Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice.

Background: Some evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due to its antioxidant and anti-inflammatory properties. Here we examined acute CBD effects on various behaviors and the endocannabinoid system in HIV Tat transgenic mice. Methods: Tat transgenic mice (female/male) were injected with CBD (3, 10, 30 mg/kg) and assessed for antinociception, activity, coordination, anxiety-like behavior, and recognition memory. Brains were taken to quantify endocannabinoids, cannabinoid receptors, and cannabinoid catabolic enzymes. Additionally, CBD and metabolite 7-hydroxy-CBD were quantified in the plasma and cortex. Results: Tat decreased supraspinal-related nociception and locomotion. CBD and sex had little to no effects on any of the behavioral measures. For the endocannabinoid system male sex was associated with elevated concentration of the proinflammatory metabolite arachidonic acid in various CNS regions, including the cerebellum that also showed higher FAAH expression levels for Tat(+) males. GPR55 expression levels in the striatum and cerebellum were higher for females compared to males. CBD metabolism was altered by sex and Tat expression. Conclusion: Findings indicate that acute CBD effects are not altered by HIV Tat, and acute CBD has no to minimal effects on behavior and the endocannabinoid system.

APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size.

The E4 variant of APOE strongly predisposes individuals to late-onset Alzheimer's disease. We demonstrate that in response to lipogenesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the endoplasmic reticulum (ER) lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts. APOE knockdown promotes fewer, larger LDs after a fatty acid pulse, which contain more unsaturated triglyceride after fatty acid pulse-chase. This LD size phenotype was rescued by chimeric APOE that targets only LDs. Like APOE depletion, APOE4-expressing astrocytes form a small number of large LDs enriched in unsaturated triglyceride. Additionally, the LDs in APOE4 cells exhibit impaired turnover and increased sensitivity to lipid peroxidation. Our data indicate that APOE plays a previously unrecognized role as an LD surface protein that regulates LD size and composition. APOE4 causes aberrant LD composition and morphology. Our study contributes to accumulating evidence that APOE4 astrocytes with large, unsaturated LDs are sensitized to lipid peroxidation, which could contribute to Alzheimer's disease risk.

Effects of acute Δ9-tetrahydrocannabinol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice.

Cannabis use is highly prevalent especially among people living with HIV (PLWH). Activation of the anti-inflammatory and neuroprotective endocannabinoid system by phytocannabinoids, i.e. Δ9-tetrahydrocannabinol (THC), has been proposed to reduce HIV symptoms. However, THC's effects on HIV-related memory deficits are unclear. Using HIV-1 Tat transgenic mice, the current study investigates acute THC effects on various behavioral outcomes and the endocannabinoid system. For the rodent tetrad model, THC doses (1, 3, 10 mg/kg) induced known antinociceptive effects, with Tat induction increasing antinociceptive THC effects at 3 and 10 mg/kg doses. Only minor or no effects were noted for acute THC on body temperature, locomotor activity, and coordination. Increased anxiety-like behavior was found for females compared to males, but acute THC had no effect on anxiety. Object recognition memory was diminished by acute THC in Tat(-) females but not Tat(+) females, without affecting males. The endocannabinoid system and related lipids were not affected by acute THC, except for THC-induced decreases in CB1R protein expression levels in the spinal cord of Tat(-) mice. Female sex and Tat induction was associated with elevated 2-AG, AEA, AA, CB1R, CB2R, FAAH and/or MAGL expression in various brain regions. Further, AEA levels in the prefrontal cortex of Tat(+) females were negatively associated with object recognition memory. Overall, findings indicate that acute THC exerts differential effects on antinociception and memory, dependent on sex and HIV Tat expression, potentially in relation to an altered endocannabinoid system, which may be of relevance in view of potential cannabis-based treatment options for PLWH.

Intrinsic and extrinsic regulation of rhabdomyolysis susceptibility by Tango2.

Rhabdomyolysis is a clinical emergency characterized by severe muscle damage, resulting in the release of intracellular muscle components, which leads to myoglobinuria and, in severe cases, acute kidney failure. Rhabdomyolysis is caused by genetic factors linked to increased disease susceptibility in response to extrinsic triggers. Recessive mutations in TANGO2 result in episodic rhabdomyolysis, metabolic crises, encephalopathy and cardiac arrhythmia. The underlying mechanism contributing to disease onset in response to specific triggers remains unclear. To address these challenges, we created a zebrafish model of Tango2 deficiency. Here, we demonstrate that the loss of Tango2 in zebrafish results in growth defects, early lethality and increased susceptibility of skeletal muscle defects in response to extrinsic triggers, similar to TANGO2-deficient patients. Using lipidomics, we identified alterations in the glycerolipid pathway in tango2 mutants, which is critical for membrane stability and energy balance. Therefore, these studies provide insight into key disease processes in Tango2 deficiency and have increased our understanding of the impacts of specific defects on predisposition to environmental triggers in TANGO2-related disorders.

A comparison of high- and low-resolution gas chromatography-mass spectrometry for herbal product classification: A case study with Ocimum essential oils.

INTRODUCTION: Selection of marker compounds for targeted chemical analysis is complicated when considering varying instrumentation and closely related plant species. High-resolution gas chromatography-mass spectrometry (GC-MS), via orbitrap detection, has yet to be evaluated for improved marker compound selection. OBJECTIVE: This study directly compares high- and low-resolution GC-MS for botanical maker compound selection using Ocimum tenuiflorum L. (OT) and Ocimum gratissimum L. (OG) for botanical ingredient authentication. METHODS: The essential oils of OT and OG were collected via hydrodistillation before untargeted chemical analysis with gas chromatography coupled to single-quadrupole (GC-SQ) and orbitrap (GC-Orbitrap) detectors. The Global Natural Products Social Molecular Networking (GNPS) software was used for compound annotation, and a manual search was used to find the 41 most common Ocimum essential oil metabolites. RESULTS: The GC-Orbitrap resulted in 1.7-fold more metabolite detection and increased dynamic range compared to the GC-SQ. Spectral matching and manual searching were improved with GC-Orbitrap data. Each instrument had differing known compound concentrations; however, there was an overlap of six compounds with higher abundance in OG than OT and three compounds with a higher abundance in OT than OG, suggesting consistent detection of the most variable compounds. An unsupervised principal component analysis (PCA) could not discern the two species with either dataset. CONCLUSION: GC-Orbitrap instrumentation improves compound detection, dynamic range, and feature annotation in essential oil analysis. However, considering both high- and low-resolution data may improve reliable marker compound selection, as GC-Orbitrap analysis alone did not improve unsupervised separation of two Ocimum species compared to GC-SQ data.

Non-esterified erythrocyte linoleic acid, arachidonic acid, and subjective sleep outcomes.

OBJECTIVE: This study investigated whether non-esterified erythrocyte omega-6 PUFAs were associated with subjective assessment of sleep quality and duration, and risk for obstructive sleep apnea. METHODS: In this secondary analysis of the cross-sectional OPPERA-II study, 538 adults completed the Pittsburgh Sleep Quality Index (PSQI), reported their usual hours of sleep, and answered STOP screening questions for obstructive sleep apnea. Circulating non-esterified erythrocyte concentrations of omega-6 PUFA linoleic acid and arachidonic acid were quantified by liquid chromatography tandem mass spectroscopy. Sleep outcomes were dichotomized as poor (PSQI ≤5) vs good (PSQI ≥6) sleep quality, insufficient or excessive (≤6 or >9 h) vs good (7-9 h) sleep duration, and high (≥2 affirmative responses) vs low (<2 affirmative responses) risk for obstructive sleep apnea. Non-esterified omega-6 PUFAs and the continuous covariates of body mass index, Short Form (SF) 12 Health Survey Physical and Mental Component scores and resting measures of systolic and diastolic blood pressure were standardized for multivariable analysis. Categorical covariates were study site, age, sex, and race/ethnicity. Multivariable-adjusted logistic regression first estimated odds ratios (OR) and 95% confidence limits (CL) for sleep outcomes using linoleic acid as the main exposure. Analysis was then repeated using arachidonic acid as the main exposure. RESULTS: In the multivariable-adjusted model, each standard deviation increase in non-esterified erythrocyte linoleic acid was associated with higher odds of poor sleep quality (OR=1.2, 95% CL: 1.1, 1.5), insufficient or excessive sleep (OR= 1.3, 95% CL: 1.1, 1.6) and high-risk for obstructive sleep apnea (OR=1.3, 95% CL: 1.1, 1.6). Likewise, for each standard deviation increase in non-esterified erythrocyte arachidonic acid, odds increased of poor sleep quality (OR=1.2, 95% CL: 1.1, 1.5), and insufficient or excessive sleep (OR=1.2, 95% CL: 1.1, 1.5). Odds of being high risk for obstructive sleep apnea increased with greater circulating arachidonic acid, but the association did not reach statistical significance (OR=1.1, 95% CL: 0.9, 1.4). CONCLUSION: Non-esterified erythrocyte linoleic acid and arachidonic acid were associated with poor sleep quality and insufficient or excessive sleep duration. Linoleic acid, but not arachidonic acid, was also associated with high risk for obstructive sleep apnea.

APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size.

The E4 variant of APOE strongly predisposes individuals to late-onset Alzheimer's disease. We demonstrate that in response to neutral lipid synthesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the ER lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts. APOE knockdown promotes fewer, larger LDs containing more unsaturated triglyceride. This LD size distribution phenotype was rescued by chimeric APOE that targets only LDs. APOE4 - expressing astrocytes also form a small number of large LDs enriched in unsaturated triglyceride. Additionally, the larger LDs in APOE4 cells exhibit impaired turnover and increased sensitivity to lipid peroxidation. Our data indicate that APOE plays a previously unrecognized role as an LD surface protein that regulates LD size and composition. APOE4 is a toxic gain of function variant that causes aberrant LD composition and morphology. We propose that APOE4 astrocytes with large, unsaturated LDs are sensitized to lipid peroxidation or lipotoxicity, which could contribute to Alzheimer's disease risk. Summary: Windham et al . discover that APOE in astrocytes can traffic to lipid droplets (LDs), where it modulates LD composition and size. Astrocytes expressing the Alzheimer's risk variant APOE4 form large LDs with impaired turnover and increased peroxidation sensitivity.

Scavenger receptor BI attenuates oxidized phospholipid-induced pulmonary inflammation.

Damage associated molecular patterns (DAMPs) are molecules released from dead/dying cells following toxicant and/or environmental exposures that activate the immune response through binding of pattern recognition receptors (PRRs). Excessive production of DAMPs or failed clearance leads to chronic inflammation and delayed inflammation resolution. One category of DAMPs are oxidized phospholipids (oxPLs) produced upon exposure to high levels of oxidative stress, such as following ozone (O3) induced inflammation. OxPLs are bound by multiple classes of PRRs that include scavenger receptors (SRs) such as SR class B-1 (SR-BI) and toll-like receptors (TLRs). Interactions between oxPLs and PRRs appear to regulate inflammation; however, the role of SR-BI in oxPL-induced lung inflammation has not been defined. Therefore, we hypothesize that SR-BI is critical in protecting the lung from oxPL-induced pulmonary inflammation/injury. To test this hypothesis, C57BL/6J (WT) female mice were dosed with oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (oxPAPC) by oropharyngeal aspiration which increased pulmonary SR-BI expression. Following oxPAPC exposure, SR-BI deficient (SR-BI-/-) mice exhibited increased lung pathology and inflammatory cytokine/chemokine production. Lipidomic analysis revealed that SR-BI-/- mice had an altered pulmonary lipidome prior to and following oxPAPC exposure, which correlated with increased oxidized phosphatidylcholines (PCs). Finally, we characterized TLR4-mediated activation of NF-κB following oxPAPC exposure and discovered that SR-BI-/- mice had increased TLR4 mRNA expression in lung tissue and macrophages, increased nuclear p65, and decreased cytoplasmic IκBα. Overall, we conclude that SR-BI is required for limiting oxPAPC-induced lung pathology by maintaining lipid homeostasis, reducing oxidized PCs, and attenuating TLR4-NF-κB activation, thereby preventing excessive and persistent inflammation.

Carboxylic Acid Amide but Not Quinone Outside Inhibitor Fungicide Resistance Mutations Show Clade-Specific Occurrence in Pseudoperonospora cubensis Causing Downy Mildew in Commercial and Wild Cucurbits.

Since its reemergence in 2004, Pseudoperonospora cubensis, the causal agent of cucurbit downy mildew (CDM), has experienced significant changes in fungicide sensitivity. Presently, frequent fungicide applications are required to control the disease in cucumber due to the loss of host resistance. Carboxylic acid amides (CAA) and quinone outside inhibitors (QoI) are two fungicide groups used to control foliar diseases in cucurbits, including CDM. Resistance to these fungicides is associated with single nucleotide polymorphism (SNP) mutations. In this study, we used population analyses to determine the occurrence of fungicide resistance mutations to CAA and QoI fungicides in host-adapted clade 1 and clade 2 P. cubensis isolates. Our results revealed that CAA-resistant genotypes occurred more prominently in clade 2 isolates, with more sensitive genotypes observed in clade 1 isolates, while QoI resistance was widespread across isolates from both clades. We also determined that wild cucurbits can serve as reservoirs for P. cubensis isolates containing fungicide resistance alleles. Finally, we report that the G1105W substitution associated with CAA resistance was more prominent within clade 2 P. cubensis isolates while the G1105V resistance substitution and sensitivity genotypes were more prominent in clade 1 isolates. Our findings of clade-specific occurrence of fungicide resistance mutations highlight the importance of understanding the population dynamics of P. cubensis clades by crop and region to design effective fungicide programs and establish accurate baseline sensitivity to active ingredients in P. cubensis populations.

Obesity reprograms the pulmonary polyunsaturated fatty acid-derived lipidome, transcriptome, and gene-oxylipin networks.

Obesity exacerbates inflammation upon lung injury; however, the mechanisms by which obesity primes pulmonary dysregulation prior to external injury are not well studied. Herein, we tested the hypothesis that obesity dysregulates pulmonary PUFA metabolism that is central to inflammation initiation and resolution. We first show that a high-fat diet (HFD) administered to C57BL/6J mice increased the relative abundance of pulmonary PUFA-containing triglycerides and the concentration of PUFA-derived oxylipins (particularly prostaglandins and hydroxyeicosatetraenoic acids), independent of an increase in total pulmonary PUFAs, prior to onset of pulmonary inflammation. Experiments with a genetic model of obesity (ob/ob) generally recapitulated the effects of the HFD on the pulmonary oxylipin signature. Subsequent pulmonary next-generation RNA sequencing identified complex and unique transcriptional regulation with the HFD. We found the HFD increased pathways related to glycerophospholipid metabolism and immunity, including a unique elevation in B cell differentiation and signaling. Furthermore, we conducted computational integration of lipidomic with transcriptomic data. These analyses identified novel HFD-driven networks between glycerophospholipid metabolism and B cell receptor signaling with specific PUFA-derived pulmonary oxylipins. Finally, we confirmed the hypothesis by demonstrating that the concentration of pulmonary oxylipins, in addition to inflammatory markers, were generally increased in mice consuming a HFD upon ozone-induced acute lung injury. Collectively, these data show that a HFD dysregulates pulmonary PUFA metabolism prior to external lung injury, which may be a mechanism by which obesity primes the lungs to respond poorly to infectious and/or inflammatory challenges.

Resolving the phylogenetic relationship among recently diverged members of the rockfish subgenus Sebastosomus.

Rapid speciation is an important aspect of adaptive radiations, but can obfuscate phylogenetic relationships among taxa. For recent radiations, there are challenges to reconstructing the relationships among the species due to often shorter branch lengths. Resolution of these relationships is further confounded when studies only use a few genetic markers. Double digest restriction-site associated DNA sequencing (ddRADseq) is a method of next generation sequencing that identifies many single nucleotide polymorphisms (SNPs) throughout the genome. This increases statistical power to resolve close phylogenetic relationships like those found within an adaptive radiation. We used this approach to understand the evolutionary history of the rockfishes of the genus Sebastes, which experienced an adaptive radiation between 3 and 5 mya. Here, we reconstructed the phylogenetic relationships among six species of rockfish within the subgenus Sebastosomus using over 11,600 SNPs. This reconstruction includes the two recently diverged species, Sebastes mystinus and S. diaconus, that were first described genetically in 2008 using mtDNA control region sequence data and six microsatellite loci. We confirmed the relationship of these cryptic species as sister-taxa and found evidence that S. melanops and S. flavidus were also sister-taxa. The latter contradicts prior studies but is supported by our reconstruction using nuclear DNA and measures of genetic differentiation tests and a discriminant analysis of principal components. The relationships between the species of Sebastosomus are further supported by morphological, biological, and ecological justifications.

Role of placental, fetal and maternal cardiovascular markers in predicting adverse outcome in women with suspected or confirmed pre-eclampsia.

OBJECTIVE: To assess the performance of placental, fetal and maternal cardiovascular markers in the prediction of adverse perinatal and maternal outcomes in women with suspected or confirmed pre-eclampsia. METHODS: This was a prospective prognostic accuracy study of women with suspected or confirmed pre-eclampsia who underwent a series of investigations to measure maternal hemodynamic indices, mean arterial pressure, augmentation index, ophthalmic artery peak systolic velocity (PSV) ratio, uterine artery pulsatility index (UtA-PI), fetal biometric and Doppler parameters, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). The performance of these markers, individually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver-operating-characteristics (ROC)-curve analysis. Adverse maternal outcome was defined as one or more of severe hypertension, admission to the intensive care unit, eclampsia, placental abruption, HELLP syndrome, disseminated intravascular coagulation, platelets < 100 × 109 /L, creatinine > 90 µmol/L and alanine aminotransferase > 100 U/L. Adverse perinatal outcome was defined as one or more of preterm birth at or before 34 + 0 weeks, neonatal intensive care unit admission for > 48 h, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity and confirmed fetal infection. RESULTS: We recruited 126 women with suspected (n = 31) or confirmed (n = 95) pre-eclampsia at a median gestational age of 33.9 weeks (interquartile range, 30.9-36.3 weeks). Pregnancies with adverse perinatal outcome compared to those without had a higher median UtA-PI (1.3 vs 0.8; P < 0.001), ophthalmic artery PSV ratio (0.8 vs 0.7; P = 0.01) and umbilical artery PI percentile (82.0 vs 68.5; P < 0.01) and lower median estimated fetal weight percentile (4.0 vs 43.0; P < 0.001), abdominal circumference percentile (4.0 vs 63.0; P < 0.001), middle cerebral artery PI percentile (28.0 vs 58.5; P < 0.001) and cerebroplacental ratio percentile (18.0 vs 46.5; P < 0.001). Pregnancies with adverse perinatal outcome also had a higher median sFlt-1 (8208.0 pg/mL vs 4508.0 pg/mL; P < 0.001), lower PlGF (27.2 pg/mL vs 76.3 pg/mL; P < 0.001) and a higher sFlt-1/PlGF ratio (445.4 vs 74.4; P < 0.001). The best performing individual marker for predicting adverse perinatal outcome was the sFlt-1/PlGF ratio (area under the ROC curve (AUC), 0.87 (95% CI, 0.81-0.93)), followed by estimated fetal weight (AUC, 0.81 (95% CI, 0.73-0.89)). Women who experienced adverse maternal outcome had a higher median sFlt-1 level (7471.0 pg/mL vs 5131.0 pg/mL; P < 0.001) and sFlt-1/PlGF ratio (204.3 vs 93.3; P < 0.001) and a lower PlGF level (37.0 pg/mL vs 66.1 pg/mL; P = 0.01) and estimated fetal weight percentile (16.5 vs 37.0; P = 0.04). All markers performed poorly in predicting adverse maternal outcome, with sFlt-1 (AUC, 0.69 (95% CI, 0.60-0.79)) and sFlt-1/PlGF ratio (AUC, 0.69 (95% CI, 0.59-0.78)) demonstrating the best individual performance. The addition of cardiovascular, fetal or other placental indices to the sFlt-1/PlGF ratio did not improve the prediction of adverse maternal or perinatal outcomes. CONCLUSIONS: The sFlt-1/PlGF ratio performs well in predicting adverse perinatal outcomes but is a poor predictor of adverse maternal outcomes in women with suspected or diagnosed pre-eclampsia. The addition of cardiovascular or fetal indices to the model is unlikely to improve the prognostic performance of the sFlt-1/PlGF ratio. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Identifying dementia in Down syndrome with the Severe Impairment Battery, Brief Praxis Test and Dementia Scale for People with Learning Disabilities.

BACKGROUND: Individuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer's disease. However, many measures regularly used for the detection of dementia in the general population are not suitable for individuals with DS due in part to floor effects. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT) and Dementia Scale for People with Learning Disabilities (DLD), have been used in clinical trials and other research with this population. Validity research is limited, particularly regarding the use of such tools for detection of prodromal dementia in the DS population. The current project presents baseline cross-sectional SIB, BPT and DLD performance in order to characterise their predictive utility in discriminating normal cognition, possible dementia and probable dementia in adult DS. METHOD: Baseline SIB, BPT and DLD performances from 100 individuals (no dementia = 68, possible dementia = 16 & probable dementia = 16) were examined from a longitudinal cohort of aging individuals with DS. Receiver operating characteristic curves investigated the accuracy of these measures in relation to consensus dementia diagnoses, diagnoses which demonstrated high percent agreement with the examining neurologist's independent diagnostic impression. RESULTS: The SIB and BPT exhibited fair discrimination ability for differentiating no/possible versus probable dementia [area under the curve (AUC) = 0.61 and 0.66, respectively]. The DLD exhibited good discrimination ability for differentiating no versus possible/probable dementia (AUC = 0.75) and further demonstrated better performance of the DLD Cognitive subscale compared with the DLD Social subscale (AUC = 0.77 and 0.67, respectively). CONCLUSIONS: Results suggest that the SIB, BPT and DLD are able to reasonably discriminate consensus dementia diagnoses in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. The general performance of these measures suggests that further work in the area of test development is needed to improve on the AUCs for dementia status discrimination in this unique population. At present, however, the current findings suggest that the DLD may be the best option for reliable identification of prodromal dementia in this population, reinforcing the importance of including informant behaviour ratings in assessment of cognition for adults with DS.

Defining the Expression, Production, and Signaling Roles of Specialized Metabolites during Bacillus subtilis Differentiation.

Bacterial specialized (or secondary) metabolites are structurally diverse molecules that mediate intra- and interspecies interactions by altering growth and cellular physiology and differentiation. Bacillus subtilis, a Gram-positive model bacterium commonly used to study biofilm formation and sporulation, has the capacity to produce more than 10 specialized metabolites. Some of these B. subtilis specialized metabolites have been investigated for their role in facilitating cellular differentiation, but only rarely has the behavior of multiple metabolites been simultaneously investigated. In this study, we explored the interconnectivity of differentiation (biofilm and sporulation) and specialized metabolites in B. subtilis. Specifically, we interrogated how development influences specialized metabolites and vice versa. Using the sporulation-inducing medium DSM, we found that the majority of the specialized metabolites examined are expressed and produced during biofilm formation and sporulation. Additionally, we found that six of these metabolites (surfactin, ComX, bacillibactin, bacilysin, subtilosin A, and plipastatin) are necessary signaling molecules for proper progression of B. subtilis differentiation. This study further supports the growing body of work demonstrating that specialized metabolites have essential physiological functions as cell-cell communication signals in bacteria. IMPORTANCE Bacterially produced specialized metabolites are frequently studied for their potential use as antibiotics and antifungals. However, a growing body of work has suggested that the antagonistic potential of specialized metabolites is not their only function. Here, using Bacillus subtilis as our model bacterium, we demonstrated that developmental processes such as biofilm formation and sporulation are tightly linked to specialized metabolite gene expression and production. Additionally, under our differentiation-inducing conditions, six out of the nine specialized metabolites investigated behave as intraspecific signals that impact B. subtilis physiology and influence biofilm formation and sporulation. Our work supports the viewpoint that specialized metabolites have a clear role as cell-cell signaling molecules within differentiated populations of bacteria.

Estimating induced land use change emissions for sustainable aviation biofuel pathways.

Sustainable aviation fuels (SAFs) are expected to play an essential role in achieving the aviation industries' goal of carbon-neutral growth. However, producing biomass-based SAFs may induce changes in global land use and the associated carbon stock. The induced land use change (ILUC) emissions, as a part of the full life-cycle emissions for SAF pathways, will affect whether and to what extent SAFs reduce emissions compared with petroleum-based jet fuels. Here, we estimate the ILUC emission intensity for seventeen SAF pathways considered by the International Civil Aviation Organization (ICAO), covering five ASTM-certified technologies, nine biomass-based feedstocks, and four geographical regions. We introduce the SAF pathways into a well-established computable general equilibrium (CGE) model, GTAP-BIO, and its coupled emission accounting model, AEZ-EF, to study economy-wide implications of SAF production and estimate ILUC emissions intensity for each pathway. The estimated SAF ILUC emission intensities, using a 25-year amortization period, range from -58.5 g CO2e MJ-1 for the USA miscanthus alcohol (isobutanol)-to-jet (ATJ) pathway to 34.6 g CO2e MJ-1 for the Malaysia & Indonesia palm oil Hydrotreated Esters of Fatty Acids (HEFA) pathway. Notably, the vegetable oil pathways tend to have higher ILUC emission intensities due to their linkage to palm expansion and peatland oxidation in Southeast Asia. The cellulosic pathways studied provide negative ILUC emissions, mainly driven by the high carbon sequestrations in crop biomass and soil. Using the core life-cycle emissions established by ICAO, we show that fifteen of the assessed pathways have a lower full life-cycle emission intensity than petroleum-based jet fuels (89 g CO2e MJ-1), offering promising options to reduce aviation emissions.

Challenging the Link Between Early Childhood Television Exposure and Later Attention Problems: A Multiverse Approach.

In 2004, Christakis and colleagues published findings that he and others used to argue for a link between early childhood television exposure and later attention problems, a claim that continues to be frequently promoted by the popular media. Using the same National Longitudinal Survey of Youth 1979 data set (N = 2,108), we conducted two multiverse analyses to examine whether the finding reported by Christakis and colleagues was robust to different analytic choices. We evaluated 848 models, including logistic regression models, linear regression models, and two forms of propensity-score analysis. If the claim were true, we would expect most of the justifiable analyses to produce significant results in the predicted direction. However, only 166 models (19.6%) yielded a statistically significant relationship, and most of these employed questionable analytic choices. We concluded that these data do not provide compelling evidence of a harmful effect of TV exposure on attention.

Stillbirth: are we making more progress than we think? A retrospective cohort study.

OBJECTIVE: To quantify how the changing stillbirth risk profile of women is affecting the interpretation of the stillbirth rate. DESIGN: A retrospective, population-based cohort study from 1983 to 2018. SETTING: Victoria, Australia. POPULATION: A total of 2 419 923 births at ≥28 weeks of gestation. METHODS: Changes in maternal characteristics over time were assessed. A multivariable logistic regression model was developed for stillbirth, based on maternal characteristics in 1983-1987, and used to calculate individual predictive probabilities of stillbirth from the regression equation. The number of expected stillbirths per year as a result of the change in maternal demographics was then calculated, assuming no changes in care and in the associations between maternal characteristics and stillbirth over time. MAIN OUTCOME MEASURE: Stillbirth. RESULTS: Compared with 1983-1987, there were more women in older age groups giving birth, more nulliparous women, more indigenous women and women born in Oceania, Asia and Africa, more multiple pregnancies and more women with pre-existing diabetes in 2014-2018. Despite this, the rate of stillbirth fell from 5.42 per 1000 births in 1983 to 1.72 per 1000 births in 2018 (P < 0.001). Applying the multivariable logistic regression equation, derived from the 1983-87 data, to each year, had there been no changes in care or in the associations between maternal characteristics and stillbirth, the rate of stillbirth would have increased by 12%, from 4.94 per 1000 in 1983 to 5.54 per 1000 in 2018, as a result of the change in maternal characteristics. CONCLUSIONS: Population rates of stillbirth are falling faster than is generally appreciated. TWEETABLE ABSTRACT: Population reductions in stillbirth have been underestimated as a result of changing maternal characteristics.

Infant effects on experimenter behavior.

The present study explored experimenters' looking behavior in a gaze-following task as a function of infant temperament. Two experienced female experimenters ran 62 15-month-olds through a six-trial gaze-following procedure in which infants were not distracted on the first three trials, but were distracted on the latter three trials by an Elmo video playing in the background. Although experimenters were trained to look at target objects for eight seconds per trial and were blind to infant temperamental status, both experimenters looked significantly longer during the non-distracted trials when infants were rated by their caregivers as high on effortful control or surgency. These results suggest that even experienced experimenters are susceptible to infant-driven influences. More importantly, these results highlight the importance of conceptualizing lab-based infant research involving human experimenters as, in Bronfenbrenner's (1977) terms, representing the totality of a functional social system that does not exclude the experimenters.