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The signaling lipid sphingosine 1-phosphate (S1P) plays key roles in many physiological processes. In the immune system, S1P's best-described function is to draw cells out of tissues into circulation. Here, we will review models of S1P distribution in the thymus, lymph nodes, spleen, and nonlymphoid tissues. These models have been challenging to construct, because of the lack of tools to map lipid gradients. Nonetheless, evidence to date suggests that S1P distribution is exquisitely tightly controlled, and that concentrations of signaling-available S1P cannot be predicted by standard rules of thumb. The fine regulation of S1P gradients may explain how S1P can simultaneously direct multiple cell movements both between tissues and circulation and within tissues. It may also make it feasible to develop drugs that enable spatially specific modulation of S1P signaling.

Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be potential alcohol markers. However, their identification is based on indirect analysis of lectin glycosidic bonds and molecular weight. We investigated the CDT content in the saliva of alcohol- and nicotine-dependent men. The CDT concentration (ng/mL, ng/mg protein) was determined by an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit in 55 men: 20 healthy social drinkers (C), 10 chronic cigarette smokers (S), 10 alcohol-dependent non-smokers (A), and 15 alcohol-dependent smokers (AS). Surprisingly, there were no differences in the concentrations of CDT between the studied groups. Salivary pH was the lowest in the AS and the highest in the A group. Therefore, salivary CDT cannot be used as an alcohol dependence marker as measured by ELISA. We suggest that direct identification of glycoproteins is necessary to search for potential salivary alcohol biomarkers. Molecules smaller than 40 kDa, which easily translocate from blood to the saliva, might be preferred as salivary alcohol markers.

Despite a growing recognition of late Palaeolithic and Mesolithic settlement in recent years, the area of Pojezierze Łagowskie still represents one of less known regions of western Poland, both in terms of Old and Middle Stone Age settlement and reconstruction of of contemporary environmental conditions. The article provides results of technological, typological, functional analyses, as well as that of raw materials used in stone industry of Mesolithic communities occupying sites 13 and 16 in Wilenko. Majority of functional tools is characterised by use-wear traces, which should be interpreted as results of variability of meat, bone, antler, and leather processing activities or game hunting. In the article an attempt has been made to reconstruct environmental conditions, on the basis of the results of pollen analysis.

Introduction Immunosuppressive therapy, necessary for graft survival, has its clinical consequences with an increased risk of developing malignancies being one of them. It seems that the maintenance of a proper balance between cytotoxic and regulatory activity of the immune system may prevent graft rejection, and with a lower risk of cancer. Aim To assess the quantitative changes in regulatory T cells (Tregs) in peripheral blood of kidney transplant recipients with post-transplantation skin neoplasm after conversion to mTOR inhibitors (mTORi) and to assess the incidence of secondary skin cancer in that group of patients. Material and methods Fourteen patients with post-transplant cutaneous malignancies converted to mTORi were included into the study. The control group consisted of eighteen patients maintained on immunosuppressive regimens without mTORi. The level of Tregs with a phenotype defined as CD4lowCD25high was measured before, and 6 months after, mTORi introduction. Results In all cases, 6 months after conversion, a significant decrease in the ratio of CD4+CD25+ to CD4lowCD25high from 6.52 to 4.29 was detected (p = 0.035). One patient converted to mTORi developed subsequent skin cancer, while in the control group, subsequent skin cancer was recognized in eight patients. Moreover, introducing mTORi significantly improved progression-free survival in this group of patients (p = 0.016). Conclusions Introducing mTORi to the immunosuppressive regimen resulted in an increase in the number of regulatory cells without increasing the incidence of secondary skin cancer in the investigated group of patients.

The field of industrial biotechnology is rapidly growing. This includes the use of biosynthesis of the fragrance-row materials in chemical industry, food industry, cosmetical and pharmaceutical industry. The production of 2-phenylethanol (PEA), which is an important flavor and fragrance compound, with a rose-like odor has been significantly increased last decade. The ionic liquids (ILs) and binary eutectic mixtures (EM) are proposed as an entrainers for the extraction of PEA in a biphasic biosynthesis. ILs and DES reveal many unique properties which make them very interesting for applications in modern ‘green’ technologies. In this work we present new experimental results on (solid, or liquid + liquid) phase equilibrium (SLE/LLE) measurements of twelve binary systems composed of pyrrolidinium-based ILs (namely: 1-butyl-1-methylpyrrolidinium chloride, [BMPYR][Cl] and 1-butyl-1-methylpyrrolidinium bis{(trifluoromethyl)sulfonyl}imide [BMPYR][NTf2] as well as 1-hexyl-1-methylpyrrolidinium chloride, [HMPYR][Cl] and 1-hexyl-1-methylpyrrolidinium bis{(trifluoromethyl)sulfonyl}imide [HMPYR][NTf2] with alcohols (1-decanol, 2-methyl-1-butanol, 2-methyl-2-butanol) and oleic acid. Additionally, three ternary LLE mixtures are presented {IL, or EM + PEA + water} at T = 308.15 K and ambient pressure. The data reveals that [HMPYR][NTf2] ionic liquid is more attractive than [BMPYR][NTf2] and that EMs ([BMPYR][NTf2] + 2-methyl-2-butanol) and ([HMPYR][NTf2] + 2-methyl-2-butanol) present worst selectivities and solute distribution ratios than those observed for pure ILs. However, they may be assumed as an alternative, less cost solvents for the separation of PEA from the water phase using liquid-liquid extraction at ambient conditions.

This paper presents the results of a multidisciplinary study that combines archaeological and palaeoenvironmental research to examine the relationship between environment and human activities in Western Poland during the Late Glacial and Early Holocene. The study area lying within the young moraine landscape produced several Late Palaeolithic and Early Mesolithic sites, varied in terms of size and function. Analyses of pollen, plant macro-remains and molluscs accompanied by geomorphological investigations and supported by series of radiocarbon dates have enabled a detailed reconstruction of environment. It has shown that despite climatic fluctuations during the Allerod and Younger Dryas, the studied area provided favourable conditions for hunter-gatherer occupation. The presence of micro- and macroscopic charcoal, charred particles of herbaceous plants and charred mosses in peat deposits of former water bodies evidence various activities carried out by Federmesser and Swiderian groups, for example...

The production of 2-phenylethanol (PEA), an important flavor and fragrance compound, with a rose-like odor has been significantly increased last decade. The aim of this study was to propose a new ionic liquids (ILs) and Deep Eutectic Solvents (DES) as an entrainers in a biphasic systems in possible bioproduction of PEA. ILs and DESs reveal many unique properties which make them very interesting for applications in modern ‘green’ technologies. In present contribution we have reported new experimental results on (solid, or liquid + liquid) phase equilibrium (SLE/LLE) measurements of eight binary systems composed of pyrrolidinium-based, imidazolium-based and phosphonium-based ILs (namely: 1-butyl-1-methylpyrrolidinium tricyanomethanide, [BMPYR][TCM], 1-butyl-1-methylpyrrolidinium tetracyanoborate, [BMPYR][TCB], 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate (triflate), [BMPYR][CF3SO3], 1-butyl-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate, [BMPYR][FAP], and 1-butyl-1-methylpyrrolidinium dicyanamid, [BMPYR][DCA], 1-butyl-1-methylimidazolium tricyanomethanide, [BMIM][TCM] and trihexyl-tetradecyl-phosphonium tricyanomethanide, [P6,6,6,14][TCM] with PEA and water. The complete miscibility with PEA was observed for [BMPYR][FAP], [BMPYR][DCA] and [BMIM][TCM]. The best solubility of solid IL in PEA was found for [BMPYR][TCM]. Complete miscibility with water was observed for [BMPYR][CF3SO3] and [BMPYR][DCA]. Moreover, new results on SLE/LLE of six binary systems of DES: {choline chloride + resorcinol (1:4), or phenylacetic acid (1:1), or phenylacetic acid (1:2), or oxalic acid (1:1), or malonic acid (1:1)} and {acetylocholine chloride + 1,10-decanediol} are shown. The initial information of the eutectic temperature and composition was found for {acetylocholine chloride + 1,10-decanediol}. Complete miscibility with PEA was observed only for {choline chloride + malonic acid (1:1)}. Simple eutectic systems of phase behavior with complete miscibility in the liquid phase for all the later mixtures were observed. The solubility of DES in water reveals SLE/LLE phase equilibrium. The best solvent was {choline chloride + malonic acid (1:1)}. The modeling of liquidus curves of ILs in PEA was proposed with excess Gibbs energy model, NRTL. It correlates the solubility with the average root mean square deviation, σT = 0.78 K. To our best knowledge this is the very first paper when the SLE/LLE of PEA and water have been tested for systems with ILs and DESs.

This work presents some important issues and topics related to chemical thermodynamics of ionic liquids (ILs). It consist of a series of experimental measurements in binary and ternary phase equilibrium systems connected with possible extraction of 2-phenylethanol (PEA) from aqueous phase “in situ” during the bioproduction. New experimental (solid + liquid) phase equilibrium (SLE) data for two binary systems {IL (1) + PEA (2)} and few (liquid + liquid) phase equilibrium (LLE) in binary systems {IL (1) + H2O (2)}, as well as LLE in five ternary systems of {IL (1) + PEA (2) + water (3)} at temperature T = 308.15 K and ambient pressure are reported. The systems are composed of the ILs: N-butyl-N-trimethylammonium bis{(trifluoromethyl)sulfonyl}imide, [N1114][NTf2], (2-hydroxyethyl)-N-trimethylammonium bis{(trifluoromethyl)sulfonyl}imide, [N1112OH][NTf2], N-N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis{(trifluoromethyl)sulfonyl}imide, [N2212OCH3][NTf2], N-methyl-N-trioctylammonium bis{(trifluoromethyl)sulfonyl}imide, [N1888][NTf2], and N-triethyl-N-octylammonium bis{(trifluoromethyl)sulfonyl}imide, [N2228][NTf2], with PEA or water. The miscibility of some of these ILs with water was known from the literature. A differential scanning calorimetry (DSC) was used to determine the melting point and the enthalpy of melting, solid-solid phase transition temperature and enthalpy, as well as glass transition of the ILs. The [N1114][NTf2] and [N1112OH][NTf2] showed complete miscibility in the liquid phase in a binary system with PEA at temperatures higher than the solubility curve. The latest ILs as [N2212OCH3][NTf2], [N1888][NTf2], and [N2228][NTf2] showed complete miscibility with PEA at temperature T = 308.15 K. The solubility of the ILs in PEA decreases in the order [N1114][NTf2] > [N1112OH][NTf2]. All systems revealed immiscibility gap with water (literature and our data). The solubility of water in the ILs increases in the order [N1888][NTf2]

Summary Basal tumor propagating cells (TPCs) control squamous cell carcinoma (SCC) growth by self-renewing and differentiating into supra-basal SCC cells, which lack proliferative potential. While transcription factors such as SOX2 and KLF4 can drive these behaviors, their molecular roles and regulatory interactions with each other have remained elusive. Here, we show that PITX1 is specifically expressed in TPCs, where it co-localizes with SOX2 and TRP63 and determines cell fate in mouse and human SCC. Combining gene targeting with chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptomic analyses reveals that PITX1 cooperates with SOX2 and TRP63 to sustain an SCC-specific transcriptional feed-forward circuit that maintains TPC-renewal, while inhibiting KLF4 expression and preventing KLF4-dependent differentiation. Conversely, KLF4 represses PITX1, SOX2, and TRP63 expression to prevent TPC expansion. This bi-stable, multi-input network reveals a molecular framework that explains self-renewal, aberrant differentiation, and SCC growth in mice and humans, providing clues for developing differentiation-inducing therapeutic strategies.

The ability to "read" the information about facial identity, expressed emotions, and intentions is crucial for non‑verbal social interaction. Neuroimaging and clinical studies consequently link face perception with fusiform gyrus (FG) and occipital face area (OFA) activity. Here we investigated face processing in an adult, patient PK, diagnosed with both high functioning autism spectrum disorder (ASD) and developmental prosopagnosia (DP). Both disorders have a significant impact on face perception and recognition, thus creating a unique neurodevelopmental condition. We used eye‑tracking and functional magnetic resonance imaging (fMRI) method. Eye‑tracking and fMRI results of PK were compared to results of control subjects. Patient PK showed atypical gaze‑fixation strategy during face perception and typical patterns of brain activations in the FG and OFA. However, a significant difference between PK and control subjects was found in the left anterior superior temporal sulcus/middle temporal gyrus (aSTS/MTG). In PK the left aSTS/MTG was hypo‑activated in comparison to the control subjects. Additionally, functional connectivity analysis revealed decreased inter‑hemispheric connectivity between right and left aSTS/MTG in 'ASD and DP' patient during face recognition performance as compared to the control subjects. The lack of activity in the left aSTS/MTG observed in the case of the clinical subject, combined with the behavioral, eye‑tracking, and neuropsychological results, suggests that impairment of the cognitive mechanism of face recognition involves higher level of processing. It seems to be related to insufficient access to semantic knowledge about the person when prompted by face stimuli.

Transposable elements can drive genome evolution, but their enhanced activity is detrimental to the host and therefore must be tightly regulated1. The Piwi-interacting small RNA (piRNA) pathway is vital for the regulation of transposable elements, by inducing transcriptional silencing or post-transcriptional decay of mRNAs2. Here we show that piRNAs and piRNA biogenesis components regulate precursor mRNA splicing of P-transposable element transcripts in vivo, leading to the production of the non-transposase-encoding mature mRNA isoform in Drosophila germ cells. Unexpectedly, we show that the piRNA pathway components do not act to reduce transcript levels of the P-element transposon during P–M hybrid dysgenesis, a syndrome that affects germline development in Drosophila3,4. Instead, splicing regulation is mechanistically achieved together with piRNA-mediated changes to repressive chromatin states, and relies on the function of the Piwi–piRNA complex proteins Asterix (also known as Gtsf1)5,6,7 and Panoramix (Silencio)8,9, as well as Heterochromatin protein 1a (HP1a; encoded by Su(var)205). Furthermore, we show that this machinery, together with the piRNA Flamenco cluster10, not only controls the accumulation of Gypsy retrotransposon transcripts11 but also regulates the splicing of Gypsy mRNAs in cultured ovarian somatic cells, a process required for the production of infectious particles that can lead to heritable transposition events12,13. Our findings identify splicing regulation as a new role and essential function for the Piwi pathway in protecting the genome against transposon mobility, and provide a model system for studying the role of chromatin structure in modulating alternative splicing during development.

The region of the Lubusz Lakeland in western Poland where there are a lot of subglacial channels provides opportunity for multi-proxy palaeoenvironmental reconstructions. None of them has not been the object of a specific study. The developmental history of the palaeolakes and their vicinity in the subglacial trough Jordanowo-Niesulice, spanning the Late Glacial and beginning of the Holocene, was investigated using geological research, lithological and geomorphological analysis, geochemical composition, palynological and archaeological research, OSL and AMS-radiocarbon dating. Geological research shows varied morphology of subglacial channel where at least two different reservoirs functioned in the end of the Last Glacial period and at the beginning of the Holocene. Mostly during the Bølling-Allerød interval and at the beginning of the Younger Dryas there took place melting of buried ice-blocks which preserved the analysied course of the Jordanowo-Niesulice trough. The level of water, and especially depth of reservoirs underwent also changes. Palynological analysis shows very diversified course of the Allerød interval.

Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide dismutase, uric acid and total antioxidant capacity), and oxidative damage products (advanced oxidation protein products, advanced glycation end products (AGE), 8-isoprostanes, 8-hydroxy-2’-deoxyguanosine and total oxidant status) were estimated in non-stimulated and stimulated saliva, as well as in plasma and erythrocytes. We show that in dementia patients the concentration/activity of major salivary antioxidants changes, and the level of oxidative damage to DNA, proteins and lipids is increased compared to healthy controls. Non-stimulated and stimulated salivary secretions were significantly reduced in dementia patients. The deterioration in mini mental state examination (MMSE) score correlated with salivary AGE levels, which when considered with receiver operating characteristic (ROC) analysis, suggests their potential role in the non-invasive diagnosis of dementia. In conclusion, dementia is associated with disturbed salivary redox homeostasis and impaired secretory function of the salivary glands. Salivary AGE may be useful in the diagnosis of dementia.

This study assessed the effect of ionic liquids (ILs) on extraction of 2-phenylethanol (PEA) from aqueous phase. It consists the synthesis of four new ILs, their physicochemical properties, and experimental solubility measurements in water as well as liquid–liquid phase equilibrium in ternary systems. ILs are an important new media for imaging and sensing applications because of their solvation property, thermal stability, and negligible vapor pressure. However, complex procedures and nonmiscibility with water are often required in PEA extraction. Herein, a facile and general strategy using four ILs as extraction media including the synthesis of new bis(fluorosulfonyl)imide-based ILs, 1-hexyl-methylmorpholinium bis(fluorosulfonyl)imide, [HMMOR][FSI], N-octylisoquinolinium bis(fluorosulfonyl)imide, [OiQuin][FSI], 1-butyl-1-methylpyrrolidinium bis(fluorosulfonyl)imide, [BMPYR][FSI], and N-triethyl-N-octylammonium bis(fluorosulfonyl)imide, [N2228][FSI], were investigated. The thermal properties, density, vis...

New experimental (solid + liquid) phase equilibrium (SLE) data for eight binary systems are reported. The systems are composed of the ILs: 1-ethyl-1-methylpiperidinium bis(trifluroromethylsulfonyl)imide, [EMPIP][NTf2], 1-propyl-1-methylpiperidinium bis(trifluroromethylsulfonyl)imide, [PMPIP][NTf2], 1-butyl-1-methylpiperidinium bis(trifluroromethylsulfonyl)imide, [BMPIP][NTf2], 1-hexyl-1-methylpiperidinium bis(trifluroromethylsulfonyl)imide, [HMPIP][NTf2], N-hexylquinolinium bis(trifluroromethylsulfonyl)imide, [HQuin][NTf2], N-hexylisoquinolinium bis(trifluroromethylsulfonyl)imide, [HiQuin][NTf2], [CCNMIM][TDI] and 1-butyl-3-methylimidazolium 4,5-dicyano-2(-trifluoromethyl)-imidazolide, [BMIM][TDI] with 2-phenylethanol (PEA). The synthesis of a new IL is presented for 1-(cyanomethyl)-3-methylimidazolium 4,5-dicyano-2-(trifluoromethyl)-imidazolide, [CCNMIM][TDI]. A differential scanning calorimetry (DSC) was used to determine the melting point and the enthalpy of melting of [CCNMIM][TDI]. The majority of the systems containing piperidinium-based ILs and [BMIM][TDI] showed complete miscibility with PEA. Simple eutectic mixture behaviour was found for the latest ILs. The solubility of the ILs decreases in the order [HQuin][NTf2] > [HiQuin][NTf2] > [EMPIP][NTf2] > [CCNMIM][TDI]. The correlation of the liquidus curves was undertaken with the NRTL excess Gibbs energy equation. The model correlates the solubility of the three systems (without [EMPIP][NTf2]) with an average root mean square deviation, σT = 0.67 K. To the best of our knowledge this is the very first paper where the SLE of PEA have been measured for systems with ILs. The solubility of six ILs in water were also measured. The solubility of the chosen ILs in water reveals SLE and/or (liquid + liquid) phase equilibrium (LLE) in these binary systems. The results of solubility of ILs in PEA and water can be used to design future alternative processes of the extraction of PEA, or separation from fermentation broth that involves these mixtures.

The Lubuskie Lake District played an important part in recolonisation of the Polish Plain due to its location and the character of the terrain. Despite that, it is and especially its northern part, poorly explored regarding both history of Late Glacial and early Holocene settlements, and the natural environment. The paper presents results of multidisciplinary research in this area. The most spectacular discoveries were connected with remains of settlements of the Hamburgian culture societies at Myszęcin - currently the richest site of this culture over the entire North European Plain. In the vicinity of this site several Late Palaeolithic and Mesolithic settlements of varied functions were recorded. First palynological records came from the Younger Dryas sediments in this area. In a log with a palynological spectrum comprising Younger Dryas and the beginning of the Holocene, a charcoal dust was found and it could indicate human activity as humans lived at a lake shore. An important complement to the image of the Late Glacial settlement at the Lubuskie Lake District was provided by the research near Lubrza that resulted in data regarding settlements of the Federmesser and Świderian culture societies. This region was not typical in a palynological spectrum of deposits during Allerød but also indicated highly diversified thickness of basal peat in a small area.

The Effects of Age on Stroop Interference in Clinical vs. Healthy Groups of Children The Stroop task is widely used to assess attentional dysfunction due to a frontal or frontoparietal deficit and is also thought to be related to the maturation of the prefrontal cortex. The study aimed to prove the diagnostic usefulness of the Polish Names and Colors Interference Test (TINiK) in a clinical setting and to investigate the pattern of performance on four TINiK subtasks according to the type of brain damage (focal or diffuse) and age of the patients. A total of 107 subjects (62 female, 45 male) aged 11-18 were divided into two groups: children aged 10;4-14;6 and adolescents aged 14;7-17;10 within each diagnostic category: healthy (H - 35), heterogeneous focal brain damage (BD - 36) and cardiac arrhythmia (CA - 36). The number of correct responses in the 60s time limit was collected for each TINiK task. The H group significantly outperformed both clinical groups. The H and CA groups show improvement of performance systematically with age on all TINiK subtasks although at a different level. The BD group displayed merely non-significant developmental improvement especially among the adolescent group. A discriminant analysis using the four basic TINiK scores was able to significantly differentiate the BD from the H group (83.1%) and the BD from the CA group (74.6%), but less well the CA from the H group (63.9%). TINiK has acquired preliminary neuro-psychological validation in Polish children. Developmental improvement in interference control may be hampered by various neuropathological mechanisms which are yet to be identified.

Interference Effect and Reading Skills in Children with Attention DisordersAim of this study was to examine the performance on Polish experimental version of classical Stroop test in 36 ADHD-C children in comparison with 35 healthy children matched for age and IQ WISC-R. It was hypothesized that children with ADHD will exhibit diminished ability to control interference and will make more errors than their healthy counterparts. In contradictory with expectations, there was showed little if any evidence for specific deficit in interference control in this ADHD sample. A remarkable finding of this study was to demonstrate the developmental differences in reading skills in age range 8-11 years between typically developing children and ADHD group which displays a virtually no progress in reading automaticity and color naming speed over the period.