Thermal biology of mosquito-borne disease

Mosquito-borne diseases cause a major burden of disease worldwide. The vital rates of these ectothermic vectors and parasites respond strongly and nonlinearly to temperature and therefore to climate change. Here, we review how trait-based approaches can synthesise and mechanistically predict the temperature dependence of transmission across vectors, pathogens, and environments. We present 11 pathogens transmitted by 15 different mosquito species – including globally important diseases like malaria, dengue, and Zika – synthesised from previously published studies. Transmission varied strongly and unimodally with temperature, peaking at 23–29ºC and declining to zero below 9–23ºC and above 32–38ºC. Different traits restricted transmission at low versus high temperatures, and temperature effects on transmission varied by both mosquito and parasite species. Temperate pathogens exhibit broader thermal ranges and cooler thermal minima and optima than tropical pathogens. Among tropical pathogens, malaria and Ross River virus had lower thermal optima (25–26ºC) while dengue and Zika viruses had the highest (29ºC) thermal optima. We expect warming to increase transmission below thermal optima but decrease transmission above optima. Key directions for future work include linking mechanistic models to field transmission, combining temperature effects with control measures, incorporating trait variation and temperature variation, and investigating climate adaptation and migration

Driving oxygen coordinated ligand exchange at nanocrystal surfaces using trialkylsilylated chalcogenides

A general, efficient method is demonstrated for exchanging native oxyanionic ligands on inorganic nanocrystals with functional trimethylsilylated (TMS) chalcogenido ligands. In addition, newly synthesized TMS mixed chalcogenides leverage preferential reactivity of TMS-S bonds over TMS-O bonds, enabling efficient transfer of luminescent nanocrystals into aqueous media with retention of their optical properties

High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction

<p>Abstract</p> <p>Background</p> <p>Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.</p> <p>Methods</p> <p>A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for <it>in vivo </it>treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for <it>in vivo </it>experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.</p> <p>Results</p> <p>No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.</p> <p>Conclusions</p> <p>H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.</p

Risks of mining to salmonid-bearing watersheds

Mining provides resources for people but can pose risks to ecosystems that support cultural keystone species. Our synthesis reviews relevant aspects of mining operations, describes the ecology of salmonid-bearing watersheds in northwestern North America, and compiles the impacts of metal and coal extraction on salmonids and their habitat. We conservatively estimate that this region encompasses nearly 4000 past producing mines, with present-day operations ranging from small placer sites to massive open-pit projects that annually mine more than 118 million metric tons of earth. Despite impact assessments that are intended to evaluate risk and inform mitigation, mines continue to harm salmonid-bearing watersheds via pathways such as toxic contaminants, stream channel burial, and flow regime alteration. To better maintain watershed processes that benefit salmonids, we highlight key windows during the mining governance life cycle for science to guide policy by more accurately accounting for stressor complexity, cumulative effects, and future environmental change.This review is based on an October 2019 workshop held at the University of Montana Flathead Lake Biological Station (more information at https://flbs.umt.edu/ newflbs/research/working-groups/mining-and-watersheds/). We thank E. O’Neill and other participants for valuable contributions. A. Beaudreau, M. LaCroix, P. McGrath, K. Schofield, and L. Brown provided helpful reviews of earlier drafts. Three anonymous reviewers provided thoughtful critiques that greatly improved the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency. Our analysis comes from a western science perspective and hence does not incorporate Indigenous knowledge systems. We acknowledge this gap and highlight that the lands and waters we explore in this review have been stewarded by Indigenous Peoples for millennia and continue to be so. Funding: The workshop was cooperatively funded by the Wilburforce Foundation and The Salmon Science Network funded by the Gordon and Betty Moore Foundation. Author contributions: C.J.S. led the review process, writing, and editing. C.J.S. and E.K.S. co-organized the workshop. E.K.S. and J.W.M. extensively contributed to all aspects of the review conceptualization, writing, and editing. A.R.W., S.A.N., J.L.E., D.M.C., S.L.O., R.L.M., F.R.H., D.C.W., and J.W. significantly contributed to portions of the review conceptualization, writing, and editing. J.C., M.Ca., M.Co., C.A.F., G.K., E.D.L., R.M., V.M., J.K.M., M.V.M., and N.S. provided writing and editing and are listed alphabetically. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.Ye

The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum

Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer’s disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p &lt; 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p &gt; 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

Driving Oxygen Coordinated Ligand Exchange at Nanocrystal Surfaces using Trialkylsilylated Chalcogenides

A general, efficient method is demonstrated for exchanging native oxyanionic ligands on inorganic nanocrystals with functional trimethylsilylated (TMS) chalcogenido ligands. In addition, newly synthesized TMS mixed chalcogenides leverage preferential reactivity of TMS-S bonds over TMS-O bonds, enabling efficient transfer of luminescent nanocrystals into aqueous media with retention of their optical properties

Spectroscopic Evidence for Exceptional Thermal Contribution to Electron-Beam Induced Fragmentation

While electron beam induced fragmentation (EBIF) has been reported to result in the formation of nanocrystals of various compositions, the physical forces driving this phenomenon are still poorly understood. We report EBIF to be a much more general phenomenon than previously appreciated, operative across a wide variety of metals, semiconductors and insulators. In addition, we leverage the temperature dependent bandgap of several semiconductors to quantify -- using in situ cathodoluminescence spectroscopy -- the thermal contribution to EBIF, and find extreme temperature rises upwards of 1000K

Seasonal temperature variation influences climate suitability for dengue, chikungunya, and Zika transmission

<div><p>Dengue, chikungunya, and Zika virus epidemics transmitted by <i>Aedes aegypti</i> mosquitoes have recently (re)emerged and spread throughout the Americas, Southeast Asia, the Pacific Islands, and elsewhere. Understanding how environmental conditions affect epidemic dynamics is critical for predicting and responding to the geographic and seasonal spread of disease. Specifically, we lack a mechanistic understanding of how seasonal variation in temperature affects epidemic magnitude and duration. Here, we develop a dynamic disease transmission model for dengue virus and <i>Aedes aegypti</i> mosquitoes that integrates mechanistic, empirically parameterized, and independently validated mosquito and virus trait thermal responses under seasonally varying temperatures. We examine the influence of seasonal temperature mean, variation, and temperature at the start of the epidemic on disease dynamics. We find that at both constant and seasonally varying temperatures, warmer temperatures at the start of epidemics promote more rapid epidemics due to faster burnout of the susceptible population. By contrast, intermediate temperatures (24–25°C) at epidemic onset produced the largest epidemics in both constant and seasonally varying temperature regimes. When seasonal temperature variation was low, 25–35°C annual average temperatures produced the largest epidemics, but this range shifted to cooler temperatures as seasonal temperature variation increased (analogous to previous results for diurnal temperature variation). Tropical and sub-tropical cities such as Rio de Janeiro, Fortaleza, and Salvador, Brazil; Cali, Cartagena, and Barranquilla, Colombia; Delhi, India; Guangzhou, China; and Manila, Philippines have mean annual temperatures and seasonal temperature ranges that produced the largest epidemics. However, more temperate cities like Shanghai, China had high epidemic suitability because large seasonal variation offset moderate annual average temperatures. By accounting for seasonal variation in temperature, the model provides a baseline for mechanistically understanding environmental suitability for virus transmission by <i>Aedes aegypti</i>. Overlaying the impact of human activities and socioeconomic factors onto this mechanistic temperature-dependent framework is critical for understanding likelihood and magnitude of outbreaks.</p></div