THE IMPACT OF CLIMATE CHANGE ON INFECTIOUS DISEASES: A COMPREHENSIVE ANALYSIS OF VECTOR-BORNE DISEASES, WATER-BORNE DISEASES, AND PUBLIC HEALTH STRATEGIES.

Climate change is long-term modifications to weather patterns and a rise in extreme weather events. It might modify the hazard to human health and exacerbate current problems. The article explores the scientific data in a description of the effects of Infectious diseases in humans and climate change. It identifies scientific advancements and gaps in potential responses from human civilization and how it might prepare for the changes that come with it by adjusting to them. The impact reflects three aspects, such as climate variables, selected infectious diseases, and infectious disease components. This study demonstrates how vulnerable people are to any ill consequences that climate change may have on their health. Humans can actively influence controllable correlated health impacts by taking proactive measures, such as increasing our understanding of the detrimental effects associated with specific diseases and the patterns in climate change. We can also carefully distribute technology and resources, encouraging exercise and public awareness. It is advised to take the following adaption measures: Considering how infectious diseases and climate change are not the only things that science has discovered and create locally efficient early warning systems for those effects to produce more scientific justifications and go beyond scientific reports. Improve prediction of the spatiotemporal processes behind climate change and changes in infectious illnesses connected at different temporal and spatial scales.

Does Binaural Stimulation Enhance Temporal Processing in Young Children?

Background and objective Temporal processing abilities help perceive signal changes over time. Efficient temporal processing is necessary for pitch perception, voice identification, and speech perception. It plays a significant role in language development. Internal redundancy of the central auditory nervous plays a role in processing sensory information. There is a need to gain more insights into the maturation of neural hardwiring that supports binaural temporal processing at a young age. The purpose of the present study was to evaluate the difference between monaural and binaural temporal processing in children aged 7-11 years. Methods Temporal processing was assessed using gap detection and temporal modulation transfer function (TMTF) tests. The tests were administered in 40 typically developing children with normal clinical auditory sensitivity. The maximum likelihood procedure (MLP), a MATLAB toolbox, was employed to deliver the stimulus. A multivariate analysis followed by post hoc analysis was performed to analyze the data. Results There was a significant difference between binaural and monoaural stimulation in children aged 7-11 years. However, there was no statistically significant difference between the right and left ears for gap detection threshold (GDT) and TMTF across all test frequencies. Conclusion Based on our findings, binaural stimulation enhances temporal processing in young children.

Malignancies diagnosed before and after anal squamous cell carcinomas: A SEER registry analysis.

BACKGROUND: Increased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single-institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC. METHODS: This work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US-population-based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population. RESULTS: A total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs. CONCLUSIONS: Our findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies.

PRC2 engages a bivalent H3K27M-H3K27me3 dinucleosome inhibitor.

A lysine-to-methionine mutation at lysine 27 of histone 3 (H3K27M) has been shown to promote oncogenesis in a subset of pediatric gliomas. While there is evidence that this "oncohistone" mutation acts by inhibiting the histone methyltransferase PRC2, the details of this proposed mechanism nevertheless continue to be debated. Recent evidence suggests that PRC2 must simultaneously bind both H3K27M and H3K27me3 to experience competitive inhibition of its methyltransferase activity. In this work, we used PRC2 inhibitor treatments in a transgenic H3K27M cell line to validate this dependence in a cellular context. We further used designer chromatin inhibitors to probe the geometric constraints of PRC2 engagement of H3K27M and H3K27me3 in a biochemical setting. We found that PRC2 binds to a bivalent inhibitor unit consisting of an H3K27M and an H3K27me3 nucleosome and exhibits a distance dependence in its affinity for such an inhibitor, which favors closer proximity of the 2 nucleosomes within a chromatin array. Together, our data precisely delineate fundamental aspects of the H3K27M inhibitor and support a model wherein PRC2 becomes trapped at H3K27M-H3K27me3 boundaries.

Nucleation and Propagation of Heterochromatin by the Histone Methyltransferase PRC2: Geometric Constraints and Impact of the Regulatory Subunit JARID2.

Polycomb Repressive Complex 2 (PRC2) catalyzes mono-, di-, and trimethylation of lysine 27 on histone H3 (H3K27me1-3) to control expression of genes important for differentiation and maintenance of cell identity. PRC2 activity is regulated by a number of different inputs, including allosteric activation by its product, H3K27me3. This positive feedback loop is thought to be important for the establishment of large domains of condensed heterochromatin. In addition to other chromatin modifications, ancillary subunits of PRC2, foremost JARID2, affect the rate of H3K27 methylation. Many gaps remain in our understanding of how PRC2 integrates these various signals to determine where and when to deposit H3K27 methyl marks. In this study, we utilize designer chromatin substrates to demonstrate that propagation of H3K27 methylation by the PRC2 core complex has geometrically defined preferences that are overridden by the presence of JARID2. Our studies also show that phosphorylation of JARID2 can partially regulate its ability to stimulate PRC2 activity. Collectively, these biochemical insights further our understanding of the mechanisms that govern PRC2 activity, and highlight a role for JARID2 in de novo deposition of H3K27me3-containing repressive domains.

Histone H3 tail binds a unique sensing pocket in EZH2 to activate the PRC2 methyltransferase.

Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2), the enzyme that catalyzes monomethylation, dimethylation, and trimethylation of lysine 27 on histone H3 (H3K27). Trimethylation at H3K27 (H3K27me3) is associated with transcriptional silencing of developmentally important genes. Intriguingly, H3K27me3 is mutually exclusive with H3K36 trimethylation on the same histone tail. Disruptions in this cross-talk result in aberrant H3K27/H3K36 methylation patterns and altered transcriptional profiles that have been implicated in tumorigenesis and other disease states. Despite their importance, the molecular details of how PRC2 "senses" H3K36 methylation are unclear. We demonstrate that PRC2 is activated in cis by the unmodified side chain of H3K36, and that this activation results in a fivefold increase in the kcat of its enzymatic activity catalyzing H3K27 methylation compared with activity on a substrate methylated at H3K36. Using a photo-cross-linking MS strategy and histone methyltransferase activity assays on PRC2 mutants, we find that EZH2 contains a specific sensing pocket for the H3K36 methylation state that allows the complex to distinguish between modified and unmodified H3K36 residues, altering enzymatic activity accordingly to preferentially methylate the unmodified nucleosome substrate. We also present evidence that this process may be disrupted in some cases of Weaver syndrome.

Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape.

Several types of pediatric cancers reportedly contain high-frequency missense mutations in histone H3, yet the underlying oncogenic mechanism remains poorly characterized. Here we report that the H3 lysine 36-to-methionine (H3K36M) mutation impairs the differentiation of mesenchymal progenitor cells and generates undifferentiated sarcoma in vivo. H3K36M mutant nucleosomes inhibit the enzymatic activities of several H3K36 methyltransferases. Depleting H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy the H3K36M mutation. After the loss of H3K36 methylation, a genome-wide gain in H3K27 methylation leads to a redistribution of polycomb repressive complex 1 and de-repression of its target genes known to block mesenchymal differentiation. Our findings are mirrored in human undifferentiated sarcomas in which novel K36M/I mutations in H3.1 are identified.

Air Quality Standards for Particulate Matter (PM) at high altitude cities.

The Air Quality Standards for Particulate Matter (PM) at high altitude urban areas in different countries, must consider the pressure and temperature due to the effect that these parameters have on the breath volume. This paper shows the importance to correct Air Quality Standards for PM considering pressure and temperature at different altitudes. Specific factors were suggested to convert the information concerning PM, from local to standard conditions, and adjust the Air Quality Standards for different high altitudes cities. The correction factors ranged from: 1.03 for Santiago de Chile to 1.47 for El Alto Bolivia. Other cities in this study include: Mexico City, México; La Paz, Bolivia; Bogota, Cali and Medellin, Colombia; Quito, Ecuador and Cuzco, Peru. If these corrections are not considered, the atmospheric concentrations will be underestimated.

Computational design of targeted inhibitors of polo-like kinase 1 (plk1).

Computational design of small molecule putative inhibitors of Polo-like kinase 1 (Plk1) is presented. Plk1, which regulates the cell cycle, is often over expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor progression. Most kinase inhibitors interact with the ATP binding site on Plk1, which is highly conserved. This makes the development of Plk1-specific inhibitors challenging, since different kinases have similar ATP sites. However, Plk1 also contains a unique region called the polo-box domain (PBD), which is absent from other kinases. In this study, the PBD site was used as a target for designed Plk1 putative inhibitors. Common structural features of several experimentally known Plk1 ligands were first identified. The findings were used to design small molecules that specifically bonded Plk1. Drug likeness and possible toxicities of the molecules were investigated. Molecules with no implied toxicities and optimal drug likeness values were used for docking studies. Several molecules were identified that made stable complexes only with Plk1 and LYN kinases, but not with other kinases. One molecule was found to bind exclusively the PBD site of Plk1. Possible utilization of the designed molecules in drugs against cancers with over expressed Plk1 is discussed.

Soybean Rust Caused by Phakopsora pachyrhizi Detected in the State of Campeche on the Yucatan Peninsula, Mexico.

Soybean rust caused by Phakopsora pachyrhizi Syd. & P. Syd is a destructive foliar disease of soybean (Glycine max L), which was first confirmed in North America in Louisiana during 2004 (4). Soybean rust (SBR) has also been reported late in the growing season as far north as Illinois, Indiana, and Iowa. SBR was first confirmed in Mexico in 2005 in the state of San Luis Potosi on soybean (3) and subsequently reported in the states of Tamaulipas, Veracruz, and the southwestern coast of Chiapas. Symptoms of SBR were observed on leaves of multiple, nearly mature soybean plants near the city of Campeche (19.72796°N, 90.0771°W) on the Gulf Coast of the Yucatan Peninsula during November 2008. Angular and irregular chlorotic lesions on leaves contained necrotic spots and pale brown, erumpent, cone-like uredinia with a central opening. Ellipsoid to obovoid, echinulate, light tan urediniospores (10 to 13 × 16 to 18 µm) were observed microscopically. DNA was extracted from leaf tissue containing uredinia and from asymptomatic tissue with the DNeasy Plant Mini Kit (Qiagen, Valencia, CA). P. pachyrhizi was confirmed in the symptomatic leaves by a PCR assay with Ppm1/Ppa2 primers, but not from the asymptomatic leaves (1). Subsequently, the DNA extracted from symptomatic and asymptomatic leaf tissues was tested again in another laboratory by a specific quantitative PCR assay (1), and positive results for the presence of soybean rust were obtained only from the symptomatic tissue. As a final confirmatory step, amplified DNA from the PCR assay was sequenced, and the results matched P. pachyrhizi sequences in the GenBank database. To our knowledge, these observations confirm for the first time the presence of P. pachyrhizi in the state of Campeche of southern Mexico. Although it was confirmed on soybean during 2008, it is not known how long the pathogen has been present or which other hosts may be infected there. The presence of SBR on the Yucatan Peninsula is significant because of its potential effects on local plant hosts. In addition, the climate allows possible year-round survival of the pathogen and long-distance transport of urediniospores to the United States. Potential transport of SBR spores from this part of Mexico to the United States has been reported through the application of NOAA's HYSPLIT (Hybrid Single Particle Lagrangian Integrated Transport) model and atmospheric back-trajectory analysis (2). References: (1) R. D. Frederick et al. Phytopathology 92:217, 2002. (2) S. V. Krupa et al. Plant Dis. 90:1254, 2006. (3) A. C. Rodriguez et al. Plant Dis. 90:1260, 2006. (4) R. W. Schneider et al. Plant Dis. 89:774, 2005.

Alfalfa nutritive quality for ruminant livestock as influenced by ambient air quality in west-central Alberta.

Alfalfa (Medicago sativa) nutritive quality response to ambient ozone (O(3)), sulfur dioxide (SO(2)) and oxides of nitrogen (NO(x)) were assessed at three locations in west-central Alberta, Canada (1998-2002). Yield data were segregated into high and low relative to overall median yield. Ozone concentrations (hourly median and 95th-percentile) and precipitation (P) contributed 69 and 29%, respectively, to the variability in crude protein (CP) concentration in low-yielding alfalfa, whereas mean temperature (T) and relative humidity (RH) collectively influenced 98% of the variation in CP in high-yielding alfalfa. Three-fourths of the accounted variation in relative feed value (RFV) of low-yielding alfalfa was attributable to P, T and RH, whereas median and 95th-percentile hourly O(3) concentrations and SO(2) and NO(x) exposure integrals contributed 25%. In contrast, air quality, (mainly O(3)) influenced 86% of the accounted variation in RFV of high-yielding alfalfa, and T and P collectively contributed 14%.

Quantifying submarine groundwater discharge in the coastal zone via multiple methods.

Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. As such, this flow may contribute to the biogeochemical and other marine budgets of near-shore waters. These discharges typically display significant spatial and temporal variability making assessments difficult. Groundwater seepage is patchy, diffuse, temporally variable, and may involve multiple aquifers. Thus, the measurement of its magnitude and associated chemical fluxes is a challenging enterprise. A joint project of UNESCO and the International Atomic Energy Agency (IAEA) has examined several methods of SGD assessment and carried out a series of five intercomparison experiments in different hydrogeologic environments (coastal plain, karst, glacial till, fractured crystalline rock, and volcanic terrains). This report reviews the scientific and management significance of SGD, measurement approaches, and the results of the intercomparison experiments. We conclude that while the process is essentially ubiquitous in coastal areas, the assessment of its magnitude at any one location is subject to enough variability that measurements should be made by a variety of techniques and over large enough spatial and temporal scales to capture the majority of these changing conditions. We feel that all the measurement techniques described here are valid although they each have their own advantages and disadvantages. It is recommended that multiple approaches be applied whenever possible. In addition, a continuing effort is required in order to capture long-period tidal fluctuations, storm effects, and seasonal variations.

A multi-variate statistical model integrating passive sampler and meteorology data to predict the frequency distributions of hourly ambient ozone (O3) concentrations.

A multi-variate, non-linear statistical model is described to simulate passive O3 sampler data to mimic the hourly frequency distributions of continuous measurements using climatologic O3 indicators and passive sampler measurements. The main meteorological parameters identified by the model were, air temperature, relative humidity, solar radiation and wind speed, although other parameters were also considered. Together, air temperature, relative humidity and passive sampler data by themselves could explain 62.5-67.5% (R(2)) of the corresponding variability of the continuously measured O3 data. The final correlation coefficients (r) between the predicted hourly O3 concentrations from the passive sampler data and the true, continuous measurements were 0.819-0.854, with an accuracy of 92-94% for the predictive capability. With the addition of soil moisture data, the model can lead to the first order approximation of atmospheric O3 flux and plant stomatal uptake. Additionally, if such data are coupled to multi-point plant response measurements, meaningful cause-effect relationships can be derived in the future.

Effects of atmospheric ammonia (NH3) on terrestrial vegetation: a review.

At the global scale, among all N (nitrogen) species in the atmosphere and their deposition on to terrestrial vegetation and other receptors, NH3 (ammonia) is considered to be the foremost. The major sources for atmospheric NH3 are agricultural activities and animal feedlot operations, followed by biomass burning (including forest fires) and to a lesser extent fossil fuel combustion. Close to its sources, acute exposures to NH3 can result in visible foliar injury on vegetation. NH3 is deposited rapidly within the first 4-5 km from its source. However, NH3 is also converted in the atmosphere to fine particle NH4+ (ammonium) aerosols that are a regional scale problem. Much of our current knowledge of the effects of NH3 on higher plants is predominantly derived from studies conducted in Europe. Adverse effects on vegetation occur when the rate of foliar uptake of NH3 is greater than the rate and capacity for in vivo detoxification by the plants. Most to least sensitive plant species to NH3 are native vegetation > forests > agricultural crops. There are also a number of studies on N deposition and lichens, mosses and green algae. Direct cause and effect relationships in most of those cases (exceptions being those locations very close to point sources) are confounded by other environmental factors, particularly changes in the ambient SO2 (sulfur dioxide) concentrations. In addition to direct foliar injury, adverse effects of NH3 on higher plants include alterations in: growth and productivity, tissue content of nutrients and toxic elements, drought and frost tolerance, responses to insect pests and disease causing microorganisms (pathogens), development of beneficial root symbiotic or mycorrhizal associations and inter species competition or biodiversity. In all these cases, the joint effects of NH3 with other air pollutants such as all-pervasive O3 or increasing CO2 concentrations are poorly understood. While NH3 uptake in higher plants occurs through the shoots, NH4+ uptake occurs through the shoots, roots and through both pathways. However, NH4+ is immobile in the soil and is converted to NO3- (nitrate). In agricultural systems, additions of NO3- to the soil (initially as NH3 or NH4+) and the consequent increases in the emissions of N2O (nitrous oxide, a greenhouse gas) and leaching of NO3- into the ground and surface waters are of major environmental concern. At the ecosystem level NH3 deposition cannot be viewed alone, but in the context of total N deposition. There are a number of forest ecosystems in North America that have been subjected to N saturation and the consequent negative effects. There are also heathlands and other plant communities in Europe that have been subjected to N-induced alterations. Regulatory mitigative approaches to these problems include the use of N saturation data or the concept of critical loads. Current information suggests that a critical load of 5-10 kg ha(-1) year(-1) of total N deposition (both dry and wet deposition combined of all atmospheric N species) would protect the most vulnerable terrestrial ecosystems (heaths, bogs, cryptogams) and values of 10-20 kg ha(-1) year(-1) would protect forests, depending on soil conditions. However, to derive the best analysis, the critical load concept should be coupled to the results and consequences of N saturation.

Use of passive ambient ozone (O3) samplers in vegetation effects assessment.

A stochastistic, Weibull probability model was developed and verified to simulate the underlying frequency distributions of hourly ozone (O3) concentrations (exposure dynamics) using the single, weekly mean values obtained from a passive (sodium nitrite absorbent) sampler. The simulation was based on the data derived from a co-located continuous monitor. Although at the moment the model output may be considered as being specific to the elevation and location of the study site, the results were extremely good. This effort for the approximation of the O3 exposure dynamics can be extended to other sites with similar data sets and in developing a generalized understanding of the stochastic O3 exposure-plant response relationships, conferring measurable benefits to the future use of passive O3 samplers, in the absence of continuous monitoring.

Saskatoon serviceberry and ambient sulfur dioxide exposures: study sites re-visited, 1999.

Field surveys for symptoms of foliar injury in a regional airshed that is influenced by a number of point sources of SOx, NOx and hydrocarbons, combined with foliar and soil sulfur analyses, confirmed earlier results that Saskatoon serviceberry (Amelanchier alnifolia Nutt.) cv. Smokey can be used as a biological indicator of chronic sulfur dioxide exposures, in the presence of other phytotoxic air pollutants such as ozone.

Relationships between passive sampler and continuous ozone (O3 ) measurement data in ecological effects research.

In ecological effects research, there is a rapid increase in the application of passive sampling techniques for measuring ambient ozone (O3) concentrations. Passive samplers provide data on cumulative exposures of a plant to a pollutant. However, O3 is not an accumulative contaminant within the plant tissue, and use of prolonged passive sampling durations cannot account for the dynamics of the occurrences of O3 that have a significant influence on the plant response. Therefore, a stochastic Weibull probability model was previously developed and applied to a site in Washington State (1650 m MSL) to simulate the cumulative exposure data from a passive sampler, to mimic the corresponding frequency distributions of hourly O3 concentrations that would otherwise have been obtained by continuous monitoring. At that site the correlation between the actual passive sampler and the continuous monitor data was R2 = 0.74. The simulation of the hourly O3 data was based on and compared with the results obtained from a colocated continuous monitor. In this paper we report the results of the model application to data from an unrelated monitoring site (New Hampshire, 476 m MSL) with poor correlation between the passive sampling and continuous monitoring (R2 = 0.24). In addition, as opposed to the previous work, we provide comparisons of the frequency distributions of the hourly O3 concentrations obtained by the simulation and the actual continuous monitoring. In spite of the major difference in the R2 values, at both sites the simulation provided very satisfactory results within the 95% confidence interval, suggesting its broad applicability. The final objective of this overall approach is to develop a generic model that can simulate reasonably well the occurrences of ambient O3 concentrations that are dependent upon the elevation of the measurement site and the synoptic and local meteorology. Such an effort would extend the relative utility of the passive sampling data in explaining stochastic plant responses.