Rapid, high-resolution, non-destructive assessments of metabolic and morphological homogeneity uniquely identify high-grade cervical precancerous lesions.

Purpose: Two-photon microscopy (2PM) is an emerging clinical imaging modality with the potential to non-invasively assess tissue metabolism and morphology in high-resolution. This study aimed to assess the translational potential of 2PM for improved detection of high-grade cervical precancerous lesions. Experimental Design: 2P images attributed to reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and oxidized flavoproteins (FP) were acquired from the full epithelial thickness of freshly excised human cervical tissue biopsies (N = 62). Fifteen biopsies harbored high-grade squamous intraepithelial lesions (HSILs), 14 biopsies harbored low-grade SILs (LSILs), and 33 biopsies were benign. Quadratic discriminant analysis (QDA) leveraged morphological and metabolic functional metrics extracted from these images to predict the presence of HSILs. We performed gene set enrichment analysis (GSEA) using datasets available on the Gene Expression Omnibus (GEO) to validate the presence of metabolic reprogramming in HSILs. Results: Integrating metabolic and morphological 2P-derived metrics from finely sampled, full-thickness epithelia achieved a high 90.8 ± 6.1% sensitivity and 72.3 ± 11.3% specificity of HSIL detection. Notably, sensitivity (91.4 ± 12.0%) and specificity (77.5 ± 12.6%) were maintained when utilizing metrics from only two images at 12- and 72-µm from the tissue surface. Upregulation of glycolysis, fatty acid metabolism, and oxidative phosphorylation in HSIL tissues validated the metabolic reprogramming captured by 2P biomarkers. Conclusion: Label-free 2P images from as few as two epithelial depths enable rapid and robust HSIL detection through the quantitative characterization of metabolic and morphological reprogramming, underscoring the potential of this tool for clinical evaluation of cervical precancers. Translational Relevance Statement: The colposcopy and biopsy paradigm for cervical pre-cancer detection leads to an excessive number of unnecessary biopsies, with significant economic and psychological costs. This study highlights the potential of label-free, high-resolution two photon imaging to improve this paradigm by introducing real-time morphofunctional tissue assessments.In an extensive dataset comprising freshly excised high-grade and low-grade cervical intraepithelial lesions, along with benign metaplastic and inflamed human cervical tissue biopsies, we successfully characterize a loss of morphofunctional heterogeneity indicative of high-grade precancerous changes. Leveraging a combination of two-photon imaging-derived quantitative morphofunctional metrics, our findings showcase a substantial improvement in both sensitivity and specificity of high-grade lesion detection compared to the current gold standard of colposcopy followed by a single biopsy. The demonstrated enhancement in sensitivity and specificity highlights the prospect of integrating non-invasive, label-free metabolic imaging into clinical practice, offering a more effective and efficient approach to identify and manage cervical precancerous lesions.

Phylogenetically diverse wild plant species use common biochemical strategies to thrive in the Atacama Desert.

The best ideotypes are under mounting pressure due to increased aridity. Understanding the conserved molecular mechanisms that evolve in wild plants adapted to harsh environments is crucial in developing new strategies for agriculture. Yet our knowledge of such mechanisms in wild species is scant. We performed metabolic pathway reconstruction using transcriptome information from 32 Atacama and phylogenetically related species that do not live in Atacama (Sisters species). We analyzed reaction enrichment to understand the commonalities and differences of Atacama plants. To gain insights into the mechanisms that ensure survival, we compared expressed gene isoform numbers and gene expression patterns between the annotated biochemical reactions from 32 Atacama and Sister species. We found biochemical convergences characterized by reactions enriched in at least 50% of the Atacama species, pointing to potential advantages against drought and nitrogen starvation, for instance. These findings suggest that the adaptation in the Atacama Desert may result in part from shared genetic legacies governing the expression of key metabolic pathways to face harsh conditions. Enriched reactions corresponded to ubiquitous compounds common to extreme and agronomic species and were congruent with our previous metabolomic analyses. Convergent adaptive traits offer promising candidates for improving abiotic stress resilience in crop species.

New uses for ancient middens: bridging ecological and evolutionary perspectives.

Rodent middens provide a fine-scale spatiotemporal record of plant and animal communities over the late Quaternary. In the Americas, middens have offered insight into biotic responses to past environmental changes and historical factors influencing the distribution and diversity of species. However, few studies have used middens to investigate genetic or ecosystem level responses. Integrating midden studies with neoecology and experimental evolution can help address these gaps and test mechanisms underlying eco-evolutionary patterns across biological and spatiotemporal scales. Fully realizing the potential of middens to answer cross-cutting ecological and evolutionary questions and inform conservation goals in the Anthropocene will require a collaborative research community to exploit existing midden archives and mount new campaigns to leverage midden records globally.

Ecological and metabolic implications of the nurse effect of Maihueniopsis camachoi in the Atacama Desert.

Plant-plant positive interactions are key drivers of community structure. Yet, the underlying molecular mechanisms of facilitation processes remain unexplored. We investigated the 'nursing' effect of Maihueniopsis camachoi, a cactus that thrives in the Atacama Desert between c. 2800 and 3800 m above sea level. We hypothesised that an important protective factor is thermal amelioration of less cold-tolerant species with a corresponding impact on molecular phenotypes. To test this hypothesis, we compared plant cover and temperatures within the cactus foliage with open areas and modelled the effect of temperatures on plant distribution. We combined eco-metabolomics and machine learning to test the molecular consequences of this association. Multiple species benefited from the interaction with M. camachoi. A conspicuous example was the extended distribution of Atriplex imbricata to colder elevations in association with M. camachoi (400 m higher as compared to plants in open areas). Metabolomics identified 93 biochemical markers predicting the interaction status of A. imbricata with 79% accuracy, independently of year. These findings place M. camachoi as a key species in Atacama plant communities, driving local biodiversity with an impact on molecular phenotypes of nursed species. Our results support the stress-gradient hypothesis and provide pioneer insights into the metabolic consequences of facilitation.

Nakazawaea atacamensis f.a., sp. nov. a novel nonconventional fermentative ascomycetous yeast species from the Atacama Desert.

In this study, we describe Nakazawaea atacamensis f. a., sp. nov., a novel species obtained from Neltuma chilensis plant samples in Chile's hyperarid Atacama Desert. In total, three strains of N. atacamensis were obtained from independent N. chilensis samples (synonym Prosopis chilensis, Algarrobo). Two strains were obtained from bark samples, while the third strain was obtained from bark-exuded gum from another tree. The novel species was defined using molecular characteristics and subsequently characterized with respect to morphological, physiological, and biochemical properties. A neighbor-joining analysis using the sequences of the D1/D2 domains of the large subunit ribosomal RNA gene revealed that N. atacamensis clustered with Nakazawaea pomicola. The sequence of N. atacamensis differed from closely related species by 1.3%-5.2% in the D1/D2 domains. A phylogenomic analysis based on single-nucleotide polymorphism's data confirms that the novel species belongs to the genus Nakazawaea, where N. atacamensis clustered with N. peltata. Phenotypic comparisons demonstrated that N. atacamensis exhibited distinct carbon assimilation patterns compared to its related species. Genome sequencing of the strain ATA-11A-BT revealed a genome size of approximately 12.4 Mbp, similar to other Nakazawaea species, with 5116 protein-coding genes annotated using InterProScan. In addition, N. atacamensis exhibited the capacity to ferment synthetic wine must, representing a potential new yeast for mono or co-culture wine fermentations. This comprehensive study expands our understanding of the genus Nakazawaea and highlights the ecological and industrial potential of N. atacamensis in fermentation processes. The holotype of N. atacamensis sp. nov. is CBS 18375T . The Mycobank number is MB 849680.

Effectiveness of an educational intervention about inhalation technique in healthcare professionals in primary care: a cluster randomized trial.

Background: Incorrect inhalation technique (IT) is an important issue for chronic obstructive pulmonary disease (COPD) patients and healthcare professionals. Studies in which counseling is carried out with healthcare professionals beforehand so that they can properly educate their patients are required. The objective of the present trial is to assess the improvement in the performance of the IT in subjects with COPD and prescribed inhaled therapy after the implementation of an educational intervention conducted by their general practitioners. Methods: A cluster randomized clinical trial was conducted. A total of 286 COPD patients received scheduled inhalation therapy from 27 general practices in seven primary care centers. A teach-back educational intervention was implemented for both healthcare professionals and patients. The primary outcome of this study was the performance of the correct inhalation technique. It is considered a good technique if all steps in the inhalation data sheet are correctly performed. The secondary outcomes were assessed using forced spirometry, the basal dyspnea index, the Medical Research Council dyspnea scale, St George's Respiratory Questionnaire (SGRQ), and EuroQoL5D-5L for health-related quality of life. A one-year follow-up was conducted using an intention-to-treat analysis. Results: After the intervention, incorrect IT was observed in 92% of professionals and patients, with rates reaching 50% and 69.2%, respectively. The effectiveness in patients was significant, with a number needed to treat of 2.14 (95% CI 1.79-2.66). Factors related to correct IT in patients included the type of intervention, length of intervention (>25 min), good pulmonary function, age (youngest <=65, oldest >83), and less limitation of activity due to dyspnea. There was no relation with the cluster. Conclusion: This study shows the effectiveness of direct inhaler technique training provided by a trained professional on an appropriate timescale (for example, a specific consultation for medication reviews), aiming to help subjects improve their performance using the teach-back method. This could be an encouraging intervention to improve medication adherence and health promotion in people with COPD. Clinical Trial Registration: clinicaltrials.gov, identifier ISRCTN93725230.

The role of numerical and nonnumerical magnitudes in pigeons' conditional discrimination behavior.

Research on approximate numerical estimation suggests that numerical representations can be influenced by nonnumerical magnitudes. Current theories of numerical cognition differ on the nature of this interaction. The present project evaluated the effect of task requirements on the stimulus control exerted by numerical and nonnumerical magnitudes on pigeons' numerical discrimination behavior. In a series of experiments, we explored the effects of cumulative area and item size on pigeons' numerical discrimination. The effect of cumulative area was assessed by presenting visual displays in which cumulative area and item number were either positively correlated, uncorrelated, or negatively correlated. The effect of item size was evaluated by presenting displays in which the size of individual items was varied across trials. Results confirmed that pigeons' numerical discrimination behavior accorded with Weber's law, a prime indicator of nonsymbolic numerical representation. The results further indicated that pigeons did not use numerical information when nonnumerical magnitudes also provided reliable information to solve the discrimination task. However, task manipulations that rendered the information provided by nonnumerical magnitudes unreliable successfully shifted stimulus control toward numerical magnitudes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk factors associated with Retinopathy of Prematurity development and progression.

Several studies propose that Retinopathy of Prematurity (ROP) is a multifactorial disorder implicating many prenatal and postnatal factors. The objective of our study was to determine the incidence and the risk factors that influenced ROP development and progression. We retrospectively compiled data of preterms with birth weight (BW) ≤ 1.500 g and/or gestational age (GA) < 32 weeks, or BW between 1.501 and 2.000 g and/or GA ≥ 32 weeks with oxygen supply > 72 h or unstable clinical course screened for ROP in Regional University Hospital of Málaga from 2015 to 2018. 202 infants (44.7%) developed ROP and 66 exhibited progression (32.7% of ROP infants). In the univariate analysis, many risk factors were associated with ROP. In the subsequent multivariate analysis, GA, oxygen therapy and weight at 28 days of life, mechanical ventilation duration, non-invasive ventilation, surfactant administration and late-onset sepsis were independently associated with the development. However, oxygen therapy duration, late-onset sepsis and weight at 28 days were associated with the progression. The ROP development and progression risk factors were different. Our results are important to facilitate screening, early diagnosis and ROP treatment while reducing unneeded examinations.

Creencias en salud bucal en personas que asisten a una facultad de odontología. Estudio cualitativo

Objetivo: Explorar las creencias en salud bucal de personas que asisten como pacientes a una facultad de odontología de una universidad privada regional chilena. Metodología: Estudio cualitativo que exploró las creencias acerca de salud bucal de 11 personas que asistían por tratamiento a una universidad privada chilena, a través de entrevistas semi-estructuradas, transcritas verbatim. Se realizó análisis de contenido en Atlas-ti 8.4, construyendo categorías y subcategorías, tanto predeterminadas como emergentes. Se realizó triangulación entre los investigadores. Se contó con la autorización del comité de ética e investigación y se realizó consentimiento informado. Resultados: Se generaron cinco categorías: creencias sobre caries dental, creencias sobre enfermedad periodontal, creencias sobre pérdida dentaria, creencias sobre higiene bucal y origen de las creencias en salud bucal, reflejando creencias en salud variadas, nutridas principalmente de su entorno cercano y no profesional. Conclusión: Las personas que acuden a una facultad de odontología por atención presentan creencias en salud más ajustadas a caries, que a periodontitis y a pérdida dentaria. El origen de las creencias usualmente es la familia y conocidos, más que de profesionales.

Aim: To explore the beliefs in oral health of people who attend a dental school of a private regional Chilean university as patients. Methods: A qualitative study explored the beliefs about oral health of 11 people attending a private Chilean university for treatment, through semi-structured interviews, transcribed verbatim. The content was analyzed in Atlas-ti 8.4, building predetermined and emerging categories and subcategories. Triangulation was carried out among the researchers. The study was authorized by the Ethics and Research Committee and informed consent was obtained. Results: Five categories were generated: beliefs about dental caries, beliefs about periodontal disease, beliefs about tooth loss, beliefs about oral care, and origin of beliefs in oral health. Varied health beliefs were reflected, influenced mainly by their close and non-professional environment. Conclusions: People who attend a dental school for care present health beliefs more related to caries than to periodontitis, oral care, and tooth loss. The origin of the beliefs is usually family and acquaintances, rather than dentists.

Adult-Onset Deficiency of Mitochondrial Complex III in a Mouse Model of Alzheimer's Disease Decreases Amyloid Beta Plaque Formation.

For decades, mitochondrial dysfunctions and the generation of reactive oxygen species have been proposed to promote the development and progression of the amyloid pathology in Alzheimer's disease, but this association is still debated. It is unclear whether different mitochondrial dysfunctions, such as oxidative phosphorylation deficiency and oxidative stress, are triggers or rather consequences of the formation of amyloid aggregates. Likewise, the role of the different mitochondrial oxidative phosphorylation complexes in Alzheimer's patients' brain remains poorly understood. Previous studies showed that genetic ablation of oxidative phosphorylation enzymes from early age decreased amyloid pathology, which were unexpected results. To better model oxidative phosphorylation defects in aging, we induced the ablation of mitochondrial Complex III (CIIIKO) in forebrain neurons of adult mice with amyloid pathology. We found that mitochondrial Complex III dysfunction in adult neurons induced mild oxidative stress but did not increase amyloid beta accumulation. On the contrary, CIIIKO-AD mice showed decreased plaque number, decreased Aß42 toxic fragment, and altered amyloid precursor protein clearance pathway. Our results support the hypothesis that mitochondrial dysfunctions alone, caused by oxidative phosphorylation deficiency, is not the cause of amyloid accumulation.

Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial.

BACKGROUND: Men with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity. METHODS: We did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18-50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL). RESULTS: In the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin -2.4, 95 % CI -4.1 to -0.8, p = 0.004; testosterone -2.7, 95 % CI -4.3 to -1.1, p = 0.001; combination -3.4, 95 % CI -5.0 to -1.8, p < 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (-0.7, 95 % CI -2.3 to 0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment. CONCLUSIONS: Among men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.

Multimodal analyses of vitiligo skin identify tissue characteristics of stable disease.

Vitiligo is an autoimmune skin disease characterized by the destruction of melanocytes by autoreactive CD8+ T cells. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells, but the persistence of white patches in stable disease is poorly understood. The interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools. We combine noninvasive multiphoton microscopy (MPM) imaging and single-cell RNA-Seq (scRNA-Seq) to identify subpopulations of keratinocytes in stable vitiligo patients. We show that, compared with nonlesional skin, some keratinocyte subpopulations are enriched in lesional vitiligo skin and shift their energy utilization toward oxidative phosphorylation. Systematic investigation of cell-to-cell communication networks show that this small population of keratinocyte secrete CXCL9 and CXCL10 to potentially drive vitiligo persistence. Pseudotemporal dynamics analyses predict an alternative differentiation trajectory that generates this new population of keratinocytes in vitiligo skin. Further MPM imaging of patients undergoing punch grafting treatment showed that keratinocytes favoring oxidative phosphorylation persist in nonresponders but normalize in responders. In summary, we couple advanced imaging with transcriptomics and bioinformatics to discover cell-to-cell communication networks and keratinocyte cell states that can perpetuate inflammation and prevent repigmentation.

Antenatal Betamethasone Every 12 Hours in Imminent Preterm Labour.

BACKGROUND: Benefits of antenatal corticosteroids have been established for preterm infants who have received the full course. In imminent preterm labours there is no time to administer the second dose 24 h later. OBJECTIVE: To determine whether the administration of two doses of betamethasone in a 12 h interval is equivalent to the effects of a full maturation. METHODS: We performed a retrospective cohort study including preterm infants ≤34 weeks gestational age at birth and ≤1500 g, admitted to an NICU IIIC level in a tertiary hospital from 2015 to 2020. The population was divided into two cohorts: complete maturation (CM) (two doses of betamethasone 24 h apart), or advanced maturation (AM) (two doses of betamethasone 12 h apart). The primary outcomes were mortality or survival with severe morbidities. The presence of respiratory distress syndrome and other morbidities of prematurity were determined. These variables were analysed in the neonates under 28 weeks gestational age cohort. Neurodevelopment at 2 years was evaluated with the validated Ages and Stages Questionnaires®, Third Edition (ASQ®-3). Multiple regression analyses were performed and adjusted for confounding factors. RESULTS: A total of 275 preterm neonates were included. Serious outcomes did not show differences between cohorts, no increased incidence of morbidity was found in AM. A lower percentage of hypotension during the first week (p = 0.04), a tendency towards lower maximum FiO2 (p = 0.14) and to a shorter mechanical ventilation time (p = 0.14) were observed for the AM cohort. Similar results were found in the subgroup of neonates under 28 weeks gestational age. There were no differences in cerebral palsy or sensory deficits at 24 months of corrected age, although the AM cohort showed a trend towards better scores on the ASQ3 scale. CONCLUSIONS: Administration of betamethasone every 12 h showed similar results to the traditional pattern with respect to mortality and severe morbidities. No deleterious neurodevelopmental effects were found at 24 months of corrected age. Earlier administration of betamethasone at 12 h after the first dose would be an alternative in imminent preterm delivery. Further studies are needed to confirm these results.

Predictive metabolomics of multiple Atacama plant species unveils a core set of generic metabolites for extreme climate resilience.

Current crop yield of the best ideotypes is stagnating and threatened by climate change. In this scenario, understanding wild plant adaptations in extreme ecosystems offers an opportunity to learn about new mechanisms for resilience. Previous studies have shown species specificity for metabolites involved in plant adaptation to harsh environments. Here, we combined multispecies ecological metabolomics and machine learning-based generalized linear model predictions to link the metabolome to the plant environment in a set of 24 species belonging to 14 families growing along an altitudinal gradient in the Atacama Desert. Thirty-nine common compounds predicted the plant environment with 79% accuracy, thus establishing the plant metabolome as an excellent integrative predictor of environmental fluctuations. These metabolites were independent of the species and validated both statistically and biologically using an independent dataset from a different sampling year. Thereafter, using multiblock predictive regressions, metabolites were linked to climatic and edaphic stressors such as freezing temperature, water deficit and high solar irradiance. These findings indicate that plants from different evolutionary trajectories use a generic metabolic toolkit to face extreme environments. These core metabolites, also present in agronomic species, provide a unique metabolic goldmine for improving crop performances under abiotic pressure.

Maternal hypercaloric diet affects factors involved in lipid metabolism and the endogenous cannabinoid systems in the hypothalamus of adult offspring: sex-specific response of astrocytes to palmitic acid and anandamide.

Aim: We aimed to investigate whether maternal malnutrition during gestation/lactation induces long-lasting changes on inflammation, lipid metabolism and endocannabinoid signaling in the adult offspring hypothalamus and the role of hypothalamic astrocytes in these changes.Methods: We analyzed the effects of a free-choice hypercaloric palatable diet (P) during (pre)gestation, lactation and/or post-weaning on inflammation, lipid metabolism and endogenous cannabinoid signaling in the adult offspring hypothalamus. We also evaluated the response of primary hypothalamic astrocytes to palmitic acid and anandamide.Results: Postnatal exposure to a P diet induced factors involved in hypothalamic inflammation (Tnfa and Il6) and gliosis (Gfap, vimentin and Iba1) in adult offspring, being more significant in females. In contrast, maternal P diet reduced factors involved in astrogliosis (vimentin), fatty acid oxidation (Cpt1a) and monounsaturated fatty acid synthesis (Scd1). These changes were accompanied by an increase in the expression of the genes for the cannabinoid receptor (Cnr1) and Nape-pld, an enzyme involved in endocannabinoid synthesis, in females and a decrease in the endocannabinoid degradation enzyme Faah in males. These changes suggest that the maternal P diet results in sex-specific alterations in hypothalamic endocannabinoid signaling and lipid metabolism. This hypothesis was tested in hypothalamic astrocyte cultures, where palmitic acid (PA) and the polyunsaturated fatty acid N-arachidonoylethanolamine (anandamide or AEA) were found to induce similar changes in the endocannabinoid system (ECS) and lipid metabolism.Conclusion: These results stress the importance of both maternal diet and sex in long term metabolic programming and suggest a possible role of hypothalamic astrocytes in this process.

It's not all the same to pigeons: Representations of difference may be shared across species.

Pigeons readily learn and transfer same-different discriminations in a variety of experimental paradigms. However, strategically designed probe tests suggest that they might only represent sameness. Here, we provide the first direct evidence that pigeons also represent difference. We first trained pigeons on a conditional same-different discrimination; then, on probe trials, we replaced either the same-item pair or the different-item pair with a familiar, but ambiguous stimulus. On different-cued probe trials, pigeons' choices were controlled by sameness: they reliably rejected the same-item pair, but they did not reliably select the different-item pair. Conversely, on same-cued probe trials, pigeons' choices were controlled by difference: they reliably rejected the different-item pair, but they did not reliably select the same-item pair. Together, these findings demonstrate that pigeons can represent both sameness and difference, providing an important clue to elucidating the evolutionary origins of same-different conceptualization.

Enhanced glycolysis and GSK3 inactivation promote brain metabolic adaptations following neuronal mitochondrial stress.

We analyzed early brain metabolic adaptations in response to mitochondrial dysfunction in a mouse model of mitochondrial encephalopathy with complex IV deficiency [neuron-specific COX10 knockout (KO)]. In this mouse model, the onset of the mitochondrial defect did not coincide with immediate cell death, suggesting early adaptive metabolic responses to compensate for the energetic deficit. Metabolomic analysis in the KO mice revealed increased levels of glycolytic and pentose phosphate pathway intermediates, amino acids and lysolipids. Glycolysis was modulated by enhanced activity of glycolytic enzymes, and not by their overexpression, suggesting the importance of post-translational modifications in the adaptive response. Glycogen synthase kinase 3 inactivation was the most upstream regulation identified, implying that it is a key event in this adaptive mechanism. Because neurons are thought not to rely on glycolysis for adenosine triphosphate production in normal conditions, our results indicate that neurons still maintain their ability to upregulate this pathway when under mitochondrial respiration stress.

ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly.

The ATPase Family AAA Domain Containing 3A (ATAD3A), is a mitochondrial inner membrane protein conserved in metazoans. ATAD3A has been associated with several mitochondrial functions, including nucleoid organization, cholesterol metabolism, and mitochondrial translation. To address its primary role, we generated a neuronal-specific conditional knockout (Atad3 nKO) mouse model, which developed a severe encephalopathy by 5 months of age. Pre-symptomatic mice showed aberrant mitochondrial cristae morphogenesis in the cortex as early as 2 months. Using a multi-omics approach in the CNS of 2-to-3-month-old mice, we found early alterations in the organelle membrane structure. We also show that human ATAD3A associates with different components of the inner membrane, including OXPHOS complex I, Letm1, and prohibitin complexes. Stochastic Optical Reconstruction Microscopy (STORM) shows that ATAD3A is regularly distributed along the inner mitochondrial membrane, suggesting a critical structural role in inner mitochondrial membrane and its organization, most likely in an ATPase-dependent manner.

Plant ecological genomics at the limits of life in the Atacama Desert.

The Atacama Desert in Chile-hyperarid and with high-ultraviolet irradiance levels-is one of the harshest environments on Earth. Yet, dozens of species grow there, including Atacama-endemic plants. Herein, we establish the Talabre-Lejía transect (TLT) in the Atacama as an unparalleled natural laboratory to study plant adaptation to extreme environmental conditions. We characterized climate, soil, plant, and soil-microbe diversity at 22 sites (every 100 m of altitude) along the TLT over a 10-y period. We quantified drought, nutrient deficiencies, large diurnal temperature oscillations, and pH gradients that define three distinct vegetational belts along the altitudinal cline. We deep-sequenced transcriptomes of 32 dominant plant species spanning the major plant clades, and assessed soil microbes by metabarcoding sequencing. The top-expressed genes in the 32 Atacama species are enriched in stress responses, metabolism, and energy production. Moreover, their root-associated soils are enriched in growth-promoting bacteria, including nitrogen fixers. To identify genes associated with plant adaptation to harsh environments, we compared 32 Atacama species with the 32 closest sequenced species, comprising 70 taxa and 1,686,950 proteins. To perform phylogenomic reconstruction, we concatenated 15,972 ortholog groups into a supermatrix of 8,599,764 amino acids. Using two codon-based methods, we identified 265 candidate positively selected genes (PSGs) in the Atacama plants, 64% of which are located in Pfam domains, supporting their functional relevance. For 59/184 PSGs with an Arabidopsis ortholog, we uncovered functional evidence linking them to plant resilience. As some Atacama plants are closely related to staple crops, these candidate PSGs are a "genetic goldmine" to engineer crop resilience to face climate change.

Two-item conditional same-different categorization in pigeons: Finding differences.

Research on same-different categorization has shown that mastery of tasks of this kind can be strongly affected by the number of items in the training arrays-for both humans and nonhuman animals. Evidence for two-item same-different categorization in pigeons is decidedly mixed: although some investigations have succeeded, others have failed. To date, no research has documented successful conditional same-different categorization using just two items, nor has research explored how pigeons' responses in this paradigm might be influenced by perceptual characteristics of the training stimuli. Through a series of methodological modifications, we provide the first successful documentation that pigeons can perform two-item conditional same-different categorization to a high degree of accuracy; further, they can do so without the support of item repetition. We also show for the first time that the perceptual disparity between the items in pairs of different stimuli plays a key part in pigeons' same-different categorization performance. (PsycInfo Database Record (c) 2021 APA, all rights reserved).