Defect-mediated time-efficient photocatalytic degradation of methylene blue and ciprofloxacin using tungsten-incorporated ternary perovskite BaSnO3 nanoparticles.

Photocatalytic water purification has been extensively explored for its economic, eco-friendly, and sustainable aspects. In this study, tungsten (W) incorporated BaSn1-xWxO3 (x = 0 to 0.05) nanoparticles synthesized by facile hydrogen peroxide precipitation route has been demonstrated for photocatalytic degradation of methylene blue (MB) dye and ciprofloxacin (CIP) antibiotic. The structural analysis indicates the presence of hybrid composite-like nanostructures with reduced crystallinity. Optical studies reveal blueshift in bandgap and decrease in oxygen vacancy defects upon W-incorporation. Pure BaSnO3 shows overall enhanced photocatalytic activity towards MB (90.22%) and CIP (78.12%) after 240 min of white LED light and sunlight irradiation respectively. The 2 % W-incorporated BaSnO3 shows superior photocatalytic degradation of MB (26.89%) and CIP (45.14%) within first 30 min of irradiation confirming the presence of W to be beneficial in the process. The free radical study revealed the dominant role of reactive hole (h+) and oxygen radical (O2•-) species during photodegradation and their intermediates are investigated to elucidate the degradation mechanism of MB within 30 min of irradiation. This study is promising towards developing defect mediated and time-efficient photocatalysts for environmental remediation.

Propulsive cell entry diverts pathogens from immune degradation by remodeling the phagocytic synapse.

Phagocytosis is a critical immune function for infection control and tissue homeostasis. During phagocytosis, pathogens are internalized and degraded in phagolysosomes. For pathogens that evade immune degradation, the prevailing view is that virulence factors are required to disrupt the biogenesis of phagolysosomes. In contrast, we present here that physical forces from motile pathogens during cell entry divert them away from the canonical degradative pathway. This altered fate begins with the force-induced remodeling of the phagocytic synapse formation. We used the parasite Toxoplasma gondii as a model because live Toxoplasma actively invades host cells using gliding motility. To differentiate the effects of physical forces from virulence factors in phagocytosis, we employed magnetic forces to induce propulsive entry of inactivated Toxoplasma into macrophages. Experiments and computer simulations show that large propulsive forces hinder productive activation of receptors by preventing their spatial segregation from phosphatases at the phagocytic synapse. Consequently, the inactivated parasites are engulfed into vacuoles that fail to mature into degradative units, similar to the live motile parasite's intracellular pathway. Using yeast cells and opsonized beads, we confirmed that this mechanism is general, not specific to the parasite used. These results reveal new aspects of immune evasion by demonstrating how physical forces during active cell entry, independent of virulence factors, enable pathogens to circumvent phagolysosomal degradation.

Direct Quantification of Serum Protein Interactions with PEGylated Micelle Nanocarriers.

A large repertoire of nanocarrier (NC) technologies exists, each with highly specified advantages in terms of targetability, stability, and immunological inertness. The characterization of such NC properties within physiological conditions is essential for the development of optimized drug delivery systems. One method that is well established for reducing premature elimination by avoiding protein adsorption on NCs is surface functionalization with poly(ethylene glycol) (PEG), aptly called PEGylation. However, recent studies revealed that some PEGylated NCs have a delayed immune response, indicating the occurrence of protein-NC interactions. Obvious protein-NC interactions, especially in micellar systems, may have been overlooked as many early studies relied on techniques less sensitive to molecular level interactions. More sensitive techniques have been developed, but a major challenge is the direct measurement of interactions, which must be done in situ, as micelle assemblies are dynamic. Here, we report the use of pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS) to interrogate the interactions between two PEG-based micelle models and serum albumin protein to compare protein adsorption differences based on linear or cyclic PEG architectures. First, by measuring micelle diffusion in isolated and mixed solutions, we confirmed the thermal stability of diblock and triblock copolymer micelle assemblies. Further, we measured the co-diffusion of micelles and serum proteins, the magnitudes of which increased with concentration and continued incubation. The results demonstrate that PIE-FCCS is capable of measuring direct interactions between fluorescently labeled NC and serum proteins, even at concentrations 500 times lower than those observed physiologically. This capability showcases the potential utility of PIE-FCCS in the characterization of drug delivery systems in biomimetic conditions.

Responses to exercise in systemic sclerosis-associated interstitial lung disease.

INTRODUCTION: Pulmonary complications in systemic sclerosis (SSc) significantly increase morbidity and mortality. Our aim was to determine the factors limiting exercise capacity in SSc patients with and without interstitial lung disease (ILD), and to identify and quantify abnormalities during exercise that might assist in clinical assessment of this complication. METHODS: Fifteen patients with SSc and ILD (SSc-ILD) were compared with 10 patients with SSc without ILD and 9 age- and sex-matched normal volunteers. Subjects performed symptom-limited incremental treadmill exercise with online measurement of respiratory gas exchange, arterial blood gas sampling and measurement of neurohormones in venous blood. RESULTS: Patients with SSc-ILD had lower exercise capacity than SSc patients without ILD or normal subjects (peak oxygen consumption (PV̇O2 ) (17.1 [4.2] vs. 22.0 [4.7] and 23.0 [5.4] ml kg-1 min-1 , respectively, mean [SD], p < 0.01 ANOVA), but PV̇O2 did not correlate with static pulmonary function measurements. Ventilatory equivalent for CO2 (V̇E/V̇CO2 ; nadir) was higher in SSc-ILD patients than the other two groups (36.6 [8.0] vs. 29.9 [4.4] and 30.0 [2.5], p < 0.005) as were peak exercise dead-space tidal volume ratio (0.44 [0.06] vs. 0.26 [0.09] and 0.26 [0.05], p < 0.001) and peak exercise alveolar-arterial difference (28.9 [16.9] vs. 18.8 [14.0] and 11.5 [6.9] mmHg, p < 0.05). Atrial natriuretic peptide was elevated in both SSc patient groups. CONCLUSIONS: SSc-ILD results in lower exercise capacity than SSc without ILD, and abnormalities of gas exchange are seen. The possible use of cardiopulmonary exercise testing to identify disease and quantify impairment in SSc-ILD merits further study.

Variability in physical therapy protocols following total shoulder arthroplasty

Background@#Physical therapy (PT) plays an important role in the recovery of function following anatomic total shoulder arthroplasty (aTSA). While several PT protocols have been published for these patients, there is no standardized protocol for aTSA rehabilitation. This lack of standardization may lead to confusion between patients and physicians, possibly resulting in suboptimal outcomes. This study examines how PT protocols provided by academic orthopedic surgery programs vary regarding therapeutic goals and activities following aTSA. @*Methods@#PT protocols for aTSA available online from the Accreditation Council for Graduate Medical Education accredited orthopedic surgery programs were included for review. Each protocol was analyzed to evaluate it for differences in recommendation of length of immobilization, range of motion (ROM) goals, start time for and progression of therapeutic exercises, and timing for return to functional activity. @*Results@#Of 175 accredited programs, 25 (14.2%) had protocols publicly available, programs (92%) recommended sling immobilization outside of therapy for an average of 4.4±2.0 weeks. Most protocols gave recommendations on starting active forward flexion (24 protocols, range 1–7 weeks), external rotation (22 protocols, range 1–7 weeks), and internal rotation (18 protocols, range 4–7 weeks). Full passive ROM was recommended at 10.8±5.7 weeks, and active ROM was 13.3±3.9 weeks, on average. ROM goals were inconsistent among protocols, with significant variations in recommended ROM and resistance exercise start times. Only 13 protocols (52%) gave recommendations on resuming recreational activities (mean, 17.4±4.4 weeks). @*Conclusions@#Publicly available PT protocols for aTSA rehabilitation are highly variable.Level of evidence: IV.

Exploring plant volatile-mediated interactions between native and introduced plants and insects.

In invasion scenarios, native and introduced species co-occur creating new interactions and modifying existing ones. Many plant-plant and plant-insect interactions are mediated by volatile organic compounds (VOCs), however, these have seldom been studied in an invasion context. To fill this knowledge gap, we explored some interactions mediated by VOCs between native and introduced plants and insects in a New Zealand system. We investigated whether a native plant, Leptospermum scoparium (manuka), changes its volatile profile when grown adjacent to two European introduced plants, Calluna vulgaris (heather) and Cytisus scoparius (Scotch broom), in a semi-field trial using potted plants without above- or below-ground physical contact. We also investigated the influence of plant cues on the host-searching behaviour of two beetles, the native Pyronota festiva (manuka beetle), and the introduced biocontrol agent Lochmaea suturalis (heather beetle), by offering them their host-plant and non-host volatiles versus clean air, and their combination in a Y-tube olfactometer. As a follow-up, we performed preference/feeding tests in Petri dishes with fresh plant material. Results of the semi-field experiment show a significant reduction in green leaf volatiles, sesquiterpenes and total volatile emissions by manuka plants neighbouring heather. In the Y-tube assays, the native beetle P. festiva performed poorly in discriminating between host and non-host plants based on plant volatile cues only. However, it performed relatively well in the Petri dish tests, where other cues (i.e., visual, gustatory or tactile) were present. In contrast, the introduced beetle L. suturalis showed high host-specificity in both Y-tube and Petri dish assays. This study illustrates the importance of VOCs in mediating interactions between introduced and native species, suggesting that invasive plants can disrupt native plants' communication and affect the host-searching behaviour of native insects. It also reinforces the relevance of regular host testing on introduced weed biocontrol agents to avoid unwanted host shifts or host-range expansion.

Sexual Orientation Change Efforts Do Not Increase Suicide: Correcting a False Research Narrative.

Sexual orientation change efforts (SOCEs) signify activities designed to change or reduce homosexual orientation. Recent studies have claimed that such therapies increase suicide risk by showing positive associations between SOCE and lifetime suicidality, without excluding behavior that pre-dated SOCE. In this way, Blosnich et al.'s (2020) recent analysis of a national probability sample of 1518 sexual minority persons concluded that SOCE "may compound or create…suicidal ideation and suicide attempts" but after correcting for pre-existing suicidality, SOCE was not positively associated with any form of suicidality. For suicidal ideation, Blosnich et al. reported an adjusted odds ratio (AOR) of 1.92 (95% CI 1.01-3.64); the corrected AOR was .44 (.20-.94). For suicide planning, Blosnich et al.'s AOR was 1.75 (1.01-3.06); corrected was .60 (.32-1.14). For suicide attempts, Blosnich et al.'s AOR was 1.75 (.99-3.08); corrected was .74 (.36-1.43). Undergoing SOCE after expressing suicidal behavior reduced subsequent suicide attempts from 72 to 80%, compared to those not undergoing SOCE, when SOCE followed a prior expression of suicidal ideation (AOR .17, .05-.55), planning (AOR .13, .04-.45) or intention (AOR .10, .03-.30); however, SOCE following an initial suicide attempt did not significantly reduce further attempts. By violating the principle that a cause cannot occur after an effect, Blosnich et al. misstated the correct conclusion. Experiencing SOCE does not result in higher suicidality, as they claim, and may sharply reduce subsequent suicide attempts. Restrictions on SOCE will not reduce suicidal risk among sexual minorities and may deprive them of an important resource for reducing suicide attempts.

Multiomic Characterization of High-Grade Serous Ovarian Carcinoma Enables High-Resolution Patient Stratification.

PURPOSE: High-grade serous ovarian carcinoma (HGSOC) is the most common ovarian cancer type; most patients experience disease recurrence that accumulates chemoresistance, leading to treatment failure. Genomic and transcriptomic features have been associated with differential outcome and treatment response. However, the relationship between events at the gene sequence, copy number, and gene-expression levels remains poorly defined. EXPERIMENTAL DESIGN: We perform multiomic characterization of a large HGSOC cohort (n = 362) with detailed clinical annotation to interrogate the relationship between patient subgroups defined by specific molecular events. RESULTS: BRCA2-mutant (BRCA2m) and EMSY-overexpressing cases demonstrated prolonged survival [multivariable hazard ratios (HR) 0.40 and 0.51] and significantly higher first- and second-line chemotherapy response rate. CCNE1-gained (CCNE1g) cases demonstrated underrepresentation of FIGO stage IV cases, with shorter survival but no significant difference in treatment response. We demonstrate marked overlap between the TCGA- and Tothill-derived subtypes. IMR/C2 cases displayed higher BRCA1/2m frequency (25.5%, 32.5%) and significantly greater immune cell infiltration, whereas PRO/C5 cases had the highest CCNE1g rate (23.9%, 22.2%) and were uniformly low in immune cell infiltration. The survival benefit for cases with aberrations in homologous recombination repair (HRR) genes was apparent across all transcriptomic subtypes (HR range, 0.48-0.68). There was significant co-occurrence of RB loss and HRR gene aberrations; RB loss was further associated with favorable survival within HRR-aberrant cases (multivariable HR, 0.50). CONCLUSIONS: These data paint a high-resolution picture of the molecular landscape in HGSOC, better defining patients who may benefit most from specific molecular therapeutics and highlighting those for whom novel treatment strategies are needed to improve outcomes.

Corrigendum: Absence of Behavioral Harm Following Non-efficacious Sexual Orientation Change Efforts: A Retrospective Study of United States Sexual Minority Adults, 2016-2018.

[This corrects the article DOI: 10.3389/fpsyg.2022.823647.].

Absence of Behavioral Harm Following Non-efficacious Sexual Orientation Change Efforts: A Retrospective Study of United States Sexual Minority Adults, 2016-2018.

BACKGROUND: Do sexual minority persons who have undergone unsuccessful sexual orientation change efforts (SOCE) suffer subsequent psychological or social harm from the attempt? Previous studies have conflated present and past, even pre-SOCE, harm in addressing this question. This study attempts, for the first time, to isolate and examine the question of current psychosocial harm for former SOCE participants among sexual minorities in representative population data. METHOD: Using nationally representative data (n = 1,518) across three cohorts of sexual minorities (centered in 1969, 1987, and 2003) in the United States (U.S.), persons exposed to SOCE were compared with the remainder not exposed to SOCE on two measures of internal distress-psychological distress (Kessler scale) and current mental health-and seven measures of behavioral harm: substance abuse (DUDIT); alcohol dependence (AUDIT-C); self-harm; suicide ideation; suicide planning; suicide intentions; and suicide attempts. RESULTS: The SOCE group was statistically indistinguishable from the non-SOCE group on any measure of harm. For behavioral harm, risk ratios were 0.97-1.02. Harm was equivalent for the two groups despite the SOCE group having experienced higher lifetime and current minority stress, greater childhood adversity, and lower socioeconomic status. Logistic regression models that adjusted for these differences suggest that SOCE exposure reduced the effect of minority stress and childhood adversity for suicide attempts, although this effect did not fully account for the equivalence between the SOCE and non-SOCE groups. CONCLUSION: Despite higher exposure to factors predicting behavioral harm-minority stress, childhood adversity, and lower socioeconomic background-sexual minority persons who had undergone failed SOCE therapy did not suffer higher psychological or social harm. Concerns to restrict or ban SOCE due to elevated harm are unfounded. Further study is needed to clarify the reasons for the absence of harm from SOCE.

Cancer-Associated SF3B1 Mutations Confer a BRCA-Like Cellular Phenotype and Synthetic Lethality to PARP Inhibitors.

Mutations in SF3B1 have been identified across several cancer types. This key spliceosome component promotes the efficient mRNA splicing of thousands of genes including those with crucial roles in the cellular response to DNA damage. Here, we demonstrate that depletion of SF3B1 specifically compromises homologous recombination (HR) and is epistatic with loss of BRCA1. More importantly, the most prevalent cancer-associated mutation in SF3B1, K700E, also affects HR efficiency and as a consequence, increases the cellular sensitivity to ionizing radiation and a variety of chemotherapeutic agents, including PARP inhibitors. In addition, the SF3B1 K700E mutation induced unscheduled R-loop formation, replication fork stalling, increased fork degradation, and defective replication fork restart. Taken together, these data suggest that tumor-associated mutations in SF3B1 induce a BRCA-like cellular phenotype that confers synthetic lethality to DNA-damaging agents and PARP inhibitors, which can be exploited therapeutically. SIGNIFICANCE: The cancer-associated SF3B1K700E mutation induces DNA damage via generation of genotoxic R-loops and stalled replication forks, defective homologous recombination, and increased replication fork degradation, which can be targeted with PARP inhibitors.

Seasonal Volatile Emission Patterns of the Endemic New Zealand Shrub Dracophyllum subulatum on the North Island Central Plateau.

Volatile organic compounds (VOCs) produced by plants are essential indicators of their physiological response to environmental conditions. But evidence of natural variation in VOC emissions and their contributing factors is still limited, especially for non-cultivated species. Here we explored the natural volatile emissions of Dracophyllum subulatum Hook.f., an endemic shrub to the North Island Central Plateau of New Zealand, and determined some environmental factors driving the plant's emissions. Volatile emissions of D. subulatum were measured on four separate occasions from December 2017 to September 2018 using the "push-pull" headspace sampling technique and analyzed using gas chromatography-mass spectrometry (GC-MS). D. subulatum was classified based on the volatiles measured on each sampling occasion using linear discriminant analysis (LDA). On each sampling occasion, we also recorded and compared ambient air temperature, herbivory damage, total soil nitrogen (N), available phosphorus (P), potassium (K), and soil moisture content. The relationship between environmental variables that differed significantly between sampling occasions and volatile emissions were estimated using generalized linear models (GLMs). Based on VOCs measured on each sampling occasion, we were able to distinguish different chemical profiles. Overall, we found that total emission and the relative proportions of all major chemical classes released by D. subulatum were significantly higher during summer. The GLMs reveal that differences in environmental factors between the four sampling occasions are highly associated with changing emissions. Higher temperatures in summer had a consistently strong positive relationship with emissions, while the impacts of soil moisture content, P and K were variable and depended on the chemical class. These results are discussed, particularly how high temperature (warming) may shape volatile emissions and plants' ecology.

Computational validation of ABCB1 gene polymorphism and its effect on tacrolimus dose concentration/levels in renal transplant individuals of South India.

Patients with end-stage renal failure require hemodialysis and peritoneal dialysis; however, kidney transplantation is considered a better treatment option for renal failure patients, improving their quality of life and longevity. Among several potent immunosuppressive agents, tacrolimus (TAC) has shown progressive improvement in the graft survival rates after renal transplantation. Fifty kidney transplant patients undergoing TAC immunosuppressive treatment were included. The human genomic DNA was isolated using the phenol-chloroform extraction procedure. CYP3A5*6, CYP3A5*2, and ABCB1 exon 21 G2677 T/A polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fisher's exact test and Chi-square analysis were performed to analyze the data, where p < 0.05 was considered statistically significant. In addition, we implemented bioinformatics studies on ABCB1 protein to determine the mutation's effect sequentially and structurally. Among the genotyped single nucleotide polymorphisms (SNPs), SNPs of CYP3A5*2 and CYP3A5*6 did not vary in the studied population. The concentration/dose (C/D) ratio of TT genotype of the ABCB1 gene was higher (95% CI: 177.38-269.46) when compared to TA and AA. However, there were no substantial differences between the ABCB1 genotypes and TAC C/D ratio (p = 0.953). The TAC dose mg/kg/day (p = 0.002) and C/D ratio (p = 0.004) exhibited a statistically significant difference. However, no significant difference was found with respect to the ABCB1 gene between the non-toxicity and toxicity groups. Mutation and residue interaction analysis results showed that the S893T mutation destabilizes the ABCB1 protein, thus reducing the protein's flexibility. The present study demonstrated a substantial relationship between the TAC dose and C/D ratio, including the non-toxicity and toxicity groups. However, no possible correlation was observed between the ABCB1 gene polymorphism and renal transplant.

Clinical Recognition of Substance Use Disorders in Medicaid Primary Care Associated With Universal Screening, Brief Intervention and Referral to Treatment (SBIRT).

OBJECTIVE: Screening, Brief Intervention and Referral to Treatment (SBIRT) programs have been effective for moderate reductions of alcohol use among participants in universal settings. However, there has been limited evidence of effectiveness in referring individuals to specialty care, and the literature now often refers to screening and brief intervention (SBI). This study examines documentation of substance use disorder (SUD) diagnoses in a low-income Medicaid population to evaluate the effect of universal SBIRT on healthcare system recognition of SUDs, a first step to obtaining a referral to treatment (RT) for individuals with SUDs. METHOD: SBI patient data from Wisconsin's Initiative to Promote Healthy Lifestyles (WIPHL) were linked to Wisconsin Medicaid claims data. A comparison group of Medicaid beneficiaries was identified from a matched sample of non-SBIRT clinics (total study N = 14,856). Hierarchical generalized linear modeling was used to assess rates of SUD diagnosis in the 12 months following receipt of SBIRT in WIPHL clinics compared with rates in non-SBIRT clinics. Analysis controlled for clinic, individual patient's health status, demographics, and baseline substance use diagnoses. RESULTS: SBIRT was associated with greater odds of being diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), alcohol abuse or dependence as well as drug abuse or dependence over the 12 months subsequent to receipt of the screen. The overall diagnostic rate for any DSM-IV substance abuse or dependence was 9.9% at baseline and 12.2% during the follow-up year. SBIRT patients had 42% (p = .003) greater odds of being diagnosed with a substance use disorder within 12 months relative to comparison clinic patients. However, there were very few claims for specialty SUD services. CONCLUSIONS: The presence of SBIRT in a primary care clinic appears to increase the awareness and recognition of patients with SUDs and a greater willingness of healthcare providers to diagnose patients with an alcohol or drug use disorder on Medicaid claims. Further research is needed to determine if this increase in diagnosis reflects integrated care for SUDs or if it leads to improved access to specialty care, in which case abandonment of the RT component of SBIRT may be premature.

Efficacy and risk of sexual orientation change efforts: a retrospective analysis of 125 exposed men.

BACKGROUND: Voluntary therapeutic interventions to reduce unwanted same-sex sexuality are collectively known as sexual orientation change efforts (SOCE).  Currently almost all evidence addressing the contested question whether SOCE is effective or safe consists of anecdotes or very small sample qualitative studies of persons who currently identify as sexual minority and thus by definition failed to change.  We conducted this study to examine the efficacy and risk outcomes for a group of SOCE participants unbiased by current sexual orientation.       Methods: We examined a convenience sample of 125 men who had undergone SOCE for homosexual-to-heterosexual change in sexual attraction, identity and behavior, and for positive and negative changes in psychosocial problem domains (depression, suicidality, self-harm, self-esteem, social function, and alcohol or substance abuse).  Mean change was assessed by parametric (t-test) and nonparametric (Wilcoxon sign rank test) significance tests.   Results: Exposure to SOCE was associated with significant declines in same-sex attraction (from 5.7 to 4.1 on the Kinsey scale, p <.000), identification (4.8 to 3.6, p < .000), and sexual activity (2.4 to 1.5 on a 4-point scale of frequency, p < .000). From 45% to 69% of SOCE participants achieved at least partial remission of unwanted same-sex sexuality; full remission was achieved by 14% for sexual attraction and identification, and 26% for sexual behavior.  Rates were higher among married men, but 4-10% of participants experienced increased same-sex orientation after SOCE.  From 0.8% to 4.8% of participants reported marked or severe negative psychosocial change following SOCE, but 12.1% to 61.3% reported marked or severe positive psychosocial change.  Net change was significantly positive for all problem domains.   Conclusion: SOCE was perceived as an effective and safe therapeutic practice by this sample of participants.  We close by offering a unifying understanding of discrepant findings within this literature and caution against broad generalizations of our results.

Potential application of γ-H2AX as a biodosimetry tool for radiation triage.

Radiation triage and biological dosimetry are two initial steps in the medical management of exposed individuals following radiological accidents. Well established biodosimetry methods such as the dicentric (DC) assay, micronucleus (MN) assay, and fluorescence in-situ hybridization (FISH) translocation assay (for residual damage) have been used for this purpose for several decades. Recent advances in scoring methodology and networking among established laboratories have increased triage capacity; however, these methods still have limitations in analysing large sample numbers, particularly because of the ∼ 48 h minimum culture time required prior to analysis. Hence, there is a need for simple, and high throughput markers to identify exposed individuals in case of radiological/nuclear emergencies. In recent years, a few markers were identified, one being phosphorylated histone 2AX (γ-H2AX), which measured a nuclear foci or nuclear staining intensity that was found to be suitable for triage. Measurement of γ-H2AX foci formed at and around the sites of DNA double-strand breaks is a rapid and sensitive biodosimetry method which does not require culturing and is thus promising for the analysis of a large number of samples. In this review, we have summarized the recent developments of γ-H2AX assay in radiation triage and biodosimetry, focusing chiefly on: i) the importance of baseline frequency and reported values among different laboratories, ii) the influence of known and unknown variables on dose estimation, iii) quality assurance such as inter-laboratory comparison between scorers and scoring methods, and iv) current limitations and potential for future development.

CryoEM and AI reveal a structure of SARS-CoV-2 Nsp2, a multifunctional protein involved in key host processes.

The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis of those functions, remain unknown. Here, we report an atomic model for full-length Nsp2 obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. The resulting structure reveals a highly-conserved zinc ion-binding site, suggesting a role for Nsp2 in RNA binding. Mapping emerging mutations from variants of SARS-CoV-2 on the resulting structure shows potential host-Nsp2 interaction regions. Using structural analysis together with affinity tagged purification mass spectrometry experiments, we identify Nsp2 mutants that are unable to interact with the actin-nucleation-promoting WASH protein complex or with GIGYF2, an inhibitor of translation initiation and modulator of ribosome-associated quality control. Our work suggests a potential role of Nsp2 in linking viral transcription within the viral replication-transcription complexes (RTC) to the translation initiation of the viral message. Collectively, the structure reported here, combined with mutant interaction mapping, provides a foundation for functional studies of this evolutionary conserved coronavirus protein and may assist future drug design.

The Case for Mom and Dad.

Is the system of norms comprising traditional, natural marriage-featuring formally enacted, irrevocable, exclusive man/woman sexual union preceded by chastity-essential for children's development and well-being, as Catholic teaching asserts? Review of an extensive body of diverse research finds that, compared to children continuously living with two parents, married parents, or their own biological parents, children in other family arrangements consistently experience lower emotional well-being, physical health, and academic achievement. Competing research has variously attributed this difference to a lack of married parents, two parents, complementary man/woman parents, or family stability, but these possibilities have not previously been studied in combination. To address this question, family structure differences and determinants of child well-being (reverse coded to show child distress) were examined using the 2008-2018 National Health Interview Surveys (n = 82,635). Adjusted odds ratios (AOR) for child emotional problems were higher with less than two parents (AOR = 1.42, 95% CI 1.27-1.56), unmarried parents (1.46, 95% CI 1.31-1.61), unstable parents (1.55, 95% CI 1.27-1.76), or less than two biological parents (AOR = 1.70, 95% CI 1.55-2.87 for one biological parent; 4.77, 95% CI 3.95-5.77 for no biological parents). When combined in the same model, only the lack of joint biological parentage accounted for higher distress, with outcomes significantly worse without the biological father than without the biological mother (interaction AOR = 1.33, 95% CI 1.04-1.71). This evidence strongly supports the claim that maximum child development occurs only in the persistent care of both of the child's own biological parents. Marriage benefits children primarily by ensuring such care. Implications are discussed. SUMMARY: Children raised apart from the care of both natural parents consistently experience lower developmental outcomes. Traditional, religious marriage norms-a lifelong, exclusive sexual union between man and woman-benefit children by establishing strong conditions that promote such care. More than any other family arrangement, marriage assures to children the care of their own mom and dad.