Potential use of Ulva intestinalis-derived biochar adsorbing phosphate ions in the cultivation of winter wheat Tristicum aestivum.

In this work, the properties of biochar produced from green macroalga Ulva intestinalis by pyrolysis were studied at temperatures of 300, 500, and 700 °C. This biochar was characterized in terms of multielemental composition, BET surface area, total pore volume, and biosorption properties toward phosphate ions. Biochar produced at 700 °C-25 m2/g had the highest surface area. The kinetics and isotherms of sorption processes of phosphate ions as sorbate by these sorbents were investigated. Modified biochar was able to remove 84.3% of phosphate ions from wastewater, whereas non-modified biochar-only 40.6%. Hence, biochar enriched with phosphate ions can serve as a valuable soil amendment. Pot experiments performed on winter wheat (Triticum aestivum) with a 3% addition of dry Ulva intestinalis, pristine biochar, and Mg-modified biochar enriched with phosphate ions showed that these amendments stimulated plant growth (length and fresh weight of plants) as well as enlarging the chlorophyll content in leaves. Our results indicate that the production of biochar (pristine and Mg-impregnated) is a sustainable option to valorize the biomass of seaweeds, and to recycle phosphorus from wastewater.

New Steroidal Selenides as Proapoptotic Factors.

Cytostatic and pro-apoptotic effects of selenium steroid derivatives against HeLa cells were determined. The highest cytostatic activity was shown by derivative 4 (GI50 25.0 µM, almost complete growth inhibition after three days of culture, and over 97% of apoptotic and dead cells at 200 µM). The results of our study (cell number measurements, apoptosis profile, relative expression of apoptosis-related APAF1, BID, and mevalonate pathway-involved HMGCR, SQLE, CYP51A1, and PDHB genes, and computational chemistry data) support the hypothesis that tested selenosteroids induce the extrinsic pathway of apoptosis by affecting the cell membrane as cholesterol antimetabolites. An additional mechanism of action is possible through a direct action of derivative 4 to inhibit PDHB expression in a way similar to steroid hormones.

PD-L1 Overexpression, SWI/SNF Complex Deregulation, and Profound Transcriptomic Changes Characterize Cancer-Dependent Exhaustion of Persistently Activated CD4+ T Cells.

Growing tumors avoid recognition and destruction by the immune system. During continuous stimulation of tumor-infiltrating lymphocytes (TILs) by tumors, TILs become functionally exhausted; thus, they become unable to kill tumor cells and to produce certain cytokines and lose their ability to proliferate. This collectively results in the immune escape of cancer cells. Here, we show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level son T cell surfaces, decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodeling complex subunits, and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell proliferation and reduction of T cell numbers. The RNAseq analysis on exhausted CD4+ T cells indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and chemokines. Some interleukins were also detected in media from CD4+ T cells co-cultured with cancer cells. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with other cell lines overexpressing PD-L1, which suggested the existence of a general mechanism of CD4+ T cell exhaustion induced by cancer cells. The ChIP analysis on the PD-L1 promoter region indicated that the BRM recruitment in control CD4+ T cells was replaced by BRG1 and EZH2 in CD4+ T cells strongly exhausted by cancer cells. These findings suggest that epi-drugs such as EZH2 inhibitors may be used as immunomodulators in cancer treatment.

Differences in the efficiency of 3-deazathiamine and oxythiamine pyrophosphates as inhibitors of pyruvate dehydrogenase complex and growth of HeLa cells in vitro.

Oxythiamine (OT) and 3-deazathiamine (DAT) are the antimetabolites of thiamine. The aim of study was to compare the effects of OT and DAT pyrophosphates (-PP) on the kinetics of mammalian pyruvate dehydrogenase complex (PDHC) and the in vitro culture of HeLa cells. The kinetic study showed that 3-deazathiamine pyrophosphate (DATPP) was a much stronger competitive inhibitor (Ki = 0.0026 µM) of PDHC than OTPP (Ki = 0.025 µM). Both Ki values were much lower versus K m for thiamine pyrophosphate (0.06 µM). However, DATPP added to the culture medium for the HeLa cells culture did not hamper the rate of cell growth and showed not significant impact on the viability of the cells, whereas OTPP and OT showed a significant cytostatic effect. The differences between the thiamine antivitamins in their effect on cell growth in vitro may be due to differences in physicochemical properties and difficulty in DAT transport across the cell membrane.

Micropore Size Distribution and Surface Characteristics Co-influence on 4-Chlorophenol Adsorption Mechanism from Organic Solvents.

The effects of co-influence of pore size distribution and surface chemistry of activated carbon (AC) on the p-chlorophenol (PCP) adsorption from water, heptane, and cyclohexane have been studied. To modify the surface basicity, commercial activated carbon and ash-free commercial activated carbon were subjected to heat treatment in a hydrogen atmosphere. The ACs were also oxidized with hydrogen peroxide to increase the acidity. All applied modifications caused negligible changes in the porous texture and a significant modification on the surface characteristics. The adsorption of PCP was carried out in static conditions at an ambient temperature. The time needed to obtain the adsorption equilibrium from organic solvent was shorter than from water. The boundary layer effect was found to increase in the direction of water < cyclohexane < heptane and was heteroatom-dependent. The equilibrium adsorption isotherms showed all spectrum of isotherm types according to the Giles classification. The strong relationship between the volume of the PCP adsorbed and the volume of ACs micropore with size smaller than 1.6 nm was presented. This work shows that the surface heterogeneity influences the adsorption mechanism in the low adsorbate concentration range, more specifically, the final adsorption capacity is pore-size-dependent regardless of the kind of solvent used.

The Association Between Dental Status and Risk of Acute Myocardial Infarction Among Poles: Case-control Study.

BACKGROUND: Results of scientific research on the effects of periodontitis on the incidence of myocardial infarction (MI) are ambiguous. OBJECTIVES: The aim of this study was to investigate the association of the severity and extent of periodontitis with acute MI in Poles. MATERIAL AND METHODS: This case-control study included 134 cases hospitalized with acute MI under the age of 70 years and 155 controls drawn from the general population with no MI history. Sociodemographic, cardiologic and periodontal variables were assessed. Three periodontal indicators were evaluated: (1) the severity of periodontitis classified in accordance with Page and Eke definition, (2) the extent of periodontitis determined on the basis of the percentage of sites with CAL ≥ 3 mm (Arbes Index) and (3) tooth loss (> 10 teeth). In a logistic regression model, the association of periodontal parameters with MI occurrence was evaluated after adjusting for well-known cardiovascular risk factors. RESULTS: The extent of periodontitis was significantly associated with the risk of acute MI even after adjusting for age, sex, tobacco smoking, hypertension, diabetes, BMI, education and income (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1 to 5.2; p = 0.0203). However, the severity of periodontitis was associated with MI after adjusting for age and sex (OR = 2.0; 95% CI = 1.2-3.5; p = 0.0109), but not after adjusting for the other above-mentioned risk factors. The association between the number of lost teeth and acute MI was significant after adjusting for age, sex, tobacco smoking, arterial hypertension and diabetes mellitus (OR = 2.1; 95% CI = 1.2-5.9; p = 0.0151). CONCLUSIONS: This study proves the positive association between periodontitis and acute MI in Poles. This association seems to be stronger with regard to the extent rather than to the severity of periodontitis.

Prospective Analysis of the Relationship Between the State of Periodontal Tissues and Changes in Selected Cardiovascular Parameters in Patients with Type 2 Diabetes.

BACKGROUND: Periodontitis is considered a risk factor in many systemic diseases, including cardiovascular pathologies and diabetes. Diabetes can also exacerbate early vascular changes, mainly due to the synthesis of advanced glycosylation end-products and oxidative stress. It has not yet been fully explained whether the additional presence of periodontal disease can affect the course of atherosclerosis and left ventricle hypertrophy in diabetic patients. OBJECTIVES: The aim of the study was to assess the relationship between periodontal and cardiovascular diseases and their progression in patients with type 2 diabetes. MATERIAL AND METHODS: The study included 119 patients diagnosed with type 2 diabetes. Periodontal pocket depth (PD), clinical attachment loss (CAL), plaque index (PI) and bleeding index (BOP) were determined. Basic laboratory tests were performed. The intima-media thickness (IMT) and the left ventricular mass index (LVMI) were determined by means of ultrasonography. After one year the examinations were repeated. The statistical analysis included the 84 patients who took part in both the first and second examinations. RESULTS: A positive correlation between the number of deep and active periodontal pockets and LVMI value was observed in men. The IMT value correlated with the mean CAL, PI and BOP, while a negative correlation was found between the IMT and the number of deep pockets, as well as between the IMT and the number of retained teeth. A multivariate analysis demonstrated a significant correlation between CAL and both IMT and LVMI change after one year. CONCLUSIONS: A relationship between periodontitis and cardiovascular diseases has been confirmed in diabetic patients. The most significant periodontal parameter in relation to the progression of atherosclerosis and left ventricle hypertrophy was shown to be clinical attachment loss - a measure of the history of periodontal disease during the patient's lifetime.

Influence of pore size distribution on the adsorption of phenol on PET-based activated carbons.

The role of pore size distribution in the adsorption of phenol in aqueous solutions on polyethylene terephthalate (PET)-based activated carbons (ACs) has been analyzed. The ACs were prepared from PET and mixtures of PET with coal-tar pitch (CTP) by means of carbonization and subsequent steam and carbon dioxide activation at 850 and 950 °C, respectively. The resultant ACs were characterized on the basis of similarities in their surface chemical features and differences in their micropore size distributions. The adsorption of phenol was carried out in static conditions at ambient temperature. The pseudo-second order kinetic model and Langmuir model were found to fit the experimental data very well. The different adsorption capacities of the ACs towards phenol were attributed to differences in their micropore size distributions. Adsorption capacity was favoured by the volume of pores with a size smaller than 1.4 nm; but restricted by pores smaller than 0.8 nm.

Integrative genetic analysis of mouse and human AML identifies cooperating disease alleles.

t(8;21) is one of the most frequent chromosomal abnormalities observed in acute myeloid leukemia (AML). However, expression of AML1-ETO is not sufficient to induce transformation in vivo. Consistent with this observation, patients with this translocation harbor additional genetic abnormalities, suggesting a requirement for cooperating mutations. To better define the genetic landscape in AML and distinguish driver from passenger mutations, we compared the mutational profiles of AML1-ETO-driven mouse models of leukemia with the mutational profiles of human AML patients. We identified TET2 and PTPN11 mutations in both mouse and human AML and then demonstrated the ability of Tet2 loss and PTPN11 D61Y to initiate leukemogenesis in concert with expression of AML1-ETO in vivo. This integrative genetic profiling approach allowed us to accurately predict cooperating events in t(8;21)(+) AML in a robust and unbiased manner, while also revealing functional convergence in mouse and human AML.

The contribution of de novo coding mutations to autism spectrum disorder.

Whole exome sequencing has proven to be a powerful tool for understanding the genetic architecture of human disease. Here we apply it to more than 2,500 simplex families, each having a child with an autistic spectrum disorder. By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses, respectively. Including copy number variants, coding de novo mutations contribute to about 30% of all simplex and 45% of female diagnoses. Almost all LGD mutations occur opposite wild-type alleles. LGD targets in affected females significantly overlap the targets in males of lower intelligence quotient (IQ), but neither overlaps significantly with targets in males of higher IQ. We estimate that LGD mutation in about 400 genes can contribute to the joint class of affected females and males of lower IQ, with an overlapping and similar number of genes vulnerable to contributory missense mutation. LGD targets in the joint class overlap with published targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. Most of the significance for the latter comes from affected females.

Proper functioning of the GINS complex is important for the fidelity of DNA replication in yeast.

The role of replicative DNA polymerases in ensuring genome stability is intensively studied, but the role of other components of the replisome is still not fully understood. One of such component is the GINS complex (comprising the Psf1, Psf2, Psf3 and Sld5 subunits), which participates in both initiation and elongation of DNA replication. Until now, the understanding of the physiological role of GINS mostly originated from biochemical studies. In this article, we present genetic evidence for an essential role of GINS in the maintenance of replication fidelity in Saccharomyces cerevisiae. In our studies we employed the psf1-1 allele (Takayama et al., 2003) and a novel psf1-100 allele isolated in our laboratory. Analysis of the levels and specificity of mutations in the psf1 strains indicates that the destabilization of the GINS complex or its impaired interaction with DNA polymerase epsilon increases the level of spontaneous mutagenesis and the participation of the error-prone DNA polymerase zeta. Additionally, a synergistic mutator effect was found for the defects in Psf1p and in the proofreading activity of Pol epsilon, suggesting that proper functioning of GINS is crucial for facilitating error-free processing of terminal mismatches created by Pol epsilon.

De novo gene disruptions in children on the autistic spectrum.

Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveal de novo small indels and point substitutions, which come mostly from the paternal line in an age-dependent manner. We do not see significantly greater numbers of de novo missense mutations in affected versus unaffected children, but gene-disrupting mutations (nonsense, splice site, and frame shifts) are twice as frequent, 59 to 28. Based on this differential and the number of recurrent and total targets of gene disruption found in our and similar studies, we estimate between 350 and 400 autism susceptibility genes. Many of the disrupted genes in these studies are associated with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. We find FMRP-associated genes are under greater purifying selection than the remainder of genes and suggest they are especially dosage-sensitive targets of cognitive disorders.

Clinical characteristics of tumors derived from colorectal cancer patients who harbor the tumor necrosis factor alpha-1031T/T and NOD2 3020insC polymorphism.

BACKGROUND: Genetic predispositions to disease have focused on highly penetrant causative changes in tumor suppressor genes or genes associated with DNA mismatch repair. New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization. METHODS: In this report we have examined the tumor characteristics in a group of patients who have been shown to harbor two polymorphisms in two genes that are associated with the immune system NOD2 and TNFalpha. RESULTS: Colorectal cancers from patients with NOD2 3020insC and TNFalpha-1031T/T constitutional changes are mostly right-sided disease (OR=2.21, p=0.03) with a tendency to higher stages (OR=2.41, p=0.06), increased number of associated polyps (OR=1.77, p=0.16) and later age of average age of disease onset (p=0.039). CONCLUSION: The results reveal that there appear to be specific characteristics associated with the tumors that may aid in determining management strategies to reduce the risk of disease.

A family with 3460G>A and 11778G>A mutations and haplogroup analysis of Polish Leber hereditary optic neuropathy patients.

Three mutations in mitochondrial DNA complex I genes are responsible for over 90% of Leber hereditary optic neuropathy (LHON) cases in Europe. A family with two LHON mutations--practically homoplasmic 11778G>A and varying levels of 3460G>A--was found during analysis of Polish patients. DNA and visual acuity was analyzed in four affected brothers and their unaffected sister and mother as well as in their step brother. Four male patients experienced vision loss around the age of 20 while for their step brother the onset was late--at the age of 33. No additional neurological symptoms were observed and both women were completely asymptomatic. The mutation occurred in a haplogroup H background, the most common one in both the Polish population and among patients. Double LHON mutations are extremely rare, and this particular combination has not been previously described in the literature.

Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk.

BACKGROUND: Patients with chronic inflammatory bowel disease (IBD) are at an increased risk of colorectal cancer (CRC) and it is estimated that one in six persons diagnosed with IBD will develop CRC. This fact suggests that genetic variations in inflammatory response genes may act as CRC disease risk modifiers. METHODS: In order to test this hypothesis we investigated a series of polymorphisms in 6 genes (NOD2, DLG5, OCTN1, OCTN2, IL4, TNFalpha) associated with the inflammatory response on a group of 607 consecutive newly diagnosed colorectal cancer patients and compared the results to controls (350 consecutive newborns and 607 age, sex and geographically matched controls). RESULTS: Of the six genes only one polymorphism in TNFalpha(-1031T/T) showed any tendency to be associated with disease risk (64.9% for controls and 71.4% for CRC) which we further characterized on a larger cohort of CRC patients and found a more profound relationship between the TNFalpha -1031T/T genotype and disease (64.5% for controls vs 74.7% for CRC cases above 70 yrs). Then, we investigated this result and identified a suggestive tendency, linking the TNFalpha -1031T/T genotype and a previously identified change in the CARD15/NOD2 gene (OR = 1.87; p = 0,02 for CRC cases above 60 yrs). CONCLUSION: The association of polymorphisms in genes involved in the inflammatory response and CRC onset suggest that there are genetic changes capable of influencing disease risk in older persons.

Development of mesoporosity during phosphoric acid activation of wood in steam atmosphere.

Oak and birch were used as precursors to produce the activated carbons (ACs) with well-developed mesoporosity by phosphoric acid-promoted activation in a steam atmosphere. The effect of experimental variables such as the amount of activating agent, the soaking time and the type of wood on the development of porous structure upon heating at 480 degrees C was investigated. The materials were characterized by N2 adsorption at 77K, mercury porosimetry and elemental analysis. It was demonstrated that increasing impregnation ratio favors the development of micropores and small mesopores of 2-5nm, whereas the soaking time promotes the creation of large mesopores, between 10 and 50nm. Compared to birch, the oak activation using phosphoric acid in the same conditions gives ACs with lower mesopore volume and higher contribution of small mesopores that reflects the differences between both precursors in their biopolymer composition. The presence of steam in the H3PO4 activation process compared to nitrogen facilitates the development of mesoporosity to much higher extent for the birch than that of oak. The ACs prepared in this work show the BET surface area ranging from 800 to 2250m2g(-1), the total pore volume of 0.35-2.04cm3g(-1) with mesopore fraction between 0.06 and 0.68.

Germline CHEK2 mutations and colorectal cancer risk: different effects of a missense and truncating mutations?

Germline mutations in cell cycle checkpoint kinase 2 (CHEK2) have been associated with a range of cancer types, in particular of the breast and prostate. Protein-truncating mutations in CHEK2 have been reported to confer higher risks of cancer of the breast and the prostate than the missense I157T variant. In order to estimate the risks of colorectal cancer associated with truncating and missense CHEK2 mutations, we genotyped 1085 unselected colorectal cancer cases and 5496 controls for four CHEK2 founder mutations present in Poland. We observed an increased risk of colorectal cancer in association with the missense I157T mutation (odds ratios (OR) = 1.5; 95% CI 1.2-2.0; P = 0.002) but not with truncating mutations (OR = 1.0; 95% CI 0.5-1.8; P = 0.9); however the difference in the two OR was not statistically significant (P = 0.2). We conclude that the I157T mutation increases the risk of colorectal cancer in the population, but that truncating mutations may confer a lower risk or no increase in risk. It is important that other studies of CHEK2 mutation carriers be conducted to confirm this hypothesis.

CDKN2A common variant and multi-organ cancer risk--a population-based study.

The population frequencies of the CDKN2A common variants remain undetermined. In Poland, there is a common variant of the CDKN2A: an alanine to threonine substitution (A148T), which has been detected in other populations. We have recently showed that it is significantly overrepresented among Polish melanoma patients when compared to general population. Herein, we ascertained the prevalence of the A148T variant in 3,583 unselected cancer cases and 3,000 random control subjects from the same Polish population. We evaluated eleven different malignancies, representing the majority of all common cancer sites. Positive association with A148T variant was observed for lung cancer (OR, 2.0; p = 0.0052). A similar trend, although nonsignificant after the Bonferroni correction, was observed for colorectal cancer (OR, 1.5; p = 0.5499). These results suggest that A148T variant may be associated with a multi-organ cancer risk in the Polish population.

Adsorption of lignite-derived humic acids on coal-based mesoporous activated carbons.

The adsorption by a coal-based mesoporous activated carbon of humic acids (HAs) isolated from two Polish lignites was studied. For comparison, a commercial Aldrich humic acid was also included into this study. The differences in chemical structure and functional groups of HAs were determined by elemental analysis and infrared spectroscopy DRIFT. Two activated carbons used differed in terms of mesopore volume, mesopore size distribution, and chemical properties of the surface. The kinetics of adsorption of HAs have been discussed using three kinetic models, i.e., the first-order Lagergren model, the pseudo-second-order model, and the intraparticle diffusion model. It was found that the adsorption of HAs from alkaline solution on mesoporous activated carbon proceeds according to the pseudo-second-order model. The correlation coefficients were close to 1. The intraparticle diffusion of HA molecules within the carbon particle was identified to be the rate-limiting step. Comparing the two activated carbons, the carbon with a higher volume of pores with widths of 10-50 nm showed a greater removal efficiency of HA. An increase in the Freundlich adsorption capacity with decreasing carbon content of HA was observed. Among the HAs studied, S-HA shows characteristics indicating the highest contribution of small-size fraction. The S-HA was removed by both activated carbons to the highest extent. The effect of pH solution on the adsorption of HA was examined over the range pH 5.4-12.2. It was found that the extent of adsorption decreased with decreasing pH of the solution.

The 3020insC Allele of NOD2 Predisposes to Cancers of Multiple Organs.

The NOD2 gene has been associated with susceptibility to Crohn's disease and individuals with Crohn's disease are at increased risk for cancer at a number of organ sites. We studied the association between the 3020insC allele of the NOD2 gene and cancer among 2604 cancer patients and 1910 controls from Poland. Patients were diagnosed with one of twelve types of cancer in the Szczecin region between 1994 and 2004. Significant associations were found for colon cancer (OR = 1.8; 95% CI 1.2 to 2.6), for lung cancer (OR = 1.7; 95% CI = 1.1 to 2.5) and for ovarian cancer (OR = 1.6; 95% CI 1.1 to 2.3). In addition, a significant association was found for early-onset laryngeal cancer (OR = 2.9; 95% CI 1.4 to 6.2) and for breast cancer in the presence of DCIS (OR = 2.1 95% CI = 1.2 to 3.6). The NOD2 3020insC allele is relatively common (in Poland 7.3% of individuals) and may be responsible for an important fraction of cancer cases. We estimate that the lifetime cancer risk among carriers of this allele is 30% higher than that of individuals with two wild-type alleles.