Relative decline in density of Northern Hemisphere tree species in warm and arid regions of their climate niches.

Although climate change is expected to drive tree species toward colder and wetter regions of their distribution, broadscale empirical evidence is lacking. One possibility is that past and present human activities in forests obscure or alter the effects of climate. Here, using data from more than two million monitored trees from 73 widely distributed species, we quantify changes in tree species density within their climatic niches across Northern Hemisphere forests. We observe a reduction in mean density across species, coupled with a tendency toward increasing tree size. However, the direction and magnitude of changes in density exhibit considerable variability between species, influenced by stand development that results from previous stand-level disturbances. Remarkably, when accounting for stand development, our findings show a significant change in density toward cold and wet climatic conditions for 43% of the species, compared to only 14% of species significantly changing their density toward warm and arid conditions in both early- and late-development stands. The observed changes in climate-driven density showed no clear association with species traits related to drought tolerance, recruitment and dispersal capacity, or resource use, nor with the temperature or aridity affiliation of the species, leaving the underlying mechanism uncertain. Forest conservation policies and associated management strategies might want to consider anticipated long-term species range shifts alongside the integration of contemporary within-distribution density changes.

Mineral protection regulates long-term global preservation of natural organic carbon.

The balance between photosynthetic organic carbon production and respiration controls atmospheric composition and climate1,2. The majority of organic carbon is respired back to carbon dioxide in the biosphere, but a small fraction escapes remineralization and is preserved over geological timescales3. By removing reduced carbon from Earth's surface, this sequestration process promotes atmospheric oxygen accumulation2 and carbon dioxide removal1. Two major mechanisms have been proposed to explain organic carbon preservation: selective preservation of biochemically unreactive compounds4,5 and protection resulting from interactions with a mineral matrix6,7. Although both mechanisms can operate across a range of environments and timescales, their global relative importance on 1,000-year to 100,000-year timescales remains uncertain4. Here we present a global dataset of the distributions of organic carbon activation energy and corresponding radiocarbon ages in soils, sediments and dissolved organic carbon. We find that activation energy distributions broaden over time in all mineral-containing samples. This result requires increasing bond-strength diversity, consistent with the formation of organo-mineral bonds8 but inconsistent with selective preservation. Radiocarbon ages further reveal that high-energy, mineral-bound organic carbon persists for millennia relative to low-energy, unbound organic carbon. Our results provide globally coherent evidence for the proposed7 importance of mineral protection in promoting organic carbon preservation. We suggest that similar studies of bond-strength diversity in ancient sediments may reveal how and why organic carbon preservation-and thus atmospheric composition and climate-has varied over geological time.

Mycobacterial RNase E cleaves with a distinct sequence preference and controls the degradation rates of most Mycolicibacterium smegmatis mRNAs.

The mechanisms and regulation of RNA degradation in mycobacteria have been subject to increased interest following the identification of interplay between RNA metabolism and drug resistance. Mycobacteria encode multiple ribonucleases predicted to participate in mRNA degradation and/or processing of stable RNAs. RNase E is hypothesized to play a major role in mRNA degradation because of its essentiality in mycobacteria and its role in mRNA degradation in gram-negative bacteria. Here, we defined the impact of RNase E on mRNA degradation rates transcriptome-wide in the nonpathogenic model Mycolicibacterium smegmatis. RNase E played a rate-limiting role in degradation of the transcripts encoded by at least 89% of protein-coding genes, with leadered transcripts often being more affected by RNase E repression than leaderless transcripts. There was an apparent global slowing of transcription in response to knockdown of RNase E, suggesting that M. smegmatis regulates transcription in responses to changes in mRNA degradation. This compensation was incomplete, as the abundance of most transcripts increased upon RNase E knockdown. We assessed the sequence preferences for cleavage by RNase E transcriptome-wide in M. smegmatis and Mycobacterium tuberculosis and found a consistent bias for cleavage in C-rich regions. Purified RNase E had a clear preference for cleavage immediately upstream of cytidines, distinct from the sequence preferences of RNase E in gram-negative bacteria. We furthermore report a high-resolution map of mRNA cleavage sites in M. tuberculosis, which occur primarily within the RNase E-preferred sequence context, confirming that RNase E has a broad impact on the M. tuberculosis transcriptome.

Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis.

BACKGROUND: Fewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases, tissue-entrapped EVs are associated with early mineralization, but their cargoes, functions, and contributions to disease remain unknown. METHODS: Disease stage-specific proteomics was performed on human carotid endarterectomy specimens (n=16) and stenotic aortic valves (n=18). Tissue EVs were isolated from human carotid arteries (normal, n=6; diseased, n=4) and aortic valves (normal, n=6; diseased, n=4) by enzymatic digestion, (ultra)centrifugation, and a 15-fraction density gradient validated by proteomics, CD63-immunogold electron microscopy, and nanoparticle tracking analysis. Vesiculomics, comprising vesicular proteomics and small RNA-sequencing, was conducted on tissue EVs. TargetScan identified microRNA targets. Pathway network analyses prioritized genes for validation in primary human carotid artery smooth muscle cells and aortic valvular interstitial cells. RESULTS: Disease progression drove significant convergence (P<0.0001) of carotid artery plaque and calcified aortic valve proteomes (2318 proteins). Each tissue also retained a unique subset of differentially enriched proteins (381 in plaques; 226 in valves; q<0.05). Vesicular gene ontology terms increased 2.9-fold (P<0.0001) among proteins modulated by disease in both tissues. Proteomics identified 22 EV markers in tissue digest fractions. Networks of proteins and microRNA targets changed by disease progression in both artery and valve EVs revealed shared involvement in intracellular signaling and cell cycle regulation. Vesiculomics identified 773 proteins and 80 microRNAs differentially enriched by disease exclusively in artery or valve EVs (q<0.05); multiomics integration found tissue-specific EV cargoes associated with procalcific Notch and Wnt signaling in carotid arteries and aortic valves, respectively. Knockdown of tissue-specific EV-derived molecules FGFR2, PPP2CA, and ADAM17 in human carotid artery smooth muscle cells and WNT5A, APP, and APC in human aortic valvular interstitial cells significantly modulated calcification. CONCLUSIONS: The first comparative proteomics study of human carotid artery plaques and calcified aortic valves identifies unique drivers of atherosclerosis versus aortic valve stenosis and implicates EVs in advanced cardiovascular calcification. We delineate a vesiculomics strategy to isolate, purify, and study protein and RNA cargoes from EVs entrapped in fibrocalcific tissues. Integration of vesicular proteomics and transcriptomics by network approaches revealed novel roles for tissue EVs in modulating cardiovascular disease.

Constitutive nuclear accumulation of endogenous alpha-synuclein in mice causes motor impairment and cortical dysfunction, independent of protein aggregation.

A growing body of evidence suggests that nuclear alpha-synuclein (αSyn) plays a role in the pathogenesis of Parkinson's disease (PD). However, this question has been difficult to address as controlling the localization of αSyn in experimental systems often requires protein overexpression, which affects its aggregation propensity. To overcome this, we engineered SncaNLS mice, which localize endogenous αSyn to the nucleus. We characterized these mice on a behavioral, histological and biochemical level to determine whether the increase of nuclear αSyn is sufficient to elicit PD-like phenotypes. SncaNLS mice exhibit age-dependent motor deficits and altered gastrointestinal function. We found that these phenotypes were not linked to αSyn aggregation or phosphorylation. Through histological analyses, we observed motor cortex atrophy in the absence of midbrain dopaminergic neurodegeneration. We sampled cortical proteomes of SncaNLS mice and controls to determine the molecular underpinnings of these pathologies. Interestingly, we found several dysregulated proteins involved in dopaminergic signaling, including Darpp32, Pde10a and Gng7, which we further confirmed was decreased in cortical samples of the SncaNLS mice compared with controls. These results suggest that chronic endogenous nuclear αSyn can elicit toxic phenotypes in mice, independent of its aggregation. This model raises key questions related to the mechanism of αSyn toxicity in PD and provides a new model to study an underappreciated aspect of PD pathogenesis.

Updated variant curation expert panel criteria and pathogenicity classifications for 251 variants for RYR1-related malignant hyperthermia susceptibility.

The ClinGen malignant hyperthermia susceptibility (MHS) variant curation expert panel specified the American College of Medical Genetics and Genomics/Association of Molecular Pathologists (ACMG/AMP) criteria for RYR1-related MHS and a pilot analysis of 84 variants was published. We have now classified an additional 251 variants for RYR1-related MHS according to current ClinGen standards and updated the criteria where necessary. Criterion PS4 was modified such that individuals with multiple RYR1 variants classified as pathogenic (P), likely pathogenic (LP), or variant of uncertain significance (VUS) were not considered as providing evidence for pathogenicity. Criteria PS1 and PM5 were revised to consider LP variants at the same amino-acid residue as providing evidence for pathogenicity at reduced strength. Finally, PM1 was revised such that if PS1 or PM5 are used PM1, if applicable, should be downgraded to supporting. Of the 251 RYR1 variants, 42 were classified as P/LP, 16 as B/LB, and 193 as VUS. The primary driver of 175 VUS classifications was insufficient evidence supporting pathogenicity, rather than evidence against pathogenicity. Functional data supporting PS3/BS3 was identified for only 13 variants. Based on the posterior probabilities of pathogenicity and variant frequencies in gnomAD, we estimated the prevalence of individuals with RYR1-related MHS pathogenic variants to be between 1/300 and 1/1075, considerably higher than current estimates. We have updated ACMG/AMP criteria for RYR1-related MHS and classified 251 variants. We suggest that prioritization of functional studies is needed to resolve the large number of VUS classifications and allow for appropriate risk assessment. RYR1-related MHS pathogenic variants are likely to be more common than currently appreciated.

Dotatate PET/CT and 225Ac-Dotatate Therapy for Somatostatin Receptor-expressing Metastatic Breast Cancer.

Background Somatostatin receptors, and specifically somatostatin receptor type 2 (SSTR2), have primarily been associated with neuroendocrine tumors and have revolutionized the imaging and therapy of patients with these tumors. SSTR2 is expressed on other tumors at lower prevalence. Purpose To evaluate the potential of SSTR2-targeted imaging and therapy in patients with breast cancer. Materials and Methods In a preclinical experiment, SSTR2 expression was assessed in tissue microarrays of breast cancer samples using H-score analysis. H-scores higher than 50 (0-300 scale) were considered positive. Then, a prospective phase 2 clinical trial of SSTR2-targeted tetraazacyclododecane tetraacetic acid octreotate (Dotatate) PET/CT was performed in participants with biopsy-proven estrogen receptor (ER)-positive breast cancer from January to August 2023. A positive Dotatate PET/CT scan was defined as tumors with a Krenning score of 3 (avidity greater than liver) or 4 (avidity greater than spleen). The proportion of positive scans and the 95% CI were calculated. One participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET/CT result underwent treatment with SSTR2-targeted actinium 225 (225Ac) Dotatate. Results Preclinical microarrays demonstrated that 63 of 123 ER-positive breast cancer tissue samples (51% [95% CI: 42, 60]) but only 22 of 121 ER-negative breast cancer tissue samples (18% [95% CI: 12, 26]) were enriched for SSTR2 (P < .001). Thirty female participants (mean age, 66 years ± 15) with metastatic ER-positive breast cancer were accrued to the phase 2 SSTR2-targeted imaging trial and underwent Dotatate PET/CT. Dotatate PET/CT demonstrated that nine of 30 participants (30% [95% CI: 15, 49]) had tumors with Krenning scores of 3 or 4, indicating strong SSTR2 expression. SSTR2-targeted therapy with alpha-emitting 225Ac-Dotatate resulted in a near complete response in a heavily pretreated participant with metastatic ER-positive breast cancer and a Krenning 4 Dotatate PET result. Conclusion Molecular imaging targeting SSTR2 and radioligand therapy with SSTR2-targeted 225Ac-Dotatate enables a new therapeutic option for patients with metastatic breast cancer. Clinical trial registration no. NCT05880394 © RSNA, 2024 See also the editorial by Lin and Choyke in this issue.

Interventional probability of causation (IPoC) with epidemiological and partial mechanistic evidence: benzene vs. formaldehyde and acute myeloid leukemia (AML).

INTRODUCTION: Causal epidemiology for regulatory risk analysis seeks to evaluate how removing or reducing exposures would change disease occurrence rates. We define interventional probability of causation (IPoC) as the change in probability of a disease (or other harm) occurring over a lifetime or other specified time interval that would be caused by a specified change in exposure, as predicted by a fully specified causal model. We define the closely related concept of causal assigned share (CAS) as the predicted fraction of disease risk that would be removed or prevented by a specified reduction in exposure, holding other variables fixed. Traditional approaches used to evaluate the preventable risk implications of epidemiological associations, including population attributable fraction (PAF) and the Bradford Hill considerations, cannot reveal whether removing a risk factor would reduce disease incidence. We argue that modern formal causal models coupled with causal artificial intelligence (CAI) and realistically partial and imperfect knowledge of underlying disease mechanisms, show great promise for determining and quantifying IPoC and CAS for exposures and diseases of practical interest. METHODS: We briefly review key CAI concepts and terms and then apply them to define IPoC and CAS. We present steps to quantify IPoC using a fully specified causal Bayesian network (BN) model. Useful bounds for quantitative IPoC and CAS calculations are derived for a two-stage clonal expansion (TSCE) model for carcinogenesis and illustrated by applying them to benzene and formaldehyde based on available epidemiological and partial mechanistic evidence. RESULTS: Causal BN models for benzene and risk of acute myeloid leukemia (AML) incorporating mechanistic, toxicological and epidemiological findings show that prolonged high-intensity exposure to benzene can increase risk of AML (IPoC of up to 7e-5, CAS of up to 54%). By contrast, no causal pathway leading from formaldehyde exposure to increased risk of AML was identified, consistent with much previous mechanistic, toxicological and epidemiological evidence; therefore, the IPoC and CAS for formaldehyde-induced AML are likely to be zero. CONCLUSION: We conclude that the IPoC approach can differentiate between likely and unlikely causal factors and can provide useful upper bounds for IPoC and CAS for some exposures and diseases of practical importance. For causal factors, IPoC can help to estimate the quantitative impacts on health risks of reducing exposures, even in situations where mechanistic evidence is realistically incomplete and individual-level exposure-response parameters are uncertain. This illustrates the strength that can be gained for causal inference by using causal models to generate testable hypotheses and then obtaining toxicological data to test the hypotheses implied by the models-and, where necessary, refine the models. This virtuous cycle provides additional insight into causal determinations that may not be available from weight-of-evidence considerations alone.

The Scalding Truth: Geospatial Analysis Identifies Communities at Risk for Pediatric Scald Burns.

INTRODUCTION: Pediatric scald burns account for 12% of all U.S. burn center admissions and are the most common type of burn in children. We hypothesized that geospatial analysis of burn registry data could identify specific geographic areas and risk factors to focus injury prevention efforts. METHODS: The burn registry of a U.S. regional burn center was used to retrospectively identify pediatric scald burn patients ages 0-17, from January 2018 to June 2023. Geocoding of patient home addresses with census tract data was performed. Area Deprivation Index (ADI) was assigned to patients at the census block group level. Burn incident hot spot analysis to identify statistically significant burn incident clusters was done using the Getis Ord Gi∗ statistic. RESULTS: There were 950 pediatric scald burn patients meeting study criteria. The cohort was 52% male and 36% White, with median age of 3 y and median total body surface area of 1.5%; 23.8% required hospital admission. On multivariable logistic regression, increased child poverty levels (P = 0.004) and children living in single-parent households (P = 0.009) were associated with increased scald burn incidence. Geospatial analysis identified burn hot spots, which were associated with higher ADI (P < 0.001). Black patients were more likely to undergo admission compared to White patients. CONCLUSIONS: Geospatial analysis of burn registry data identified geographic areas at high risk of pediatric scald burn. ADI, poverty, and children in single-parent households were the greatest predictors of injury. Addressing these inequalities requires targeted injury prevention education, enhanced outpatient support systems and more robust community resources.

A dyadic investigation of shy children's behavioral and affective responses to delivering a speech.

Shyness is typically associated with avoidant social behavior and restricted affect in new social situations. However, we know considerably less about how one child's shyness influences another child's behavior and affect in new social situations. Children's shyness was parent-reported when children were age 3 (N = 105, 52 girls, Mage = 3.50 years), and children were tested approximately 1 year later (Mage = 4.76 years) in same-gender dyads where they were asked to give an impromptu speech about their most recent birthday in front of an experimenter and the other member of the dyad. We examined whether children's shyness and speech order influenced their own and their social partner's observed behavior and affect during the speech. Regardless of speech order, children's own shyness was positively associated with their own avoidant social behavior and gaze aversion. Regardless of shyness, children who gave their speech second averted their gaze more than children who gave their speech first. We also found that children who gave their speech second displayed less positive affect if their social partner who they watched give the speech first was shyer. We speculate that some 4-year-old children may be sensitive to the avoidant behaviors of their shy peers and, in turn, respond with less animation when it is their turn to participate in the same activity. RESEARCH HIGHLIGHTS: We examined whether preschool children's shyness and speech order influenced their own and their social partner's observed behavior and affect during a dyadic speech task Children's own shyness was positively associated with their own avoidant social behavior and gaze aversion Children who gave their speech second averted their gaze more than children who gave their speech first. Children who gave their speech second displayed less positive affect if their social partner who they watched give a speech first was shyer These findings suggest that preschool-aged children are sensitive to learning about their environment indirectly through social observation.

Biochar derivation at low temperature: A novel strategy for harmful resource usage of antibiotic mycelial dreg.

Antibiotic mycelial dreg (AMD) has been categorized as hazardous waste due to the high residual hazardous contaminants. Inappropriate management and disposal of AMD can cause potential environmental and ecological risks. In this study, the potential of pleuromutilin mycelial dreg (PMD) as a novel feedstock for preparing tetracycline hydrochloride (TC) adsorbent was explored to achieve safe management of PMD. The results suggested that residual hazardous contaminants were completely eliminated after pyrolysis. With the increase of pyrolysis temperature, the yields, H/C, O/C, (O + N)/C, and pore size in PMD-derived biochars (PMD-BCs) decreased, while BET surface area and pore volume increased, resulting in the higher stability of the PMD-BCs prepared from higher temperatures. The TC adsorption of the PMD-BCs increased from 27.3 to 46.9 mg/g with the increase of the pyrolysis temperature. Surprisingly, pH value had a strong impact on the TC adsorption, the adsorption capacity of BC-450 increased from 6.5 to 71.1 mg/g when the solution pH value increased from 2 to 10. Lewis acid-base interaction, pore filling, π-π interaction, hydrophobic interaction, and charge-assisted hydrogen bond (CAHB) are considered to drive the adsorption. This work provides a novel pathway for the concurrent detoxification and reutilization of AMD.

Public health nurse-delivered cognitive behavioral therapy for postpartum depression: Assessing the effects of maternal treatment on infant emotion regulation.

The effects of maternal postpartum depression (PPD) on offspring emotion regulation (ER) are particularly deleterious as difficulties with ER predict an increased risk of psychopathology. This study examined the impact of maternal participation in a public health nurse (PHN)-delivered group cognitive behavioral therapy (CBT) intervention on infant ER. Mothers/birthing parents were ≥ 18 years old with an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10, and infants were < 12 months. Between 2017 and 2020, 141 mother-infant dyads were randomized to experimental or control groups. Infant ER was measured at baseline (T1) and nine weeks later (T2) using two neurophysiological measures (frontal alpha asymmetry (FAA) and high-frequency heart rate variability (HF-HRV)), and informant-report of infant temperament. Mothers were a mean of 30.8 years old (SD = 4.7), 92.3% were married/ common-law, and infants were a mean of 5.4 months old (SD = 2.9) and 52.1% were male. A statistically significant group-by-time interaction was found to predict change in HF-HRV between T1 and T2 (F(1,68.3) = 4.04, p = .04), but no significant interaction predicted change in FAA or temperament. Results suggest that PHN-delivered group CBT for PPD may lead to adaptive changes in a neurophysiological marker of infant ER, highlighting the importance of early maternal intervention.

Siblings at home: Moderating influence of sibling presence and composition on the relation between problem behaviors and Theory of Mind in early childhood.

Despite the prevalence of internalizing and externalizing difficulties in children, the impact of these problem behaviors on the development of important social cognitive skills, such as Theory of Mind (ToM), is not well-understood. Indeed, many studies that have explored relations between problem behaviors and ToM report inconsistent findings. A possible reason for these disparities may be a lack of accounting for social protective factors within the home, such as the presence and number of siblings. Here, we explored the moderating influence of sibling presence and number on the relation between problem behaviors (i.e., internalizing and externalizing) and ToM. A total of 184 children (88 boys; Mage = 64.6 months, SD = 10.39) completed six well-validated ToM tasks while mothers reported on their children's externalizing and internalizing behaviors. Children who had siblings living in the same home exhibited higher ToM than children without siblings. In addition, both sibling presence and number of siblings moderated the relation between children's externalizing behaviors and ToM, such that in children without siblings externalizing behaviors were negatively associated with ToM. In contrast, children with siblings had similar ToM regardless of externalizing behaviors. As well, children with relatively fewer siblings and higher externalizing behaviors displayed lower ToM than children with relatively more siblings and higher externalizing behaviors. We did not detect a moderating effect of sibling presence or number on the relation between internalizing behaviors and ToM. These findings provide support for siblings' protective utility within the context of children's social cognition.

Effect-based monitoring of two rivers under urban and agricultural influence reveals a range of biological activities in sediment and water extracts.

Chemical contaminants, such as pesticides, pharmaceuticals and industrial compounds are ubiquitous in surface water and sediment in areas subject to human activity. While targeted chemical analysis is typically used for water and sediment quality monitoring, there is growing interest in applying effect-based methods with in vitro bioassays to capture the effects of all active contaminants in a sample. The current study evaluated the biological effects in surface water and sediment from two contrasting catchments in Aotearoa New Zealand, the highly urbanised Whau River catchment in Tamaki Makaurau (Auckland) and the urban and mixed agricultural Koreti (New River) Estuary catchment. Two complementary passive sampling devices, Chemcatcher for polar chemicals and polyethylene (PED) for non-polar chemicals, were applied to capture a wide range of contaminants in water, while composite sediment samples were collected at each sampling site. Bioassays indicative of induction of xenobiotic metabolism, receptor-mediated effects, genotoxicity, cytotoxicity and apical effects were applied to the water and sediment extracts. Most sediment extracts induced moderate to strong estrogenic and aryl hydrocarbon (AhR) activity, along with moderate toxicity to bacteria. The water extracts showed similar patterns to the sediment extracts, but with lower activity. Generally, the polar Chemcatcher extracts showed greater estrogenic activity, photosynthesis inhibition and algal growth inhibition than the non-polar PED extracts, though the PED extracts showed greater AhR activity. The observed effects in the water extracts were compared to available ecological effect-based trigger values (EBT) to evaluate the potential risk. For the polar extracts, most sites in both catchments exceeded the EBT for estrogenicity, with many sites exceeding the EBTs for AhR activity and photosynthesis inhibition. Of the wide range of endpoints considered, estrogenic activity, AhR activity and herbicidal activity appear to be the primary risk drivers in both the Whau and Koreti Estuary catchments.

Sociability across Eastern-Western cultures: Is it the same underlying construct?

In this study, we examined cross-cultural differences in sociability, a core personality facet of the higher order extraversion trait, which has been reported at lower levels in Eastern versus Western cultures several decades ago. Up until now, however, East-West cultural comparisons on the Western-defined construct of sociability have been limited, despite the extensive research published on extraversion indicating that this personality dimension is globally relevant across cultures. Following current practices, we first assessed for measurement invariance (MI) on the Cheek and Buss sociability scale between Chinese (n = 816, 47.2% male, M = 18.51 years, SD = 1.26 years) and Canadian (n = 995, 30.8% male, M = 19.62 years, SD = 1.25 years) young adult samples to ensure any comparisons would be valid and meaningful. Results from a multigroup confirmatory factor analysis (exact invariance) showed that there was measurement non-invariance at the scalar level in the sociability construct across country and country by sex, and the newer alignment method (approximate invariance) confirmed these results, suggesting that mean level comparisons of sociability were biased and noninformative. Our findings indicated that although a few of the higher-level personality dimensions such as extraversion are considered universal, the facets underlying their meaning, like sociability, are not as clearly delineated between cultures. Alongside the present-day pursuit of understanding personality across cultures through an indigenous measurement lens in tandem with the notion of universality, researchers should also consider narrowing their focus onto lower-level facets, each of which is likely to be uniquely embedded into a cultural context.

HEMATOLOGY AND BIOCHEMICAL REFERENCE INTERVALS FOR FREE-RANGING PRONGHORN (ANTILOCAPRA AMERICANA) IN WEST TEXAS.

Pronghorn (Antilocapra americana) are considered a keystone species of North American grasslands and an important economic source for many landowners in Texas. Pronghorn restoration projects routinely capture and translocate individuals from surplus populations to restoration areas. The objective of this study was to generate normal hematological and biochemical reference intervals (RI) for free-ranging pronghorn populations in Texas as a health monitoring tool for pronghorn restoration efforts. Blood samples were collected by jugular venipuncture and divided among an EDTA tube, serum separator tube, and a single blood smear on site. Complete blood counts and biochemical profiles were completed at the Texas Veterinary Medical Diagnostic Laboratory. In total, 417 individuals (41 males, 376 females) were included in the analysis. RI were determined by robust methods (R Studio) and mixed models' analysis of variance (SPSS 28) to examine differences in blood parameters due to fever, sex, age (adult versus yearling [<1 yr of age]), cell abnormalities, and pathogen exposure reported by the testing laboratory. Sex, age, and pathogen exposure affected mean blood values, but did not warrant development of separate RI by class. Bluetongue virus was identified in 46.8% (195/417) of pronghorns and epizootic hemorrhagic disease in 89.4% (194/217) of pronghorns; 84.8% (184/217) of the pronghorns tested positive for both diseases. This information provides baseline hematology and biochemical parameters to assess the health of free-ranging pronghorn and guide wildlife managers in decision-making for future translocations and restoration objectives.

Reversible Switch in Charge Storage Enabled by Selective Ion Transport in Solid Electrolyte Interphase.

Solid-electrolyte interphases (SEIs) in advanced rechargeable batteries ensure reversible electrode reactions at extreme potentials beyond the thermodynamic stability limits of electrolytes by insulating electrons while allowing the transport of working ions. Such selective ion transport occurs naturally in biological cell membranes as a ubiquitous prerequisite of many life processes and a foundation of biodiversity. In addition, cell membranes can selectively open and close the ion channels in response to external stimuli (e.g., electrical, chemical, mechanical, and thermal), giving rise to "gating" mechanisms that help manage intracellular reactions. We wondered whether the chemistry and structure of SEIs can mimic those of cell membranes, such that ion gating can be replicated. That is, can SEIs realize a reversible switching between two electrochemical behaviors, i.e., the ion intercalation chemistry of batteries and the ion adsorption of capacitors? Herein, we report such SEIs that result in thermally activated selective ion transport. The function of open/close gate switches is governed by the chemical and structural dynamics of SEIs under different thermal conditions, with precise behaviors as conducting and insulating interphases that enable battery and capacitive processes within a finite temperature window. Such an ion gating function is synergistically contributed by Arrhenius-activated ion transport and SEI dissolution/regrowth. Following the understanding of this new mechanism, we then develop an electrochemical method to heal the SEI layer in situ. The knowledge acquired in this work reveals the possibility of hitherto unknown biomimetic properties of SEIs, which will guide us to leverage such complexities to design better SEIs for future battery chemistries.

Kidney tubular epithelial cell ferroptosis links glomerular injury to tubulointerstitial pathology in lupus nephritis.

Ferroptosis is a druggable, iron-dependent form of cell death that is characterized by lipid peroxidation but has received little attention in lupus nephritis. Kidneys of lupus nephritis patients and mice showed increased lipid peroxidation mainly in the tubular segments and an increase in Acyl-CoA synthetase long-chain family member 4, a pro-ferroptosis enzyme. Nephritic mice had an attenuated expression of SLC7A11, a cystine importer, an impaired glutathione synthesis pathway, and low expression of glutathione peroxidase 4, a ferroptosis inhibitor. Lipidomics of nephritic kidneys confirmed ferroptosis. Using nephrotoxic serum, we induced immune complex glomerulonephritis in congenic mice and demonstrate that impaired iron sequestration within the proximal tubules exacerbates ferroptosis. Lupus nephritis patient serum rendered human proximal tubular cells susceptibility to ferroptosis which was inhibited by Liproxstatin-2, a novel ferroptosis inhibitor. Collectively, our findings identify intra-renal ferroptosis as a pathological feature and contributor to tubular injury in human and murine lupus nephritis.

Spatial scale impacts microbial community composition and distribution within and across stream ecosystems in North and Central America.

A mechanistic understanding of factors that structure spatiotemporal community composition is a major challenge in microbial ecology. Our study of microbial communities in the headwaters of three freshwater stream networks showed significant community changes at the small spatial scale of benthic habitats when compared to changes at mid- and large-spatial scales associated with stream order and catchment. Catchment (which included temperate and tropical catchments) had the strongest influence on community composition followed by habitat type (epipsammon or epilithon) and stream orders. Alpha diversity of benthic microbiomes resulted from interactions between catchment, habitat, and canopy. Epilithon contained relatively more Cyanobacteria and algae while Acidobacteria and Actinobacteria proportions were higher in epipsammic habitats. Turnover from replacement created ~60%-95% of beta diversity differences among habitats, stream orders, and catchments. Turnover within a habitat type generally decreased downstream indicating longitudinal linkages in stream networks while between habitat turnover also shaped benthic microbial community assembly. Our study suggests that factors influencing microbial community composition shift in dominance across spatial scales, with habitat dominating locally and catchment dominating globally.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.