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Purpose Mapping and genome sharing among affected individuals continue to be important for establishing a link between a genomic variant and its phenotypic consequences. In one large Ecuadorian keratoconus (KC) family a mutation and three other sequence variants were recognized, showing 100% segregation with disease phenotype in DOCK9, IPO5 and STK24 at 13q32 locus. Here we present further linkage and sequencing results of candidate KC genes identified in other Ecuadorian families. Methods Linkage analyses were performed in 3 large KC families. Next, candidate genes at indentified loci were screened by standard techniques using genomic DNA samples from these families and selected individuals from other Ecuadorian families and control Ecuadorian individuals. Coding exons and intron‐exon boundaries of the genes were evaluated. Results Suggestive keratoconus loci, 2q13‐q14.3, 20p13, and 5q31 were identified. Sequencing of IL1A, IL1B and IL1RN at 2q13‐q14.3, SLC4A11 at 20p13, TGFBI, PITX1 and IL9 at 5q31 have been completed. Numerous SNV were identified in coding and non‐coding regions. Conclusion Identified keratoconus loci and the sequence variants are specific for the studied families only. Our results indicate high complexity of genetics in familial keratoconus. Support: Polish Ministry of Science and Higher Education, Grant NN402591740 and National Science Center, Grant 2011/03/N/NZ5/01470 [ABSTRACT FROM AUTHOR]

Purpose Mapping and genome sharing among affected individuals continue to be important for establishing a link between a genomic variant and its phenotypic consequences. Several loci responsible for a familial form of keratoconus (KTCN) have been mapped, however; no mutations in any genes have been identified for any of these loci. Here we present further sequencing results of candidate keratoconus genes localized to 13q32 and 13q34 and accompanying linkage analyses performed in Ecuadorian families. Methods Genes were screened by standard techniques using 48 genomic DNA samples from individuals from family KTCN‐014 and selected affected and unaffected individuals from other Ecuadorian families. Coding exons and intron‐exon boundaries of the genes were evaluated. Additional bioinformatics analyses were carried out based on the genomewide scan data obtained from 79 patients with keratoconus and 66 healthy family members. Results Sequencing of COL4A1 and COL4A2 genes at 13q34 have been completed. Several single nucleotide polymorphisms were identified in coding and non‐coding regions. Haplotype analysis in family KTCN‐014 at 13q32 revealed three sequence variants segregating with keratoconus phenotype. Bioinformatics analyses revealed distinct keratoconus loci in particular Ecuadorian families indicating complexity of genetics in familial keratoconus. Conclusion Our results show high complexity of genetics in familial keratoconus [ABSTRACT FROM AUTHOR]

The examination of caecal contents allows one to investigate the exposure of colon mucosa to dietary toxins and the chemical contaminants present in animal feed. The objective of the present study was to examine the influence of Fusarium mycotoxins (zearalenone, ZEN, and deoxynivalenol, DON), administered separately and as a mixture, on the genotoxicity of caecal water (CW) from gilts fed these mycotoxins. CW genotoxicity was evaluated with the comet assay using the LLC-PK1 porcine epithelial kidney cell line. It was shown that after the first week of the experiment, the presence of DON in animal feed led to increased CW genotoxicity in the proximal colon, while the presence of DON and ZEN + DON had a similar effect in the distal colon (ANOVA, P < 0.05). After the third week of experiment, elevated genotoxicity in the distal colon was observed for all experimental groups of gilts, and it was 62%, 52.4%, and 52.8% higher for ZEN-, DON-, and ZEN + DON-fed animals, respectively, than for control group animals. However, no effect on CW genotoxicity in the proximal colon was seen. After six weeks, the presence of ZEN in the proximal colon increased CW genotoxicity by 103% in comparison with the control group. In the distal colon, after the sixth week, CW genotoxicity in all groups of animals fed with mycotoxin was significantly (by 80% to 116%) higher than in the control group. ZEN and DON administered as a mixture did not lead to an increased genotoxicity compared to either agent administered separately. Generally, the mycotoxins clearly started to increase the genotoxicity of CW from the third week of administration. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the head and neck (HNSCC) most frequently arise in the epithelial tissues of the upper aerodigestive tract. Patients with HNSCC, aged \45 years are categorized as young adults (YA). They are characterized by more severe form of this disease and often lack of classical, causative risk factors (tobacco smoking, alcohol abusing) in comparison to older (typical) patients (OP). The study purpose was to establish an anticipated protective role of DNA repair genes polymorphisms against cancer-causing agents. It was assumed that the polymorphisms in these genes may have a significant role in the etiology of HNSCC in YA. Studies were carried out on three groups: YA group with HNSCC (n = 90), young healthy group without cancer (YH, n = 160) and OP with HNSCC (n = 205). Three polymorphisms in DNA repair genes were analyzed: XPD ex23: A35931C, XRCC1 ex10: G28152A, and XRCC3 ex7: C18067T. The choice of these genes was connected with their involvement in three different DNA repair pathways. Genotyping was carried out by polymerase chain reaction with restriction fragment length polymorphism (PCR–RFLP) technique. Statistical analysis included: calculation of odds ratio (ORs), 95 % confidence intervals (CIs) and p value. There was no significant difference in the distribution of XPD genotypes in YA compared to OP or YH. The XRCC1 AA genotype variant was observed less frequently in HNSCC YA (4.7 %) than in YH and in OP group (17.1 and 10.8 %, respectively). XRCC3 CT genotype variant was observed more frequently in HNSCC YA (61.8 %) than in YH (36.3 %) and this result is statistically significant. This variant was associated with the borderline increased risk of HNSCC development in an early age, however, a similar tendency was not observed in case of double mutated TT variant. The established differences of genotypes distribution do not seem to differentiate substantially YA and OP in head and neck cancer risk. [ABSTRACT FROM AUTHOR]

In the present study, the crystal structure, microstructure, mechanical and corrosion properties of bulk Ti31Mo x HA composites (x = 0, 2.5, 5 and 10 wt %) were investigated. The sintering of Ti31Mo x HA powders led to the formation of a bulk composite with grain size of approx. 1 μm. All these composites have elastic modulus lower than CP microcrystalline α-Ti, and their hardness is two times higher. The ultrafine Ti31Mo5HA composite was more corrosion resistant in Ringer solution than the bulk Ti31Mo alloy. Surface wettability measurements revealed the higher surface hydrophilicity of the bulk ultrafine-grained Ti31Mo10HA sample in comparison to microcrystalline Ti sample. Ti31Mo5HA composites with the addition of 1 wt % Ag, 2 wt % Ta 2 O 5 or 2 wt % CeO 2 were synthesized, too. The antibacterial activity of Ti31Mo5HA composite containing silver (Ag), tantalum (V) oxide (Ta 2 O 5) or cerium (IV) oxide (CeO 2) against Staphylococcus aureus was studied. In vitro bacterial adhesion, study indicated a significantly reduced number of S. aureus on the bulk ultrafine-grained Ti31Mo5HA-Ag (Ce 2 O 3) plate surfaces in comparison to microcrystalline Ti plate surface. Ultrafine-grained Ti31Mo5HA - Ag or CeO 2 biomaterials can be considered to be the future generation of medical implants. • Ti31Mo composites with the HA and Ag, Ta 2 O 5 , CeO 2 were studied. • XRD was used to investigate the volume fractions of phases. • Young's modulus is around 95 GPa for composites with Ag and CeO 2. • The composites with Ag and CeO 2 have the lowest adhesion levels of S. aureus [ABSTRACT FROM AUTHOR]

Purpose Keratoconus (KC) is a disease of the eye characterized by thinning and protrusion of the cornea. The causes of KC remain unknown. Our mutation screening of genes from 13q32 KC locus have revealed substitution in STK24 showing 100% segregation with KC phenotype in the Ecuadorian family. To continue the KC causes search, some non‐coding RNA from 13q32 locus were selected for further molecular analysis. Here, we present sequencing results of lincRNA localized ~1kb from 5' end of STK24. Methods The lincRNA was screen by sequencing technique using DNA samples from 23 members of KC‐014 family and selected affected and unaffected individuals from Ecuador. Results Sequencing analysis of lincRNA localized ~1kb from 5' end of STK24 have revealed g.99230266C>T substitution showing segregation with KC phenotype in the Ecuadorian KC‐014 family. Conclusion Mutation analysis of lincRNA mapped at the 13q32 locus have revealed sequence alteration segregating with the KC phenotype in Ecuadorian family. Since it is known, that lincRNAs are co‐expressed with neighboring coding genes and may function as a regulator of epigenetic marks and gene expression, we suggest that this lincRNA localized in close proximity to STK24 gene might play a role in development and/or progression of familial KC in patients from Ecuador. To our knowledge, this is the first report presenting lincRNA analysis in KC. Support: Polish Ministry of Science and Higher Education, Grant NN402591740 [ABSTRACT FROM AUTHOR]

Purpose Keratoconus (KTCN) is described as a non‐inflammatory thinning and anterior protrusion of the central cornea which results in altered refractive powers, and loss of visual acuity. The etiology of KTCN remains unknown. Both genetic and environmental factors are associated with the disorder. The purpose of this study was to identify novel genetic factors involved in familial form of KTCN by extensive analysis of multigenerational Ecuadorian family. Methods A total of 22 individuals from KTCN‐019 family were included into this study. Genomic DNA samples of all members of KTCN‐019 family were genotyped with highly polymorphic microsatellite markers. After linkage was established, two positional and functional candidate genes, IL1A and IL1B, were examined with polymerase chain reaction amplification, and direct sequencing of all exons, and intron‐exon boundaries was performed. Results The disease susceptibility locus was mapped on 2q13 chromosome in KTCN‐019 family. Sequencing analysis of the candidate genes, IL1A and IL1B have revealed numerous alterations in coding and non‐coding sequences of both genes including several novel single nucleotide polymorphisms. No mutations segregated with KTCN phenotype have been identified. Conclusion Analysis of IL1A and IL1B genes revealed no mutations segregating with affected phenotype in large Ecuadorian family, indicating that other genes are involved in KTCN causation in this family. [ABSTRACT FROM AUTHOR]