Orbital changes, variation in solar activity and increased anthropogenic activities: controls on the Holocene flood frequency in the Lake Ledro area, Northern Italy

International audienceTwo lacustrine sediment cores from Lake Ledro in northern Italy were studied to produce chronologies of floodevents for the past 10 000 yr. For this purpose, we have developed an automatic method that objectively identifies the sedimentary imprint of river floods in the downstream lake basin. The method was based on colour data extracted from processed core photographs, and the count data were analysed to capture the flood signal. Flood frequency and reconstructed sedimentary dynamics were compared with lake-level changes and pollen inferred vegetation dynamics. The results suggest a record marked by low flood frequency during the early and middle Holocene (10 000–4500 cal BP). Only modest increases during short intervals are recorded at ca. 8000, 7500, and 7100 cal BP. After 4500–4000 cal BP, the record shows a shift toward increased flood frequency. With the exception of two short intervals around 2900–2500 and 1800–1400 cal BP, which show a slightly reduced number of floods, the trend of increasing flood frequency prevailed until the 20th century, reaching a maximum between the 16th and the 19th centuries. Brief-flood frequency increases recorded during the early and middle Holocene can be attributed to climatic oscillations. On a centennial time scale, major changes in flood frequency, such as those observed after ca. 4500/4000 and 500 cal BP, can be attributed to large-scale climatic changes such as the Neo-glacial and Little Ice Age, which are under orbital and possibly solar control. However, in the Bronze Age and during the Middle Ages and modern times, forest clearing and land use probably partially control the flood activity

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Sex Differences in Diabetes Risk and the Effect of Intensive Lifestyle Modification in the Diabetes Prevention Program

OBJECTIVE—In participants of the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS), meeting ILS goals strongly correlated with prevention of diabetes in the group as a whole. Men met significantly more ILS goals than women but had a similar incidence of diabetes. Therefore, we explored sex differences in risk factors for diabetes and the effect of ILS on risk factors

A Spectroscopic Study of a Large Sample of Wolf-Rayet Galaxies

We analyze long-slit spectral observations of 39 Wolf-Rayet (WR) galaxies with heavy element mass fraction ranging over 2 orders of magnitude, from Zsun/50 to 2Zsun. Nearly all galaxies in our sample show broad WR emission in the blue region of the spectrum (the blue bump) consisting of an unresolved blend of N III 4640, C III 4650, C IV 4658 and He II 4686 emission lines. Broad C IV 5808 emission (the red bump) is detected in 30 galaxies. Additionally, weaker WR emission lines are identified, most often the N III 4512 and Si III 4565 lines, which have very rarely or never been seen and discussed before in WR galaxies. These emission features are characteristic of WN7-WN8 and WN9-WN11 stars respectively. We derive the numbers of early WC (WCE) and late WN (WNL) stars from the luminosities of the red and blue bumps, and the number of O stars from the luminosity of the Hbeta emission line. Additionally, we propose a new technique for deriving the numbers of WNL stars from the N III 4512 and Si III 4565 emission lines. This technique is potentially more precise than the blue bump method because it does not suffer from contamination of WCE and early WN (WNE) stars and nebular gaseous emission. The N(WR)/N(O+WR) ratio decreases with decreasing metallicity, in agreement with predictions of evolutionary synthesis models. The N(WC)/N(WN) ratios and the equivalent widths of the blue bump EW(4650) and of the red bump EW(5808) derived from observations are also in satisfactory agreement with theoretical predictions.Comment: 49 pages, 9 figures, to appear in Astrophys.

Association of Intrauterine Exposure to Maternal Diabetes and Obesity With Type 2 Diabetes in Youth: The SEARCH Case-Control Study

OBJECTIVE—Limited data exist on the association between in utero exposure to maternal diabetes and obesity and type 2 diabetes in diverse youth. These associations were explored in African-American, Hispanic, and non-Hispanic white youth participating in the SEARCH Case-Control Study

Rapid and multi-level characterization of trastuzumab using sheathless capillary electrophoresis-tandem mass spectrometry

Monoclonal antibodies (mAbs) are highly complex proteins that display a wide range of microheterogeneity that requires multiple analytical methods for full structure assessment and quality control. As a consequence, the characterization of mAbs on different levels is particularly product - and time - consuming. This work presents the characterization of trastuzumab sequence using sheathless capillary electrophoresis (referred as CESI) – tandem mass spectrometry (CESIMS/MS). Using this bottom-up proteomic-like approach, CESI-MS/MS provided 100% sequence coverage for both heavy and light chain via peptide fragment fingerprinting (PFF) identification. The result was accomplished in a single shot, corresponding to the analysis of 100 fmoles of digest. The same analysis also enabled precise characterization of the post-translational hot spots of trastuzumab, used as a representative widely marketed therapeutic mAb, including the structural confirmation of the five major N-glycoforms

PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response

Poly(ADP-ribose) polymerases (PARPs; also known as ADP-ribosyl transferase D proteins) modify acceptor proteins with ADP-ribose modifications of varying length (reviewed in refs 1, 2, 3). PARPs regulate key stress response pathways, including DNA damage repair and the cytoplasmic stress response. Here, we show that PARPs also regulate the unfolded protein response (UPR) of the endoplasmic reticulum (ER). Human PARP16 (also known as ARTD15) is a tail-anchored ER transmembrane protein required for activation of the functionally related ER stress sensors PERK and IRE1α during the UPR. The third identified ER stress sensor, ATF6, is not regulated by PARP16. As is the case for other PARPs that function during stress, the enzymatic activity of PARP16 is upregulated during ER stress when it ADP-ribosylates itself, PERK and IRE1α. ADP-ribosylation by PARP16 is sufficient for activating PERK and IRE1α in the absence of ER stress, and is required for PERK and IRE1α activation during the UPR. Modification of PERK and IRE1α by PARP16 increases their kinase activities and the endonuclease activity of IRE1α. Interestingly, the carboxy-terminal luminal tail of PARP16 is required for PARP16 function during ER stress, suggesting that it transduces stress signals to the cytoplasmic PARP catalytic domain.National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051)National Institutes of Health (U.S.) (Grant 5R01 GM087465-02)Kathy and Curt Marble Cancer Research FundJeptha H. and Emily V. Wade FundVirginia and D.K. Ludwig Fund for Cancer Researc

Cardiovascular Risk Factors Among Youth With and Without Type 2 Diabetes: Differences and possible mechanisms

OBJECTIVE—To compare cardiovascular disease (CVD) risk factors among recently diagnosed youth with type 2 diabetes and nondiabetic youth and investigate whether demographic, behavioral, or metabolic factors might account for observed differences