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Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. Methods: Blood samples from 30 healthy GnRH antagonist treated males were collected at three time points: (1) before GnRH antagonist administration; (2) 3 weeks later, just before testosterone undecanoate injection, and (3) after additional 2 weeks. Subsequently, they were analyzed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardiometabolic parameters, bone mineral density as well as androgen receptor (AR) CAG repeat lengths, were explored. Results: Using receiver operating characteristic analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (12 nmol/l) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD also showed association with AR CAG repeat lengths. Conclusions: We identified potential new protein biomarkers of testosterone action. Further investigations to elucidate their clinical potential are warranted. Funding: The work was supported by ReproUnion2.0 (grant no. 20201846), which is funded by the Interreg V EU program.

Pathogens find diverse niches for survival including inside a host cell where replication occurs in a relatively protective environment. Vibrio parahaemolyticus is a facultative intracellular pathogen that uses its type 3 secretion system 2 (T3SS2) to invade and replicate inside host cells. Analysis of the T3SS2 pathogenicity island encoding the T3SS2 appeared to lack a mechanism for egress of this bacterium from the invaded host cell. Using a combination of molecular tools, we found that VPA0226, a constitutively secreted lipase, is required for escape of V. parahaemolyticus from the host cells. This lipase must be delivered into the host cytoplasm where it preferentially uses fatty acids associated with innate immune response to esterify cholesterol, weakening the plasma membrane and allowing egress of the bacteria. This study reveals the resourcefulness of microbes and the interplay between virulence systems and host cell resources to evolve an ingenious scheme for survival and escape.

Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.

The article presents the principles of shaping material systems of modern building joints in terms of thermal and humidity requirements. An integral part of the work is the calculation of the physical parameters of the connection between the external wall and the window using a computer program. The choice of material solutions for construction joints should be based on calculations and analyzes of their physical parameters. The physical parameters of the connection between the external wall and the window in the cross-section through the lintel depend on the arrangement of the material layers of the joint: e.g. type and thickness of thermal insulation, window location. Improper shaping of the arrangement of material layers results in increased heat losses in the form of heat flux Φ [W] and linear heat transfer coefficient Ψ [W/(m·K)] and a decrease in temperature on the internal surface of the partition at the thermal bridge, which may lead to the risk of the occurrence of condensation on the inner surface of the partition.

IntroductionWhile Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy.MethodsEvaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders.ResultsSix proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort.DiscussionOur study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.

Background: Coronary aneurysms are an infrequent finding in diagnostic angiography, with a reported incidence of 0.35–0.7% in the largest contemporary registries. At least half of them have an atherosclerotic etiology and as such they are often diagnosed in the setting of acute coronary syndrome. The wiring of a thrombosed aneurysm is a difficult task and after successful recanalization, the operator has to decide on the optimal method of aneurysm exclusion. Covered stents are commonly deployed, but their use involves the risk of delivery failure as well as device dislodgement and loss due to their stiffness and size. Moreover, proper stent sizing and apposition is difficult in the case of thrombosed aneurysms. Case presentation: We present a case of coronary aneurysm recanalization and exclusion with a covered stent, with a postdilation-induced stent foreshortening. Due to the subsequent stent migration into the aneurysm sac, its repositioning was attempted. The pitfalls of coronary aneurysm stenting and neurointerventional techniques of prolapsed device realignment are discussed. Conclusions: An adequate landing zone is of the utmost importance in aneurysm exclusion with covered stents. In the case of a short stent anchoring in the normal vessel, another covered or conventional stent should be deployed to mitigate the risk of the device migration.

Abstract PEAK pseudokinases are molecular scaffolds which dimerize to regulate cell migration, morphology, and proliferation, as well as cancer progression. The mechanistic role dimerization plays in PEAK scaffolding remains unclear, as there are no structures of PEAKs in complex with their interactors. Here, we report the cryo-EM structure of dimeric PEAK3 in complex with an endogenous 14-3-3 heterodimer. Our structure reveals an asymmetric binding mode between PEAK3 and 14-3-3 stabilized by one pseudokinase domain and the SHED domain of the PEAK3 dimer. The binding interface contains a canonical phosphosite-dependent primary interaction and a unique secondary interaction not observed in previous structures of 14-3-3/client complexes. Additionally, we show that PKD regulates PEAK3/14-3-3 binding, which when prevented leads to PEAK3 nuclear enrichment and distinct protein-protein interactions. Altogether, our data demonstrate that PEAK3 dimerization forms an unusual secondary interface for 14-3-3 binding, facilitating 14-3-3 regulation of PEAK3 localization and interactome diversity.

Abstract In nervous systems, retrograde signals are key for organizing circuit activity and maintaining neuronal homeostasis. We identify the conserved Allnighter (Aln) pseudokinase as a cell non-autonomous regulator of proteostasis responses necessary for normal sleep and structural plasticity of Drosophila photoreceptors. In aln mutants exposed to extended ambient light, proteostasis is dysregulated and photoreceptors develop striking, but reversible, dysmorphology. The aln gene is widely expressed in different neurons, but not photoreceptors. However, secreted Aln protein is retrogradely endocytosed by photoreceptors. Inhibition of photoreceptor synaptic release reduces Aln levels in lamina neurons, consistent with secreted Aln acting in a feedback loop. In addition, aln mutants exhibit reduced night time sleep, providing a molecular link between dysregulated proteostasis and sleep, two characteristics of ageing and neurodegenerative diseases.

Abstract The pathogenic Legionella bacteria are notorious for delivering numerous effector proteins into the host cell with the aim of disturbing and hijacking cellular processes for their benefit. Despite intensive studies, many effectors remain uncharacterized. Motivated by the richness of Legionella effector repertoires and their oftentimes atypical biochemistry, also by several known atypical Legionella effector kinases and pseudokinases discovered recently, we undertook an in silico survey and exploration of the pan-kinome of the Legionella genus, i.e., the union of the kinomes of individual species. In this study, we discovered 13 novel (pseudo)kinase families (all are potential effectors) with the use of non-standard bioinformatic approaches. Together with 16 known families, we present a catalog of effector and non-effector protein kinase-like families within Legionella, available at http://bioinfo.sggw.edu.pl/kintaro/ . We analyze and discuss the likely functional roles of the novel predicted kinases. Notably, some of the kinase families are also present in other bacterial taxa, including other pathogens, often phylogenetically very distant from Legionella. This work highlights Nature’s ingeniousness in the pathogen–host arms race and offers a useful resource for the study of infection mechanisms.

Background Functionally related genes are well known to be often grouped in close vicinity in the genomes, particularly in prokaryotes. Notwithstanding the diverse evolutionary mechanisms leading to this phenomenon, it can be used to predict functions of uncharacterized genes. Methods Here, we provide a simple but robust statistical approach that leverages the vast amounts of genomic data available today. Considering a protein domain as a functional unit, one can explore other functional units (domains) that significantly often occur within the genomic neighborhoods of the queried domain. This analysis can be performed across different taxonomic levels. Provisions can also be made to correct for the uneven sampling of the taxonomic space by genomic sequencing projects that often focus on large numbers of very closely related strains, e.g., pathogenic ones. To this end, an optional procedure for averaging occurrences within subtaxa is available. Results Several examples show this approach can provide useful functional predictions for uncharacterized gene families, and how to combine this information with other approaches. The method is made available as a web server at http://bioinfo.sggw.edu.pl/neighborhood_analysis.

The interventional treatment of acute ischemic stroke with large vessel occlusion has revolutionized patient care in recent years. The Mechanical Thrombectomy Pilot Program in Poland is due to end soon. It seems the right time to summarize the achievements and name the problems of a centralized stroke care system and decide what future model of treatment and transportation to implement. In order to provide the best care for our patients, it is crucial to establish the actual needs in stroke and tailor the mechanical thrombectomy system structure accordingly. The analysis of data from well-organized health systems in the world suggests that to deliver adequate numbers of mechanical thrombectomy to stroke patients in Poland, we would need to at least double the number of procedures currently performed. To achieve this, an essential system reorganization and adjustments are required, with special emphasis on the number of mechanical thrombectomy centers and transportation models. The strengths and weaknesses of two dominant transportation models (mothership and drip-and-ship) are herein discussed, and a proposal on how to build an efficient and cost-effective mechanical thrombectomy stroke network in Poland is put forward. The article is an invitation to open an interdisciplinary discussion on the best treatment model of acute ischemic stroke patients requiring mechanical thrombectomy in Poland.

Despite inconclusive and conflicting results of trials and meta-analyses assessing aspiration thrombectomy in ST-segment elevation myocardial infarction (STEMI), trends toward reduced mortality were observed in the high thrombus burden subgroup [1–3]. With a large thrombus being one of the strongest predictors of the no flow phenomenon, manual thromboaspiration remains an effective method of its prevention, especially in patients who cannot undergo a staged procedure after IIB/IIIA inhibitor administration because satisfactory reperfusion has not been achieved during the initial intervention [4–8]. Since standard monorail coronary aspiration devices are often ineffective in the case of a large thrombus, guide extension catheters have been used for clot extraction. Their bigger lumen comes at a cost of worse trackability and a higher risk of artery dissection [9].

The article introduces selected aspects of creating material sets for an external wall connection with a balcony slab. The integral part of this work are calculations and analyses concerning the thermal quality of joints with balcony slabs produced using various construction and material solutions. Proper selections of the material layers of a building case in regards to thermal aspects and humidity essentially influence the building demand for energy (EU, EK i EP) and pollutant emissions into the natural environment.

We propose and benchmark a Gross-Pitaevskii-like equation for two-component Bose mixtures with competing interactions in 1D. Our approach follows the density functional theory with the energy functional based on the exact quantum Monte Carlo (QMC) simulations. Our model covers, but goes beyond, the popular approach with the Lee-Huang-Yang corrections. We first benchmark our approach against available QMC data in all interaction regimes and then study dynamical properties, inaccessible by ab initio many-body simulations. Our analysis includes a study of monopole modes and reveals the presence of anomalous dark solitons.

Abstract Background Pancreatic cancer is a major cause of cancer-related mortality. The identification of effective biomarkers is essential in order to improve management of the disease. Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway, a signal transduction system implicated in tissue repair and regeneration, as well as tumorigenesis. Here we evaluate the biomarker potential of YAP1 in pancreatic cancer tissue. Methods YAP1 was selected as a possible biomarker for pancreatic cancer from global protein sequencing of fresh frozen pancreatic cancer tissue samples and normal pancreas controls. The prognostic utility of YAP1 was evaluated using mRNA expression data from 176 pancreatic cancer patients in The Cancer Genome Atlas (TCGA), as well as protein expression data from immunohistochemistry analysis of a local tissue microarray (TMA) cohort comprising 140 pancreatic cancer patients. Ingenuity Pathway Analysis was applied to outline the interaction network for YAP1 in connection to the pancreatic tumor microenvironment. The expression of YAP1 target gene products was evaluated after treatment of the pancreatic cancer cell line Panc-1 with three substances interrupting YAP–TEAD interaction, including Super-TDU, Verteporfin and CA3. Results Mass spectrometry based proteomics showed that YAP1 is the top upregulated protein in pancreatic cancer tissue when compared to normal controls (log2 fold change 6.4; p = 5E−06). Prognostic analysis of YAP1 demonstrated a significant correlation between mRNA expression level data and reduced overall survival (p = 0.001). In addition, TMA and immunohistochemistry analysis suggested that YAP1 protein expression is an independent predictor of poor overall survival [hazard ratio (HR) 1.870, 95% confidence interval (CI) 1.224–2.855, p = 0.004], as well as reduced disease-free survival (HR 1.950, 95% CI 1.299–2.927, p = 0.001). Bioinformatic analyses coupled with in vitro assays indicated that YAP1 is involved in the transcriptional control of target genes, associated with extracellular matrix remodeling, which could be modified by selected substances disrupting the YAP1-TEAD interaction. Conclusions Our findings indicate that YAP1 is an important prognostic biomarker for pancreatic cancer and may play a regulatory role in the remodeling of the extracellular matrix.

In the article, there are introduced the selected design and executive aspects of low-energy buildings in relation to binding legal regulations. The integral part of this article are calculations and analyses concerning the thermal quality of low energy buildings and factors which form their energy consumption. Proper shaping of material sets for external envelopes and their junction in thermal and humidity aspects essentially influences building needs for energy and pollution emission of the natural environment.

The purpose of this paper was to compare the investment amounts and efficiency of productive input between Polish and Romanian dairy farms depending on whether they access funds under the second pillar of EU’s CAP. The study covered the particularities of farms who access investment funds under the 2ndpillar of EU’s CAP, which allowed to identify the differences between beneficiaries and the control group (i.e. non-beneficiary farms). This paper relies on unpublished 2004–2015 microdata at a farm level, as retrieved from the FADN of the European Commission’s Directorate-General for Agriculture and Rural Development (DG AGRI-C.3; data source: EU-FADN – DG AGRI). The analysis period starts from the moment the two countries joined the EU and launched the FADN system (which is2004 for Poland and2007 for Romania) and ends in2015. The research task defined for Polish and Romanian dairy farms was performed with the use of Propensity Score Matching, a counterfactual method. The calculations were carried out using STATA. As shown by the analysis, in Poland, no considerable differences existed between dairy farms run by the beneficiaries of EU investment funds and the control group. Conversely, in Romania, investment aid was accessed by farms demonstrating a more efficient use of productive input.

Background: Pancreatic cancer is a heterogenous disease with a poor prognosis. This study aimed to discover and validate prognostic tissue biomarkers in pancreatic cancer using a mass spectrometry (MS) based proteomics approach. Methods: Global protein sequencing of fresh frozen pancreatic cancer and healthy pancreas tissue samples was conducted by MS to discover potential protein biomarkers. Selected candidate proteins were further verified by targeted proteomics using parallel reaction monitoring (PRM). The expression of biomarker candidates was validated by immunohistochemistry in a large tissue microarray (TMA) cohort of 141 patients with resectable pancreatic cancer. Kaplan-Meier and Cox proportional hazard modelling was used to investigate the prognostic utility of candidate protein markers. Findings: In the initial MS-discovery phase, 165 proteins were identified as potential biomarkers. In the subsequent MS-verification phase, a panel of 45 candidate proteins was verified by the development of a PRM assay. Brain acid soluble protein 1 (BASP1) was identified as a new biomarker candidate for pancreatic cancer possessing largely unknown biological and clinical functions and was selected for further analysis. Importantly, bioinformatic analysis indicated that BASP1 interacts with Wilms tumour protein (WT1) in pancreatic cancer. TMA-based immunohistochemistry analysis showed that BASP1 was an independent predictor of prolonged survival (HR 0.468, 95% CI 0.257–0.852, p = .013) and predicted favourable response to adjuvant chemotherapy, whereas WT1 indicated a worsened survival (HR 1.636, 95% CI 1.083–2.473, p = .019) and resistance to chemotherapy. Interaction analysis showed that patients with negative BASP1 and high WT1 expression had the poorest outcome (HR 3.536, 95% CI 1.336–9.362, p = .011). Interpretation: We here describe an MS-based proteomics platform for developing biomarkers for pancreatic cancer. Bioinformatic analysis and clinical data from our study suggest that BASP1 and its putative interaction partner WT1 can be used as biomarkers for predicting outcomes in pancreatic cancer patients. Keywords: Pancreatic cancer, Mass spectrometry, Biomarkers, BASP1, WT1, Prognosis, Chemotherapy response

Abstract The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in‐depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.

Abstract The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease.

The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers full understanding of the functioning of the living cells. ADP-ribosylation is a common post-translational modification of proteins; also nucleic acids and small molecules can be modified by the covalent attachment of ADP-ribose. This modification, important in cellular signalling and infection processes, is usually executed by enzymes from the large superfamily of ADP-ribosyltransferases (ARTs). Here, using bioinformatics approaches, we identify a novel putative ADP-ribosyltransferase family, conserved in eukaryotic evolution, with a divergent active site. The hallmark of these proteins is the ART domain nestled between flanking leucine-rich repeat (LRR) domains. LRRs are typically involved in innate immune surveillance. The novel family appears as putative novel ADP-ribosylation-related actors, most likely pseudoenzymes. Sequence divergence and lack of clearly detectable “classical” ART active site suggests the novel domains are pseudoARTs, yet atypical ART activity, or alternative enzymatic activity cannot be excluded. We propose that this family, including its human member LRRC9, may be involved in an ancient defense mechanism, with analogies to the innate immune system, and coupling pathogen detection to ADP-ribosyltransfer or other signalling mechanisms.

Poruszono wybrane aspekty projektowe przegród i złączy budowlanych budynków o niskim zużyciu energii. Określono wymagania prawne w zakresie oszczędno-ści energii i ochrony cieplnej oraz uniknięcia kondensacji powierzchniowej i mię-dzywarstwowej. W celu wytypowania przegród zewnętrznych i złączy spełniających wymagania dla budynków o niskim zużyciu energii wykonano obliczenia parametrów fizykalnych przy zastosowaniu profesjonalnych programów komputerowych. Zastosowanie nowoczesnych materiałów termoizolacyjnych oraz poprawne kształ-towanie układów w materiałach przegród zewnętrznych i ich złączy gwarantuje minimalizację strat ciepła przez przenikanie oraz osiągnięcie standardu niskoenergetycznego budynków.

The Directive 2010/31/EU introduces a new building standard (NZEB) in all member states of the European Union from 1.01.2021. In Poland, a low-energy building has been defined. The design, construction and use of such building is a complex process and requires knowledge of many aspects concerning building materials, general construction, building physics, installations, renewable energy systems and architectural design. Implementation of the current technical requirements in this area encompasses examining many parameters of an entire building but also of its external walls and joints. Defining them according to the applicable legal regulations and relevant standards evokes many questions and uncertainties regarding calculation procedures and interpretation of physical aspects. On the basis of conducted calculations and analyses, the authors have started a discussion on calculation methods in this field, proposing changes in legal regulations and calculation procedures. The paper describes selected factors influencing low-energy buildings: physical parameters of building envelope elements, support of modern ventilation systems, energy performance parameters. The calculation part of the work concerns the analysis of physical parameters of the elements of low-energy building envelope and energy performance parameters of a buildings with consideration of energy saving and thermal insulation criteria. Formation of material systems of external walls and building joints requires taking into account innovative insulation materials and specific parameters of the air inside and outside of a building. The use of professional software for calculations and analyses provides reliable results. Many coherent factors such as: architecture of a building, structural and material solutions of the external walls and their joints (elements of the building envelope), type and efficiency of the ventilation, central heating and hot water systems, use of renewable energy sources, integral management of the building in the field of energy production help to obtain optimal parameters of energy performance of the building and reduce emissions of CO2 to the atmosphere.

W pracy przedstawiono analizę porównawczą parametrów fizykalnych wybranych złączy przegród zewnętrznych po dociepleniu od strony wewnętrznej i zewnętrznej przy zastosowaniu programu komputerowego TRISCO. Na podstawie otrzymanych wyników obliczeń z uwzględnieniem parametrów powietrza wewnętrznego i zewnętrznego oraz wariantowych układów materiałowych przegród zewnętrznych przeprowadzono ocenę jakości cieplno-wilgotnościowej złączy z uwzględnieniem obowiązujących przepisów prawnych. Dobór układów warstw materiałowych przegród zewnętrznych i ich złączy po dociepleniu powinien być przeprowadzony na podstawie szczegółowych obliczeń i analiz z uwzględnieniem warunków eksploatacji oraz zmiennych parametrów powietrza zewnętrznego.

Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term T alterations were induced. We designed a human model of 30 healthy young males with pharmacologically induced T changes, which resulted in three time points for blood collection: (A) baseline, (B) low T (3 weeks post administration of gonadotropin releasing hormone antagonist) and (C) restored T (2 weeks after injection of T undecanoate). The influence of T on AAs was analyzed by spectrophotometry on plasma samples. Levels of 9 out of 23 AAs, of which 7 were essential AAs, were significantly increased at low T and are restored upon T supplementation. Levels of tyrosine and phenylalanine were most strongly associated to T changes. Short-term effect of T changes suggests an increased protein breakdown that is restored upon T supplementation. Fasting AA levels are able to monitor the early metabolic changes induced by the T fluctuations.

The article is focused on the airflow in a ventilation system in a building. The work examines the methods which enhance the chimney effect. In this paper, three cases with different chimneys were analyzed for the full-scale experiment. These cases were characterized by different geometrical and material parameters, leading to differences in the intensity of the ventilation airflow. The common denominator of the cases was the room with the air inlet and outlet to the ventilation system. The differences between the experimental cases concerned the chimney canal itself, and more precisely its part protruding above the roof slope. The first experimental case concerned a ventilation canal made in a traditional way, from solid ceramic brick. The second experimental case concerned the part that led out above the roof slope with a transparent barrier, called a solar chimney. In the third experimental case, a rotary type of chimney cap was installed on the chimney to improve the efficiency of stack ventilation. All these cases were used to determine the performance of natural ventilation—Air Change per Hour (CH). Additionally, the paper presents a technical and economic comparison of the solutions used.

The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers a full understanding of the functioning of living cells. One such example is the human protein C12ORF4, which belongs to the DUF2362 family, present in many eukaryotic lineages and conserved in metazoans. The only functional information available on C12ORF4 (Chromosome 12 Open Reading Frame 4) is its involvement in mast cell degranulation and its being a genetic cause of autosomal intellectual disability. Bioinformatics analysis of the DUF2362 family provides strong evidence that it is a novel member of the Macro clan/superfamily. Sequence similarity analysis versus other representatives of the Macro superfamily of ADP-ribose-binding proteins and mapping sequence conservation on predicted three-dimensional structure provides hypotheses regarding the molecular function for members of the DUF2362 family. For example, the available functional data suggest a possible role for C12ORF4 in ADP-ribosylation signaling in asthma and related inflammatory diseases. This novel family appears to be a likely novel ADP-ribosylation “reader” and “eraser,” a previously unnoticed putative new player in cell signaling by this emerging post-translational modification.

Various methods can be used to reduce energy consumption in buildings. One of them is the tightening of energy requirements, which, like other methods, cannot result in a worsening of the indoor environmental quality. The article presents a study on the impact of changes in the thermal insulation of the building envelope on the energy demand, heating costs, and emissions. Mathematical models of the dependence of the index of annual usable energy demand for heating (EUH) of a residential house on the thermal transmittance coefficients (Ui) of selected building elements were developed. Values of Ui were adopted at three levels, corresponding to the maximum required values—as approved in Polish law for the periods from 2014, 2017, and 2021. The analyses were conducted for the location of the building in three of the five climate zones of Poland. It turned out that the differences in the energy demand in various locations in Poland amount to 32.6%. The change in Ui in the analyzed period causes a decrease of EUH by almost 27%. Financial savings and a reduction of emissions strongly depend on the fuel used in the building. Increasing the level of thermal insulation of walls increases the perceptible temperature in rooms by 1.2–1.5%.

This paper presents a case study on how to improve the energy efficiency of an institutional building of significant heritage value through retrofitting the external wall system. This building is located in Upper Silesia, Poland. Due to the architectural value of the facade, thermal insulation had to be applied from the inside. As part of this publication, basing on the measurements and simulations, the authors present the results involving the improvement of energy efficiency of the insulated wall. On this basis, they also demonstrate the impact of insulation from the inside on the change of humidity inside the room. The tests were carried out both quantitatively by means of heat flux measurement and qualitatively by means of infrared temperature measurement. The research was supported by numerical modeling. The obtained results indicate that the thermal insulation used in the form of mineral insulation boards applied from the inside improves thermal insulation of the wall. Thus, heat losses through the examined envelope were limited. Computer simulations indicated that no condensation may occur under the condition considered.

We study how dark solitons, i.e., solutions of one-dimensional, single-particle, nonlinear, time-dependent Schrödinger equation, emerge from eigenstates of a linear many-body model of contact-interacting bosons moving on a ring, the Lieb-Liniger model. This long-standing problem has been addressed by various groups, which presented different, seemingly unrelated, procedures to reveal the solitonic waves directly from the many-body model. Here, we propose a unification of these results using a simple ansatz for the many-body eigenstate of the Lieb-Liniger model, which gives us access to systems of hundreds of atoms. In this approach, mean-field solitons emerge in a single-particle density through repeated measurements of particle positions in the ansatz state. The postmeasurement state turns out to be a wave packet of yrast states of the reduced system.

The ability to induce a defense response after pathogen attack is a critical feature of the immune system of any organism. Nucleotide-binding leucine-rich repeat receptors (NLRs) are key players in this process and perceive the occurrence of nonself-activities or foreign molecules. In plants, coevolution with a variety of pests and pathogens has resulted in repertoires of several hundred diverse NLRs in single individuals and many more in populations as a whole. However, the mechanism by which defense signaling is triggered by these NLRs in plants is poorly understood. Here, we show that upon pathogen perception, NLRs use their N-terminal domains to transactivate other receptors. Their N-terminal domains homo- and heterodimerize, suggesting that plant NLRs oligomerize upon activation, similar to the vertebrate NLRs; however, consistent with their large number in plants, the complexes are highly heterometric. Also, in contrast to metazoan NLRs, the N-terminus, rather than their centrally located nucleotide-binding (NB) domain, can mediate initial partner selection. The highly redundant network of NLR interactions in plants is proposed to provide resilience to perturbation by pathogens.

Poza dostarczaniem niezwykle cennych produktów, pszczoły są jednym z gatunków zdolnych do zapylania roślin entomofilnych. Stąd wspieranie rozwoju pszczelarstwa w obliczu ich znaczenia dla ludzkości wydaje się być niezwykle istotne. W Polsce zadanie to jest realizowane także przy użyciu środków pochodzących z Unii Europejskiej w ramach Programów Wsparcia Rynku Produktów Pszczelich. Celem artykułu jest zatem określenie roli środków pochodzących z Unii Europejskiej w rozwoju pszczelarstwa w województwie wielkopolskim na przykładzie Wojewódzkiego Związku Pszczelarzy w Poznaniu. Do badań wykorzystano niepublikowane dane WZP w Poznaniu, a także wyniki przeprowadzonej ankiety. Wyniki badań wskazują na pozytywne oddziaływanie środków z UE na rozwój pszczelarstwa w województwie wielkopolskim, zwłaszcza ze względu na spore zainteresowanie mechanizmem wśród pszczelarzy.