Polyamine metabolism is a central determinant of helper T cell lineage fidelity.

Polyamine synthesis represents one of the most profound metabolic changes during T cell activation, but the biological implications of this are scarcely known. Here, we show that polyamine metabolism is a fundamental process governing the ability of CD4+ helper T cells (TH) to polarize into different functional fates. Deficiency in ornithine decarboxylase, a crucial enzyme for polyamine synthesis, results in a severe failure of CD4+ T cells to adopt correct subset specification, underscored by ectopic expression of multiple cytokines and lineage-defining transcription factors across TH cell subsets. Polyamines control TH differentiation by providing substrates for deoxyhypusine synthase, which synthesizes the amino acid hypusine, and mice in which T cells are deficient for hypusine develop severe intestinal inflammatory disease. Polyamine-hypusine deficiency caused widespread epigenetic remodeling driven by alterations in histone acetylation and a re-wired tricarboxylic acid (TCA) cycle. Thus, polyamine metabolism is critical for maintaining the epigenome to focus TH cell subset fidelity.

Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection.

Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4+ T cells during mouse in vivo influenza infection. Conditional ablation of Arg1 in CD4+ T cells accelerated both virus-specific T helper 1 (Th1) effector responses and its resolution, resulting in efficient viral clearance and reduced lung pathology. Using unbiased transcriptomics and metabolomics, we found that Arg1-deficiency was distinct from Arg2-deficiency and caused altered glutamine metabolism. Rebalancing this perturbed glutamine flux normalized the cellular Th1 response. CD4+ T cells from rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion in healthy donor cells phenocopied the murine cellular phenotype. Collectively, CD4+ T cell-intrinsic Arg1 functions as an unexpected rheostat regulating the kinetics of the mammalian Th1 lifecycle with implications for Th1-associated tissue pathologies.

Female terminalia morphology and cladistic relations among Tok-Tok beetles (Tenebrionidae: Sepidiini).

Tok-tokkies are one of the most iconic lineages within Tenebrionidae. In addition to containing some of the largest darkling beetles, this tribe is recognized for its remarkable form of sexual communication known as substrate tapping. Nevertheless, the phylogenetic relationships within the group remain poorly understood. This study investigates the usefulness of female terminalia morphology for delimiting Sepidiini and reconstructing relationships among it. Data on the structure of the ovipositors, genital tubes and spicula ventrali have been generated for >200 species representing 28 Pimeliinae tribes. This dataset was used in a comparative analysis at the subfamilial level, which resulted in recognition of several unique features of tok-tokkie terminalia. Additionally, new features linking phenotypically challenging tribes also were recovered (Cryptochilini + Idisiini + Pimeliini). Secondly, 23 characters linked to the structure of female terminalia were defined for tok-tok beetles. Cladistic analysis demonstrates the nonmonophyletic nature of most of the recognized subtribes. The morphological dataset was analysed separately and in combination with available molecular data (CAD, Wg, cox1, cox2, 28S). All obtained topologies were largely congruent, supporting the following changes: Palpomodina Kaminski & Gearner subtr.n. is erected to accommodate the genera Namibomodes and Palpomodes; Argenticrinis and Bombocnodulus are transferred from Hypomelina to Molurina; 153 species and subspecies previously classified within Psammodes are distributed over three separate genera (Mariazofia Kaminski nom.n., Piesomera stat.r., Psammodes sens.n.). Psammodes sklodowskae Kaminski & Gearner sp.n. is described. Preliminary investigation of the ovipositor of Mariazofia basuto (Koch) comb.n. was carried out with the application of microcomputed tomography, illuminating the muscular system as a reliable reference point for recognizing homologous elements in highly modified ovipositors.

Metabolic maintenance of cell asymmetry following division in activated T lymphocytes.

Asymmetric cell division, the partitioning of cellular components in response to polarizing cues during mitosis, has roles in differentiation and development. It is important for the self-renewal of fertilized zygotes in Caenorhabditis elegans and neuroblasts in Drosophila, and in the development of mammalian nervous and digestive systems. T lymphocytes, upon activation by antigen-presenting cells (APCs), can undergo asymmetric cell division, wherein the daughter cell proximal to the APC is more likely to differentiate into an effector-like T cell and the distal daughter is more likely to differentiate into a memory-like T cell. Upon activation and before cell division, expression of the transcription factor c-Myc drives metabolic reprogramming, necessary for the subsequent proliferative burst. Here we find that during the first division of an activated T cell in mice, c-Myc can sort asymmetrically. Asymmetric distribution of amino acid transporters, amino acid content, and activity of mammalian target of rapamycin complex 1 (mTORC1) is correlated with c-Myc expression, and both amino acids and mTORC1 activity sustain the differences in c-Myc expression in one daughter cell compared to the other. Asymmetric c-Myc levels in daughter T cells affect proliferation, metabolism, and differentiation, and these effects are altered by experimental manipulation of mTORC1 activity or c-Myc expression. Therefore, metabolic signalling pathways cooperate with transcription programs to maintain differential cell fates following asymmetric T-cell division.

Metaheuristic Approach to Synthesis of Suspension System of Mobile Robot for Mining Infrastructure Inspection.

The article describes the problem of geometric synthesis of the inspection robot suspension system, designed for operation in difficult conditions with the presence of scattered obstacles. The exemplary application of a mine infrastructure inspection robot is developed and supported by the ideas. The brief introduction presents current trends, requirements and known design approaches of platforms enabled to cross the obstacles. The idea of a nature-inspired wheel-legged robot is given, and the general outline of its characteristics is provided. Then the general idea of kinematic system elements selection is discussed. The main subject of geometrical synthesis of the chosen four-bar mechanism is described in detail. The mathematical model of the suspension and connections between the parts of the structure is clarified. The well-known analytical approach of brute force search is analyzed and validated. Then the method inspired by the branch and bound algorithm is developed. Finally, a novel application of the nature-inspired algorithm (the Chameleon Swarm Algorithm) to synthesis is proposed. The obtained results are analyzed, and a brief comparison of methods is given. The successful implementation of the algorithm is presented. The obtained results are effectively tested with simulations and experimental tests. The designed structure developed with the CSA is assembled and attached to the prototype of a 14-DOF wheel-legged robot. Furthermore, the principles of walking and the elements forming the control structure were also discussed. The paper is summarized with the description of the developed wheel-legged robot LegVan 1v2.

Polarization and asymmetry in T cell metabolism.

T cell activation results in a rapidly proliferating T cell endowed with a metabolic phenotype necessary for growth and division. However, before the cell can proceed towards this burst of cell division a phase of quiescence occurs, during which the basic mechanisms governing regulation of metabolic reprograming are established. This review focuses on key cellular processes controlling early metabolic regulation and how these circuits of metabolic control dictate distinct cellular fates upon the first asymmetric division.

Structural basis for ADP-dependent glucokinase inhibition by 8-bromo-substituted adenosine nucleotide.

In higher eukaryotes, several ATP-utilizing enzymes known as hexokinases activate glucose in the glycolysis pathway by phosphorylation to glucose 6-phosphate. In contrast to canonical hexokinases, which use ATP, ADP-dependent glucokinase (ADPGK) catalyzes noncanonical phosphorylation of glucose to glucose 6-phosphate using ADP as a phosphate donor. Initially discovered in Archaea, the human homolog of ADPGK was described only recently. ADPGK's involvement in modified bioenergetics of activated T cells has been postulated, and elevated ADPGK expression has been reported in various cancer tissues. However, the physiological role of ADPGK is still poorly understood, and effective ADPGK inhibitors still await discovery. Here, we show that 8-bromo-substituted adenosine nucleotide inhibits human ADPGK. By solving the crystal structure of archaeal ADPGK in complex with 8-bromoadenosine phosphate (8-Br-AMP) at 1.81 Å resolution, we identified the mechanism of inhibition. We observed that 8-Br-AMP is a competitive inhibitor of ADPGK and that the bromine substitution induces marked structural changes within the protein's active site by engaging crucial catalytic residues. The results obtained using the Jurkat model of activated human T cells suggest its moderate activity in a cellular setting. We propose that our structural insights provide a critical basis for rational development of novel ADPGK inhibitors.

The tracheal system in post-embryonic development of holometabolous insects: a case study using the mealworm beetle.

The tracheal (respiratory) system is regarded as one of the key elements which enabled insects to conquer terrestrial habitats and, as a result, achieve extreme species diversity. Despite this fact, anatomical data concerning this biological system is relatively scarce, especially in an ontogenetic context. The purpose of this study is to provide novel and reliable information on the post-embryonic development of the tracheal system of holometabolous insects using micro-computed tomography methods. Data concerning the structure of the respiratory system acquired from different developmental stages (larvae, pupae and adults) of a single insect species (Tenebrio molitor) are co-analysed in detail. Anatomy of the tracheal system is presented. Sample sizes used (29 individuals) enabled statistical analysis of the results obtained. The following aspects have been investigated (among others): the spiracle arrangement, the number of tracheal ramifications originating from particular spiracles, the diameter of longitudinal trunks, tracheal system volumes, tracheae diameter distribution and fractal dimension analysis. Based on the data acquired, the modularity of the tracheal system is postulated. Using anatomical and functional factors, the following respiratory module types have been distinguished: cephalo-prothoracic, metathoracic and abdominal. These modules can be unambiguously identified in all of the studied developmental stages. A cephalo-prothoracic module aerates organs located in the head capsule, prothorax and additionally prolegs. It is characterised by relatively thick longitudinal trunks and originates in the first thoracic spiracle pair. Thoracic modules support the flight muscles, wings, elytra, meso- and metalegs. The unique feature of this module is the presence of additional longitudinal connections between the neighbouring spiracles. These modules are concentrated around the second prothoracic and the first abdominal spiracle pairs. An abdominal module is characterised by relatively thin ventral longitudinal trunks. Its main role is to support systems located in the abdomen; however, its long visceral tracheae aerate organs situated medially from the flight muscles. Analysis of changes of the tracheal system volume enabled the calculation of growth scaling among body tissues and the volume of the tracheal system. The data presented show that the development of the body volume and tracheal system is not linear in holometabola due to the occurrence of the pupal stage causing a decrease in body volume in the imago and at the same time influencing high growth rates of the tracheal system during metamorphosis, exceeding that ones observed for hemimetabola.

Chromatographic separation, determination and identification of ecdysteroids: Focus on Maral root (Rhaponticum carthamoides, Leuzea carthamoides).

The review presents general principles for choosing optimal conditions for ecdysteroid separation, identification, and isolation using HPLC/TLC techniques in RP, NP-HILIC or NP modes. Analytics of ecdyteroids pose a still insufficiently resolved problem. Plant-derived ecdysteroids are a point of interest of pharmaceutical industry and sport medicine due to their postulated adaptogenic and anabolic properties. In insects, ecdysteroids regulate larval transformation. Maral root (Rhaponticum carthamoides, Leuzea carthamoides), traditional Siberian folk-medicine plant used as stimulant to boost overall health and fitness, is a particularly rich source of a wide variety of phytoecdysteroids. The similarity of molecular structures of ecdysteroids present in its extracts together with high content of unrelated compounds of similar chromatographic characteristics makes optimization of separation, identification and isolation of ecdysteroids a difficult analytical task. In that respect, two-dimensional separations, two-dimensional separations, 2D HPLC or 2D TLC, could be of use. For identification, the hyphenated techniques are particularly important. Thus, comprehensive overview of MS spectral parameters of ecdysteroids is provided. Described principles could easily be applied for separation of ecdysteroids in extracts from other sources. They are also useful for development of separation procedures for isolation of ecysteroids in preparative-scale applications.

CHA2 DS2 VASc score predicts unsuccessful electrical cardioversion in patients with persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia occurring in 2% of the population. It is known that AF increases morbidity and limits quality of life. The CHA2 DS2 VASc score (congestive heart failure/left ventricular dysfunction, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65-74 and sex category (female)) is widely used to assess thrombotic complications. The CHA2 DS2 VASc score was not used until now in predicting the effectiveness of electrical cardioversion. AIM: To assess the value of CHA2 DS2 VASc score in predicting unsuccessful electrical cardioversion. METHODS: We analysed 258 consecutive patients with persistent AF who underwent electrical cardioversion between January 2012 and April 2016 in a Cardiology University Centre in Poland. RESULTS: Out of 3500 hospitalised patients with AF, 258 (mean age 64 ± 11 years, 64% men) underwent electrical cardioversion. The CHA2 DS2 VASc score in analysed population (258 patients) was 2.5 ± 1.7 (range 0-8), and the HAS-BLED (hypertension, abnormal liver or renal function, stroke, bleeding, labile international normalised ratio, elderly, drugs or alcohol) was 1 ± 0.9 (range 0-4). Electrical cardioversion was unsuccessful in 12%. Factors associated with unsuccessful cardioversion were age (P = 0.0005), history of ischaemic stroke (P = 0.04), male gender (P = 0.01) and CHA2 DS2 VASc score (P = 0.002). The CHA2 DS2 VASc score in patients who had unsuccessful cardioversion was higher compared to patients who had successful cardioversion - 3.5 versus 2.4 (P = 0.001). In the logistic regression model, if the CHA2 DS2 VASc score increases by 1, the odds of unsuccessful cardioversion increase by 39% (odds ratio (OR) 1.39; confidence interval (CI): 1.12-1.71; P = 0.002). The odds of unsuccessful cardioversion are three times higher in patients with a CHA2 DS2 VASc score ≥ 2 than in patients with a CHA2 DS2 VASc score of 0 or 1 (OR 3.06; CI: 1.03-9.09; P = 0.044). CONCLUSION: The CHA2 DS2 VASc score routinely used in thromboembolic risk assessment may be a simple, easy and reliable scoring system that can be used to predict unsuccessful electrical cardioversion.

Differences in Assessment of Suicidal Tendencies in Men and Women: A Pilot Study.

Suicidal behaviors in psychiatric patients are one of the main challenges in current clinical practice. The aim of this study was to investigate the gender differences in suicide risk for psychiatric patients in Poland and the influence of life satisfaction in different stages of life on suicidal tendencies. A descriptive-exploratory approach to inquiry was used for this study. Sixty patients aged 16-67 (45% males and 55% females) answered the demographic-descriptive questionnaire, the Suicide Behaviors Questionnaire-Revised (SBQ-R) and the Cantril Self-Anchoring Striving Scale (CSASS). The results suggest that women turned out to show higher risk of suicidal behavior than men (p<0.001). Moreover, women displayed strong negative correlation between suicide risk and the anticipated life satisfaction in the future (rho=-0.542), while men displayed negative correlation between suicide risk and the pre-illness level of functioning (rho=-0.638). The findings suggest that different therapeutic approaches for each gender should be applied in suicide prevention process.

The Development and the Structure of the Verbal Suicide Scale (VSS) - Measuring Attitudes Toward Suicide in the Group of Patients Hospitalized in the Psychiatric Unit.

AIM: The assessment of suicidal risk is one of the most difficult diagnostic challenges. The aim of present article is to report the process of development and preliminary validation of the Verbal Suicide Scale. MATERIAL AND METHOD: A total of 121 psychiatric inpatients aged 19-67 anonymously completed Verbal Suicide Scale (VSS). The study took place in the Clinic of Psychiatry, Medical University of Warsaw in Mazovia Specialist Health Center in Pruszków, Poland. RESULTS: Factor analysis validated the three factor structure. Cronbach's alpha reliability for each factor was satisfactory: 0.876 for scale 1, 0.700 for scale 2 and 0.710 for scale 3. CONCLUSIONS: VSS is a short instrument for evaluating the attitude toward suicide and can be a useful tool in mental health nursing practice. Further research and analyses are required to refine the theoretical and external reliability of the method.

Review Study on Mechanical Properties of Cellular Materials.

Cellular materials are fundamental elements in civil engineering, known for their porous nature and lightweight composition. However, the complexity of its microstructure and the mechanisms that control its behavior presents ongoing challenges. This comprehensive review aims to confront these uncertainties head-on, delving into the multifaceted field of cellular materials. It highlights the key role played by numerical and mathematical analysis in revealing the mysterious elasticity of these structures. Furthermore, the review covers a range of topics, from the simulation of manufacturing processes to the complex relationships between microstructure and mechanical properties. This review provides a panoramic view of the field by traversing various numerical and mathematical analysis methods. Furthermore, it reveals cutting-edge theoretical frameworks that promise to redefine our understanding of cellular solids. By providing these contemporary insights, this study not only points the way for future research but also illuminates pathways to practical applications in civil and materials engineering.

Relative Entropy Application to Study the Elastoplastic Behavior of S235JR Structural Steel.

The main issue in this work is to study the limit functions necessary for the reliability assessment of structural steel with the use of the relative entropy apparatus. This will be done using a few different mathematical theories relevant to this relative entropy, namely those proposed by Bhattacharyya, Kullback-Leibler, Jeffreys, and Hellinger. Probabilistic analysis in the presence of uncertainty in material characteristics will be delivered using three different numerical strategies-Monte Carlo simulation, the stochastic perturbation method, as well as the semi-analytical approach. All of these methods are based on the weighted least squares method approximations of the structural response functions versus the given uncertainty source, and they allow efficient determination of the first two probabilistic moments of the structural responses including stresses, displacements, and strains. The entire computational implementation will be delivered using the finite element method system ABAQUS and computer algebra program MAPLE, where relative entropies, as well as polynomial response functions, will be determined. This study demonstrates that the relative entropies may be efficiently used in reliability assessment close to the widely engaged first-order reliability method (FORM). The relative entropy concept enables us to study the probabilistic distance of any two distributions, so that structural resistance and extreme effort in elastoplastic behavior need not be restricted to Gaussian distributions.

Pentraxin 3 as a marker of development and severity of stable coronary artery disease.

PURPOSE: Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement. MATERIALS AND METHODS: The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72 â€‹% men). The control group consisted of 40 patients without CAD. RESULTS: The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 â€‹ng/ml for the exclusion of angiographically significant atherosclerotic lesions. CONCLUSIONS: Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis.

Manganese superoxide dismutase: a regulator of T cell activation-induced oxidative signaling and cell death.

Mitochondrial reactive oxygen species (ROS) are indispensible for T cell activation-induced expression of interleukin 2 (IL-2) and CD95 ligand (CD95L, FasL/Apo-1L) genes, and in turn, for CD95L-mediated activation-induced cell death (AICD). Here, we show that manganese superoxide dismutase (MnSOD/SOD2), a major mitochondrial antioxidative enzyme, constitutes an important control switch in the process of activation-induced oxidative signal generation in T cells. Analysis of the kinetics of T cell receptor (TCR)-triggered ROS production revealed a temporal association between higher MnSOD abundance/activity and a shut-down phase of oxidative signal generation. Transient or inducible MnSOD overexpression abrogated T cell activation-triggered mitochondrial ROS production as well as NF-κB- and AP-1-mediated transcription. Consequently, lowered expression of IL-2 and CD95L genes resulted in decreased IL-2 secretion and CD95L-dependent AICD. Moreover, upregulation of the mitochondrial MnSOD level is dependent on oxidation-sensitive transcription and not on the increase of mitochondrial mass. Thus, MnSOD-mediated negative feedback regulation of activation-induced mitochondrial ROS generation exemplifies a process of retrograde mitochondria-to-nucleus communication. Our finding underlines the critical role for MnSOD and mitochondria in the regulation of human T cell activation.

Taxonomy and distribution of the Afrotropical genus Anchophthalmops Koch, 1956 with a key to species (Coleoptera: Tenebrionidae: Pedinini).

The taxonomic and distributional data concerning the representatives of the genus Anchophthalmops were revised. Lectotypes for Anchophthalmopsfoveipennis and A. ventralis were designated to fix the taxonomic status of these species. A. neumanni and A. zablockii were described as new species. Maximum entropy modeling was used to test the probability of occurrence of A. menouxi on Madagascar. An identification key is provided to all known species of Anchophthalmops.

Taxonomy of the genus Kochogaster Kaminski et Ras, 2011 (Coleoptera: Tenebrionidae: Pedinini), with description of a second known species.

A second species of the genus Kochogaster Kaminski et Ras (K. gerardi sp. n.) is described from the surroundings of Garissa (Kenya). The taxonomic concept and phylogenetic relationships of Kochogaster are discussed. A distributional map is presented with complete faunistic data on the genus. Additionally, the original spelling of the name Anchophthalmus inuelleri Schimrosczyk, 2010 is emended to A. muellerae due the rules of the International Code of Zoological Nomenclature.

Probabilistic Relative Entropy in Homogenization of Fibrous Metal Matrix Composites (MMCs).

The main aim of this work is to deliver uncertainty propagation analysis for the homogenization process of fibrous metal matrix composites (MMCs). The homogenization method applied here is based on the comparison of the deformation energy of the Representative Volume Element (RVE) for the original and for the homogenized material. This part is completed with the use of the Finite Element Method (FEM) plane strain analysis delivered in the ABAQUS system. The probabilistic goal is achieved by using the response function method, where computer recovery with a few FEM tests enables approximations of polynomial bases for the RVE displacements, and further-algebraic determination of all necessary uncertainty measures. Expected values, standard deviations, and relative entropies are derived in the symbolic algebra system MAPLE; a few different entropy models have been also contrasted including the most popular Kullback-Leibler measure. These characteristics are used to discuss the influence of the uncertainty propagation in the MMCs' effective material tensor components, but may serve in the reliability assessment by quantification of the distance between extreme responses and the corresponding admissible values.

Taxonomic revision of the genus Phylacastus Fairmaire (Tenebrionidae, Eurynotina): shortfalls of anatomical nomenclature with notes on aedeagal homology.

The genus Phylacastus Fairmaire (Tenebrionidae, Blaptinae, Platynotini, Eurynotina) is revised. Two new species and one new synonymy are presented along with new diagnoses, descriptions, a distribution map, and key to species. The resulting species of Phylacastus are: P.ancoralium sp. nov., P.crypticoides Koch (= P.pretoriensis Koch syn. nov.), P.makskacymirowi sp. nov., P.rhodesianus Koch, and P.striolatus Fairmaire. Lectotypes are designated for the type species, P.striolatus, to fix the taxonomic status of the species and genus. As a result of examination and subsequent description of P.ancoralium sp. nov., a brief review and treatment of aedeagal morphology is presented. The nomenclature ("clavae" versus "laciniae") and phylogenetic occurrence of accessory structures of the paramere-median lobe area within Blaptinae Leach and Adelinina LeConte (Diaperinae, Diaperini) are discussed. New descriptive terminology (i.e., ancora [singular] and ancorae [plural]) is proposed for these aedeagal structures in Blaptinae to clarify their function and resolve past ambiguities. The morphology within representatives of Adelina Dejean, Alphitophagus Stephens, Gnatocerus Thunberg, and Sitophagus Mulsant is also briefly contrasted and outlined.