Complexity of diatom response to Lateglacial and Holocene climate and environmental change in ancient, deep and oligotrophic Lake Ohrid (Macedonia and Albania)

© Author(s) 2016. Lake Ohrid (Macedonia and Albania) is a rare example of a deep, ancient Mediterranean lake and is a key site for palaeoclimate research in the northeastern Mediterranean region. This study conducts the analysis of diatoms as a proxy for Lateglacial and Holocene climate and environmental change in Lake Ohrid at a higher resolution than in previous studies. While Lake Ohrid has the potential to be sensitive to water temperature change, the data demonstrate a highly complex diatom response, probably comprising a direct response to temperature-induced lake productivity in some phases and an indirect response to temperaturerelated lake stratification or mixing and epilimnetic nutrient availability in others. The data also demonstrate the possible influence of physical limnological (e.g. the influence of wind stress on stratification or mixing) and chemical processes (e.g. the influence of catchment dynamics on nutrient input) in mediating the complex response of diatoms. During the Lateglacial (ca. 12 300-11 800 cal yr BP), the low-diversity dominance of hypolimnetic Cyclotella fottii indicates low lake productivity, linked to low water temperature. Although the subsequent slight increase in small, epilimnetic C. minuscula during the earliest Holocene (ca. 11 800-10 600 cal yr BP) suggests climate warming and enhanced stratification, diatom concentration remains as low as during the Lateglacial, suggesting that water temperature increase was muted across this major transition. The early Holocene (ca. 10 600-8200 cal yr BP) is characterised by a sustained increase in epilimnetic taxa, with mesotrophic C. ocellata indicating high water-temperature-induced productivity between ca. 10 600-10 200 cal yr BP and between ca. 9500-8200 cal yr BP and with C. minuscula in response to low nutrient availability in the epilimnion between ca. 10 200-9500 cal yr BP. During the middle Holocene (ca. 8200-2600 cal yr BP), when sedimentological and geochemical proxies provide evidence for maximum Holocene water temperature, anomalously low C. ocellata abundance is probably a response to epilimnetic nutrient limitation, almost mimicking the Lateglacial flora apart from the occurrence of mesotrophic Stephanodiscus transylvanicus in the hypolimnion. During the late Holocene (ca. 2600 cal yr BP-present), high abundance and fluctuating composition of epilimnetic taxa are probably a response more to enhanced anthropogenic nutrient input, particularly nitrogen enrichment, than to climate. Overall, the data indicate that previous assumptions concerning the linearity of diatom response in this deep, ancient lake are invalid, and multi-proxy analysis is essential to improve understanding of palaeolimnological dynamics in future research on the long, Quaternary sequence

Pollen-based temperature and precipitation changes in the Ohrid Basin (western Balkans) between 160 and 70 ka

Our study aims to reconstruct climate changes that occurred at Lake Ohrid (south-western Balkan Peninsula), the oldest extant lake in Europe, between 160 and 70&thinsp;ka (covering part of marine isotope stage 6, MIS 6; all of MIS 5; and the beginning of MIS 4). A multi-method approach, including the “Modern Analog Technique” and the “Weighted Averaging Partial Least-Squares Regression”, is applied to the high-resolution pollen sequence of the DEEP site, collected from the central part of Lake Ohrid, to provide quantitative estimates of climate and bioclimate parameters. This allows us to document climatic change during the key periods of MIS 6 and MIS 5 in southern Europe, a region where accurate climate reconstructions are still lacking for this time interval. Our results for the penultimate glacial show cold and dry conditions, while the onset of the “last interglacial” is characterized by wet and warm conditions, with temperatures higher than today (by ca. 2&thinsp;∘C). The Eemian also shows the well-known climatic tri-partition in the Balkans, with an initial pre-temperate phase of abrupt warming (128–121&thinsp;ka), a central temperate phase with decreasing temperatures associated with wet conditions (121–118&thinsp;ka), followed by a post-temperate phase of progressive change towards cold and dry conditions (118–112&thinsp;ka). After the Eemian, an alternation of four warm/wet periods with cold/dry ones, likely related to the succession of Greenland stadials and cold events known from the North Atlantic, occurred. The observed pattern is also consistent with hydrological and isotopic data from the central Mediterranean. The Lake Ohrid climate reconstruction shows greater similarity with climate patterns inferred from northern European pollen records than with southern European ones, which is probably due to its intermediate position and the mountainous setting. However, this hypothesis needs further testing as very few climate reconstructions are available for southern Europe for this key time period.</p

Study and optimization of RPCs for high rate applications

Due to the low cost, good time resolution and the properties of RPCs with respect to electronics damage protection, they are chosen for many large experiments. These detectors are reliable and stable in their operation with counting rates up to kHz/cm2. The aim of this work is to understand the fundamental rate limits of RPCs in order to find an efficient way for their optimization and hence, extend their applications. Several types of materials have been used and operational parameters have been optimized in this work comprising simulations and experiment. High efficiency, excellent position resolution, low noise and high rate capability is demonstrated. These type of RPCs open new avenues in several applications, for example in crystallography, biology and medicine

Accelerating the reconstruction of genome-scale metabolic networks

BACKGROUND: The genomic information of a species allows for the genome-scale reconstruction of its metabolic capacity. Such a metabolic reconstruction gives support to metabolic engineering, but also to integrative bioinformatics and visualization. Sequence-based automatic reconstructions require extensive manual curation, which can be very time-consuming. Therefore, we present a method to accelerate the time-consuming process of network reconstruction for a query species. The method exploits the availability of well-curated metabolic networks and uses high-resolution predictions of gene equivalency between species, allowing the transfer of gene-reaction associations from curated networks. RESULTS: We have evaluated the method using Lactococcus lactis IL1403, for which a genome-scale metabolic network was published recently. We recovered most of the gene-reaction associations (i.e. 74 – 85%) which are incorporated in the published network. Moreover, we predicted over 200 additional genes to be associated to reactions, including genes with unknown function, genes for transporters and genes with specific metabolic reactions, which are good candidates for an extension to the previously published network. In a comparison of our developed method with the well-established approach Pathologic, we predicted 186 additional genes to be associated to reactions. We also predicted a relatively high number of complete conserved protein complexes, which are derived from curated metabolic networks, illustrating the potential predictive power of our method for protein complexes. CONCLUSION: We show that our methodology can be applied to accelerate the reconstruction of genome-scale metabolic networks by taking optimal advantage of existing, manually curated networks. As orthology detection is the first step in the method, only the translated open reading frames (ORFs) of a newly sequenced genome are necessary to reconstruct a metabolic network. When more manually curated metabolic networks will become available in the near future, the usefulness of our method in network prediction is likely to increase

Efficient Replication of Over 180 Genetic Associations with Self-Reported Medical Data

While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for amassing large amounts of medical information in a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggests that online collection of self-reported data in a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations

Reconstructing palaeoclimate and hydrological fluctuations in the Fezzan Basin (southern Libya) since 130 ka: a catchment-based approach

We propose a novel method to evaluate regional palaeoclimate that can be used to alleviate the problems caused by the discontinuous nature of palaeoenvironmental data found in deserts. The technique involves processing satellite imagery and DEM’s to map past rivers, catchments and evaluate the areas and volumes of palaeolakes. This information is used to determine the new Lake Evaluation Index (LEI) that allows a qualitative estimate of the amount of sediment received by lakes and how long-lived those lakes are. Lakes with considerable longevity and large sediment stores are selected for study. Validation is performed using image interpretation of remote sensing data, UltraGPR surveys and fieldwork. These techniques are also used to identify and study spring deposits and fluvial landforms that provide valuable palaeoclimate information. The method is applied to the Fezzan Basin in southern Libya focusing on the Wadi ash Shati and Wadi el-Agial catchments. Results indicate that the palaeohydrology is accurately mapped except within dune fields. We analysed the sedimentology of the key deposits identified by this methodology, developing a chronology using optically stimulated luminescence (OSL) and radiocarbon dating. We find evidence for relatively humid conditions during MIS 5c/d and e, as well as during the early to middle Holocene. Larger lakes and more extensive river systems were present during MIS 5 than are found during the Holocene, suggestive of greater humidity. The Holocene humid period started at ~11 ka and continued until ~5 ka being interrupted by abrupt periods of aridity at ~8.2 ka and ~6 ka that coincide with North Atlantic cooling. After each of these arid events the climate was less humid than previously, suggesting that they were superimposed upon an overall drying trend. The termination of the Holocene humid period in the Sahara has received much scrutiny in recent years, and sediments of Palaeolake Shati provide a continuous record of this. We do not find evidence to support the hypothesis of either sudden or gradual aridification of the Sahara at ~5 ka, instead we find that that aridity started to develop at ~6.5 ka, whereupon the lake levels oscillated until finally drying-up by 5.3 ka. Most of the other lakes in the Fezzan also dried up at ~ 5ka. We suggest that thousands of years of aridification prior to 5 ka shrunk these lakes so that additional aridity at this time led to their final desiccation. Because lakes are prodigious dust sources this mechanism potentially explains the rapid rise in dust flux to the Atlantic at 5 ka, with this final drying being the culmination of longer term aridity, albeit overprinted with considerable climate variability

Iron deficiency after kidney transplantation

Iron deficiency (ID) is highly prevalent in kidney transplant recipients (KTRs) and has been independently associated with an excess mortality risk in this population. Several causes lead to ID in KTRs, including inflammation, medication and an increased iron need after transplantation. Although many studies in other populations indicate a pivotal role for iron as a regulator of the immune system, little is known about the impact of ID on the immune system in KTRs. Moreover, clinical trials in patients with chronic kidney disease or heart failure have shown that correction of ID, with or without anaemia, improves exercise capacity and quality of life, and may improve survival. ID could therefore be a modifiable risk factor to improve graft and patient outcomes in KTRs; prospective studies are warranted to substantiate this hypothesis.</p

Body composition is associated with tacrolimus pharmacokinetics in kidney transplant recipients

PURPOSE: A population pharmacokinetic (popPK) model may be used to improve tacrolimus dosing and minimize under- and overexposure in kidney transplant recipients. It is unknown how body composition parameters relate to tacrolimus pharmacokinetics and which parameter correlates best with tacrolimus exposure. The aims of this study were to investigate which body composition parameter has the best association with the pharmacokinetics of tacrolimus and to describe this relationship in a popPK model. METHODS: Body composition was assessed using bio-impedance spectroscopy (BIS). Pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM). Lean tissue mass, adipose tissue mass, over-hydration, and phase angle were measured with BIS and then evaluated as covariates. The final popPK model was evaluated using goodness-of-fit plots, visual predictive checks, and a bootstrap analysis. RESULTS: In 46 kidney transplant recipients, 284 tacrolimus concentrations were measured. The base model without body composition parameters included age, plasma albumin, plasma creatinine, CYP3A4 and CYP3A5 genotypes, and hematocrit as covariates. After full forward inclusion and backward elimination, only the effect of the phase angle on clearance (dOFV =  − 13.406; p < 0.01) was included in the final model. Phase angle was positively correlated with tacrolimus clearance. The inter-individual variability decreased from 41.7% in the base model to 34.2% in the final model. The model was successfully validated. CONCLUSION: The phase angle is the bio-impedance spectroscopic parameter that correlates best with tacrolimus pharmacokinetics. Incorporation of the phase angle in a popPK model can improve the prediction of an individual’s tacrolimus dose requirement after transplantation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-022-03323-0