Identification and Quantification of 11 Airborne Biochemicals Emitted by the Brown Recluse and Another Primitive Hunting Spider Using Headspace Solid-Phase Microextraction-GC/MS

Loxosceles reclusa, or brown recluse spider, is a harmful household spider whose habitat extends throughout the Midwest in the USA and other regions in the world. The pheromones and other biomolecules that facilitate signaling for brown recluses and other spider species are poorly understood. A rapid and sensitive method is needed to analyze airborne spider signaling biomolecules to better understand the structure and function of these biochemicals in order to control the population of the spiders. In this study, we developed a novel headspace solid-phase microextraction (HS-SPME)-GC/MS method to analyze potential pheromones and biomolecules emitted by the brown recluse spider. The method is highly selective and sensitive for biomolecule identification and quantification from a single live spider. Using this novel nondestructive HS-SPME-GC/MS technique, we identified 11 airborne biomolecules, including 4-methylquinazoline, dimethyl sulfone, 2-methylpropanoic acid, butanoic acid, hexanal, 3-methylbutanoic acid, 2-methylbutanoic acid, 2,4-dimethylbenzaldehyde, 2-phenoxyethanol, and citral (contains both isomers of neral and geranial). Some of these airborne biomolecules were also reported as semiochemicals associated with biological functions of other spiders and insects. The method was also applied to study the airborne biochemicals of Plectreurys tristis, another primitive hunting spider with a poor web, enabling quantitation of the same compounds and demonstrating a difference in signaling molecule concentrations between the two species. This method has potential application in the study of pheromones and biological signaling in other species, which allows for the possibility of utilizing attractant or deterrent functions to limit household populations of harmful species

Implementation-effectiveness trial of an ecological intervention for physical activity in ethnically diverse low income senior centers.

BackgroundAs the US population ages, there is an increasing need for evidence based, peer-led physical activity programs, particularly in ethnically diverse, low income senior centers where access is limited.Methods/designThe Peer Empowerment Program 4 Physical Activity' (PEP4PA) is a hybrid Type II implementation-effectiveness trial that is a peer-led physical activity (PA) intervention based on the ecological model of behavior change. The initial phase is a cluster randomized control trial randomized to either a peer-led PA intervention or usual center programming. After 18 months, the intervention sites are further randomized to continued support or no support for another 6 months. This study will be conducted at twelve senior centers in San Diego County in low income, diverse communities. In the intervention sites, 24 peer health coaches and 408 adults, aged 50 years and older, are invited to participate. Peer health coaches receive training and support and utilize a tablet computer for delivery and tracking. There are several levels of intervention. Individual components include pedometers, step goals, counseling, and feedback charts. Interpersonal components include group walks, group sharing and health tips, and monthly celebrations. Community components include review of PA resources, walkability audit, sustainability plan, and streetscape improvements. The primary outcome of interest is intensity and location of PA minutes per day, measured every 6 months by wrist and hip accelerometers and GPS devices. Secondary outcomes include blood pressure, physical, cognitive, and emotional functioning. Implementation measures include appropriateness & acceptability (perceived and actual fit), adoption & penetration (reach), fidelity (quantity & quality of intervention delivered), acceptability (satisfaction), costs, and sustainability.DiscussionUsing a peer led implementation strategy to deliver a multi-level community based PA program can enhance program adoption, implementation, and sustainment.Trial registrationClinicalTrials.gov, USA ( NCT02405325 ). Date of registration, March 20, 2015. This website also contains all items from the World Health Organization Trial Registration Data Set

Effects of L-DOPA on Nigral Dopamine Neurons and Local Field Potential: Comparison with Apomorphine and Muscimol

ABSTRACT L-DOPA is more effective than direct dopamine (DA) agonists in relieving the motor deficits in Parkinson's disease. Using in vivo recording, we compared the effect of L-DOPA and the direct DA agonist apomorphine on DA neurons in rat substantia nigra (SN). L-DOPA (50 -100 mg/kg i.v.) decreased the firing rate as well as the variability and slow oscillation (SO) of firing. All effects were blocked by raclopride and mimicked by quinpirole, suggesting that they are mediated through D2-like receptors. Autoreceptor-selective doses of apomorphine (5-20 g/kg i.v.) also inhibited all three parameters. The magnitude of the inhibition, however, was significantly greater than that induced by L-DOPA. Neither L-DOPA nor apomorphine had a consistent effect on SN local field potentials (LFPs). The GABA agonist muscimol, known to preferentially inhibit SN non-DA neurons, consistently inhibited the SO in both DA cell firing and LFPs. These results suggest that SN LFPs mainly reflect the synaptic potentials in non-DA neurons, and L-DOPA and apomorphine, unlike muscimol, affect DA neurons primarily through DA autoreceptors. DA autoreceptor activation is known to hyperpolarize DA cells by increasing the membrane conductance to K ϩ . This increase in membrane conductance would shunt synaptic input to DA neurons, thereby decreasing the variability and SO in DA cell firing. The low potency of L-DOPA to inhibit DA cell firing and reduce their responses to synaptic input may partially account for its superior therapeutic efficacy in Parkinson's disease compared with apomorphine and other direct DA agonists

OpenTEL: lessons from a pandemic for the future of distance education

The move to introduce technology enhanced learning (TEL) is a trend that has been observed for decades. Following the disruption arising from Covid-19 pandemic, there has been a move to remote teaching in universities across the world. This move has put the transformation or digital revolution in the limelight in the media. TEL is of strategic importance to the conduct of teaching, learning and research in education internationally. TEL, when combined with the growing benefits of open approaches to education, leads to a potentially transformational means of learning. In this paper the authors introduce some examples of research projects from the Open University’s OpenTEL research grouping. These examples highlight some of the work conducted relating to supporting students, universities, and communities using TEL during the pandemic. OpenTEL research has identified that Covid-19 has exposed the need for better institutional support for students who are facing stress and disruption in their studies; collaboration among higher educational institutions to share knowledge; better engagement in the online pivot ; and understanding of the possibilities (and limitations) for online tools to maintain existing research communities

Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression.

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST

Effects of sacubitril/valsartan on biomarkers of extracellular matrix regulation in patients with HFrEF

Background: Myocardial fibrosis is an important pathophysiological mechanism underlying the development of heart failure (HF). Given the biochemical targets of sacubitril/valsartan, we hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix (ECM) homeostasis, including collagen synthesis, processing, and degradation, are altered by sacubitril/valsartan in comparison to enalapril. Objectives: The purpose of this study was to examine the effects of sacubitril/valsartan on biomarkers of ECM homeostasis and the association between the rate of primary composite outcome (cardiovascular death or HF hospitalization) and these biomarkers. Methods: Biomarkers at baseline (n = 2,067) and both baseline and 8 months after randomization (n = 1,776) included aldosterone, soluble ST2 (sST2), tissue inhibitor of matrix metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-2, MMP-9, Galectin-3 (Gal-3), N-terminal propeptide of collagen I (PINP), and N-terminal propeptide of collagen III (PIIINP). The effects of sacubitril/valsartan on biomarkers were compared with enalapril. Baseline biomarker values and changes from baseline to 8 months were related to primary outcome. Results: At baseline, the profibrotic biomarkers aldosterone, sST2, TIMP-1, Gal-3, PINP, and PIIINP were higher, and biomarkers associated with collagen degradation, MMP-2 and -9, were lower than published referent control values. Eight months after randomization, aldosterone, sST2, TIMP-1, MMP-9, PINP, and PIIINP had decreased more in the sacubitril/valsartan than enalapril group. At baseline, higher values of sST-2, TIMP-1, and PIIINP were associated with higher primary outcome rates. Changes from baseline to 8 months in sST-2 and TIMP-1 were associated with change in outcomes. Conclusions: Biomarkers associated with profibrotic signaling are altered in HF with reduced ejection fraction, sacubitril/valsartan significantly decreased many of these biomarkers, and these biomarkers have important prognostic value. These findings suggest that sacubitril/valsartan may reduce profibrotic signaling, which may contribute to the improved outcomes. (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure [PARADIGM-HF]; NCT01035255

Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis

SummaryDefective apoptosis renders immortalized epithelial cells highly tumorigenic, but how this is impacted by other common tumor mutations is not known. In apoptosis-defective cells, inhibition of autophagy by AKT activation or by allelic disruption of beclin1 confers sensitivity to metabolic stress by inhibiting an autophagy-dependent survival pathway. While autophagy acts to buffer metabolic stress, the combined impairment of apoptosis and autophagy promotes necrotic cell death in vitro and in vivo. Thus, inhibiting autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors, but this necrosis is associated with inflammation and accelerated tumor growth. Thus, autophagy may function in tumor suppression by mitigating metabolic stress and, in concert with apoptosis, by preventing death by necrosis

Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa)

The aim of our project was to study the effect of streptozotocin (STZ)—induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products), and its ligands—S100B and Carboxymethyl Lysine (CML)-advanced glycation endproduct (AGE) in the laboratory pig. Six months after STZ—injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products—methyl-glyoxal (MG) were performed. The results of our study revealed that STZ—injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT) and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy

Delivering sustained, coordinated and integrated observations of the Southern Ocean for global impact

The Southern Ocean is disproportionately important in its effect on the Earth system, impacting climatic, biogeochemical, and ecological systems, which makes recent observed changes to this system cause for global concern. The enhanced understanding and improvements in predictive skill needed for understanding and projecting future states of the Southern Ocean require sustained observations. Over the last decade, the Southern Ocean Observing System (SOOS) has established networks for enhancing regional coordination and research community groups to advance development of observing system capabilities. These networks support delivery of the SOOS 20-year vision, which is to develop a circumpolar system that ensures time series of key variables, and delivers the greatest impact from data to all key end-users. Although the Southern Ocean remains one of the least-observed ocean regions, enhanced international coordination and advances in autonomous platforms have resulted in progress toward sustained observations of this region. Since 2009, the Southern Ocean community has deployed over 5700 observational platforms south of 40°S. Large-scale, multi-year or sustained, multidisciplinary efforts have been supported and are now delivering observations of essential variables at space and time scales that enable assessment of changes being observed in Southern Ocean systems. The improved observational coverage, however, is predominantly for the open ocean, encompasses the summer, consists of primarily physical oceanographic variables, and covers surface to 2000 m. Significant gaps remain in observations of the ice-impacted ocean, the sea ice, depths >2000 m, the air-ocean-ice interface, biogeochemical and biological variables, and for seasons other than summer. Addressing these data gaps in a sustained way requires parallel advances in coordination networks, cyberinfrastructure and data management tools, observational platform and sensor technology, two-way platform interrogation and data-transmission technologies, modeling frameworks, intercalibration experiments, and development of internationally agreed sampling standards and requirements of key variables. This paper presents a community statement on the major scientific and observational progress of the last decade, and importantly, an assessment of key priorities for the coming decade, toward achieving the SOOS vision and delivering essential data to all end-users.Fil: Newman, Louise. University of Tasmania; AustraliaFil: Heil, Petra. Australian Antarctic Division; Australia. Antarctic Climate And Ecosystems Cooperative Research Centre; AustraliaFil: Trebilco, Rowan. Australian Antarctic Division; Australia. Antarctic Climate And Ecosystems Cooperative Research Centre; AustraliaFil: Katsumata, Katsuro. Japan Agency For Marine earth Science And Technology; JapónFil: Constable, Andrew J.. Antarctic Climate And Ecosystems Cooperative Research Centre; Australia. Australian Antarctic Division; AustraliaFil: Wijk, Esmee van. Commonwealth Scientific And Industrial Research Organization; Australia. Antarctic Climate And Ecosystems Cooperative Research Centre; AustraliaFil: Assmann, Karen. University Goteborg; SueciaFil: Beja, Joana. British Oceanographic Data Centre; AustraliaFil: Bricher, Phillippa. University of Tasmania; AustraliaFil: Coleman, Richard. University of Tasmania; AustraliaFil: Costa, Daniel. University of California; Estados UnidosFil: Diggs, Steve. University of California; Estados UnidosFil: Farneti, Riccardo. The Abdus Salam; Italia. The Abdus Salam. International Centre for Theoretical Physics; ItaliaFil: Fawcett, Sarah. University of Cape Town; SudáfricaFil: Gille, Sarah. University of California; Estados UnidosFil: Hendry, Katharine R.. University of Bristol; Reino UnidoFil: Henley, Sian F.. University of Edinburgh; Reino UnidoFil: Hofmann, Eileen. Old Dominion University; Estados UnidosFil: Maksym, Ted. University of California; Estados UnidosFil: Mazloff, Matthew. University of California; Estados UnidosFil: Meijers, Andrew J.. British Antartic Survey; Reino UnidoFil: Meredith, Michael. British Antartic Survey; Reino UnidoFil: Moreau, Sebastien. Norwegian Polar Institute; NoruegaFil: Ozsoy, Burcu. Istanbul Teknik Üniversitesi; TurquíaFil: Robertson, Robin. Xiamen University; ChinaFil: Schloss, Irene Ruth. Universidad Nacional de Tierra del Fuego; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Schofield, Oscar. State University of New Jersey; Estados UnidosFil: Shi, Jiuxin. Ocean University Of China; ChinaFil: Sikes, Elisabeth L.. State University of New Jersey; Estados UnidosFil: Smith, Inga J.. University of Otago; Nueva Zeland