Functional Aspects Research Articles

Which aspect of functional diversity shapes ecosystem functioning in exploited marine demersal fish community?

The biodiversity-ecosystem functioning (BEF) relationship is a critical topic in ecological research, as it guides the maintenance of ecosystem functioning in the face of climate change and human disturbance. However, the BEF relationship is complicated by the fact that biodiversity has multiple dimensions, and in particular functional diversity may be strongly correlated with community productivity. But the understanding is still lacking about how different functional traits determine community productivity. The present study tested the relationship between biodiversity and community productivity empirically in a demersal fish community, based on continuous bottom trawl surveys in Haizhou Bay, China from 2013 to 2022. Structural equation modeling (SEM) with composite variables was used to evaluate the relationships among environmental factors, species diversity (SD), functional diversity (FD), community weighted mean traits (CWM), and community productivity (CP), and the roles of different aspects of functional traits were further compared. The results showed that there were considerable heterogeneities in the temporal and spatial distributions of CP, and PCA revealed that the CP was weakly correlated with both species and functional diversity. SEM showed that CWM had the greatest influences on CP (r = 0.63), followed by SD (r = 0.52), and FD had the least impact (r = -0.42). This finding supported the mass ratio hypothesis, indicating that functional traits of dominant species determined community productivity. Environmental factors showed no direct impacts on CP but had indirect effects through biodiversity. Regarding the role of different functional traits, the trait of locomotion was the most important driver of CP in terms of CWM, while the food acquisition was more important than other components in terms of FD. Our study can contribute to an improved comprehension of the BEF linkages in marine fish communities, and serve as a guideline for fisheries management and biodiversity protection in the face of climate changes.

Lower Childhood Socioeconomic Status Is Associated with Greater Neural Responses to Ambient Auditory Changes in Adulthood.

Humans' early life experience varies by socioeconomic status (SES), raising the question of how this difference is reflected in the adult brain. An important aspect of brain function is the ability to detect salient ambient changes while focusing on a task. Here, we ask whether subjective social status during childhood is reflected by the way young adults' brain detecting changes in irrelevant information. In two studies (total n = 58), we examine electrical brain responses in the frontocentral region to a series of auditory tones, consisting of standard stimuli (80%) and deviant stimuli (20%) interspersed randomly, while participants were engaged in various visual tasks. Both studies showed stronger automatic change detection indexed by MMN in lower SES individuals, regardless of the unattended sound's feature, attended emotional content, or study type. Moreover, we observed a larger MMN in lower-SES participants, although they did not show differences in brain and behavior responses to the attended task. Lower-SES people also did not involuntarily orient more attention to sound changes (i.e., deviant stimuli), as indexed by the P3a. The study indicates that individuals with lower subjective social status may have an increased ability to automatically detect changes in their environment, which may suggest their adaptation to their childhood environments.

Comparative Analysis of Traditional Methods and Building Information Modeling (BIM) in Construction Project Cost Estimation

Abstract: Building Information Modeling (BIM) has revolutionized the construction industry by providing digital images of the physical and functional aspects of the site. This article explores the use of BIM in project management and compares it to traditional methods. The study focused on parameters such as efficiency, cost, accuracy, and coordination. Research shows that BIM increases efficiency, accuracy, and coordination while reducing costs and risks. However, challenges remain, such as developing regulations and reaching consensus on requirements among stakeholders. Despite these challenges, the article concludes that BIM has the potential to transform project management.

Management of fractures involving the mandibular body, parasymphyseal, and subcondylar regions

Background: The mandibular bone plays a crucial role in various aspects of facial anatomy, including digestion, speech, and facial aesthetics. Given its significance in these functions, surgeons must not only address functional aspects but also consider aesthetic concerns during treatment. Mandibular fractures represent a prevalent form of traumatic injury in the maxillofacial region. Despite the existence of established treatment methods that have been in use for a considerable time, untreated fractures and complications following surgery can still significantly impact the patient's quality of life. Purpose: Understand the principles of managing cases of mandibular corpus, mandibular parasymphysis, subcondyle fractures using a combination of Mini Plate and Reconstruction Plate. Case: A 54-year-old man with mandibular parasymphysis fracture Dekstra, corpus mandibular fracture sinistra, subcondyle fracture sinistra, dentoalveolar fracture regions 32-42 accompanied by avulsions 32, 31, 41, 42, and hypertension was reported. Results: The treatment in this case was Open Reduction and Internal Fixation (ORIF). Fixation of the fracture segments with 2 vertical mini-plates on the parasymphysis of the dextral mandible, 1 mini-plate and reconstruction plate on the corpus and subcondyle fracture sinistra. Conclusion: The use of two plates and screws in the parasymphysis of the mandible, one mini-plate and one reconstruction plate in mandibular corpus and subcondyle fractures, resulted in good occlusion with minimal complications.

Reframing acute kidney injury as a pathophysiological continuum of disrupted renal excretory function.

Surrogate measures of glomerular filtration rate (GFR) continue to serve as pivotal determinants of the incidence, severity, and management of acute kidney injury (AKI), as well as the primary reference point underpinning knowledge of its pathophysiology. However, several clinically important deficits in aspects of renal excretory function during AKI other than GFR decline, including acid-base regulation, electrolyte and water balance, and urinary concentrating capacity, can evade detection when diagnostic criteria are built around purely GFR-based assessments. The use of putative markers of tubular injury to detect "sub-clinical" AKI has been proposed to expand the definition and diagnostic criteria for AKI, but their diagnostic performance is curtailed by ambiguity with respect to their biological meaning and context specificity. Efforts to devise new holistic assessments of overall renal functional compromise in AKI would foster the capacity to better personalize patient care by replacing biomarker threshold-based diagnostic criteria with a shift to assessment of compromise along a pathophysiological continuum. The term AKI refers to a syndrome of sudden renal deterioration, the severity of which is classified by precise diagnostic criteria that have unquestionable utility in patient management as well as blatant limitations. Particularly, the absence of an explicit pathophysiological definition of AKI curtails further scientific development and clinical handling, entrapping the field within its present narrow GFR-based view. A refreshed approach based on a more holistic consideration of renal functional impairment in AKI as the basis for a new diagnostic concept that reaches beyond the boundaries imposed by the current GFR threshold-based classification of AKI, capturing broader aspects of pathogenesis, could enhance AKI prevention strategies and improve AKI patient outcome and prognosis.

The Meaning of Hope for Polish Male Patients Dying from Cancer Depending on Their Age: An Interdisciplinary Study with the Use of Osgood’s Semantic Differential Method

Background/Objectives: The subject of this article is the reflection on hope—one of the most important predictors and motivators of human actions. Hope is our response to a threat, and it is also the emotion that allows us to overcome hopelessness and to reduce suffering. Hoping is a human capacity with varying cognitive, emotional, and functional dimensions. Psychological, pedagogical (particularly in the framework of special-needs pedagogy and thanatological pedagogy), and theological reflection on hope can be helpful for dying people. The objective of this study was to characterize hope in the semantic space of individuals in the terminal stage of cancer and to verify whether age is a variable that determines this hope. Methods: To complete the study, the Osgood semantic differential method was applied, as modified by Polish psychologist Dr. Boguslaw Block (the DSN-3 test). The research technique consisted of a therapeutic conversation. Results: Research results show that, in general, those in the terminal stage have positive associations with hope. In all three aspects of the used test, namely the cognitive, emotional, and functional aspects, the highest scores assigned to the perception of hope were obtained from men up to 35 years of age. Depending on the ages of patients, one could observe certain semantic shifts, but they did not prove to be statistically significant. Conclusions: Polish males surveyed at the end of life due to cancer generally perceived hope as a supportive force. Therefore, hope can provide emotional support to patients in the terminal stage of cancer and improve their quality of life.

Conceptualizing avoidant/restrictive food intake disorder via an executive functioning lens.

Avoidant/restrictive food intake disorder (ARFID) is a heterogeneous disorder wherein restrictive eating is primarily attributed to non-shape/weight-based reasons (e.g., sensory sensitivity) that empirical research continues to explore. Mounting evidence suggests that ARFID often presents alongside neurodevelopmental diagnoses (NDs) or divergent neurodevelopment broadly. Executive functioning (EF) differences often characterize divergent neurodevelopmental trajectories. Additionally, restrictive eating in anorexia nervosa has been conceptualized as related to EF factors (e.g., set shifting). Given the neurodevelopmental phenotype that may be associated with ARFID and the role of EF in anorexia nervosa, this paper proposes EF as a potentially important, yet understudied factor in ARFID pathology. We posit that various observed ARFID behavioral/cognitive tendencies can be conceptualized in relation to EF differences. We contextualize commonly observed ARFID presentations within "core" EF components (i.e., cognitive flexibility, working memory, inhibitory control), leading to hypotheses about EF in ARFID. Finally, we offer additional considerations/directions for future research on EF in ARFID. Increased research on EF in ARFID is needed to consider this potential common factor in the etiology and maintenance of this heterogeneous disorder. We aim to promote further consideration of EF in ARFID etiology, maintenance, and treatment-outcome research. PUBLIC SIGNIFICANCE: This article proposes that aspects of executive functioning (EF) may play a role in the onset and maintenance of avoidant/restrictive food intake disorder (ARFID), although this notion is largely untested by existing research. Further research on the role of EF in ARFID may assist with refining models and treatments for this heterogeneous disorder.

Relationship between lncRNA MALAT1 and Chemo-radiotherapy Resistance of Cancer Cells: Uncovered Truths.

The advancement of novel technologies, coupled with bioinformatics, has led to the discovery of additional genes, such as long noncoding RNAs (lncRNAs), that are associated with drug resistance. LncRNAs are composed of over 200 nucleotides and do not possess any protein coding function. These lncRNAs exhibit lower conservation across species, are typically expressed at low levels, and often display high specificity towards specific tissues and developmental stages. The LncRNA MALAT1 plays crucial regulatory roles in various aspects of genome function, encompassing gene transcription, splicing, and epigenetics. Additionally, it is involved in biological processes related to the cell cycle, cell differentiation, development, and pluripotency. Recently, MALAT1 has emerged as a novel mechanism contributing to drug resistance or sensitivity, attracting significant attention in the field of cancer research. This review aims to explore the mechanisms through which MALAT1 confers resistance to chemotherapy and radiotherapy in cancer cells.

Comprehensive analysis of the Spartina alterniflora WD40 gene family reveals the regulatory role of SaTTG1 in plant development

IntroductionThe WD40 gene family, prevalent in eukaryotes, assumes diverse roles in cellular processes. Spartina alterniflora, a halophyte with exceptional salt tolerance, flood tolerance, reproduction, and diffusion ability, offers great potential for industrial applications and crop breeding analysis. The exploration of growth and development-related genes in this species offers immense potential for enhancing crop yield and environmental adaptability, particularly in industrialized plantations. However, the understanding of their role in regulating plant growth and development remains limited.MethodsIn this study, we conducted a comprehensive analysis of WD40 genes in S. alterniflora at the whole-genome level, delving into their characteristics such as physicochemical properties, phylogenetic relationships, gene architecture, and expression patterns. Additionally, we cloned the TTG1 gene, a gene in plant growth and development across diverse species.ResultsWe identified a total of 582 WD40 proteins in the S. alterniflora genome, exhibiting an uneven distribution across chromosomes. Through phylogenetic analysis, we categorized the 582 SaWD40 proteins into 12 distinct clades. Examining the duplication patterns of SaWD40 genes, we observed a predominant role of segmental duplication in their expansion. A substantial proportion of SaWD40 gene duplication pairs underwent purifying selection through evolution. To explore the functional aspects, we selected SaTTG1, a homolog of Arabidopsis TTG1, for overexpression in Arabidopsis. Subcellular localization analysis revealed that the SaTTG1 protein localized in the nucleus and plasma membrane, exhibiting transcriptional activation in yeast cells. The overexpression of SaTTG1 in Arabidopsis resulted in early flowering and increased seed size.DiscussionThese outcomes significantly contribute to our understanding of WD40 gene functions in halophyte species. The findings not only serve as a valuable foundation for further investigations into WD40 genes in halophyte but also offer insights into the molecular mechanisms governing plant development, offering potential avenues in molecular breeding.

Does internal audit function outsourcing policy matter for environmental, social and governance performance score? Evidence from Bursa Malaysia

Purpose Anecdotal evidence indicates the internal audit function may be crucial in supporting the implementation of ESG practices and reporting. However, thus far, no study has been empirically conducted to check how and why internal audit function might affect ESG performance. This study aims to address this gap by examining whether the internal audit budget is positively related to the ESG performance of Malaysian listed firms. It also explores whether the sourcing arrangement of the internal audit function can moderate the internal audit budget – ESG nexus. Design/methodology/approach The secondary data for the paper is extracted from two main sources, namely, the Thomson Reuters Eikon database and firms’ annual reports that were downloaded from the Bursa Malaysia website. The final sample consists of public firms listed on Bursa Malaysia over the period 2010 to 2019. Multivariate tests are used to examine the linkage between the variables. Findings The results show that the relationship between the annual internal audit budget and ESG performance is contingent on the sourcing arrangement of the internal audit function. Specifically, the results show that the annual internal audit budget has a positive impact on ESG performance for firms with an in-house internal audit function but not for firms outsourcing an internal audit function to external providers. Overall, the results suggest that the annual internal audit budget promotes ESG performance for firms performing their internal audit activities internally. Practical implications The findings of this paper provide a strong motivation for authorities in Malaysia to develop new policies and rules aiming at ensuring that internal audit departments are adequately resourced to function effectively, thereby promoting corporate ESG performance. Moreover, the findings may be useful in informing the board of directors and other policymakers that establishing an in-house internal audit department assists in advancing corporate sustainability performance. Social implications The findings of this paper suggest that investors, creditors and other stakeholders should link ESG reporting with the attributes of the internal audit function and outsourcing arrangement when evaluating firm performance. The total annual costs allocated to the internal audit function coupled with the outsourcing arrangement by an external provider should be considered for the overall assessment of the ESG performance and provide additional warranty towards corporate goals’ achievement and sustainability for the society. Originality/value This study extends previous studies on the determinants of ESG performance by focusing on two crucial aspects of the internal audit function: the annual budget and the outsourcing arrangement, a hitherto largely unexplored mechanism by the existing literature.

Female Characters in Fyodor Dostoevsky’s Novels in Interpretation of Vyacheslav Ivanov

The article analyzes the works of Vyacheslav Ivanov on Fyodor Dostoevsky. Using the material from the book “Dostoevsky: Tragedy — Myth — Mysticism” (1932), the research principles and interpretive strategies implemented by Vyacheslav Ivanov in interpreting the female characters in Dostoevsky’s novels “Crime and Punishment,” “The Devils,” and “The Idiot” are identified. It is shown that Ivanov’s conception of the artistic features of characters such as Sonya Marmeladova, Alena Ivanovna, Maria Timofeevna, and Nastasya Filippovna are revealed in the context of the “main myth” of the works. The mythopoetic and functional aspects are highlighted as the most significant in Ivanov’s interpretations of the female characters. Additionally, it is argued that the psychological and spiritual characteristics of the heroines are not overlooked by the hermeneutist, as understanding the nuances of their inner world was necessary for him to reveal the mythopoetic functions. Through Ivanov’s interpretations of Dostoevsky’s female characters, it becomes evident that the poet-thinker’s approach to the writer’s works represents a synthesis of philosophical conceptualization and historical-literary perspective.

Diverse task-driven modeling of macaque V4 reveals functional specialization towards semantic tasks.

Responses to natural stimuli in area V4-a mid-level area of the visual ventral stream-are well predicted by features from convolutional neural networks (CNNs) trained on image classification. This result has been taken as evidence for the functional role of V4 in object classification. However, we currently do not know if and to what extent V4 plays a role in solving other computational objectives. Here, we investigated normative accounts of V4 (and V1 for comparison) by predicting macaque single-neuron responses to natural images from the representations extracted by 23 CNNs trained on different computer vision tasks including semantic, geometric, 2D, and 3D types of tasks. We found that V4 was best predicted by semantic classification features and exhibited high task selectivity, while the choice of task was less consequential to V1 performance. Consistent with traditional characterizations of V4 function that show its high-dimensional tuning to various 2D and 3D stimulus directions, we found that diverse non-semantic tasks explained aspects of V4 function that are not captured by individual semantic tasks. Nevertheless, jointly considering the features of a pair of semantic classification tasks was sufficient to yield one of our top V4 models, solidifying V4's main functional role in semantic processing and suggesting that V4's selectivity to 2D or 3D stimulus properties found by electrophysiologists can result from semantic functional goals.

Central dogma rates in human mitochondria.

In human cells, the nuclear and mitochondrial genomes engage in a complex interplay to produce dual-encoded oxidative phosphorylation (OXPHOS) complexes. The coordination of these dynamic gene expression processes is essential for producing matched amounts of OXPHOS protein subunits. This review focuses on our current understanding of the mitochondrial central dogma rates, highlighting the striking differences in gene expression rates between mitochondrial and nuclear genes. We synthesize a coherent model of mitochondrial gene expression kinetics, highlighting the emerging principles and emphasizing where more precise measurements would be beneficial. Such an understanding is pivotal for grasping the unique aspects of mitochondrial function and its role in cellular energetics, and it has profound implications for aging, metabolic disorders, and neurodegenerative diseases.

Employment of diverse in vitro systems for analyzing multiple aspects of disease, hereditary hemorrhagic telangiectasia (HHT)

BackgroundIn vitro disease modeling enables translational research by providing insight into disease pathophysiology and molecular mechanisms, leading to the development of novel therapeutics. Nevertheless, in vitro systems have limitations for recapitulating the complexity of tissues, and a single model system is insufficient to gain a comprehensive understanding of a disease.ResultsHere we explored the potential of using several models in combination to provide mechanistic insight into hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder. Genome editing was performed to establish hPSCs (H9) with ENG haploinsufficiency and several in vitro models were used to recapitulate the functional aspects of the cells that constitute blood vessels. In a 2D culture system, endothelial cells showed early senescence, reduced viability, and heightened susceptibility to apoptotic insults, and smooth muscle cells (SMCs) exhibited similar behavior to their wild-type counterparts. Features of HHT were evident in 3D blood-vessel organoid systems, including thickening of capillary structures, decreased interaction between ECs and surrounding SMCs, and reduced cell viability. Features of ENG haploinsufficiency were observed in arterial and venous EC subtypes, with arterial ECs showing significant impairments. Molecular biological approaches confirmed the significant downregulation of Notch signaling in HHT-ECs.ConclusionsOverall, we demonstrated refined research strategies to enhance our comprehension of HHT, providing valuable insights for pathogenic analysis and the exploration of innovative therapeutic interventions. Additionally, these results underscore the importance of employing diverse in vitro systems to assess multiple aspects of disease, which is challenging using a single in vitro system.

The Development and Content Validation of Brief International Classification of Functioning, Disability and Health Category Sets for 6 - 12-Year-Old Children with Cerebral Palsy, from the Perspective of Iranian Occupational Therapists

Background: There is uncertainty in identifying which aspects of functioning should be prioritized in the clinical brief assessment of children with cerebral palsy (CP). Brief ICF category sets specify the essential aspects of functioning that should be addressed in such assessments. Objectives: This study aimed to develop five brief ICF category sets based on the functional limitations of children with CP, as viewed by Iranian occupational therapists (OTs). Methods: This cross-sectional, multi-method study was conducted from January to May 2022 in Iran. Nineteen OTs were recruited through purposive sampling for a Delphi process, and ten OTs through snowball sampling for an expert panel, all experienced in CP and ICF. The Delphi involved two rounds of electronic surveys, where participants identified categories that should be minimally addressed in brief assessments of children aged 6 - 12 with CP based on their functional limitations. The content validity of these sets was then quantitatively evaluated by the expert panel. Results: Most confirmed categories in the gross and fine motor brief sets pertained to body structure and function, while those in the eating-and-drinking and communication-function brief sets related to cognition and motor reflexes. Categories in the visual function brief set pertained to activity, participation, and environmental factors. Content validity ratio (CVR) and item-content validity indexes (I-CVI) ranged from 0.80 to 1 across all categories/brief sets, with scale-content validity index/Average (S-CVI/Ave) ranging from 0.95 to 0.98. Conclusions: These functional-based ICF brief sets are the first developed for children with CP in this age group and provide occupational therapists with tools to address crucial aspects of functioning, tailored to specific functional limitations. However, cultural biases and the generalizability of these brief sets remain limitations.

A novel approach to runway overrun risk assessment using FRAM and flight data monitoring

Abstract Runway overruns (ROs) are the result of an aircraft rolling beyond the end of a runway, which is one of the accident’s types that most frequently occurs on aviation. The risk of an RO arises from the synergistic effect among its precursors, such as unstable approaches, long touchdowns and inadequate use of deceleration devices. To analyse this complex socio-technical system, the current work proposes a customised functional resonance analysis method, called FRAM-FDM, as traditional techniques of risk and safety assessment do not identify the interactions and couplings between the various functional aspects of the system itself, especially regarding human and organisational components. Basically, FRAM-FDM is the coupling of a traditional FRAM with flight data monitoring (FDM) techniques, used here to quantify the variabilities of the flight crew performance while executing the required activity (i.e. the landing). In this proposal, these variabilities (i.e. the FRAM functions aspects) are aggregated by the addend of a logistic regression, resulting in a model to evaluate the flare operations and the brake application profile effect on the remaining distance to the end of the runway, used as a reference to classify the landing as acceptable or not. The present application of the FRAM-FDM assesses the operational risk of a sample fleet in overrunning the runway during landing, highlighting the brake pedal application profile as the most relevant contributor. The model improves the knowledge about the system behaviour, being useful to direct flight crew training.

Polygenic Risk Scores Validated in Patient-Derived Cells Stratify for Mitochondrial Subtypes of Parkinson's Disease.

The aim of our study is to better understand the genetic architecture and pathological mechanisms underlying neurodegeneration in idiopathic Parkinson's disease (iPD). We hypothesized that a fraction of iPD patients may harbor a combination of common variants in nuclear-encoded mitochondrial genes ultimately resulting in neurodegeneration. We used mitochondria-specific polygenic risk scores (mitoPRSs) and created pathway-specific mitoPRSs using genotype data from different iPD case-control datasets worldwide, including the Luxembourg Parkinson's Study (412 iPD patients and 576 healthy controls) and COURAGE-PD cohorts (7,270 iPD cases and 6,819 healthy controls). Cellular models from individuals stratified according to the most significant mitoPRS were subsequently used to characterize different aspects of mitochondrial function. Common variants in genes regulating Oxidative Phosphorylation (OXPHOS-PRS) were significantly associated with a higher PD risk in independent cohorts (Luxembourg Parkinson's Study odds ratio, OR = 1.31[1.14-1.50], p-value = 5.4e-04; COURAGE-PD OR = 1.23[1.18-1.27], p-value = 1.5e-29). Functional analyses in fibroblasts and induced pluripotent stem cells-derived neuronal progenitors revealed significant differences in mitochondrial respiration between iPD patients with high or low OXPHOS-PRS (p-values < 0.05). Clinically, iPD patients with high OXPHOS-PRS have a significantly earlier age at disease onset compared to low-risk patients (false discovery rate [FDR]-adj p-value = 0.015), similar to prototypic monogenic forms of PD. Finally, iPD patients with high OXPHOS-PRS responded more effectively to treatment with mitochondrially active ursodeoxycholic acid. OXPHOS-PRS may provide a precision medicine tool to stratify iPD patients into a pathogenic subgroup genetically defined by specific mitochondrial impairment, making these individuals eligible for future intelligent clinical trial designs. ANN NEUROL 2024.

Beyond Usability: A Critical Analysis of Interface Research

This article addresses the profound and multifaceted understanding of interfaces in the modern technological era, focusing on integrating ontological, ethical, and aesthetical approaches in interface research. It considers various aspects of human-machine interaction from philosophical, ethical, and aesthetic viewpoints, revealing the complex connections between technological progress and human experience. This study provides a comprehensive analysis of contemporary approaches to interface research, covering its complexity and diversity, as well as identifying current trends and challenges in the field. The findings indicate that successful interface study requires an integrated approach, including the analysis of functional, ethical, aesthetic, and cultural aspects. The article highlights the importance of cross-disciplinary research in developing interfaces that can reflect and develop contemporary cultural and social contexts. The conclusions of this article are relevant to the researchers in the field of interface design, implementators, and a broad audience interested in understanding the interplay between technological innovations and the socio-cultural context.

IMPROVEMENT OF CAPILLAROSCOPY METHOD FOR STUDYING HUMAN MICROCIRCULATION

The human circulatory system has historically captivated researchers in the field of medicine. Modern medicine, however, has moved beyond identifying a single crucial element, such as the heart or venous system, for maintaining blood flow. Instead, it emphasizes a more analytical approach, focusing on the interconnected functioning of all components within the system. The aim of this work is to analyze the existing methods of studying blood microcirculation and to improve the technology of capillaroscopy, technical means of raster microphotography to determine the physiological state and disorders of capillary circulation. To achieve this objective, we address the following tasks: analyzing existing non-invasive methods for studying the human vascular system; enhancing the optical capillaroscopy method through the utilization of modern high-resolution digital cameras, computer, and multimedia equipment, along with appropriate software for analyzing electronic images; developing a technological scheme and equipment design for digital microphotography of capillaries in the periungual region of the upper extremities; providing software solutions for registering and analyzing digital microphotographic images obtained through capillaroscopy; conducting experimental studies to explore the structure and properties of capillaries utilizing the developed technologies and equipment. Magnetic resonance imaging (MRI) enables the comprehensive evaluation of both anatomical and functional aspects of blood flow. Magnetic resonance angiography (MRA) capitalizes on the distinction between the signal emitted by moving tissue (blood) and that of surrounding stationary tissue, facilitating the acquisition of vascular images without the need for radiopaque contrast agents. Ultrasonography integrates Doppler and conventional ultrasound techniques, providing physicians with insights into blood vessel structure and blood flow dynamics. Traditional ultrasound employs sound waves that are imperceptible to the human ear and bounce off blood vessels, while Doppler ultrasound measures the velocity of sound wave reflection from moving elements. Ophthalmoscopy constitutes a fundamental component of standard ophthalmological examinations, serving as a pivotal tool for diagnosing eye conditions and evaluating the condition of blood vessels. Additionally, ophthalmoscopy aids in diagnosing autoimmune disorders. Capillaroscopy enables comprehensive assessments of both systemic and regional microcirculation disorders, facilitating the characterization of tissue metabolism. Dysfunction in capillary function contributes to circulatory impairments, leading to blood stasis, metabolic irregularities, and compromised immunity, thereby exacerbating existing conditions and predisposing individuals to new diseases. Optical computerized capillaroscopy offers a non-invasive means of visualizing, examining, and archiving capillary images, enabling clinicians to make informed assessments regarding blood microcirculation. Experimental validation of the optimized hardware and software capillaroscopy system was conducted using nail bed capillaries of a patient with type II diabetes mellitus undergoing insulin therapy for 10 years. This study underscores the importance of refining and enhancing optical capillaroscopy methodologies by leveraging high-resolution camera sensors and modern computational tools for image processing.

Methods for investigating STAT3 regulation of lysosomal function in mammary epithelial cells

The transcription factor STAT3 is activated by multiple cytokines and other extrinsic factors. It plays a key role in immune and inflammatory responses and, when dysregulated, in tumourigenesis. STAT3 is also an indispensable mediator of the cell death process that occurs during post-lactational regression of the mammary gland, one of the most dramatic examples of physiological cell death in adult mammals. During this involution of the gland, STAT3 powerfully enhances the lysosomal system to efficiently remove superfluous milk-producing mammary epithelial cells via a lysosomal-mediated programmed cell death pathway. The lysosome is a membrane-enclosed cytoplasmic organelle that digests and recycles cellular waste, with an important role as a signalling centre that monitors cellular metabolism. Here, we describe key strategies for investigating the role of STAT3 in regulating lysosomal function using a mammary epithelial cell culture model system. These include protocols for lysosome enrichment and enzyme activity assays, in addition to microscopic analyses of the vesicular compartment in cell lines. Collectively, these approaches provide the tools to investigate multiple aspects of lysosome biogenesis and function, and to define both direct and indirect roles for STAT3.