Functional Domains Research Articles

Architecture and activation of single-pass transmembrane receptor guanylyl cyclase.

The heart, in addition to its primary role in blood circulation, functions as an endocrine organ by producing cardiac hormone natriuretic peptides. These hormones regulate blood pressure through the single-pass transmembrane receptor guanylyl cyclase A (GC-A), also known as natriuretic peptide receptor 1. The binding of the peptide hormones to the extracellular domain of the receptor activates the intracellular guanylyl cyclase domain of the receptor to produce the second messenger cyclic guanosine monophosphate. Despite their importance, the detailed architecture and domain interactions within full-length GC-A remain elusive. Here we present cryo-electron microscopy structures, functional analyses and molecular dynamics simulations of full-length human GC-A, in both the absence and the presence of atrial natriuretic peptide. The data reveal the architecture of full-length GC-A, highlighting the spatial arrangement of its various functional domains. This insight is crucial for understanding how different parts of the receptor interact and coordinate during activation. The study elucidates the molecular basis of how extracellular signals are transduced across the membrane to activate the intracellular guanylyl cyclase domain.

Patterns of psychosocial functioning of treatment-seeking veterans following military sexual trauma: The differential association of functioning and identity.

Veterans with a history of military sexual trauma (MST) often experience poorer social, psychological, and physical outcomes compared with civilians and veterans who have experienced sexual assault outside of the military. Studies suggest some differences in endorsement of MST and its symptoms based on ethnoracial, age, sexuality, and gender-related factors. However, investigations into potential diversity-related patterns of functioning are sparse. This study examined the associations between identity factors and psychosocial functioning among veterans seeking mental health treatment following MST. During intake assessments, veterans (n = 144) completed semistructured clinical interviews and the World Health Organization Disability Assessment Schedule 2.0 as part of routine clinical care at a Midwestern Veterans Healthcare Administration hospital. Psychosocial functioning domains (cognition, mobility, self-care, getting along, life activities, and participation in society) were analyzed across veterans' race, age, sex, and sexual identity. Results revealed differences in participation in society based on sex and race and in mobility based on race and age. No significant differences were observed in functional domains for sexual identity. These findings highlight the importance of assessing salient identity factors and delivering culturally sensitive trauma-focused care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Advances in the structure and function of the nucleolar protein fibrillarin

Fibrillarin (FBL) is a highly conserved and well-researched nucleolar protein found in eukaryotes. Its presence was first identified in 1985 through protein immunoblotting analyses using antisera from patients with autoimmune scleroderma. Through immunoelectron microscopy, FBL was shown to be localized in the dense fibrillar component of the nucleolus, leading to the term “fibrillarin”. The FBL protein is composed of 321 amino acids and contains two significant functional domains: the GAR domain and the methyltransferase domain. It is expressed in the nucleolus of eukaryotes. This makes FBL one of the most studied nucleolar proteins. While methylation is not essential for cell survival, the FBL gene is crucial for eukaryotic cells, underscoring the importance of investigating additional functions that do not rely on FBL methylation. This review will primarily examine the protein structural domains of FBL and its classic methyltransferase activity. Additionally, our review will examine the importance of the eukaryote-specific GAR structural domain of FBL in regulating intracellular phase separation. Furthermore, this paper analyzes recent developments in the utilization of FBL in the study of pathogen infections and cancer research over the past decade.

Abstract 4136847: Administration of the Recombinant Activated Protein C Rescues the Cardiac Vulnerability to Ischemic Insults in Aging through Modulating Inflammatory Response during Ischemia and Reperfusion

Introduction: Activated protein C (APC) is an endogenous vitamin-K-dependent serine protease and exhibits therapeutic potential for ischemic heart disease. The APC derivatives with anticoagulant and/or cytoprotective properties were produced through chemical engineering to characterize the functional domain of APC for limiting ischemia/reperfusion (I/R) injury. Hypothesis: The thromboinflammatory regulation by APC ameliorates ischemic insults caused by I/R through the receptor EPCR/PAR1. Methods: Young (3 months)/aged (24 months) wild type C57BL/6J mice and PAR1 R46Q/R46Q (block cleavage by APC) knock in mutant (3 months, C57BL/6J) mice were subjected to ligation of left anterior descending coronary artery with 45 min of ischemia. 5 min prior to reperfusion, wild type APC, cytoprotective selective APC-2Cys, or anticoagulant selective APC-E170A (0.2 μg/kg i.v.) was administered followed by 24 hr of reperfusion. The left ventricles of hearts were used for immunoblotting and flow cytometry analysis. Results: APC and APC-2Cys but not APC-E170A reduced I/R-induced myocardial infarction. Echocardiography showed that APC and APC-2Cys but not APC-E170A can rescue systolic dysfunction by I/R in young/aged WT but not in PAR1 R46Q/R46Q mice. Biochemical analysis showed that administration of APC and APC-2Cys inhibited activation of inflammation signaling c-Jun N-terminal protein kinase (JNK) and NF-κB by I/R and reduced mRNA levels of the proinflammatory cytokines TNFα and IL-6 in young/aged WT but not in PAR1 R46Q/R46Q hearts. The plasma cytokine array demonstrated that APC and APC2-Cys reduced potency of pro-inflammatory cytokines and apoptotic signaling cytokines during I/R. Moreover, I/R-triggered inflammasome NLRP3 was reduced by APC and APC-2Cys in young/aged WT but not in PAR1 R46Q/R46Q hearts. The flow cytometry showed that APC and APC-2Cys increased lymphocyte and decreased myeloid cell abundance and increased the recruitment of inflammation-mediating CD8a + T-cells during I/R in young/aged WT but not PAR1 R46Q/R46Q hearts, indicating that the APC/EPCR/PAR1 axis mediates APC's immune regulation under I/R. Moreover, APC and APC-2Cys reduced I/R-triggered macrophage abundance in young/aged WT hearts, although the proportion of M1 and M2 macrophages was unchanged. Conclusions: The cytoprotective domain of APC is critical for its cardioprotection against ischemic insults. EPCR/PAR1 receptor complex mediates APC's immune regulation in aging during I/R conditions.

The Capicua C1 Domain is Required for Full Activity of the CIC::DUX4 Fusion Oncoprotein.

Rearrangements between genes can yield neomorphic fusions that drive oncogenesis. Fusion oncogenes are made up of fractional segments of the partner genes that comprise them, with each partner potentially contributing some of its own function to the nascent fusion oncoprotein. Clinically, fusion oncoproteins driving one diagnostic entity are typically clustered into a single molecular subset and are often treated a similar fashion. However, knowledge of where specific fusion breakpoints occur in partner genes, and the resulting retention of functional domains in the fusion, is an important determinant of fusion oncoprotein activity and may differ between patients. This study investigates this phenomena through the example of CIC::DUX4, a fusion between the transcriptional repressor capicua (CIC) and the double homeobox 4 gene (DUX4), which drives an aggressive subset of undifferentiated round cell sarcoma. Using a harmonized dataset of over 100 patient fusion breakpoints from the literature, we show that most bona fide CIC::DUX4 fusions retain the C1 domain, which is known to contribute to DNA binding by wild type CIC. Mechanistically, deletion or mutation of the C1 domain reduces, but does not eliminate, activation of CIC target genes by CIC::DUX4. We also find that expression of C1-deleted CIC::DUX4 is capable of exerting intermediate transformation-related phenotypes compared with those imparted by full-length CIC::DUX4, but was not sufficient for tumorigenesis in a subcutaneous mouse model. In summary, our results suggest a supercharging role for the C1 domain in the activity of CIC::DUX4.

TRIM28 regulates the coagulation cascade inhibited by p72 of African swine fever virus.

In 2018, African swine fever virus (ASFV) emerged in China, causing extremely serious economic losses to the domestic pig industry. Infection with ASFV can cause disseminated coagulation, leading to the consumption of platelets and coagulation factors and severe bleeding. However, the mechanism of virus-induced coagulation has yet to be established. In our study, ASFV downregulated the coagulation process, as detected by D-dimer (D2D) and Factor X (F10) expression in pigs challenged with ASFV HLJ/18. In vitro, ASFV infection increased Factor IX (F9) and Factor XII (F12) expression while downregulating F10 expression in porcine alveolar macrophages (PAMs). African swine fever virus induced both intrinsic and extrinsic coagulation cascades. In addition, several encoded proteins affect the expression of the crucial coagulation protein F10, and among the encoded proteins, p72 inhibits the activity and expression of F10. Proteomic analysis also revealed that p72 is involved in the coagulation cascade. p72 can interact with F10, and its inhibitory functional domains include amino acids 423-432 and amino acids 443-452. Finally, we found that F10 and p72 interact with tripartite motif-containing protein 28 (TRIM28). TRIM28 knockdown resulted in a decrease in F10 expression. Importantly, TRIM28 contributes to the reduction in F10 protein expression regulated by p72. Our findings revealed an inhibitory effect of the viral protein p72 on the ASFV infection-induced coagulation cascade and revealed a role of TRIM28 in reducing F10 expression, revealing a molecular mechanism of ASFV-associated coagulation.

Characteristic spatial and frequency distribution of mutations in SCN1A

BackgroundSCN1A is the most well-recognized and commonly mutated gene related to epilepsy. This study analyzed the characteristic spatial and frequency distributions of SCN1A mutations, aiming to provide important insight into the mutagenesis etiopathology of SCN1A-associated epilepsy.MethodsEpilepsy-associated SCN1A variants were retrieved from the SCN1A mutation database, the HGMD database, and literature reviews. The base substitutions, mutation frequencies in CpG dinucleotides, and spatial distributions of mutations in terms of exons and structural domains were analyzed.ResultsA total of 2621 SCN1A variants were identified in 5106 unrelated cases. The most common type was missense mutation, followed by frameshift mutations and splice site mutations. Among the missense mutations, transitions within CpG dinucleotides were much more recurrently identified than transitions within non-CpG dinucleotides, and the most common type was the G > A transition. Among the nonsense mutations, the most predominant type of single-base substitution was the C > T transition, among which 75.3% (235/312) were within CpG sites. The most common “hotspot” codons for missense mutations were codons 101, 946, and 1783; while for nonsense mutations it was codon 712. One-base deletion or insertion was the most common type of frameshift mutation, causing protein truncation. The three most common frameshift mutations were c.5536_5539delAAAC, c.4554dupA, and c.5010_5013delGTTT. Splice mutations were the most frequently identified in exon 4 with a hotspot site c.602 + 1G > A. The spatial distribution of missense mutations showed that exons 22 and 4 had the highest mutation density (111 and 84 mutations per 100 bp, respectively), and exon 12 had the lowest mutation density, with 4 mutations per 100 bp. Further distribution analysis of the protein domains revealed that missense mutations were more common in the pore region and voltage sensor (231 mutations per 100 amino acids, respectively), and the protein truncation mutations were distributed evenly among the domains.ConclusionsSCN1A mutations tend to cluster at distinct sites, depending on the characteristic CpG dinucleotides, exons, and functional domains. Higher mutation density in particular regions, such as exon 22 and exon 4, offers promising targets for therapeutic genetic interventions.

Effects of a Virtual Trauma Clinic on admissions and length of stay for minor to moderate trauma.

To investigate the feasibility of a Virtual Trauma Clinic (VTC) for patients with minor to moderate trauma, and evaluate patient satisfaction and outcomes. One hundred VTC patients were matched 1:1 with historical patients from the hospital trauma registry who received conventional care. Matching was based on age ± 5 years, sex, mechanism of injury, Injury Severity Score ± 2, trauma team activation and day of week of presentation. VTC patients were sent surveys on experience and outcome measures. VTC was associated with reduced average hospital length of stay for admitted patients by 1.81 days (95% CI = -2.82, -0.79; P = 0.001) and reduced hospital admissions (odds ratio 0.26; 95% CI = 0.14, 0.48; P < 0.001). There was an avoidance of 199 inpatient bed days in total, with no trauma-related readmissions within 30 days post-hospital discharge. 92% of respondents (n = 22) rated the care they received from VTC as excellent or good. Patient-reported outcome surveys showed overall improvement in functional domains but evidence of ongoing disability, with persistent issues of pain and psychological distress at 1 month post-injury. Patients with minor to moderate trauma have ongoing care needs with high rates of pain, psychological distress and disability remaining prevalent long after discharge. VTC provided an innovative strategy for hospital avoidance with high levels of patient satisfaction and no adverse effects on safety. The overall quality of care for these patients was enhanced through the provision of standardised, patient-centred and multidisciplinary follow-up.

Anomalies of ATP-dependent chromatin remodeling complexes and human neurodevelopmental genetic disorders

ATP-dependent chromatin remodeling complexes play crucial roles in various biological processes including enhancing local DNA accessibility, regulating gene transcription, and facilitating DNA replication and repair. Based on their functional structural domains, these complexes may be categorized into four families, including SWI/SNF, ISWI, CHD and INO80. Such families are vital factors for regulating gene expression and play pivotal roles in developmental processes. Variants of genes encoding the components of such complexes have been closely associated with human developmental disorders and neurodevelopmental genetic syndromes. This review has summarized the classification, fundamental functions and underlying mechanism of the ATP-dependent chromatin remodeling complexes, as well as common neurological genetic disorders due to variants of genes encoding the subunits of such complexes.

Evaluation of patient satisfaction and maximum biting force of three differently constructed bars on two implants retaining mandibular overdenture - one year follow-up (a randomized controlled clinical trial)

BackgroundDifferent bar construction techniques will affect the bar passive fitness, which may induce stresses or strain on the implant and/or tightening screw and sequentially may affect the biting force and patient satisfaction.Aim of the studyThis clinical investigation assessed patient satisfaction and maximum biting force (MBF) using three differently constructed (conventional casting, milling, and 3D printing CAD/CAM techniques) cobalt-chromium (Co-Cr) bar-retained implants mandibular overdentures over a one-year period of follow-up.Materials and methodsThirty edentulous patients seeking for two implants bar-retained mandibular overdentures were randomly assigned into three groups as the following: Group I: 10 patients received a Co-Cr conventional casting bar, Group II: 10 patients received a Co-Cr CAD/CAM milled bar, and Group III: 10 patients received a Co-Cr CAD/CAM 3D-printed bar. All the bar groups were connected to two implants in the canine area bilaterally. Within the first two weeks following implant placement, patients received the definitive prosthesis. Patient satisfaction was evaluated by using the (OHIP-EDENT-19) questionnaire form after 6, and 12 months. Additionally, the maximum biting force was tested at after delivery, 3, 6, and 12 months for each group. The results were collected, tabulated, and statistically analyzed. Trial registration: This study was recorded on ClinicalTrials.gov retrospectively registered (ID: NCT06401187) on 30/04/2024.ResultsAfter one year follow up, regrading patient satisfaction the three groups showed no statistically significant difference. Although, the functional limitation domain was in favor of the milled bar. Regarding the maximum biting force, no statistically significant difference was found among three groups. However, at 12 mouths follow-up the milled bar showed statistically value.ConclusionWithin the limitations of this study, the conventional, milled and 3D printed bar overdentures groups can be used as a satisfactory treatment modality for edentulous mandible in terms of patient satisfaction and maximum biting force.

Predictive Utility of Four Instrumental Activities of Daily Living Assessments and Cognitive Status Changes Among Cognitively In-Tact Older Adults.

To examine the factor structure and predictive utility of four instrumental activities of daily living (IADL) measures to identify cognitive status changes among older adults enrolled in the ACTIVE Trial. Extracted factors represented IADL instruments. Baseline performance on the Everyday Problems Test (EPT) predicted 5-year MMSE scores (est. = .08, p < .001), adjusting for demographic and health covariates, baseline MMSE, self-reported IADL function, and the performance-based Observed Tasks of Daily Living and Timed Instrumental Activities of Daily Living assessments. For each 1-point increase in baseline EPT financial performance, the odds of cognitive impairment decreased by 26%. IADL functional domains were not interchangeable across instruments. The EPT demonstrated better predictive utility compared to other instruments for detecting subsequent cognitive decline/impairment. This is a useful step in developing effective tools to detect early functional deficits indicating subsequent clinical impairment. Advanced Cognitive Training for Independent and Vital Elderly Trial (ACTIVE), NCT00298558, https://clinicaltrials.gov/study/NCT00298558.

Sensor-Derived Measures of Motor and Cognitive Functions in People With Multiple Sclerosis Using Unsupervised Smartphone-Based Assessments: Proof-of-Concept Study.

Smartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem. This analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS). The proposed framework was applied to data from a cross-sectional study involving 85 people with MS and 68 healthy participants who underwent in-clinic supervised and remote unsupervised smartphone-based assessments. The assessment provided high-quality recordings from cognitive, manual dexterity, and mobility tests, from which 47 SDMs, based on established literature, were extracted using previously developed and publicly available algorithms. These SDMs were first separately and then jointly screened for bias and normality by 2 expert assessors. Selected SDMs were then analyzed to establish their reliability, using an intraclass correlation coefficient and minimal detectable change at 95% CI. The convergence of selected SDMs with in-clinic MS functional measures and patient-reported outcomes was also evaluated. A total of 16 (34%) of the 47 SDMs passed the selection framework. All selected SDMs demonstrated moderate-to-good reliability in remote settings (intraclass correlation coefficient 0.5-0.85; minimal detectable change at 95% CI 19%-35%). Selected SDMs extracted from the smartphone-based cognitive test demonstrated good-to-excellent correlation (Spearman correlation coefficient, |ρ|>0.75) with the in-clinic Symbol Digit Modalities Test and fair correlation with Expanded Disability Status Scale (EDSS) scores (0.25≤|ρ|<0.5). SDMs extracted from the manual dexterity tests showed either fair correlation (0.25≤|ρ|<0.5) or were not correlated (|ρ|<0.25) with the in-clinic 9-hole peg test and EDSS scores. Most selected SDMs from mobility tests showed fair correlation with the in-clinic timed 25-foot walk test and fair to moderate-to-good correlation (0.5<|ρ|≤0.75) with EDSS scores. SDM correlations with relevant patient-reported outcomes varied by functional domain, ranging from not correlated (cognitive test SDMs) to good-to-excellent correlation (|ρ|>0.75) for mobility test SDMs. Overall, correlations were similar when smartphone-based tests were performed in a clinic or remotely. Reported results highlight that smartphone-based assessments are suitable tools to remotely obtain high-quality SDMs of cognitive and motor function in people with MS. The presented SDM selection framework promises to increase the interpretability and standardization of smartphone-based SDMs in people with MS, paving the way for their future use in interventional trials.

Patient-reported outcomes after treatment for rectal cancer-A prospective nationwide study.

While modern treatment has improved rectal cancer (RC) survival, it can cause late side effects that impact health-related quality of life (HRQoL). The aim of this study was to evaluate HRQoL and late effects 1 year after diagnosis in patients who underwent major resection for Stage I-III RC. All patients with RC registered in the Cancer Registry of Norway between 1 January 2019 and 31 December 2020, aged ≥ 18 years, and a control group without colorectal cancer were invited to participate in the study by answering a questionnaire on HRQoL and late effects. Functional domains and symptoms were compared in different patient groups and between patients and controls. There were 558 patients and 1693 controls eligible for analysis. Response rates were 41% for patients and 23% for controls. Some differences in HRQoL were observed between treatment modalities. Major low anterior resection syndrome (LARS) was prevalent in 60.8% of patients, and was associated with lower functional and higher symptom scores compared with patients with no/minor LARS. Patients with major chronic pain [n = 86 (15.4%)] had significantly lower scores for most of the functional items and higher symptom scores than patients with no/minor chronic pain. Patients had some lower functional scores and several higher symptoms score compared with controls. Patients who suffered from major LARS or major chronic pain had significantly impaired functions and more symptoms beyond change in bowel function and pain, respectively. Identification and treatment of these patient may hopefully be beneficial for their HRQoL.

Waveflow: Boundary-conditioned normalizing flows applied to fermionic wave functions

An efficient and expressive wave function Ansatz is key to scalable solutions for complex many-body electronic structures. While Slater determinants are predominantly used for constructing antisymmetric electronic wave function Ansätze, this construction can result in limited expressiveness when the targeted wave function is highly complex. In this work, we introduce Waveflow, an innovative framework for learning many-body fermionic wave functions using boundary-conditioned normalizing flows. Instead of relying on Slater determinants, Waveflow imposes antisymmetry by defining the fundamental domain of the wave function and applying necessary boundary conditions. A key challenge in using normalizing flows for this purpose is addressing the topological mismatch between the prior and target distributions. We propose using O-spline priors and I-spline bijections to handle this mismatch, which allows for flexibility in the node number of the distribution while automatically maintaining its square-normalization property. We apply Waveflow to a one-dimensional many-electron system, where we variationally minimize the system’s energy using variational quantum Monte Carlo (VQMC). Our experiments demonstrate that Waveflow can effectively resolve topological mismatches and faithfully learn the ground-state wave function.

Multimedia-Based Education Led to Improvement in Disease Knowledge Among Patients with Cirrhosis.

Current evidence shows limited patient understanding of liver disease, coupled with no standard guidelines or methods to offer patient education in a busy clinical environment. We developed multimedia-based education (MBE) for those with cirrhosis & tested its effectiveness in improving patient knowledge from baseline to 1 month. This prospective study enrolled cirrhotic patients who had a scheduled visit with a hepatologist at an ambulatory academic practice or were admitted to the liver inpatient service. Once consented, patients completed a baseline knowledge questionnaire, and were given a link to watch the videos (text or email). Four videos were developed by the study team with input from clinicians and patients (liver function, symptoms and complications, medical management and preventive actions & nutrition). At month 1, the study coordinator confirmed with the patient that they had watched the videos at least once, and patients completed the same knowledge questionnaire. The scores between pre- and post-intervention were compared using the Wilcoxon signed rank test. Of the 120 enrolled, 113 completed baseline and 75 completed follow-up. 48% had alcohol-related liver disease as the underlying cause of cirrhosis. Mean MELD score at enrollment was 14.7 ± 8.14. There was a statistically significant improvement in knowledge scores across all domains from baseline to month 1 (p < 0.05). The overall knowledge score improved from 65 to 83% (p < 0.001), with highest improvement by 40% in the domain of liver function and causes of cirrhosis. MBE can help improve patients' knowledge about liver function, management, and prevention and can be used in both ambulatory and inpatient hepatology practice.

Bioengineering approach for the design of magnetic bacterial cellulose membranes

Biopolymer research has led to the development of novel products through innovative strategies. Their functionalization is typically achieved by physical/chemical methods that require harsh chemicals or mechanical treatments. These functionalities could be alternatively achieved by employing bioengineering design methods. We demonstrate, a bioengineered dual-microbial approach to create functional bacterial cellulose from microbial workhorses. Komagataeibacter hansenii ATCC 53582 is used to produce bacterial cellulose and engineered E. coli is used to functionalize the matrix with a recombinant fibrous protein. The E. coli harbours synthetic genes for the secretion of amyloid curli protein subunit (CsgA) tagged with short functional M6A peptide domains. The incorporation of M6A-functionalized amyloid proteins into bacterial cellulose facilitates magnetite nanoparticle nucleation. We achieved a saturation magnetization of 40 emu g−1, a three-fold increase compared to existing strategies. The magnetic bacterial cellulose films demonstrate cytocompatibility and accelerate cell migration in the presence of magnetic field.

Gene Targeting via CRISPR/Cas9-Mediated DNA Double-Strand Break Induction in Rice.

Gene targeting (GT) is a precise genome editing tool to achieve desired modification of a target gene, e.g., introduction of point mutations, knock-in of a reporter gene, or swapping of a functional domain, through homologous recombination. However, due to its low frequency, it has proved difficult to establish a universal GT system. The availability of the CRISPR/Cas9 system for genome editing in plants has opened up possibilities to apply GT successfully to some plant species. Here, we provide protocols for CRISPR/Cas9-mediated DNA double-strand break (DSB)-induced GT in rice.

Behavioural profiling following acute stress uncovers associations with future stress sensitivity and past childhood abuse.

Background: Individuals greatly differ in their responses to acute stress, ranging from resilience to vulnerability that may yield stress-related psychopathology. Stress-related psychopathologies involve, by definition, substantial modifications across multiple behavioural domains, including impaired cognitive, affective and social functioning. Nevertheless, and despite extensive investigation of individual variability in stress responsivity, no study to date simultaneously assessed the impact of acute stress across multiple behavioural domains within a given individual.Objective: To address this critical gap, 84 healthy female participants (mean age 24.45 ± 3.02, range 19-35) underwent an established acute stress induction procedure and completed three behavioural tasks, probing the functional domains of positive, cognitive and social processing, both before and after the acute stress procedure.Method: A novel behavioural profiling algorithm was implemented to identify individuals whose performance was substantially impacted by stress across all three functional domains.Results: Approximately 30% of participants exhibited substantial deviation in their performance from before to after stress in all three tasks, hereon defined as stress-affected. Stress-affected participants did not differ in their psychological and physiological responses to the acute stress procedure from the other stress-unaffected 70% of the sample. However, follow-up assessments in 66 of these participants revealed higher levels of stress six months following the procedure among the stress-affected compared to the stress-unaffected group. Stress-affected individuals also reported more aversive childhood experiences, such that the odds of participants who were sexually abused at an early age to be affected behaviourally by acute stress later in life increased by more than five-fold.Conclusions: Taken together, these findings suggest that being affected by acute stress across multiple functional domains is associated with future stress sensitivity and past childhood sexual abuse. Probing individual differences in the impact of acute stress across domains of functionality may better align with the multi-dimensional nature of stress responsivity, uncovering latent vulnerability.

Evolution of light-dependent functions of GIGANTEA.

GIGANTEA is a multifaceted plant-specific protein that originated in a streptophyte ancestor. The current known functions of GI include circadian clock control, light signalling, flowering time regulation, stomata response, chloroplast biogenesis, accumulation of anthocyanin, chlorophyll, and starch, phytohormone signalling, senescence and response to drought, salt, and oxidative stress. Six decades since its discovery, no functional domains have been defined, and its mechanism of action is still not well-characterised. In this review, we explore the functional evolution of GI to distinguish between ancestral and more recently acquired roles. GI integrated itself into various existing signalling pathways of the circadian clock, blue light, photoperiod, and osmotic and oxidative stress response. It also evolved parallelly to acquire new functions for chloroplast accumulation, red light signalling and anthocyanin production. In this review, we have encapsulated the known mechanisms of various biological functions of GI. Additionally, this manuscript will throw light on the evolution of GI in plant lineage.

Bagworm Silk‐Mimetic Protein Fibers with Extraordinary Stiffness via In Vivo Polymerization and Hierarchical Self‐Assembly

AbstractBagworm silk proteins, which contain crystalline structures with large β‐nanocrystal sizes, are ideal candidates for biosynthetic high‐performance fibers. However, the extremely high glycine content and greater molecular weight limit their heterologous expression efficiency and further application exploration. Here, a multi‐module assembly strategy is developed to engineer novel chimeric structural proteins by incorporating the mechanical functional domains of bagworm silk proteins with the C‐terminal self‐assembly domains of spider silk proteins. By selecting a single repetitive unit of the functional region of bagworm silk proteins, the challenge of low heterologous expression efficiency is successfully addressed. Furthermore, the content and ordering of β‐sheet structure are enhanced in the chimeric proteins through the alignment mediated by the spider silk C‐terminal domain and ligation facilitated by split inteins, resulting in a remarkable Young's modulus of ≈15 GPa. This surpasses many artificial protein fibers, synthetic polymer fibers, and even natural spider silk. Notably, these protein fibers are drawn into surgical sutures and demonstrate superior wound healing effects compared to clinical suture in a skin wound model. This research presents a novel strategy for developing high‐performance protein fibers, which will expand the scope of their mechanically demanding applications.