PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

Epigenetic regulation of plastin 3 expression by the macrosatellite DXZ4 and the transcriptional regulator CHD4.

Dysregulated Plastin 3 (PLS3) levels associate with a wide range of skeletal and neuromuscular disorders and the most common types of solid and hematopoietic cancer. Most importantly, PLS3 overexpression protects against spinal muscular atrophy. Despite its crucial role in F-actin dynamics in healthy cells and its involvement in many diseases, the mechanisms that regulate PLS3 expression are unknown. Interestingly, PLS3 is an X-linked gene and all asymptomatic SMN1-deleted individuals in SMA-discordant families who exhibit PLS3 upregulation are female, suggesting that PLS3 may escape X chromosome inactivation. To elucidate mechanisms contributing to PLS3 regulation, we performed a multi-omics analysis in two SMA-discordant families using lymphoblastoid cell lines and iPSC-derived spinal motor neurons originated from fibroblasts. We show that PLS3 tissue-specifically escapes X-inactivation. PLS3 is located ∼500 kb proximal to the DXZ4 macrosatellite, which is essential for X chromosome inactivation. By applying molecular combing in a total of 25 lymphoblastoid cell lines (asymptomatic individuals, individuals with SMA, control subjects) with variable PLS3 expression, we found a significant correlation between the copy number of DXZ4 monomers and PLS3 levels. Additionally, we identified chromodomain helicase DNA binding protein 4 (CHD4) as an epigenetic transcriptional regulator of PLS3 and validated co-regulation of the two genes by siRNA-mediated knock-down and overexpression of CHD4. We show that CHD4 binds the PLS3 promoter by performing chromatin immunoprecipitation and that CHD4/NuRD activates the transcription of PLS3 by dual-luciferase promoter assays. Thus, we provide evidence for a multilevel epigenetic regulation of PLS3 that may help to understand the protective or disease-associated PLS3 dysregulation.

MEnTaT: A machine-learning approach for the identification of mutations to increase protein stability.

Enhancing protein thermal stability is important for biomedical and industrial applications as well as in the research laboratory. Here, we describe a simple machine-learning method which identifies amino acid substitutions that contribute to thermal stability based on comparison of the amino acid sequences of homologous proteins derived from bacteria that grow at different temperatures. A key feature of the method is that it compares the sequences based not simply on the amino acid identity, but rather on the structural and physicochemical properties of the side chain. The method accurately identified stabilizing substitutions in three well-studied systems and was validated prospectively by experimentally testing predicted stabilizing substitutions in a polyamine oxidase. In each case, the method outperformed the widely used bioinformatic consensus approach. The method can also provide insight into fundamental aspects of protein structure, for example, by identifying how many sequence positions in a given protein are relevant to temperature adaptation.

Integrated conjugal plasmid pLS20 in the Bacillus subtilis genome produced 850-kbp circular subgenomes transmissible to another B. subtilis.

Bacillus subtilis was engineered to produce circular subgenomes that are directly transmittable to another B. subtilis. The conjugational plasmid pLS20 integrated into the B. subtilis genome supported not only subgenome replication but also transmission to another B. subtilis species. The subgenome system developed in this study completes a streamlined platform from the synthesis to the transmission of giant DNA by B. subtilis.

Menopause Status and Within-Group Differences in Chronological Age Affect the Functional Neural Correlates of Spatial Context Memory in Middle-Aged Females.

Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife-a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged premenopausal and postmenopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal females (age range, 39.55-53.30 years; mean age, 44.28 years; SD age, 3.12 years) and 41 postmenopausal females (age range, 46.70-65.14 years; mean age, 57.56 years; SD age, 3.93 years). We found that postmenopausal status, and advanced age within postmenopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal cortices during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife.SIGNIFICANCE STATEMENT This is the first fMRI study to examine how premenopause and postmenopause status affect the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age-related and performance-related correlations with brain activity in inferior parietal, parahippocampal, and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at premenopause compared with postmenopause.

DYW cytidine deaminase domains have a long-range impact on RNA recognition by the PPR array of chimeric plant C-to-U RNA editing factors and strongly affect target selection.

The protein factors for the specific C-to-U RNA editing events in plant mitochondria and chloroplasts possess unique arrays of RNA-binding pentatricopeptide repeats (PPRs) linked to carboxy-terminal cytidine deaminase DYW domains via the extension motifs E1 and E2. The E1 and E2 motifs have distant similarities to tetratricopeptide repeats known to mediate protein-protein interactions but their precise function is unclear. Here, we investigate the tolerance of PPR56 and PPR65, two functionally characterized RNA editing factors of the moss Physcomitrium patens, for the creation of chimeras by variably replacing their C-terminal protein regions. Making use of a heterologous RNA editing assay system in Escherichia coli we find that heterologous DYW domains can strongly restrict or widen the spectrum of off-targets in the bacterial transcriptome for PPR56. Surprisingly, our data suggest that these changes are not only caused by the preference of a given heterologous DYW domain for the immediate sequence environment of the cytidine to be edited but also by a long-range impact on the nucleotide selectivity of the upstream PPRs.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation. METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS. RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10-39; OR = 4.73, p = 2 × 10-10; OR = 2.3, p = 7.49 × 10-9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10-7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10-16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10-6). CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.

Metabolic profiling and biomarkers identification in cluster bean under drought stress using GC-MS technique.

INTRODUCTION: The Cluster bean is an economically significant annual legume, widely known as guar. Plant productivity is frequently constrained by drought conditions. OBJECTIVE: In this work, we have identified the untargeted drought stress-responsive metabolites in mature leaves of cluster beans under drought and control condition. METHODS: To analyse the untargeted metabolites, gas chromatography-mass spectrometry (GC-MS) technique was used. Supervised partial least-squares discriminate analysis and heat map were used to identify the most significant metabolites for drought tolerance. RESULTS: The mature leaves of drought-treated C. tetragonoloba cv. 'HG-365' which is a drought-tolerant cultivar, showed various types of amino acids, fatty acids, sugar alcohols and sugars as the major classes of metabolites recognized by GC-MS metabolome analysis. Metabolite profiling of guar leaves showed 23 altered metabolites. Eight metabolites (proline, valine, D-pinitol, palmitic acid, dodecanoic acid, threonine, glucose, and glycerol monostearate) with VIP score greater than one were considered as biomarkers and three metabolite biomarkers (D-pinitol, valine, and glycerol monostearate) were found for the first time in guar under drought stress. In this work, four amino acids (alanine, valine, serine and aspartic acid) were also studied, which played a significant role in drought-tolerant pathway in guar. CONCLUSION: This study provides information on the first-ever GC-MS metabolic profiling of guar. This work gives in-depth details on guar's untargeted drought-responsive metabolites and biomarkers, which can plausibly be used for further identification of biochemical pathways, enzymes, and the location of various genes under drought stress.

Early-Onset Osteoporosis: Molecular Analysis in Large Cohort and Focus on the PLS3 Gene.

Osteoporosis is a skeletal disorder characterized by abnormal bone microarchitecture and low bone mineral density (BMD), responsible for an increased risk of fractures and skeletal fragility. It is a common pathology of the aging population. However, when osteoporosis occurs in children or young adults, it strongly suggests an underlying genetic etiology. Over the past two decades, several genes have been identified as responsible for this particular kind of considered monogenic early-onset osteoporosis (EOOP) or juvenile osteoporosis, the main ones being COL1A1, COL1A2, LRP5, LRP6, WNT1, and more recently PLS3. In this study, the objective was to characterize a large cohort of patients diagnosed with primary osteoporosis and to establish its diagnosis yield. The study included 577 patients diagnosed with primary osteoporosis and its diagnosis yield was established. To this end, next-generation sequencing (NGS) of a panel of 21 genes known to play a role in bone fragility was carried out. A genetic etiology was explained in about 18% of cases, while the others remain unexplained. The most frequently identified gene associated with EOOP is LRP5, which was responsible for 8.2% of the positive results (47 patients). As unexpected, 17 patients (2.9%) had a variant in PLS3 which encodes plastin 3. Alterations of PLS3 are associated with dominant X-linked osteoporosis, an extremely rare disease. Given the rarity of this disease, we focused on it. It was observed that males were more affected than females, but it is noteworthy that three females with a particularly severe phenotype were identified. Of these three, two had a variant in an additional gene involved in EOP, illustrating the probable existence of digenism. We significantly increase the number of variants potentially associated with EOOP, especially in PLS3. The results of our study demonstrate that molecular analysis in EOOP is beneficial and useful.

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13 years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10 months to 2 years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

Predictive modeling for cell culture in commercial manufacturing of biotherapeutics.

The biopharmaceutical industry continually seeks advancements in the commercial manufacturing of therapeutic proteins, where mammalian cell culture plays a pivotal role. The current work presents a novel data-driven predictive modeling application designed to enhance the efficiency and predictability of cell culture processes in biotherapeutic production. The capability of the cloud-based digital data science application, developed using open-source tools, is demonstrated with respect to predicting bioreactor potency from at-line process parameters over a 5-day horizon. The uncertainty in model's prediction is quantified, providing valuable insights for process control and decision-making. Model validation on unseen data confirms the model's robust generalizability. An interactive dashboard, tailored to process scientist's requirements is also developed to streamline biopharmaceutical manufacturing processes, ultimately leading to enhanced productivity and product quality.

Enhancing real-time cell culture monitoring: Automated Raman model optimization with Taguchi method.

Raman spectroscopy has found widespread usage in monitoring cell culture processes both in research and practical applications. However, commonly, preprocessing methods, spectral regions, and modeling parameters have been chosen based on experience or trial-and-error strategies. These choices can significantly impact the performance of the models. There is an urgent need for a simple, effective, and automated approach to determine a suitable procedure for constructing accurate models. This paper introduces the adoption of a design of experiment (DoE) method to optimize partial least squares models for measuring the concentration of different components in cell culture bioreactors. The experimental implementation utilized the orthogonal test table L25(56). Within this framework, five factors were identified as control variables for the DoE method: the window width of Savitzky-Golay smoothing, the baseline correction method, the order of preprocessing steps, spectral regions, and the number of latent variables. The evaluation method for the model was considered as a factor subject to noise. The optimal combination of levels was determined through the signal-to-noise ratio response table employing Taguchi analysis. The effectiveness of this approach was validated through two cases, involving different cultivation scales, different Raman spectrometers, and different analytical components. The results consistently demonstrated that the proposed approach closely approximated the global optimum, regardless of data set size, predictive components, or the brand of Raman spectrometer. The performance of models recommended by the DoE strategy consistently surpassed those built using raw data, underscoring the reliability of models generated through this approach. When compared to exhaustive all-combination experiments, the DoE approach significantly reduces calculation times, making it highly practical for the implementation of Raman spectroscopy in bioprocess monitoring.

Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis.

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified. Here, we indicated that suppression of Golgi protein acyl-coenzyme A binding domain A containing 3 (ACBD3) increased the sensitivity of Henrieta Lacks and PANC1 cells to ferroptosis. ACBD3 knockdown increases labile iron levels by promoting ferritinophagy. This increase in free iron, coupled with reduced levels of glutathione peroxidase 4 due to ACBD3 knockdown, leads to the accumulation of reactive oxygen species and lipid peroxides. Moreover, ACBD3 knockdown also results in elevated levels of polyunsaturated fatty acid-containing glycerophospholipids through mechanisms that remain to be elucidated. Furthermore, inhibition of ferrtinophagy in ACBD3 downregulated cells by knocking down the nuclear receptor co-activator 4 or Bafilomycin A1 treatment impeded ferroptosis. Collectively, our findings highlight the pivotal role of ACBD3 in governing cellular resistance to ferroptosis and suggest that pharmacological manipulation of ACBD3 levels is a promising strategy for cancer therapy.

Estimation of age and sex from fingernail clippings by using ATR-FTIR spectroscopy coupled with chemometric interpretation.

Fingernails can act as important forensic evidence as they can be a source of DNA that may link the victim or accused to the crime scene and may also contain traces of drugs such as cocaine and heroin, in regular users. Moreover, previous studies have shown that analyzing fingernails with various techniques can reveal important information, such as age and sex. In this work, ATR-FTIR spectroscopy with chemometric tools has been used to estimate the age and sex from fingernails by analyzing 140 fingernail samples (70 males, and 70 females) collected from volunteers aged between 10 and 70 years old. The amide bands obtained from spectra confirmed the presence of keratin proteins in the samples. PCA and PLS-R were used for the classification of samples. For sex estimation, samples were divided into four categories based on age groups, followed by the differentiation of sex in each group. Similarly, for age estimation, all samples were divided into two sets based on male and female followed by differentiation of age groups in each set. The result showed that PLS-R was able to differentiate fingernail samples based on sex in groups G1, G2, G3, and G4 with R-square values of 0.972, 0.993, 0.991, and 0.996, respectively, and based on age in females, and males with R-square values of 0.93 and 0.97, respectively. External validation and blind tests were also performed which showed results with 100% accuracy. This approach has proved to be effective for the estimation of sex and age from fingernail samples.

A comparison of principal component analysis, reduced-rank regression, and partial least-squares in the identification of dietary patterns associated with cardiometabolic risk factors in Iranian overweight and obese women.

BACKGROUND: According to epidemiological studies, unhealthy dietary patterns and lifestyle lead to rising obesity and cardiometabolic diseases in Iran. Hybrid techniques were used to identify a dietary pattern characterized by fiber, folic acid, and carotenoid intake due to their association with cardiometabolic risk factors such as anthropometric measurements, blood pressure, lipid profile, C-Reactive Protein (CRP), Plasminogen Activator Inhibitor (PAI), Homeostatic Model Assessment Index (HOMA Index), cardiometabolic index (CMI), and monocyte chemoattractant protein (MCP-1). So, the objective of the recent study is to compare the reduced-rank regression (RRR) and partial least-squares (PLS) approaches to principal component analysis (PCA) for estimating diet-cardiometabolic risk factor correlations in Iranian obese women. METHODS: Data on dietary intake was gathered from 376 healthy overweight and obese females aged 18 to 65 years using a 147-item food frequency questionnaire (FFQ). In this cross-sectional study, participants were referred to health centers of Tehran. Dietary patterns were developed using PCA, PLS, and RRR, and their outputs were assessed to identify reasonable patterns connected to cardiometabolic risk factors. The response variables for PLS and RRR were fiber, folic acid, and carotenoid intake. RESULTS: In this study, 3 dietary patterns were identified by the PCA method, 2 dietary patterns by the PLS method, and one dietary pattern by the RRR method. High adherence to the plant-based dietary pattern identified by all methods were associated with higher fat free mass index (FFMI) (P < 0.05). Women in the highest tertile of the plant-based dietary pattern identified by PLS had 0.06 mmol/L (95% CI: 0.007,0.66, P = 0.02), 0.36 mmHg (95% CI: 0.14,0.88, P = 0.02), and 0.46 mg/l (95% CI: 0.25,0.82, P < 0.001), lower FBS, DBP, and CRP respectively than women in the first tertile. Also, PLS and RRR-derived patterns explained greater variance in the outcome (PCA: 1.05%; PLS: 11.62%; RRR: 25.28%), while the PCA dietary patterns explained greater variance in the food groups (PCA: 22.81%; PLS: 14.54%; RRR: 1.59%). CONCLUSION: PLS was found to be more appropriate in determining dietary patterns associated with cardiometabolic-related risk factors. Nevertheless, the advantage of PLS over PCA and RRR must be confirmed in future longitudinal studies with extended follow-up in different settings, population groups, and response variables.

Sustaining the mobile medical units to bring equity in healthcare: a PLS-SEM approach.

BACKGROUND: Equitable access to healthcare for rural, tribal, and underprivileged people has been an emerging area of interest for researchers, academicians, and policymakers worldwide. Improving equitable access to healthcare requires innovative interventions. This calls for clarifying which operational model of a service innovation needs to be strengthened to achieve transformative change and bring sustainability to public health interventions. The current study aimed to identify the components of an operational model of mobile medical units (MMUs) as an innovative intervention to provide equitable access to healthcare. METHODS: The study empirically examined the impact of scalability, affordability, replicability (SAR), and immunization performance on the sustainability of MMUs to develop a framework for primary healthcare in the future. Data were collected via a survey answered by 207 healthcare professionals from six states in India. Partial least squares structural equation modeling (PLS-SEM) was conducted to empirically determine the interrelationships among various constructs. RESULTS: The standardized path coefficients revealed that three factors (SAR) significantly influenced immunization performance as independent variables. Comparing the three hypothesized relationships demonstrates that replicability has the most substantial impact, followed by scalability and affordability. Immunization performance was found to have a significant direct effect on sustainability. For evaluating sustainability, MMUs constitute an essential component and an enabler of a sustainable healthcare system and universal health coverage. CONCLUSION: This study equips policymakers and public health professionals with the critical components of the MMU operational model leading toward sustainability. The research framework provides reliable grounds for examining the impact of scalability, affordability, and replicability on immunization coverage as the primary public healthcare outcome.

Calibration transfer between NIR instruments using optimally predictive calibration subsets.

In this study, a new approach for the selection of informative standardization samples from the original calibration set for the transfer of a calibration model between NIR instruments is proposed and evaluated. First, a calibration model is developed, after variable selection by the Final Complexity Adapted Models (FCAM) method, using the significance of the PLS regression coefficients (FCAM-SIG) as selection criterion. Then, the resulting model is used for the selection of the best fitting subset of calibration samples with optimally predictive ability, called the optimally predictive calibration subset (OPCS). Next, the standardization samples are selected from the OPCS. The spectra on the slave instruments are transferred to corresponding spectra on the master instrument by the widely used Piecewise Direct Standardization (PDS) method. Thereafter, for the test set on the slave instrument, a 3D response surface plot is drawn for the root mean squared error of prediction (RMSEP) as a function of the number of OPCS samples and window sizes used for the PDS method. Finally, the smallest set of calibration samples, in combination with the optimal window size, providing the optimal RMSEP, is selected as standardization set. The proposed OPCS approach for the selection of standardization samples is tested on two real-life NIR data sets providing 13 X-y combinations to model. The results show that the obtained numbers of OPCS-based standardization samples are statistically significantly lower than those obtained with the widely used representative sample selection method of Kennard and Stone, while the predictive performances are similar.

Cortico-muscular coherence in primary lateral sclerosis reveals abnormal cortical engagement during motor function beyond primary motor areas.

Primary lateral sclerosis (PLS) is a slowly progressing disorder, which is characterized primarily by the degeneration of upper motor neurons (UMNs) in the primary motor area (M1). It is not yet clear how the function of sensorimotor networks beyond M1 are affected by PLS. The aim of this study was to use cortico-muscular coherence (CMC) to characterize the oscillatory drives between cortical regions and muscles during a motor task in PLS and to examine the relationship between CMC and the level of clinical impairment. We recorded EEG and EMG from hand muscles in 16 participants with PLS and 18 controls during a pincer-grip task. In PLS, higher CMC was observed over contralateral-M1 (α- and γ-band) and ipsilateral-M1 (ß-band) compared with controls. Significant correlations between clinically assessed UMN scores and CMC measures showed that higher clinical impairment was associated with lower CMC over contralateral-M1/frontal areas, higher CMC over parietal area, and both higher and lower CMC (in different bands) over ipsilateral-M1. The results suggest an atypical engagement of both contralateral and ipsilateral M1 during motor activity in PLS, indicating the presence of pathogenic and/or adaptive/compensatory alterations in neural activity. The findings demonstrate the potential of CMC for identifying dysfunction within the sensorimotor networks in PLS.

Does the morphology of residential greenspaces contribute to the development of a cardiovascular-healthy city?

BACKGROUNDS: Greenspaces are indispensable for the construction of a healthy city. Research has shown that greenspaces contribute to the reduction of cardiovascular risks. However, the role of greenspace morphology in the development of a healthy city is not well understood. METHODS: Our study utilized data from a cardiovascular disease screening cohort comprising 106,238 residents in Anhui Province, China, aged between 35 and 75 years. We calculated landscape indices of each participant using high-resolution land cover data to measure the greenness, fragmentation, connectivity, aggregation, and shape of greenspaces. We used a multivariate linear regression model to assess the associations between these landscape indices and triglyceride risk, and employed a structural equation model to explore the potential contributions of heatwaves and fine particulate matter (PM2.5) to this association. RESULTS: Overall, triglyceride was expected to increase by 0.046% (95% CI: 0.040%, 0.052%) with a 1% increase in the percentage of built-up area. Conversely, an increase in the percentage of greenspace was associated with a 0.270% (95% CI: 0.337%, -0.202%) decrease in triglyceride levels. Furthermore, when the total greenspace was held constant, the shape, connectedness, and aggregation of greenspace were inversely correlated with triglyceride levels, with effects of -0.605% (95% CI: 1.012%, -0.198%), -0.031% (95% CI: 0.039%, -0.022%), and -0.049% (95% CI: 0.058%, -0.039%), respectively. Likewise, the protective effect of the area-weighed mean shape index was higher than that of the total amount of greenspace. The stratification results showed that urban residents benefited more from greenspace exposure. Greenspace morphology can minimize triglyceride risk by reducing pollutant and heatwaves, with aggregation having the greatest effect on reducing pollutants whereas fragmentation is more efficient at reducing heatwaves. CONCLUSION: Exposure to the greenspaces morphology is associated with a reduction in triglyceride risk. The study has important practical and policy implications for early health monitoring and the spatial layout of greenspace and will provide scientific information for healthy urban planning by reducing unfavorable health consequences.

Eutrophication-induced shifts cause diverse responses in the phoD community of a plateau freshwater lake.

Eutrophication is a critical environmental challenge affecting lakes globally. Mitigating trophic level under endogenous phosphorus release is an unsolved problem in eutrophic lakes. However, understanding the dynamics and assembly of microbial communities encoding the alkaline phosphatase (phoD community) and their responses during trophic transitions in eutrophic lakes is limited. In this study, we compared the composition and assembly mechanisms of phoD communities in four seasons in the Yilong Lake, a shallow lake of the Yunnan-Guizhou Plateau. The lake exhibits slightly eutrophic conditions in summer and mesotrophic conditions in spring, autumn, and winter. By analyzing seasonal variations, we observed that during summer, the relative abundance of Pseudomonas in the water had the highest value, while the Shannon-Wiener index of phoD communities was lowest. Mantel tests showed an increased Bray-Curtis dissimilarity of phoD communities in the water with rising eutrophication, a trend not observed in sediment. Notably, eutrophication heightened the homogeneity selection governing the assembly of phoD communities in water. The co-occurrence networks showed that the OTUs in the summer exhibited closer interconnections than those in other seasons. Additionally, the topological parameters from networks indicated that eutrophication is poised to instigate changes and modulate the dynamics of the microbial phoD community, resulting in markedly distinct seasonal behaviors. pH was identified as a critical factor directly influencing phoD community diversity via partial least squares path modeling (PLS-PM). This study shed light on our understanding of the seasonal dynamics of phoD communities and their pivotal role in phosphorus cycling in eutrophic lakes.