Acetate is a bioenergetic substrate for human glioblastoma and brain metastases.

Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using (13)C-NMR analysis of brain tumors resected from patients during infusion of (13)C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-(13)C]acetate and can do so while simultaneously oxidizing [1,6-(13)C]glucose. The tumors do not oxidize [U-(13)C]glutamine. In vivo oxidation of [1,2-(13)C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth.

Root angle is controlled by EGT1 in cereal crops employing an antigravitropic mechanism.

Root angle in crops represents a key trait for efficient capture of soil resources. Root angle is determined by competing gravitropic versus antigravitropic offset (AGO) mechanisms. Here we report a root angle regulatory gene termed ENHANCED GRAVITROPISM1 (EGT1) that encodes a putative AGO component, whose loss-of-function enhances root gravitropism. Mutations in barley and wheat EGT1 genes confer a striking root phenotype, where every root class adopts a steeper growth angle. EGT1 encodes an F-box and Tubby domain-containing protein that is highly conserved across plant species. Haplotype analysis found that natural allelic variation at the barley EGT1 locus impacts root angle. Gravitropic assays indicated that Hvegt1 roots bend more rapidly than wild-type. Transcript profiling revealed Hvegt1 roots deregulate reactive oxygen species (ROS) homeostasis and cell wall-loosening enzymes and cofactors. ROS imaging shows that Hvegt1 root basal meristem and elongation zone tissues have reduced levels. Atomic force microscopy measurements detected elongating Hvegt1 root cortical cell walls are significantly less stiff than wild-type. In situ analysis identified HvEGT1 is expressed in elongating cortical and stele tissues, which are distinct from known root gravitropic perception and response tissues in the columella and epidermis, respectively. We propose that EGT1 controls root angle by regulating cell wall stiffness in elongating root cortical tissue, counteracting the gravitropic machinery's known ability to bend the root via its outermost tissues. We conclude that root angle is controlled by EGT1 in cereal crops employing an antigravitropic mechanism.

Electroreduction of Captured CO2 on Silver Catalysts: Influence of the Capture Agent and Proton Source.

In the context of carbon reutilization, the direct electroreduction of captured CO2 (c-CO2RR) appears as an appealing approach since it avoids the energetically costly separation of CO2 from the capture agent. In this process, CO2 is directly reduced from its captured form. Here, we investigate the influence of the capture agent and proton source on that reaction from a combination of theory and experiment. Specifically, we consider methoxide-captured CO2, NH3-captured CO2, and bicarbonate on silver electrocatalysts. We show that the proton source plays a key role in the interplay of the chemistries for the electroreduction of protons, free CO2, and captured CO2. Our density functional theory calculations, including the influence of the potential, demonstrate that a proton source with smaller pKa improves the reactivity for c-CO2RR, but also increases the selectivity toward the hydrogen evolution reaction (HER) on silver surfaces. Since c-CO2RR requires an additional chemical protonation step, the influence of the proton source is stronger than that of the HER. However, c-CO2RR cannot compete with the HER on Ag, Experimentally, the dominant product observed is H2 with low amounts of CO being produced. Through a rotating cylinder electrode cell of well-defined mass-transport properties, we conclude that although methanol solvent exhibits a lower HER activity, HER remains dominant over c-CO2RR. Our work suggests that methoxide is a potential alternative capture agent to NH3 for direct reduction of captured CO2, though challenges in catalyst design, particularly in reducing the onset potential of c-CO2RR to surpass the HER, remain to be addressed.

Astrocytic stress response is induced by exposure to astrocyte-binding antibodies expressed by plasmablasts from pediatric patients with acute transverse myelitis.

BACKGROUND: Pediatric acute transverse myelitis (ATM) accounts for 20-30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical presentation of a relapsing ADS such as multiple sclerosis (MS). B cells have been strongly implicated in the pathogenesis of adult MS. However, little is known about B cells in pediatric MS, and even less so in pediatric ATM. Our lab previously showed that plasmablasts (PB), the earliest B cell subtype producing antibody, are expanded in adult ATM, and that these PBs produce self-reactive antibodies that target neurons. The goal of this study was to examine PB frequency and phenotype, immunoglobulin selection, and B cell receptor reactivity in pediatric patients presenting with ATM to gain insight to B cell involvement in disease. METHODS: We compared the PB frequency and phenotype of 5 pediatric ATM patients and 10 pediatric healthy controls (HC) and compared them to previously reported adult ATM patients using cytometric data. We purified bulk IgG from the plasma samples and cloned 20 recombinant human antibodies (rhAbs) from individual PBs isolated from the blood. Plasma-derived IgG and rhAb autoreactivity was measured by mean fluorescence intensity (MFI) in neurons and astrocytes of murine brain or spinal cord and primary human astrocytes. We determined the potential impact of these rhAbs on astrocyte health by measuring stress and apoptotic response. RESULTS: We found that pediatric ATM patients had a reduced frequency of peripheral blood PB. Serum IgG autoreactivity to neurons in EAE spinal cord was similar in the pediatric ATM patients and HC. However, serum IgG autoreactivity to astrocytes in EAE spinal cord was reduced in pediatric ATM patients compared to pediatric HC. Astrocyte-binding strength of rhAbs cloned from PBs was dependent on somatic hypermutation accumulation in the pediatric ATM cohort, but not HC. A similar observation in predilection for astrocyte binding over neuron binding of individual antibodies cloned from PBs was made in EAE brain tissue. Finally, exposure of human primary astrocytes to these astrocyte-binding antibodies increased astrocytic stress but did not lead to apoptosis. CONCLUSIONS: Discordance in humoral immune responses to astrocytes may distinguish pediatric ATM from HC.

Somatic mutation effects diffused over microRNA dysregulation.

MOTIVATION: As an important player in transcriptome regulation, microRNAs may effectively diffuse somatic mutation impacts to broad cellular processes and ultimately manifest disease and dictate prognosis. Previous studies that tried to correlate mutation with gene expression dysregulation neglected to adjust for the disparate multitudes of false positives associated with unequal sample sizes and uneven class balancing scenarios. RESULTS: To properly address this issue, we developed a statistical framework to rigorously assess the extent of mutation impact on microRNAs in relation to a permutation-based null distribution of a matching sample structure. Carrying out the framework in a pan-cancer study, we ascertained 9008 protein-coding genes with statistically significant mutation impacts on miRNAs. Of these, the collective miRNA expression for 83 genes showed significant prognostic power in nine cancer types. For example, in lower-grade glioma, 10 genes' mutations broadly impacted miRNAs, all of which showed prognostic value with the corresponding miRNA expression. Our framework was further validated with functional analysis and augmented with rich features including the ability to analyze miRNA isoforms; aggregative prognostic analysis; advanced annotations such as mutation type, regulator alteration, somatic motif, and disease association; and instructive visualization such as mutation OncoPrint, Ideogram, and interactive mRNA-miRNA network. AVAILABILITY AND IMPLEMENTATION: The data underlying this article are available in MutMix, at http://innovebioinfo.com/Database/TmiEx/MutMix.php.

Heterogeneity promotes resilience in restored prairie: Implications for the environmental heterogeneity hypothesis.

Enhancing resilience in formerly degraded ecosystems is an important goal of restoration ecology. However, evidence for the recovery of resilience and its underlying mechanisms require long-term experiments and comparison with reference ecosystems. We used data from an experimental prairie restoration that featured long-term soil heterogeneity manipulations and data from two long-term experiments located in a comparable remnant (reference) prairie to (1) quantify the recovery of ecosystem functioning (i.e., productivity) relative to remnant prairie, (2) compare the resilience of restored and remnant prairies to a natural drought, and (3) test whether soil heterogeneity enhances resilience of restored prairie. We compared sensitivity and legacy effects between prairie types (remnant and restored) and among four prairie sites that included two remnant prairie sites and prairie restored under homogeneous and heterogeneous soil conditions. We measured sensitivity and resilience as the proportional change in aboveground net primary productivity (ANPP) during and following drought (sensitivity and legacy effects, respectively) relative to average ANPP based on 4 pre-drought years (2014-2017). In nondrought years, total ANPP was similar between remnant and restored prairie, but remnant prairie had higher grass productivity and lower forb productivity compared with restored prairie. These ANPP patterns generally persisted during drought. The sensitivity of total ANPP to drought was similar between restored and remnant prairie, but grasses in the restored prairie were more sensitive to drought. Post-drought legacy effects were more positive in the restored prairie, and we attributed this to the more positive and less variable legacy response of forb ANPP in the restored prairie, especially in the heterogeneous soil treatment. Our results suggest that productivity recovers in restored prairie and exhibits similar sensitivity to drought as in remnant prairie. Furthermore, creating heterogeneity promotes forb productivity and enhances restored prairie resilience to drought.

Metabolic scaling of an invasive mussel depends on temperature and chemical cues from an invasive predator.

Metabolism drives various biological processes, potentially influencing the ecological success and evolutionary fitness of species. Understanding diverse metabolic rates is fundamental in biology. Mechanisms underlying adaptation to factors like temperature and predation pressure remain unclear. Our study explored the role of temperature and predation pressure in shaping the metabolic scaling of an invasive mussel species (Brachidontes pharaonis). Specifically, we performed laboratory-based experiments to assess the effects of phenotypic plasticity on the metabolic scaling by exposing the mussels to water conditions with and without predator cues from another invasive species (the blue crab, Callinectes sapidus) across various temperature regimes. We found that temperature effects on metabolic scaling of the invasive mussels are mediated by the presence of chemical cues of an invasive predator, the blue crab. Investigating temperature-predator interactions underscores the importance of studying the ecological effects of global warming. Our research advances our understanding of how environmental factors jointly impact physiological processes.

Is There a Functional Role for the Knotted Topology in Protein UCH-L1?

Knotted proteins are present in nature, but there is still an open issue regarding the existence of a universal role for these remarkable structures. To address this question, we used classical molecular dynamics (MD) simulations combined with in vitro experiments to investigate the role of the Gordian knot in the catalytic activity of UCH-L1. To create an unknotted form of UCH-L1, we modified its amino acid sequence by truncating several residues from its N-terminus. Remarkably, we find that deleting the first two N-terminal residues leads to a partial loss of enzyme activity with conservation of secondary structural content and knotted topological state. This happens because the integrity of the N-terminus is critical to ensure the correct alignment of the catalytic triad. However, the removal of five residues from the N-terminus, which significantly disrupts the native structure and the topological state, leads to a complete loss of enzymatic activity. Overall, our findings indicate that UCH-L1's catalytic activity depends critically on the integrity of the N-terminus and the secondary structure content, with the latter being strongly coupled with the knotted topological state.

ISG20L2: an RNA nuclease regulating T cell activation.

ISG20L2, a 3' to 5' exoribonuclease previously associated with ribosome biogenesis, is identified here in activated T cells as an enzyme with a preferential affinity for uridylated miRNA substrates. This enzyme is upregulated in T lymphocytes upon TCR and IFN type I stimulation and appears to be involved in regulating T cell function. ISG20L2 silencing leads to an increased basal expression of CD69 and induces greater IL2 secretion. However, ISG20L2 absence impairs CD25 upregulation, CD3 synaptic accumulation and MTOC translocation towards the antigen-presenting cell during immune synapsis. Remarkably, ISG20L2 controls the expression of immunoregulatory molecules, such as AHR, NKG2D, CTLA-4, CD137, TIM-3, PD-L1 or PD-1, which show increased levels in ISG20L2 knockout T cells. The dysregulation observed in these key molecules for T cell responses support a role for this exonuclease as a novel RNA-based regulator of T cell function.

The Association between Psychosocial Stressors and Gestational Weight Gain: Analysis of the National Pregnancy Risk Assessment Monitoring System (PRAMS) Results from 2012 to 2015.

OBJECTIVE: Both psychosocial stress and gestational weight gain are independently associated with adverse maternal and fetal outcomes. Studies of the association between psychosocial stress and gestational weight gain (GWG) have yielded mixed results. The objective of this study was to evaluate the association between psychosocial stress and GWG in a large population-based cohort. METHODS: Data from the nationally representative Pregnancy Risk Assessment Monitoring System (PRAMS) Phase 7 questionnaire 2012-2015 was utilized. Maternal psychosocial stress was assessed through response to questions designed to examine four domains of psychosocial stress (i.e., traumatic, financial, emotional, partner-related) three months prior to or during pregnancy. GWG was categorized using pre-pregnancy BMI and total GWG into inadequate, adequate, or excessive according to the Institute of Medicine's GWG guidelines. Multinomial logistic regression was used to evaluate the association between psychosocial stressors and adequacy of GWG. Analyses took into account complex survey design. RESULTS: All respondents who delivered ≥ 37 weeks gestation with GWG information available were included in the analysis (n = 119,183). After adjusting for confounders, patients who reported financial stress were more likely to experience excessive versus adequate GWG (RRR 1.09 [95%CI: 1.02-1.17]). Exposure to any of the stressor groups did not significantly increase the risk of inadequate GWG. CONCLUSIONS: This large, population-based study revealed that among pregnant people in the US, exposure to financial stress is associated with higher risk of excessive GWG. Understanding the role stress plays in GWG will help to inform initiatives targeting this important aspect of prenatal care.

ENHANCED GRAVITROPISM 2 encodes a STERILE ALPHA MOTIF-containing protein that controls root growth angle in barley and wheat.

The root growth angle defines how roots grow toward the gravity vector and is among the most important determinants of root system architecture. It controls water uptake capacity, nutrient use efficiency, stress resilience, and, as a consequence, yield of crop plants. We demonstrated that the egt2 (enhanced gravitropism 2) mutant of barley exhibits steeper root growth of seminal and lateral roots and an auxin-independent higher responsiveness to gravity compared to wild-type plants. We cloned the EGT2 gene by a combination of bulked-segregant analysis and whole genome sequencing. Subsequent validation experiments by an independent CRISPR/Cas9 mutant allele demonstrated that egt2 encodes a STERILE ALPHA MOTIF domain-containing protein. In situ hybridization experiments illustrated that EGT2 is expressed from the root cap to the elongation zone. We demonstrated the evolutionary conserved role of EGT2 in root growth angle control between barley and wheat by knocking out the EGT2 orthologs in the A and B genomes of tetraploid durum wheat. By combining laser capture microdissection with RNA sequencing, we observed that seven expansin genes were transcriptionally down-regulated in the elongation zone. This is consistent with a role of EGT2 in this region of the root where the effect of gravity sensing is executed by differential cell elongation. Our findings suggest that EGT2 is an evolutionary conserved regulator of root growth angle in barley and wheat that could be a valuable target for root-based crop improvement strategies in cereals.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Towards a sustainable fisher-dolphin coexistence: Understanding depredation, assessing economic damage and evaluating management options.

Finding solutions for a sustainable coexistence between wildlife and humans is considered among the most challenging environmental management issues for scientists, conservationists, managers, and stockholders world-wide. Depredation by the common bottlenose dolphin (Tursiops truncatus) on small scale fisheries has increased in the recent years, leading to a growing conflict in many areas of the Mediterranean Sea and pressing for urgent management solutions. This study aims at developing a management framework for a sustainable coexistence between fishers and dolphins in Sardinia (Mediterranean Sea). Relying on the combination of different approaches (field study, literature review and Multi Criteria Decision Analysis), the scientific evidence necessary for understanding dolphin depredation were updated and improved, the related economic damage was calculated, and different management options were identified and evaluated by several stakeholder groups to support the decision-making process. Averaging for all investigated net types (gillnet and trammel net), a depredation frequency of 53% was found, the highest values ever found in both Sardinia and many other Mediterranean sites. Depredation probability was influenced by different factors, such as net type, fishing operation duration, depth of the fishing site and period. The estimated economic damage due to depredation ranges on average between 6492 and 11,925 euro per year and depends on the type of fishing net. The results from the field study, the literature review and the stakeholder involvement allowed us to define the most plausible and shared management options, identifying a framework for assessing and managing the conflict between fishers and dolphins for the creation of a more sustainable vision for the future.

STAT family of transcription factors in breast cancer: Pathogenesis and therapeutic opportunities and challenges.

Breast cancer is the most commonly diagnosed cancer and second-leading cause of cancer deaths in women. Breast cancer stem cells (BCSCs) promote metastasis and therapeutic resistance contributing to tumor relapse. Through activating genes important for BCSCs, transcription factors contribute to breast cancer metastasis and therapeutic resistance, including the signal transducer and activator of transcription (STAT) family of transcription factors. The STAT family consists of six major isoforms, STAT1, STAT2, STAT3, STAT4, STAT5, and STAT6. Canonical STAT signaling is activated by the binding of an extracellular ligand to a cell-surface receptor followed by STAT phosphorylation, leading to STAT nuclear translocation and transactivation of target genes. It is important to note that STAT transcription factors exhibit diverse effects in breast cancer; some are either pro- or anti-tumorigenic while others maintain dual, context-dependent roles. Among the STAT transcription factors, STAT3 is the most widely studied STAT protein in breast cancer for its critical roles in promoting BCSCs, breast cancer cell proliferation, invasion, angiogenesis, metastasis, and immune evasion. Consequently, there have been substantial efforts in developing cancer therapeutics to target breast cancer with dysregulated STAT3 signaling. In this comprehensive review, we will summarize the diverse roles that each STAT family member plays in breast cancer pathobiology, as well as, the opportunities and challenges in pharmacologically targeting STAT proteins and their upstream activators in the context of breast cancer treatment.

Impact of time between faecal immunochemical tests in colorectal cancer screening on screening results: A natural experiment.

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT2 ), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT1 ), and time between the two screening rounds. 18 522 individuals with negative FIT1 who attended FIT2 were included in this study. 245 AN were detected at FIT2 , of which 34 were CRC. The CRC detection rate at FIT2 for participants with FIT1  = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT1 ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT1 -value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT1 ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.

State-specific fertility rate changes across the USA following the first two waves of COVID-19.

STUDY QUESTION: How did the first two coronavirus disease 2019 (COVID-19) waves affect fertility rates in the USA? SUMMARY ANSWER: States differed widely in how their fertility rates changed following the COVID-19 outbreak and these changes were influenced more by state-level economic, racial, political, and social factors than by COVID-19 wave severity. WHAT IS KNOWN ALREADY: The outbreak of the COVID-19 pandemic contributed to already declining fertility rates in the USA, but not equally across states. Identifying drivers of differential changes in fertility rates can help explain variations in demographic shifts across states in the USA and motivate policies that support families in general, not only during crises. STUDY DESIGN, SIZE, DURATION: This is an ecological study using state-level data from 50 US states and the District of Columbia (n = 51). The study period extends from 2020 to 2021 with historical data from 2016 to 2019. We identified Wave 1 as the first apex for each state after February 2020 and Wave 2 as the second apex, during Fall/Winter 2020-2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: State-level COVID-19 wave severity, defined as case acceleration during each 3-month COVID-19 wave (cases/100 000 population/month), was derived from 7-day weekly moving average COVID-19 case rates from the US Centers for Disease Control and Prevention (CDC). State-level fertility rate changes (change in average monthly fertility rate/100 000 women of reproductive age (WRA)/year) were derived from the CDC Bureau of Vital Statistics and from 2020 US Census and University of Virginia 2021 population estimates 9 months after each COVID-19 wave. We performed univariate analyses to describe national and state-level fertility rate changes following each wave, and simple and multivariable linear regression analyses to assess the relation of COVID-19 wave severity and other state-level characteristics with fertility rate changes. MAIN RESULTS AND THE ROLE OF CHANCE: Nationwide, fertility dropped by 17.5 births/month/100 000 WRA/year following Wave 1 and 9.2 births/month/100 000 WRA/year following Wave 2. The declines following Wave 1 were largest among majority-Democrat, more non-White states where people practiced greater social distancing. Greater COVID-19 wave severity was associated with steeper fertility rate decline post-Wave 1 in simple regression, but the association was attenuated when adjusted for other covariates. Adjusting for the economic impact of the pandemic (hypothesized mediator) also attenuated the effect. There was no relation between COVID-19 wave severity and fertility rate change following Wave 2. LIMITATIONS, REASONS FOR CAUTION: Our study harnesses state-level data so individual-level conclusions cannot be inferred. There may be residual confounding in our multivariable regression and we were underpowered to detect some effects. WIDER IMPLICATIONS OF THE FINDINGS: The COVID-19 pandemic initially impacted the national fertility rate but, overall, the fertility rate rebounded to the pre-pandemic level following Wave 2. Consistent with prior literature, COVID-19 wave severity did not appear to predict fertility rate change. Economic, racial, political, and social factors influenced state-specific fertility rates during the pandemic more than the severity of the outbreak alone. Future studies in other countries should also consider whether these factors account for internal heterogeneity when examining the impact of the COVID-19 pandemic and other crises on fertility. STUDY FUNDING/COMPETING INTEREST(S): L.G.K. received funding from the National Institute of Environmental Health Sciences (R00ES030403), M.C. from the National Science Foundation Graduate Research Fellowship Program (20-A0-00-1005789), and M.L. and E.S. from the National Institute of Environmental Health Sciences (R01ES032808). None of the authors have competing interests. TRIAL REGISTRATION NUMBER: N/A.

Paleoenvironmental inferences on the Late Miocene hominoid-bearing site of Can Llobateres (NE Iberian Peninsula): An ecometric approach based on functional dental traits.

Hispanopithecus laietanus from the Late Miocene (9.8 Ma) of Can Llobateres 1 (CLL1; Vallès-Penedès Basin, NE Iberian Peninsula) represents one of the latest occurrences of fossil apes in Western mainland Europe, where they are last recorded at ∼9.5 Ma. The paleoenvironment of CLL1 is thus relevant for understanding the extinction of European hominoids. To refine paleoenvironmental inferences for CLL1, we apply ecometric models based on functional crown type (FCT) variables-a scoring scheme devised to capture macroscopic functional traits of occlusal shape and wear surfaces of herbivorous large mammal molars. Paleotemperature and paleoprecipitation estimates for CLL1 are provided based on published regional regression models linking average FCT of large herbivorous mammal communities to climatic conditions. A mapping to Whittaker's present-day biome classification is also attempted based on these estimates, as well as a case-based reasoning via canonical variate analysis of FCT variables from five relevant biomes. Estimates of mean annual temperature (25 °C) and mean annual precipitation (881 mm) classify CLL1 as a tropical seasonal forest/savanna, only in partial agreement with the canonical variate analysis results, which classify CLL1 as a tropical rainforest with a higher probability. The former biome agrees better with previous inferences derived from fossil plants and mammals, as well as preliminary isotopic data. The misclassification of CLL1 as a tropical forest is attributed to the mixture of forest-adapted taxa with others adapted to more open environments, given that faunal and plant composition indicates the presence of a dense wetland/riparian forest with more open woodlands nearby. The tested FCT ecometric approaches do not provide unambiguous biome classification for CLL1. Nevertheless, our results are consistent with those from other approaches, thus suggesting that FCT variables are potentially useful to investigate paleoenvironmental changes through time and space-including those that led to the extinction of European Miocene apes.

Prenatal phthalate exposure and fetal penile length and width.

BACKGROUND: Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. METHODS: Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. RESULTS: 57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. CONCLUSIONS: In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. IMPACT: First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

Persistent decadal differences in plant communities assembled under contrasting climate conditions.

Plant community assembly outcomes can be contingent upon establishment year (year effects) due to variations in the environment. Stochastic events such as interannual variability in climate, particularly in the first year of community assembly, contribute to unpredictable community outcomes over the short term, but less is known about whether year effects produce transient or persistent states on a decadal timescale. To test for short-term (5-year) and persistent (decadal) effects of establishment year climate on community assembly outcomes, we restored prairie in an agricultural field using the same methods in four different years (2010, 2012, 2014, and 2016) that captured a wide range of initial (planting) year climate conditions. Species composition was measured for 5 years in all four restored prairies and for 9 and 11 years in the two oldest restored prairies established under average precipitation and extreme drought conditions. The composition of the four assembled communities showed large and significant differences in the first year of restoration, followed by dynamic change over time along a similar trajectory due to a temporary flush of annual volunteer species. Sown perennial species eventually came to dominate all communities, but communities remained distinct from each other in year five. Precipitation in June and July of the establishment year explained short-term coarse community metrics (i.e., species richness and grass/forb cover), with wet establishment years resulting in a higher cover of grasses and dry establishment years resulting in a higher cover of forbs in restored communities. Short-term differences in community composition, species richness, and grass/forb cover in restorations established under average precipitation and drought conditions persisted for 9-11 years, with low interannual variability in the composition of each prairie over the long term, indicating persistently different states on a decadal timescale. Thus, year effects resulting from stochastic variation in climate can have decadal effects on community assembly outcomes.

Elastic Modulus and Its Relation to Apparent Mineral Density in Juvenile Equine Bones of the Lower Limb.

Density-modulus relationships are necessary to develop finite element models of bones that may be used to evaluate local tissue response to different physical activities. It is unknown if juvenile equine trabecular bone may be described by the same density-modulus as adult equine bone, and how the density-modulus relationship varies with anatomical location and loading direction. To answer these questions, trabecular bone cores from the third metacarpal (MC3) and proximal phalanx (P1) bones of juvenile horses (age <1 yr) were machined in the longitudinal (n = 134) and transverse (n = 90) directions and mechanically tested in compression. Elastic modulus was related to apparent computed tomography density of each sample using power law regressions. We found that density-modulus relationships for juvenile equine trabecular bone were significantly different for each anatomical location (MC3 versus P1) and orientation (longitudinal versus transverse). Use of the incorrect density-modulus relationship resulted in increased root mean squared percent error of the modulus prediction by 8-17%. When our juvenile density-modulus relationship was compared to one of an equivalent location in adult horses, the adult relationship resulted in an approximately 80% increase in error of the modulus prediction. Moving forward, more accurate models of young bone can be developed and used to evaluate potential exercise regimens designed to encourage bone adaptation.