Causal Influence of Linguistic Learning on Perceptual and Conceptual Processing: A Brain-Constrained Deep Neural Network Study of Proper Names and Category Terms.

Language influences cognitive and conceptual processing, but the mechanisms through which such causal effects are realized in the human brain remain unknown. Here, we use a brain-constrained deep neural network model of category formation and symbol learning and analyze the emergent model's internal mechanisms at the neural circuit level. In one set of simulations, the network was presented with similar patterns of neural activity indexing instances of objects and actions belonging to the same categories. Biologically realistic Hebbian learning led to the formation of instance-specific neurons distributed across multiple areas of the network, and, in addition, to cell assembly circuits of "shared" neurons responding to all category instances-the network correlates of conceptual categories. In two separate sets of simulations, the network learned the same patterns together with symbols for individual instances ["proper names" (PN)] or symbols related to classes of instances sharing common features ["category terms" (CT)]. Learning CT remarkably increased the number of shared neurons in the network, thereby making category representations more robust while reducing the number of neurons of instance-specific ones. In contrast, proper name learning prevented a substantial reduction of instance-specific neurons and blocked the overgrowth of category general cells. Representational similarity analysis further confirmed that the neural activity patterns of category instances became more similar to each other after category-term learning, relative to both learning with PN and without any symbols. These network-based mechanisms for concepts, PN, and CT explain why and how symbol learning changes object perception and memory, as revealed by experimental studies.

Role of tissue biomechanics in the formation and function of myocardial trabeculae in zebrafish embryos.

Cardiac trabeculae are uneven ventricular muscular structures that develop during early embryonic heart development at the outer curvature of the ventricle. Their biomechanical function is not completely understood, and while their formation is known to be mechanosensitive, it is unclear whether ventricular tissue internal stresses play an important role in their formation. Here, we performed imaging and image-based cardiac biomechanics simulations on zebrafish embryonic ventricles to investigate these issues. Microscopy-based ventricular strain measurements show that the appearance of trabeculae coincided with enhanced deformability of the ventricular wall. Image-based biomechanical simulations reveal that the presence of trabeculae reduces ventricular tissue internal stresses, likely acting as structural support in response to the geometry of the ventricle. Passive ventricular pressure-loading experiments further reveal that the formation of trabeculae is associated with a spatial homogenization of ventricular tissue stiffnesses in healthy hearts, but gata1 morphants with a disrupted trabeculation process retain a spatial stiffness heterogeneity. Our findings thus suggest that modulating ventricular wall deformability, stresses, and stiffness are among the biomechanical functions of trabeculae. Further, experiments with gata1 morphants reveal that a reduction in fluid pressures and consequently ventricular tissue internal stresses can disrupt trabeculation, but a subsequent restoration of ventricular tissue internal stresses via vasopressin rescues trabeculation, demonstrating that tissue stresses are important to trabeculae formation. Overall, we find that tissue biomechanics is important to the formation and function of embryonic heart trabeculation. KEY POINTS: Trabeculations are fascinating and important cardiac structures and their abnormalities are linked to embryonic demise. However, their function in the heart and their mechanobiological formation processes are not completely understood. Our imaging and modelling show that tissue biomechanics is the key here. We find that trabeculations enhance cardiac wall deformability, reduce fluid pressure stresses, homogenize wall stiffness, and have alignments that are optimal for providing load-bearing structural support for the heart. We further discover that high ventricular tissue internal stresses consequent to high fluid pressures are needed for trabeculation formation through a rescue experiment, demonstrating that myocardial tissue stresses are as important as fluid flow wall shear stresses for trabeculation formation.

Genome-Enabled Analysis of Population Dynamics and Virulence-Associated Loci in the Oat Crown Rust Fungus Puccinia coronata f. sp. avenae.

Puccinia coronata f. sp. avenae (Pca) is an important fungal pathogen causing crown rust that impacts oat production worldwide. Genetic resistance for crop protection against Pca is often overcome by the rapid virulence evolution of the pathogen. This study investigated the factors shaping adaptive evolution of Pca using pathogen populations from distinct geographic regions within the United States and South Africa. Phenotypic and genome-wide sequencing data of these diverse Pca collections, including 217 isolates, uncovered phylogenetic relationships and established distinct genetic composition between populations from northern and southern regions from the United States and South Africa. The population dynamics of Pca involve a bidirectional movement of inoculum between northern and southern regions of the United States and contributions from clonality and sexuality. The population from South Africa is solely clonal. A genome-wide association study (GWAS) employing a haplotype-resolved Pca reference genome was used to define 11 virulence-associated loci corresponding to 25 oat differential lines. These regions were screened to determine candidate Avr effector genes. Overall, the GWAS results allowed us to identify the underlying genetic factors controlling pathogen recognition in an oat differential set used in the United States to assign pathogen races (pathotypes). Key GWAS findings support complex genetic interactions in several oat lines, suggesting allelism among resistance genes or redundancy of genes included in the differential set, multiple resistance genes recognizing genetically linked Avr effector genes, or potentially epistatic relationships. A careful evaluation of the composition of the oat differential set accompanied by the development or implementation of molecular markers is recommended. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Tripolar concentric ring electrodes for capturing localised electroencephalography signals during sleep.

By design, tripolar concentric ring electrodes (TCRE) provide more focal brain activity signals than conventional electroencephalography (EEG) electrodes placed further apart. This study compared spectral characteristics and rates of data loss to noisy epochs with TCRE versus conventional EEG signals recorded during sleep. A total of 20 healthy sleepers (12 females; mean [standard deviation] age 27.8 [9.6] years) underwent a 9-h sleep study. Participants were set up for polysomnography recording with TCRE to assess brain activity from 18 sites and conventional electrodes for EEG, eyes, and muscle movement. A fast Fourier transform using multitaper-based estimation was applied in 5-s epochs to scored sleep. Odds ratios with Bonferroni-adjusted 95% confidence intervals were calculated to determine the proportional differences in the number of noisy epochs between electrode types. Relative power was compared in frequency bands throughout sleep. Linear mixed models showed significant main effects of signal type (p < 0.001) and sleep stage (p < 0.001) on relative spectral power in each power band, with lower relative spectral power across all stages in TCRE versus EEG in alpha, beta, sigma, and theta activity, and greater delta power in all stages. Scalp topography plots showed distinct beta activation in the right parietal lobe with TCRE versus EEG. EEG showed higher rates of noisy epochs compared to TCRE (1.3% versus 0.8%, p < 0.001). TCRE signals showed marked differences in brain activity compared to EEG, consistent with more focal measurements and region-specific differences during sleep. TCRE may be useful for evaluating regional differences in brain activity with reduced muscle artefact compared to conventional EEG.

Neonatal outcomes in the surgical management of placenta accreta spectrum disorders: a retrospective single-center observational study from 468 Vietnamese pregnancies beyond 28 weeks of gestation.

BACKGROUND: Placenta accreta spectrum disorders (PASDs) increase the mortality rate for mothers and newborns over a decade. Thus, the purpose of the study is to evaluate the neonatal outcomes in emergency cesarean section (CS) and planned surgery as well as in Cesarean hysterectomy and the modified one-step conservative uterine surgery (MOSCUS). The secondary aim is to reveal the factors relating to poor neonatal outcomes. METHODS: This was a single-center retrospective study conducted between 2019 and 2020 at Tu Du Hospital, in the southern region of Vietnam. A total of 497 pregnant women involved in PASDs beyond 28 weeks of gestation were enrolled. The clinical outcomes concerning gestational age, birth weight, APGAR score, neonatal intervention, neonatal intensive care unit (NICU) admission, and NICU length of stay (LOS) were compared between emergency and planned surgery, between the Cesarean hysterectomy and the MOSCUS. The univariate and multivariable logistic regression were used to assess the adverse neonatal outcomes. RESULTS: Among 468 intraoperatively diagnosed PASD cases who underwent CS under general anesthesia, neonatal outcomes in the emergency CS (n = 65) were significantly poorer than in planned delivery (n = 403). Emergency CS increased the odds ratio (OR) for earlier gestational age, lower birthweight, lower APGAR score at 5 min, higher rate of neonatal intervention, NICU admission, and longer NICU LOS ≥ 7 days with OR, 95% confidence interval (CI) were 10.743 (5.675-20.338), 3.823 (2.197-6.651), 5.215 (2.277-11.942), 2.256 (1.318-3.861), 2.177 (1.262-3.756), 3.613 (2.052-6.363), and 2.298 (1.140-4.630), respectively, p < 0.05. Conversely, there was no statistically significant difference between the neonatal outcomes in Cesarean hysterectomy (n = 79) and the MOSCUS method (n = 217). Using the multivariable logistic regression, factors independently associated with the 5-min-APGAR score of less than 7 points were time duration from the skin incision to fetal delivery (min) and gestational age (week). One minute-decreased time duration from skin incision to fetal delivery contributed to reduce the risk of adverse neonatal outcome by 2.2% with adjusted OR, 95% CI: 0.978 (0.962-0.993), p = 0.006. Meanwhile, one week-decreased gestational age increased approximately two fold odds of the adverse neonatal outcome with adjusted OR, 95% CI: 1.983 (1.600-2.456), p < 0.0001. CONCLUSIONS: Among pregnancies with PASDs, the neonatal outcomes are worse in the emergency group compared to planned group of cesarean section. Additionally, the neonatal comorbidities in the conservative surgery using the MOSCUS method are similar to Cesarean hysterectomy. Time duration from the skin incision to fetal delivery and gestational age may be considered in PASD surgery. Further data is required to strengthen these findings.

Prediction of Protein-Protein Interactions Based on Integrating Deep Learning and Feature Fusion.

Understanding protein-protein interactions (PPIs) helps to identify protein functions and develop other important applications such as drug preparation and protein-disease relationship identification. Deep-learning-based approaches are being intensely researched for PPI determination to reduce the cost and time of previous testing methods. In this work, we integrate deep learning with feature fusion, harnessing the strengths of both approaches, handcrafted features, and protein sequence embedding. The accuracies of the proposed model using five-fold cross-validation on Yeast core and Human datasets are 96.34% and 99.30%, respectively. In the task of predicting interactions in important PPI networks, our model correctly predicted all interactions in one-core, Wnt-related, and cancer-specific networks. The experimental results on cross-species datasets, including Caenorhabditis elegans, Helicobacter pylori, Homo sapiens, Mus musculus, and Escherichia coli, also show that our feature fusion method helps increase the generalization capability of the PPI prediction model.

Platelet rich fibrin and MTA in the treatment of teeth with open apices.

BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.

Photorefinery of Biomass and Plastics to Renewable Chemicals using Heterogeneous Catalysts.

The photocatalytic conversion of biomass and plastic waste provides opportunities for sustainable fuel and chemical production. Heterogeneous photocatalysts, typically composed of semiconductors with distinctive redox properties in their conduction band (CB) and valence band (VB), facilitate both the oxidative and reductive valorization of organic feedstocks. This article provides a comprehensive overview of recent advancements in the photorefinery of biomass and plastics from the perspective of the redox properties of photocatalysts. We explore the roles of the VB and CB in enhancing the value-added conversion of biomass and plastics via various pathways. Our aim is to bridge the gap between photocatalytic mechanisms and renewable carbon feedstock valorization, inspiring further development in photocatalytic refinery of biomass and plastics.

Outbreak of Sexually Transmitted Nongroupable Neisseria meningitidis-Associated Urethritis, Vietnam.

We report on an outbreak of nongroupable Neisseria meningitidis-associated urethritis, primarily among men who have sex with men in southern Vietnam. Nearly 50% of N. meningitidis isolates were resistant to ciprofloxacin. This emerging pathogen should be considered in the differential diagnosis and management of urethritis.

Clinical characteristics and treatment outcomes of tuberculous tenosynovitis of the hand and wrist.

Objective: Vietnam is endemic with tuberculosis (TB), which is highly prevalent in the community. TB tenosynovitis of the wrist and hand is uncommon. Because of its insidious progression and atypical presentations, it is often difficult to diagnose, leading to treatment delays. This study investigates the characteristics of clinical and subclinical signs and treatment outcomes of patients with TB tenosynovitis in Vietnam. Patients and Methods: This prospective longitudinal cross-sectional study included 25 TB tenosynovitis patients in the Rheumatology Clinic at University Medical Center Ho Chi Minh City. The diagnosis was made based on a tuberculous cyst in histopathological specimens. The data were collected through medical history, physical examination, and medical records, including demographics, signs, symptoms, condition duration, and related laboratory tests and imaging. The outcomes of all participants were assessed after 12 months of treatment. Results: The most common symptom of TB tenosynovitis was swelling of the hand and wrist, which was present in all patients. Its other symptoms included mild pain and numbness of the hand in 72% and 24% of patients, respectively. It can affect any site on the hand. Hand ultrasound findings included thickening of the synovial membrane (80%), peritendinous effusion (64%), and soft tissue swelling (88%). Most patients (18/22) had a good outcome after the treatment with anti-tubercular drugs. Conclusions: TB tenosynovitis progression is often insidious. Its most common symptoms are swelling of the hand and mild pain. Ultrasound is a useful tool to support the diagnosis. A histological examination confirms the diagnosis. Most cases respond and have a good outcome after 9-12 months of anti-tuberculosis treatment.

Retroperitoneal ectopic pregnancy: successful expectant management in condition of early pregnancy failure.

BACKGROUND: Retroperitoneal ectopic pregnancy (REP) refers to abnormal implantation of the fertilized egg in the retroperitoneal cavity. REP can be divided into pelvic and abdominal positions. Extremely rare, the incidence of REP is less than 1% of ectopic pregnancy (EP). Herein, we report the first case of paraaortic-located REP in association with successful expectant management, thus raising awareness among healthcare providers, particularly in low-resource settings. CASE PRESENTATION: A reproductive-age woman presented at our tertiary referral hospital because of amenorrhea and a positive pregnancy test. Based on serial serum ß-hCG levels and imaging modalities including transabdominal ultrasound, transvaginal sonography, and magnetic resonance imaging (MRI), a REP of 7-9 weeks of gestational age adherent to abdominal paraaortic region was detected. Since the pregnancy was spontaneously arrested without clinical symptoms, expectant management was first indicated following careful evaluation. After a 1-month follow-up, the ectopic mass naturally degenerated without complications and her ß-hCG concentration returned to a negative value. Therefore, the patient recovered completely and avoided unnecessary surgery as well as toxicity of medical treatment when using systemic methotrexate. CONCLUSIONS: In addition to transvaginal and transabdominal ultrasound, MRI is necessary for the diagnosis of nonviable REP. Alongside the great vessels in the abdominal cavity should be taken into consideration in all suspected cases relating to this rare entity. Expectant management may be carefully indicated in conditions of nonviable REP and unruptured REP, where applicable.

Multiplexed single-cell profiling of chromatin states at genomic loci by expansion microscopy.

Proper regulation of genome architecture and activity is essential for the development and function of multicellular organisms. Histone modifications, acting in combination, specify these activity states at individual genomic loci. However, the methods used to study these modifications often require either a large number of cells or are limited to targeting one histone mark at a time. Here, we developed a new method called Single Cell Evaluation of Post-TRanslational Epigenetic Encoding (SCEPTRE) that uses Expansion Microscopy (ExM) to visualize and quantify multiple histone modifications at non-repetitive genomic regions in single cells at a spatial resolution of ∼75 nm. Using SCEPTRE, we distinguished multiple histone modifications at a single housekeeping gene, quantified histone modification levels at multiple developmentally-regulated genes in individual cells, and evaluated the relationship between histone modifications and RNA polymerase II loading at individual loci. We find extensive variability in epigenetic states between individual gene loci hidden from current population-averaged measurements. These findings establish SCEPTRE as a new technique for multiplexed detection of combinatorial chromatin states at single genomic loci in single cells.

Rectal Ectopic Pregnancy Managed Successfully by Minimally Invasive Treatment Using Local Methotrexate Injection and Systemic Methotrexate Administration: An Extremely Rare Case at Tu Du Hospital in Vietnam and Literature Review.

Rectal ectopic pregnancy (REP) is one of the most extremely rare forms of ectopic pregnancy that strongly leads to maternal mortality higher than common types. An early diagnosis of unruptured REP remains a challenge and its management ought to be individualized depending on the clinical scenario. Currently, owing to the paucity of data, there are no practical guidelines for an appropriate treatment until today. We hereby present a very unusual case at our maternity care center. A 30-year-old pregnant woman (gravidity: 2, parity: 2) complained with abdominal pain and retard menstrual cycle. After serum beta-human chorionic gonadotropin (ß-hCG) levels and ultrasonic examinations, a diagnosis of ovarian ectopic pregnancy was established. Thus, the patient underwent explanatory laparoscopy for confirming the diagnosis and for the treatment. However, on the 5th day postoperative course, her ß-hCG level continued to increase every 48 hours. By magnetic resonance imaging and pelvic ultrasonography, a gestational sac adherent to the rectal wall was clearly detected. After counseling with multidisciplinary team, a minimally invasive laparoscopy followed by a local injection of methotrexate under ultrasound guidance for gestational sac access and a systemic multidose methotrexate regimen were indicated. In result, her serum ß-hCG declined substantially. Although it is very rare, extrauterine pregnancy involving the rectum may be presented. Early diagnosis helps in avoiding the fatal complications and a proper management should be counseled carefully. Conservative treatment with minimally surgical intervention could be an alternative option in appropriate condition. Further data are required to summarize this occult entity.

Increased virulence of Puccinia coronata f. sp.avenae populations through allele frequency changes at multiple putative Avr loci.

Pathogen populations are expected to evolve virulence traits in response to resistance deployed in agricultural settings. However, few temporal datasets have been available to characterize this process at the population level. Here, we examined two temporally separated populations of Puccinia coronata f. sp. avenae (Pca), which causes crown rust disease in oat (Avena sativa) sampled from 1990 to 2015. We show that a substantial increase in virulence occurred from 1990 to 2015 and this was associated with a genetic differentiation between populations detected by genome-wide sequencing. We found strong evidence for genetic recombination in these populations, showing the importance of the alternate host in generating genotypic variation through sexual reproduction. However, asexual expansion of some clonal lineages was also observed within years. Genome-wide association analysis identified seven Avr loci associated with virulence towards fifteen Pc resistance genes in oat and suggests that some groups of Pc genes recognize the same pathogen effectors. The temporal shift in virulence patterns in the Pca populations between 1990 and 2015 is associated with changes in allele frequency in these genomic regions. Nucleotide diversity patterns at a single Avr locus corresponding to Pc38, Pc39, Pc55, Pc63, Pc70, and Pc71 showed evidence of a selective sweep associated with the shift to virulence towards these resistance genes in all 2015 collected isolates.

Using dinoprostone slow release vaginal insert for cervical ripening in term-pregnancy with oligohydramnios.

AIMS: The study purposed to evaluate the success rate of cervical ripening using dinoprostone controlled-release vaginal insert and reveal some factors relating to successful cervical ripening. METHODS: This cross-sectional study was conducted at Tu Du Hospital in Vietnam from December 2021 to August 2022. The study enrolled 200 pregnant women with gestational age ≥37 weeks diagnosed with oligohydramnios. These candidates underwent dinoprostone cervical ripening (DCR) according to the local protocol. The Bishop score ≥7 after 24 h was determined for the successful cervical ripening (SCR). RESULTS: In total, the success rate of DCR achieved at 57.5% and the cesarean delivery rate was 46.5%. None of the severe side-effects and complications was present. Using multivariable logistic regression, the study found that the body mass index ≥25 kg/m2 and oxytocin infusion drip related to SCR with adjusted odds ratio (aOR): 3.67 (95% confidence intervals [CI]: 1.78-7.57) and aOR: 4.68 (95% CI: 1.84-11.93), p < 0.001. Using the Kaplan-Meier curve, the present study revealed a significant difference between Bishop <3 and ≥3 following the duration time of cervical ripening, with hazard ratio: 1.38 (95% CI: 1.19-1.59), p < 0.001. The time duration of cervical ripening was not significantly different following amniotic fluid index from 3 to 5 cm. CONCLUSIONS: Cervical ripening using a dinoprostone vaginal insert is a potentially acceptable method in term pregnancy accompanying with oligohydramnios. The probability of SCR can be predicted on a careful assessment of relative factors by obstetricians. Further studies are required to strengthen these findings.

Ethyl Caffeate Can Inhibit Aryl Hydrocarbon Receptor (AhR) Signaling and AhR-Mediated Potentiation of Mast Cell Activation.

Ethyl caffeate (EC) is a natural phenolic compound that is present in several medicinal plants used to treat inflammatory disorders. However, its anti-inflammatory mechanisms are not fully understood. Here, we report that EC inhibits aryl hydrocarbon receptor (AhR) signaling and that this is associated with its anti-allergic activity. EC inhibited AhR activation, induced by the AhR ligands FICZ and DHNA in AhR signaling-reporter cells and mouse bone marrow-derived mast cells (BMMCs), as assessed by AhR target gene expressions such as CYP1A1. EC also inhibited the FICZ-induced downregulation of AhR expression and DHNA-induced IL-6 production in BMMCs. Furthermore, the pretreatment of mice with orally administered EC inhibited DHNA-induced CYP1A1 expression in the intestine. Notably, both EC and CH-223191, a well-established AhR antagonist, inhibited IgE-mediated degranulation in BMMCs grown in a cell culture medium containing significant amounts of AhR ligands. Furthermore, oral administration of EC or CH-223191 to mice inhibited the PCA reaction associated with the suppression of constitutive CYP1A1 expression within the skin. Collectively, EC inhibited AhR signaling and AhR-mediated potentiation of mast cell activation due to the intrinsic AhR activity in both the culture medium and normal mouse skin. Given the AhR control of inflammation, these findings suggest a novel mechanism for the anti-inflammatory activity of EC.

Advanced Fabrication and Multi-Properties of Aluminum-Based Aerogels from Aluminum Waste for Thermal Insulation and Oil Absorption Applications.

Metal-based aerogels have attracted numerous studies due to their unique physical, structural, thermal, and chemical properties. Utilizing aluminum waste, a novel, facile, environmentally friendly approach to aluminum-based aerogels is proposed. In this work, the aluminum-based aerogels produced do not use toxic chemicals unlike conventional aerogel production. Aluminum powder, with poly(acrylic acid) and carboxymethyl cellulose as binders, is converted into aluminum-based aerogels using the freeze-drying method. The aluminum-based aerogels have low density (0.08-0.12 g/cm3) and high porosity (93.83-95.68%). The thermal conductivity of the aerogels obtained is very low (0.038-0.045 W/m·K), comparable to other types of aerogels and commercial heat insulation materials. Additionally, the aerogels can withstand temperatures up to 1000 °C with less than 40% decomposition. The aerogels exhibited promising oil absorption properties with their absorption capacity of 9.8 g/g and 0.784 g/cm3. The Young's modulus of the aerogels ranged from 70.6 kPa to 330.2 kPa. This study suggests that aluminum-based aerogels have potential in thermal insulation and oil absorption applications.

Protective role of the mitochondrial fusion protein OPA1 in hypertension.

Hypertension is associated with excessive reactive oxygen species (ROS) production in vascular cells. Mitochondria undergo fusion and fission, a process playing a role in mitochondrial function. OPA1 is essential for mitochondrial fusion. Loss of OPA1 is associated with ROS production and cell dysfunction. We hypothesized that mitochondria fusion could reduce oxidative stress that defect in fusion would exacerbate hypertension. Using (a) Opa1 haploinsufficiency in isolated resistance arteries from Opa1+/- mice, (b) primary vascular cells from Opa1+/- mice, and (c) RNA interference experiments with siRNA against Opa1 in vascular cells, we investigated the role of mitochondria fusion in hypertension. In hypertension, Opa1 haploinsufficiency induced altered mitochondrial cristae structure both in vascular smooth muscle and endothelial cells but did not modify protein level of long and short forms of OPA1. In addition, we demonstrated an increase of mitochondrial ROS production, associated with a decrease of superoxide dismutase 1 protein expression. We also observed an increase of apoptosis in vascular cells and a decreased VSMCs proliferation. Blood pressure, vascular contractility, as well as endothelium-dependent and -independent relaxation were similar in Opa1+/- , WT, L-NAME-treated Opa1+/- and WT mice. Nevertheless, chronic NO-synthase inhibition with L-NAME induced a greater hypertension in Opa1+/- than in WT mice without compensatory arterial wall hypertrophy. This was associated with a stronger reduction in endothelium-dependent relaxation due to excessive ROS production. Our results highlight the protective role of mitochondria fusion in the vasculature during hypertension by limiting mitochondria ROS production.

Annual Research Review: Attention-deficit/hyperactivity disorder in girls and women: underrepresentation, longitudinal processes, and key directions.

Attention-deficit/hyperactivity disorder (ADHD) - and its underlying behavioral dimensions of inattention and hyperactivity-impulsivity - have been understudied in females. We first cover the conceptual issues of prevalence, diagnostic practices, diversity, comorbidity, and causal factors, plus forces limiting awareness of ADHD in females. After a narrative review of cross-sectional and longitudinal findings, we conclude the following. (a) Girls meet diagnostic criteria for ADHD at just under half the rates of boys, a ratio that becomes much closer to equal by adulthood. (b) Girls and women with ADHD show a predominance of inattention and associated internalizing problems; boys and men display greater levels of hyperactive-impulsive symptoms and associated externalizing problems. (c) Sex differences in ADHD symptoms and related outcomes depend heavily on the clinical versus nonreferred nature of the samples under investigation. (d) Females with ADHD experience, on average, serious impairments, with a particularly heightened risk for problems in close relationships and engagement in self-harm. (e) Clinicians may overlook symptoms and impairments in females because of less overt (but still impairing) symptom manifestations in girls and women and their frequent adoption of compensatory strategies. Our review of predictors and mediators of adult outcomes highlights (a) the potential for heterotypically continuous pathways in females with childhood ADHD and (b) developmental progressions to self-harm, intimate partner violence, unplanned pregnancy, and comorbid psychopathology. Focusing on ADHD in females is necessary to characterize causal and maintaining mechanisms with accuracy and to foster responsive interventions, as highlighted in our closing list of clinical implications and research priorities.

Unsupervised discovery of dynamic cell phenotypic states from transmitted light movies.

Identification of cell phenotypic states within heterogeneous populations, along with elucidation of their switching dynamics, is a central challenge in modern biology. Conventional single-cell analysis methods typically provide only indirect, static phenotypic readouts. Transmitted light images, on the other hand, provide direct morphological readouts and can be acquired over time to provide a rich data source for dynamic cell phenotypic state identification. Here, we describe an end-to-end deep learning platform, UPSIDE (Unsupervised Phenotypic State IDEntification), for discovering cell states and their dynamics from transmitted light movies. UPSIDE uses the variational auto-encoder architecture to learn latent cell representations, which are then clustered for state identification, decoded for feature interpretation, and linked across movie frames for transition rate inference. Using UPSIDE, we identified distinct blood cell types in a heterogeneous dataset. We then analyzed movies of patient-derived acute myeloid leukemia cells, from which we identified stem-cell associated morphological states as well as the transition rates to and from these states. UPSIDE opens up the use of transmitted light movies for systematic exploration of cell state heterogeneity and dynamics in biology and medicine.