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Abstract Aerosols influence weather and climate by interacting with radiation through absorption and scattering. These effects heavily rely on the optical properties of aerosols, which are mainly governed by attributes such as morphology, size distribution, and chemical composition. These attributes undergo continuous changes due to chemical reactions and aerosol micro-physics, resulting in significant spatio-temporal variations. Most atmospheric models struggle to incorporate this variability because they use pre-calculated tables to handle aerosol optics. This offline approach often leads to substantial errors in estimating the radiative impacts of aerosols along with posing significant computational burdens. To address this challenge, we introduce a computationally efficient and robust machine learning approach called MieAI. It allows for relatively inexpensive calculation of the optical properties of internally mixed aerosols with a log-normal size distribution. Importantly, MieAI fully incorporates the variability in aerosol chemistry and microphysics. Our evaluation of MieAI against traditional Mie calculations, using number concentrations from the ICOsahedral Nonhydrostatic model with Aerosol and Reactive Trace gases (ICON-ART) simulations, demonstrates that MieAI exhibits excellent predictive accuracy for aerosol optical properties. MieAI achieves this with errors well within 10%, and it operates more than 1000 times faster than the benchmark approach of Mie calculations. Due to its generalized nature, the MieAI approach can be implemented in any chemistry transport model which represents aerosol size distribution in the form of log-normally distributed internally mixed modes. This advancement has the potential to replace frequently employed look-up tables and plays a substantial role in the ongoing attempts to reduce uncertainties in estimating aerosol radiative forcing.

Objective: Picalm (phosphatidylinositol-binding clathrin assembly protein), a ubiquitously expressed clathrin-adapter protein, is a well-known susceptibility gene for Alzheimer's disease, but its role in white adipose tissue (WAT) function has not yet been studied. Transcriptome analysis revealed differential expression of Picalm in WAT of diabetes-prone and diabetes-resistant mice, hence we aimed to investigate the potential link between Picalm expression and glucose homeostasis, obesity-related metabolic phenotypes, and its specific role in insulin-regulated GLUT4 trafficking in adipocytes. Methods: Picalm expression and epigenetic regulation by microRNAs (miRNAs) and DNA methylation were analyzed in WAT of diabetes-resistant (DR) and diabetes-prone (DP) female New Zealand Obese (NZO) mice and in male NZO after time-restricted feeding (TRF) and alternate-day fasting (ADF). PICALM expression in human WAT was evaluated in a cross-sectional cohort and assessed before and after weight loss induced by bariatric surgery. siRNA-mediated knockdown of Picalm in 3T3-L1-cells was performed to elucidate functional outcomes on GLUT4-translocation as well as insulin signaling and adipogenesis. Results: Picalm expression in WAT was significantly lower in DR compared to DP female mice, as well as in insulin-sensitive vs. resistant NZO males, and was also reduced in NZO males following TRF and ADF. Four miRNAs (let-7c, miR-30c, miR-335, miR-344) were identified as potential mediators of diabetes susceptibility-related differences in Picalm expression, while 11 miRNAs (including miR-23a, miR-29b, and miR-101a) were implicated in TRF and ADF effects. Human PICALM expression in adipose tissue was lower in individuals without obesity vs. with obesity and associated with weight-loss outcomes post-bariatric surgery. siRNA-mediated knockdown of Picalm in mature 3T3-L1-adipocytes resulted in amplified insulin-stimulated translocation of the endogenous glucose transporter GLUT4 to the plasma membrane and increased phosphorylation of Akt and Tbc1d4. Moreover, depleting Picalm before and during 3T3-L1 differentiation significantly suppressed adipogenesis, suggesting that Picalm may have distinct roles in the biology of pre- and mature adipocytes. Conclusions: Picalm is a novel regulator of GLUT4-translocation in WAT, with its expression modulated by both genetic predisposition to diabetes and dietary interventions. These findings suggest a potential role for Picalm in improving glucose homeostasis and highlight its relevance as a therapeutic target for metabolic disorders.

Abstract Background Depression is a leading cause of disability worldwide and a significant contributor to the global burden of disease. Altered leptin levels are known to be associated with depressive symptoms, however discrepancies in the results of increased or decreased levels exist. Due to various limitations associated with commonly used antidepressant drugs, alternatives such as exercise therapy are gaining more importance. Therefore, the current study investigates whether depressed patients have higher leptin levels compared to healthy controls and if exercise is efficient to reduce these levels. Methods Leptin levels of 105 participants with major depressive disorder (MDD; 45.7% female, age mean ± SEM: 39.1 ± 1.0) and 34 healthy controls (HC; 61.8% female, age mean ± SEM: 36.0 ± 2.0) were measured before and after a bicycle ergometer test. Additionally, the MDD group was separated into three groups: two endurance exercise intervention groups (EX) differing in their intensities, and a waiting list control group (WL). Leptin levels were measured pre and post a 12-week exercise intervention or the waiting period. Results Baseline data showed no significant differences in leptin levels between the MDD and HC groups. As expected, correlation analyses displayed significant relations between leptin levels and body weight (HC: r = 0.474, p = 0.005; MDD: r = 0.198, p = 0.043) and even more with body fat content (HC: r = 0.755, p

Type 2 diabetes (T2D) represents a multifactorial metabolic disease with a strong genetic predisposition. Despite elaborate efforts in identifying the genetic variants determining individual susceptibility towards T2D, the majority of genetic factors driving disease development remain poorly understood. With the aim to identify novel T2D risk genes we previously generated an N2 outcross population using the two inbred mouse strains New Zealand obese (NZO) and C3HeB/FeJ (C3H). A linkage study performed in this population led to the identification of the novel T2D-associated quantitative trait locus (QTL) Nbg15 (NZO blood glucose on chromosome 15, Logarithm of odds (LOD) 6.6). In this study we used a combined approach of positional cloning, gene expression analyses and in silico predictions of DNA polymorphism on gene/protein function to dissect the genetic variants linking Nbg15 to the development of T2D. Moreover, we have generated congenic strains that associated the distal sublocus of Nbg15 to mechanisms altering pancreatic beta cell function. In this sublocus, Cbx6, Fam135b and Kdelr3 were nominated as potential causative genes associated with the Nbg15 driven effects. Moreover, a putative mutation in the Kdelr3 gene from NZO was identified, negatively influencing adaptive responses associated with pancreatic beta cell death and induction of endoplasmic reticulum stress. Importantly, knockdown of Kdelr3 in cultured Min6 beta cells altered insulin granules maturation and pro-insulin levels, pointing towards a crucial role of this gene in islets function and T2D susceptibility.

During the AeroRadCity-2018 spring aerosol experiment at the Moscow State University Meteorological Observatory the aerosol properties of the atmosphere and radiative aerosol effects were analyzed using a wide complex of measurements and model COSMO-ART simulations over Moscow domain. The program of measurements consisted of columnar aerosol AERONET retrievals, surface PM10, black carbon (BC) and aerosol gas precursors mass concentrations, as well as radiative measurements under various meteorological conditions. We obtained a positive statistically significant dependence of total and fine aerosol optical depth (AOD) mode (R2 ~0.4) with PM concentrations. This dependence has revealed a pronounced bifurcation point around PM10=0.04 mgm-3. The modelled BC concentration is in agreement with the observations and has a pronounced correlation with PM, but not with the AODs. The analysis of radiative effects of aerosol has revealed up to 30% loss for UV irradiance and 15% - for shortwave irradiance at high AOD in Moscow. Much intensive radiation attenuation is observed in the afternoon when remote pollution sources may affect solar fluxes at elevated boundary layer conditions. Negative (cooling) radiative forcing effect at the top of the atmosphere from -18 Wm-2 to -4 Wm-2 has been evaluated. Mean difference in visible AOD between urban and background conditions in Moscow and Zvenigorod was about 0.01 according to measurements and model simulations, while in some days the difference may increase up to 0.05. The generation of urban aerosol was shown to be more favorable in conditions with low intensity of pollutant dispersion, when mean deltaAOD550 was doubled from 0.01 to 0.02.

The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.

Objective: Altered gene expression contributes to the development of type 2 diabetes (T2D); thus, the analysis of differentially expressed genes between diabetes-susceptible and diabetes-resistant mouse models is an important tool for the determination of candidate genes that participate in the pathology. Based on RNA-seq and array data comparing pancreatic gene expression of diabetes-prone New Zealand Obese (NZO) mice and diabetes-resistant B6.V-ob/ob (B6-ob/ob) mice, the gap junction protein beta 4 (Gjb4) was identified as a putative novel T2D candidate gene. Methods: Gjb4 was overexpressed in primary islet cells derived from C57BL/6 (B6) mice and INS-1 cells via adenoviral-mediated infection. The proliferation rate of cells was assessed by BrdU incorporation, and insulin secretion was measured under low (2.8 mM) and high (20 mM) glucose concentration. INS-1 cell apoptosis rate was determined by Western blotting assessing cleaved caspase 3 levels. Results: Overexpression of Gjb4 in primary islet cells significantly inhibited the proliferation by 47%, reduced insulin secretion of primary islets (46%) and INS-1 cells (51%), and enhanced the rate of apoptosis by 63% in INS-1 cells. Moreover, an altered expression of the miR-341-3p contributes to the Gjb4 expression difference between diabetes-prone and diabetes-resistant mice. Conclusions: The gap junction protein Gjb4 is highly expressed in islets of diabetes-prone NZO mice and may play a role in the development of T2D by altering islet cell function, inducing apoptosis and inhibiting proliferation.

Current attempts to prevent and manage type 2 diabetes have been moderately effective, and a better understanding of the molecular roots of this complex disease is important to develop more successful and precise treatment options. Recently, we initiated the collective diabetes cross, where four mouse inbred strains differing in their diabetes susceptibility were crossed with the obese and diabetes-prone NZO strain and identified the quantitative trait loci (QTL) Nidd13/NZO, a genomic region on chromosome 13 that correlates with hyperglycemia in NZO allele carriers compared to B6 controls. Subsequent analysis of the critical region, harboring 644 genes, included expression studies in pancreatic islets of congenic Nidd13/NZO mice, integration of single-cell data from parental NZO and B6 islets as well as haplotype analysis. Finally, of the five genes (Acot12, S100z, Ankrd55, Rnf180, and Iqgap2) within the polymorphic haplotype block that are differently expressed in islets of B6 compared to NZO mice, we identified the calcium-binding protein S100z gene to affect islet cell proliferation as well as apoptosis when overexpressed in MIN6 cells. In summary, we define S100z as the most striking gene to be causal for the diabetes QTL Nidd13/NZO by affecting β-cell proliferation and apoptosis. Thus, S100z is an entirely novel diabetes gene regulating islet cell function.

The evolution and the properties of a Saharan dust plume were studied near the city of Karlsruhe in southwest Germany (8.4298°E, 49.0953°N) from 7 to 9 April 2018, combining a scanning LiDAR (90°, 30°), a vertically pointing LiDAR (90°), a sun photometer, and the transport model ICON-ART. Based on this Saharan dust case, we discuss the advantages of a scanning aerosol LiDAR and validate a method to determine LiDAR ratios independently. The LiDAR measurements at 355 nm showed that the dust particles had backscatter coefficients of 0.86 ± 0.14 Mm−1 sr−1, extinction coefficients of 40 ± 0.8 Mm−1, a LiDAR ratio of 46 ± 5 sr, and a linear particle depolarisation ratio of 0.27 ± 0.023. These values are in good agreement with those obtained in previous studies of Saharan dust plumes in Western Europe. Compared to the remote sensing measurements, the transport model predicted the plume arrival time, its layer height, and its structure quite well. The comparison of dust plume backscatter values from the ICON-ART model and observations for two days showed a correlation with a slope of 0.9 ± 0.1 at 355 nm. This work will be useful for future studies to characterise aerosol particles employing scanning LiDARs.

Pancreatic steatosis associates with β-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.

Type 2 diabetes (T2D) is a complex metabolic disease regulated by an interaction of genetic predisposition and environmental factors. To understand the genetic contribution in the development of diabetes, mice varying in their disease susceptibility were crossed with the obese and diabetes-prone New Zealand obese (NZO) mouse. Subsequent whole-genome sequence scans revealed one major quantitative trait loci (QTL), Nidd/DBA on chromosome 4, linked to elevated blood glucose and reduced plasma insulin and low levels of pancreatic insulin. Phenotypical characterization of congenic mice carrying 13.6 Mbp of the critical fragment of DBA mice displayed severe hyperglycemia and impaired glucose clearance at week 10, decreased glucose response in week 13, and loss of β-cells and pancreatic insulin in week 16. To identify the responsible gene variant(s), further congenic mice were generated and phenotyped, which resulted in a fragment of 3.3 Mbp that was sufficient to induce hyperglycemia. By combining transcriptome analysis and haplotype mapping, the number of putative responsible variant(s) was narrowed from initial 284 to 18 genes, including gene models and non-coding RNAs. Consideration of haplotype blocks reduced the number of candidate genes to four (Kti12, Osbpl9, Ttc39a, and Calr4) as potential T2D candidates as they display a differential expression in pancreatic islets and/or sequence variation. In conclusion, the integration of comparative analysis of multiple inbred populations such as haplotype mapping, transcriptomics, and sequence data substantially improved the mapping resolution of the diabetes QTL Nidd/DBA. Future studies are necessary to understand the exact role of the different candidates in β-cell function and their contribution in maintaining glycemic control.

Objective: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. Methods: A computational framework (miR-QTL-Scan) was applied by combining QTL, miRNA prediction, and transcriptomics in order to enhance the power for the discovery of miRNAs as regulative elements. Expression of several miRNAs was analyzed in human adipose tissue and blood cells and miR-31 was manipulated in a human fat cell line. Results: In 17 partially overlapping QTL for obesity and T2D 170 miRNAs were identified. Four miRNAs (miR-15b, miR-30b, miR-31, miR-744) were recognized in gWAT (gonadal white adipose tissue) and six (miR-491, miR-455, miR-423-5p, miR-132-3p, miR-365-3p, miR-30b) in BAT (brown adipose tissue). To provide direct functional evidence for the achievement of the miR-QTL-Scan, miR-31 located in the obesity QTL Nob6 was experimentally analyzed. Its expression was higher in gWAT of obese and diabetic mice and humans than of lean controls. Accordingly, 10 potential target genes involved in insulin signaling and adipogenesis were suppressed. Manipulation of miR-31 in human SGBS adipocytes affected the expression of GLUT4, PPARγ, IRS1, and ACACA. In human peripheral blood mononuclear cells (PBMC) miR-15b levels were correlated to baseline blood glucose concentrations and might be an indicator for diabetes. Conclusion: Thus, miR-QTL-Scan allowed the identification of novel miRNAs relevant for obesity and T2D. Keywords: QTL, Computational biology, Insulin signalling, miR-31, Adipogenesis, Type 2 diabetes

Objective: Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown. Methods: In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-weight men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02:45–07:00 h), and after two nights of normal sleep (NS; sleep opportunity 22:30–07:00 h). Fecal samples were collected within 24 h before, and after two in-lab nights, of either NS or PSD. In addition, participants underwent an oral glucose tolerance test following each sleep intervention. Results: Microbiota composition analysis (V4 16S rRNA gene sequencing) revealed that after two days of PSD vs. after two days of NS, individuals exhibited an increased Firmicutes:Bacteroidetes ratio, higher abundances of the families Coriobacteriaceae and Erysipelotrichaceae, and lower abundance of Tenericutes (all P

Summary: An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with diabetes-resistant B6-ob/ob mice. Among 327 differentially expressed mouse cilia genes, 81 human orthologs are also affected in islets of diabetic donors. Islets of nondiabetic mice and humans show a substantial overlap of upregulated cilia genes that are linked to cell-cycle progression. The shRNA-mediated suppression of KIF3A, essential for ciliogenesis, impairs division of MIN6 beta cells as well as in dispersed primary mouse and human islet cells, as shown by decreased BrdU incorporation. These findings demonstrate the substantial role of cilia-gene regulation on islet function and T2D risk. : Kluth et al. identify a significant enrichment of cilia-annotated genes that are differentially expressed in pancreatic islets of obese mice. Many of the genes were also linked to human T2D, suggesting that dysregulation of cilia-associated genes may participate in T2D risk. Keywords: beta-cell proliferation, cilia genes, human pancreatic islets, islet transcriptomics, New Zealand Obese mouse, pathway enrichment analysis, primary cilia, type 2 diabetes

The area of the Dead Sea valley and the adjacent regions are often affected by mineral dust. This study focuses on an extreme dust episode occurring on 22 March 2013, where near-surface dust concentrations of up to 7000 µg m−3 were encountered in the Dead Sea region. This episode is of great interest as it was accompanied by high wind speeds and a gust front that rapidly passed the Judean Mountains. Wind was even accelerated on the lee side of the Judean Mountains leading to a severe downslope wind. We simulated this situation with the comprehensive online-coupled weather forecast model COSMO-ART. Fair agreement was found between the simulated meteorological variables and the observations. The model was capable of producing a reasonable spatiotemporal distribution of near-surface dust concentration, consistent with available measurements in this area. With respect to the time of the maximum near-surface dust concentration in the Dead Sea valley, the model captured it almost perfectly compared to the observed total suspended particle (TSP) concentrations. COSMO-ART showed that the high near-surface dust concentration in the Dead Sea valley was mainly determined by local emissions. These emissions were caused by strong winds on the lee side of the Judean Mts. The model showed that an ascending airflow in the Dead Sea valley lifted dust particles, originating mainly from the upwind side of the Judean Mts., up to approximately 7 km. These dust particles contributed to the pronounced maximum in modelled dust aerosol optical depth (AOD) over the valley. Here we highlight the important point that the simulated maximum dust AOD was reached in the eastern part of the Dead Sea valley, while the maximum near-surface dust concentration was reached in the western part of the valley.

Obesity has become a worldwide health problem, but we still do not understand the molecular mechanisms that contribute to overeating and low expenditure of energy. Leptin has emerged as a major regulator of energy balance through its actions in the hypothalamus. Importantly, obese people exhibit high circulating levels of leptin, yet the hypothalamus no longer responds normally to this hormone to suppress appetite or to increase energy expenditure. Several well-known hypotheses have been proposed to explain impaired central responsiveness to the effects of leptin in obesity, including defective transit across the blood–brain barrier at the arcuate nucleus, hypothalamic endoplasmic reticulum stress, maladaptive sterile inflammation in the hypothalamus, and overexpression of molecules that may inhibit leptin signaling. We also discuss a new explanation that is based on our group’s recent discovery of a signaling pathway that we named “NSAPP” after its five main protein components. The NSAPP pathway consists of an oxide transport chain that causes a transient, targeted burst in intracellular hydrogen peroxide (H2O2) to inactivate redox-sensitive members of the protein tyrosine phosphatase gene family. The NSAPP oxide transport chain is required for full activation of canonical leptin signaling in neurons but fails to function normally in states of overnutrition. Remarkably, leptin and insulin both require the NSAPP oxide transport chain, suggesting that a defect in this pathway could explain simultaneous resistance to the appetite-suppressing effects of both hormones in obesity.

We carried out simulations with predefined and simulated aerosol distributions in order to investigate the improvement in the forecasting capabilities of an operational weather forecast model by the use of an improved aerosol representation. This study focuses on convective cumulus clouds developing after the passage of a cold front on 25 April 2008 over Germany. The northerly flow after the cold front leads to increased sea salt aerosol concentrations compared to prefrontal conditions. High aerosol number concentrations are simulated in the interactive scenario representing typically polluted conditions. Nevertheless, due to the presence of sea salt particles, effective radii of cloud droplets reach values typical of pristine clouds (between 7 µm and 13 µm) at the same time. Compared to the predefined continental and maritime aerosol scenarios, the simulated aerosol distribution leads to a significant change in cloud properties such as cloud droplet radii and number concentrations. Averaged over the domain covered by the convective cumuli clouds, we found a systematic decrease in precipitation with increasing aerosol number concentrations. Differences in cloud cover, short wave radiation and cloud top heights are buffered by systematic differences in precipitation and the related diabatic effects. Comparisons with measured precipitation show good agreement for the interactive aerosol scenario as well as for the extreme maritime aerosol scenario.

Beta-cell apoptosis and failure to induce beta-cell regeneration are hallmarks of type 2-like diabetes in mouse models. Here we show that islets from obese, diabetes-susceptible New Zealand Obese (NZO) mice, in contrast to diabetes-resistant C57BL/6J (B6)-ob/ob mice, do not proliferate in response to an in-vivo glucose challenge but lose their beta-cells. Genome-wide RNAseq based transcriptomics indicated an induction of 22 cell cycle-associated genes in B6-ob/ob islets that did not respond in NZO islets. Of all genes differentially expressed in islets of the two strains, seven mapped to the diabesity QTL Nob3, and were hypomorphic in either NZO (Lefty1, Apoa2, Pcp4l1, Mndal, Slamf7, Pydc3) or B6 (Ifi202b). Adenoviral overexpression of Lefty1, Apoa2, and Pcp4l1 in primary islet cells increased proliferation, whereas overexpression of Ifi202b suppressed it. We conclude that the identified genes in synergy with obesity and insulin resistance participate in adaptive islet hyperplasia and prevention from severe diabetes in B6-ob/ob mice.

Birch trees produce large amounts of highly allergenic pollen grains that are distributed by wind and impact human health by causing seasonal hay fever, pollen-related asthma, and other allergic diseases. Traditionally, pollen forecasts are based on conventional microscopic counting techniques that are labor-intensive and limited in the reliable identification of species. Molecular biological techniques provide an alternative approach that is less labor-intensive and enables identification of any species by its genetic fingerprint. A particularly promising method is quantitative Real-Time polymerase chain reaction (qPCR), which can be used to determine the number of DNA copies and thus pollen grains in air filter samples. During the birch pollination season in 2010 in Mainz, Germany, we collected air filter samples of fine (

We applied a parameterization for the emission of mineral dust particles which takes into account the relevant processes such as saltation and combines previous, physically based parameterizations. The size distribution of the soil particles is taken into account to describe the saltation. The emitted particles are described by three log-normal distributions with fixed standard deviations. A comparison of the results of a stand alone version of our parameterization with observations shows that despite tuning of model parameters there are still differences. Finally, we included the parameterization within our three-dimensional mesoscale model system for the area of the Dead Sea. The channelling effect of the Jordan Valley and stable stratification during the day modifies the horizontal distribution of the dust particles. At greater distances the size and the mass distributions of the particles is shifted towards smaller diameters due to sedimentation which is important for radiative feedback mechanisms. Sensitivity runs show the advantage of the parameterization which allows a time dependent ratio of the saltation and the emission flux at each grid point.

A region on mouse distal chromosome 1 (Chr. 1) that is highly enriched in quantitative trait loci (QTLs) controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38), which we identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6). By positional cloning we recently identified a microdeletion within this locus causing the disruption of Ifi202b that protects from adiposity by suppressing expression of 11β-Hsd1. Here we show that the Nob3.38 segment also corresponds with the QTL rich region (Qrr1) on Chr. 1 and associates with increased voluntary running wheel activity, Rota-rod performance, decreased grip strength, and anxiety-related traits. The characterization of a subcongenic line carrying 14.2 Mbp of Nob3.38 with a polymorphic region of 4.4 Mbp indicates that the microdeletion and/or other polymorphisms in its proximity alter body weight, voluntary activity, and exploration. Since 27 out of 32 QTL were identified in crosses with B6, we hypothesized that the microdeletion and or adjacent SNPs are unique for B6 mice and responsible for some of the complex Qrr1-mediated effects. Indeed, a phylogenic study of 28 mouse strains revealed a NZO-like genotype for 22 and a B6-like genotype for NZW/LacJ and 4 other C57BL strains. Thus, we suggest that a Nob3.38 interval (173.0-177.4 Mbp) does not only modify adiposity but also neurobehavioral traits by a haplotype segregating with C57BL strains.

Recent discoveries indicate an important role for ghrelin in drug and alcohol reward and an ability of ghrelin to regulate mesolimbic dopamine activity. The role of dopamine in novelty seeking, and the association between this trait and drug and alcohol abuse, led us to hypothesize that ghrelin may influence novelty seeking behavior. To test this possibility we applied several complementary rodent models of novelty seeking behavior, i.e. inescapable novelty-induced locomotor activity (NILA), novelty-induced place preference and novel object exploration, in rats subjected to acute ghrelin receptor (growth hormone secretagogue receptor; GHSR) stimulation or blockade. Furthermore we assessed the possible association between polymorphisms in the genes encoding ghrelin and GHSR and novelty seeking behavior in humans. The rodent studies indicate an important role for ghrelin in a wide range of novelty seeking behaviors. Ghrelin-injected rats exhibited a higher preference for a novel environment and increased novel object exploration. Conversely, those with GHSR blockade drastically reduced their preference for a novel environment and displayed decreased NILA. Importantly, the mesolimbic ventral tegmental area selective GHSR blockade was sufficient to reduce the NILA response indicating that the mesolimbic GHSRs might play an important role in the observed novelty responses. Moreover, in untreated animals, a striking positive correlation between NILA and sucrose reward behavior was detected. Two GHSR single nucleotide polymorphisms (SNPs), rs2948694 and rs495225, were significantly associated with the personality trait novelty seeking, as assessed using the Temperament and Character Inventory (TCI), in human subjects. This study provides the first evidence for a role of ghrelin in novelty seeking behavior in animals and humans, and also points to an association between food reward and novelty seeking in rodents.

Polygenic type 2 diabetes in mouse models is associated with obesity and results from a combination of adipogenic and diabetogenic alleles. Here we report the identification of a candidate gene for the diabetogenic effect of a QTL (Nidd/SJL, Nidd1) contributed by the SJL, NON, and NZB strains in outcross populations with New Zealand Obese (NZO) mice. A critical interval of distal chromosome 4 (2.1 Mbp) conferring the diabetic phenotype was identified by interval-specific congenic introgression of SJL into diabetes-resistant C57BL/6J, and subsequent reporter cross with NZO. Analysis of the 10 genes in the critical interval by sequencing, qRT-PCR, and RACE-PCR revealed a striking allelic variance of Zfp69 encoding zinc finger domain transcription factor 69. In NZO and C57BL/6J, a retrotransposon (IAPLTR1a) in intron 3 disrupted the gene by formation of a truncated mRNA that lacked the coding sequence for the KRAB (Krüppel-associated box) and Znf-C2H2 domains of Zfp69, whereas the diabetogenic SJL, NON, and NZB alleles generated a normal mRNA. When combined with the B6.V-Lep(ob) background, the diabetogenic Zfp69(SJL) allele produced hyperglycaemia, reduced gonadal fat, and increased plasma and liver triglycerides. mRNA levels of the human orthologue of Zfp69, ZNF642, were significantly increased in adipose tissue from patients with type 2 diabetes. We conclude that Zfp69 is the most likely candidate for the diabetogenic effect of Nidd/SJL, and that retrotransposon IAPLTR1a contributes substantially to the genetic heterogeneity of mouse strains. Expression of the transcription factor in adipose tissue may play a role in the pathogenesis of type 2 diabetes.