A report on <Emphasis Type="Italic">Penicillium</Emphasis> in the intramural and extramural air of residential areas of Nagpur city (India)

Prevalence of different species of Penicillium and their concentrations per cubic meter of air were evaluated with the use of Hi-Air sampler system Mark II (Hi-Media Laboratories Ltd., India) in the air of homes (bed-rooms) at four different sites in Nagpur. At each of these sites, air sampling was done fortnightly in triplicate for 2 years duration from June 2000 to May 2002. The sampling was also done in triplicate for the outdoor air in the vicinity of each home on the same day immediately after the indoor sampling was over. The mean concentration of Penicillium colony forming units at four different sites in the indoor air was 32, 46.9, 35 and 35.4 CFU/m³, respectively, whereas in the outdoor air at these same four sites, the mean concentration was 24, 28, 25 and 25.8 CFU/m³ respectively. The Penicillium concentration in the indoor air was found to be higher in winter than in other seasons (ANOVA, p < 0.05). Concentration of Penicillium spp. in intramural environment was always higher than that in extramural environment. Statistically significant difference existed between intramural and extramural environments at all the sites, with maximum difference at a site, which is old crowded area of the city. During the 2-years investigations, 11 species of Penicillium were isolated from the indoor air while nine species were isolated from the air outside the homes. The dominant species of Penicillium in indoor as well as outdoor air were P. citrinum (33.78 and 32.81), P. oxalicum (19.70 and 22.60), and P. chrysogenum (17.64 and 14.50). The percentage of the Penicillium in the indoor air was 10.70 while it was 8.36 in outdoor air. Indoor air showed the presence of P. glaber and P. sclerotiorum, which were absent in the outdoor air.     

Antibody Profiling by Proteome Microarray with Multiplex Isotype Detection Reveals Overlap between Human and Aotus nancymaae Controlled Malaria Infections

The development of vaccines against malaria and serodiagnostic tests for detecting recent exposure requires tools for antigen discovery and suitable animal models. The protein microarray is a high‐throughput, sample sparing technique, with applications in infectious disease research, clinical diagnostics, epidemiology, and vaccine development. We recently demonstrated Qdot‐based indirect immunofluorescence together with portable optical imager ArrayCAM using single isotype detection could replicate data using the conventional laser confocal scanner system. We developed a multiplexing protocol for simultaneous detection of IgG, IgA, and IgM and compared samples from a controlled human malaria infection model with those from controlled malaria infections of Aotus nancymaae, a widely used non‐human primate model of human malaria. IgG profiles showed the highest concordance in number of reactive antigens; thus, of the 139 antigens recognized by human IgG antibody, 111 were also recognized by Aotus monkeys. Interestingly, IgA profiles were largely non‐overlapping. Finally, on the path toward wider deployment of the portable platform, we show excellent correlations between array data obtained in five independent laboratories around the United States using the multiplexing protocol (R²: 0.60–0.92). This study supports the use of this platform for wider deployment, particularly in endemic areas where such a tool will have the greatest impact on global human health.     

The role of Neuropilin-1 in COVID-19

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.     

Alirocumab,a Therapeutic Human Antibody to PCSK9, Does Not Affect CD81 Levels or Hepatitis C Virus Entry and Replication into Hepatocytes

BackgroundProprotein convertase subtilisin/kexin type 9 (PSCK9) is secreted mainly from the liver and binds to the low-density lipoprotein receptor (LDLR), reducing LDLR availability and thus resulting in an increase in LDL-cholesterol. While the LDLR has been implicated in the cell entry process of the hepatitis C virus (HCV), overexpression of an artificial non-secreted, cell membrane-bound form of PCSK9 has also been shown to reduce surface expression of CD81, a major component of the HCV entry complex, leading to concerns that pharmacological inhibition of PCSK9 may increase susceptibility to HCV infection by increasing either CD81 or LDLR availability. Here, we evaluated effects of PCSK9 and PCSK9 blockade on CD81 levels and HCV entry with a physiologically relevant model using native secreted PCSK9 and a monoclonal antibody to PCSK9, alirocumab.ConclusionThese results suggest that inhibition of PCSK9 with alirocumab has no effect on CD81 and does not result in increased susceptibility to HCV entry.     

Revisiting an Old Riddle: What Determines Genetic Diversity Levels within Species?

Understanding why some species have more genetic diversity than others is central to the study of ecology and evolution, and carries potentially important implications for conservation biology. Yet not only does this question remain unresolved, it has largely fallen into disregard. With the rapid decrease in sequencing costs, we argue that it is time to revive it.What evolutionary forces maintain genetic diversity in natural populations? How do diversity levels relate to census population sizes (Box 1)? Do low levels of diversity limit adaptation to novel selective pressures? Efforts to address such questions spurred the rise of modern population genetics and contributed to the development of the neutral theory of molecular evolution—the null hypothesis for much of evolutionary genetics and comparative genomics [1]–[3]. Yet these questions remain wide open and, for close to two decades, have been neglected [4]. Most notably, little progress has been made to resolve a riddle first pointed out 40 years ago on the basis of allozyme data: the mysteriously narrow range of genetic diversity levels seen across taxa that vary markedly in their census population sizes [5]. This gap in our understanding is glaring, and may hamper efforts at conservation (e.g., [6]).

Box 1. Glossary

Allozymes: Allelic variants of a protein, often detected by differences in gel electrophoresis. Balancing selection: Natural selection that maintains variation longer than expected from genetic drift alone. Census population size: The actual number of individuals in a population; methods to estimate this number vary depending on the species and may involve aerial, transect, or capture/recapture counts. Diversity levels: The measure used here is the probability that a pair of randomly chosen haplotypes differ at a site. Effective population size: The size of an idealized population with some of the same properties as the actual one, e.g., the same rate of genetic drift. Under simplifying assumptions, notably a constant population size and no population structure, this parameter can be estimated from observed diversity levels, given an independent estimate of the mutation rate. Fluctuating selection: When the fitness of an allele changes over time or over space. Genetic draft: A dramatic loss of genetic variation due to strong, frequent selection at nearby sites [8]. Genetic drift: In a finite population, the loss of genetic variation due to the random sampling of gametes at each generation. Local adaptation: Adaptation to a particular environment that is not shared by the entire species. Nearly neutral theory of molecular evolution: A modification of the neutral theory, in which many mutations are slightly deleterious, rather than strictly neutral or strongly deleterious [75]. Neutral theory of molecular evolution: The theory that most genetic variation seen within populations and between species is neutral, and most mutations are either neutral or strongly deleterious [11]. Panmixia: Random mating among individuals, and hence no population structure. Phylogenetically independent contrasts: A statistical method that allows one to compare properties of species controlling for their evolutionary relationship. Purifying (negative) selection: Natural selection that favors the common, fitter allele against rare, deleterious alleles. Selection at linked sites: Selection at sites linked to the locus under consideration, which can affect the population dynamics of alleles at that locus. Silent sites: A general term for synonymous, intronic, and intergenic sites—all sites at which mutations do not change an amino acid. Variation-reducing selection: Selection that leads to a decrease in diversity at linked sites.With the recent technological revolution in sequencing, the data needed to address questions about the determinants of genetic diversity levels are now within reach. As a first step towards reviving these questions, we compile existing estimates of nuclear sequence diversity. These data are highly preliminary, but they underscore how little is known about the narrow span of diversity levels across species or why some species maintain more genetic variation than others [5],[7],[8], and they offer a glimpse of trends that may be worth pursuing.     

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh,India: A community-based,cluster randomized,open-label controlled trial

BackgroundHospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings.Methods and findingsThis was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation.ConclusionsIn this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility–community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function.Trial registrationISRCTN Registry ISRCTN38965585 and Clinical Trials Registry—India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

In a cluster randomized trial, Aarti Kumar and colleagues study the effectiveness of a topical sunflower seed oil therapy in reducing neonatal mortality in Uttar Pradesh, India.     

Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease

Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot (BR) juice would increase plasma NO(2)(-) concentration, increase exercise tolerance, and decrease gastrocnemius fractional O(2) extraction, compared with placebo (PL). This was a randomized, open-label, crossover study. At each visit, subjects (n = 8) underwent resting blood draws, followed by consumption of 500 ml BR or PL and subsequent blood draws prior to, during, and following a maximal cardiopulmonary exercise (CPX) test. Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy. There were no changes from rest for [NO(2)(-)] (152 ± 72 nM) following PL. BR increased plasma [NO(2)(-)] after 3 h (943 ± 826 nM; P ≤ 0.01). Subjects walked 18% longer before the onset of claudication pain (183 ± 84 s vs. 215 ± 99 s; P ≤ 0.01) and had a 17% longer peak walking time (467 ± 223 s vs. 533 ± 233 s; P ≤ 0.05) following BR vs. PL. Gastrocnemius tissue fractional O(2) extraction was lower during exercise following BR (7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units; P ≤ 0.01). Diastolic blood pressure was lower in the BR group at rest and during CPX testing (P ≤ 0.05). These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD.     

HIV-mediated phosphatidylinositol 3-kinase/serine-threonine kinase activation in APCs leads to programmed death-1 ligand upregulation and suppression of HIV-specific CD8 T cells

Recent evidence demonstrates that HIV-1 infection leads to the attenuation of cellular immune responses, which has been correlated with the increased expression of programmed death (PD)-1 on virus-specific CD8(+) T cells. PD-1 is induced upon T cell activation, and its prolonged expression facilitates CD8(+) T cell inhibitory signals when bound to its B7 family ligands, PD-ligand (L)1/2, which are expressed on APCs. Importantly, early reports demonstrated that blockade of the PD-1/PD-L interaction by Abs may help to counter the development of immune exhaustion driven by HIV viral persistence. To better understand the regulation of the PD-1 pathway during HIV infection, we examined the ability of the virus to induce PD-L expression on macrophages and dendritic cells. We found a direct relationship between the infection of APCs and the expression of PD-L1 in which virus-mediated upregulation induced a state of nonresponsiveness in uninfected HIV-specific T cells. Furthermore, this exhaustion phenotype was revitalized by the blockade of PD-L1, after which T cells regained their capacity for proliferation and the secretion of proinflammatory cytokines IFN-γ, IL-2, and IL-12 upon restimulation. In addition, we identify a critical role for the PI3K/serine-threonine kinase signaling pathway in PD-L1 upregulation of APCs by HIV, because inhibition of these intracellular signal transducer enzymes significantly reduced PD-L1 induction by infection. These data identify a novel mechanism by which HIV exploits the immunosuppressive PD-1 pathway and suggest a new role for virus-infected cells in the local corruption of immune responses required for viral suppression.     

Versatility of thermoluminescence materials and radiation dosimetry – A review

Thermoluminescence (TL) materials exhibit a wide range of applications in different areas such as personal dosimetry, environmental dosimetry, medical research etc. Doping of different rare earth impurities in different hosts is responsible for changing the properties of materials useful for various applications in different fields. These materials can be irradiated by different types of beams such as γ‐rays, X‐rays, electrons, neutrons etc. Various radiation regimes, as well as their dose–response range, play an important role in thermoluminescence dosimetry. Several TL materials, such as glass, microcrystalline, nanostructured inorganic materials and recently developed materials, are reviewed and described in this article.