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This paper presents the earliest evidence for the exploitation of lignite (brown coal) in Europe and sheds new light on the use of combustion fuel sources in the 2nd millennium BCE Eastern Mediterranean. We applied Thermal Desorption/Pyrolysis-Gas Chromatography-Mass Spectrometry and Polarizing Microscopy to the dental calculus of 67 individuals and we identified clear evidence for combustion markers embedded within this calculus. In contrast to the scant evidence for combustion markers within the calculus samples from Egypt, all other individuals show the inhalation of smoke from fires burning wood identified as Pinaceae, in addition to hardwood, such as oak and olive, and/ or dung. Importantly, individuals from the Palatial Period at the Mycenaean citadel of Tiryns and the Cretan harbour site of Chania also show the inhalation of fire-smoke from lignite, consistent with the chemical signature of sources in the northwestern Peloponnese and Western Crete respectively. This first evidence for lignite exploitation was likely connected to and at the same time enabled Late Bronze Age Aegean metal and pottery production, significantly by both male and female individuals.

A conservação dos remanescentes de Floresta Ombrófila Mista (FOM) representa um grande desafio, mas com potencial de redução dos níveis de desmatamento à medida que o manejo sustentável dos seus recursos é estimulado. No entanto, a realização de pesquisas sobre o tema não tem sido incentivada, principalmente em função das atuais restrições legais. Nesse sentido, esse trabalho apresenta a metodologia de ordenamento florestal por talhões, técnica amplamente utilizada com êxito na Europa Central, aplicada à FOM, tendo como área de estudo a Estação Experimental da Embrapa em Caçador ? SC. A metodologia proposta envolveu duas etapas principais: a divisão territorial e a descrição e definição de técnicas silviculturais gerais. Como resultado, caracterizaram-se áreas de uso restrito para o manejo florestal e seis subtipologias distintas, que foram agrupadas em quatro unidades silviculturais (floresta com araucária; floresta estruturada; floresta degradada e vegetação de solos úmidos). As subtipologias mapeadas e descritas neste trabalho representam as mesmas variações que ocorrem ao longo do território ocupado pela FOM, de forma que os regimes silviculturais gerais apresentados também podem ser aplicados em áreas com características similares. Entre os regimes silviculturais propostos encontram-se intervenções pelo método de seleção, cortes de melhoramento, plantios de adensamento e de enriquecimento, raleio de espécies pioneiras, controle da taquara e coleta de produtos florestais não-madeireiros. A metodologia aqui apresentada pode dar suporte na tomada de decisões no que se refere à gestão da propriedade rural, visando, principalmente, o uso e conservação dos remanescentes florestais. Made available in DSpace on 2020-08-18T04:10:54Z (GMT). No. of bitstreams: 1 Augsta-8379-Article-Text-39644-1-10-20200628-1.pdf: 754252 bytes, checksum: b4e927bdc4263e456865d4e9cc5b803c (MD5) Previous issue date: 2020

Neste trabalho são abordados aspectos metodológicos da análise do mosaico da paisagem aplicada à avaliação do risco de degradação de habitats. A técnica se baseia no uso de janelas móveis para medir as contribuições relativas de três tipos-chave de uso e cobertura da terra (ambientes naturais ou seminaturais, áreas de cultivo agrícola e áreas urbanizadas), na vizinhança de um determinado pixel do mapa correspondente. Sobre esses resultados é sobreposta uma máscara dos habitats florestais (Floresta Natural, Outras Terras com Vegetação Lenhosa e Outras Terras com Árvores) para caracterizar o contexto da paisagem florestal no seu entorno, que pode ser natural ou uma mescla de zonas de interface floresta/não-floresta com áreas de agricultura ou urbanizadas. O módulo Dominance do programa GuidosToolbox empregado na análise utiliza cinco diferentes tamanhos de janela móvel, gerando cinco diferentes áreas de vizinhança, além de resultados numa abordagem integrada multiescala. Para demonstrar os procedimentos metodológicos foi utilizada uma subamostra de 425 Unidades Amostrais de Paisagem (UAPs) que integram a componente espacial do Inventário Florestal Nacional do Brasil (IFN-BR), distribuídas nos biomas Pampa, Mata Atlântica e Caatinga. O efeito da escala de observação sobre os resultados foi demonstrado em UAPs individuais. Para o conjunto de todas as UAPs da subamostra foram calculados três índices de mosaico da paisagem usando a abordagem multiescala. O valor do índice padrão de paisagem florestal natural foi utilizado como indicativo do grau de risco de degradação de habitats. Entre os três biomas amostrados, as UAPs da Caatinga são as que possuem o menor risco de degradação de habitats, pois 60% delas consistem em paisagens onde 60% ou mais das áreas de cobertura arbórea/arbustiva possuem vizinhança natural. Os biomas Mata Atlântica e Pampa são mais susceptíveis à degradação, considerando que, em mais de 75% das UAPs amostradas em cada um deles, o percentual de áreas florestais com vizinhança natural é inferior a 60%.

Monoallelic PMS2 germline mutations cause 5-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional MMR deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined PMS2 mutation detection yield and mutation spectrum in a nationwide cohort of 396 probands. Furthermore, we studied concordance between tumor IHC/ MSI (immunohistochemistry/ microsatellite-instability) profile and mutation carrier state. Overall, we found 52 different pathogenic PMS2 variants explaining 121 Lynch syndrome and nine CMMRD patients. In vitro MMR assays suggested pathogenicity for three missense variants. Ninety-one PMS2 mutation carriers (70%) showed isolated loss of PMS2 in their tumors, for 31 (24%) no or inconclusive IHC was available, and eight carriers (6%) showed discordant IHC (presence of PMS2 or loss of both MLH1 and PMS2). Ten cases with isolated PMS2 loss (10%; 10/97) harbored MLH1 mutations. We confirmed that recently improved mutation analysis provides a high yield of PMS2 mutations in patients with isolated loss of PMS2 expression. Application of universal tumor pre-screening methods will however miss some PMS2 germline mutation carriers. This article is protected by copyright. All rights reserved.

Von Hippel-Lindau (VHL) disease is an autosomal dominant rare tumor syndrome characterized by high penetrance. VHL mutation carriers develop numerous manifestations in multiple organs during life. The natural course of development of new and growth of existing VHL-related manifestations is still unclear. In this study we aimed to gain insight into the development of subsequent manifestations in VHL disease. We retrospectively scored each new VHL-related manifestation as detected by standard follow-up (retina, central nervous system, kidneys and pancreas, excluding adrenal and endolymfatic sac manifestations) in 75 VHL mutation carriers. The Kaplan–Meier method was used to plot the cumulative proportions of all consecutive manifestations in each organ against age. The cumulative average number of manifestations in all organs during life was calculated by summating these cumulative proportions. Poisson model parameters were used to calculate average time to the detection of consecutive VHL manifestations in each organ. Consecutive VHL-related kidney and retina manifestations during life occur linearly according to Poisson distribution model. The total number of VHL manifestations rises linearly, with an average of seven VHL-related lesions at age 60 years. The incidence of consecutive VHL-related manifestations is constant during life in VHL mutation carriers. Our data is consistent with the notion that somatic inactivation of the remaining allele (Knudson’s “two-hit” hypothesis) is the determining factor in developing new VHL-related manifestations. Electronic supplementary material The online version of this article (10.1007/s10689-019-00131-x) contains supplementary material, which is available to authorized users.

Background: PMS2-associated Lynch syndrome is characterized by a relatively low colorectal cancer penetrance compared with other Lynch syndromes. However, age at colorectal cancer diagnosis varies widely, and a strong genetic anticipation effect has been suggested for PMS2 families. In this study, we examined proposed genetic anticipation in a sample of 152 European PMS2 families. Methods: The 152 families (637 family members) that were eligible for analysis were mainly clinically ascertained via clinical genetics centers. We used weighted Cox-type random effects model, adjusted by birth cohort and sex, to estimate the generational effect on the age of onset of colorectal cancer. Probands and young birth cohorts were excluded from the analyses. Weights represented mutation probabilities based on kinship coefficients, thus avoiding testing bias. Results: Family data across three generations, including 123 colorectal cancers, were analyzed. When compared with the first generation, the crude HR for anticipation was 2.242 [95% confidence interval (CI), 1.162–4.328] for the second generation and 2.644 (95% CI, 1.082–6.464) for the third generation. However, after correction for birth cohort and sex, the effect vanished [HR = 1.302 (95% CI, 0.648–2.619) and HR = 1.074 (95% CI, 0.406–2.842) for second and third generations, respectively]. Conclusions: Our study did not confirm previous reports of genetic anticipation in PMS2-associated Lynch syndrome. Birth-cohort effect seems the most likely explanation for observed younger colorectal cancer diagnosis in subsequent generations, particularly because there is currently no commonly accepted biological mechanism that could explain genetic anticipation in Lynch syndrome. Impact: This new model for studying genetic anticipation provides a standard for rigorous analysis of families with dominantly inherited cancer predisposition.

Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2–3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5–4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients. Electronic supplementary material The online version of this article (10.1007/s10689-017-0061-3) contains supplementary material, which is available to authorized users.

Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors that are hereditary in up to 50% of patients. The gene encoding transmembrane-protein-127 (TMEM127) is one of the PCC/PGL-susceptibility genes with an autosomal dominant inheritance pattern. Here, we report 2 patients with bilateral PCC who both harbored a homozygous TMEM127-mutation. In a 31-year-old mentally retarded patient, the homozygous c.410-2A > G mutation was discovered during an update of DNA analysis. A 26-year-old mentally retarded patient was found to have a homozygous c.3G > A mutation. The parents of both patients were consanguineous. We reviewed previously reported clinical features of TMEM127 mutation carriers and compared our findings with case descriptions of homozygous mutations in other PGL/PCC-susceptibility genes. Homozygosity for an autosomal dominant inherited disorder is an extremely rare phenomenon and has, to our knowledge, not been reported before for the gene encoding TMEM127. In the present cases, the clinical picture does not seem to be very different from heterozygous TMEM127 mutation carriers, except for a relatively large tumor size and more pronounced plasma metanephrine concentration. It is unclear whether the mental retardation is causally related to homozygosity of the TMEM127 mutations. Updating genetic screening in patients in whom PCC/PGL has been diagnosed in the past should be considered as it might provide clinically relevant information.

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer. Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome. Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein–Taybi syndrome, ARID1A-based Coffin–Siris syndrome, ACTB-based Baraitser–Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition. Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. Clin Cancer Res; 24(7); 1594–603. ©2018 AACR.

Purpose: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole-exome sequencing on a selected cohort of children with cancer. Experimental Design: To identify mutations in known and novel cancer-predisposing genes, we performed trio-based whole-exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer, or (4) an adult type of cancer. We first analyzed the sequence data for germline mutations in 146 known cancer-predisposing genes. If no causative mutation was found, the analysis was extended to the whole exome. Results: Four patients carried causative mutations in a known cancer-predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome sequencing revealed mutations causing syndromes that might have contributed to the malignancy (EP300-based Rubinstein-Taybi syndrome, ARID1A-based Coffin-Siris syndrome, ACTB-based Baraitser-Winter syndrome, and EZH2-based Weaver syndrome). In addition, we identified two genes, KDM3B and TYK2, which are possibly involved in genetic cancer predisposition. Conclusions: In our selected cohort of patients, pathogenic germline mutations causative or likely causative of the cancer phenotype were found in 8 patients, and two possible novel cancer-predisposing genes were identified. Therewith, our study shows the added value of sequencing beyond a cancer gene panel in selected patients, to recognize childhood cancer predisposition. (C) 2018 AACR.

The objective of this present study is to investigate the efficiency of chitosan as an adsorbent to treat egg processing industry wastewater. Parameters affecting the effluent treatment process such as pH, chitosan dosage, settling time and initial chemical oxygen demand (COD) concentration on the reduction percentage of turbidity, COD and biochemical oxygen demand (BOD) were studied. Optimum condition was found to be pH of 4, chitosan dosage of 1.1 g L-1 and settling time of 40 min respectively. The maximum reduction percentage of turbidity, COD and BOD were found to be 94 %, 88 % and 83 % respectively. The effective adsorption process was confirmed by FT-IR spectra analysis. The experimental data was analyzed by different isotherm and kinetic models. Langmuir isotherm type I model was satisfactorily described the adsorption mechanism and the rate of COD reduction followed the pseudo-first-order kinetic model. A four factor, three levels Box-Behnken response surface design was employed to develop second order polynomial mathematical models from the experimental data.

Transport jars from the Mycenaean citadel of Tiryns, a coastal centre in the Bronze Age, were analysed in a macroscopic and petrographic study. Over 400 vessels and vessel fragments, mostly Transport Stirrup Jars (TSJs) and Canaanite jars, were recorded; around a quarter of them were selected for analysis. The vessels derive from both the upper and lower citadel, with a few from the lower town. Their chronological span ranges from Late Helladic (LH) IIIB1 to LH IIIC Developed (ca 1300–1070 BC) but the bulk of the material dates to LH IIIB2 (ca 1200 BC), and comes from dumps derived from the final destruction of the palace. Several sources are suggested for the TSJs, some of which are inscribed with Linear B: Kythera, the eastern Aegean (perhaps Kos), Kontopigado-Alimos in Attica, Corinth and several other mainland sources, as yet unidentified. It is suggested that a large group of TSJs with shape and decoration derived from central Cretan types were produced in the vicinity of the Argive Plain. Two thirds of the TSJs, however, come from Crete. With the exception of one from the Vrokastro area of east Crete, these are evenly derived from the Chania plain and the western edge of the Mesara plain in central Crete, where the Minoan centres of Kommos, Phaistos and Ayia Triada are located. We discuss the implications of all this for our understanding of the economy and society of Crete after the destruction of the palace of Knossos, and for the relationship between Crete and the Mycenaean palatial centres in the Argolid.

O bioma florestal mais característico do Sul do Brasil é a Floresta Ombrófila Mista, fortemente marcada pela presença da espécie Araucaria angustifolia. Entretanto, a exploração irracional e descontrolada desta espécie reduziu drasticamente sua área de ocorrência a 2% de sua área original. Assim, esforços devem ser feitos para auxiliar e promover sua regeneração natural, visando a sua preservação e o uso sustentável de seus recursos econômicos. Com o objetivo de avaliar a germinação, sobrevivência e predação de mudas e sementes de Araucaria angustifolia foi implantado um experimento em delineamento inteiramente casualizado, no qual foram investigados os efeitos de dois fatores com dois níveis cada (tipo de plantio: puro/ misto; material plantado: mudas/sementes), com três repetições, perfazendo um total de quatro tratamentos. Após 14 meses restaram 17% das covas ocupadas por mudas e 14% das ocupadas por pinhões; 60% das sementes germinadas foram consumidas pela fauna; o percentual de sobrevivência médio das mudas foi de 41,1% no plantio puro e de 20,0% no plantio misto. No tratamento misto, as perdas de sementes, devido à ação fauna, foram menores (42,2%) quando comparadas ao tratamento puro (68,9%); o contrário foi válido no caso das mudas.

AIM: Patients with germline phosphatase and tensin homologue (PTEN) mutations develop hamartomatous lesions in several organs and are at increased risk of various malignancies. We assessed the lifetime risk of benign and malignant gastrointestinal lesions in patients with a proven PTEN mutation. METHOD: Data on gender, mutation, dates of birth, last contact, and diagnosis, location and type of gastrointestinal lesions were collected from nine countries. The lifetime risk of gastrointestinal lesions was calculated by Kaplan-Meier methods. RESULTS: A total of 156 patients (67 men, 43%) from 101 families with a PTEN mutation were included. Patients were born between 1928 and 2008. Benign gastrointestinal polyps were reported in 49 (31%) patients at a mean age of 38 years (range 18-62 years) and were most often hamartomas. Twenty-two (44%) patients had upper as well as lower gastrointestinal lesions, 14 (29%) had only colonic lesions and 13 (27%) had gastrointestinal lesions at unknown sites. The cumulative risk of developing benign gastrointestinal polyps was 70% at age 60. Four patients (two men) developed colorectal carcinoma at 53, 57, 59 and 62 years, respectively. The cumulative risk of developing colorectal carcinoma was 18% at age 60. Except for one carcinoid in the small intestine, no upper gastrointestinal cancers were observed. CONCLUSION: Benign gastrointestinal lesions are common in PTEN mutation carriers, and a three- to four-fold increased lifetime risk of colorectal cancer compared with the general population may exist. Colorectal screening of patients with germline PTEN mutations is recommended, starting at age 40 years.