Reconstructions of deltaic environments from Holocene palynological records in the Volga delta, northern Caspian Sea

This article was made available through open access by the Brunel Open Access Publishing Fund.New palynological and ostracod data are presented from the Holocene Volga delta, obtained from short cores and surface samples collected in the Damchik region, near Astrakhan, Russian Federation in the northern Caspian Sea. Four phases of delta deposition are recognized and constrained by accelerated mass spectrometry (AMS) radiocarbon ages. Palynological records show that erosive channels, dunes (Baer hills) and inter-dune lakes were present during the period 11,500–8900 cal. BP at the time of the Mangyshlak Caspian lowstand. The period 8900–3770 cal. BP was characterized regionally by extensive steppe vegetation, with forest present at times with warmer, more humid climates, and with halophytic and xerophytic vegetation present at times of drought. The period 3770–2080 cal. BP was a time of active delta deposition, with forest or woodland close to the delta, indicating relatively warm and humid climates and variable Caspian Sea levels. From 2080 cal. BP to the present-day, aquatic pollen is frequent in highstand intervals and herbaceous pollen and fungal hyphae frequent in lowstand intervals. Soils and incised valley sediments are associated with the regional Derbent regression and may be time-equivalent with the ‘Medieval Warm Period’. Fungal spores are an indicator of erosional or aeolian processes, whereas fungal hyphae are associated with soil formation. Freshwater algae, ostracods and dinocysts indicate mainly freshwater conditions during the Holocene with minor brackish influences. Dinocysts present include Spiniferites cruciformis, Caspidinium rugosum, Impagidinium caspienense and Pterocysta cruciformis, the latter a new record for the Caspian Sea. The Holocene Volga delta is a partial analogue for the much larger oil and gas bearing Mio-Pliocene palaeo-Volga delta.Funding for the data collection and field work was provided from the following sources: 1 – IGCP-UNESCO 2003–2008 (Project 481 CASPAGE, Dating Caspian Sea Level Change); 2 – NWO, Netherlands Science Foundation and RFFI, Russian Science Foundation 2005–2008 (Programme: ‘VHR Seismic Stratigraphy and Paleoecology of the Holocene Volga Delta’); and 3 – BP Exploration (Caspian Sea) Sea Ltd. (Azeri-Chirag-Gunashli) 2005–2008 (‘Unravelling the Small-Scale Stratigraphy and Sediment Dynamics of the Modern Volga Delta Using VHR Marine Geophysics’). The palynological work was funded jointly by BP Exploration (Caspian Sea) Ltd., Delft University of Technology and KrA Stratigraphic Ltd. Ostracod analyses were funded by StrataData Ltd. and funding for two additional radiocarbon dates provided by Deltares

Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD

Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n = 9, FEV1 80–110% predicted) and moderate (n = 9, FEV1 50–60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis

Metatypical basal cell carcinoma: a clinical review

Background. Metatypical cell carcinoma can be considered as a new entity of skin cancer, being an intermediate typology between basal cell carcinomas and squamous cell carcinomas. The behaviour of the metatypical cell carcinoma lies between these two varieties of skin cancer. It is difficult to perform a differential diagnosis based on morphological and clinical features - therefore it is only possible by accurate histology. Methods. The authors have retrospectively analysed clinical records of 240 patients who were affected by metatypical skin cancer and who were treated by surgery, radiotherapy and chemotherapy. Results. MTC affected more males than females (62.5% vs 37.5%) than males. The most affected site was the cervicofacial area, 71.7%; then the trunk, 10%; the limbs, 9.6%; the scalp 3.7%; and other regions 5%. A recurrence occurred in 24 cases (10%), mainly in head and neck area. Conclusion. In this manuscript, the authors have emphasised the importance of conducting a differential diagnosis, and the importance of the specific treatment for metatypical skin cancer, even though more clinical studies and long-term follow-ups are required before establishing specific guidelines. © 2008 Tarallo et al; licensee BioMed Central Ltd

The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation

The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome

Atlantic cod (Gadus morhua) hemoglobin genes: multiplicity and polymorphism

Background: Hemoglobin (Hb) polymorphism, assessed by protein gel electrophoresis, has been used almost exclusively to characterize the genetic structure of Atlantic cod (Gadus morhua) populations and to establish correlations with phenotypic traits such as Hb oxygen binding capacity, temperature tolerance and growth characteristics. The genetic system used to explain the results of gel electrophoresis entails the presence of one polymorphic locus with two major alleles (HbI-1; HbI-2). However, vertebrates have more than one gene encoding Hbs and recent studies have reported that more than one Hb gene is present in Atlantic cod. These observations prompted us to re-evaluate the number of Hb genes expressed in Atlantic cod, and to perform an in depth search for polymorphisms that might produce relevant phenotypes for breeding programs. Results: Analysis of Expressed Sequence Tags (ESTs) led to the identification of nine distinct Hb transcripts; four corresponding to the α Hb gene family and five to the β Hb gene family. To gain insights about the Hb genes encoding these transcripts, genomic sequence data was generated from heterozygous (HbI-1/2) parents and fifteen progeny; five of each HbI type, i.e., HbI-1/1, HbI-1/2 and HbI-2/2. β Hb genes displayed more polymorphism than α Hb genes. Two major allele types (β1A and β1B) that differ by two linked non-synonymous substitutions (Met55Val and Lys62Ala) were found in the β1 Hb gene, and the distribution of these β1A and β1B alleles among individuals was congruent with that of the HbI-1 and HbI-2 alleles determined by protein gel electrophoresis. RT-PCR and Q-PCR analysis of the nine Hb genes indicates that all genes are expressed in adult fish, but their level of expression varies greatly; higher expression of almost all Hb genes was found in individuals displaying the HbI-2/2 electrophoretic type. Conclusion: This study indicates that more Hb genes are present and expressed in adult Atlantic cod than previously documented. Our finding that nine Hb genes are expressed simultaneously in adult fish suggests that Atlantic cod, similarly to fish such as rainbow trout, carp, and goldfish, might be able to respond to environmental challenges such as chronic hypoxia or long-term changes in temperature by altering the level of expression of these genes. In this context, the role of the non-conservative substitution Lys62Ala found in the β1 Hb gene, which appears to explain the occurrence of the HbI-1 and HbI-2 alleles described by gel electrophoresis, and which was found to be present in other fish such as eel, emerald rockcod, rainbow trout and moray, requires further investigation

Comparative study of fungal cell disruption—scope and limitations of the methods

Simple and effective protocols of cell wall disruption were elaborated for tested fungal strains: Penicillium citrinum, Aspergillus fumigatus, Rhodotorula gracilis. Several techniques of cell wall disintegration were studied, including ultrasound disintegration, homogenization in bead mill, application of chemicals of various types, and osmotic shock. The release of proteins from fungal cells and the activity of a cytosolic enzyme, glucose-6-phosphate dehydrogenase, in the crude extracts were assayed to determine and compare the efficacy of each method. The presented studies allowed adjusting the particular method to a particular strain. The mechanical methods of disintegration appeared to be the most effective for the disintegration of yeast, R. gracilis, and filamentous fungi, A. fumigatus and P. citrinum. Ultrasonication and bead milling led to obtaining fungal cell-free extracts containing high concentrations of soluble proteins and active glucose-6-phosphate dehydrogenase systems

Generation of ESTs for Flowering Gene Discovery and SSR Marker Development in Upland Cotton

BACKGROUND: Upland cotton, Gossypium hirsutum L., is one of the world's most important economic crops. In the absence of the entire genomic sequence, a large number of expressed sequence tag (EST) resources of upland cotton have been generated and used in several studies. However, information about the flower development of this species is rare. METHODOLOGY/PRINCIPAL FINDINGS: To clarify the molecular mechanism of flower development in upland cotton, 22,915 high-quality ESTs were generated and assembled into 14,373 unique sequences consisting of 4,563 contigs and 9,810 singletons from a normalized and full-length cDNA library constructed from pooled RNA isolated from shoot apexes, squares, and flowers. Comparative analysis indicated that 5,352 unique sequences had no high-degree matches to the cotton public database. Functional annotation showed that several upland cotton homologs with flowering-related genes were identified in our library. The majority of these genes were specifically expressed in flowering-related tissues. Three GhSEP (G. hirsutum L. SEPALLATA) genes determining floral organ development were cloned, and quantitative real-time PCR (qRT-PCR) revealed that these genes were expressed preferentially in squares or flowers. Furthermore, 670 new putative microsatellites with flanking sequences sufficient for primer design were identified from the 645 unigenes. Twenty-five EST-simple sequence repeats were randomly selected for validation and transferability testing in 17 Gossypium species. Of these, 23 were identified as true-to-type simple sequence repeat loci and were highly transferable among Gossypium species. CONCLUSIONS/SIGNIFICANCE: A high-quality, normalized, full-length cDNA library with a total of 14,373 unique ESTs was generated to provide sequence information for gene discovery and marker development related to upland cotton flower development. These EST resources form a valuable foundation for gene expression profiling analysis, functional analysis of newly discovered genes, genetic linkage, and quantitative trait loci analysis

Partial Loss of Ataxin-1 Function Contributes to Transcriptional Dysregulation in Spinocerebellar Ataxia Type 1 Pathogenesis

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a CAG repeat that encodes a polyglutamine tract in ATAXIN1 (ATXN1). Molecular and genetic data indicate that SCA1 is mainly caused by a gain-of-function mechanism. However, deletion of wild-type ATXN1 enhances SCA1 pathogenesis, whereas increased levels of an evolutionarily conserved paralog of ATXN1, Ataxin 1-Like, ameliorate it. These data suggest that a partial loss of ATXN1 function contributes to SCA1. To address this possibility, we set out to determine if the SCA1 disease model (Atxn1154Q/+ mice) and the loss of Atxn1 function model (Atxn1−/− mice) share molecular changes that could potentially contribute to SCA1 pathogenesis. To identify transcriptional changes that might result from loss of function of ATXN1 in SCA1, we performed gene expression microarray studies on cerebellar RNA from Atxn1−/− and Atxn1154Q/+ cerebella and uncovered shared gene expression changes. We further show that mild overexpression of Ataxin-1-Like rescues several of the molecular and behavioral defects in Atxn1−/− mice. These results support a model in which Ataxin 1-Like overexpression represses SCA1 pathogenesis by compensating for a partial loss of function of Atxn1. Altogether, these data provide evidence that partial loss of Atxn1 function contributes to SCA1 pathogenesis and raise the possibility that loss-of-function mechanisms contribute to other dominantly inherited neurodegenerative diseases

Exome Sequencing and Genetic Testing for MODY

Context: Genetic testing for monogenic diabetes is important for patient care. Given the extensive genetic and clinical heterogeneity of diabetes, exome sequencing might provide additional diagnostic potential when standard Sanger sequencing-based diagnostics is inconclusive. Objective: The aim of the study was to examine the performance of exome sequencing for a molecular diagnosis of MODY in patients who have undergone conventional diagnostic sequencing of candidate genes with negative results. Research Design and Methods: We performed exome enrichment followed by high-throughput sequencing in nine patients with suspected MODY. They were Sanger sequencing-negative for mutations in the HNF1A, HNF4A, GCK, HNF1B and INS genes. We excluded common, non-coding and synonymous gene variants, and performed in-depth analysis on filtered sequence variants in a pre-defined set of 111 genes implicated in glucose metabolism. Results: On average, we obtained 45 X median coverage of the entire targeted exome and found 199 rare coding variants per individual. We identified 0–4 rare non-synonymous and nonsense variants per individual in our a priori list of 111 candidate genes. Three of the variants were considered pathogenic (in ABCC8, HNF4A and PPARG, respectively), thus exome sequencing led to a genetic diagnosis in at least three of the nine patients. Approximately 91% of known heterozygous SNPs in the target exomes were detected, but we also found low coverage in some key diabetes genes using our current exome sequencing approach. Novel variants in the genes ARAP1, GLIS3, MADD, NOTCH2 and WFS1 need further investigation to reveal their possible role in diabetes. Conclusion: Our results demonstrate that exome sequencing can improve molecular diagnostics of MODY when used as a complement to Sanger sequencing. However, improvements will be needed, especially concerning coverage, before the full potential of exome sequencing can be realized