CONODONTS OF THE LOWERMOST TRIASSIC OF SPITI, AND NEW ZONATION BASED ON NEOGONDOLELLA SUCCESSIONS

Conodonts from the lowermost Triassic Otoceras woodwardi beds and adjacent strata of Spiti are described and compared with Permian-Triassic (P-T) boundary bed faunas from elsewhere. A new pelagic zonation based on Neogondolella is introduced: the interval characterized by N. carinata-N. taylorae is subdivided into three parts based on successive first appearances of N. meishanensis, N. krystyni Orchard n. sp. and N. discreta Orchard and Krystyn n. sp., the nominal species of three successive zones. The development of these Griesbachian species involves a progressive morphological change in the configuration of the axial part (blade-carina-cusp) of the pectiniform elements. The pelagic conodont zonation is intercalibrated with the parallel zonation based on species of Hindeodus and Isarcicella, and with ammonoid faunas from Spiti, other Himalayan localities, and the Arctic. The meishanensis Zone embraces the parvus Zone and part of the overlying staeschei Zone. Strata containing O. woodwardi in Spiti carry the indices to the staeschei and krystyni zones. The Neogondolella conodont fauna associated with Otoceras differs from that of the latest Permian Changshing Limestone of China, but resembles that from the P-T boundary transition beds at Meishan, where a meishanensis Zone of restricted scope occurs beneath the parvus datum. The faunal change which introduces the characteristic Neogondolella species of the N. carinata-N. taylorae fauna occurs at the base of the P-T boundary transition beds at Meishan, the proposed boundary stratotype. Slightly above this level, the disappearance of most Neogondolella species and the introduction of new Hindeodus species coincides with a change in conodont biofacies rather than an extinction event. In the Spiti sections, the N. carinata-N. taylorae fauna, associated at first with H. parvus (as in Selong, Tibet), persists through the entire Griesbachian. Indices of the three Neogondolella zones are also recognized in the Salt Range and the Canadian Arctic. Four new conodont species are described: Neogondolella discreta, N. kazi, N. krystyni, and N. nassichuki.&nbsp

Intercalibration of Boreal and Tethyan timescales: the magneto-biostratigraphy of the Middle Triassic and the latest Early Triassic from Spitsbergen, Arctic Norway

An integrated bio-magnetostratigraphic study of the latest Early Triassic to the upper parts of the Middle Triassic, at Milne Edwardsfjellet in central Spitsbergen, Svalbard, allows a detailed correlation of Boreal and Tethyan biostratigraphies. The biostratigraphy consists of ammonoid and palynomorph zonations, supported by conodonts, through some 234 m of succession in two adjacent sections. The magnetostratigraphy consists of ten substantive normal–reverse polarity chrons defined by sampling at 150 stratigraphic levels. The magnetization is carried by magnetite and an unidentified magnetic sulphide, and is difficult to fully separate from a strong present-day like magnetization. The bio-magnetostratigraphy from the late Olenekian (Vendomdalen Member) is supplemented by data from nearby Vikinghøgda. The early and mid-Anisian has a high sedimentation rate, comprising over half the ca. 140-m thickness of the Botneheia Formation, whereas the late Anisian and lower Ladinian is condensed into about 20 m. The two latest Boreal Ladinian ammonoid zones are absent due to erosional truncation below the Tschermakfjellet Formation. Correlation to Tethyan bio-magnetostratigraphies shows the traditional base of the Boreal Anisian (base of G. taimyrensis Zone) precedes the base Anisian (using here definitions based on the Desli Caira section in Romania). The Boreal upper Anisian G. rotelliforme and F. nevadanus ammonoid zones correlate to most of the Tethyan Pelsonian and Illyrian substages. The base Ladinian defined in the Tethyan global boundary stratotype and point (GSSP) is closely equivalent to the traditional base of the Boreal Ladinian at the I. oleshkoi Zone. The latest Olenekian to early Anisian magnetic polarity timescale is refined using the Spitsbergen data

The influence of viscosity on the motility and sensory ability of the dinoflagellate Heterocapsa triquetra

Seawater viscosity is influenced by temperature as well as through excretion of exopolymers by some plankton. We examined the role of viscosity on the movement patterns and sensory abilities of the dinoflagellate Heterocapsa triquetra, manipulating the viscosity of seawater to simulate a 10+1.58C temperature change. In a second treatment, we seeded the water with microbeads to examine swimming behaviours in the presence of a mechanical stimulus. Increased viscosity reduced distances between conspecifics 4.7-fold and increased distances between protists and microbeads by 3.4-fold. Increased viscosity also affected other aspects of motility, with an overall reduction in swimming speed of 2.0- and 7.0-fold for treatments with and without mechanical stimuli. Higher viscosities were associated with upward vertical migration, in both the presence and absence of microbeads. Cells were highly sensitive to disturbances to the velocity field, by as little as 1.5%, and different approach distances of H. triquetra to conspecifics over mechanical stimuli suggest sensory capacity to distinguish types of particles. Mediation of motility and migratory behaviours through viscosity implies ramifications for the distribution of protists and their encounters with resources, predators and conspecifics triggered by events such as temperature changes and phytoplankton bloom events

PET Imaging a MPTP-Induced Mouse Model of Parkinson’s Disease Using the Fluoropropyl-Dihydrotetrabenazine Analog [18F]-DTBZ (AV-133)

Parkinson’s disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand 18F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of 18F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that 18F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality

Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

Genetic regulatory signatures underlying islet gene expression and type 2 diabetes

The majority of genetic variants associated with type 2 diabetes (T2D) are located outside of genes in noncoding regions that may regulate gene expression in disease-relevant tissues, like pancreatic islets. Here, we present the largest integrated analysis to date of high-resolution, high-throughput human islet molecular profiling data to characterize the genome (DNA), epigenome (DNA packaging), and transcriptome (gene expression). We find that T2D genetic variants are enriched in regions of the genome where transcription Regulatory Factor X (RFX) is predicted to bind in an islet-specific manner. Genetic variants that increase T2D risk are predicted to disrupt RFX binding, providing a molecular mechanism to explain how the genome can influence the epigenome, modulating gene expression and ultimately T2D risk

Transcriptional profiling defines histone acetylation as a regulator of gene expression during human-to-mosquito transmission of the malaria parasite Plasmodium falciparum

Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression. While epigenetic gene control has been studied during erythrocytic schizogony of P. falciparum, little is known about this process during human-to-mosquito transmission of the parasite. To unveil the potential role of histone acetylation during gene expression in gametocytes, we carried out a microarray-based transcriptome analysis on gametocytes treated with the histone deacetylase inhibitor trichostatin A (TSA). TSA-treatment impaired gametocyte maturation and lead to histone hyper-acetylation in these stages. Comparative transcriptomics identified 294 transcripts, which were more than 2-fold up-regulated during gametocytogenesis following TSA-treatment. In activated gametocytes, which were less sensitive to TSA, the transcript levels of 48 genes were increased. TSA-treatment further led to repression of ~145 genes in immature and mature gametocytes and 7 genes in activated gametocytes. Up-regulated genes are mainly associated with functions in invasion, cytoadherence, and protein export, while down-regulated genes could particularly be assigned to transcription and translation. Chromatin immunoprecipitation demonstrated a link between gene activation and histone acetylation for selected genes. Among the genes up-regulated in TSA-treated mature gametocytes was a gene encoding the ring finger (RING)-domain protein PfRNF1, a putative E3 ligase of the ubiquitin-mediated signaling pathway. Immunochemistry demonstrated PfRNF1 expression mainly in the sexual stages of P. falciparum with peak expression in stage II gametocytes, where the protein localized to the nucleus and cytoplasm. Pfrnf1 promoter and coding regions associated with acetylated histones, and TSA-treatment resulted in increased PfRNF1 levels. Our combined data point to an essential role of histone acetylation for gene regulation in gametocytes, which can be exploited for malaria transmission-blocking interventions