A Look at a WATER Exhibit in Appalachia

Climate change is an oft-controversial challenge – even uttering that term can cause discomfort, especially in the heavily rural areas where land is central to living, such as Appalachia. Visual art exhibitions and creatively designed educational information have the potential to open minds and transform perspectives. We explored this idea through a recent collaborative, interdisciplinary project between the West Virginia Water Research Institute and the West Virginia University Libraries, two organizations that don’t read as necessarily creative in the hills of Appalachia

Reversible conjugation of a CBASS nucleotide cyclase regulates bacterial immune response to phage infection

Funding: This work was funded by a European Research Council Advanced Grant (grant number 101018608) to M.F.W. L.K. was funded by an EMBO postdoctoral fellowship (grant number ALTF 234-2022). L.G.-M. was funded by the UKRI Biotechnology and Biological Sciences Research Council (BBSRC) (grant number BB/T00875X/1).Prokaryotic antiviral defence systems are frequently toxic for host cells and stringent regulation is required to ensure survival and fitness. These systems must be readily available in case of infection but tightly controlled to prevent activation of an unnecessary cellular response. Here we investigate how the bacterial cyclic oligonucleotide-based antiphage signalling system (CBASS) uses its intrinsic protein modification system to regulate the nucleotide cyclase. By integrating a type II CBASS system from Bacillus cereus into the model organism Bacillus subtilis, we show that the protein-conjugating Cap2 (CBASS associated protein 2) enzyme links the cyclase exclusively to the conserved phage shock protein A (PspA) in the absence of phage. The cyclase–PspA conjugation is reversed by the deconjugating isopeptidase Cap3 (CBASS associated protein 3). We propose a model in which the cyclase is held in an inactive state by conjugation to PspA in the absence of phage, with conjugation released upon infection, priming the cyclase for activation.Peer reviewe

How Does Dew Affect L–band Backscatter? Analysis of PALS Data at the Iowa Validation Site and Implications for SMAP

NASA\u27s Soil Moisture Active Passive satellite mission will use both an L-band radiometer and radar to produce global-scale measurements of soil moisture. L-band backscatter is also sensitive to the water content of vegetation. We found that a moderate dew increased the L-band backscatter of a soybean canopy by 1 dB. Dew thus has the potential to add error to satellite observations of soil moisture

The synthesis and characterisation of coordination and hydrogen-bonded networks based on 4-(3,5-dimethyl-1H-pyrazol-4-yl)benzoic acid

The synthesis, structural and thermal characterisation of a number of coordination complexes featuring the N,O-heteroditopic ligand 4-(3,5-dimethyl-1H-pyrazol-4-yl)benzoate, HL are reported. The reaction of H2L with cobalt(II) and nickel(II) nitrates at room temperature in basic DMF/H2O solution gave discrete mononuclear coordination complexes with the general formula {[M(HL)2(H2O)4]·2DMF} (M = Co (1), Ni (2)), whereas the reaction with zinc(II) nitrate gave [Zn(HL)2]∞, 3, a coordination polymer with distorted diamondoid topology and fourfold interpenetration. Coordination about the tetrahedral Zn(II) nodes in 3 are furnished by two pyrazolyl nitrogen atoms and two carboxylate oxygen atoms to give a mixed N2O2 donor set. Isotopological coordination polymers of zinc(II), {[Zn(HL)2]·2CH3OH·H2O}∞, 4, and cobalt(II), [Co(HL)2]∞, 5, are formed when the reactions are carried out under solvothermal conditions in methanol (80 °C) and water (180 °C), respectively. The reaction of H2L with cadmium(II) nitrate at room temperature in methanol gives {[Cd(HL)2(MeOH)2]·1.8MeOH}∞6, a 2-D (4,4)-connected coordination polymer, whereas with copper(II) the formation of green crystals that transform into purple crystals is observed. The metastable green phase [Cu3(HL)4(μ2-SO4)(H2O)3]∞, 7, crystallises with conserved binding domains of the heteroditopic ligand and contains two different metal nodes: a dicopper carboxylate paddle wheel motif, and, a dicopper unit bridged by sulfate ions and coordinated by ligand pyrazolyl nitrogen atoms. The resultant purple phase {[Cu(HL)2]·4CH3OH·H2O}∞, 8, however, has single copper ion nodes coordinated by mixed N2O2 donor sets with trans-square planar geometry and is threefold interpenetrated. The desolvation of 8 was followed by powder X-ray diffraction and single crystal X-ray diffraction which show desolvation induces the transition to a more closely packed structure while the coordination geometry about the copper ions and the network topology is retained. Powder X-ray diffraction and microanalysis were used to characterise the bulk purity of the coordination materials 1-6 and 8. The thermal characteristics of 1-2, 4-6 and 8 were studied by TG-DTA. This led to the curious observation of small exothermic events in networks 4, 6, and 8 that appear to be linked to their decomposition. In addition, the solid state structures of H2L and that of its protonated salt, H2L·HNO3, were also determined and revealed that H2L forms a 2-D hydrogen bonded polymer incorporating helical chains formed through N-HO and O-HN interactions, and that [H3L]NO3 forms a 1-D hydrogen-bonded polymer

α-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra

The protein α-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal α-synuclein burden. Here, feasibility and safety of α-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA) directed against α-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of α-synuclein mRNA and protein in the infused (left) vs. untreated (right) hemisphere and revealed a significant 40–50% suppression of α-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in α-synuclein. Infusion with α-synuclein siRNA, while lowering α-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i) the number and phenotype of nigral dopaminergic neurons, and (ii) the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-α-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics

“I can't lie to your face”: Minimal face-to-face interaction promotes honesty

Scholars have noted that face-to-face (FTF) interaction promotes honesty because it provides opportunities for conversation in which parties exchange information and build rapport. However, it is unclear whether FTF interaction promotes honesty even in the absence of opportunities for back-and-forth conversation. We hypothesized a minimal interaction effect whereby FTF interaction promotes honesty by increasing potential deceivers' consideration of their own moral-interest. To test this account of how FTF interaction may promote honesty, we used a modified version of the deception game (Gneezy, 2005). We found that people were more honest when communicating FTF as opposed to through an intermediary. While FTF interaction tended to promote honesty irrespective of whether it occurred prior to or during the game, the effect was more pronounced when it occurred during the game. The effect of in-game communication medium was mediated by the activation of potential deceivers' moral-interest. We also ruled out alternate accounts involving interpersonal liking, expected counterpart trust, and retaliation fear as honesty-promoting mechanisms. Furthermore, because these effects were not moderated by whether participants had been visually identified during a pre-game interaction, we suggest that our effects are distinct from theoretical accounts involving anonymity. © 2014

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral