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Background: Autosomal dominant tubulointerstitial kidney disease (ADTKD) results from mutations in various genes, including REN, UMOD, MUC1, and HNF1B. ADTKD due to REN mutations (ADTKD-REN) is often characterized as a proteinopathy that triggers the endoplasmic reticulum stress (ERS) cascade, potentially sharing similarities with ADTKD-UMOD and ADTKD-MUC1 at the cellular level. This study, inspired by a patient harboring a W17R mutation, investigates ERS activation by this mutation alongside two other renin variants, W10R and L381P. Methods: We established stable cell lines expressing both wild-type and mutated renin forms (W17R, W10R, and L381P). Using luciferase reporter assays, RT-qPCR, and confocal microscopy, we evaluated ERS activation, determined the cellular localization of the renin variants, and characterized the mitochondrial network in the W17R line. Results: The L381P line exhibited ERS activation, including transcriptional upregulation of MANF and CRELD2. No ERS activation was observed in the W17R line, while the W10R line exhibited intermediate characteristics. Notably, the W17R variant was misrouted to the mitochondria resulting in changes of the mitochondrial network organisation. Conclusions: ERS activation is not a universal response to different renin mutations in ADTKD-REN. The pathogenesis of the W17R mutation may involve mitochondrial dysfunction rather than the ER pathway, albeit further research is needed to substantiate this hypothesis fully. Testing CRELD2 and MANF as targeted therapy markers for a specific subgroup of ADTKD-REN patients is recommended. Additionally, fludrocortisone treatment has shown efficacy in stabilizing the renal function of our patient over a four-year period without significant side effects. [ABSTRACT FROM AUTHOR]

The construction of the St. Adalbert Church in Gdansk dates to 1310. It is a church of rich history and great historical value, and its care is challenging. In this study, the combination of unmanned aerial vehicle (UAV) photogrammetry and terrestrial laser scanning (TLS) was used to accurately build a 3D model of the church. Together with the collected historical inventory documentation, the historic building information model (HBIM) was generated. The Autodesk-Revit® tool was used for this purpose. On the basis of the generated model, the reflection properties of the laser scanner beam and red–green–blue (RGB) images, a methodology was proposed for analysing the degradation of the church's components. The main hypothesis of this study is based on the analysis of sunlight outside the church. In addition to the importance of the method for determining the risks of church degradation, a high-quality method for model visualization combining two photogrammetric techniques (TLS + UAV) is presented. [ABSTRACT FROM AUTHOR]

Molluscs are one of the sources of biologically active substances, which are now intensively studied, especially for their anti-cancer properties. Malignant melanoma originates from melanocytes, develops very quickly and is associated with poor prognosis. Therefore, the aim of the study was to assess the properties of biologically active compounds in sterile mucus isolated from slugs Limax maximus and Arion rufus. Tested mucus were isolated using the new self-developed method which is safe for the environment and the animal donors. The impact of the mucus on human keratinocytes CCD 1106 KERTr and malignant melanoma cells A-375 was examined using MTT assay and SRB assay, which allowed us to determine the cell metabolic activity and cell number after treating them with slug mucus isolated from Limax maximus and Arion rufus decreased human keratinocytes and melanoma cells metabolic activity as well as manifested properties of reducing the number of cells in both tested cell lines, and therefore can be a source of biologically active substances with anticancer potential. [ABSTRACT FROM AUTHOR]

Molluscs are one of the sources of biologically active substances, which are now intensively studied, especially for their anti-cancer properties. Malignant melanoma originates from melanocytes, develops very quickly and is associated with poor prognosis. Therefore, the aim of the study was to assess the properties of biologically active compounds in sterile mucus isolated from slugs Limax maximus and Arion rufus. Tested mucus were isolated using the new self-developed method which is safe for the environment and the animal donors. The impact of the mucus on human keratinocytes CCD 1106 KERTr and malignant melanoma cells A-375 was examined using MTT assay and SRB assay, which allowed us to determine the cell metabolic activity and cell number after treating them with slug mucus isolated from Limax maximus and Arion rufus decreased human keratinocytes and melanoma cells metabolic activity as well as manifested properties of reducing the number of cells in both tested cell lines, and therefore can be a source of biologically active substances with anticancer potential. [ABSTRACT FROM AUTHOR]

The wild boar Sus scrofa is one of the widely spread ungulate species in Europe, yet the origin and genetic structure of the population inhabiting Central and Eastern Europe are not well recognized. We analysed 101 newly obtained sequences of complete mtDNA genomes and 548 D-loop sequences of the species and combined them with previously published data. We identified five phylogenetic clades in Europe with clear phylogeographic pattern. Two of them occurred mainly in western and central part of the continent, while the range of the third clade covered North-Eastern, Central and South-Eastern Europe. The two other clades had rather restricted distribution. In Central Europe, we identified a contact zone of three mtDNA clades. Population genetic structure reflected clear phylogeographic pattern of wild boar in this part of Europe. The contribution of lineages originating from the southern (Dinaric-Balkan) and eastern (northern cost of the Black Sea) areas to the observed phylogeographic pattern of the species in Central and Eastern Europe was larger than those from the regions located in southern France, Iberian, and Italian Peninsulas. The present work was the first mitogenomic analysis conducted in Central and Eastern Europe to study genetic diversity and structure of wild boar population. [ABSTRACT FROM AUTHOR]

Polymorphism in innate immune genes in host populations can structure spatial variation in the prevalence of infectious diseases. In Europe, Borrelia afzelii is an important tick-borne pathogen of small mammals including the bank voles (Myodes glareolus). The Toll-like receptor 2 (TLR2) is an innate immune receptor that is important for detecting Borrelia burgdorferi sensu lato pathogens. The TLR2 gene is polymorphic in bank vole populations and is classified into four distinct clusters: C1, C2, C3, and C4. The C2 and C4 clusters versus the C1 and C3 clusters are associated with lower versus higher infection prevalence, respectively. We detected three TLR2 clusters in 487 bank voles from 30 populations in NE Poland: 84.2% of the obtained sequences belonged to the C1 variant, 7.2% to C2, and 8.6% to C3. However, no clear spatial structure of TLR2 clusters among the populations was detected. B. afzelii infection prevalence across all studied individuals was 12.1% and varied from 0 to 37.5% among populations. There were no significant differences in B. afzelii prevalence among voles carrying alleles of different TLR2 clusters, or between individuals belonging to two mtDNA lineages. Most infected individuals were adults, and males were infected more often than females. There was no significant relationship between the prevalence of TLR2 clusters in the vole populations and climatic and environmental factors within the study area. We therefore could not confirm an adaptive role of the TLR2 C2 alleles in reducing B. afzelii infection prevalence in bank voles. [ABSTRACT FROM AUTHOR]

The digit ratio (2D:4D) is said to be a potential marker of exposure to prenatal sex steroids. Some studies suggest that the 2D:4D is also linked with the testosterone response to challenging situations due to organizational effect of prenatal hormonal milieu on adult endocrine functioning. However, up to date, there were only four studies (conducted on small samples) that examined the 2D:4D and the testosterone response to a challenging situation (i.e. physical exertion or aggressive context). Here, we examined the relationship between the 2D:4D and the testosterone change under an acute exercise among 97 men. We found that the digit ratios (the right 2D:4D, the left 2D:4D, and the right minus left 2D:4D) were neither predictors of pre-exercise testosterone, nor the change in testosterone level after a cycling task. Our results add a contradictory to previous studies evidence in a discussion on the links of the 2D:4D and the testosterone change. [ABSTRACT FROM AUTHOR]

Present-day species distribution and patterns of genetic diversity in Europe are a result of post-glacial re-colonization from glacial refugia after the Last Glacial Maximum. This process led to the formation of secondary contact zones (suture zones) between the haplogroups of different species, and were induced by several factors, including climate and evolutionary processes like selection and adaptation. One such suture zone has been found in Poland, where a complex network of different phylogenetic lineages of predators, ungulates, and rodents is present. The phylogeography of mammals in western Europe has been widely studied, but central and eastern Europe have been treated cursorily. Only a few samples from these areas were analyzed in previous studies, resulting in a simplified and false description of local genetic structure. In this review, results of previous phylogeographic studies on carnivore, ungulate, and rodent species from central and eastern Europe were collected and synthesized to verify the Polish suture zone hypothesis and examine how it is affected by different variables (geomorphological features like the Carpathian Mountains and Vistula River, climate, or anthropogenic factors). Our data reflects the importance of precise studies in this region and the value they contribute to further studies of large-scale European phylogeography. [ABSTRACT FROM AUTHOR]

This paper focuses on negative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on element content in male chicken calvaria and α-tocopherol (vitamin E) ability to reduce its toxic potential on bone mineralization in offspring. In the experiment carried out once, a solution containing only DMSO, TCDD, TCDD + α-tocopherol, and exclusively α-tocopherol was administrated. Subsequently, on the 5th day after hatching, the mineral composition of the chicken calvaria was evaluated. The results obtained suggest that the use of α-tocopherol contributes to the maintenance of the concentration of calcium, magnesium, and manganese in the chicken calvaria treated with TCDD in the embryonic period. In turn, vitamin E increases the level of zinc. It has been found that α-tocopherol in chicken embryos has a protective effect against disturbance of level of chosen trace elements in the bones of offspring caused by the TCDD. [ABSTRACT FROM AUTHOR]

Domestic waste combustion in central heating furnaces is illegal in many countries, including Poland, but unfortunately still occurs. These activities have a negative influence on the environment and human health. The local nature of this process makes it difficult to effectively counteract this phenomenon. Information campaigns about the impact of domestic waste combustion in central heating furnaces, especially the impact on human health, are necessary, but undertaking parallel control activities is much more important. To control activity, support is necessary to develop a suitable method to confirm domestic waste combustion in central heating furnaces. In the present preliminary study, we have investigated two methods. The first method is indirect, it is based on the analytical pyrolysis of organic residues in ash and provides direct information on the type of plastic subjected to combustion. The second method is based on the principal component analysis (PCA) of polycyclic aromatic hydrocarbon (PAH) concentrations in ash samples. Special attention was paid to sixteen PAHs: naphthalene, acenaphthene, acenaphthylene, fluorene, anthracene, phenanthrene, fluoranthene, pyrene, chrysene, benzo(a)anthracene, benzo(a)pyrene, benzo(e)pyrene, benzo(b+k)fluoranthene, dibenzo(a,h)anthracene+ indeno(1,2,3-cd)pyrene, benzo(g,h,i)perylene, and perylene. [ABSTRACT FROM AUTHOR]

The genetic structure of rodent populations may reflect their glacial and postglacial history. We studied the genetic structure of bank vole Myodes glareolus populations in north-eastern Poland, where two divergent mtDNA lineages met in the secondary contact zone. We investigated 441 specimens from 24 local populations using 10 microsatellite loci. We detected two clusters according to STRUCTURE and three genetic clusters in Geneland analysis. The observed spatial pattern of those groups was concordant with previously described distribution of mtDNA lineages in the area. The width of the transition zone between the genetic groups varied from 2.3 to 180.2 km in various parts of the study area. The observed genetic structure and the localization of range borders between the detected genetic clusters in the western part of study area were correlated with open, deforested habitats, which may have suppressed gene flow between the clusters. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine the level of awareness of hypoglycemia, the level of fear for hypoglycemia, and the response to hypoglycemic events among insulin-treated diabetes patients from Central and Eastern Europe (CEE). The impact of hypoglycemia on the use of healthcare resources and patient productivity was also assessed. Methods: This was a multicenter, non-interventional, two-part, patient self-reported questionnaire study that comprised both a retrospective cross-sectional evaluation and a prospective observational evaluation. Study participants were insulin-treated adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from CEE. Results: Most patients (85.4% T1DM and 83.6% T2DM) reported normal hypoglycemia awareness. The median hypoglycemia fear score was 5 out of 10 for T1DM and 4 out of 10 for T2DM patients. Patients increased glucose monitoring, consulted a doctor/nurse, and/or reduced the insulin dose in response to hypoglycemia. As a consequence of hypoglycemia, patients took leave from work/studies or arrived late and/or left early. Hospitalization was required for 31 (1.2%) patients with T1DM and 66 (2.1%) patients with T2DM. Conclusion: Hypoglycemia impacts patients' personal and social functioning, reduces productivity, and results in additional costs, both direct (related to increased use of healthcare resources) and indirect (related to absenteeism. [ABSTRACT FROM AUTHOR]

Goose fat (GF) and rapeseed oil (RSO) 2:3 m m blend was enzymatically interesterified at 60 °C with and without microwaves assistance. As the catalyst, a commercial preparation of the immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) containing 2 % of water was used, and the catalyst load was 8 % in each case. The starting mixture and the interesterified products were separated by column chromatography into pure triacylglycerols fraction (TAG) and a non-triacylglycerol fraction, which contained free fatty acids (FFA), mono- and diacylglycerols (MAG and DAG). The oxidative stabilities of fats studied and TAG derived from them were assessed by Rancimat at 100 °C and by pressure differential scanning calorimetry (PDSC) under oxygen at 110-140 °C. Interesterification reduced the oxidative stability of GF and RSO blend. The main factors influenced on the oxidative stabilities of fats studied were concentrations of tocopherols and the presence of FFA, MAG and DAG. The structures of TAGs were of minor importance. From the resulting PDSC exotherms, their times to reach the onset ( τ) and peak maximum ( τ) were measured and used for calculations of parameters of the Arrhenius type kinetics for thermaloxidative decomposition of fats studied. [ABSTRACT FROM AUTHOR]

Analyzing non-native species after their establishment can shed light on factors responsible for their colonization success. The zebra mussel ( Dreissena polymorpha), a species of Ponto-Caspian origin, is a worldwide invader, and was first reported in northern France in the nineteenth century. The genetic diversity and structure of D. polymorpha from five river basins (nine locations) in France were estimated using nuclear markers (amplified fragment length polymorphisms, AFLPs; 154 loci) and sequences from a 514 bp mitochondrial DNA region (cytochrome c oxidase subunit I; COI). Results from the two types of markers were generally congruent, although COI sequences showed limited genetic polymorphism, with one predominant and cosmopolitan haplotype (84 % of the individuals). Both COI and AFLPs revealed that the most divergent and the least polymorphic sample was the one from southern France. This population was the most distant geographically from all the others and among the most recent introductions reported in France. In addition, in northern France, AFLP loci revealed a significant river basin effect, despite a common pathway of introduction. This result suggests a shift in local population dynamics, perhaps due to stochastic recruitment, and underlines the importance of local dispersal (e.g. via planktonic larvae) compared to overland transport in shaping the population structure of this naturalized freshwater mollusk. [ABSTRACT FROM AUTHOR]

The Southern Ocean benthic communities are characterized by their levels of endemism and their diversity of invertebrate brooding species. Overall, biological processes acting within these species remain poorly understood despite their importance to understand impacts of ongoing global change. We take part in filling this gap by studying the genetic structure over different spatial scales (from centimeters to tens of kilometers) in Abatus cordatus, an endemic and brooding sea urchin from the Kerguelen Islands. We developed three microsatellites and two exon-primed intron crossing markers and conducted a two-scale sampling scheme (from individuals to patches) within two dense localities of Abatus cordatus. Between patches, all pairwise comparisons, covering distances from few meters (between patches within locality) to 25 km (between localities), revealed significant genetic differentiation, a higher proportion of the molecular variance being explained by the comparisons between localities than within localities, in agreement with an isolation by distance model. Within patches, we found no significant correlation between individual pairwise spatial and genetic distances, except for the most polymorphic locus in the patch where the largest range of geographical distances had been analyzed. This study provides an estimation of the dispersal capacities of Abatus cordatus and highlights its low recolonization ability. Similar low recolonization capacities are thus expected in other Antarctic and Subantarctic brooding invertebrate species and suggest a high vulnerability of these species facing global change. [ABSTRACT FROM AUTHOR]

Here we present evidence that in water/acetonitrile solvent detailed structural and dynamic information can be obtained for important proteins that are naturally present as oligomers under native conditions. An NMR-derived human insulin monomer structure in H2O/CD3CN, 65/35 vol%, pH 3.6 is presented and compared with the available X-ray structure of a monomer that forms part of a hexamer (Acta Crystallogr. 2003 Sec. D59, 474) and with NMR structures in water and organic cosolvent. Detailed analysis using PFGSE NMR, temperature-dependent NMR, dilution experiments and CSI proves that the structure is monomeric in the concentration and temperature ranges 0.1–3 mM and 10–30°C, respectively. The presence of long-range interstrand NOEs, as found in the crystal structure of the monomer, provides the evidence for conservation of the tertiary structure. Starting from structures calculated by the program CYANA, two different molecular dynamics simulated annealing refinement protocols were applied, either using the program AMBER in vacuum (AMBER_VC), or including a generalized Born solvent model (AMBER_GB). [ABSTRACT FROM AUTHOR]

Summary  ARLTS1 – a member of ADP-ribosylation factor family, is a newly described candidate tumour suppressor gene. Recent studies show that a nonsense polymorphism, G446A (Trp149Stop), in ARLTS1 gene is significantly more frequent in familial cancer cases than in sporadic cancer cases. This study presents analysis of the germ-line G446A polymorphism in the ARLTS1 gene among 1686 consecutively collected patients with breast cancer, prostate cancer, malignant melanoma, thyroid papillary cancer or laryngeal cancer in Poland. The G446A allele was present in 1.81% (9/497) breast cancer patients, 1.46% (5/343) prostate cancer patients, 1.76% (7/397) melanoma patients, 1.65% (3/182) thyroid papillary carcinoma patients and 2.68% (8/299) of laryngeal cancer patients. The frequency of this polymorphism in the control group was 1.45% (8/552). Differences in the frequency of the G446A polymorphism between case and control groups were not statistically significant. In addition, there was no significant difference in the number of Cancer Familial Aggregations (CFA) among breast, prostate, thyroid or laryngeal cancer cases harbouring the G446A polymorphism, when compared to the G446A negative cases. Interestingly out of the CFA melanoma cases, 4/6 (66.6%) were found to harbour the change compared to only 20.2% (69/341) sporadic melanoma cases. This difference was statistically significant (p = 0.02, OR = 7.8). The results of this study suggest that the G446A in ARLTS1 gene is probably not associated with an increased risk of sporadic breast cancer, prostate cancer, melanoma, thyroid papillary cancer or laryngeal cancer. Moreover, the G446A polymorphism is not significantly more frequent in CFA cases except for families in which the proband had melanoma. To confirm this result more cases of melanoma should be analysed. [ABSTRACT FROM AUTHOR]

Recent studies suggest that there are groups of genes that predispose simultaneously to both early-onset breast and laryngeal cancer. Studies were performed on a large series of unselected patients with laryngeal cancer diagnosed in Szczecin, Poland. Pedigrees of 683 laryngeal cancer patients were analysed for the frequency of early-onset and late-onset breast cancer among first degree relatives. The observed frequencies of breast cancer in these families were compared to those expected. In addition, common mutations/variants in the 3 genes BRCA1, NOD2 and CYP1B1, known to be associated with early-onset breast cancer, were assessed to determine their frequency in 348 unselected laryngeal cancers. The average age at diagnosis of LC among patients, who had relatives affected by BC diagnosed under the age of 50 years was 57.62. In comparison LC patients reporting a first degree relative affected by BC diagnosed above 50 years of age, had an average age of diagnosis of 66.00 years, which was significantly different (p=0.0064). Similarly, the average age of diagnosis of BC among patients with LC diagnosed under age of 50 years was 46.7 years and whereas LC patients with tumors diagnosed above 50 years had relatives diagnosed with breast cancer at an average age of 53.37 years, which was significantly different (p=0.02). [ABSTRACT FROM AUTHOR]

Eight new chiral macrocyclic bisamides, containing binaphthyl and some other aromatic (phenyl or naphthyl) subunits, are obtained in racemic form. Preliminary results concerning their ability for complexation of alkali metal cations, using ESI-MS technique, are presented. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1038/s41598-021-98183-6. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-98183-6, published online 21 September 2021 The original version of this Article contained errors in the spelling of the authors Anna Le'sków, Malgorzata Tarnowska, Izabela Szczuka & Dorota Diakowska which were incorrectly given as Le'sków Anna, Tarnowska Malgorzata, Szczuka Izabela & Diakowska Dorota respectively. [Extracted from the article]

Glucosamine synthase (E.C. 2.6.1.16) is a promising target in antifungal drug design. It has been reported that its potent inhibitor, N-(4-methoxyfu-maroyl)-L-2,3-diaminopropanoic acid (FMDP), inactivates the enzyme by the Michael addition of the S-H group to the FMDP molecule followed by cyclisation reactions. In this study we have investigated, by means of semiempirical MNDO, PM3 and molecular mechanics methods, the energetics and kinetic possibility of the formation of various stereoisomers of the products of cyclisation of the Michael addition products detected experimentally. It was found that the substituted 1,4-thiazin-3-one can be formed in one step under alkaline conditions; the stereoisomers of this compound predicted to be the most stable on the basis of theoretical calculations are also the dominant ones in reality. [ABSTRACT FROM AUTHOR]

Diazomethyl ketones are one of the most effective irreversible inhibitors of cysteine proteinases and are therefore very important in drug design. In the present study a mechanism of inactivation is proposed based on the results of model MNDO calculations of the possible pathways. It was found that the mercaptide nucleophile, on approaching the carbonyl carbon as in the catalytic reaction path, binds to the inner diazo nitrogen. The intermediate thus formed can rearrange giving a stable product, β-thioketone, and molecular nitrogen, with a considerable energy gain. The energy barrier to this process is equal to 36.9 kcal/mol, and corresponds to a pyramidal transition state with the vertex at the methylene carbon and the base formed by the carbonyl, thiol, and diazo groups. The energy barrier can be lowered on deprotonation of the intermediate. Based on the results obtained it was concluded that good irreversible inhibitors of cysteine proteases must fulfil two structural requirements: i) the dimensions and charge distribution must be similar to those of the peptide bond and ii) a second electrophilic center must be present in the neighbourhood of the carbonyl carbon. These are requirements which are satisfied by other strong cysteine proteinase inhibitors: β-chloroketones and β-ketooxiranes. [ABSTRACT FROM AUTHOR]

Continuing our theoretical studies of glucosamine synthase catalysis, we have carried out MNDO and ab initio calculations of the first stage of the reaction, which involves the attack of a cysteine thiol group from the enzyme active site on the side chain carboxyamide group of glutamine, producing ammonia and thioester. The reactants were modelled by methyl mercaptate and acetamide, respectively. For two considered mechanisms of the reaction the energy surfaces were evaluated. Mechanism I, proposed by Chmara et al. (1985) involves the nucleophilic attack of a deprotonated thiol group on the carbonyl carbon atom. Mechanism II, postulated in our previous work (Tempczyk et al. 1989), assumes the concerted binding of the mercaptate sulphur to the carbonyl carbon and the sulfhydryl hydrogen to the amide nitrogen with simultaneous breaking of the S-H bond. The energy surface of mechanism I shows no minimum on the approach of the mercaptide anion towards the carbonyl carbon, which is also consistent with ab initio calculations in a 4-31 G basis set. Therefore, mechanism I seems to be unlikely. The same analysis of mechanism II shows that it leads to the desired products: methyl thioacetate and ammonia. The presence of a sulfhydryl hydrogen causes apparent pyramidicity of the amido nitrogen and lengthening of the C-N bond in the transition state, making conditions for the release of the ammonia molecule. The MNDO calculated energy barrier of the reaction is 50.1 kcal/mol and the approximate 4-31 G ab initio barrier (at the MNDO geometries of the substrate complex and the transition state) is 63 kcal/mol. The biggest energy contribution to the barrier comes from the breaking of the S-H bond, which also causes a large charge separation in the transition state. The latter affect may result in the stabilisation of the transition state in a real enzymatic environment when compared to the gas phase, e.g. by the interaction of the reacting center with a pair of oppositely charged amino acid side chains such as lysinium and glutamate (aspartate), which are present in the enzyme studied. To estimate the magnitude of this effect, molecular mechanics calculations were carried out on the reaction center at the transition state in our proposed model of the enzymatic active site. The site was supplemented by ammonium and acetate ion, which were to mimic the lysinium and glutamate/aspartate side chains. A transition state stabilization energy of 20 kcal/mol was obtained and this lowers the energy barrier to about 30 kcal/mol. This value is within the thermal energy range of an average protein and indicates that our mechanism is a possible route of glucosamine synthase catalysis. [ABSTRACT FROM AUTHOR]

Glucosamine synthase transfers the γ-amino group of glutamine to fructose, producing 1-glucosamine which is the key constituent of bacterial and fungal cell walls. In this study, model calculations were performed on substrate binding to the enzyme active site. Two models of the active site of glucosamine synthase were proposed, which assume two different sequences of aminoacids, Cys-Gly-Ile and Cys-Ala-Cys, the first one being the N-terminal sequence of the Escherichia coli enzyme. Several initial geometries were assumed for these tripeptides, the energy was then optimized by means of molecular mechanics. It has been found that the structure which is both energy optimal and satisfies the assumed cysteine sulphur arrangement consists of combinations of Cand Cconformations of single residues. Molecular mechanics calculations were then performed on glutamine and d-fructose-6-phosphate, which are the substrates of the enzymatic satalysis, and on their complex with the enzyme glutamine-binding site. The spatial configuration of the compounds under study, which is optimal as far as the reaction path is concerned, also turned out to be an energy minimum. [ABSTRACT FROM AUTHOR]

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This study analyzes the incidence of different types of cancer among 2839 first-degree relatives of 760 consecutive, unselected laryngeal cancer patients, compared with the general population. A statistically significant excess was seen for other cancers of the larynx (SIR: 400), lung (SIR: 135) and stomach (SIR: 271), and early-onset breast cancer (SIR: 287). Familial laryngeal cancer may not be a single site-specific cancer syndrome. [ABSTRACT FROM AUTHOR]

The publisher regret that in the Table 1 the data under column "Estimated age (kya)" aligned with the table entry "European moose (Alces alces)" was interchanged, original reading "20–35 Eastern/Western/Central" should have been "Eastern/Western/Central 20–35". The original article has been corrected. [ABSTRACT FROM AUTHOR]