Interpretable Classification of Tauopathies with a Convolutional Neural Network Pipeline Using Transfer Learning and Validation against Post-Mortem Clinical Cases of Alzheimer's Disease and Progressive Supranuclear Palsy.

Neurodegenerative diseases, tauopathies, constitute a serious global health problem. The etiology of these diseases is unclear and an increase in their incidence has been projected in the next 30 years. Therefore, the study of the molecular mechanisms that might stop these neurodegenerative processes is very relevant. Classification of neurodegenerative diseases using Machine and Deep Learning algorithms has been widely studied for medical imaging such as Magnetic Resonance Imaging. However, post-mortem immunofluorescence imaging studies of the brains of patients have not yet been used for this purpose. These studies may represent a valuable tool for monitoring aberrant chemical changes or pathological post-translational modifications of the Tau polypeptide. We propose a Convolutional Neural Network pipeline for the classification of Tau pathology of Alzheimer's disease and Progressive Supranuclear Palsy by analyzing post-mortem immunofluorescence images with different Tau biomarkers performed with models generated with the architecture ResNet-IFT using Transfer Learning. These models' outputs were interpreted with interpretability algorithms such as Guided Grad-CAM and Occlusion Analysis. To determine the best classifier, four different architectures were tested. We demonstrated that our design was able to classify diseases with an accuracy of 98.41% on average whilst providing an interpretation concerning the proper classification involving different structural patterns in the immunoreactivity of the Tau protein in NFTs present in the brains of patients with Progressive Supranuclear Palsy and Alzheimer's disease.

E-cigarette Use, or Vaping, Practices and Characteristics Among Persons with Associated Lung Injury - Utah, April-October 2019.

In August 2019, the Utah Department of Health (UDOH) received reports from health care providers of several cases of lung injury in persons who reported use of electronic cigarette (e-cigarette), or vaping, products (1,2). To describe the characteristics of medical care, potentially related conditions, and exposures among 83 patients in Utah, detailed medical abstractions were completed for 79 (95%) patients. Among patients receiving chart abstractions, 70 (89%) were hospitalized, 39 (49%) required breathing assistance, and many reported preexisting respiratory and mental health conditions. Interviews were conducted by telephone or in person with 53 (64%) patients or their proxies, and product samples from eight (15%) of the interviewed patients or proxies were tested. Among 53 interviewed patients, all of whom reported using e-cigarette, or vaping, products within 3 months of acute lung injury, 49 (92%) reported using any products containing tetrohydrocannabinol (THC), the principal psychoactive component of cannabis; 35 (66%) reported using any nicotine-containing products, and 32 (60%) reported using both. As reported in Wisconsin and Illinois (1), most THC-containing products were acquired from informal sources such as friends or illicit in-person and online dealers. THC-containing products were most commonly used one to five times per day, whereas nicotine-containing products were most commonly used >25 times per day. Product sample testing at the Utah Public Health Laboratory (UPHL) showed evidence of vitamin E acetate in 17 of 20 (89%) THC-containing cartridges, which were provided by six of 53 interviewed patients. The cause or causes of this outbreak is currently unknown (2); however, the predominant use among patients of e-cigarette, or vaping, products with prefilled THC-containing cartridges suggests that the substances in these products or the way in which they are heated and aerosolized play an important role in the outbreak. At present, persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific cause or causes of lung injury are not yet known and while the investigation continues, persons should consider refraining from use of all e-cigarette, or vaping, products.

Clinical periodontal variables in patients with and without dementia-a systematic review and meta-analysis.

BACKGROUND: Considering the increasing number of elderly people, dementia has gained an important role in today's society. Although the contributing factors for dementia have not been fully understood, chronic periodontitis (CP) seems to have a possible link to dementia. AIM: To conduct a systematic review including meta-analysis in order to assess potential differences in clinical periodontal variables between patients with dementia and non-demented individuals. METHODS: The following focused question was evaluated: is periodontitis associated with dementia? Electronic searches in two databases, MEDLINE and EMBASE, were conducted. Meta-analysis was performed with the collected data in order to find a statistically significant difference in clinical periodontal variables between the group of dementia and the cognitive normal controls. RESULTS: Forty-two articles remained for full text reading. Finally, seven articles met the inclusion criteria and only five studies provided data suitable for meta-analysis. Periodontal probing depth (PPD), bleeding on probing (BOP), gingival bleeding index (GBI), clinical attachment level (CAL), and plaque index (PI) were included as periodontal variables in the meta-analysis. Each variable revealed a statistically significant difference between the groups. In an attempt to reveal an overall difference between the periodontal variables in dementia patients and non-demented individuals, the chosen variables were transformed into units that resulted in a statistically significant overall difference (p < 0.00001). CONCLUSION: The current findings indicate that compared to systemically healthy individuals, demented patients show significantly worse clinical periodontal variables. However, further epidemiological studies including a high numbers of participants, the use of exact definitions both for dementia and chronic periodontitis and adjusted for cofounders is warranted. CLINICAL RELEVANCE: These findings appear to support the putative link between CP and dementia. Consequently, the need for periodontal screening and treatment of elderly demented people should be emphasized.

Seasonal Differences in Contaminant Accumulation in Neotropical Migrant and Resident Songbirds.

For many years, it has been hypothesized that Neotropical migrants breeding in the United States and Canada accumulate organochlorine pesticides (OCPs) while on their wintering grounds in Latin America. We investigated the seasonal accumulation of persistent organic pollutant (POPs) in migrant and resident passerines in Texas, Yucatán, and Costa Rica collected during the fall, winter, and spring from 2011 to 2013. A total of 153 birds were collected, and all contained detectable levels of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and OCPs with dichlorodiphenyldichloroethylene (DDE) being the most predominant pesticide. OCPs and PCBs were the predominant contaminants, accounting for ≥80 % of the total POPs burden, whereas PBDEs accounted for ≤16 %. Only spring migrants from Texas had significantly greater DDE concentrations (64.6 ng/g dry weight [dw]) than migrants collected in Costa Rica (23.2 ng/g dw). Resident birds in Texas had significantly greater levels of DDE (121 ng/g dw) and ΣPBDEs (34.8 ng/g dw) compared with residents in Yucatán and Costa Rica. For ΣPCBs, resident birds from Costa Rica had significantly lower concentrations (9.60 ng/g dw) compared with their migrant counterparts (43.7 ng/g dw) and residents from Texas (48.3 ng/g dw) and the Yucatán (32.1 ng/g dw). Migrant and resident passerines had similar congener profiles for PCBs and PBDEs suggesting similar exposure and retention of these contaminants. No significant accumulation of DDE was observed in migrants while on their wintering grounds. Relatively high concentrations of PBDEs in resident birds from Costa Rica warrant future studies of PBDE contamination in Latin America.

Engineering carboxylic acid reductases and unspecific peroxygenases for flavor and fragrance biosynthesis.

Emerging consumer demand for safer, more sustainable flavors and fragrances has created new challenges for the industry. Enzymatic syntheses represent a promising green production route, but the broad application requires engineering advancements for expanded diversity, improved selectivity, and enhanced stability to be cost-competitive with current methods. This review discusses recent advances and future outlooks for enzyme engineering in this field. We focus on carboxylic acid reductases (CARs) and unspecific peroxygenases (UPOs) that enable selective productions of complex flavor and fragrance molecules. Both enzyme types consist of natural variants with attractive characteristics for biocatalytic applications. Applying protein engineering methods, including rational design and directed evolution in concert with computational modeling, present excellent examples for property improvements to unleash the full potential of enzymes in the biosynthesis of value-added chemicals.

Human vascular smooth muscle cells utilise chymase for the atypical cleavage and activation of Interleukin-1ß.

BACKGROUND AND AIMS: Atherosclerosis and other cardiovascular diseases (CVD) are well established to be both instigated and worsened by inflammation. Indeed, CANTOS formally proved that targeting the inflammatory cytokine IL-1ß only could reduce both cardiovascular events and death. However, due to the central role of IL-1ß in host defence, blockade increased fatal infections, suggesting targeting key immune mediators over the long natural history of CVD is unsuitable. Thus, discovering alternative mechanisms that generate vascular inflammation may identify more actionable targets. METHODS: We used primary human VSMCs and a combination of biochemical, pharmacological and molecular biological techniques to generate the data. Human carotid atherosclerotic plaques were also assessed histologically. RESULTS: We showed that VSMCs expressed and efficiently processed pro-IL-1ß to the active form after receiving a single stimulus via IL-1R1 or TLR4. Importantly, pro-IL-1ß processing did not utilise inflammasomes or caspases. Unusually, we found that cathepsin C-activated chymase was responsible for cleaving IL-1ß in VSMCs, and provided evidence for chymase expression in cultured VSMCs and in the fibrous cap of human plaques. Chymase also efficiently cleaved and activated recombinant pro-IL-1ß. CONCLUSIONS: Thus, VSMCs are efficient activators of IL-1ß that do not use canonical inflammasomes or caspases. Hence, this alternative pathway could be targeted for long-term treatment of CVDs, as it is not central to everyday host defence.

Thrombin-activated interleukin-1α drives atherogenesis, but also promotes vascular smooth muscle cell proliferation and collagen production.

AIMS: Atherosclerosis is driven by multiple processes across multiple body systems. For example, the innate immune system drives both atherogenesis and plaque rupture via inflammation, while coronary artery-occluding thrombi formed by the coagulation system cause myocardial infarction and death. However, the interplay between these systems during atherogenesis is understudied. We recently showed that coagulation and immunity are fundamentally linked by the activation of interleukin-1α (IL-1α) by thrombin, and generated a novel knock-in mouse in which thrombin cannot activate endogenous IL-1α [IL-1α thrombin mutant (IL-1αTM)]. METHODS AND RESULTS: Here, we show significantly reduced atherosclerotic plaque formation in IL-1αTM/Apoe-/- mice compared with Apoe-/- and reduced T-cell infiltration. However, IL-1αTM/Apoe-/- plaques have reduced vascular smooth muscle cells, collagen, and fibrous caps, indicative of a more unstable phenotype. Interestingly, the reduced atherogenesis seen with thrombin inhibition was absent in IL-1αTM/Apoe-/- mice, suggesting that thrombin inhibitors can affect atherosclerosis via reduced IL-1α activation. Finally, bone marrow chimeras show that thrombin-activated IL-1α is derived from both vessel wall and myeloid cells. CONCLUSIONS: Together, we reveal that the atherogenic effect of ongoing coagulation is, in part, mediated via thrombin cleavage of IL-1α. This not only highlights the importance of interplay between systems during disease and the potential for therapeutically targeting IL-1α and/or thrombin, but also forewarns that IL-1 may have a role in plaque stabilization.

A Novel Automatic Quantification Protocol for Biomarkers of Tauopathies in the Hippocampus and Entorhinal Cortex of Post-Mortem Samples Using an Extended Semi-Siamese U-Net.

Efforts have been made to diagnose and predict the course of different neurodegenerative diseases through various imaging techniques. Particularly tauopathies, where the tau polypeptide is a key participant in molecular pathogenesis, have significantly increased their morbidity and mortality in the human population over the years. However, the standard approach to exploring the phenomenon of neurodegeneration in tauopathies has not been directed at understanding the molecular mechanism that causes the aberrant polymeric and fibrillar behavior of the tau protein, which forms neurofibrillary tangles that replace neuronal populations in the hippocampal and cortical regions. The main objective of this work is to implement a novel quantification protocol for different biomarkers based on pathological post-translational modifications undergone by tau in the brains of patients with tauopathies. The quantification protocol consists of an adaptation of the U-Net neural network architecture. We used the resulting segmentation masks for the quantification of combined fluorescent signals of the different molecular changes tau underwent in neurofibrillary tangles. The quantification considers the neurofibrillary tangles as an individual study structure separated from the rest of the quadrant present in the images. This allows us to detect unconventional interaction signals between the different biomarkers. Our algorithm provides information that will be fundamental to understanding the pathogenesis of dementias with another computational analysis approach in subsequent studies.

The Impact of the pH Value on Biofilm Formation.

The pH value of a biofilm influences the pathogenesis and therapy of oral diseases such as caries and periodontitis. This study aimed to investigate the influence of different initial pH values on the microbial composition, bacterial counts, metabolic activity, and quantity of three defined biofilms representing oral health, caries, and periodontal disease. Respective bacterial suspensions in the nutrient broth were initially adjusted to pH values between 5 and 8. Then biofilms were cultured on polystyrene surfaces coated with a proteinaceous solution for 2 h ("healthy" biofilm), 6 h ("healthy," and "cariogenic" biofilms), 24 h ("cariogenic," and "periodontitis" biofilms), and 48 h ("periodontitis" biofilm). In all biofilms, total bacterial counts were lower at an initial pH of 5 or 5.5 than at higher pH values. In the biofilm representing caries, the percentage of cariogenic bacteria (Streptococcus mutans, S. sobrinus, Lactobacillus acidophilus) was higher at a low pH, the metabolic activity was highest at pH 6-6.5, and biofilm mass was greatest at pH 7-7.5. In the biofilm representing periodontitis, the percentage of Porphyromonas gingivalis increased with the pH. Also, the metabolic activity was highest at pH 8, whereas mass had the highest value at pH 7. In conclusion, the initial pH value influences biofilm formation. In particular, metabolic activity and the amount of bacteria associated with disease correlated with the respective pH known to be of importance in the development of caries (relatively low pH) and periodontitis (higher pH). Modifying the pH level in oral biofilms might be an alternative concept in (primary) prevention and treatment, not only of caries but also of periodontitis.

[Pentoxifylline and tocopherol - The importance in the treatment of osteoradionecrosis - Literature review and case report]. / Pentoxifyllin und Tocopherol. Die Bedeutung in der Behandlung der Osteoradionekrose ­ Literaturreview und Fallbericht.

Osteoradionecrosis (ORN) is a serious complication after radiotherapy for head and neck cancer and is a challenging condition for both the therapist and the patient because of its difficult treatment. Different non-invasive approaches have been published for the treatment of low-grade ORN cases without establishing a standard regimen for treatment. Based on the approach of ORN pathogenesis, the so-called radiatio-induced fibroathrophic process (RIF), a new treatment concept with pentoxifylline and tocopherol (PENTO) has been published. The results of PENTO therapy seem promising as a conservative treatment approach for mild ORN or as an alternative when surgical intervention is not possible or desired. The present study summarizes the current state of the literature and shows the effectiveness of PENTO therapy based on a case report.

Examining the temporality of vitamin E acetate in illicit THC-containing e-cigarette, or vaping, products from a public health and law enforcement response to EVALI - Utah, 2018-2020.

BACKGROUND: In the summer of 2019, e-cigarette, or vaping, product use-associated lung injury (EVALI) was detected in the United States. Multiple agencies reported illicit tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, products containing vitamin E acetate (VEA) as a substance of concern. METHODS: As an expansion of the Utah Department of Health's response to EVALI, the Utah Public Health Laboratory and the Utah Department of Public Safety screened 170 products from 96 seizures between October 2018 and January 2020. Using Pearson's correlation coefficient, we analyzed the temporal correlation of national, and Utah specific case counts, and the percentage of seizures indicating VEA by month. RESULTS: The findings indicate strong and significant correlations between seizures indicating VEA and both the national (r = 0.70, p = 0.002) and Utah specific (r = 0.78, p < 0.001) case counts. CONCLUSION: These findings underscore that VEA should not be added to e-cigarettes, or vaping, products and the importance of collaboration with law enforcement when responding to outbreaks associated with illicit substances.

Molecular Processing of Tau Protein in Progressive Supranuclear Palsy: Neuronal and Glial Degeneration.

BACKGROUND: Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are examples of neurodegenerative diseases, characterized by abnormal tau inclusions, that are called tauopathies. AD is characterized by highly insoluble paired helical filaments (PHFs) composed of tau with abnormal post-translational modifications. PSP is a neurodegenerative disease with pathological and clinical heterogeneity. There are six tau isoforms expressed in the adult human brain, with repeated microtubule-binding domains of three (3R) or four (4R) repeats. In AD, the 4R:3R ratio is 1:1. In PSP, the 4R isoform predominates. The lesions in PSP brains contain phosphorylated tau aggregates in both neurons and glial cells. OBJECTIVE: Our objective was to evaluate and compare the processing of pathological tau in PSP and AD. METHODS: Double and triple immunofluorescent labeling with antibodies to specific post-translational tau modifications (phosphorylation, truncation, and conformational changes) and thiazin red (TR) staining were carried out and analyzed by confocal microscopy. RESULTS: Our results showed that PSP was characterized by phosphorylated tau in neurofibrillary tangles (NFTs) and glial cells. Tau truncated at either Glu391 or Asp421 was not observed. Extracellular NFTs (eNFTs) and glial cells in PSP exhibited a strong affinity for TR in the absence of intact or phosphorylated tau. CONCLUSION: Phosphorylated tau was as abundant in PSP as in AD. The development of eNFTs from both glial cells and neuronal bodies suggests that truncated tau species, different from those observed in AD, could be present in PSP. Additional studies on truncated tau within PSP lesions could improve our understanding of the pathological processing of tau and help identify a discriminatory biomarker for AD and PSP.

Citrullination in periodontium is associated with Porphyromonas gingivalis.

OBJECTIVE: To analyse the citrulline level in the periodontium in association with the presence of or antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. DESIGN: Gingival crevicular fluid (GCF), subgingival biofilm and blood serum were sampled from 98 subjects (26 with RA, 72 without RA (NoRA)). GCF was analyzed for the level of citrulline, for interleukin (IL)-1ß, IL-17, IL-10 and monocyte-chemoattractant protein (MCP)-1. Microorganisms were identified in subgingival biofilms. Antibodies againstP. gingivalis, and Aggregatibacter actinomycetemcomitans were quantified in serum. RESULTS: GCF citrulline level was the lowest (by trend) in NoRA group without periodontitis. In NoRA, but not in RA an association between GCF citrulline level and P. gingivalis antibody levels was found and the GCF citrulline levels were higher in P. gingivalis positive samples. Any association of A. actinomycetemcomitans with GCF citrulline level did not exist. A model of univariate variance analysis (p = 0.001) showed a dependence of GCF citrulline level from the number of sites with PD (probing depth) ≥5 mm (p = 0.003) and the GCF MCP-1/CCL2 level (p = 0.019). Compared with NoRA in RA the number of teeth was lower, the number of sites with PD ≥ 5 mm was less, GCF levels of interleukin-17 and MCP-1/CCL2 were higher and those of IL-10 lower. Yeasts were only cultured in 15 RA patients (p < 0.001). CONCLUSION: Citrullination in periodontium might be associated with P. gingivalis supporting the potential role as a trigger in the development of RA. Pathogenesis of periodontal disease in RA patients seems to differ from that in NoRA and should be investigated further.

Influence of periodontitis on pregnancy and childbirth / Einfluss der Parodontitis auf Schwangerschaft und Geburt

For two decades, in periodontology, the effects of periodontal disease on pregnancy, low birth weight or premature birth have been investigated. Even hypertensive diseases during pregnancy have an influence on pregnancy possibly leading to the death of the untreated mother. Due to the stable increase in birth rates,in addition to women's employment and careers, this topic has become more relevant in dentistry than ever before. Rates of prematurity and reduced birth weight are both increasing worldwide and are the main cause of neonatal morbidity and mortality. The need for action regarding the prevention, education and health care of pregnant women is given worldwide. This article first gives an overview of the topic and further discusses the necessary interdisciplinary gynecological and dental therapy. In the daily practice, dentists will be able to make a small but not insignificant contribution to improving the situation of affected women and their children.

[Pseudomonas aeruginosa: Pathogenicity and antimicrobial resistance in urinary tract infection]. / Pseudomonas aeruginosa: patogenicidad y resistencia antimicrobiana en la infección urinaria.

Among the most frequent nosocomial infections associated with polyresistant bacteria and with a worse prognosis, are those produced by Pseudomonas aeruginosa. This bacterium has a high capacity to adapt to adverse conditions such as pH and osmolarity of urine. Pseudomonas aeruginosa is one of the main pathogens involved in nosocomial infections and immunosuppressed patients. This bacterium is considered an opportunistic infectious agent that has diverse mechanisms of pathogenicity, as well as resistance to antimicrobials, which contributes to the difficulty in the treatment of these infections. In the present bibliographic review, the taxonomy, pathogenicity mechanisms and resistance genes of P. aeruginosa are analyzed. Likewise, the micro-environmental factors of the urinary infection produced by this bacterium are approached, making an approach to the understanding of the pathophysiological bases of this infection.

Phospho-Tau Protein Expression in the Cell Cycle of SH-SY5Y Neuroblastoma Cells: A Morphological Study.

It has been reported that the main function of tau protein is to stabilize microtubules and promote the movement of organelles through the axon in neurons. In Alzheimer's disease, tau protein is the major constituent of the paired helical filament, and it undergoes post-translational modifications including hyperphosphorylation and truncation. Whether other functions of tau protein are involved in Alzheimer's disease is less clear. We used SH-SY5Y human neuroblastoma cells as an in vitro model to further study the functions of tau protein. We detected phosphorylated tau protein as small dense dots in the cell nucleus, which strongly colocalize with intranuclear speckle structures that were also labelled with an antibody to SC35, a protein involved in nuclear RNA splicing. We have shown further that tau protein, phosphorylated at the sites recognized by pT231, TG-3, and AD2 antibodies, is closely associated with cell division. Different functions may be characteristic of phosphorylation at specific sites. Our findings suggest that the presence of tau protein is involved in separation of sister chromatids in anaphase, and that tau protein also participates in maintaining the integrity of the DNA (pT231, prophase) and chromosomes during cell division (TG-3).

Periodontal Pathogens and Associated Intrathecal Antibodies in Early Stages of Alzheimer's Disease.

BACKGROUND: Recent studies suggest a link between periodontitis and Alzheimer's disease (AD). OBJECTIVE: Verification of the presence of periodontal pathogens and the intrathecal generation of pathogen-specific antibodies in 20 patients with AD and 20 with other forms of dementia (DEM-noAD). METHODS: Clinical periodontal indices were recorded. Cerebrospinal fluid (CSF) was analyzed for total tau protein (T-tau) and amyloid-ß (Aß1-42). In serum and CSF, antibody levels against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema species were quantified. The presence of selected bacteria and inflammatory biomarkers were determined in periodontium, serum, and CSF. RESULTS: In line with diagnoses, CSF-levels of Aß1-42 were significantly lower in AD than DEM-noAD patients. Periodontal destruction and inflammation were omnipresent with no difference between groups. P. gingivalis, T. forsythia, and Treponema species were detected in more than 50% of subgingival biofilm samples, but neither in serum nor in the CSF. Elevated levels of anti-pathogen antibodies in CSF of 16 patients (7 AD; 9 DEM-noAD) compared to serum highlight a possibility of the intrathecal immune response to pathogens. There was no significant difference in antibodies levels against selected bacteria in CSF and serum between groups. Multivariate regression analysis and general linear models revealed an association of the T-tau level in AD group with both serum levels of anti-P. gingivalis antibodies and MCP-1/CCL-2. CONCLUSION: Periodontal pathogens may enter the brain and stimulate a local immune response. However, in patients with dementia at the age up to 70 years, periodontal pathogens do not act as a trigger for developing AD.

Aging-related tau astrogliopathy (ARTAG): not only tau phosphorylation in astrocytes.

Aging-related tau astrogliopathy (ARTAG) is defined by the presence of two types of tau-bearing astrocytes: thorn-shaped astrocytes (TSAs) and granular/fuzzy astrocytes in the brain of old-aged individuals. The present study is focused on TSAs in rare forms of ARTAG with no neuronal tau pathology or restricted to entorhinal and transentorhinal cortices, to avoid bias from associated tauopathies. TSAs show 4Rtau phosphorylation at several specific sites and abnormal tau conformation, but they lack ubiquitin and they are not immunostained with tau-C3 antibodies which recognize truncated tau at Asp421. Astrocytes in ARTAG have atrophic processes, reduced glial fibrillary acidic protein (GFAP) and increased superoxide dismutase 2 (SOD2) immunoreactivity. Gel electrophoresis and western blotting of sarkosyl-insoluble fractions reveal a pattern of phospho-tau in ARTAG characterized by two bands of 68 and 64 kDa, and several middle bands between 35 and 50 kDa which differ from what is seen in AD. Phosphoproteomics of dissected vulnerable regions identifies an increase of phosphorylation marks in a large number of proteins in ARTAG compared with controls. GFAP, aquaporin 4, several serine-threonine kinases, microtubule associated proteins and other neuronal proteins are among the differentially phosphorylated proteins in ARTAG thus suggesting a hyper-phosphorylation background that affects several molecules, including many kinases and proteins from several cell compartments and various cell types. Finally, present results show for the first time that tau seeding is produced in neurons of the hippocampal complex, astrocytes, oligodendroglia and along fibers of the corpus callosum, fimbria and fornix following inoculation into the hippocampus of wild type mice of sarkosyl-insoluble fractions enriched in hyper-phosphorylated tau from selected ARTAG cases. These findings show astrocytes as crucial players of tau seeding in tauopathies.

Racial Differences in Perceptions of Air Pollution Health Risk: Does Environmental Exposure Matter?

This article extends environmental risk perception research by exploring how potential health risk from exposure to industrial and vehicular air pollutants, as well as other contextual and socio-demographic factors, influence racial/ethnic differences in air pollution health risk perception. Our study site is the Greater Houston metropolitan area, Texas, USA-a racially/ethnically diverse area facing high levels of exposure to pollutants from both industrial and transportation sources. We integrate primary household-level survey data with estimates of excess cancer risk from ambient exposure to industrial and on-road mobile source emissions of air toxics obtained from the U.S. Environmental Protection Agency. Statistical analysis is based on multivariate generalized estimation equation models which account for geographic clustering of surveyed households. Our results reveal significantly higher risk perceptions for non-Hispanic Black residents and those exposed to greater cancer risk from industrial pollutants, and also indicate that gender influences the relationship between race/ethnicity and air pollution risk perception. These findings highlight the need to incorporate measures of environmental health risk exposure in future analysis of social disparities in risk perception.