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The complex involvement of neutrophils in inflammatory diseases makes them intriguing but challenging targets for therapeutic intervention. Here, we tested the hypothesis that varying endocytosis capacities would delineate functionally distinct neutrophil subpopulations that could be specifically targeted for therapeutic purposes. By using uniformly sized (∼120 nm in diameter) albumin nanoparticles (ANP) to characterize mouse neutrophils

TLR4 signaling via endotoxemia in macrophages promotes macrophage transition to the inflammatory phenotype through NLRP3 inflammasome activation. This transition event has the potential to trigger acute lung injury (ALI). However, relatively little is known about the regulation of NLRP3 and its role in the pathogenesis of ALI. Here we interrogated the signaling pathway activated by CD38, an ectoenzyme expressed in macrophages, in preventing ALI through suppressing NLRP3 activation. Wild-type and Cd38-knockout (Cd38(−/−)) mice were used to assess inflammatory lung injury, and isolated macrophages were used to delineate underlying TLR4 signaling pathway. We showed that CD38 suppressed TLR4 signaling in macrophages by inhibiting Bruton’s tyrosine kinase (Btk) through the recruitment of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) and resulting in the dephosphorylation of activated Btk. Cd38(−/−) mice show enhanced lung polymorphonuclear leukocyte extravasation and severe lung injury. LPS- or polymicrobial sepsis-induced mortality in Cd38(−/−) mice were markedly augmented compared with wild types. CD38 in macrophages functioned by inhibiting Btk activation through activation of SHP2 and resulting dephosphorylation of Btk, and thereby preventing activation of downstream targets NF-κB and NLRP3. Cd38(−/−) macrophages displayed markedly increased activation of Btk, NF-κB, and NLRP3, whereas in vivo administration of the Btk inhibitor ibrutinib (a Food and Drug Administration-approved drug) prevented augmented TLR4-induced inflammatory lung injury seen in Cd38(−/−) mice. Our findings together show upregulation of CD38 activity and inhibition of Btk activation downstream of TLR4 activation as potential strategies to prevent endotoxemic ALI.

The engineering of virus-like particles (VLPs) is a viable strategy for the development of vaccines and for the identification of therapeutic targets without using live viruses. Here, we report the generation and characterization of quadruple-antigen SARS-CoV-2 VLPs. VLPs were generated by transient transfection of two expression cassettes in adherent HEK293T cells─one cassette containing M

The pathogenesis of lung fibrosis involves hyperactivation of innate and adaptive immune pathways that release inflammatory cytokines and growth factors such as tumor growth factor (TGF)β1 and induce aberrant extracellular matrix protein production. During the genesis of pulmonary fibrosis, resident alveolar macrophages are replaced by a population of newly arrived monocyte-derived interstitial macrophages that subsequently transition into alveolar macrophages (Mo-AMs). These transitioning cells initiate fibrosis by releasing profibrotic cytokines and remodeling the matrix. Here, we describe a strategy for leveraging the up-regulation of the mannose receptor CD206 in interstitial macrophages and Mo-AM to treat lung fibrosis. We engineered mannosylated albumin nanoparticles, which were found to be internalized by fibrogenic CD206+ monocyte derived macrophages (Mo-Macs). Mannosylated albumin nanoparticles incorporating TGFβ1 small-interfering RNA (siRNA) targeted the profibrotic subpopulation of CD206+ macrophages and prevented lung fibrosis. The findings point to the potential utility of mannosylated albumin nanoparticles in delivering TGFβ-siRNA into CD206+ profibrotic macrophages as an antilung fibrosis strategy.

During the 1991 Gulf War, oil wells in the oil fields of Kuwait were set aflame and destroyed. This resulted in severe crude oil pollution of the countries only fresh water aquifers. Here, for the first time the natural attenuation and biodegradation of the persisting groundwater contamination was investigated to assess potential processes in the aquifer. Biodegradation experiments were conducted under aerobic and multiple anaerobic conditions using microcosms of the contaminated groundwater from Kuwait. Under the conditions tested, a portion of the total petroleum hydrocarbon (TPH) component was degraded, however there was only a slight change in the bulk concentration of the contaminant measured as dissolved organic carbon (DOC), suggesting the presence of a recalcitrant pollutant. Changes in the associated microbial community composition under different reduction-oxidation conditions were observed and known hydrocarbon degraders identified. The results of this study indicate that lingering contaminant still persists in the groundwater and is recalcitrant to further biodegradation, which presents challenges for future remediation plans.

We test the Grumiller's quantum motivated modified gravity model, which at large distances modifies the Newtonian potential and describes the galactic rotation curves of disk galaxies in terms of a Rindler acceleration term without the need of any dark matter, against the baryonic Tully-Fisher feature that relates the total baryonic mass of a galaxy with flat rotation velocity of the galaxy. We estimate the Rindler acceleration parameter from observed baryonic mass versus rotation velocity data of a sample of sixty galaxies. Grumiller's model is found to describe the observed data reasonably well., 4 pages, two figures, To appear in Gravitation and Cosmology

Inflammatory tissue injury such as acute lung injury (ALI) is a disorder that leads to respiratory failure, a major cause of morbidity and mortality worldwide. Excessive neutrophil influx is a critical pathogenic factor in the development of ALI. Here, we identify the subset of neutrophils that is responsible for ALI and lethality in polymicrobial sepsis. The pro-inflammatory neutrophil subpopulation was characterized by its unique ability to endocytose albumin nanoparticles (ANP), upregulation of pro-inflammatory cytokines and chemokines as well as the excessive production of reactive oxygen species (ROS) in models of endotoxemia and septicemia. ANP delivery of the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, to the susceptible subset of neutrophils, prevented ALI and mortality in mice subjected to polymicrobial infection. Targeted inhibition of Syk in ANP-susceptible neutrophils had no detrimental effect on neutrophil-dependent host defense because the subset of ANPlowneutrophils effectively controlled polymicrobial infection. The results show that neutrophil heterogeneity can be leveraged therapeutically to prevent ALI without compromising host defense.

Previously, we showed that Rab5a and Rab5b differentially regulate fluid-phase and receptor-mediated endocytosis in Leishmania, respectively. To unequivocally demonstrate the role of Rab5b in hemoglobin endocytosis in Leishmania, we generated null-mutants of Rab5b parasites by sequentially replacing both copies of LdRab5b with the hygromycin and neomycin resistance gene cassettes. LdRab5b−/− null-mutant parasite was confirmed by qPCR analysis of genomic DNA using LdRab5b specific primers. LdRab5b−/− cells showed severe growth defect indicating essential function of LdRab5b in parasite. To characterize the role of Rab5b in Hb endocytosis in parasites, LdRab5b−/− cells were rescued by exogenous addition of hemin in growth medium. Our results showed that LdRab5b−/− cells are relatively smaller in size. Ultrastructural analysis revealed the presence of relatively enlarged flagellar pocket and bigger intracellular vesicles in these cells in comparison to control cells. Both promastigotes and amastigotes of Rab5b null-mutant parasites were unable to internalize Hb but fluid phase endocytosis of different markers was not affected. However, complementation of LdRab5b:WT in LdRab5b−/− cells (LdRab5b−/−:pRab5b:WT) rescued Hb internalization in these cells. Interestingly, LdRab5b−/− cells showed significantly less Hb-receptor on cell surface in comparison to control cells indicating a block in HbR trafficking. Finally, we showed that LdRab5b−/− parasites can infect the macrophages but are unable to survive after 96 h of infection in comparison to control cells. However, supplementation of hemin in the growth medium significantly rescued LdRab5b−/− Leishmania survival in macrophage indicating that LdRab5b function is essential for the acquisition of heme from internalized Hb for the survival of Leishmania.

Intracellular pathogens can modulate host Rabs and SNAREs to support their replication and immune evasion. Singh et al. show that the Salmonella effector SipA functionally mimics an R-SNARE and recruits host Q-SNAREs to promote membrane fusion. Thus, SNARE mimicry by this intracellular pathogen effector modulates the host trafficking machinery for Salmonella survival., SipA is a major effector of Salmonella, which causes gastroenteritis and enteric fever. Caspase-3 cleaves SipA into two domains: the C-terminal domain regulates actin polymerization, whereas the function of the N terminus is unknown. We show that the cleaved SipA N terminus binds and recruits host Syntaxin8 (Syn8) to Salmonella-containing vacuoles (SCVs). The SipA N terminus contains a SNARE motif with a conserved arginine residue like mammalian R-SNAREs. SipAR204Q and SipA1–435R204Q do not bind Syn8, demonstrating that SipA mimics a cognate R-SNARE for Syn8. Consequently, Salmonella lacking SipA or that express the SipA1–435R204Q SNARE mutant are unable to recruit Syn8 to SCVs. Finally, we show that SipA mimicking an R-SNARE recruits Syn8, Syn13, and Syn7 to the SCV and promotes its fusion with early endosomes to potentially arrest its maturation. Our results reveal that SipA functionally substitutes endogenous SNAREs in order to hijack the host trafficking pathway and promote Salmonella survival.

Leishmania donovani possess two isoforms of Rab5 (Rab5a and Rab5b), which are involved in fluid phase and receptor-mediated endocytosis, respectively. We have characterized the solution structure and dynamics of a stabilized truncated LdRab5a mutant. For the purpose of NMR structure determination, protein stability was enhanced by systematically introducing various deletions and mutations. Deletion of hypervariable C-terminal and the 20 residues LdRab5a specific insert slightly enhanced the stability, which was further improved by C107S mutation. The final construct, truncated LdRab5a with C107S mutation, was found to be stable for longer durations at higher concentration, with an increase in melting temperature by 10°C. Solution structure of truncated LdRab5a shows the characteristic GTPase fold having nucleotide and effector binding sites. Orientation of switch I and switch II regions match well with that of guanosine 5'-(β, γ-imido)triphosphate (GppNHp)-bound human Rab5a, indicating that the truncated LdRab5a attains the canonical GTP bound state. However, the backbone dynamics of the P-loop, switch I, and switch II regions were slower than that observed for guanosine 5'-(β, γ-imido)triphosphate (GMPPNP)-bound H-Ras. This dynamic profile may further complement the residue-specific complementarity in determining the specificity of interaction with the effectors. In parallel, biophysical investigations revealed the urea induced unfolding of truncated LdRab5a to be a four-state process that involved two intermediates, I1 and I2. The maximal 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (Bis-ANS) binding was observed for I2 state, which was inferred to have molten globule like characteristics. Overall, the strategy presented would have significant impact for studying other Rab and small GTPase proteins by NMR spectroscopy.

Multiparticle emission data in nucleus–nucleus collisions are studied in a graph theoretical approach. The sandbox algorithm used to analyze complex networks is employed to characterize the multifractal properties of the visibility graphs associated with the pseudorapidity distribution of charged particles produced in high-energy heavy-ion collisions. Experimental data on 28Si+Ag/Br interaction at laboratory energy E lab = 14 . 5 A GeV, and 16O+Ag/Br and 32S+Ag/Br interactions both at E lab = 200 A GeV, are used in this analysis. We observe a scale free nature of the degree distributions of the visibility and horizontal visibility graphs associated with the event-wise pseudorapidity distributions. Equivalent event samples simulated by ultra-relativistic quantum molecular dynamics, produce degree distributions that are almost identical to the respective experiment. However, the multifractal variables obtained by using sandbox algorithm for the experiment to some extent differ from the respective simulated results.

We present a simulation study on the dynamical fluctuations of conserved charges in a baryon-rich environment that is expected to be created in high-energy nucleus–nucleus (AB) collisions. Microscopic transport models like the ultra-relativistic quantum molecular dynamics and a multi-phase transport model are used to generate Au + Au collision events at an incident beam energy of 30 A GeV in the laboratory system. We investigate the centrality and rapidity window size dependence of the event-by-event (e-by-e) fluctuations of the multiplicity ratios of particles belonging to different species. It is observed that e-by-e dynamical fluctuations in the K/π, K/p and π/p ratios diminish with increasing centrality. Our results in this regard indicate that an AB collision can not be viewed as a mere superposition of many incoherent nucleon–nucleon (NN) collisions. Similarly, due to diffusion process the dynamical fluctuations get diluted with increasing window size of rapidity. The simulation results in general could be interpreted in terms of conventional mechanisms of particle production like resonance decays. Our simulation based analysis provides a useful reference baseline to the compressed baryonic matter experiment to be held at the Facility for Antiproton and Ion Research (FAIR).

Non-minimally coupled global monopole or a Schwarzschild black hole that swallowed a global monopole at the center of a galaxy can correctly describe the observed flat rotation curve of galaxies without the need of dark matter. To become a viable alternative to dark matter the global monopole based model also needs to explain the other observations hinting for the existence of dark matter. Here we have studied weak gravitational lensing due to Schwarzchild space time with global monopole and compare with the findings of galaxy-galaxy weak lensing and also the lensing observations of the rich galaxy cluster Abell 370. We find that global monopole based model cannot describe the mentioned lensing observations without the presence of dark matter.

Metalloprotease gp63 (Leishmania donovani gp63 (Ldgp63)) is a critical virulence factor secreted by Leishmania. However, how newly synthesized Ldgp63 exits the endoplasmic reticulum (ER) and is secreted by this parasite is unknown. Here, we cloned, expressed, and characterized the GTPase LdSar1 and other COPII components like LdSec23, LdSec24, LdSec13, and LdSec31 from Leishmania to understand their role in ER exit of Ldgp63. Using dominant-positive (LdSar1:H74L) and dominant-negative (LdSar1:T34N) mutants of LdSar1, we found that GTP-bound LdSar1 specifically binds to LdSec23, which binds, in turn, with LdSec24(1–702) to form a prebudding complex. Moreover, LdSec13 specifically interacted with His6–LdSec31(1–603), and LdSec31 bound the prebudding complex via LdSec23. Interestingly, dileucine 594/595 and valine 597 residues present in the Ldgp63 C-terminal domain were critical for binding with LdSec24(703–966), and GFP–Ldgp63L594A/L595A or GFP–Ldgp63V597S mutants failed to exit from the ER. Moreover, Ldgp63-containing COPII vesicle budding from the ER was inhibited by LdSar1:T34N in an in vitro budding assay, indicating that GTP-bound LdSar1 is required for budding of Ldgp63-containing COPII vesicles. To directly demonstrate the function of LdSar1 in Ldgp63 trafficking, we coexpressed RFP–Ldgp63 along with LdSar1:WT–GFP or LdSar1:T34N–GFP and found that LdSar1:T34N overexpression blocks Ldgp63 trafficking and secretion in Leishmania. Finally, we noted significantly compromised survival of LdSar1:T34N–GFP–overexpressing transgenic parasites in macrophages. Taken together, these results indicated that Ldgp63 interacts with the COPII complex via LdSec24 for Ldgp63 ER exit and subsequent secretion.

In this work the space-time geometry of the halo region in spiral galaxies is obtained considering the observed flat galactic rotation curve feature, invoking the Tully-Fisher relation and assuming the presence of cold dark matter in the galaxy. The gravitational lensing analysis is performed treating the so obtained space-time as a gravitational lens. It is found that the aforementioned space-time as the gravitational lens can consistently explain the galaxy-galaxy weak gravitational lensing observations and the lensing observations of the well-known Abell 370 galaxy cluster., 17 pages, 1 figure, to appear in IJMPD

The expression of gravitational time advancement (negative time delay) for particles with non-zero mass in Schwarzschild geometry has been obtained. The influences of the gravitational field that describes the observed rotation curves of spiral galaxies and that of dark energy (in the form of cosmological constant) on time advancement of particles have also been studied. The present findings suggest that in presence of dark matter gravitational field the time advancement may take place irrespective of gravitational field of the observer, unlike the case of pure Schwarzschild geometry where gravitational time advancement takes place only when the observer is situated at stronger gravitational field compare to the gravitational field encountered by the particle during its journey. When applied to the well known case of SN 1987a, it is found that the net time delay of a photon/gravitational wave is much smaller than quoted in the literature. In the presence of dark matter field, the photon and neutrinos from SN 1987a should have been suffered gravitational time advancement rather than the delay., Comment: 13 pages, 1 figure

Immune memory has been well-established in adaptive immunity but recent studies suggest a key for memory in innate immunity. However, the precise mechanisms and phenotypes of innate immune memory in macrophages remain poorly understood. Here, we studied the memory responses of lung alveolar macrophages (AMs) exposed consecutively (2 exposures, one week apart) intratracheally to the bacterial endotoxin lipopolysaccharide (LPS). We observed a 60%–80% loss of AMs following the initial LPS exposure, consistent with the known cell death of resident AMs during severe inflammatory injury followed by gradual replenishment. Importantly, AM loss following the second LPS injury was markedly attenuated. Lineage tracing using a CX3CR1-monocyte reporter showed no increase in monocyte-derived AMs, thus suggesting that the higher AM numbers after the second LPS exposure were due to greater resilience of AMs and not due to rapid replenishment by circulating monocytes. RNA-Seq analysis of showed higher expression of pro-survival genes and anti-inflammatory cytokines such as IL-10 in memory AMs (post 1 week LPS) than in naïve AMs. Ex vivo and in vivo functional assay showed that these memory AMs demonstrated enhanced efferocytosis of cellular debris, consistent with a pro-resolving phenotype. We also found upregulation of the transcription factor KLF4 which promotes cell survival as well as pro-resolving macrophage polarization. Our findings suggest that alveolar macrophages are reprogrammed by an initial inflammatory exposure to increase their resilience to pro-apoptotic stimuli and to promote resolution of inflammation. Such a memory mechanism could be leveraged therapeutically in severe inflammatory diseases.

Correlation among singly charged particles emitted in the forward and backward pseudo-rapidity cones is measured in [Formula: see text]O-Ag/Br and [Formula: see text]S-Ag/Br interactions at an incident energy of [Formula: see text] GeV/nucleon. Event-by-event fluctuations in the charged particle multiplicities and their pseudo-rapidity values are also investigated in terms of some known statistical measures. Evidences of short-ranged particle correlation and cluster formation in the pseudo-rapidity space are found from our analysis. A microscopic transport model based on the Ultra-relativistic Quantum Molecular Dynamics could not match the experimental results. The differences between experimental observation and corresponding simulation could neither be accounted for even when a Bose–Einstein type of correlation effect is implemented into the simulated data.

Differential functions of Rab5 isoforms in endocytosis are not well characterized. Here, we cloned, expressed, and characterized Rab5a and Rab5b from Leishmania and found that both of them are localized in the early endosome. To understand the role of LdRab5 isoforms in different modes of endocytosis in Leishmania, we generated transgenic parasites overexpressing LdRab5a, LdRab5b, or their dominant-positive (LdRab5a:Q93L and LdRab5b:Q80L) or dominant-negative mutants (LdRab5a:N146I and LdRab5b:N133I). Using LdRab5a or its mutants overexpressing parasites, we found that LdRab5a specifically regulates the fluid-phase endocytosis of horseradish peroxidase and also specifically induced the transport of dextran-Texas Red to the lysosomes. In contrast, cells overexpressing LdRab5b or its mutants showed that LdRab5b explicitly controls receptor-mediated endocytosis of hemoglobin, and overexpression of LdRab5b:WT enhanced the transport of internalized Hb to the lysosomes in comparison with control cells. To unequivocally demonstrate the role of Rab5 isoforms in endocytosis in Leishmania, we tried to generate null-mutants of LdRab5a and LdRab5b parasites, but both were lethal indicating their essential functions in parasites. Therefore, we used heterozygous LdRab5a(+/-) and LdRab5b(+/-) cells. LdRab5a(+/-) Leishmania showed 50% inhibition of HRP uptake, but hemoglobin endocytosis was uninterrupted. In contrast, about 50% inhibition of Hb endocytosis was observed in LdRab5b(+/-) cells without any significant effect on HRP uptake. Finally, we tried to identify putative LdRab5a and LdRab5b effectors. We found that LdRab5b interacts with clathrin heavy chain and hemoglobin receptor. However, LdRab5a failed to interact with the clathrin heavy chain, and interaction with hemoglobin receptor was significantly less. Thus, our results showed that LdRab5a and LdRab5b differentially regulate fluid phase and receptor-mediated endocytosis in Leishmania.

Fluctuations in particle density functions in 28 Si+Ag(Br) collision at 14.5A GeV and 32 S+Ag(Br) collision at 200A GeV are investigated using the multifractal detrended moving average (MFDMA) method. Multifractal parameters obtained from the data analysis are systematically compared with the ultra-relativistic quantum molecular dynamics (UrQMD) model simulation. It is found that the single particle density functions in both the experiments are multifractal in nature. Further, the degree of multifractality in the simulated event samples is almost equal to the corresponding empirical data. The results of this analysis differ significantly from those obtained from other conventional techniques of multifractal analysis previously used for the same sets of data.

Leishmania secretes a large number of its effectors to the extracellular milieu. However, regulation of the secretory pathway in Leishmania is not well characterized. Here, we report the cloning, expression, and characterization of the Rab1 homologue from Leishmania. We have found that LdRab1 localizes in Golgi in Leishmania. To understand the role of LdRab1 in the secretory pathway of Leishmania, we have generated transgenic parasites overexpressing GFP-LdRab1:WT, GFP-LdRab1:Q67L (a GTPase-deficient dominant positive mutant of Rab1), and GFP-LdRab1:S22N (a GDP-locked dominant negative mutant of Rab1). Surprisingly, our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N does not disrupt the trafficking and localization of hemoglobin receptor in Leishmania. To determine whether the Rab1-dependent secretory pathway is conserved in parasites, we have analyzed the role of LdRab1 in the secretion of secretory acid phosphatase and Ldgp63 in Leishmania. Our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N significantly inhibits the secretion of secretory acid phosphatase by Leishmania. We have also found that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N retains RFP-Ldgp63 in Golgi and blocks the secretion of Ldgp63, whereas the trafficking of RFP-Ldgp63 in GFP-LdRab1:WT-expressing cells is unaltered in comparison with control cells. Taken together, our results have shown that the Rab1-regulated secretory pathway is well conserved, and hemoglobin receptor trafficking follows an Rab1-independent secretory pathway in Leishmania.

During the First Gulf War (1991) a large number of oil wells were destroyed and oil fires subsequently extinguished with seawater. As a result Kuwait's sparse fresh groundwater resources were severely contaminated with crude oil. Since then limited research has focused on the microbial community ecology of the groundwater and their impact on the associated contamination. Here, the microbial community ecology (bacterial, archaeal and eukaryotic) and how it relates to the characteristics of the hydrocarbon contaminants were examined for the first time since the 1991 event. This study was conducted using 15 wells along the main groundwater flow direction and detected several potential hydrocarbon degrading microorganisms such as Hyphomicrobiaceae, Porphyromonadaceae and Eurotiomycetes. The beta diversity of the microbial communities correlated significantly with total petroleum hydrocarbon (TPH) concentrations and salinity. The TPH consisted mainly of polar compounds present as an unresolved complex mixture (UCM) of a highly recalcitrant nature. Based on the proportions of TPH to dissolved organic carbon (DOC), the results indicate that some minor biodegradation has occurred within highly contaminated aquifer zones. However, overall the results from this study suggest that the observed variations in TPH concentrations among the sampled wells are mainly induced by mixing/dilution with pristine groundwater rather than by biodegradation of the contaminants. The findings make an important contribution to better understand the fate of the groundwater pollution in Kuwait, with important implications for the design of future remediation efforts.

Groundwater constitutes an important natural resource in Kuwait and thus requires effective management policies based on a sound knowledge of its flow, recharge, and factors affecting the quality of the water. An assessment of the flow and water quality changes of the southern Kuwait groundwaters over the past decades was made based on the available hydrogeological, hydrochemical, pumping and tracer tests, and environmental isotopes data. The predevelopment potentiometric surface of the Dammam aquifer was higher than that of the Kuwait Group aquifer. The Dammam groundwater is old and no recharge occurred in Kuwait during pre-development times. The Kuwait Group aquifer was recharged mainly by an upward leakage from the Dammam aquifer, with local recharge largely restricted to the Dibdibba depressions. The continuous groundwater pumping has resulted in the reversal of flow direction. The salinity of the Dammam aquifer at Al-Shegaya and Umm-Gudair has been relatively stable since 1960, whereas the Kuwait Group aquifer has a stable to freshening trend.

Azimuthal distributions of radial velocities of charged hadrons produced in nucleus-nucleus $(AB)$ collisions are compared with the corresponding azimuthal distribution of charged hadron multiplicity in the framework of a multiphase transport (AMPT) model at two different collision energies. The mean radial velocity seems to be a good probe for studying radial expansion. While the anisotropic part of the distributions indicates a kind of collective nature of radial expansion, the isotropic part characterizes a thermal motion. The present investigation is carried out keeping the upcoming Compressed Baryonic Matter (CBM) experiment to be held at the Facility for Anti-proton Ion Research (FAIR) in mind. As far as high-energy heavy-ion interactions are concerned, CBM will supplement the Relativistic Heavy Ion Collider (RHIC) and Large Hadron Collider (LHC) experiments. In this context our simulation results at high baryochemical potential would be interesting, when scrutinized from the perspective of almost a baryon free environment achieved at RHIC and LHC., Comment: 6 pages, 8 figures

We have studied the dynamical fluctuation of net charge of hadrons produced in Au+Au collisions at energies that in near future will be available at the Facility for Antiproton and Ion Research (FAIR). Data simulated by a microscopic transport model based on ultrarelativistic quantum molecular dynamics are analyzed for this purpose. The centrality and pseudorapidity dependence of the net-charge fluctuation of hadrons are examined. Our simulated results are compared with the results available for nucleus-nucleus collision experiments held at similar energies. The gross features of our simulated results on net-charge fluctuations are found to be consistent with the experiment. At incident beam energy ${E}_{\mathrm{lab}}=10A$ GeV, the magnitude of net-charge fluctuation is very large, and in comparison with the rest its centrality dependence appears to be a little unusual. The effect of global charge conservation is expected to be very crucial at FAIR energies. The charge fluctuations measured with varying pesudorapidity window size depend on the collision centrality. The dependence is, however, exactly opposite in nature to that observed in the Pb+Pb collision at $\sqrt{{s}_{{}_{NN}}}=2.76$ TeV.

a b s t r a c t The detrended fluctuation analysis (DFA) and the multifractal DFA (MF-DFA) techniques are employed to characterize the pseudorapidity (η) distribution of charged mesons pro- duced in 28 Si + Ag/Br interaction at 14.5 GeV/nucleon and 32 S + Ag/Br interaction at 200 GeV/nucleon. Various multifractal parameters are calculated and compared with a Monte- Carlo simulation based on the ultra-relativistic quantum molecular dynamics (UrQMD) model. The results of this analysis show that the single particle distributions in both ex- periments and in their respective UrQMD simulations are multifractal in nature. The dif- ferences between the experiment and corresponding simulation however, are not always very significant. But the present results are significantly different from those obtained by using other conventional methods of multifractal analysis. The observations also indicate that the detrended multifractal analysis might be an efficient tool for characterizing the multiparticle emission data, but the method requires some improvement so that it can dif- ferentiate between the non-statistical signal and the statistical noise.

Various flow effects of nuclear and hadronic origin are investigated in nucleus-nucleus collisions. Nuclear emulsion data collected from 84Kr + Ag/Br interaction at an incident energy of 1.52 GeV per nucleon and from 28Si + Ag/Br interaction at an incident energy of 14.5 GeV per nucleon are used in the investigation. The transverse momentum distribution and the flow angle analysis show that collective behavior, like a bounce-off effect of the projectile spectators and a sidesplash effect of the target spectators, are present in our event samples. From an azimuthal angle analysis of the data we also see a direct flow of the projectile fragments and of the produced charged particles. On the other hand, for both data samples the target fragments exhibit a reverse flow, while the projectile fragments exhibit an elliptic flow. Relevant flow parameters are measured.

Anisotropic flow of hadronic matter is considered as a sensitive tool to detect the early stage dynamics of high-energy heavy-ion collisions. Taking the event by event fluctuations of the collision geometry into account, the elliptic flow parameter and the triangular flow parameter derived from the azimuthal distribution of produced hadrons, are investigated within the framework of a multiphase transport (AMPT) model, at a collision energy that in near future will typically be available at the Facility for Antiproton and Ion Research. The dependence of elliptic and triangular flow parameters on initial fluctuations, on parton scattering cross-sections, their mass ordering on different hadron species and on the constituent quark number scaling are examined. The AMPT simulation can not exactly match the elliptic flow results on Pb + Pb collision at 40A GeV of the NA49 experiment. The simulation results presented in this work are expected to provide us with an insight to study flow properties at high baryonic density but moderate temperature, and also with an opportunity to compare similar results available from RHIC and LHC experiments., Comment: 10 pages, 19 figures

Several intracellular pathogens arrest the phagosome maturation in the host cells to avoid transport to lysosomes. In contrast, the Leishmania containing parasitophorous vacuole (PV) is shown to recruit lysosomal markers and thus Leishmania is postulated to be residing in the phagolysosomes in macrophages. Here, we report that Leishmania donovani specifically upregulates the expression of Rab5a by degrading c-Jun via their metalloprotease gp63 to downregulate the expression of miR-494 in THP-1 differentiated human macrophages. Our results also show that miR-494 negatively regulates the expression of Rab5a in cells. Subsequently, L. donovani recruits and retains Rab5a and EEA1 on PV to reside in early endosomes and inhibits transport to lysosomes in human macrophages. Similarly, we have also observed that Leishmania PV also recruits Rab5a by upregulating its expression in human PBMC differentiated macrophages. However, the parasite modulates the endosome by recruiting Lamp1 and inactive pro-CathepsinD on PV via the overexpression of Rab5a in infected cells. Furthermore, siRNA knockdown of Rab5a or overexpression of miR-494 in human macrophages significantly inhibits the survival of the parasites. These results provide the first mechanistic insights of parasite-mediated remodeling of endo-lysosomal trafficking to reside in a specialized early endocytic compartment., Author summary Leishmania donovani causes visceral leishmaniasis in human. This parasite is thought to reside and replicate in a phagolysosomal compartment in macrophages. But, how Leishmania survives in such a detrimental compartment in macrophages is not known. In contrast, most of the intracellular pathogens avoid targeting to lysosomes in the host cells. We have found that Leishmania upregulates the expression of Rab5a, an early endosomal protein, by downregulating the expression of miR-494 in infected human macrophage as a consequence of gp63-dependent degradation of c-Jun. Subsequently, parasites recruit and retain Rab5a and EEA1 on their parasitophorous vacuoles demonstrating that Leishmania resides in the early endosomal compartment and consequently inhibits their transport to the lysosomes. However, we have found that parasites also recruit Lamp1 and inactive pro-CathepsinD on PV which led to previous conclusion that Leishmania resides in the phagolysosomal compartment. We have also shown that parasites block the processing of the lysosomal enzymes in the early endosomal compartment by overexpressing Rab5a which also helps the parasites to survive in human macrophages. Finally, we have shown that overexpression of Rab5a by downregulating miR-494 in macrophages is essential for parasite survival. These results unequivocally prove that L. donovani resides in a modified early compartment in human macrophages.

Groundwater in North Kuwait was polluted by hydrocarbons from destroyed oil wells during the 1991 Gulf War, and by salts derived from seawater used for fighting oil fires. The results of eight rounds of monitoring the groundwater chemistry over the years 2012–2015 have been assessed, based mainly on the presence of organic matter derived from petroleum hydrocarbons and on the total dissolved solids content of groundwater. Good correlations between these two parameters suggest that there is simultaneous movement of hydrocarbons and salts that are leached from the surface soil by the infiltration of surface runoff. It has been concluded that although these parameters have shown some periodical fluctuations in their values, there has been no significant change in the overall extent and severity of groundwater contamination over the period of the study. The fluctuations observed are possibly the results of seasonal addition of pollutants that are carried downwards by the infiltration of rainfall; the effects of biogeochemical reactions within the aquifer; and the movement of pollutants with groundwater flow and dilution by mixing with unpolluted groundwater within the aquifer. The removal of the sources of pollution (oil lakes, oil pits and polluted surface soil) from the study area has been recommended before the adoption of any remedial measures to avoid seasonal addition of pollutants to the treated groundwater.

Centrality and system geometry dependence of azimuthal anisotropy of charged hadrons measured in terms of the elliptic flow parameter are investigated using Au+Au event samples at incident beam energy $20\mathrm{A}$ and $40\mathrm{A}\phantom{\rule{0.16em}{0ex}}\mathrm{GeV}$ generated by ultrarelativistic quantum molecular dynamics (UrQMD) and a multiphase transport (AMPT) models. The Monte Carlo--Glauber model is employed to estimate the eccentricity of the overlapping zone at an early stage of the collisions. Anisotropies present both in the particle multiplicity distribution and in the kinetic radial expansion are examined by using standard statistical and phenomenological methods. In the context of the upcoming Compressed Baryonic Matter experiment to be held at the Facility for Antiproton and Ion Research (FAIR), the present set of simulated results provide us not only with an opportunity to examine the expected collective behavior of hadronic matter at high baryon density and moderate temperature, but when compared with similar results obtained from Relativistic Heavy Ion Collider (RHIC) and Large Hadron Collider (LHC) experiments, they also allow us to investigate how anisotropy of hadronic matter may differ or agree with its low-baryon-density and high-temperature counterpart.

The multifractal detrended fluctuation analysis technique is employed to analyze the time series of gold consumer price index (CPI) and the market trend of three world's highest gold consuming countries, namely China, India and Turkey for the period: 1993-July 2013. Various multifractal variables, such as the generalized Hurst exponent, the multifractal exponent and the singularity spectrum, are calculated and the results are fitted to the generalized binomial multifractal (GBM) series that consists of only two parameters. Special emphasis is given to identify the possible source(s) of multifractality in these series. Our analysis shows that the CPI series and all three market series are of multifractal nature. The origin of multifractality for the CPI time series and Indian market series is found due to a long-range time correlation, whereas it is mostly due to the fat-tailed probability distributions of the values for the Chinese and Turkey markets. The GBM model series more or less describes all the time series analyzed here., 20 pages, 7 figures, 1 table