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Estuaries are important fish nursery areas, yet little is known of how environmental forcing influences estuarine fishes during their early life stages. We analyzed environmental and larval-juvenile fish community data in the upper San Francisco Estuary (SFE) from spring to early summer 1995–2017, to better understand drivers of spatiotemporal community patterns in this highly modified estuary. We evaluated community patterns based on the relative abundance and diversity of native and introduced fish in the SFE and their predominant distribution (pelagic, demersal). The upper SFE experienced a downward trend of freshwater outflow and upward trends of temperature and salinity intrusion. Fish relative abundance only showed long-term downtrends for native and introduced pelagic fish groups. The most influential habitat components for relative abundance and diversity of fish groups were in decreasing order: temperature, salinity, Secchi depth, bottom depth, and zooplankton biomass. Early life stages of native and introduced fishes were generally segregated spatially and temporally, with native fishes more associated with cooler, saltier, and higher turbidity habitats during early to mid-spring compared to introduced fishes during late spring to early summer. Community ordination showed that environmental (temperature, salinity, outflow, Secchi depth, and zooplankton biomass) and spatiotemporal factors (month and depth), explained nearly 40% of the total variance. Our results suggest that the shorter duration of planktonic and nektonic stages of demersal fish groups results in higher resiliency compared to pelagic fishes. The declining abundance of pelagic fishes overall seems to be linked to drought effects and human-induced synergistic interactions intensified by climate change.

Purpose To investigate the differences in maximal (isometric and concentric peak torque) and explosive (rate of torque development (RTD)) hamstring and quadriceps strength symmetry between males and females during early- and late-phase rehabilitation after anterior cruciate ligament reconstruction (ACLR) using hamstring tendon (HT) autografts and to determine the interaction of time and sex on maximal and explosive strength symmetry. Methods A total of 38 female and 51 male participants were assessed during early (3–6 months post-operative) and late (7–12 months post-operative) phases of rehabilitation following ACLR. Maximal (concentric and isometric peak torque) and explosive (isometric RTD) hamstring and quadriceps strength were assessed and presented as limb symmetry index (LSI). Results Maximal concentric hamstrings asymmetry (Early: 86 ± 14; Late 92 ± 13; p = 0.005) as well as maximal concentric (Early, 73 ± 15; Late 91 ± 12; p p = 0.03) quadriceps asymmetry decreased from early to late rehabilitation. However, there were no significant changes in maximal isometric quadriceps strength and explosive isometric hamstring strength in the same time period. Females had a larger asymmetry in maximal concentric (Females: 75 ± 17; Males: 81 ± 15; p = 0.001) and explosive (Females: 81 ± 32; Males: 89 ± 25; p = 0.01) quadriceps strength than males throughout rehabilitation. There were no sex differences in maximal and explosive hamstring strength. There were no sex by time interactions for any variables. Conclusion Explosive hamstring strength asymmetry did not improve despite recovery of maximal hamstring strength during rehabilitation following ACLR with HT autografts. While sex did not influence strength recovery, females had larger maximal and explosive quadriceps strength asymmetry compared to males throughout rehabilitation following ACLR. Level of evidence Level III

The longleaf pine (LLP) savanna ecosystem once covered ~ 92 million acres of the Southeast USA, but due to anthropogenic activities such as logging and fire suppression, only 3% of its once widespread historic range remains. While many restoration efforts are underway to conserve this biodiverse ecosystem, restoration must be done in the context of climate change. In the last few decades, heatwaves have increased in frequency and intensity across the Southeastern USA with further increases predicted. To expand our understanding of LLP savanna restoration in light of these changes, we ran a series of three simulated heatwave greenhouse experiments through a Course-based Undergraduate Research Experience (CURE) incorporating ~ 150 undergraduate researchers per experiment. We measured plant growth metrics for four understory grasses commonly used in LLP savanna restoration efforts. We found that while most grass plug individuals survived heatwave conditions, aboveground production was reduced due to heatwaves. This productivity decrease could result in less biomass available for the essential vegetation fire feedback loop, where fire increases grass biomass, and in turn, more grass provides more fuel for fire. These results imply that land managers can proactively compensate for biomass loss due to heatwaves by planting more grass plugs during initial restoration. Supplementary Information The online version contains supplementary material available at 10.1007/s11258-021-01212-7.

The aim of this study was to determine the impacts of anterior cruciate ligament reconstruction (ACLR) and recent (

Background Single-cell proteomic analysis provides valuable insights into cellular heterogeneity allowing the characterization of the cellular microenvironment which is difficult to accomplish in bulk proteomic analysis. Currently, single-cell proteomic studies utilize data-dependent acquisition (DDA) mass spectrometry (MS) coupled with a TMT labelled carrier channel. Due to the extremely imbalanced MS signals among the carrier channel and other TMT reporter ions, the quantification is compromised. Thus, data-independent acquisition (DIA)-MS should be considered as an alternative approach towards single-cell proteomic study since it generates reproducible quantitative data. However, there are limited reports on the optimal workflow for DIA-MS-based single-cell analysis. Methods We report an optimized DIA workflow for single-cell proteomics using Orbitrap Lumos Tribrid instrument. We utilized a breast cancer cell line (MDA-MB-231) and induced drug resistant polyaneuploid cancer cells (PACCs) to evaluate our established workflow. Results We found that a short LC gradient was preferable for peptides extracted from single cell level with less than 2 ng sample amount. The total number of co-searching peptide precursors was also critical for protein and peptide identifications at nano- and sub-nano-gram levels. Post-translationally modified peptides could be identified from a nano-gram level of peptides. Using the optimized workflow, up to 1500 protein groups were identified from a single PACC corresponding to 0.2 ng of peptides. Furthermore, about 200 peptides with phosphorylation, acetylation, and ubiquitination were identified from global DIA analysis of 100 cisplatin resistant PACCs (20 ng). Finally, we used this optimized DIA approach to compare the whole proteome of MDA-MB-231 parental cells and induced PACCs at a single-cell level. We found the single-cell level comparison could reflect real protein expression changes and identify the protein copy number. Conclusions Our results demonstrate that the optimized DIA pipeline can serve as a reliable quantitative tool for single-cell as well as sub-nano-gram proteomic analysis.

Pannexin-1 (Panx1) channels have been shown to regulate leukocyte trafficking and tissue inflammation but the mechanism of Panx1 in chronic vascular diseases like abdominal aortic aneurysms (AAA) is unknown. Here we demonstrate that Panx1 on endothelial cells, but not smooth muscle cells, orchestrate a cascade of signaling events to mediate vascular inflammation and remodeling. Mechanistically, Panx1 on endothelial cells acts as a conduit for ATP release that stimulates macrophage activation via P2X7 receptors and mitochondrial DNA release to increase IL-1β and HMGB1 secretion. Secondly, Panx1 signaling regulates smooth muscle cell-dependent intracellular Ca2+ release and vascular remodeling via P2Y2 receptors. Panx1 blockade using probenecid markedly inhibits leukocyte transmigration, aortic inflammation and remodeling to mitigate AAA formation. Panx1 expression is upregulated in human AAAs and retrospective clinical data demonstrated reduced mortality in aortic aneurysm patients treated with Panx1 inhibitors. Collectively, these data identify Panx1 signaling as a contributory mechanism of AAA formation.

Renal cell carcinoma (RCC) accounts for over 400,000 new cases and 175,000 deaths annually. Diagnostic RCC biomarkers may prevent overtreatment in patients with early disease. Extracellular vesicles (EVs) are a promising source of RCC biomarkers because EVs carry proteins and messenger RNA (mRNA) among other biomolecules. We aimed to identify biomarkers and assess biological functions of EV cargo from clear cell RCC (ccRCC), papillary RCC (pRCC), and benign kidney cell lines. EVs were enriched from conditioned cell media by size exclusion chromatography. The EV proteome was assessed using Tandem Mass Tag mass spectrometry (TMT-MS) and NanoString nCounter technology was used to profile 770 cancer-related mRNA present in EVs. The heterogeneity of protein and mRNA abundance and identification highlighted the heterogeneity of EV cargo, even between cell lines of a similar pathological group (e.g., ccRCC or pRCC). Overall, 1726 proteins were quantified across all EV samples, including 181 proteins that were detected in all samples. In the targeted profiling of mRNA by NanoString, 461 mRNAs were detected in EVs from at least one cell line, including 159 that were present in EVs from all cell lines. In addition to a shared EV cargo signature, pRCC, ccRCC, and/or benign renal cell lines also showed unique signatures. Using this multi-omics approach, we identified 34 protein candidate pRCC EV biomarkers and 20 protein and 8 mRNA candidate ccRCC EV biomarkers for clinical validation. Supplementary Information The online version contains supplementary material available at 10.1007/s12032-021-01554-2.

Strength training is a valuable component of hamstring strain injury prevention programmes; however, in recent years a significant body of work has emerged to suggest that the acute responses and chronic adaptations to training with different exercises are heterogeneous. Unfortunately, these research findings do not appear to have uniformly influenced clinical guidelines for exercise selection in hamstring injury prevention or rehabilitation programmes. The purpose of this review was to provide the practitioner with an evidence-base from which to prescribe strengthening exercises to mitigate the risk of hamstring injury. Several studies have established that eccentric knee flexor conditioning reduces the risk of hamstring strain injury when compliance is adequate. The benefits of this type of training are likely to be at least partly mediated by increases in biceps femoris long head fascicle length and improvements in eccentric knee flexor strength. Therefore, selecting exercises with a proven benefit on these variables should form the basis of effective injury prevention protocols. In addition, a growing body of work suggests that the patterns of hamstring muscle activation diverge significantly between different exercises. Typically, relatively higher levels of biceps femoris long head and semimembranosus activity have been observed during hip extension-oriented movements, whereas preferential semitendinosus and biceps femoris short head activation have been reported during knee flexion-oriented movements. These findings may have implications for targeting specific muscles in injury prevention programmes. An evidence-based approach to strength training for the prevention of hamstring strain injury should consider the impact of exercise selection on muscle activation, and the effect of training interventions on hamstring muscle architecture, morphology and function. Most importantly, practitioners should consider the effect of a strength training programme on known or proposed risk factors for hamstring injury.

The nearshore is a critical zone for northeast Pacific Ocean fish communities, including ecologically and culturally important salmon species. The largest dam removal in the world was recently completed on the Elwha River, with the goal of restoring fisheries and ecosystems to the watershed. The nearshore Elwha fish community was monitored monthly from January 2008 to November 2015 before, during and after dam removal. As of September 2015, approximately 2.6 million m3 of sediment material had increased the area of the Elwha delta to over 150 ha. Newly formed nearshore habitats were quickly colonized by fish communities during the dam removal period but the communities were similar in total species richness and Shannon diversity before and after dam removal, and were similar to a nearby reference site (Salt Creek estuary). Select fish species, including ESA-listed Pacific salmon and trout Oncorhynchus spp., and eulachon Thaleichthys pacificus, and non-native, American shad (Alosa sapidissima), appeared quickly in these new habitats. Hatchery releases of Chinook, O. tshawytscha, coho, O. kisutch, and steelhead, O. mykiss (over 3 million total fish annually to the lower river), dominated the Elwha estuary catch from April through August of each year before, during, and after dam removal. Chum salmon catch rate, size, and duration of estuary occupancy declined during and after dam removal. Overall catches of chum salmon fry prior to, during, and after dam removal were significantly negatively correlated with Chinook salmon catches but significantly, and positively, correlated with coho salmon. When assessed at the Elwha estuary separately, chum abundance was significantly positively correlated with Chinook, coho, and steelhead abundance. These patterns indicate overlap, and likely interaction between these respective groups of hatchery and wild fish. Continued hatchery releases may therefore further challenge chum salmon recovery and should be considered when planning for watershed recovery.

Globally, approximately 2.2 billion people rely on groundwater for daily consumption. It is widely accepted that groundwater is more pristine than surface water but while this assumption is frequently the case, groundwater is not ubiquitously free of contaminants; accordingly, this presumption can result in an unfounded and potentially hazardous sense of security among owners, operators and users. The current paper presents a review of published literature providing epidemiological evidence of the contribution of groundwater to global human enteric infection. An emphasis is placed on enteric pathogens transmitted via the faecal-oral route, and specifically those associated with acute gastrointestinal illness (AGI). The review identified 649 published groundwater outbreaks globally between 1948 and 2013 and several epidemiological studies that show there is an increased risk of AGI associated with the consumption of untreated groundwater. The review identified that the following five pathogens were responsible for most outbreaks: norovirus, Campylobacter, Shigella, Hepatitis A and Giardia. Crudely, the authors estimate that between 35.2 and 59.4 million cases of AGI per year globally could be attributable to the consumption of groundwater. Although groundwater is frequently presumed to be a microbiologically safe source of water for consumption, this review demonstrates that consumers served by an untreated groundwater supply remain at risk to enteric disease. The authors conclude that collaboration between microbiologists, hydrogeologists and epidemiologists is needed to better understand pathogen occurrence, persistence, detection and transport in groundwater as well as build stronger epidemiological evidence documenting the true magnitude of disease associated with groundwater globally.

Atypical sensory perception is one of the most ubiquitous symptoms of autism, including a tendency towards a local-processing bias. We investigated whether local-processing biases were associated with global-processing impairments on a global/local attentional-scope paradigm in conjunction with a composite-face task. Behavioural results were related to individuals' levels of autistic traits, specifically the Attention to Detail subscale of the Autism Quotient, and the Sensory Profile Questionnaire. Individuals showing high rates of Attention to Detail were more susceptible to global attentional-scope manipulations, suggesting that local-processing biases associated with Attention to Detail do not come at the cost of a global-processing deficit, but reflect a difference in default global versus local bias. This relationship operated at the attentional/perceptual level, but not response criterion.

It is difficult to determine if smaller urban landscapes such as foundation plantings around buildings are just ornamental or if they have crossed a threshold and become functional communities. We hypothesize that one measure of functionality is the emergence of symbiotic relationships and ecosystem engineers, in particular the appearance of mycorrhizae. The mycorrhizae themselves are difficult to detect but a good indicator of their presence would be the grazers of mycorrhizae and their predators, in particular the microarthropods (Oribatid, Mesostigmatid and Prostigmatid mites and Collembolans). We hypothesize that microarthropod diversity and abundance can indicate when the functional threshold has been crossed. In this study microarthropods in the top two cm of soil were compared among urban, mid-urban (transitional) and natural sites on the University of Victoria campus, British Columbia. We found significantly fewer total microarthropods in the urban sites compared with mid-urban and natural sites. When microarthropods were separated by trophic level, we found that low trophic level microarthropods (dominated by Oribatid mites and Collembolans), were significantly more abundant in natural sites, while predaceous microarthropods (Mesostigmatid mites and Pseudoscorpions) were significantly more abundant in the mid-urban sites. We conclude that soil microarthropod diversity and bundance can indicate when a community has become ecologically functional and is not just ornamental.

Mitochondrial uncoupling protein 1 (UCP1) is enriched within interscapular brown adipose tissue (iBAT) and beige (also known as brite) adipose tissue1,2, but its thermogenic potential is reduced with obesity and type 2 diabetes3–5 for reasons that are not understood. Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in non-neuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively6–8. Recent findings suggest that increased peripheral serotonin9 and polymorphisms in TPH1 are associated with obesity10; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts β-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities.

A systematic study was conducted to further understand the physical origin of stress modification in AlN overgrown on Si(111) upon ion implantation and annealing. Implantation parameters including ion size, energy, dosage, and current density were varied, and their effects on the amorphization process in Si(111) substrates were examined. The creation of a thick (>120 nm) amorphous Si (a-Si) layer was previously shown to result in isolation of an epitaxial AlN film grown on a Si(111) substrate through implantation-induced amorphization of the substrate, and this mechanical isolation resulted in stress dilution in the AlN layer. Results show that implanting at current density of 2 mA/cm2 allows for only a thin amorphous layer to be created because of the effects of dynamic annealing, which simultaneously eliminates any damage created from the ion implantation, regardless of ion species, dosage, and energy. Lowering the current density to 0.2 mA/cm2 does create a thick a-Si layer; however, the amorphization disappears during a high-temperature (HT) anneal. Lowering the current further to 0.2 μA/cm2 creates a thick a-Si layer that can be maintained through a HT anneal, with this difference arising from the interfacial quality of the a-Si and crystalline Si (c-Si) boundary.

Drug dose, high local target tissue concentration and prolonged duration of exposure are essential criteria in achieving optimal drug performance. However, systemically delivered drugs often fail to effectively address these factors with only fractions of the injected dose reaching the target tissue. This is especially evident in the treatment of peritoneal cancers, including mesothelioma, ovarian and pancreatic cancer, which regularly employ regimens of intravenous and/or intraperitoneal chemotherapy (e.g., gemcitabine, cisplatin, pemetrexed and paclitaxel) with limited results. Here, we show that a “two-step” nanoparticle (NP) delivery system may address this limitation. This two-step approach involves the separate administration of NP and drug where, first, the NP localizes to tumor. Second, subsequent administration of drug then rapidly concentrates into the NP already stationed within the target tissue. This two-step method results in a greater than 5-fold increase in intratumoral drug concentrations compared to conventional “drug-alone” administration. These results suggest that this unique two-step delivery may provide a novel method for increasing drug concentrations in target tissues.

Inflammation in obesity increases the levels of the suppressor of cytokine signalling-3 (SOCS3) protein in adipose tissue, but the physiological importance of this protein in regulating whole-body insulin sensitivity in obesity is not known.We generated Socs3 floxed (wild-type, WT) and Socs3 aP2 (also known as Fabp4)-Cre null (Socs3 AKO) mice. Mice were maintained on either a regular chow or a high-fat diet (HFD) for 16 weeks during which time body mass, adiposity, glucose homeostasis and insulin sensitivity were assessed.The HFD increased SOCS3 levels in adipose tissue of WT but not Socs3 AKO mice. WT and Socs3 AKO mice had similar body mass and adiposity, assessed using computed tomography (CT) imaging, irrespective of diet or sex. On a control chow diet there were no differences in insulin sensitivity or glucose tolerance. When fed a HFD, female but not male Socs3 AKO mice had improved glucose tolerance as well as lower fasting glucose and insulin levels compared with WT littermates. Hyperinsulinaemic-euglycaemic clamps and positron emission tomography (PET) imaging demonstrated that improved insulin sensitivity was due to elevated adipose tissue glucose uptake. Increased insulin-stimulated glucose uptake in adipose tissue was associated with enhanced levels and activating phosphorylation of insulin receptor substrate-1 (IRS1).These data demonstrate that inhibiting SOCS3 production in adipose tissue of female mice is effective for improving whole-body insulin sensitivity in obesity.