Extracellular Vesicles and Asthma—More Than Just a Co-Existence

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.     

Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. The pathogenicity of TDP-43 cytoplasmic aggregates may be linked with both a loss of nuclear function and a gain of toxic functions. The cellular processes involved in ALS and FTLD disease pathogenesis include changes to RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments to axonal transport and autophagy, abnormal neuromuscular junctions, endoplasmic reticulum stress and the subsequent induction of the unfolded protein response. Here, we review and discuss the evidence for alterations to these processes that have been reported in cellular and animal models of TDP-43 proteinopathy.     

An Emerging Role for Calcium Signaling in Cancer-Associated Fibroblasts

Tumors exist in a complex milieu where interaction with their associated microenvironment significantly contributes to disease progression. Cancer-associated fibroblasts (CAFs) are the primary component of the tumor microenvironment and participate in complex bidirectional communication with tumor cells. CAFs support the development of various hallmarks of cancer through diverse processes, including direct cell–cell contact, paracrine signaling, and remodeling and deposition of the extracellular matrix. Calcium signaling is a key second messenger in intra- and inter-cellular signaling pathways that contributes to cancer progression; however, the links between calcium signaling and CAFs are less well-explored. In this review, we put into context the role of calcium signaling in interactions between cancer cells and CAFs, with a focus on migration, proliferation, chemoresistance, and genetic instability.     

Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.     

Optimized etching of porcelain and polycrystalline alumina with a glass phase

Chemical and thermal etching techniques are commonly used in ceramography to enhance microstructural features. While thermal etching works well for high purity ceramic systems, this technique may not be appropriate where glass is present. Porcelain and industrial alumina both contain a glass phase, typically 40?60 vol% and 4?30 vol%, respectively, and these glass chemistries are proposed to be similar. Chemical etching of porcelain is common, but the images published in the literature are frequently over-etched. When glass is present in the grain boundaries of alumina, thermal etching can cause the glass to disappear or to recrystallize, obscuring the microstructure. Because of this, it is proposed that both chemical and thermal etching are necessary to prepare an industrial alumina microstructure for grain size measurements. In addition, it was observed that chemical etching is sensitive to the residual stress in the glass phase, becoming more aggressive when there is residual tension in the glass.     

Evaluating the potential efficacy of mercury total maximum daily loads on aqueous methylmercury levels in four coastal watersheds

Of the approximately 780 U.S. EPA approved mercury total maximum daily loads (TMDLs), most specify a reduction in total mercury (Hg(T)) loads to reduce methylmercury levels in fish tissue, assuming a 1:1 correspondence. However, mercury methylation is more complex, and therefore, proposed load reductions may not be adequate. Using multiple regression with microlevel and macrolevel variables, the potential efficacy of mercury TMDLs on decreasing aqueous methylmercury levels was investigated in four coastal watersheds: Mugu Lagoon (CA), San Francisco Bay Estuary, Long Island Sound, and south Florida. Hg(T) and methylmercury levels were positively correlated in all watersheds except in Long Island Sound, where spatial differences explained over 40% of the variability in methylmercury levels. A mercury TMDL would be least effective in Long Island Sound due to spatial heterogeneity but most effective in south Florida, where the ratio between aqueous Hg(T) and methylmercury levels was close to 1 and the 95% confidence interval was narrow, indicating a probable reduction in aqueous methylmercury levels if Hg(T) loads were reduced.     

Iodine-131: a potential short-lived, wastewater-specific particle tracer in an urbanized estuarine system

The short-lived, fission-produced radioisotope, 131I (t1/2 = 8.04 days), was detected in wastewater, surficial sediment, and suspended particulate matter (SPM) samples collected from New York Harbor (NYH) between 2001 and 2002. lodine-131 is used as a radiopharmaceutical for medical imaging, diagnostics, and treatments for conditions of the thyroid. It is introduced into the municipal waste stream by medical facilities and patients and is subsequently released into the estuary via wastewater effluent. Measured 131I activities in surface sediments were correlated with those of 7Be (t1/2 = 53.2 days), a naturally occurring radioisotope that is widely used to quantify particle dynamics, sediment focusing, and short-term sediment deposition and accumulation in aquatic systems. Surficial sediment 131I activities were also compared with measured trace metal (Cu, Pb) and organic carbon (OC(sed)) concentrations which can be linked to wastewater inputs. These preliminary results from NYH introduce 131I as a potentially valuable source-specific, shortlived biogeochemical tracer (timescales < 1 month) for particles, sediments, and wastewater-sourced contaminants in urbanized aquatic systems.     

Assessing downstream aquatic habitat availability relative to headwater reservoir management in the Henrys Fork Snake River

Reservoirs are sometimes managed to meet agricultural and other water demands, while also maintaining streamflow for aquatic species and ecosystems. In the Henrys Fork Snake River, Idaho (USA), irrigation-season management of a headwater reservoir is informed by a flow target in a management reach ~95 km downstream. The target is in place to meet irrigation demand and maintain aquatic habitat within the 11.4 km management reach and has undergone four flow target assignments from 1978 to 2021. Recent changes to irrigation-season management to maximize reservoir carryover warranted investigation into the flow target assignment. Thus, we created a streamflow-habitat model using hydraulic measurements, habitat unit mapping, and published habitat suitability criteria for Brown Trout (Salmo trutta), Rainbow Trout (Oncorhynchus mykiss), and Mountain Whitefish (Prosopium williamsoni). We used model output to compare habitat availability across two management regimes (1978–2017 and 2018–2021). We found that efforts to minimize reservoir releases in 2018–2021 did not reduce mean irrigation-season fish habitat relative to natural flow, but did reduce overall fish habitat variability during the irrigation season compared to streamflow management in 1978–2017. Field observations for this research led to an adjusted flow target in 2020 that moved the target location downstream of intervening irrigation diversions. Using our model output, we demonstrated that moving the location of the target to account for local irrigation diversions will contribute to more consistently suitable fish habitat in the reach. Our study demonstrates the importance of site selection for establishing environmental flow targets.     

Are staff management practices and inspection risk ratings associated with foodborne disease outbreaks in the catering industry in England and Wales?

Despite structured enforcement of food hygiene requirements known to prevent foodborne disease outbreaks, catering businesses continue to be the most common setting for outbreaks in the United Kingdom. In a matched case control study of catering businesses, 148 businesses associated with outbreaks were compared with 148 control businesses. Hazard analysis critical control point systems and/or formal food hygiene training qualifications were not protective. Food hygiene inspection scores were not useful in predicting which catering businesses were associated with outbreaks. Businesses associated with outbreaks were more likely to be larger small and medium-sized enterprises (SMEs) or to serve Chinese cuisine and less likely to have the owner or manager working in the kitchen, but when size of the SME was taken into account these two differences were no longer significant. In larger businesses, case businesses were more likely to be hotels and were more commonly associated with viral foodborne outbreaks, but there was no explanation within the data for this association.     

A new energy future for South Africa: The political ecology of South African renewable energy

Renewable energy remains a contested topic in South Africa. This paper argues that South Africa can build on the momentum surrounding its introduction of a feed-in tariff by enacting policies that may, if given adequate funding and political effort, allow the country to be a world leader in renewable energy. Given a variety of renewable energy policy options for moving forward, a majority of stakeholders consulted in this study strongly prefer the development of a renewable energy manufacturing cluster, in which government develops coordinated policy mechanisms that attract renewable energy manufacturers, over three other policies suggested by the authors. Interviews with key informants that play critical roles in this decision-making process suggest that there are reasons to remain cautiously optimistic about the country's renewable energy future while cognizant of the challenges that must still be overcome. Opportunities for a low carbon renewable energy transition in South Africa include the prevalence of broad stakeholder consultation, facilitated by civil society, and an innovative policy development context. Significant impediments also exist, however, and include pervasive social issues such as poverty and political inertia, along with the ongoing difficulties facing renewable energy technologies in reaching grid parity with inexpensive and abundant South African coal.