Functional Role Research Articles

A cellulosomal double-dockerin module from Clostridium thermocellum shows distinct structural and cohesin-binding features.

Cellulosomes are intricate cellulose-degrading multi-enzymatic complexes produced by anaerobic bacteria, which are valuable for bioenergy development and biotechnology. Cellulosome assembly relies on the selective interaction between cohesin modules in structural scaffolding proteins (scaffoldins) and dockerin modules in enzymes. Although the number of tandem cohesins in the scaffoldins is believed to determine the complexity of the cellulosomes, tandem dockerins also exist, albeit very rare, in some cellulosomal components whose assembly and functional roles are currently unclear. In this study, we characterized the structure and mode of assembly of a tandem bimodular double-dockerin, which is connected to a putative S8 protease in the cellulosome-producing bacterium, Clostridium thermocellum. Crystal and NMR structures of the double-dockerin revealed two typical type I dockerin folds with significant interactions between them. Interaction analysis by isothermal titration calorimetry and NMR titration experiments revealed that the double-dockerin displays a preference for binding to the cell-wall anchoring scaffoldin ScaD through the first dockerin with a canonical dual-binding mode, while the second dockerin module was unable to bind to any of the tested cohesins. Surprisingly, the double-dockerin showed a much higher affinity to a cohesin from the CipC scaffoldin of Clostridium cellulolyticum than to the resident cohesins from C. thermocellum. These results contribute valuable insights into the structure and assembly of the double-dockerin module, and provide the basis for further functional studies on multiple-dockerin modules and cellulosomal proteases, thus highlighting the complexity and diversity of cellulosomal components.

Kinetic Ensemble of Tau Protein through the Markov State Model and Deep Learning Analysis.

The ordered assembly of Tau protein into filaments characterizes Alzheimer's and other neurodegenerative diseases, and thus, stabilization of Tau protein is a promising avenue for tauopathies therapy. To dissect the underlying aggregation mechanisms on Tau, we employ a set of molecular simulations and the Markov state model to determine the kinetics of ensemble of K18. K18 is the microtubule-binding domain of Tau protein and plays a vital role in the microtubule assembly, recycling processes, and amyloid fibril formation. Here, we efficiently explore the conformation of K18 with about 150 μs lifetimes in silico. Our results observe that all four repeat regions (R1-R4) are very dynamic, featuring frequent conformational conversion and lacking stable conformations, and the R2 region is more flexible than the R1, R3, and R4 regions. Additionally, it is worth noting that residues 300-310 in R2-R3 and residues 319-336 in R3 tend to form sheet structures, indicating that K18 has a broader functional role than individual repeat monomers. Finally, the simulations combined with Markov state models and deep learning reveal 5 key conformational states along the transition pathway and provide the information on the microsecond time scale interstate transition rates. Overall, this study offers significant insights into the molecular mechanism of Tau pathological aggregation and develops novel strategies for both securing tauopathies and advancing drug discovery.

IGF2BP3 prevent HMGB1 mRNA decay in bladder cancer and development

BackgroundIGF2BP3 functions as an RNA-binding protein (RBP) and plays a role in the posttranscriptional control of mRNA localization, stability, and translation. Its dysregulation is frequently associated with tumorigenesis across various cancer types. Nonetheless, our understanding of how the expression of the IGF2BP3 gene is regulated remains limited. The specific functions and underlying mechanisms of IGF2BP3, as well as the potential benefits of targeting it for therapeutic purposes in bladder cancer, are not yet well comprehended.MethodsThe mRNA and protein expression were examined by RT-qPCR and western blotting, respectively. The methylation level of CpG sites was detected by Bisulfite sequencing PCR (BSP). The regulation of IGF2BP3 expression by miR-320a-3p was analyzed by luciferase reporter assay. The functional role of IGF2BP3 was determined through proliferation, colony formation, wound healing, invasion assays, and xenograft mouse model. The regulation of HMGB1 by IGF2BP3 was investigated by RNA immunoprecipitation (RIP) and mRNA stability assays.ResultsWe observed a significant elevation in IGF2BP3 levels within bladder cancer samples, correlating with more advanced stages and grades, as well as an unfavorable prognosis. Subsequent investigations revealed that the upregulation of IGF2BP3 expression is triggered by copy number gain/amplification and promoter hypomethylation in various tumor types, including bladder cancer. Furthermore, miR-320a-3p was identified as another negative regulator in bladder cancer. Functionally, the upregulation of IGF2BP3 expression exacerbated bladder cancer progression, including the proliferation, migration, and invasion of bladder cancer. Conversely, IGF2BP3 silencing produced the opposite effects. Moreover, IGF2BP3 expression positively correlated with inflammation and immune infiltration in bladder cancer. Mechanistically, IGF2BP3 enhanced mRNA stability and promoted the expression of HMGB1 by binding to its mRNA, which is a factor that promotes inflammation and orchestrates tumorigenesis in many cancers. Importantly, pharmacological inhibition of HMGB1 with glycyrrhizin, a specific HMGB1 inhibitor, effectively reversed the cancer-promoting effects of IGF2BP3 overexpression in bladder cancer. Furthermore, the relationship between HMGB1 mRNA and IGF2PB3 is also observed in mammalian embryonic development, with the expression of both genes gradually decreasing as embryonic development progresses.ConclusionsOur present study sheds light on the genetic and epigenetic mechanisms governing IGF2BP3 expression, underscoring the critical involvement of the IGF2BP3-HMGB1 axis in driving bladder cancer progression. Additionally, it advocates for the investigation of inhibiting IGF2BP3-HMGB1 as a viable therapeutic approach for treating bladder cancer.Graphical

Microclimatic Influences on the Abundance of Three Non-Troglobiont Species

Subterranean environments are often characterized by a natural gradient of microclimatic conditions and trophic resources, showing a higher trophic availability and a lower microclimatic stability in the shallowest area (close to the cave entrance), while the opposite occurs in the deepest sections. The shallowest areas of subterranean environments (e.g., the entrance and twilight zone, Mesovoid Shallow Substratum) act as ecotones between the surface habitats and the deep areas, creating a particular habitat which can be exploited by numerous species with different degrees of adaptation to subterranean environments. Species living in these ecotones may hold a key role in sustaining the entire ecosystem, as they are likely one of the major drivers of allochthonous organic matter. Indeed, these species are usually facultative cave-dwellers, meaning that they are able to exit and forage on the surface. Once these species are back inside the cave, they provide the local community with different typologies of organic matter (e.g., feces, eggs), which represent one of the most important sources of organic carbon. Therefore, studying which ecological features may exert significant effects on the abundance of these species may be of great help in understanding the ecosystem dynamics and the functional role of each species. In this study we analyzed the data collected through a year-round monitoring program, aiming to assess the potential effects that both abiotic and biotic features may have on the abundance of three facultative cave species. We focused on seven caves located in Monte Albo (Sardinia, Italy). The cave environments were divided into 3-meter sectors, and within each cave sector, microclimatic and biological data were seasonally recorded. We focused on the following facultative cave species: the spiders Metellina merianae and Tegenaria sp. and the snail Oxychilus oppressus. Different relationships were observed between the ecological features and the abundance of the three species. The two spiders were more abundant in warmer cave sectors closer to the cave entrance, especially the M. merianae. On the other hand, the snail tended to be more abundant farther from the cave entrance and in more illuminated cave sectors, probably because sunlight promotes the abundance of some of its trophic resources (e.g., lichens, vegetation). Furthermore, O. oppressus was the only species whose abundance and cave distribution was significantly affected by seasonality. This study provides useful and novel information to understand the population dynamics of facultative cave species and their role in subterranean ecosystems.

Responses of soil bacterial and fungal community structure and functions to different plant species in a mixed forest plantation in a semi-arid region of China

Soil microbial communities play important roles in biogeochemical cycles and ecosystem functioning. However, how tree and grass species affect soil microbial structure and functions in semi-arid regions is poorly understood. In this study, we used sequencing of representative genes and bioinformatic analysis to compare the soil bacterial and fungal communities and their functional groups among legume and non-legume broad-leaved plantations, conifer plantations, artificial grassland, and adjacent farmland in a semi-arid area of Northern China. We found that soil bacterial diversity and abundance were significantly increased by legume plantations, especially Robinia pseudoacacia, compared to farmland. Soil bacterial communities were dominated by K-strategists in plantation soils and by r-strategists in farmland and grassland soils. Soil fungal communities showed contrasting patterns between Ascomycetes and Basidiomycota across treatments, and the highest abundance of nutrient indicator taxa Mortierellomycota was observed in plantation soils. Functional analysis revealed that afforestation altered the capacity of soil bacteria for organic compound mineralization and C and N cycling, and that different plant species enriched different types of ectomycorrhizal and saprophytic fungi. Moreover, we found that plantations and grasslands formed more connected but less complex and stable bacterial co-occurrence networks than farmland, and that conifer plantations increased the closeness of soil fungal networks compared to broad-leaved plantations. Our results suggest that tree and grass species play a key role in shaping the soil microbial community structure and functional groups, and provide valuable information for choosing suitable tree and grass species for ecosystem restoration and management in semi-arid regions.

Reading comprehension improvement in autism.

A subset of autistic children excel at word decoding but have difficulty with reading comprehension (i.e., the discrepant poor comprehender reading profile). Prior research suggests the Visualizing and Verbalizing (V/V) for language comprehension and thinking intervention helps improve reading comprehension in autistic children with this reading profile. Previous studies have demonstrated the role of vocabulary, memory, and social functioning in reading comprehension; however, predictors and moderators of reading comprehension within this specific profile of autistic readers have not been thoroughly explored. In this study, we examined the effectiveness of the V/V intervention by comparing reading comprehension scores between groups and across time. Participants included a sample of autistic children (AUT-EXP; n=22) and a waitlist control group of autistic children (AUT-WLC; n=17) with reading comprehension difficulties, as well as a sample of non-autistic children (Non-AUT; n=26) (all age 8-13 years). AUT-EXP and AUT-WLC groups completed a battery of cognitive assessments during pre and post tests. We also analyzed whether cognitive assessment scores predicted reading comprehension, and examined the moderating effects of group (AUT-EXP vs. AUT-WLC) on these relationships. The AUT-EXP group significantly improved in their pre to post reading comprehension scores (t(21)=4.19, p<.001, d=.89), whereas the AUT-WLC group did not. Verbal memory significantly predicted reading comprehension, though group did not moderate relationships between cognitive test performance and reading comprehension. Results suggest that the V/V intervention may help improve reading comprehension for autistic children with the discrepant poor comprehender reading profile. Additionally, strategies for improving verbal memory may indirectly enhance reading comprehension in autistic children with this reading profile.

Hyperhidrosis: problems and solutions

The functional role of sweating is not limited only to thermoregulation and excretion. There are other functions of it — the ability to enhance and maintain hydration and barrier function of the skin. Excessive sweating can lead to an exacerbation or cause many skin diseases, form psychological discomfort in a person due to wet clothes or an accompanying unpleasant odor. Primary hyperhidrosis may be an autosomal dominant genetic disease. Secondary, usually generalized hyperhidrosis is often associated with drug effects on the body or a systemic disease. The following approaches are used in the treatment of hyperhidrosis: 1) blocking the release of sweat to the skin surface (aluminum salts and formaldehyde); 2) physiotherapy (iontophoresis); 3) destruction of sweat glands and cessation of sweat production (excision of a skin flap with subcutaneous fat, curettage, microwave technology, etc.); 4) termination of the signal from the central nervous system to the sweat glands (transthoracic endoscopic sympathectomy, percutaneous radiofrequency sympathectomy, botulinum toxin injections, systemic anticholinergic drugs). External remedies for excessive sweating include the Russian drug Formagel®, containing 3.7% formaldehyde. This drug is a non-invasive, easily doable, effective, safe method of treating hyperhidrosis.

Entrepreneurship and mental well-being in China: the moderating roles of work autonomy and subjective socioeconomic status

Entrepreneurs’ mental well-being has been a nascent research topic in the entrepreneurship domain, but it remains unclear whether and how entrepreneurship affects mental well-being in the context of emerging economies. Drawing on the self-determination theory (SDT), we developed a model in which entrepreneurship, compared to wage–employment, was identified as a career choice more conducive to work-related and socioeconomic status (SES)-related psychological functioning (i.e., work autonomy and subjective SES), which, in turn, produces mental well-being benefits. We tested this model in the Chinese context by providing evidence based on data from the Chinese General Social Survey (CGSS) between 2010 and 2021 (N = 28,419). We found that entrepreneurs had higher levels of positive mental well-being and lower levels of negative mental well-being than paid employees. Mediation analysis showed that subjective SES mediated the relationship between entrepreneurship and mental well-being and explained this relationship better than work autonomy. These findings indicated that the mental well-being benefits of entrepreneurship existed in emerging economies like China and highlighted the crucial role of SES-related psychological functioning in facilitating entrepreneurs’ mental well-being.

A Systematic Review of Health-Related Quality of Life in Women with HER2-Positive Metastatic Breast Cancer Treated with Trastuzumab.

Many trials of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer treatment with trastuzumab have provided evidence of improved clinical outcomes. This systematic review examined how a regimen that includes trastuzumab affects patients' health-related quality of life (HRQoL) during and after treatment. A systematic search for articles published up to February 2023 without restrictions of language or publication year was performed using the Pubmed, Embase, and Scopus databases. We included studies of women aged >18 years with metastatic HER2-positive breast cancer treated with a trastuzumab-containing regimen. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) tool (2.0) for randomized controlled trials (RCTs) and the Risk Of Bias In Non-randomised Studies-of Interventions (ROBINS-I) tool for cross-sectional studies. We used Microsoft Excel to extract and synthesize data, and documented the review procedure following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In total, eight studies compared 1104 trastuzumab-treated patients and 1003 non-trastuzumab-treated patients. Most studies were RCTs (n=7) and one was a prospective observational study. All the included studies used the EORTC-QLQ-C30, EORTC-QLQ-BR23, FACT-B, or FACT-G questionnaires. During treatment, patients taking regimens that included trastuzumab showed clinical improvement in HRQoL, social functioning, and role functioning. After the treatment, patients' HRQoL profiles in the trastuzumab and chemotherapy arms were similar. However, trastuzumab (versus chemotherapy) treatment led to clinically improved functional status, role and physical functioning, and fatigue. The quality assessment revealed some concerns in most RCTs, with the risk of bias being high in two studies, low in one study, and moderate in the cross-sectional study. Trastuzumab-containing regimens administered to HER2-positive breast cancer patients at the metastatic stage evidenced beneficial effects on total HRQoL during and after treatment. Upon therapy cessation, patients' HRQoL scores for both interventions improved. Nevertheless, HRQoL profiles of patients treated with trastuzumab were more favorable, particularly for functional status, role functioning, physical well-being, and fatigue. This review was registered in PROSPERO (registration number: CRD42021259826).

Extracellular vesicles as carriers for noncoding RNA-based regulation of macrophage/microglia polarization: an emerging candidate regulator for lung and traumatic brain injuries.

Macrophage/microglia function as immune defense and homeostatic cells that originate from bone marrow progenitor cells. Macrophage/microglia activation is historically divided into proinflammatory M1 or anti-inflammatory M2 states based on intracellular dynamics and protein production. The polarization of macrophages/microglia involves a pivotal impact in modulating the development of inflammatory disorders, namely lung and traumatic brain injuries. Recent evidence indicates shared signaling pathways in lung and traumatic brain injuries, regulated through non-coding RNAs (ncRNAs) loaded into extracellular vesicles (EVs). This packaging protects ncRNAs from degradation. These vesicles are subcellular components released through a paracellular mechanism, constituting a group of nanoparticles that involve exosomes, microvesicles, and apoptotic bodies. EVs are characterized by a double-layered membrane and are abound with proteins, nucleic acids, and other bioactive compounds. ncRNAs are RNA molecules with functional roles, despite their absence of coding capacity. They actively participate in the regulation of mRNA expression and function through various mechanisms. Recent studies pointed out that selective packaging of ncRNAs into EVs plays a role in modulating distinct facets of macrophage/microglia polarization, under conditions of lung and traumatic brain injuries. This study will explore the latest findings regarding the role of EVs in the progression of lung and traumatic brain injuries, with a specific focus on the involvement of ncRNAs within these vesicles. The conclusion of this review will emphasize the clinical opportunities presented by EV-ncRNAs, underscoring their potential functions as both biomarkers and targets for therapeutic interventions.

Teaching Biophysics II. Biophysical approach of transport through cellular membranes

Cellular metabolism implies a permanent transport through membranes of a great diversity of particles (e.g., ions, molecules, macromolecules, protein vesicles, etc.) in and out of the cells. The transport phenomena can be classified as passive (down the concentration gradients, driven solely by thermal agitation) or active (against the concentration gradients, driven by an energy supply) and selective (i.e., through specific pathways) or nonselective through membrane lipid bilayers. This paper will describe in an accessible manner all the types of membrane transport from a biophysical point of view along with their crucial roles in normal cellular functioning. This paper is the successor of a previous work (A. I. Popescu, C. G. Chilom, Rom. Rep. Phys. 75, 605 (2023), Ref. [1]) in a series aiming to disseminate Biophysics in an accessible manner.

Exploring the Role of Therapeutic Alliance and Client Functioning in Vocational Rehabilitation Engagement Among Clients with Mental Disabilities

Exploring the Role of Therapeutic Alliance and Client Functioning in Vocational Rehabilitation Engagement Among Clients with Mental Disabilities

Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high-grade serous ovarian cancer cells.

No data are currently available on the functional role of small conductance Ca2+-activated K+ channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non-cell-permeant SK2 inhibitor Lei-Dab7, we identified functional SK2 channels at the plasma membrane, regulating store-operated Ca2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei-Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei-Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro-migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression-free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination.

Can I see it in the eyes? An investigation of freezing-like motion patterns in response to avoidable threat.

Freezing is one of the most extensively studied defensive behaviors in rodents. Both reduced body and gaze movements during anticipation of threat also occur in humans and have been discussed as translational indicators of freezing but their relationship remains unclear. We thus set out to elucidate body and eye movements and concomitant autonomic dynamics in anticipation of avoidable threat. Specifically, 50 participants viewed naturalistic pictures that were preceded by a colored fixation cross, signaling them whether to expect an inevitable (shock), no (safety), or a potential shock (flight) that could be avoided by a quick button press. Body sway, eye movements, the heart rate and skin conductance were recorded. We replicated previously described reductions in body sway, gaze dispersion, and the heart rate, and a skin conductance increase in flight trials. Stronger reductions in gaze but not in body sway predicted faster motor reactions on a trial-wise basis, highlighting their functional role in action preparation. We failed to find a trait-like relationship between body and gaze movements across participants, but their temporal profiles were positively related within individuals, suggesting that both metrics partly reflect the same construct. However, future research is desirable to assess these response patterns in naturalistic environments. A more ethological examination of different movement dynamics upon threat would not only warrant better comparability between rodent and human research but also help determine whether and how eye-tracking could be implemented as a proxy for fear-related movements in restricted brain imaging environments.

Revealing the Indispensable Role of the RFamide Functionality using a Novel Acid Labile Benzofuranone based Amine (ALBA) Linker

AbstractThe RFamide family of peptides represents an important class of GPCR ligand neuropeptides covering a wide range of biological functions. While many analogues of the highly conserved C‐terminal RFamide motif within this peptide class have been synthesized and their functional significance elucidated, additional exploration of the structure activity relationship is of value. We have developed a novel linker for solid phase peptide synthesis (SPPS) which is able to anchor amine functionalised compounds for further elaboration. The acid labile benzofuranone based amine (ALBA) linker (5‐(3‐aminopropylcarbamoyl)‐2‐[[tert‐butyl(diphenyl)silyl]oxymethyl]benzoic acid) is compatible with Fmoc based SPPS and has two cleavage modes. As a proof of concept, the ALBA linker was used to successfully synthesise a novel analogue of Kisspeptin 10, the natural ligand for GPCR54, whereby the natural RFamide motif was replaced with an RFamine. Biological evaluation of the amine‐containing analogue revealed that the group is not compatible with receptor activation.

Differentiation of bacterial communities on five common plastics after six days of exposure to Caribbean coastal waters

Plastic pollution in coastal areas, particularly in subtropical and tropical regions, remains a pervasive environmental issue. Marine plastic debris provides an artificial surface that rapidly accumulates a dynamic microbial biofilm upon entering the marine ecosystem. Especially the early stages of colonization are critical in shaping the microbial community. This study investigates the early microbial colonization, in less than a week, on five different plastic polymers in Caribbean coastal waters through 16S rRNA gene amplicon sequencing. We discovered shared bacterial taxa among the various plastic polymers and sampling timepoints, with dominant orders being Flavobacteriales, Rhodobacterales, Rhizobiales, and Pseudomonadales. Statistical analysis confirmed significant differences in community composition between the two sampling points, with polystyrene exhibiting a distinct microbial community on day 6 compared to polyethylene, polypropylene, and nylon. We found the same for polyethylene compared to nylon and polyethylene-terephthalate. Further examination identified 47 genera responsible for these differences, primarily belonging to the phyla Proteobacteria and Bacteroidota. Our data indicate an influence of both environmentally related stochastic processes and plastic-related specific factors during early colonization. Interestingly, we noticed an increase in the relative abundance of hydrocarbon and potentially plastic-degrading bacteria (PDB) from 12.4 to 34.5 % between the first and sixth day, suggesting their vital role in shaping the epiplastic community. Notably, some identified PDB have been reported to degrade the specific polymers studied, thus the monitored increase in relative abundance supports their role in plastic degradation. However, more research is required to fully understand their functioning and potential role in the epiplastic community. Our study provides insights into the prokaryotic colonization of marine plastics in the Caribbean basin, where to date studies have been limited despite high pollution rates.

Functional roles of CD26/DPP4 in lipopolysaccharide-induced lung injury.

Acute respiratory distress syndrome (ARDS) is characterized by dysregulated inflammation and increased permeability of lung microvascular cells. CD26/dipeptidyl peptidase-4 (DPP4) is a type II membrane protein that is expressed in several cell types and mediates multiple pleiotropic effects. We previously reported that DPP4 inhibition by sitagliptin attenuates lipopolysaccharide (LPS)-induced lung injury in mice. The current study characterized the functional role of CD26/DPP4 expression in LPS-induced lung injury in mice, isolated alveolar macrophages, and cultured lung endothelial cells. In LPS-induced lung injury, inflammatory responses [bronchoalveolar lavage fluid (BALF) neutrophil numbers and several proinflammatory cytokine levels] were attenuated in Dpp4 knockout (Dpp4 KO) mice. However, multiple assays of alveolar capillary permeability were similar between the Dpp4 KO and wild-type mice. TNF-α and IL-6 production was suppressed in alveolar macrophages isolated from Dpp4 KO mice. In contrast, in cultured mouse lung microvascular endothelial cells (MLMVECs), reduction in CD26/DPP4 expression by siRNA resulted in greater ICAM-1 and IL-6 expression after LPS stimulation. Moreover, the LPS-induced vascular monolayer permeability in vitro was higher in MLMVECs treated with Dpp4 siRNA, suggesting that CD26/DPP4 plays a protective role in endothelial barrier function. In summary, this study demonstrated that genetic deficiency of Dpp4 attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential functional roles of CD26/DPP4 expression in resident cellular components of the lung. CD26/DPP4 may be a potential therapeutic target for ARDS and warrants further exploration to precisely identify the multiple functional effects of CD26/DPP4 in ARDS pathophysiology.NEW & NOTEWORTHY We aimed to clarify the functional roles of CD26/DPP4 in ARDS pathophysiology using Dpp4-deficient mice and siRNA reduction techniques in cultured lung cells. Our results suggest that CD26/DPP4 expression plays a proinflammatory role in alveolar macrophages while also playing a protective role in the endothelial barrier. Dpp4 genetic deficiency attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential roles of CD26/DPP4 expression in the resident cellular components of the lung.

The functional role of P2 purinergic receptors in the progression of gastric cancer.

Studies have confirmed that P2 purinergic receptors (P2X receptors and P2Y receptors) expressed in gastric cancer (GC) cells and GC tissues and correlates with their function. Endogenous nucleotides including ATP, ADP, UTP, and UDP, as P2 purinergic receptors activators, participate in P2 purinergic signal transduction pathway. These activated P2 purinergic receptors regulate the progression of GC mainly by mediating ion channels and intracellular signal cascades. It is worth noting that there is a difference in the expression of P2 purinergic receptors in GC, which may play different roles in the progression of GC as a tumor promoting factor or a tumor suppressor factor. Among them, P2 × 7, P2Y2 and P2Y6 receptors have certain clinical significance in patients with GC and may be used as biological molecular markers for the prediction of patients with GC. Therefore, in this paper, we discuss the functional role of nucleotide / P2 purinergic receptors signal axis in regulating the progression of GC and that these P2 purinergic receptors may be used as potential molecular targets for the prevention and treatment of GC.

Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons.

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal targets, display different activity patterns in vivo, and are thought to have distinct network functions. However, a complete understanding of the functional roles of these interneurons requires a precise description of their intrinsic computational properties and their synaptic interactions. In the current study we generated, analyzed, and make available several key data sets that enable a quantitative comparison of various anatomical and physiological properties of OLM and HS cells in mouse. The data set includes detailed scanning electron microscopy (SEM)-based 3D reconstructions of OLM and HS cells along with their excitatory and inhibitory synaptic inputs. Combining this core data set with other anatomical data, patch-clamp electrophysiology, and compartmental modeling, we examined the precise morphological structure, inputs, outputs, and basic physiological properties of these cells. Our results highlight key differences between OLM and HS cells, particularly regarding the density and distribution of their synaptic inputs and mitochondria. For example, we estimated that an OLM cell receives about 8,400, whereas an HS cell about 15,600 synaptic inputs, about 16% of which are GABAergic. Our data and models provide insight into the possible basis of the different functionality of OLM and HS cell types and supply essential information for more detailed functional models of these neurons and the hippocampal network.

Neuropsychological correlates of early grief in bereaved older adults.

Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample and further explored the relationship between multidomain cognitive measures and grief severity. A total of ninety-three nondemented older adults (high grief: n = 44; low grief: n = 49) within 12 months post-bereavement and non-bereaved comparison participants (n = 43) completed neuropsychological battery including global and multiple domain-specific cognitive functioning. Linear regression models were used to analyze differences in multidomain cognitive measures between the groups and specifically examine the associations between cognitive performance and grief severity in the bereaved, after covariate adjustment, including depressive symptoms. Bereaved older adults with higher grief symptoms performed worse than those with lower symptoms and non-bereaved participants on executive functioning and attention and processing speed measures. In the bereaved, poorer executive functioning, attention and processing speed correlated with higher grief severity. Attention/processing speed-grief severity correlation was seen in those with time since loss ≤ 6 months, but not > 6 months. Intense early grief is characterised by poorer executive functioning, attention, and processing speed, resembling findings in PGD. The putative role of poorer cognitive functioning during early grief on the transition to integrated grief or the development of PGD remains to be elucidated.