Grammatical gender influences semantic categorization and implicit cognition in Polish

Wpływ rodzaju gramatycznego na procesy poznawcze jest ważnym zagadnieniem we współczesnej psycholingwistyce i psychologii języka, szczególnie w badaniach dotyczących relacji między gramatyką a semantyką. Zakres tego wpływu jest uzależniony od systemu rodzaju gramatycznego danego języka i jego specyfiki gramatycznej. Celem prezentowanych eksperymentów było zbadanie efektów rodzaju gramatycznego w języku polskim - języku słowiańskim z trzema rodzajami gramatycznymi w liczbie pojedynczej i dwoma w liczbie mnogiej. W Eksperymencie 1 zastosowano oceny podobieństwa triad i okazało się, że rodzaj gramatyczny rzeczowników wpływa na postrzegane podobieństwo słów w przypadku zwierząt, ale nie nazw obiektów nieożywionych czy pojęć abstrakcyjnych. W Eksperymencie 2 użyto zmodyfikowanego Testu Utajonych Skojarzeń; wyniki sugerują, że wpływ rodzaju gramatycznego rzeczowników wydaje się mieć utajony charakter, ponieważ spójność rodzaju gramatycznego nazw i płci odnośnika wpływa na czas reakcji i liczbę błędów klasyfikacji. W Eksperymencie 3 uczestnicy przypisywali głosy męskie lub żeńskie zwierzętom i przedmiotom martwym (ich nazwy miały męski lub żeński rodzaj gramatyczny), które były prezentowane jako słowa lub obrazy. Efekty rodzaju gramatycznego występowały zarówno dla obiektów żywych, jak i nieożywionych i były podobne dla bodźców słownych i wizualnych. Okazało się, że w języku polskim wpływ rodzaju gramatycznego może występować na poziomie leksyko-semantycznym i konceptualnym i dotyczy zarówno obiektów żywych, jak i nieożywionych. Wyniki omówiono w kontekście hipotezy podobieństwa i rodzaju oraz hipotezy płci i rodzaju.The influence of grammatical gender on cognitive processes is an important issue in contemporary psycholinguistics and language psychology, particularly in research concerning the relations between grammar and semantics. The extent of this effect is dependent on a given language's gender system and its grammatical specifics. The aim of the presented research was to investigate grammatical gender effects in Polish - a Slavic language with three singular and two plural grammatical genders. In Experiment 1, triadic similarity judgments were used, and it turned out that the grammatical gender of nouns influenced perceived similarity of words in case of animals, but not inanimate objects or abstract concepts. In Experiment 2 we used a modified Implicit Association Test; results suggest that grammatical gender seems to be of implicit nature, as grammatical gender consistency influenced reaction times and the number of classification errors. In Experiment 3 participants assigned male and female voices to animals and inanimate objects, which were presented either as words or as pictures. Grammatical gender effects occurred for both animate and inanimate objects and were similar for verbal and visual stimuli. It turned out that in the Polish language the influence of grammatical gender may occur on the lexicosemantic level and the conceptual level, and concerns both animate and inanimate objects. Results are discussed in context of the similarity and gender and the sex and gender hypotheses

Characterization of in vitro and in vivo metabolism of antazoline using liquid chromatography-tandem mass spectrometry

Antazoline (ANT) was recently shown to be an effective and safe antiarrhythmic drug in the termination of atrial fibrillation. However, the drug is still not listed in clinical guidelines. No data on ANT metabolism in humans is available. We used liquid chromatography coupled with tandem mass spectrometry to identify and characterize metabolites of ANT. We analyzed plasma of volunteers following a single intravenous administration of 100 mg of ANT mesylate and in in vitro cultures of human hepatocytes. We revealed that ANT was transformed into at least 15 metabolites and we investigated the role of cytochrome P450 isoforms. CYP2D6 was the main one involved in the fast metabolism of ANT. The biotransformation of ANT by CYP2C19 was much slower. The main Phase I metabolite was M1 formed by the removal of phenyl and metabolite M2 with hydroxyl in the para position of phenyl. Glucuronidation was the leading Phase II metabolism. Further study on pharmacokinetics of the metabolites would allow us to better understand the activity profile of ANT and to predict its potential clinical applications. Ultimately, further investigation of the activity profile of the new hydroxylated M2 metabolite of ANT might result in an active substance with a different pharmacological profile than the parent molecule, and potentially a new drug candidate

Evolutionary algorithms in modeling aerodynamic properties of spray-dried microparticulate systems

Spray drying is a single step process in which solutions or dispersions are converted into dry particles. It is widely used in pharmaceutical technology to produce inhalable particles. Dry particle behavior during inhalation, described as the emitted dose (ED) and fine particle fraction (FPF), is determined in vitro by standardized procedures. A large number of factors influencing the spray drying process and particle interaction makes it difficult to predict the final product properties in advance. This work presents the development of predictive models based on experimental data obtained by aerodynamic assessment of respirable dry powders. Developed models were tested according to the 10-fold cross-validation procedure and yielded good predictive ability. Both models were characterized by normalized root-mean-square error (NRMSE) below 8.50% and coefficient of determination (R2) above 0.90. Moreover, models were analyzed to establish a relationship between spray drying process parameters and the final product quality measures. Presented work describes the strategy of implementing the evolutionary algorithms in empirical model’s development. Obtained models can be applied as an expert system during pharmaceutical formulation development. The models have the potential for product optimization and a knowledge extraction to improve final quality of the drug

The relationships between the isoelectric point and: length of proteins, taxonomy and ecology of organisms

<p>Abstract</p> <p>Background</p> <p>The distribution of isoelectric point (pI) of proteins in a proteome is universal for all organisms. It is bimodal dividing the proteome into two sets of acidic and basic proteins. Different species however have different abundance of acidic and basic proteins that may be correlated with taxonomy, subcellular localization, ecological niche of organisms and proteome size.</p> <p>Results</p> <p>We have analysed 1784 proteomes encoded by chromosomes of Archaea, Bacteria, Eukaryota, and also mitochondria, plastids, prokaryotic plasmids, phages and viruses. We have found significant correlation in more than 95% of proteomes between the protein length and pI in proteomes – positive for acidic proteins and negative for the basic ones. Plastids, viruses and plasmids encode more basic proteomes while chromosomes of Archaea, Bacteria, Eukaryota, mitochondria and phages more acidic ones. Mitochondrial proteomes of Viridiplantae, Protista and Fungi are more basic than Metazoa. It results from the presence of basic proteins in the former proteomes and their absence from the latter ones and is related with reduction of metazoan genomes. Significant correlation was found between the pI bias of proteomes encoded by prokaryotic chromosomes and proteomes encoded by plasmids but there is no correlation between eukaryotic nuclear-coded proteomes and proteomes encoded by organelles. Detailed analyses of prokaryotic proteomes showed significant relationships between pI distribution and habitat, relation to the host cell and salinity of the environment, but no significant correlation with oxygen and temperature requirements. The salinity is positively correlated with acidicity of proteomes. Host-associated organisms and especially intracellular species have more basic proteomes than free-living ones. The higher rate of mutations accumulation in the intracellular parasites and endosymbionts is responsible for the basicity of their tiny proteomes that explains the observed positive correlation between the decrease of genome size and the increase of basicity of proteomes. The results indicate that even conserved proteins subjected to strong selectional constraints follow the global trend in the pI distribution.</p> <p>Conclusion</p> <p>The distribution of pI of proteins in proteomes shows clear relationships with length of proteins, subcellular localization, taxonomy and ecology of organisms. The distribution is also strongly affected by mutational pressure especially in intracellular organisms.</p

Usefulness of the Polish versions of the Montreal Cognitive Assessment 7.2 and the Mini-Mental State Examination as screening instruments for the detection of mild neurocognitive disorder

Introduction. Screening tests are a key step in the diagnosis of dementia and should therefore be highly sensitive to the detection of mild neurocognitive disorders (NCD). The Mini Mental State Examination (MMSE) is the most commonly used screening method. The Montreal Cognitive Assessment (MoCA) is a newer and less well-known screening tool, which has none of the limitations of the MMSE.Aim. The aim of this study was to analyse the reliability of the Polish versions of MoCA 7.2 vs MMSE in the detection of mild NCD among people aged over 60.Material and methods. The study was carried out at the Department and Clinic of Geriatrics from September 2014 to March 2017. The study included 281 participants, 91 of whom were assigned to the group without NCD. The other 190 had been diagnosed with mild NCD.Results. In the analysis of the ROC curve of the MoCA 7.2 results, the AUC was 0.925 (p &lt; 0.001). The optimal cut-off point for mild NCD was 23/24 points, with sensitivity and specificity of 83.2% and 79.1%. In the ROC curve of MMSE results, the AUC was 0.847 (p &lt; 0.001). The optimal cut-off point for mild NCD was 27/28 points, with sensitivity and specificity of 75.8% and 66.7%. The difference between AUC MoCA 7.2 and MMSE was 0.078 (p = 0.036).Conclusions. MoCA 7.2 detects mild NCD with more sensitivity than MMSE. We recommend using the cut-off point for MoCA of 23/24 points, because this is characterised by a higher sensitivity than the previously recommended cut-off point of 25/26 points. For the MMSE, the recommended cut-off point should be 27/28, which gives greater diagnostic accuracy than the previously recommended 25/26 points

SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism

Spleen tyrosine kinase (SYK) is an important oncogene and signaling mediator activated by cell surface receptors crucial for acute myeloid leukemia (AML) maintenance and progression. Genetic or pharmacologic inhibition of SYK in AML cells leads to increased differentiation, reduced proliferation, and cellular apoptosis. Herein, we addressed the consequences of SYK inhibition to leukemia stem-cell (LSC) function and assessed SYK-associated pathways in AML cell biology. Using gain-of-function MEK kinase mutant and constitutively active STAT5A, we demonstrate that R406, the active metabolite of a small-molecule SYK inhibitor fostamatinib, induces differentiation and blocks clonogenic potential of AML cells through the MEK/ERK1/2 pathway and STAT5A transcription factor, respectively. Pharmacological inhibition of SYK with R406 reduced LSC compartment defined as CD34+CD38-CD123+ and CD34+CD38-CD25+ in vitro, and decreased viability of LSCs identified by a low abundance of reactive oxygen species. Primary leukemic blasts treated ex vivo with R406 exhibited lower engraftment potential when xenotransplanted to immunodeficient NSG/J mice. Mechanistically, these effects are mediated by disturbed mitochondrial biogenesis and suppression of oxidative metabolism (OXPHOS) in LSCs. These mechanisms appear to be partially dependent on inhibition of STAT5 and its target gene MYC, a well-defined inducer of mitochondrial biogenesis. In addition, inhibition of SYK increases the sensitivity of LSCs to cytarabine (AraC), a standard of AML induction therapy. Taken together, our findings indicate that SYK fosters OXPHOS and participates in metabolic reprogramming of AML LSCs in a mechanism that at least partially involves STAT5, and that SYK inhibition targets LSCs in AML. Since active SYK is expressed in a majority of AML patients and confers inferior prognosis, the combination of SYK inhibitors with standard chemotherapeutics such as AraC constitutes a new therapeutic modality that should be evaluated in future clinical trials

B-cell Zone Reticular Cell Microenvironments Shape CXCL13 Gradient Formation

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B-cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradient

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele