Specific Functions Research Articles

Age-appropriate design of domestic intelligent medical products: An example of smart blood glucose detector for the elderly with AHP-QFD Joint KE

BackgroundIn response to the rise of intelligent products and the increasing prevalence of urban "empty nesters," we have developed a product specifically tailored for elderly diabetic patients. This product fulfils functional requirements and addresses stylistic preferences, contributing to the age-friendly evolution of home intelligent medical devices, particularly in intelligent blood glucose monitoring. MethodsOur approach commenced with a comprehensive user experience analysis to ascertain the needs of elderly users regarding home blood glucose meters. This involved constructing a hierarchy of user demands, followed by analysing and prioritising these needs. Utilizing Quality Function Deployment (QFD), we aligned user requirements with design specifications, identifying specific product functionalities and service design elements. Further, we employed Kansei Engineering (KE) to select sample designs that resonate with the concept of sensual imagery, leading to the derivation of specific modelling intentions. Combining these design elements, we proposed product design strategies and conducted practical case studies. The effectiveness of these designs was then assessed through fuzzy evaluation methods, allowing for user feedback. ResultsEmploying the Analytic Hierarchy Process for goal analysis, along with Quality Function Deployment theory and Kansei Engineering, we developed a home intelligent blood glucose meter catered to the elderly. This device not only meets its users' physiological and psychological needs but also provides an operationally convenient, health-conscious, and aesthetically pleasing experience. ConclusionsThis methodology enhances the age-appropriate design of home-based smart glucose monitors for the elderly, offering innovative insights and optimization strategies for designing elderly-centric smart medical products.

Enhancer of zeste homolog 2 (EZH2)-dependent sirtuin-3 determines sensitivity to glucose starvation in radioresistant head and neck cancer cells

Sirtuin 3 (SIRT3) regulates mitochondrial function as a mitochondrial deacetylase during oxidative stress. However, the specific regulatory mechanism and function of SIRT3 in radioresistant cancer cells are unclear. In this study, we aim to investigate how SIRT3 determines the susceptibility to glucose deprivation and its regulation in p53-based radioresistant head and neck cancer cells. We observed mitochondrial function using two established isogenic radioresistant subclones (HN3R-A [p53 null] and HN3R-B [p53 R282W]) with intratumoral p53 heterogeneity. Cell counting analysis was performed to evaluate cell proliferation and cell death. The correlation between the regulation of SIRT3 and enhancer of zeste homolog 2 (EZH2) was confirmed by immunoblotting and chromatin immunoprecipitation assay. p53-deficient radioresistant cells (HN3R-A) expression reduced SIRT3 levels and increased sensitivity to glucose deprivation due to mitochondrial dysfunction compared to other cells. In these cells, activation of SIRT3 significantly prevented glucose deprivation-induced cell death, whereas the loss of SIRT3 increased the susceptibility to glucose deficiency. We discovered that radiation-induced EZH2 directly binds to the SIRT3 promoter and represses the expression. Conversely, inhibiting EZH2 increased the expression of SIRT3 through epigenetic changes. Our findings indicate that p53-deficient radioresistant cells with enhanced EZH2 exhibit increased sensitivity to glucose deprivation due to SIRT3 suppression. The regulation of SIRT3 by EZH2 plays a critical role in determining the cell response to glucose deficiency in radioresistant cancer cells. Therefore, EZH2-dependent SIRT3 could be used as a predictive biomarker to select treatment options for patients with radiation-resistance.

Multifunctional scaffolds for biomedical applications: Crafting versatile solutions with polycaprolactone enriched by graphene oxide.

The pressing need for multifunctional materials in medical settings encompasses a wide array of scenarios, necessitating specific tissue functionalities. A critical challenge is the occurrence of biofouling, particularly by contamination in surgical environments, a common cause of scaffolds impairment. Beyond the imperative to avoid infections, it is also essential to integrate scaffolds with living cells to allow for tissue regeneration, mediated by cell attachment. Here, we focus on the development of a versatile material for medical applications, driven by the diverse time-definite events after scaffold implantation. We investigate the potential of incorporating graphene oxide (GO) into polycaprolactone (PCL) and create a composite for 3D printing a scaffold with time-controlled antibacterial and anti-adhesive growth properties. Indeed, the as-produced PCL-GO scaffold displays a local hydrophobic effect, which is translated into a limitation of biological entities-attachment, including a diminished adhesion of bacteriophages and a reduction of E. coli and S. aureus adhesion of ∼81% and ∼69%, respectively. Moreover, the ability to 3D print PCL-GO scaffolds with different heights enables control over cell distribution and attachment, a feature that can be also exploited for cellular confinement, i.e., for microfluidics or wound healing applications. With time, the surface wettability increases, and the scaffold can be populated by cells. Finally, the presence of GO allows for the use of infrared light for the sterilization of scaffolds and the disruption of any bacteria cell that might adhere to the more hydrophilic surface. Overall, our results showcase the potential of PCL-GO as a versatile material for medical applications.

On the uniqueness of a solution to the multiplicative control problem for the electron drift–diffusion model

The multiplicative control problem for a stationary diffusion-drift model of charging a polar dielectric is studied. The role of control is played by a leading coefficient in the model equation, which has the meaning of the electron diffusion coefficient. The global solvability of the boundary value problem and the local uniqueness of its solution, as well as the solvability of the extremum problem under consideration, have been proved in the previous papers of the authors. In this paper, an optimality system is derived for the control problem and local regularity conditions for the Lagrange multiplier are established. Based on the analysis of this system, the local uniqueness of the multiplicative control problem's solution for specific cost functionals is proved.

Non-Muscle Myosin IIC as a Prognostic and Therapeutic Target in Cancer

Cancer metastasis is associated with epithelial-mesenchymal transition (EMT), and NMII is linked to EMT. Calcium sensitization through ROCK activates myosin II, contributing to metastasis. NMII undergoes phosphorylation at Thr18/Ser19, affecting its function and involvement in processes like exocytosis, apoptosis, and transcellular intravasations. Inhibition of myosin II ATPase activity blocks cytokinesis, highlighting its role in cell cycle regulation. NMII has distinct binding motifs and sites for regulation, including Thr18/Ser19 via kinases/phosphatases, Ser1/Ser2/Thr9 via phosphokinase C, and involvement in cytokinesis via contractile ring formation. These characteristics make NMII a potential therapeutic target. NMII-C is found to be less expressive in glioma (40% low expression, 60% high expression), not showing prognostic value. However, in stomach cancer (35–65% expression) and renal cancer (40–60% expression), NMII-C appears to have prognostic significance. NMII-C’s prognostic value has not been reported in various other cancers, including thyroid, lung, liver, colorectal, urothelial, endometrial, head and neck, melanoma, prostate, testicular, pancreatic, breast, cervical, and ovarian cancers, highlighting a need for further research in these areas. Some pharmacological agents such as Blebbistatin, DT-13, Statins, and Y27632 have shown promising potential against NMII-C in cancer therapy, with positive results in pre-clinical studies and ongoing clinical trials. Understanding the specific functions and regulation of NMII isoforms, particularly NMII-C, may provide valuable insights into the development of targeted cancer therapies. Additionally, the study suggests that NMII-C may have prognostic importance in specific cancer stages, offering a foundation for further exploration of NMII-C’s mechanisms of action for future medical interventions.

The Use of Lexical Bundles in English Language Academic Writing among University Learners: A Systematic Literature Review

Lexical bundles have been widely studied in English academic writing, but not as extensive in university learners’ academic writing. This study conducted a systematic review of the literature on lexical bundles in academic writing among university learners from 2017 to 2022 to describe the directions of and limitations of recent studies on how lexical bundles influence the fluency and coherence of academic writing among university learners. The review relied on two major databases, Scopus and Web of Science, and adhered to the PRISMA 2020 guidelines. The study analyzed 28 articles them based on three content-based themes: the research context, the research contents, and the research objectives. Recent research on lexical bundles in academic writing among university students 1) lacks an in-depth analysis of specific functions, such as text-oriented bundles, which predominate and play an important coherence role in more advanced academic writing; 2) addressing the analysis of lexical bundles solely through a phraseological lens fails to account for their genre-specific characteristics. It is crucial to merge insights from both genre and phraseology for a thorough analysis; 3) comparing the academic writing of native English-speaking learners, that of university learners in East Asia and the Middle East are unevenly distributed and limited in scope. There is limited research on academic writing at higher academic levels, university learners in Southeast Asia, and cross-regional comparative studies.

Multifunctional metalens optical tweezers for optical information recognition.

Traditional optical information recognition (OIR), particle capture and manipulation require many optical devices or mechanical moving system components to achieve a specific function, which is difficult to achieve integration. This paper proposes a new method to realize these functions by using multi-focus metalens combining spectrum and polarization selection. The design incorporates three spectral bands, namely 500 nm, 580 nm, and 660 nm, within the visible light range. Additionally, it utilizes either left-handed or right-handed circularly polarized (LCP/RCP) light, resulting in six distinct focus focusing effects on a single focal plane. By analyzing the normalized light intensity (NLI) at the corresponding focus position, the OIR of any wavelength and polarization detection in the design can be realized, and the particle capture at different focusing positions can be realized. Our work can provide a new idea for the high integration of on-chip light recognition and operation and inspire the design of a highly integrated optical system with a smaller size and more substantial function.

Efficacy of a Rehabilitation Program Using Mirror Therapy and Cognitive Therapeutic Exercise on Upper Limb Functionality in Patients with Acute Stroke.

Applying evidence-based therapies in stroke rehabilitation plays a crucial role in this process, as they are supported by studies and results that demonstrate their effectiveness in improving functionality, such as mirror therapy (MT), cognitive therapeutic exercise (CTE), and task-oriented training. The aim of this study was to assess the effectiveness of MT and CTE combined with task-oriented training on the functionality, sensitivity, range, and pain of the affected upper limb in patients with acute stroke. A longitudinal multicenter study recruited a sample of 120 patients with acute stroke randomly and consecutively, meeting specific inclusion and exclusion criteria. They were randomly allocated into three groups: a control group only for task-oriented training (TOT) and two groups undergoing either MT or CTE, both combined with TOT. The overall functionality of the affected upper limb, specific functionality, sensitivity, range of motion, and pain were assessed using the Fugl-Meyer Assessment Upper Extremity (FMA-UE) scale validated for the Spanish population. An initial assessment was conducted before the intervention, a second assessment after completing the 20 sessions, and another three months later. ANCOVA analysis revealed statistically significant differences between the assessments and the experimental groups compared to the control group, indicating significant improvement in the overall functionality of the upper limb in these patients. However, no significant differences were observed between the two experimental groups. The conclusion drawn was that both therapeutic techniques are equally effective in treating functionality, sensitivity, range of motion, and pain in the upper limb following a stroke.

Pragmatic Skills in Late Adulthood.

Research investigating pragmatic abilities in healthy aging suggests that both production and comprehension might be compromised; however, it is not clear how pragmatic abilities evolve in late adulthood, as well as when difficulties are more likely to arise. The aim of this study is to investigate the decline of pragmatic skills in aging, and to explore what cognitive and demographic factors support pragmatic competence. We assessed pragmatic production skills, including discourse abilities such as speech, informativeness, information flow, paralinguistic aspects, as well as the ability to produce informative descriptions of pictures, and pragmatic comprehension skills, which encompassed the ability to understand discourse and the main aspects of a narrative text, to infer non-literal meanings and to comprehend verbal humor in a group of elderly individuals and in a sample of younger participants. Moreover, specific cognitive functions (short-term memory, verbal and visuospatial working memory, inhibition Theory of Mind, and Cognitive Reserve) were assessed in both groups. Pragmatic difficulties seem to occur in late adulthood, likely around 70years, and emerge more prominently when participants are asked to understand verbal humor. Age was the only predictor of general pragmatic performance in a sample of cognitively unimpaired older adults; conversely, when elderly individuals with less intact inhibitory control are considered, a general role of inhibition emerged, in addition to working memory and ToM in specific tasks.

Tetrandrine alleviates inflammation and promotes macrophage M2 polarization in gouty arthritis by NF-κB-mediated Lcp1.

Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate (MSU) crystals into joints. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from the root of Stephania tetrandra and can exert an anti-inflammatory function in different diseases. Nevertheless, the specific function of TET in GA remains unclear. We established the GA mouse model by MSU injection into joints of mice. Paw volume and gait score were detected for measuring the degree of joint swelling and the situation of joint dysfunction. Western blot were utilized to test the alterations of M1-related factors (IL-6, IL-1β, TNF-α, IL-12, and iNOS) and M2-related factors (Mgl1, Mgl2, Pgc1-β, Arg-1, and IL-10). The activity of NF-κB p65 in tissues was determined. The interaction of NF-κB p65 and Lcp1 was measured by ChIP and luciferase reporter assay. Lcp1 KO mice were utilized to detect the effect of Lcp1 depletion on GA process. TET treatment markedly suppressed MSU-induced joint swelling, joint dysfunction, and joint injury in GA mice. TET can also reduce inflammatory reactions in MUS-induced mice. Furthermore, we proved that TET facilitated M2 macrophage polarization and inhibited M1 macrophage polarization in GA mice. In addition, TET was found to inhibit NF-κB activity and NF-κB-mediated Lcp1 expression. Lcp1 knockdown can improve joint injury and promote M2 macrophage polarization in GA mice, while this effect was further enhanced by TET. TET alleviates inflammation and facilitates macrophage M2 polarization in GA by NF-κB-mediated Lcp1.

Securing Supply Chains in Open Source Ecosystems: Methodologies for Determining Version Numbers of Components Without Package Management Files

In the case of supply chain security detection research, determining the component version number is a crucial task for the open source components of package-free management files. This paper aims to explore the new perspective of the determination of component version numbers based on various methods and to propose an effective method. First, by analyzing the source code of the component, you can try to determine the version number of the component by a specific mode, function, or variable in the code. This approach requires in-depth study and analysis of the source code to extract key code snippets that may contain version information. Second, the submission history of the component can be used to track the change of the version number. The modification content and update information for each version is obtained by viewing the submission records of the components in the version control system. Such an approach is relatively feasible for those components with a canonical versioning history. In addition, the metadata or metadata information of the component can be used to determine the version number. Some open-source components may contain version-related information in their code or documentation, such as release date, release instructions, version labels, etc. By parsing and extraction of these metadata, the version number of the components is obtained. In addition, the version number of the component can be obtained through communication with the community or the developer. Participate in the relevant open source community or contact component developers to consult them for information about the component version. This approach may require more time and resources, but is a viable option for those components that are difficult to determine the version number through other means. To sum up, the determination of the version number of open source components without package management files is an important link in supply chain security detection.

The Influence of the Chemical Composition of Flax and Hemp Fibers on the Value of Surface Free Energy.

The article presents the exploration of flax and hemp fibers' surface free energy depending on the chemical composition of the fiber, which is closely related to the plant variety and the method of extracting the fiber. For this purpose, tests of the surface free energy (SFE), evaluation of the percentage content of individual fiber components and FTIR analyses were conducted. The research was carried out with the use of fibrous materials prepared in three different ways: 1. To analyze the effect of subsequent stages of flax fibers refining process on chemical composition and SFE, 2. to explore the dependence of fiber SFE on hemp variety, the water-retting hemp fibers were used, 3. To evaluate the influence of the retting method of hemp fibers BIAŁOBRZESKIE variety on SFE, the fibers extracted with the use of dew and water retting were used as the research material. The study confirmed that the content of individual components in the fiber influenced its sorption capacity and therefore determined its hydrophilic properties. The values of Pearson's linear correlation coefficients determined in the statistical analysis proved that the surface free energy was strongly correlated with the content of individual components in the fibers. Understanding the wettability characteristics of bast fibers will allow modeling the properties of products made of these fibers and designing surface modification processes in order to obtain specific functionality of textile products, depending on their intended utilization.

LncRNA Gm15232 Promotes Lipogenesis in Aging Mice Through the miR-192-3p/GCR Pathway.

Recent scientific studies have highlighted the importance of long-chain noncoding RNAs (lncRNAs) in a variety of metabolic diseases, but the specific functions and mechanisms of lncRNAs in aberrant lipid synthesis associated with aging are unknown. In this work, we inspected the effects of lncRNAs on the lipid metabolism in aging mice, as substantial evidence suggests that aging disturbs lipid metabolism. The results revealed that the expression of lncRNA Gm15232 was significantly elevated in the epididymal white adipose tissue of aging mice compared to adult mice. This upregulation of Gm15232 functioned as a competitive endogenous RNA by inhibiting the expression of miR-192-3p, and the ensuing downregulation of miR-192-3p increased the expression of the glucocorticoid receptor gene, which ultimately stimulated fat synthesis. The upregulation of Gm15232 thus increased lipogenesis through this mechanism. This study reveals a potential target for the treatment of age-related abnormalities of lipid metabolism.

Competition of Memories? The Memory of the Łódź/Litzmannstadt Ghetto in Contemporary Museums in Łódź

Abstract There is no individual museum dedicated to the Łódź Ghetto in which 200,000 Jews were confined. However, there are institutions actively working to preserve the memory of the Jewish community in Łódź. This article focuses on two recently established museums in the city: the Radegast Station, founded in 2009, and the Museum of Polish Children, established in 2021. The aim is to analyze the mechanisms that led to the creation of these historical museums and explore their specific functions. I am interested not only in how these institutions shape and present the Jewish heritage, but also in the conceptualisation of the social role of these institutions and the analysis of their presence in the public space. To achieve this, I examine local micro-interactions within the current framework of Poland’s politics of history. Given that nationalism is the predominant ideology of modernity, my text demonstrates how nationalist discourses impact the commemoration of the Łódź/Litzmannstadt Ghetto and influence the remembrance of Second World War.

When Data Are Lacking: Physics-Based Inverse Design of Biopolymers Interacting with Complex, Fluid Phases.

Biomolecular research traditionally revolves around comprehending the mechanisms through which peptides or proteins facilitate specific functions, often driven by their relevance to clinical ailments. This conventional approach assumes that unraveling mechanisms is a prerequisite for wielding control over functionality, which stands as the ultimate research goal. However, an alternative perspective emerges from physics-based inverse design, shifting the focus from mechanisms to the direct acquisition of functional control strategies. By embracing this methodology, we can uncover solutions that might not have direct parallels in natural systems, yet yield crucial insights into the isolated molecular elements dictating functionality. This provides a distinctive comprehension of the underlying mechanisms.In this context, we elucidate how physics-based inverse design, facilitated by evolutionary algorithms and coarse-grained molecular simulations, charts a promising course for innovating the reverse engineering of biopolymers interacting with intricate fluid phases such as lipid membranes and liquid protein phases. We introduce evolutionary molecular dynamics (Evo-MD) simulations, an approach that merges evolutionary algorithms with the Martini coarse-grained force field. This method directs the evolutionary process from random amino acid sequences toward peptides interacting with complex fluid phases such as biological lipid membranes, offering significant promises in the development of peptide-based sensors and drugs. This approach can be tailored to recognize or selectively target specific attributes such as membrane curvature, lipid composition, membrane phase (e.g., lipid rafts), and protein fluid phases. Although the resulting optimal solutions may not perfectly align with biological norms, physics-based inverse design excels at isolating relevant physicochemical principles and thermodynamic driving forces governing optimal biopolymer interaction within complex fluidic environments. In addition, we expound upon how physics-based evolution using the Evo-MD approach can be harnessed to extract the evolutionary optimization fingerprints of protein-lipid interactions from native proteins. Finally, we outline how such an approach is uniquely able to generate strategic training data for predictive neural network models that cover the whole relevant physicochemical domain. Exploring challenges, we address key considerations such as choosing a fitting fitness function to delineate the desired functionality. Additionally, we scrutinize assumptions tied to system setup, the targeted protein structure, and limitations posed by the utilized (coarse-grained) force fields and explore potential strategies for guiding evolution with limited experimental data. This discourse encapsulates the potential and remaining obstacles of physics-based inverse design, paving the way for an exciting frontier in biomolecular research.

Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. Consequently, a complex interplay among epidermal cells, immune cells, and sensory neurons contributes to the development and progression of psoriasis. In these cellular contexts, various ion channels, such as acetylcholine receptors, TRP channels, Ca2+ release-activated channels, chloride channels, and potassium channels, each serve specific functions to maintain the homeostasis of the skin. The dysregulation of ion channels plays a major role in the pathophysiology of psoriasis, affecting various aspects of epidermal cells, immune responses, and sensory neuron signaling. Impaired function of ion channels can lead to altered calcium signaling, inflammation, proliferation, and sensory signaling, all of which are central features of psoriasis. This overview summarizes the pathophysiological roles of ion channels in epidermal cells, immune cells, and sensory neurons during early and late psoriatic processes, thereby contributing to a deeper understanding of ion channel involvement in the interplay of psoriasis and making a crucial advance toward more precise and personalized approaches for psoriasis treatment.

Cancer cells employ lipid droplets to survive toxic stress.

Lipid reprogramming is a known mechanism to increase the energetic demands of proliferating cancer cells to drive and support tumorigenesis and progression. Elevated lipid droplets (LDs) are a well-known alteration of lipid reprogramming in many cancers, including prostate cancer (PCa), and are associated with high tumor aggressiveness as well as therapy resistance. The mechanism of LD accumulation and specific LD functions are still not well understood; however, it has been shown that LDs can form as a protective mechanism against lipotoxicity and lipid peroxidation in the cell. This study investigated the significance of LDs in PCa. This was done by staining, imaging, image quantification, and flow cytometry analysis of LDs in PCa cells. Additionally, lipidomics and metabolomics experiments were performed to assess the difference of metabolites and lipids in control and treatment surviving cancer cells. Lastly, to assess clinical significance, multiple publicly available datasets were mined for LD-related data. Our study demonstrated that prostate and breast cancer cells that survive 72 h of chemotherapy treatment have elevated LDs. These LDs formed in tandem with elevated reactive oxygen species levels to sequester damaged and excess lipids created by oxidative stress, which promoted cell survival. Additionally, by inhibiting diacylglycerol O-acyltransferase 1 (DGAT1) (which catalyzes triglyceride synthesis into LDs) and treating with chemotherapy simultaneously, we were able to decrease the overall amount of LDs and increase cancer cell death compared to treating with chemotherapy alone. Overall, our study proposes a potential combination therapy of DGAT1 inhibitors and chemotherapy to increase cancer cell death.

CHL1 inhibits cell proliferation, migration and invasion by regulating the NF‑κB signaling pathway in colorectal cancer.

Cell adhesion molecule close homolog of L1 (CHL1) is implicated in tumorigenesis of various malignancies. However, its role and underlying molecular mechanisms in colorectal cancer (CRC) remain unclear. The present study aimed to evaluate the specific biological functions and mechanisms of CHL1, in order to provide a theoretical basis for the use of CHL1 as a biological target in CRC. CHL1 expression was originally determined in CRC cell lines. Subsequently, CHL1 overexpression was induced by plasmid transfection in HT29 and SW480 cells, and cell proliferation, migration and invasion were evaluated using the Cell Counting Kit-8, clone formation, organoids formation and Transwell assays. Immunofluorescence and western blotting were performed to assess the protein expression of E-cadherin or N-cadherin. Differentially expressed genes (DEGs) were further evaluated using RNA-sequencing (RNA-seq) in HT29 and SW480 cells following CHL1 overexpression and functional enrichment analysis. Western blotting was performed to validate the expression of proteins related to the nuclear factor κB (NF-κB) signaling pathway. The TNMplot online database revealed the significant downregulation of CHL1 in CRC tissues. The results indicated that exogenous CHL1 overexpression significantly inhibited the proliferative, organoid-forming, migratory and invasive abilities of HT29 and SW480 cells, and increased E-cadherin protein expression. Additionally, CHL1 overexpression reduced xenograft tumor growth in vivo. RNA-seq and functional analysis revealed that DEGs in CHL1 overexpressing cells were mainly enriched in the NF-κB signaling pathway. The expression of p-p65 and p-p65/p65 ratio were significantly reduced in HT29 and SW480 cells, following CHL1 overexpression. Additionally, the inhibitory effects of CHL1 overexpression on CRC cell proliferation, organoid formation, migration and invasion were partially counteracted following the overexpression of p65 expression. Overall, the present study demonstrates that CHL1 inhibits CRC cell growth, migration and invasion through the inactivation of the NF-κB signaling pathway.

Loss of function in somatostatin receptor 5 has no impact on the growth of medaka fish due to compensation by the other paralogs

Somatic growth in vertebrates is regulated endocrinologically by the somatotropic axis, headed by the growth hormone (GH) and the insulin growth factor-I (IGF-I). Somatostatin (Sst), a peptide hormone synthesized in the hypothalamus, modulates GH actions through its receptors (Sstr). Four Sstr subtypes (Sstr 1–3 and 5) have been identified in teleosts. However, little is known about whether they have a specific function or tissue expression. The aim of this study was to determine the role of sstr2 and sstr5 in the growth of the medaka (Oryzias latipes). The assessed expression pattern across diverse tissues highlighted greater prevalence of sstr1 and sstr3 in brain, intestine and muscle than in pituitary or liver. The expression of sstr2 was high in all the tissues tested, while sstr5 was predominantly expressed in the pituitary gland. A CRISPR/Cas9 sstr5 mutant with loss of function (sstr5-/-) was produced. Assessment of sstr5-/- indicated no significant difference with the wild type regarding growth parameters such as standard length, body depth, or peduncle depth. Furthermore, the functional loss of sstr5 had no impact on the response to a nutritional challenge. The fact that several sstr subtypes were upregulated in different tissues in sstr5-/- medaka suggests that in the mutant fish, there may be a compensatory effect on the different tissues, predominantly by sstr1 in the liver, brain and pituitary, with sstr2 being upregulated in pituitary and liver, and sstr3 only presenting differential expression in the brain. Analysis of the sstr subtype and the sstr5-/- fish showed that sstr5 was not the only somatostatin receptor responsible for Sst-mediated Gh regulation.

Lamin A/C and PI(4,5)P2-A Novel Complex in the Cell Nucleus.

Lamins, the nuclear intermediate filaments, are important regulators of nuclear structural integrity as well as nuclear functional processes such as DNA transcription, replication and repair, and epigenetic regulations. A portion of phosphorylated lamin A/C localizes to the nuclear interior in interphase, forming a lamin A/C pool with specific properties and distinct functions. Nucleoplasmic lamin A/C molecular functions are mainly dependent on its binding partners; therefore, revealing new interactions could give us new clues on the lamin A/C mechanism of action. In the present study, we show that lamin A/C interacts with nuclear phosphoinositides (PIPs), and with nuclear myosin I (NM1). Both NM1 and nuclear PIPs have been previously reported as important regulators of gene expression and DNA damage/repair. Furthermore, phosphorylated lamin A/C forms a complex with NM1 in a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent manner in the nuclear interior. Taken together, our study reveals a previously unidentified interaction between phosphorylated lamin A/C, NM1, and PI(4,5)P2 and suggests new possible ways of nucleoplasmic lamin A/C regulation, function, and importance for the formation of functional nuclear microdomains.