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Background: The role of nitric oxide (NO) in plant stress tolerance, as well as in increasing post-harvest quality, has been extensively demonstrated in several fruits and vegetable crops; however, the effects of its pre-harvest application on post-harvest quality are still poorly documented. Therefore, the pre-harvest application of NO in red beet (Beta vulgaris subsp. vulgaris) plants cultivated under well-watered and drought conditions was evaluated to assess whether it improves the post-harvest quality of their storage roots. Red beet plants cultivated under well-watered (80% of water holding capacity) or drought condition (15% of water holding capacity) were sprayed weekly with water (control) or 100 μmol L -1 sodium nitroprusside (SNP), an NO donor. Sixty-six days after sowing, red beet roots were harvested, and root yield, total sugar yield, reducing sugars, non-reducing sugars, proteins, lipids, root ashes, root moisture, soluble solids, titratable acidity, pH, vitamin C, total phenolics, total betalains, betacyanins, betaxanthins and antioxidant capacity were determined., Results: While drought led to a reduction in root yield, sugars, lipids and titratable acidity, it increased phenolic compounds, betalains and the antioxidant capacity of beets. SNP reversed the negative effects of drought on sugar, lipid and organic acid contents and increased antioxidant capacity independent of stress., Conclusion: Pre-harvest SNP treatment reversed drought-induced yield reductions in beets, while boosting bioactive compounds and antioxidant capacity. It also enhanced vitamin C content independently, indicating its dual role in stress mitigation and beet quality improvement. Future research should explore other crops and stress conditions. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Hydrogen peroxide (H 2 O 2 ) plays a central role in responses to salt stress, a major abiotic stress that impacts crop yield worldwide. Despite the evidence that H 2 O 2 mitigates salt stress and improves post-harvest quality on several species, its effects on radish were not investigated so far. Thus, the objective of this study was to evaluate the exogenous application of H 2 O 2 on salt stress mitigation of radish growth, physiology, and post-harvest quality. For this, radish plants were grown in pots for 30 days, being watered with non-saline (0.31 dS m -1 ) or saline water (120 mM NaCl, 12.25 dS m -1 ). Plants were leaf-sprayed weekly with water (control - 0 µM H 2 O 2 ) or H 2 O 2 (150 or 1500 µM) solutions. The experimental design was completely randomized in a 3 × 2 factorial scheme (H 2 O 2 treatments × salt stress conditions). The growth, physiology (gas exchanges, photochemical efficiency, relative water content, electrolyte leakage, and the contents of chlorophylls and carotenoids), and post-harvest attributes of globular roots (color, anthocyanins, vitamin C, phenolic compounds, and soluble solids) were determined. Salt stress decreased gas exchanges and increased electrolyte leakage, which resulted in stunted radish growth, and increased the contents of antioxidants, such as anthocyanins, soluble solids, and vitamin C, improving globular root quality. Conversely, H 2 O 2 did not mitigate salt stress effects on radish growth, photosynthetic capacity, and oxidative damages. Although H 2 O 2 increased vitamin C under non-stressed condition, it was decreased under salt stress. Thus, we conclude that H 2 O 2 did not mitigate salt stress on radish growth and quality., Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01476-z., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© Prof. H.S. Srivastava Foundation for Science and Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Many biogeochemical processes are modulated by dissolved organic matter (DOM), but the drivers influencing the chemodiversity of DOM compounds in Amazonian soils are poorly understood. It has also been theorized whether deforestation controls the decline of DOM. In this study, we collected soil samples from thirty sites across different regions of Brazil's Legal Amazon, and we investigated the trade-offs among soil physical-chemical properties and DOM chemodiversity. We employed optical spectroscopy, Fourier transform ion cyclotron resonance, and multivariate analysis. Our results indicated that, despite variations in land use and soil physical-chemical properties, factors such as the deforested site, geometric mean diameter, weighted average diameter, and soil organic carbon were the main influencers of DOM chemodiversity variation. These findings highlight the importance of considering DOM chemodiversity as closely related to land use and its potential use in developing deforestation models for predicting soil quality decline in Brazil's Legal Amazon.

Purpose: Due to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage., Experimental Design: Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning., Results: We identified CD79b + neutrophils (CD3 - CD56 - CD19 - Siglec8 - CD203c - CD86 Lo CD66b + CD79b + ) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b + neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b + neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b + neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis., Conclusion: Our work suggests that CD79b + neutrophils are associated with early-stage melanoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AR declared a shared affiliation with the authors YZ and CO to the handling editor at the time of review., (Copyright © 2023 Meyer, Dinh, Alimadadi, Araujo, Chatterjee, Gutierrez, Zhu, Hunter, Liang, Seumois, Kiosses, Catz, Vijayanand, Ottensmeier and Hedrick.)

Brain-derived transcriptomes are known to correlate with resting-state brain activity in humans. Whether this association holds in nonhuman primates remains uncertain. Here, we search for such molecular correlates by integrating 757 transcriptomes derived from 100 macaque cortical regions with resting-state activity in separate conspecifics. We observe that 150 noncoding genes explain variations in resting-state activity at a comparable level with protein-coding genes. In-depth analysis of these noncoding genes reveals that they are connected to the function of nonneuronal cells such as oligodendrocytes. Co-expression network analysis finds that the modules of noncoding genes are linked to both autism and schizophrenia risk genes. Moreover, genes associated with resting-state noncoding genes are highly enriched in human resting-state functional genes and memory-effect genes, and their links with resting-state functional magnetic resonance imaging (fMRI) signals are altered in the brains of patients with autism. Our results highlight the potential for noncoding RNAs to explain resting-state activity in the nonhuman primate brain., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

CD8 + T cells drive anti-cancer immunity in response to antigen-presenting cells such as dendritic cells and subpopulations of monocytes and macrophages. While CD14 + classical monocytes modulate CD8 + T cell responses, the contributions of CD16 + nonclassical monocytes to this process remain unclear. Herein we explored the role of nonclassical monocytes in CD8 + T cell activation by utilizing E2-deficient (E2 -/- ) mice that lack nonclassical monocytes. During early metastatic seeding, modeled by B16F10-OVA cancer cells injected into E2 -/- mice, we noted lower CD8 + effector memory and effector T cell frequencies within the lungs as well as in lung-draining mediastinal lymph nodes in the E2 -/- mice. Analysis of the myeloid compartment revealed that these changes were associated with depletion of MHC-II lo Ly6C lo nonclassical monocytes within these tissues, with little change in other monocyte or macrophage populations. Additionally, nonclassical monocytes preferentially trafficked to primary tumor sites in the lungs, rather than to the lung-draining lymph nodes, and did not cross-present antigen to CD8 + T cells. Examination of the lung microenvironment in E2 -/- mice revealed reduced CCL21 expression in endothelial cells, which is chemokine involved in T cell trafficking. Our results highlight the previously unappreciated importance of nonclassical monocytes in shaping the tumor microenvironment via CCL21 production and CD8 + T cell recruitment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Padgett, Marcovecchio, Olingy, Araujo, Steel, Dinh, Alimadadi, Zhu, Meyer, Kiosses, Thomas and Hedrick.)

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in severe immune dysfunction, hospitalization, and death. Many patients also develop long-COVID-19, experiencing symptoms months after infection. Although significant progress has been made in understanding the immune response to acute SARS-CoV-2 infection, gaps remain in our knowledge of how innate immunity influences disease kinetics and severity. We hypothesized that cytometry by time-of-flight analysis of PBMCs from healthy and infected subjects would identify novel cell surface markers and innate immune cell subsets associated with COVID-19 severity. In this pursuit, we identified monocyte and dendritic cell subsets that changed in frequency during acute SARS-CoV-2 infection and correlated with clinical parameters of disease severity. Subsets of nonclassical monocytes decreased in frequency in hospitalized subjects, yet increased in the most severe patients and positively correlated with clinical values associated with worse disease severity. CD9, CD163, PDL1, and PDL2 expression significantly increased in hospitalized subjects, and CD9 and 6-Sulfo LacNac emerged as the markers that best distinguished monocyte subsets amongst all subjects. CD9 + monocytes remained elevated, whereas nonclassical monocytes remained decreased, in the blood of hospitalized subjects at 3-4 months postinfection. Finally, we found that CD9 + monocytes functionally released more IL-8 and MCP-1 after LPS stimulation. This study identifies new monocyte subsets present in the blood of COVID-19 patients that correlate with disease severity, and links CD9 + monocytes to COVID-19 progression., (©2022 Society for Leukocyte Biology.)

Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related deaths globally. Immune checkpoint blockade (ICB) has transformed cancer medicine, with anti-programmed cell death protein 1 (anti-PD-1) therapy now well-utilized for treating NSCLC. Still, not all patients with NSCLC respond positively to anti-PD-1 therapy, and some patients acquire resistance to treatment. There remains an urgent need to find markers predictive of anti-PD-1 responsiveness. To this end, we performed mass cytometry on peripheral blood mononuclear cells from 26 patients with NSCLC during anti-PD-1 treatment. Patients who responded to anti-PD-1 ICB displayed significantly higher levels of antigen-presenting myeloid cells, including CD9 + nonclassical monocytes, and CD33 hi classical monocytes. Using matched pre-post treatment samples, we found that the baseline pre-treatment frequencies of CD33 hi monocytes predicted patient responsiveness to anti-PD-1 therapy. Moreover, some of these classical and nonclassical monocyte subsets were associated with reduced immunosuppression by T regulatory (CD4 + FOXP3 + CD25 + ) cells in the same patients. Our use of machine learning corroborated the association of specific monocyte markers with responsiveness to ICB. Our work provides a high-dimensional profile of monocytes in NSCLC and links CD33 expression on monocytes with anti-PD-1 effectiveness in patients with NSCLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Olingy, Alimadadi, Araujo, Barry, Gutierrez, Werbin, Arriola, Patel, Ottensmeier, Dinh and Hedrick.)

Objective: CD4 T cells are important regulators of atherosclerotic progression. The metabolic profile of CD4 T cells controls their signaling and function, but how atherosclerosis affects T-cell metabolism is unknown. Here, we sought to determine the impact of atherosclerosis on CD4 T-cell metabolism and the contribution of such metabolic alterations to atheroprogression., Approach and Results: Using PCR arrays, we profiled the expression of metabolism genes in CD4 T cells from atherosclerotic apolipoprotein-E knockout mice fed a Western diet. These cells exhibited dysregulated expression of genes critically involved in glycolysis and fatty acid degradation, compared with those from animals fed a standard laboratory diet. We examined how T-cell metabolism was changed in either Western diet–fed apolipoprotein-E knockout mice or samples from patients with cardiovascular disease by measuring glucose uptake, activation, and proliferation in CD4 T cells. We found that naive CD4 T cells from Western diet–fed apolipoprotein-E knockout mice failed to uptake glucose and displayed impaired proliferation and activation, compared with CD4 T cells from standard laboratory diet–fed animals. Similarly, we observed that naive CD4 T-cell frequencies were reduced in the circulation of human subjects with high cardiovascular disease compared with low cardiovascular disease. Naive T cells from high cardiovascular disease subjects also showed reduced proliferative capacity., Conclusions: These results highlight the dysfunction that occurs in CD4 T-cell metabolism and immune responses during atherosclerosis. Targeting metabolic pathways within naive CD4 T cells could thus yield novel therapeutic approaches for improving CD4 T-cell responses against atheroprogression.

Objective: Cardiovascular disease (CVD) remains a significant global health concern with a high degree of mortality. While CD4 + T cells have been extensively studied in CVD, the importance of CD8 + T cells in this disease, despite their abundance and increased activation in human atherosclerotic plaques, remains largely unknown. Thus, the objective of this study was to compare peripheral T-cell signatures between humans with a high (severe) risk of CVD (including myocardial infarction or stroke) and those with a low risk of CVD. Approach and Results: Using mass cytometry, we uncovered a naive CD8 + T (T N ) cell population expressing CD95 (termed CD95 + CD8 + stem cell memory T [CD8 T SCM ] cells) that was enriched in patients with high compared with low CVD. This T-cell subset enrichment within individuals with high CVD was a relative increase and resulted from the loss of CD95 lo cells within the T N compartment. We found that CD8 T SCM cells positively correlated with CVD risk in humans, while CD8 + T N cells were inversely correlated. Atherosclerotic apolipoprotein E-deficient (ApoE -/- ) mice also displayed respective 7- and 2-fold increases in CD8 + T SCM frequencies within the peripheral blood and aorta-draining paraaortic lymph nodes compared with C57BL/6J mice. CD8 + T SCM cells were 1.7-fold increased in aortas from western diet fed ApoE -/- mice compared with normal laboratory diet-fed ApoE -/- mice. Importantly, transfer of T SCM cells into immune-deficient Rag.Ldlr recipient mice that lacked T cells increased atherosclerosis, illustrating the importance of these cells in atherogenesis., Conclusions: CD8 + T SCM cells are increased in humans with high CVD. As these T SCM cells promote atherosclerosis, targeting them may attenuate atherosclerotic plaque progression.

Background: Understanding neutrophil heterogeneity and its relationship to disease progression has become a recent focus of cancer research. Indeed, several studies have identified neutrophil subpopulations associated with protumoral or antitumoral functions. However, this work has been hindered by a lack of widely accepted markers with which to define neutrophil subpopulations., Methods: To identify markers of neutrophil heterogeneity in cancer, we used single-cell cytometry by time-of-flight (CyTOF) coupled with high-dimensional analysis on blood samples from treatment-naïve patients with melanoma., Results: Our efforts allowed us to identify seven blood neutrophil clusters, including two previously identified individual populations. Interrogation of these neutrophil subpopulations revealed a positive trend between specific clusters and disease stage. Finally, we recapitulated these seven blood neutrophil populations via flow cytometry and found that they exhibited diverse capacities for phagocytosis and reactive oxygen species production in vitro., Conclusions: Our data provide a refined consensus on neutrophil heterogeneity markers, enabling a prospective functional evaluation in patients with solid tumors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Monocytes and monocyte-derived cells, including Mϕs and dendritic cells, exhibit a diverse array of phenotypic states that are dictated by their surrounding microenvironment. These cells direct T cell activation and function via cues that range from being immunosuppressive to immunostimulatory. Solid tumors and atherosclerotic plaques represent two pathological niches with distinct immune microenvironments. While monocytes and their progeny possess a phenotypic spectrum found within both disease contexts, most within tumors are pro-tumoral and support evasion of host immune responses by tumor cells. In contrast, monocyte-derived cells within atherosclerotic plaques are usually pro-atherogenic, pro-inflammatory, and predominantly directed against self-antigens. Consequently, cancer immunotherapies strive to enhance the immune response against tumor antigens, whereas atherosclerosis treatments seek to dampen the immune response against lipid antigens. Insights into monocyte-T cell interactions within these niches could thus inform therapeutic strategies for two immunologically distinct diseases. Here, we review monocyte diversity, interactions between monocytes and T cells within tumor and plaque microenvironments, how certain therapies have leveraged these interactions, and novel strategies to assay such associations., (©2020 Society for Leukocyte Biology.)

Nonclassical monocytes maintain vascular homeostasis by patrolling the vascular endothelium, responding to inflammatory signals, and scavenging cellular debris. Nonclassical monocytes also prevent metastatic tumor cells from seeding new tissues, but whether the patrolling function of nonclassical monocytes is required for this process is unknown. To answer this question, we utilized an inducible-knockout mouse that exhibits loss of the integrin-adaptor protein Kindlin-3 specifically in nonclassical monocytes. We show that Kindlin-3-deficient nonclassical monocytes are unable to patrol the vascular endothelium in either the lungs or periphery. We also find that Kindlin-3-deficient nonclassical monocytes cannot firmly adhere to, and instead "slip" along, the vascular endothelium. Loss of patrolling activity by nonclassical monocytes was phenocopied by ablation of LFA-1, an integrin-binding partner of Kindlin-3. When B16F10 murine melanoma tumor cells were introduced into Kindlin-3-deficient mice, nonclassical monocytes showed defective patrolling towards tumor cells and failure to ingest tumor particles in vivo. Consequently, we observed a significant, 4-fold increase in lung tumor metastases in mice possessing Kindlin-3-deficient nonclassical monocytes. Thus, we conclude that the patrolling function of nonclassical monocytes is mediated by Kindlin-3 and essential for these cells to maintain vascular endothelial homeostasis and prevent tumor metastasis to the lung., (©2020 Society for Leukocyte Biology.)

Vegetation health assessment by using airborne multispectral images throughout crop production cycles, among other precision agriculture technologies, is an important tool for modern agriculture practices. However, to really take advantage of crop fields imagery, specialized analysis techniques are needed. In this paper we present a geographic object-based image analysis (GEOBIA) approach to examine a set of very high resolution (VHR) multispectral images obtained by the use of small unmanned aerial vehicles (UAVs), to evaluate plant health states and to generate cropland maps for Capsicum annuum L. The scheme described here integrates machine learning methods with semi-automated training and validation, which allowed us to develop an algorithmic sequence for the evaluation of plant health conditions at individual sowing point clusters over an entire parcel. The features selected at the classification stages are based on phenotypic traits of plants with different health levels. Determination of areas without data dependencies for the algorithms employed allowed us to execute some of the calculations as parallel processes. Comparison with the standard normalized difference vegetation index (NDVI) and biological analyses were also performed. The classification obtained showed a precision level of about 95 % in discerning between vegetation and non-vegetation objects, and clustering efficiency ranging from 79 % to 89 % for the evaluation of different vegetation health categories, which makes our approach suitable for being incorporated at C. annuum crop's production systems, as well as to other similar crops. This methodology can be reproduced and adjusted as an on-the-go solution to get a georeferenced plant health estimation.

Microglia are the resident, innate immune cells of the central nervous system (CNS) and are critical in managing CNS injuries and infections. Microglia also maintain CNS homeostasis by influencing neuronal development, viability, and function. However, aberrant microglial activity and phenotypes are associated with CNS pathology, including autism spectrum disorder (ASD). Thus, improving our knowledge of microglial regulation could provide insights into the maintenance of CNS homeostasis as well as the prevention and treatment of ASD. Control of microglial activity is in part overseen by small, lipid-derived molecules known as endogenous cannabinoids (endocannabinoids). Endocannabinoids are one component of the endocannabinoid system (ECS), which also includes the enzymes that metabolize these ligands, in addition to cannabinoid receptor 1 (CB 1 ) and 2 (CB 2 ). Interestingly, increased ECS signaling leads to an anti-inflammatory, neuroprotective phenotype in microglia. Here, we review the literature and propose that ECS signaling represents a largely untapped area for understanding microglial biology and its relationship to ASD, with special attention paid to issues surrounding the use of recreational cannabis (marijuana). We also discuss major questions within the field and suggest directions for future research., (Copyright © 2019 Araujo, Tjoa and Saijo.)

Genetic perturbations of the transcription factor Forkhead Box P1 ( FOXP1 ) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out ( Foxp1 cKO ) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1 cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1 cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1 cKO mice associated with synaptic function and development. Furthermore, using magnetic resonance imaging, we uncovered a significant reduction in the volumes of both the entire hippocampus as well as individual hippocampal subfields of Foxp1 cKO mice. Finally, we observed reduced maintenance of LTP in area CA1 of the hippocampus in these mutant mice. Together, these data suggest that proper expression of Foxp1 in the pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors reminiscent of those seen in autism and intellectual disability. In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning. SIGNIFICANCE STATEMENT Loss-of-function mutations in the transcription factor Forkhead Box P1 ( FOXP1 ) lead to autism spectrum disorder and intellectual disability. Understanding the potential brain-region-specific contributions of FOXP1 to disease-relevant phenotypes could be a critical first step in the management of patients with these mutations. Here, we report that Foxp1 conditional knock-out ( Foxp1 cKO ) mice with loss of Foxp1 in the neocortex and hippocampus display autism and intellectual-disability-relevant behaviors. We also show that these phenotypes correlate with changes in both the genomic and physiological profiles of the hippocampus in Foxp1 cKO mice. Our work demonstrates that brain-region-specific FOXP1 expression may relate to distinct, clinically relevant phenotypes., (Copyright © 2017 the authors 0270-6474/17/3710918-15$15.00/0.)

The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 are not fully understood. To elucidate the contribution of FOXP1-mediated signaling to brain development and, in particular, neocortical development, we generated forebrain-specific Foxp1 conditional knockout mice. We show that deletion of Foxp1 in the developing forebrain leads to impairments in neonatal vocalizations as well as neocortical cytoarchitectonic alterations via neuronal positioning and migration. Using a genomics approach, we identified the transcriptional networks regulated by Foxp1 in the developing neocortex and found that such networks are enriched for downstream targets involved in neurogenesis and neuronal migration. We also uncovered mechanistic insight into Foxp1 function by demonstrating that sumoylation of Foxp1 during embryonic brain development is necessary for mediating proper interactions between Foxp1 and the NuRD complex. Furthermore, we demonstrated that sumoylation of Foxp1 affects neuronal differentiation and migration in the developing neocortex. Together, these data provide critical mechanistic insights into the function of FOXP1 in the developing neocortex and may reveal molecular pathways at risk in ASD., (© 2017 Usui et al.; Published by Cold Spring Harbor Laboratory Press.)

Mutations in the transcription factor Forkhead box p1 (FOXP1) are causative for neurodevelopmental disorders such as autism. However, the function of FOXP1 within the brain remains largely uncharacterized. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and patient-relevant heterozygous Foxp1 mouse brains. We demonstrate a role for FoxP1 in the transcriptional regulation of autism-related pathways as well as genes involved in neuronal activity. We show that Foxp1 regulates the excitability of striatal medium spiny neurons and that reduction of Foxp1 correlates with defects in ultrasonic vocalizations. Finally, we demonstrate that FoxP1 has an evolutionarily conserved role in regulating pathways involved in striatal neuron identity through gene expression studies in human neural progenitors with altered FOXP1 levels. These data support an integral role for FoxP1 in regulating signaling pathways vulnerable in autism and the specific regulation of striatal pathways important for vocal communication., (© 2015 Araujo et al.; Published by Cold Spring Harbor Laboratory Press.)

Objective: We aimed to characterize severity and occurrence of knee osteoarthritis (OA), and effects of age, sex, body mass, and reproductive status on population-level normal variation in this condition in the baboon, a natural model of human knee OA., Methods: We visually inspected articular cartilage of distal right femora of 464 baboons (309 females, 155 males) and assigned an OA severity score (comparable to a modified Outerbridge score) from 1 = unaffected to 4 = advanced OA (eburnation). Presence/absence of osteophytes was recorded. We tested for significant effects of age, sex, body mass, and, in females, reproductive status (pre-, peri-, or post-menopausal) on OA. When appropriate, analyses were repeated on an age-matched subset (153 of each sex)., Results: Knee OA was more frequent and severe in older animals (P < 0.0001), but significant age variation was apparent in each severity grade. Sex differences within the younger and older age groups suggest that males develop knee OA earlier, but females progress more quickly to advanced disease. There is a strong relationship between reproductive status and OA severity grade in females (P = 0.0005) with more severe OA in peri- and post-menopausal female baboons, as in humans., Conclusions: Idiopathic knee OA is common in adult baboons. Occurrence and severity are influenced strongly by reproductive status in females, and by sex with regard to patterns of disease progression - providing an animal model to investigate sex-specific variation in OA susceptibility in which the environmental heterogeneity inherent in human populations is vastly reduced., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Tradescantia pallida cv. purpurea, a plant species widely employed for ornamentation in Brazil, has been successfully used for monitoring the genotoxicity of various agents by the micronucleus assay. To amplify knowledge about its suitability as a bioindicator species, its capacity for accumulating trace elements from urban air pollution was evaluated. T. pallida was rooted using standardized soil, and the vases were distributed in two highly polluted sites of the urban area of São Paulo, Brazil (Cerqueira Cesar and Congonhas districts), and in one unpolluted control site situated approximately 50 km from downtown São Paulo (in Caucaia do Alto). Approximately six months after exposure to pollutants, adult leaves of this plant were collected monthly for 12 months. The leaves were washed with deionized water, dried, and ground for analyses. Characterization of element levels was carried out by neutron activation analysis. Powdered samples and standards were irradiated at the IEA-R1 nuclear reactor for short and long periods, and concentrations of As, Ba, Br, Ca, Ce, Cl, Cr, Co, Fe, K, La, Mn, Na, Rb, Sb, Sc, Sr, Th, and Zn were determined. Analysis of variance applied to the results indicated that samples from polluted sites present the highest concentrations of Ba, Ce, Cr, Co, Fe, La, Sb, and Sc (p < 0.05). Discriminant analysis revealed that it was possible to distinguish the two polluted areas with a precision of 97.5%, based on the amount of pollutant elements measured in the plants at each site. The results indicated the potential use of T. pallida as an accumulator plant for air pollution biomonitoring.