bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroED structure of lipid-embedded mammalian mitochondrial voltage dependent anion channel
Authors: Martynowycz Michael W. , Khan Farha , Hattne Johan , Abramson Jeff , Gonen Tamir 
Published: September 2020

AbstractA near-atomic resolution structure of the mouse voltage dependent anion channel (mVDAC) is determined by combining cryogenic focused ion-beam (FIB) milling and microcrystal electron diffraction (MicroED). The crystals were grown in a viscous modified bicelle suspension which limited their size and made them unsuitable for conventional X-ray crystallography. Individual thin, plate-like crystals were identified using scanning electron microscopy (SEM) and focused ion-beam (FIB) imaging at high magnification. Three crystals were milled into thin lamellae. MicroED data were collected from each lamellae and merged to increase completeness. Unmodelled densities were observed between protein monomers, suggesting the presence of lipids that likely mediate crystal contacts. This work demonstrates the utility of milling membrane protein microcrystals grown in viscous media using a focused ion-beam for subsequent structure determination by MicroED for samples that are not otherwise tractable by other crystallographic methods. To our knowledge, the structure presented here is the first of a membrane protein crystallized in a lipid matrix and solved by MicroED.
Chronic lithium treatment alters the excitatory/inhibitory balance of synaptic networks and reduces mGluR5-PKC signaling
Authors: Khayachi A. , Ase A. R. , Liao C. , Kamesh A. , Kuhlmann N. , Schorova L. , Chaumette B. , Dion P. , Alda M. , Séguéla P. , Rouleau G.A. , Milnerwood A. J. 
Published: September 2020

ABSTRACTBipolar disorder (BD) is characterized by cyclical alternations between mania and depression, often comorbid with psychosis, and suicide. The mood stabilizer lithium, compared to other medications, is the most efficient treatment for prevention of manic and depressive episodes. The pathophysiology of BD, and lithium’s mode of action, are yet to be fully understood. Evidence suggests a change in the balance of excitatory/inhibitory activity, favouring excitation in BD. Here, we sought to establish a holistic appreciation of the neuronal consequences of lithium exposure in mouse cortical neurons and identify underlying mechanisms. We found that chronic (but not acute) lithium treatment significantly reduced intracellular calcium flux, specifically through the activation of the metabotropic glutamatergic receptor mGluR5. This was associated with altered phosphorylation of PKC and GSK3 kinases, reduced neuronal excitability, and several alterations to synapse function. Consequently, lithium treatment shifts the excitatory/inhibitory balance in the network toward inhibition. Together, the results revealed how lithium dampens neuronal excitability and glutamatergic network activity, which are predicted to be overactive in the manic phase of BD. Our working model of lithium action enables the development of targeted strategies to restore the balance of overactive networks, mimicking the therapeutic benefits of lithium, but with reduced toxicity.
The stem loop 2 motif is a site of vulnerability for SARS-CoV-2
Authors: Lulla Valeria , Wandel Michal P. , Bandyra Katarzyna J. , Ulferts Rachel , Wu Mary , Dendooven Tom , Yang Xiaofei , Doyle Nicole , Oerum Stephanie , Beale Rupert , O’Rourke Sara M. , Randow Felix , Maier Helena J. , Scott William , Ding Yiliang , Firth Andrew E. , Bloznelyte Kotryna , Luisi Ben F. 
Published: September 2020

SummaryRNA structural elements occur in numerous single stranded (+)-sense RNA viruses. The stemloop 2 motif (s2m) is one such element with an unusually high degree of sequence conservation, being found in the 3’ UTR in the genomes of many astroviruses, some picornaviruses and noroviruses, and a variety of coronaviruses, including SARS-CoV and SARS-CoV-2. The evolutionary conservation and its occurrence in all viral subgenomic transcripts implicates a key role of s2m in the viral infection cycle. Our findings indicate that the element, while stably folded, can nonetheless be invaded and remodelled spontaneously by antisense oligonucleotides (ASOs) that initiate pairing in exposed loops and trigger efficient sequence-specific RNA cleavage in reporter assays. ASOs also act to inhibit replication in an astrovirus replicon model system in a sequence-specific, dose-dependent manner and inhibit SARS-CoV-2 infection in cell culture. Our results thus permit us to suggest that the s2m element is a site of vulnerability readily targeted by ASOs, which show promise as anti-viral agents.
Experimental warming reduces gut prokaryotic diversity, survival and thermal tolerance of the eastern subterranean termite,Reticulitermes flavipes(Kollar)
Authors: Arango Rachel A. , Schoville Sean D. , Currie Cameron R. , Carlos-Shanley Camila 
Published: September 2020

AbstractUnderstanding the effects of environmental disturbances on the health and physiology of insects is crucial in predicting the impact of climate change on their distribution, abundance, and ecology. As microbial symbionts have been shown to play an integral role in a diversity of functions within the insect host, research examining how organisms adapt to environmental fluctuations should include their associated microbiota. Previous studies have shown that temperature affects the diversity of protists in termite gut, but less is known about the bacterial symbionts. In this study, subterranean termites (Reticulitermes flavipes(Kollar)) were exposed to three different temperature treatments characterized as low (15 °C), medium (27 °C), and high (35 °C). Results showed low temperature exposed termites had significantly lower CTmin and significantly higher SCP values compared to termites from medium or high temperature groups. This suggests that pre-exposure to cold allowed termites to stay active longer in decreasing temperatures but caused termites to freeze at higher temperatures. High temperature exposure had the most deleterious effects on termites with a significant reduction in termite survival as well as reduced ability to withstand cold stress. The microbial community of high temperature exposed termites showed a reduction in bacterial richness and decreased relative abundance of Spirochaetes, Elusimicrobia, and methanogenic Euryarchaeota. Our results indicate a potential link between gut bacterial symbionts and termite’s physiological response to environmental changes and highlight the need to consider microbial symbionts in studies relating to insect thermosensitivity.
Selling Together: The Benefits of Cooperatives to Women Honey Producers in Ethiopia
Authors: Serra Renata , Davidson Kelly A. 
Published: September 2020

AbstractSmallholder farmers in developing countries encounter multiple barriers in access to inputs and technology, which prevent them from reaping the benefits from market participation. Women farmers face additional constraints due to gender norms that further limit their engagement in productive activities. While collective action has been shown to improve access to markets and economic outcomes for farmers overall, the evidence on the effects of cooperative membership for women smallholders remains limited. We investigate empirically the economic benefits of collective action for women farmers in the honey sector in Ethiopia. Relying on a rich data set on women honey producers, both cooperative members and non‐members, we evaluate the effects of belonging to a cooperative on three outcome variables through coarsened exact matching and regression analysis. Our results indicate that cooperative membership significantly increases the market price and the production quantity and, while the average effect on the share of product marketed is statistically insignificant, significant differences emerge for women with given characteristics. These results are shown to be robust to a number of tests that address biases from selection on observables and unobservables. An analysis of the heterogeneous effects of household membership in multiple groups finds that membership of self‐help groups or farmer associations amplifies the positive outcomes from belonging to a formal cooperative. Finally, qualitative findings derived from the same communities indicate self‐reported improvements in agency and self‐esteem among women members, thus reinforcing the importance of the quantitative findings.
Electrophysiological priming effects confirm that the extrastriate symmetry network is not gated by luminance polarity
Authors: Makin Alexis D. J. , Piovesan Andrea , Tyson‐Carr John , Rampone Giulia , Derpsch Yiovanna , Bertamini Marco 
Published: September 2020

AbstractIt is known that the extrastriate cortex is activated by visual symmetry. This activation generates an ERP component called the Sustained Posterior Negativity (SPN). SPN amplitude increases (i.e., becomes more negative) with repeated presentations. We exploited this SPN priming effect to test whether the extrastriate symmetry response is gated by element luminance polarity. On each trial, participants observed three stimuli (patterns of dots) in rapid succession (500 ms. with 200 ms. gaps). The patterns were either symmetrical or random. The dot elements were either black or white on a grey background. The triplet sequences either showed repeated luminance (black > black > black, or white > white > white) or changing luminance (black > white > black, or white > black > white). As predicted, SPN priming was comparable in repeated and changing luminance conditions. Therefore, symmetry with black elements is not processed independently from symmetry with white elements. Source waveform analysis confirmed that this priming happened within the extrastriate symmetry network. We conclude that the network pools information across luminance polarity channels.
Sarcoptic mange severity is associated with reduced genomic variation and evidence of selection in Yellowstone National Park wolves (Canis lupus)
Authors: DeCandia Alexandra L. , Schrom Edward C. , Brandell Ellen E. , Stahler Daniel R. , vonHoldt Bridgett M. 
Published: September 2020

AbstractPopulation genetic theory posits that molecular variation buffers against disease risk. Although this “monoculture effect” is well supported in agricultural settings, its applicability to wildlife populations remains in question. In the present study, we examined the genomics underlying individual‐level disease severity and population‐level consequences of sarcoptic mange infection in a wild population of canids. Using gray wolves (Canis lupus) reintroduced to Yellowstone National Park (YNP) as our focal system, we leveraged 25 years of observational data and biobanked blood and tissue to genotype 76,859 loci in over 400 wolves. At the individual level, we reported an inverse relationship between host genomic variation and infection severity. We additionally identified 410 loci significantly associated with mange severity, with annotations related to inflammation, immunity, and skin barrier integrity and disorders. We contextualized results within environmental, demographic, and behavioral variables, and confirmed that genetic variation was predictive of infection severity. At the population level, we reported decreased genome‐wide variation since the initial gray wolf reintroduction event and identified evidence of selection acting against alleles associated with mange infection severity. We concluded that genomic variation plays an important role in disease severity in YNP wolves. This role scales from individual to population levels, and includes patterns of genome‐wide variation in support of the monoculture effect and specific loci associated with the complex mange phenotype. Results yielded system‐specific insights, while also highlighting the relevance of genomic analyses to wildlife disease ecology, evolution, and conservation.
Inter‐shift handoff: Changes over a 6‐year interval
Authors: Gu Xiuzhu , Itoh Kenji 
Published: September 2020

AbstractAimsTo capture inter‐shift handoff changes over a 6‐year interval and to verify whether the handoff supporting system and aids (e.g., guidelines, training, and protocols) and environment really affect handoff performance.DesignA non‐experimental cross‐sectional research design. Data from the 2017 and 2011 surveys were used for comparisons.MethodsA questionnaire survey was conducted among nursing staff in 31 general hospitals in 2017 and 4,282 staff responses were collected from inpatient wards such as internal medicine and surgery, the intensive care unit, emergency department and operating room. These were compared with the 1,182 responses collected in the previous 2011 survey.ResultsChanges in the 6‐year interval included the introduction of handoff guidelines and increased provision of training. The handoff approach changed significantly and relied more on electronic systems, especially in inpatient wards. However, there was no significant improvement in interruptions. Information transfer improvement was limited and only observed in the surgery wards. Significant correlations verified that in hospitals where nursing staff more positively evaluated the effectiveness of the guidelines, faced fewer interruptions and had more time, handoff performance was better overall, and a higher frequency of sufficient information transfer was evident.ConclusionAlthough the inter‐shift handoff supporting system had great changes, improvement of information transfer occurred only in the surgery wards and was limited. It was verified that more effective handoff guidelines and a better handoff environment contributed significantly to improving inter‐shift handoff performance.ImpactThis study addressed the question as to whether inter‐shift handoffs have really improved. The answer is yes, but in a limited way. Based on the survey results and handoff practices in Japanese hospitals, a mixed approach (verbal, written, technological) is suggested for inter‐shift handoffs. In addition, it is important to improve the current handoff procedures, guidelines and training.
Prevalence and prognosis of the 2018 vs 2008 AHA definitions of apparent treatment‐resistant hypertension in high‐risk hypertension patients
Authors: Chun Kyeong‐Hyeon , Lee Chan Joo , Oh Jaewon , Lee Sang‐Hak , Kang Seok‐Min , Kario Kazuomi , Park Sungha 
Published: September 2020

AbstractResistant hypertension was defined according to the 2008 scientific statement as office blood pressure ≥ 140/90 mm Hg and the 2018 scientific statement as office blood pressure ≥ 130/80 mm Hg. We investigated the prognostic significance of lowered blood pressure threshold for defining resistant hypertension in the 2018 American Heart Association scientific statement compared with that in the 2008 scientific statement. The participants of this prospective cohort were enrolled from December 2013 to November 2018. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke, and heart failure hospitalization. Renal event was defined as a ≥ 50% decline in estimated glomerular filtration rate or progression to end‐stage renal disease. A total of 206 patients among 2018 (10.2%) were diagnosed with resistant hypertension by the previous definition (≥140/90 mm Hg), and 276 patients among 2011 (13.7%) were diagnosed with resistant hypertension by the updated definition (≥130/80 mm Hg). During a median follow‐up of 4.5 years, 33 MACEs (3.7 per 1000 patient‐years) and 164 renal events (19.9 per 1000 patient‐years) occurred in the study population. Treatment‐resistant hypertension groups had a higher incidence rate of MACEs and renal events than the control groups. In multivariate Cox proportional hazards regression analysis, resistant hypertension by both definitions was significantly associated with increased risk of MACE and renal event. Both the previous and updated definitions of resistant hypertension were significant predictors of MACEs and renal events. This finding supports the adoption of the updated criteria for resistant hypertension in clinical practice.
Brain structural trajectories in youth at familial risk for schizophrenia or bipolar disorder according to development of psychosis spectrum symptoms
Authors: Sugranyes Gisela , de la Serna Elena , Ilzarbe Daniel , Pariente Jose Carlos , Borras Roger , Romero Soledad , Rosa Mireia , Baeza Inmaculada , Moreno Maria Dolores , Bernardo Miguel , Vieta Eduard , Castro‐Fornieles Josefina 
Published: September 2020

BackgroundThe evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period.MethodsOne hundred twenty‐eight individuals (33 SzO and 46 BpO, considered jointly as ‘Familial High Risk’ (FHR), and 49 controls) aged 6–17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2‐ and 4‐year follow‐up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow‐up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume.ResultsFHR participants who developed psychotic spectrum symptoms over time showed greater time‐related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction.ConclusionThe emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross‐sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth.
Exclusive predation of sea turtle hatchlings by juvenile blacktip reef sharks Carcharhinus melanopterus at a turtle nesting site in Malaysia
Authors: Bashir Zalina , Abdullah Maizah M. , Ghaffar Mazlan Abd. , Rusli Mohd Uzair 
Published: September 2020

AbstractThis study reports the discovery of the exclusive predation of sea turtle hatchlings by several juvenile blacktip reef sharks (Carcharhinus melanopterus) in Chagar Hutang bay on Redang Island, Malaysia, in the South China Sea. Three dead specimens of C. melanopterus were retrieved from ghost nets, and the entire digestive tracts of these sharks solely contained the partially digested bodies of sea turtle hatchlings, with no evidence of the remains of any other prey. Thus, juvenile C. melanopterus may opportunistically feed primarily on turtle hatchlings during times when hatchling abundance is high.
Netherton syndrome: Temporary response to dupilumab
Authors: Aktas Meryem , Salman Andac , Apti Sengun Ozlem , Comert Ozer Elif , Hosgoren Tekin Selcen , Akin Cakici Ozlem , Demir Gizem , Ergun Tulin 
Published: September 2020

AbstractNetherton syndrome (NS) is an orphan disease characterized by congenital ichthyosis, hair abnormalities, and atopy, with limited treatment options. We achieved temporary improvement only during the initial 6 weeks of treatment with dupilumab, which differs from the sustained improvement observed in 2 other recently published cases. Although the clinical presentation of atopy and increased pre‐allergic cytokines in NS patients suggest that dupilumab may be beneficial, larger studies are required.
Learning About the Effects of Alert Uncertainty in Attack and Defend Decisions via Cognitive Modeling
Authors: Aggarwal Palvi , Moisan Frederic , Gonzalez Cleotilde , Dutt Varun 
Published: September 2020

Objective We aim to learn about the cognitive mechanisms governing the decisions of attackers and defenders in cybersecurity involving intrusion detection systems (IDSs). Background Prior research has experimentally studied the role of the presence and accuracy of IDS alerts on attacker’s and defender’s decisions using a game-theoretic approach. However, little is known about the cognitive mechanisms that govern these decisions. Method To investigate the cognitive mechanisms governing the attacker’s and defender’s decisions in the presence of IDSs of different accuracies, instance-based learning (IBL) models were developed. One model (NIDS) disregarded the IDS alerts and one model (IDS) considered them in the instance structure. Both the IDS and NIDS models were trained in an existing dataset where IDSs were either absent or present and they possessed different accuracies. The calibrated IDS model was tested in a newly collected test dataset where IDSs were present 50% of the time and they possessed different accuracies. Results Both the IDS and NIDS models were able to account for human decisions in the training dataset, where IDS was absent or present and it possessed different accuracies. However, the IDS model could accurately predict the decision-making in only one of the several IDS accuracy conditions in the test dataset. Conclusions Cognitive models like IBL may provide some insights regarding the cognitive mechanisms governing the decisions of attackers and defenders in conditions not involving IDSs or IDSs of different accuracies. Application IBL models may be helpful for penetration testing exercises in scenarios involving IDSs of different accuracies.