Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients

Fetal haemoglobin (HbF) is a major ameliorating factor in sickle cell disease. We investigated if a quantitative trait locus on chromosome 6q23 was significantly associated with HbF and F cell levels in individuals of African descent. Single nucleotide polymorphisms (SNPs) in a 24-kb intergenic region, 33-kb upstream of the HBS1L gene and 80-kb upstream of the MYB gene, were typed in 177 healthy Afro-Caribbean subjects (AC) of approximately 7% European admixture, 631 healthy Afro-Germans (AG, a group of African and German descendents located in rural Jamaica with about 20% European admixture), 87 West African and Afro-Caribbean individuals with sickle cell anaemia (HbSS), as well as 75 Northern Europeans, which served as a contrasting population. Association with a tag SNP for the locus was detected in all four groups (AC, P = 0.005, AG, P = 0.002, HbSS patients, P = 0.019, Europeans, P = 1.5×10⁻⁷). The association signal varied across the interval in the African-descended groups, while it is more uniform in Europeans. The 6q QTL for HbF traits is present in populations of African origin and is also acting in sickle cell anaemia patients. We have started to distinguish effects originating from European and African ancestral populations in our admixed study populations.     

Experimental Study on Localized Surface Plasmon Mode Hybridization in the Near and Mid Infrared

We investigate plasmon excitations within a regular grating of double-layered gold/insulator nanoparticles in the infrared and visible spectral region. Provided a flat gold film as substrate, strong coupling between the localized surface plasmon modes and their image-like excitations in the metal is observed. The interaction results in a strong red shift of the plasmon mode as well as the splitting of the modes into levels of different angular momenta, often referred to as plasmon hybridization. The diameters of the nanoparticles are designed in a way that the splitting of the resonances occurs in the spectral region between 0.1 and 1 eV, thus being accessible using an infrared microscope. Moreover, we investigated the infrared absorption signal of gratings that contain two differently sized nanoparticles. The interaction between two autonomous localized surface plasmon excitations is investigated by analyzing their crossing behavior. In contrast to the interaction between localized surface plasmons and propagating plasmon excitations which results in pronounced anticrossing, the presented structures show no interaction between two autonomous localized surface plasmons. Finally, plasmon excitations of the nanostructured surfaces in the visible spectral region are demonstrated through photographs acquired at three different illumination angles. The change in color of the gratings demonstrates the complex interaction between propagating and localized surface plasmon modes.     

Whole genome sequencing of Turkish genomes reveals functional private alleles and impact of genetic interactions with Europe,Asia and Africa

Background

Turkey is a crossroads of major population movements throughout history and has been a hotspot of cultural interactions. Several studies have investigated the complex population history of Turkey through a limited set of genetic markers. However, to date, there have been no studies to assess the genetic variation at the whole genome level using whole genome sequencing. Here, we present whole genome sequences of 16 Turkish individuals resequenced at high coverage (32 × -48×).

Results

We show that the genetic variation of the contemporary Turkish population clusters with South European populations, as expected, but also shows signatures of relatively recent contribution from ancestral East Asian populations. In addition, we document a significant enrichment of non-synonymous private alleles, consistent with recent observations in European populations. A number of variants associated with skin color and total cholesterol levels show frequency differentiation between the Turkish populations and European populations. Furthermore, we have analyzed the 17q21.31 inversion polymorphism region (MAPT locus) and found increased allele frequency of 31.25% for H1/H2 inversion polymorphism when compared to European populations that show about 25% of allele frequency.

Conclusion

This study provides the first map of common genetic variation from 16 western Asian individuals and thus helps fill an important geographical gap in analyzing natural human variation and human migration. Our data will help develop population-specific experimental designs for studies investigating disease associations and demographic history in Turkey.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-963) contains supplementary material, which is available to authorized users.     

Sustained Na+/H+ Exchanger Activation Promotes Gliotransmitter Release from Reactive Hippocampal Astrocytes following Oxygen-Glucose Deprivation

Hypoxia ischemia (HI)-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na⁺/H⁺ exchanger isoform 1 (NHE1) protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX). 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H⁺ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1–5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na⁺ and Ca²⁺ overload. The latter was mediated by reversal of Na⁺/Ca²⁺ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα) during 1–24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na⁺ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H⁺ homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na⁺ and Ca²⁺ homeostasis, which reduces Na⁺-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.     

Live-cell imaging of Aspergillus nidulans autophagy

We exploited the amenability of the fungus Aspergillus nidulans to genetics and live-cell microscopy to investigate autophagy. Upon nitrogen starvation, GFP-Atg8-containing pre-autophagosomal puncta give rise to cup-shaped phagophores and circular (0.9-μm diameter) autophagosomes that disappear in the vicinity of the vacuoles after their shape becomes irregular and their GFP-Atg8 fluorescence decays. This ‘autophagosome cycle’ gives rise to characteristic cone-shaped traces in kymographs. Autophagy does not require endosome maturation or ESCRTs, as autophagosomes fuse with vacuoles directly in a RabS (homolog of Saccharomyces cerevisiae Ypt7 and mammalian RAB7; written hereafter as RabS^RAB7)-HOPS-(homotypic fusion and vacuole protein sorting complex)-dependent manner. However, by removing RabS^RAB7 or Vps41 (a component of the HOPS complex), we show that autophagosomes may still fuse, albeit inefficiently, with the endovacuolar system in a process almost certainly mediated by RabA^RAB5/RabB^RAB5 (yeast Vps21 homologs)-CORVET (class C core vacuole/endosome tethering complex), because acute inactivation of HbrA/Vps33, a key component of HOPS and CORVET, completely precludes access of GFP-Atg8 to vacuoles without affecting autophagosome biogenesis. Using a FYVE₂-GFP probe and endosomal PtdIns3P-depleted cells, we imaged PtdIns3P on autophagic membranes. PtdIns3P present on autophagosomes decays at late stages of the cycle, preceding fusion with the vacuole. Autophagy does not require Golgi traffic, but it is crucially dependent on RabO^RAB1. TRAPPIII-specific factor AN7311 (yeast Trs85) localizes to the phagophore assembly site (PAS) and RabO^RAB1 localizes to phagophores and autophagosomes. The Golgi and autophagy roles of RabO^RAB1 are dissociable by mutation: rabO^A136D hyphae show relatively normal secretion at 28°C but are completely blocked in autophagy. This finding and the lack of Golgi traffic involvement pointed to the ER as one potential source of membranes for autophagy. In agreement, autophagosomes form in close association with ring-shaped omegasome-like ER structures resembling those described in mammalian cells.     

Airborne pollen concentration in Ankara,Turkey 1990–1993

Atmospheric pollen was collected with a Burkard spore trap in Ankara, Turkey, from January 1990 to January 1993. A total of 135.787 grains/m³ belonging to 47 taxa were observed. The local pollen season started in February in 1990 and 1991 and in March in 1992. Relatively low pollen concentrations were recorded in 1990 and 1992, probably because of precipitation and low wind speed in the spring. A relatively high pollen concentration was recorded in 1991 which could be caused by higher wind speed in the spring and more precipitation during the winter. Cupressaceae/Taxaceae, Pinaceae, Gramineae, Betula, Moraceae, Platanus, Populus, Acer, Quercus, Chenopodiaceae/Amaranthaceae, Plantago, Rumex are found to be the dominant pollen types in the atmosphere in Ankara. The pollen composition generally reflects the vegetation of gardens, parks and roadsides, while the natural steppe vegetation of the area around Ankara is not properly represented.     

Novel Cytotoxic Sesquiterpene Ester Derivatives from the Roots of Ferula mervynii

This study is the first chemical investigation of Ferula mervynii M. Sağıroğlu & H. Duman, an endemic species to Eastern Anatolia. The isolations of nine compounds including six previously undescribed sesquiterpene esters, 8-trans-cinnamoyltovarol ( 1 ), 8-trans-cinnamoylantakyatriol ( 3 ), 6-acetyl-8-trans-cinnamoyl-3-epi-antakyatriol ( 5 ), 6-acetyl-8-trans-cinnamoylshiromodiol ( 6 ), 6-acetyl-8-trans-cinnamoylfermedurone ( 7 ), and 6-acetyl-8-trans-cinnamoyl-(1S),2-epoxyfermedurone ( 8 ), were described along with three known sesquiterpene esters, 6-acetyl-8-benzoyltovarol ( 2 ), 6-acetyl-8-trans-cinnamoylantakyatriol ( 4 ), and ferutinin ( 9 ). The structures of novel compounds were elucidated through extensive spectroscopic analyses and quantum chemistry calculations. The putative biosynthetic pathways for compounds 7 and 8 were discussed. The extracts and isolated compounds were tested for cytotoxic activity against the COLO 205, K-562, MCF-7 cancer cell lines, and Human Umbilical Vein Endothelial Cell (HUVEC) lines using MTT assay. Compound 4 showed the highest activity against the MCF-7 cell lines with an IC₅₀ value of 16.74±0.21 μM.     

Removal of High Concentrations of Nitrate from Industrial Wastewaters by Bacteria

Klebsiella oxytoca isolate 15 was isolated from the grounds of a nitration factory and was found to be tolerant to nitrate at concentrations up to 0.5 to 1 M. Physicochemical parameters for optimal growth conditions for K. oxytoca isolate 15 were established. Growth took place when the nitrate concentration in the medium was less than 150 mM, and full nitrate consumption required about 14 g of C per g of N. This strain was able to remove nitrate without accumulating nitrite. The system was scaled up to a 40-liter pilot plant and was operated on-site satisfactorily.     

Amyloid Beta Peptides Affect Pregnenolone and Pregnenolone Sulfate Levels in PC-12 and SH-SY5Y Cells Depending on Cholesterol

Increased amyloid beta (AB) peptide concentration is one of the initiating factors in the neurodegeneration process. It has been suggested that cholesterol induces the synthesis of AB peptide from amyloid precursor protein or facilitates the formation of amyloid plaque by lowering the aggregation threshold of the peptide. It is also shown that AB peptides may affect cholesterol metabolism and the synthesis of steroid hormones such as progesterone and estradiol. Pregnenolone (P) and pregnenolone sulfate (PS) are the major steroids produced from cholesterol in neural tissue. In toxicity conditions, the effect of AB peptides on P and PS levels has not yet been determined. Furthermore, it has not been clearly defined how changes in cellular P and PS levels affect neuronal cell survival. The aim of this study was to determine the effects of AB peptides on cellular changes in P and PS levels depending on the level of their main precursor, cholesterol. Cholesterol and toxic concentrations of AB fragments (AB 25–35, AB 1–40 and AB 1–42) were applied to PC-12 and SH-SY5Y cells. Changes in cellular cholesterol, P and PS levels were determined simultaneously in a dose—and time-dependent manner. The cell viability and cell death types were also evaluated. AB peptides affected both cell viability and P/PS levels. Steroid levels were altered depending on AB fragment type and the cholesterol content of the cells. Treatment with each of the AB fragments alone increased P levels by twofold. However, combined treatment with AB peptides and cholesterol increased P levels by approximately sixfold, while PS levels were increased only about 2.5 fold in both cell lines. P levels in the groups treated with AB 25–35 were higher than those in AB 1–40 and AB 1–42 groups. The cell viabilities were significantly low in the group treated by AB and cholesterol (9 mM). The effect of AB peptides on P levels might be a result of cellular self-defense. On the other hand, the rate of P increase might be playing a key role in the cell death mechanism of AB toxicity depending on cellular cholesterol levels.