been completely successful in curbing the activities that result in the degradation of our environment. These pollutants are harmful, carcinogenic and have adverse health effects to all forms of life. Thus, remarkable efforts have been geared up to obtain clean water by exploiting science and technology. The application of Ionic liquids (ILs) as sustainable materials have received widespread attention since the last decade. Their interesting properties, simplicity in operation and satisfactory binding capacities in elimination of the contaminants makes them a valuable prospect to be utilized in wastewater treatment. Immobilizing and grafting the solid supports with ILs have fetched efficient results to exploit their potential in the adsorptive removal processes. This review provides an understanding of the recent developments and outlines the possible utility of IL based nano adsorbents in the removal of organic compounds, dyes and heavy metal ions from aqueous medium. Effect of several parameters such as sorbent dosage, pH and temperature on the removal efficiency has also been discussed. Moreover, the adsorption isotherms, thermodynamics and mechanism are comprehensively studied. It is envisioned that the literature gathered in this article will guide the budding scientists to put their interest in this area of research in the days to come.

The precise control and knowledge over the atomic dynamics is central to the advancement of quantum technology. The different experimental conditions namely, atoms in a vacuum, an anti-relaxation coated and a buffer gas filled atomic cell provides complementary platform for such investigations. The extent of changes in optical pumping, velocity changing collision and hyperfine changing collision rates associated with these conditions are discussed. There is a phenomenal change in the optical density by a factor of >25 times in presence of a control field in buffer gas environment. In contrary to earlier reports, we found confinement induced enhanced optical pumping as the mechanism behind the observed transparency in buffer gas cell. The feeble interplay of radiation trapping under specific conditions are pointed out. The diffusive velocity of atoms is measured to be ~25+-12 m/s and, 9 pages, 8 Figures

PURPOSE OF REVIEW: Atopic dermatitis (AD) and allergic asthma are complex disorders with significant public health burden. This review provides an overview of the recent developments on Mas-related G protein-coupled receptor-X2 (MRGPRX2; mouse counterpart MrgprB2) as a potential candidate to target neuro-immune interaction in AD and allergic asthma. RECENT FINDINGS: Domestic allergens directly activate sensory neurons to release substance P (SP), which induces mast cell degranulation via MrgprB2 and drives type 2 skin inflammation in AD. MRGPRX2 expression is upregulated in human lung mast cells and serum of asthmatic patients. Both SP and hemokinin-1 (HK-1 generated from macrophages, bronchial cells, and mast cells) cause degranulation of human mast cells via MRGPRX2. SUMMARY: MrgprB2 contributes to mast cell-nerve interaction in the pathogenesis of AD. Furthermore, asthma severity is associated with increased MRGPRX2 expression in mast cells. Thus, MRGPRX2 could serve as a novel target for modulating AD and asthma.

Perioperative hypersensitivity (POH) to the neuromuscular blocking drug (NMBD) rocuronium was previously thought to be IgE and mast cell (MC)-mediated. However, the recent seminal observation that rocuronium induces degranulation in murine peritoneal MCs (PMCs) via Mas-related G protein-coupled receptor B2 (MrgprB2) led to the idea that POH to this drug involves the activation of MRGPRX2 (human ortholog of MrgprB2). Furthermore, based on the demonstration that a patient with POH to rocuronium displayed three missense mutations (M196I, L226P and L237P) in MRGPRX2’s transmembrane domains, it was proposed that this hypersensitivity reaction resulted from aberrant activation of this receptor. We found that rocuronium at 20 µg/mL caused degranulation in mouse PMCs via MrgprB2 but required at least 500 µg/mL to induce degranulation in human MCs via MRGPRX2. Furthermore, RBL-2H3 cells transiently expressing M196I, L226P and L237P variants did not display enhanced degranulation in response to rocuronium when compared to the wild-type receptor. These findings provide the first demonstration that rocuronium induces degranulation in human MCs via MRGPRX2. Furthermore, the important differences between MrgprB2 and MRGPRX2 and the inability of rocuronium to induce enhanced response in cells expressing MRGPRX2 variants suggest that the mechanism of its POH is more complex than previously thought.

Unlike quantum correlations, the shareability of classical correlations (CCs) between two-parties of a multipartite state is assumed to be free since there exist states for which CCs for each of the reduced states can simultaneously reach their algebraic maximum value. However, when one randomly picks out states from the state space, we find that the probability of obtaining those states possessing the algebraic maximum value is vanishingly small. We explore the possibility of nontrivial upper bound by Haar uniformly generating random multipartite states and computing the frequency distribution for various CC measures, conventional classical correlators, and two axiomatic measures of classical correlations, namely the classical part of quantum discord and local work of work-deficit. We find that the distributions are typically Gaussian-like and their standard deviations decrease with the increase in number of parties. It also reveals that among the multiqubit random states, most of the reduced density matrices possess a low amount of CCs which can also be confirmed by the mean of the distributions, thereby showing a kind of restrictions on the sharability of classical correlations for random states. Furthermore, we also notice that the maximal value for random states is much lower than the algebraic maxima obtained for a set of states, and the gap between the two increases further for states with a higher number of parties. We report that for a higher number of parties, the classical part of quantum discord and local work can follow monogamy-based upper bound on sharability while classical correlators have a different upper bound. The trends of sharability for classical correlation measures in random states clearly demarcate between the axiomatic definition of classical correlations and the conventional ones., 15 pages, 11 figures, close to the published version

Genuine multimode entanglement in continuous variable systems can be quantified by exploring the geometry of the state-space, namely via the generalized geometric measure (GGM) which is defined as the shortest distance of a given multimode state from a nongenunely multimode entangled state. For multimode Gaussian states, we derive a closed form expression of GGM in terms of the symplectic invariants of the reduced states. Following that prescription, the characteristics of GGM for typical three- and four-mode Gaussian states are investigated. In the non-Gaussian paradigm, we compute GGM for photon-added as well as -subtracted states having three- and four-modes and find that both addition and subtraction of photons lead to enhancement of the genuine multimode entanglement content of the state compared to its Gaussian counterpart. Our analysis reveals that when an initial three-mode vacuum state is evolved according to an interacting Hamiltonian, photon addition is more beneficial in increasing GGM compared to photon subtraction while the picture is opposite for four-mode case. Specifically, subtracting photons from four-mode squeezed vacuum states almost always results in higher multimode entanglement content than that of photon addition with both single as well as multimode and constrained as well as unconstrained operations. Furthermore, we observe a novel freezing feature of GGM during some specific cases of photon subtraction with respect to the number of photons subtracted., 16 pages, 9 figures, close to the published version

We report dynamical quantum phase transition portrait in the alternating field transverse XY spin chain with Dzyaloshinskii-Moriya interaction by investigating singularities in the Loschmidt echo and the corresponding rate function after a sudden quench of system parameters. Unlike the Ising model, the analysis of Loschmidt echo yields non-uniformly spaced transition times in this model. Comparative study between the equilibrium and the dynamical quantum phase transitions in this case reveals that there are quenches where one occurs without the other, and the regimes where they co-exist. However, such transitions happen only when quenching is performed across at least a single gapless or critical line. Contrary to equilibrium phase transitions, bipartite entanglement measures do not turn out to be useful for the detection, while multipartite entanglement emerges as a good identifier of this transition when the quench is done from a disordered phase of this model., Comment: 10 pages, 6 figures; close to published version

Quantum teleportation is one of the most pioneering features of the quantum world. Typically, the quality of a teleportation protocol is solely judged by its average fidelity. In this work, we analyze the performance of teleportation in terms of both fidelity and the deviation in fidelity. Specifically, we define a quantity called teleportability score, which incorporates contributions from both the fidelity and its deviation. It also takes into account the sensitivity one requires for a protocol in which the teleportation of a quantum state is required in one or many intermediate steps. We compute the teleportability score in the noiseless scenario and find that it increases monotonically with the entanglement content of the resource state. The result remains same even if we consider an n-chain repeater-like configuration. However, in the presence of noise, the teleportability score, can sometime display a nonmonotonic behaviour with respect to the entanglement content of the initially shared resource state. Specifically, under local bit-flip and bit-phase-flip noise, lesser entangled states can have higher teleportability score for certain choice of system parameters. In the presence of global depolarizing noise, for low entangled resource states and high sensitivity requirements, the noisy states can have better a teleportability score in comparison to the noiseless scenario., 9 pages, 4 figures; close to the published version

Quantum teleportation with a two-qubit state can be suitably characterized in terms of maximal fidelity and fidelity deviation, where the former is the maximal value of the average fidelity achievable within the standard protocol and local unitary operations and the latter is the standard deviation of fidelity over all input states. In this paper, we consider the problem of characterizing two-qubit states that are optimal for quantum teleportation for a given value of some state property. The optimal states are defined as those states that, for a given value of the state property under consideration, achieve the largest maximal fidelity and also exhibit zero fidelity deviation. We provide a complete characterization of optimal states for a given linear entropy, maximum mean value of the Bell-CHSH observable, and concurrence, respectively. We find that for a given linear entropy or Bell-CHSH violation, the largest maximal fidelity states are optimal, but for a given concurrence, the optimal states form a strict subset of the largest maximal fidelity states., Comment: 25 pages; published version

Prior information about the input state can be utilized to enhance the efficiency of quantum teleportation which we quantify using the first two moments of fidelity. The input knowledge is introduced by relaxing the uniformity assumption in the distribution of the input state and considering non-uniform distributions, namely the polar cap and von Mises-Fisher densities. For these distributions,we show that the average fidelity increases while the deviation decreases with the increase of information content about the input ensemble thereby establishing its role as a resource. Our comparative study between these two distributions reveals that for the same amount of information content about inputs, although the average fidelity yield is the same for both, the polar cap distribution is "better" as it offers a smaller deviation. Moreover, we contrast the resource of prior information with other resources involved in the protocol like shared entanglement and classical communication. Specifically, we observe that unlike uniform distribution, the amount of classical communication required to fulfill the task decreases with the increase of information available for inputs. We also investigate the role of prior information in higher (three) dimensional teleportation and report the signatures of dimensional advantage in prior information-based teleportation., Comment: 13 pages, 10 figures

Distribution of quantum entanglement is investigated for an anisotropic quantum XY model with variable range interactions and in the presence of a uniform transverse magnetic field. We report the possibility of \emph{qualitative} growth in the entanglement between distant sites with an increase in the range of interactions that vary either exponentially or polynomially as the distance between the sites increases. Interestingly, we find that such entanglement enhancement is not ubiquitous and is dependent on the factorization points, a specific set of system parameters where the zero-temperature state of the system is fully separable. In particular, we observe that at zero-temperature, when the system parameters are chosen beyond the pair of factorization points, the increments in entanglement length due to variable range interactions are more pronounced compared to the situation when the parameters lie in between the factorization points. By employing the sum of all the bipartite entanglements with respect to a single site, we also show that the shareability of the bipartite entanglements are constrained, thereby establishing their monogamous nature. Furthermore, we note that the factorization points get reallocated depending on the laws of interaction fall-offs and provide an ansatz for the same. We reveal that the temperature at which the canonical equilibrium state becomes entangled from an unentangled one increases with the increase in the range of interactions, thereby demonstrating enhanced robustness in entanglement against temperature in the presence of long-range interactions and only when the system parameters are chosen between the pair of factorization points. We apply an energy-based entanglement witness to provide a justification to the observed robustness with temperature., Comment: v1: 13 pages, 8 figures; v2: 16 pages, 11 figures, new results added, close to the published version

Preserving the robustness of the procedure has, at the present time, become almost a default requirement for statistical data analysis. Since efficiency at the model and robustness under misspecification of the model are often in conflict, it is important to choose such inference procedures which provide the best compromise between these two concepts. Some minimum Bregman divergence estimators and related tests of hypothesis seem to be able to do well in this respect, with the procedures based on the density power divergence providing the existing standard. In this paper we propose a new family of Bregman divergences which is a superfamily encompassing the density power divergence. This paper describes the inference procedures resulting from this new family of divergences, and makes a strong case for the utility of this divergence family in statistical inference., 33 Pages, 6 Figures, 6 Tables

BackgroundParamphistomosis is a pathogenic disease of domesticated ruminants, causing great economic loss in dairy industry and meat production. It is considered as a neglected tropical disease with highest prevalence throughout tropical and subtropical regions, particularly in Africa, Asia, Europe, and Australia. There are few trematocidal drugs available in the market. Most are resistant and have elevated side effects. Therefore, alternative trematocidal drugs need to discover. This study was conducted to evaluate three plants leaf extracts (fromSenna alata,S. alexandrina,andS. occidentalis) as effective remedies against gastrointestinal trematode parasite (Paramphistomum gracile) of ruminants.Live adult parasites were collected in 0.1 M phosphate-buffered saline (PBS) from fresh autopsied goat’s rumen. Parasites were incubated in leaf extracts ofS. alata,S. alexandrinaand,S. occidentalisindividually and in combination (1:1) ratio at 37 ± 1°C. Treatment media contain extracts at different concentrations (10, 20 and 40 mg/mL) in 10 mL of 0.1 M PBS with 1% dimethylsulphoxide (DMSO). Parasites in control group were incubated in PBS without extract. The efficacy of threeSennaextracts was evaluated on the basis of dose-dependent motility and mortality of the trematode. Immediately after paralysis, all treated parasites were collected for histology, SEM and biochemical study.ResultsDose-dependent efficacy was observed in terms of motility and time of mortality in all treated parasites after exposure in various concentrations of theSennaplant extracts.S. occidentalisandS. alexandrinashowed better efficacy in combination than comparing with individual treatment groups. Histological study and scanning electron microscopic observations revealed conspicuous deformity of surface architecture in all treated parasites. Scanning electron micrographs also revealed shrinkage, vacuolization, infoldings and blebbings on the body surface of treated worms. Activities of tegumental enzymes were inhibited in all treatment groups compared to control.ConclusionThe overall findings from this study revealed that all threeSennaleaf extracts individually and in combination showed potential antitrematocidal activity againstParamphistomum gracileby damaging body tegument and neural propagation. Thus, this study confirmed that all threeSennaextracts can be considered as a potential drug-like candidate in indigenous system of traditional medicine against trematode infections in livestock.Graphical abstract

Altered sialylation is generally maintained by a fine balance between sialidases and sialyltransferases, which plays an essential role during disease pathogenesis. TLR4 is a membrane-bound highly sialylated glycoprotein predominantly having α2,3-linked sialic acids. It is one of the most important client molecules in the anti-leishmanial innate immune arm. Here, we initiated a comprehensive study on the modulation of TLR4 sialylation in Leishmania donovani (L. d)-infected macrophages by a mammalian sialidase/neuraminidase-1 (Neu1) having substrate specificity toward α2,3-linked sialic acids. We observed reduced membrane-associated Neu1 with its decreased enzyme activity in infected macrophages. Moreover, we demonstrated reduced association of Neu1 with TLR4 leading to enhanced sialylation of TLR4 in these infected cells. Conversely, Neu1 over expression exhibited enhanced association of TLR4 with Neu1 leading to reduced sialylation which possibly linked to increased association of TLR4 with its downstream adaptor protein, MyD88. This, in turn, activated downstream MAP kinase signaling pathway, with enhanced nuclear translocation of NFκB that resulted in increased genetic and protein levels expression of Th1 cytokines and effector molecule nitric oxide secretion which ultimately leads to reduced parasite burden in macrophages. This was further validated by Neu1 silencing in infected macrophages which reversed such a situation. Such events strongly confirm the importance of Neu1 in modulation of TLR4 sialylation during parasite infection resulting in impairment of innate immune response. Furthermore, decreased membrane-bound Neu1 in infected macrophages could be attributed to its reduced tyrosine-phosphorylation as well as diminished association with cathepsin A. Both these phenomenon possibly play significant roles in inhibiting translocation of the sialidase from cytosol to membrane. Taken together, our study first time demonstrated impaired translocation of cytosolic Neu1 to the membrane of L. donovani-infected macrophages due to impaired phosphorylation of this enzyme. This novel finding establishes a link between enhanced α2,3-linked sialic acids on TLR4 and reduced membrane-bound Neu1 which plays a significant role for inhibiting downstream signaling to establish successful infection in the host cells.

At finite temperatures, the quantum critical region (QCR) emerges as a consequence of the interplay between thermal and quantum fluctuations. We seek for suitable physical quantities, which during dynamics can give prominent response to QCR in the transverse field quantum $XY$ model. We report that the maximum energy absorbed, the nearest neighbor entanglement and the quantum mutual information of the time evolved state after a quench of the transverse magnetic field exhibits a faster fall off with temperature when the initial magnetic field is taken from within the QCR, compared to the choice of the initial point from different phases. We propose a class of dynamical quantifiers, originated from the response of these physical quantities and show that they can faithfully mimic the equilibrium physics, namely detection of the QCR at finite temperatures., 8 pages, 4 figures, close to the published version

Quantum teleportation with an arbitrary two-qubit state can be appropriately characterized in terms of maximal fidelity and fidelity deviation. The former quantifies optimality of the process and is defined as the maximal average fidelity achievable within the standard protocol and local unitary strategies, whereas the latter, defined as the standard deviation of fidelity over all input states, is a measure of fidelity fluctuations. The maximal fidelity for a two-qubit state is known and is given by a simple formula that can be exactly computed, but no such formula is known for the fidelity deviation. In this paper, we derive an exact computable formula for the fidelity deviation in optimal quantum teleportation with an arbitrary state of two qubits. From this formula, we obtain the dispersion-free condition, also known as the universality condition: the condition that all input states are teleported equally well and provide a necessary and sufficient condition for a state to be both useful (maximal fidelity larger than the classical bound) and universal (zero fidelity deviation). We also show that for any given maximal fidelity, larger than the classical bound, there always exist dispersion-free or universal states and argue that such states are the most desirable ones within the set of useful states. We illustrate these results with well-known families of two-qubit states: pure entangled states, Bell-diagonal states, and subsets of $X$ states., 21 pages; minor revisions, references added; accepted for publication in Journal of Physics A; minor typos corrected, published version