Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism

The Tricarboxylic Acid Cycle (TCA) cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of research, a comprehensive investigation into the consequences of TCA cycle dysfunction remains elusive. Here, we targeted two TCA cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), and combined metabolomics, transcriptomics, and proteomics analyses to fully appraise the consequences of TCA cycle inhibition (TCAi) in kidney epithelial cells. Our comparative approach shows that TCAi elicits a convergent rewiring of redox and amino acid metabolism dependent on the activation of ATF4 and the integrated stress response (ISR). Furthermore, we also uncover a divergent metabolic response, whereby acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis. Our work highlights an important interplay between the TCA cycle, redox biology and amino acid homeostasis. Highlights TCA cycle inhibition promotes GSH synthesis and impairs de novo aspartate and proline synthesis Disruption of mitochondrial thiol redox homeostasis phenocopies TCA cycle inhibition by promoting GSH synthesis and impairing proline and aspartate synthesis Acute FHi, but not SDHi, can maintain asparagine levels via reductive carboxylation and maintenance of cytosolic aspartate synthesis TCA cycle inhibition mimics an amino acid deprivation-type response and activates ATF4 via the integrated stress response to maintain redox and amino acid homeostasis
Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes reminiscent of absence epilepsy, here termed absence-like activity (ALA), with decreased behavior and vacant staring coinciding with low-frequency oscillations. DBS modulated ALA likelihood in a frequency-specific manner. ALA events corresponded to decreases in measures of neural complexity (entropy) and integration (Φ*), an index of consciousness, and substantial changes to communication in CST circuits. During ALA, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of ALA and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method – but at different stimulation frequencies – can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of absence epilepsy and other consciousness disorders. SIGNIFICANCE We use tailored, multi-microelectrode thalamic deep brain stimulation to reversibly decrease consciousness for otherwise healthy, wakeful animals in a stimulation frequency-dependent manner. This represents a bidirectional mechanism for controlling consciousness, as the same method can increase consciousness under certain conditions. Theories of consciousness debate the relative contribution of parietal and frontal lobes, and largely ignore subcortical contributions. In this study, changes in consciousness predominantly involve changes in subcortical and parietal regions, implying that they contribute more to consciousness than frontal regions. Further, decreases in consciousness (indexed by Φ*) coincide with decreased movement, staring, and low-frequency activity in the EEG, similar to absence epilepsy. Thus, the systems-level mechanisms for decreased consciousness in this study have broader clinical implications for absence epilepsy.
Electron Microscopy Characterization of Sargassum Spp. from the Mexican Caribbean for Application as a Bioconstruction Material

In recent years, the influx of Sargassum spp. on the coasts of the Mexican Caribbean has increased considerably [1–3], generating effects on the marine ecosystem and the tourism sector. Recently, various applications of these algae have been explored, for example energy production, biofertilizers and as a bioconstruction material [1,4]. The thermal conductivity of Sargassum spp. is low, so it can be used as a bioconstruction material for conventional houses, and increase energy efficiency in these constructions [4,5]. The characterization of Sargassum spp. by means of scanning electron microscopy is shown below, to show the identification of some compounds that justify their use as bio-construction material for houses.
Soot Formation in Premixed Hydrocarbon Flames: Prediction of Temperature and Pressure Dependence

Premixed sooting burner stabilized ethene-air flames at pressures from 0.1 to 1.0 MPa that have been investigated experimentally by Wagner et al. have been simulated numerically. The numerical calculations have been performed on the basis of the conservation equations for that system including a detailed chemical model for soot formation. The maximum temperatures in the flames have been varied in the experiments by changing the flow rates of the feed. In accordance with the experimental data the numerical calculations predict a bell shaped dependence of the final soot volume fraction on the maximum flame temperature. A sensitivity analysis of the final soot volume fraction with respect to the rate coefficients of the different reactions identifies the classes of reactions that are most important for soot formation. These are "pre-soot" gas phase reactions. The dependence of the final soot volume fraction on pressure is calculated to be proportional to p2 at 0.1 MPa and proportional to p1 at 1 MPa. This is in accordance with the experiments of Wagner et al. The agreement between predictions and experimental results is reasonable. Important phenomena connected with the formation of soot in premixed hydrocarbon flames are reproduced in the framework of the employed model. A further validation of the model, in particular through the investigation of the reaction rates of the involved elementary steps and their pressure dependence should corroborate the qualitative dependence predicted by the model as it stands now.
I Know Some People: The Association of Social Capital With Primary Health Care Utilization of Residents in China

Background: Primary health care (PHC) services are underused due to the unbalanced distribution of medical resources. This is especially true in developing countries where the construction of PHC systems has begun to take effect. Social capital is one of the important factors affecting primary health care utilization. Method: This study investigated the utilization of PHC services by Chinese community residents in the past year. Social capital, PHC utilization, age, health care insurance, etc., were measured. A multilevel negative binomial model was adopted to analyze the association of social capital with PHC utilization. Results: Data of 5,471 residents from 283 communities in China were collected through a questionnaire survey in 2018. The results showed that community social capital (CSC) is significantly associated with PHC utilization in China, but individual social capital (ISC) had no significant association with PHC utilization. A one-standard deviation increase in the CSC leads to a 1.9% increase in PHC utilization. Other factors like gender, education, income, health insurance, health status, etc., are significantly associated with PHC utilization in China. Conclusions: Community social capital plays a more important role in promoting PHC utilization, while ISC plays an unclear role in PHC utilization by the residents of China.
Integrated Chromatin Accessibility and Transcriptome Landscapes of Doxorubicin-Resistant Breast Cancer Cells

Background Doxorubicin is one of the most effective chemotherapeutic drugs for breast cancer while its common drug resistance leads to poor patient prognosis and survival. Growing evidence indicate dynamically reorganized chromatin allows rapid access of the gene regulatory machinery to open genomic regions facilitating subsequent gene expression through direct transcription factor (TF) activation and regulatory element binding. Methods To better understand the regulatory network underlying doxorubicin resistance in breast cancer cells, we explored the systematic alterations of chromatin accessibility and gene expression by the assay for transposase-accessible chromatin using sequencing (ATAC-seq) in combination with RNA sequencing, followed by integrative analysis to identify potential regulators and their targets associated with differentially accessible regions (DARs) in doxorubicin-resistant MCF7 (MCF7-DR) cells. Results A total of 3,963 differentially expressed genes (DEGs) related to doxorubicin resistance were identified, including dramatically up-regulated MT1E, GSTP1, LDHB, significantly down-regulated TFF1, UBB, DSCAM-AS1, and histone-modifying enzyme coding genes HDAC2, EZH2, PRMT5, etc. By integrating with transcriptomic datasets, we identified 18,228 DARs in MCF7-DR cells compared to control, which were positively correlated with their nearest DEGs (r = 0.6). There were 11,686 increased chromatin-accessible regions, which were enriched in up-regulated genes related to diverse KEGG pathways, such as the cell cycle, regulation of actin cytoskeleton, signaling pathways of MAPK, PI3K/Akt and Hippo, which play essential roles in regulating cell apoptosis, proliferation, metabolism, and inflammatory responses. The 6,542 decreased chromatin-accessible regions were identified for the declined doxorubicin-associated biological processes, for instance, endocrine and insulin resistance, central carbon metabolism, signaling pathways of TGF-beta and P53. Combining data from TCGA, analyses of the DAR sequences associated with the DNA-binding motifs of significantly enriched TF families including AP-1, TEAD and FOX, indicated that the loss-function of FOXA1 might play a critical role in doxorubicin-resistant breast cancer cells (DOX-R BCCs). Conclusion These data exhibit the non-genetic landscape of chromatin accessibility and transcript levels in the DOX-R BCCs, and provide clear insights and resources for the detection of critical TFs and potential cis-regulatory elements-based putative therapeutic targets.
In situ Estimation of Coral Recruitment Patterns From Shallow to Mesophotic Reefs Using an Optimized Fluorescence Imaging System

Coral recruitment represents a key element for coral reef persistence and resilience in the face of environmental disturbances. Studying coral recruitment patterns is fundamental for assessing reef health and implementing appropriate management strategies in an era of climate change. The FluorIS system has been developed to acquire high resolution, wide field-of-view (FOV) in situ images of coral recruits fluorescence and has proven successful in shallow reef environments. However, up to now, its applicability to mesophotic coral ecosystems remains unknown due to the complexity of the system and the limited time available when working at mesophotic depth. In this study we optimized the FluorIS system by utilizing a single infrared-converted camera instead of the bulkier regular dual-camera system, substantially reducing the system complexity and significantly decreasing the acquisition time to an average of 10 s for a set of 3 images. Moreover, the speed-FluorIS system is much more economical, decreasing the cost of the full set-up by roughly 40% compared to the original dual-camera system. We tested the utility of the speed-FluorIS by surveying coral recruits across shallow and mesophotic reefs of the Red Sea (Gulf of Eilat) and Bermuda, two of the most northerly reefs in the world with markedly different substrate and topography, and demonstrate that the modified system enables fast imaging of fluorescence to study coral recruitment patterns over a broader range of depths and reef topographies than previous fluorescence methods. Our single-camera system represents a valuable, non-invasive and rapid underwater tool which will help standardize surveys and long-term monitoring of coral recruits, contributing to our understanding of these vital and delicate early life stages of corals.
Fuzzy System Based Medical Image Processing for Brain Disease Prediction

The present work aims to explore the performance of fuzzy system-based medical image processing for predicting the brain disease. The imaging mechanism of NMR (Nuclear Magnetic Resonance) and the complexity of human brain tissues cause the brain MRI (Magnetic Resonance Imaging) images to present varying degrees of noise, weak boundaries, and artifacts. Hence, improvements are made over the fuzzy clustering algorithm. A brain image processing and brain disease diagnosis prediction model is designed based on improved fuzzy clustering and HPU-Net (Hybrid Pyramid U-Net Model for Brain Tumor Segmentation) to ensure the model safety performance. Brain MRI images collected from a Hospital, are employed in simulation experiments to validate the performance of the proposed algorithm. Moreover, CNN (Convolutional Neural Network), RNN (Recurrent Neural Network), FCM (Fuzzy C-Means), LDCFCM (Local Density Clustering Fuzzy C-Means), and AFCM (Adaptive Fuzzy C-Means) are included in simulation experiments for performance comparison. Results demonstrate that the proposed algorithm has more nodes, lower energy consumption, and more stable changes than other models under the same conditions. Regarding the overall network performance, the proposed algorithm can complete the data transmission tasks the fastest, basically maintaining at about 4.5 s on average, which performs remarkably better than other models. A further prediction performance analysis reveals that the proposed algorithm provides the highest prediction accuracy for the Whole Tumor under DSC (Dice Similarity Coefficient), reaching 0.936. Besides, its Jaccard coefficient is 0.845, proving its superior segmentation accuracy over other models. In a word, the proposed algorithm can provide higher accuracy, a more apparent denoising effect, and the best segmentation and recognition effect than other models while ensuring energy consumption. The results can provide an experimental basis for the feature recognition and predictive diagnosis of brain images.
High-Frequency Oscillations on Interictal Epileptiform Discharges in Routinely Acquired Scalp EEG: Can It Be Used as a Prognostic Marker?

Introduction Despite all the efforts for optimizing epilepsy management in children over the past decades, there is no clear consensus regarding whether to treat or not to treat epileptiform discharges (EDs) after a first unprovoked seizure or the optimal duration of therapy with anti-seizure medication (ASM). It is therefore highly needed to find markers on scalp electroencephalogram (EEG) that can help identify pathological EEG discharges that require treatment. Aim of the study This retrospective study aimed to identify whether the coexistence of ripples/high-frequency oscillations (HFOs) with interictal EDs (IEDs) in routinely acquired scalp EEG is associated with a higher risk of seizure recurrence and could be used as a prognostic marker. Methods 100 children presenting with new onset seizure to Children’s Medical Center- Dallas during 2015–2016, who were not on ASM and had focal EDs on an awake and sleep EEG recorded with sample frequency of 500 HZ, were randomly identified by database review. EEGs were analyzed blinded to the data of the patients. HFOs were visually identified using review parameters including expanded time base and adjusted filter settings. Results The average age of patients was 6.3 years (±4.35 SD). HFOs were visually identified in 19% of the studied patients with an inter-rater reliability of 99% for HFO negative discharges and 78% agreement for identification of HFOs. HFOs were identified more often in the younger age group; however, they were identified in 11% of patients >5 years old. They were more frequently associated with spikes than with sharp waves and more often with higher amplitude EDs. Patients with HFOs were more likely to have a recurrence of seizures in the year after the first seizure (P < 0.05) and to continue to have seizures after 2 years (P < 0.0001). There was no statistically significant difference between the two groups with regards to continuing ASM after 2 years. Conclusion Including analysis for HFOs in routine EEG interpretation may increase the yield of the study and help guide the decision to either start or discontinue ASM. In the future, this may also help to identify pathological discharges with deleterious effects on the growing brain and set a new target for the management of epilepsy.
Relationship Between Dams, Knickpoints and the Longitudinal Profile of the Upper Indus River

Mass movements in mountainous areas are capable of damming rivers and can have a lasting effect on the river longitudinal profile. The long profile is commonly used to retrieve regional tectonic information, but how much dams may compromise geomorphometry-based tectonic analysis has not been systematically researched. In this study, we investigate the relationship between river dams and the longitudinal profile of the upper Indus River basin, based on interpretation and analysis of remote sensing imagery and digital elevation models (DEMs) and local field work. We identified 178 landslide, glacier and debris flow dams. Using TopoToolbox, we automatically extracted the river longitudinal profile from the 30 m SRTM DEM, determined the location of convex knickpoints and calculated the channel steepness index. One hundred and two knickpoints were detected with heights above 148 m, of which 55 were related to dams. There is good spatial correspondence between dams, convexities in the river longitudinal profile and relatively high steepness index. Different dam types have different impacts on the river profile; on the upper Indus, debris flow dams have a greater impact than landslide and glacier dams and can form knickpoints of up to 900 m. Therefore, dams may have a significant influence on the river longitudinal profile, knickpoints and steepness index, and should be considered when extracting information on regional tectonics using these indices.
Cognitive Effect Following a Blended (Face to Face and Videoconference-Delivered) Format Mindfulness Training

While evidence supports the feasibility of online mindfulness training (MT), the effect of this approach on cognition remains unclear. The present study investigated changes in cognition following a newly developed 6-week videoconference-delivered MT program on cognitive function in two groups. The first group (n = 17) had two baseline assessments prior to MT [3 weeks after group two (n = 15)] to allow for evaluation of practice and learning effects. Four participants from each group were excluded from the final analysis due to missing data. Following MT, there was an improvement in switching of attention, working memory, executive function, and social cognition, but some of these effects were not easily accounted for by learning or practice effects. No significant changes were found on tasks measuring sustained attention, cognitive flexibility and inhibition, information processing, and sensory-motor function. Our findings suggest that domain-specific cognition might be enhanced by a brief videoconference-delivered MT, and larger, controlled studies to delineate the effects of online MT on subdomains of cognition are needed.
Molecular Characterization and Expression Analysis of a Novel Glutaredoxin 3 Gene in Pacific White Shrimp (Litopenaeus vannamei)

Glutaredoxins (Grxs), small heat-stable oxidoreductases, are key members of the thioredoxin (Trx) superfamily. Recently, an emerging subclass of Grxs with a cysteine residue in the active site was found in shrimps. However, molecular functions of Grx-related proteins in decapods were rarely reported. In this study, a novel full-length Grx 3 (LvGrx 3) complementary DNA (cDNA) was identified in Pacific white shrimp (Litopenaeus vannamei), which had a 975-bp open reading frame (ORF) encoding a polypeptide of 324 amino acids. The nucleic acid sequence of Pacific white shrimp glutaredoxin 3 (LvGrx 3) showed 99.59% identity with genomic DNA (gDNA) sequence and 63.49% coverage. Sequence alignment showed that the amino acid sequence of LvGrx 3 shared 97% identity with black tiger shrimp (Penaeus monodon) Grx 3 and 62% identity with amphipod (Hyalella azteca) Grx 3. LvGrx 3 showed higher expression in the intestine, gill, and hepatopancreas, and lower expression in epithelium and abdominal nerve. In response to ammonia-N stress, LvGrx 3 was significantly upregulated in both the hepatopancreas and gill, and the peak value appeared after 24 h exposure. After lipopolysaccharide (LPS) injection, expression levels of LvGrx 3 in the hepatopancreas were increased in the middle stage, and LvGrx 3 in gill was upregulated in the middle and later periods (24 and 48 h). These results indicate that LvGrx 3 can participate in immune responses against ammonia-N stress and pathogen infection. However, RNA interference (RNAi) assay showed that LvGrx 3 silencing in ammonia-N-challenged shrimp could significantly induce the gene expression of antioxidant enzymes and aggravate the oxidative damage of protein and lipid. These results suggest that LvGrx 3 is involved in regulating the antioxidant system and plays a vital role in defense responses against environmental stress.
Personal Identity After an Autism Diagnosis: Relationships With Self-Esteem, Mental Wellbeing, and Diagnostic Timing

Adults are increasingly seeking autism diagnoses, although less is known about their experiences of diagnosis and personal identity (i.e., autism as part of “me”), and how this relates to self-esteem and wellbeing. One-hundred and fifty-one autistic adults completed an online survey including measures of self-esteem, psychological wellbeing, and autistic personal identity, which considered whether participants took pride in or were dissatisfied with being autistic. Fifty-four participants answered a qualitative question about the impact of receiving an autism diagnosis on their sense of self. Regression analyses found that greater time elapsed since diagnosis related to less dissatisfaction with autistic personal identity. We also found that more dissatisfaction with autistic personal identity predicted lower self-esteem, and more autism pride predicted higher self-esteem. Content analysis of participants’ experiences supported the quantitative findings and was suggestive of an emotive post-diagnostic adjustment process. Future research should aim to identify ways to promote the development of a positive autistic personal identity post-diagnosis in adulthood.