Middle Jurassic ooidal ironstones (southern Tibet): Formation processes and implications for the paleoceanography of eastern Neo-Tethys

The major facies changes documented in shallow-marine sediments of the northern Indian passive margin of Neo-Tethys throughout the Jurassic, from widespread platform carbonates in the Early Jurassic to organic-rich black shales in the Late Jurassic, imply a substantial turnover in oceanic conditions. All along the Tethys (Tibetan) Himalaya, from the Zanskar Range to southern Tibet, a peculiar interval characterized by ooidal ironstones of Dingjie Formation (Ferruginous Oolite Formation, FOF) marks the base of the organic-rich Spiti Shale. This laterally-extensive ooidal ironstone interval is a fundamental testimony of the mechanisms that led to major paleoceanographic changes that occurred in the eastern Neo-Tethys during the Middle Jurassic. In this article, we illustrate in detail the petrology, mineralogy, and geochemistry of ooidal ironstones and the major element contents of the entire Lanongla section. The FOF is characterized by significantly high contents of Fe2O3 (56.80% ± 9.07%, n = 7) and P2O5 (1.72% ± 1.19%, n = 7). In contrast, the Fe2O3 and P2O5 contents average 3.58% and 0.15% in the overlain carbonates of Lanongla Fm., and 5.55% and 0.16% in the overlying Spiti Shale. The ooidal ironstones are mainly composed of iron ooids with a few quartz grains and bioclasts cemented by sparry calcite. The iron ooids consist of concentric dark layers of francolite (carbonate fluorapatite), hence enriched in Ca, P, and F, and bright layers of chamosite, enriched in Fe, Si, Al, and Mg. Precipitation of francolite ensued from oversaturation of phosphorous ascribed to intensified upwelling, high biogenous productivity, and degradation of organic matter, whereas the formation of chamosite reflects enhanced continental weathering and erosion leading to increased Fe input to the ocean during transgressive stages characterized by low sedimentation rate and scarce oxygenation at the seafloor. Modern upwelling zones in outer shelf or slope areas perform similar geochemical characteristics to those as observed in this study. Under the Mesozoic greenhouse background, fluctuating redox conditions induced the alternate growth of francolite under anoxic conditions and of chamosite under suboxic conditions. Ooids were thus formed on the seafloor during continued resuspension and vertical oscillations of the chemocline rather than from interstitial waters after burial. The mineralogy of iron ooids indicates mainly reducing conditions in the water column, suggesting that extensive upwelling along the continental margin of eastern Neo-Tethys contributed significantly to the transition from carbonate deposits to organic-rich black shales during the Jurassic, as testified by the transition from well-oxygenated in Lanongla Fm. To a reduceing condition in Spiti Shale indicated by the Mn/Al ratios compared to PAAS

Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy

Hypoglycosylation and reduced laminin-binding activity of α-dystroglycan are common characteristics of dystroglycanopathy, which is a group of congenital and limb-girdle muscular dystrophies. Fukuyama-type congenital muscular dystrophy (FCMD), caused by a mutation in the fukutin gene, is a severe form of dystroglycanopathy. A retrotransposal insertion in fukutin is seen in almost all cases of FCMD. To better understand the molecular pathogenesis of dystroglycanopathies and to explore therapeutic strategies, we generated knock-in mice carrying the retrotransposal insertion in the mouse fukutin ortholog. Knock-in mice exhibited hypoglycosylated α-dystroglycan; however, no signs of muscular dystrophy were observed. More sensitive methods detected minor levels of intact α-dystroglycan, and solid-phase assays determined laminin binding levels to be ∼50% of normal. In contrast, intact α-dystroglycan is undetectable in the dystrophic Largemyd mouse, and laminin-binding activity is markedly reduced. These data indicate that a small amount of intact α-dystroglycan is sufficient to maintain muscle cell integrity in knock-in mice, suggesting that the treatment of dystroglycanopathies might not require the full recovery of glycosylation. To examine whether glycosylation defects can be restored in vivo, we performed mouse gene transfer experiments. Transfer of fukutin into knock-in mice restored glycosylation of α-dystroglycan. In addition, transfer of LARGE produced laminin-binding forms of α-dystroglycan in both knock-in mice and the POMGnT1 mutant mouse, which is another model of dystroglycanopathy. Overall, these data suggest that even partial restoration of α-dystroglycan glycosylation and laminin-binding activity by replacing or augmenting glycosylation-related genes might effectively deter dystroglycanopathy progression and thus provide therapeutic benefits

A Dominant X-Linked QTL Regulating Pubertal Timing in Mice Found by Whole Genome Scanning and Modified Interval-Specific Congenic Strain Analysis

BACKGROUND: Pubertal timing in mammals is triggered by reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and modulated by both genetic and environmental factors. Strain-dependent differences in vaginal opening among inbred mouse strains suggest that genetic background contribute significantly to the puberty timing, although the exact mechanism remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: We performed a genome-wide scanning for linkage in reciprocal crosses between two strains, C3H/HeJ (C3H) and C57BL6/J (B6), which differed significantly in the pubertal timing. Vaginal opening (VO) was used to characterize pubertal timing in female mice, and the age at VO of all female mice (two parental strains, F1 and F2 progeny) was recorded. A genome-wide search was performed in 260 phenotypically extreme F2 mice out of 464 female progeny of the F1 intercrosses to identify quantitative trait loci (QTLs) controlling this trait. A QTL significantly associated was mapped to the DXMit166 marker (15.5 cM, LOD = 3.86, p<0.01) in the reciprocal cross population (C3HB6F2). This QTL contributed 2.1 days to the timing of VO, which accounted for 32.31% of the difference between the original strains. Further study showed that the QTL was B6-dominant and explained 10.5% of variation to this trait with a power of 99.4% at an alpha level of 0.05.The location of the significant ChrX QTL found by genome scanning was then fine-mapped to a region of approximately 2.5 cM between marker DXMit68 and rs29053133 by generating and phenotyping a panel of 10 modified interval-specific congenic strains (mISCSs). CONCLUSIONS/SIGNIFICANCE: Such findings in our study lay a foundation for positional cloning of genes regulating the timing of puberty, and also reveal the fact that chromosome X (the sex chromosome) does carry gene(s) which take part in the regulative pathway of the pubertal timing in mice

Physiological response of Saccharomyces cerevisiae to weak acids present in lignocellulosic hydrolysate

Weak acids are present in lignocellulosic hydrolysate as potential inhibitors that can hamper the use of this renewable resource for fuel and chemical production. To study the effects of weak acids on yeast growth, physiological investigations were carried out in batch cultures using glucose as carbon source in the presence of acetic, formic, levulinic, and vanillic acid at three different concentrations at pH 5.0. The results showed that acids at moderate concentrations can stimulate the glycolytic flux, while higher levels of acid slow down the glycolytic flux for both aerobically and anaerobically grown yeast cells. In particular, the flux distribution between respiratory and fermentative growth was adjusted to achieve an optimal ATP generation to allow a maintained energy level as high as it is in nonstressed cells grown exponentially on glucose under aerobic conditions. In addition, yeast cells exposed to acids suffered from severe reactive oxygen species stress and depletion of reduced glutathione commensurate with exhaustion of the total glutathione pool. Furthermore, a higher cellular trehalose content was observed as compared to control cultivations, and this trehalose probably acts to enhance a number of stress tolerances of the yeast

Physiological responses to acid stress by Saccharomyces cerevisiae when applying high initial cell density

High initial cell density is used to increase volumetric productivity and shorten production time in lignocellulosic hydrolysate fermentation. Comparison of physiological parameters in high initial cell density cultivation of Saccharomyces cerevisiae in the presence of acetic, formic, levulinic and cinnamic acids demonstrated general and acid-specific responses of cells. All the acids studied impaired growth and inhibited glycolytic flux, and caused oxidative stress and accumulation of trehalose. However, trehalose may play a role other than protecting yeast cells from acid-induced oxidative stress. Unlike the other acids, cinnamic acid did not cause depletion of cellular ATP, but abolished the growth of yeast on ethanol. Compared with low initial cell density, increasing initial cell density reduced the lag phase and improved the bioconversion yield of cinnamic acid during acid adaptation. In addition, yeast cells were able to grow at elevated concentrations of acid, probable due to the increase in phenotypic cell-to-cell heterogeneity in large inoculum size. Furthermore, the specific growth rate and the specific rates of glucose consumption and metabolite production were significantly lower than at low initial cell density, which was a result of the accumulation of a large fraction of cells that persisted in a viable but non-proliferating state

Characterization and fermentation of side streams from sulfite pulping

The fermentability of four different side streams produced in sulfite pulping has been compared in ethanol production with Saccharomyces cerevisiae. The results show that the fermentability of the different side streams varies, depending on where in the process they are produced, and the additional treatment applied to them. Side streams spent sulfite liquor, spent sulfite liquor derivative and spent sulfite liquor after ethanol fermentation that were fermentable benefited from the main cooking process, during which 90% of the sulfite was removed, whereas the side stream produced in the first cooking step, containing 11.0 g/L sulfite, was unfermentable. The fermentation of the side streams resulted in lower yields and productivity than fermentation in a defined medium. Furthermore, the fermentability of the side streams was improved after over-liming, evaporation, and laccase treatment. Over-liming was the most efficient means of detoxifying the side-streams, resulting in better fermentability. Sulfite treatment, however, had a counterproductive effect on fermentation due to the toxicity of this chemical to yeast metabolism. When the side-streams were detoxified by over-liming, loss of sugars was observed. Laccase treatment was less efficient, but it should be further explored as it offers a sustainable method of detoxifying side streams in situ

Changes in lipid metabolism convey acid tolerance in Saccharomyces cerevisiae

Background: The yeast Saccharomyces cerevisiae plays an essential role in the fermentation of lignocellulosic hydrolysates. Weak organic acids in lignocellulosic hydrolysate can hamper the use of this renewable resource for fuel and chemical production. Plasma-membrane remodeling has recently been found to be involved in acquiring tolerance to organic acids, but the mechanisms responsible remain largely unknown. Therefore, it is essential to understand the underlying mechanisms of acid tolerance of S. cerevisiae for developing robust industrial strains.[br/] Results: We have performed a comparative analysis of lipids and fatty acids in S. cerevisiae grown in the presence of four different weak acids. The general response of the yeast to acid stress was found to be the accumulation of triacylglycerols and the degradation of steryl esters. In addition, a decrease in phosphatidic acid, phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine, and an increase in phosphatidylinositol were observed. Loss of cardiolipin in the mitochondria membrane may be responsible for the dysfunction of mitochondria and the dramatic decrease in the rate of respiration of S. cerevisiae under acid stress. Interestingly, the accumulation of ergosterol was found to be a protective mechanism of yeast exposed to organic acids, and the ERG1 gene in ergosterol biosynthesis played a key in ergosterol-mediated acid tolerance, as perturbing the expression of this gene caused rapid loss of viability. Interestingly, overexpressing OLE1 resulted in the increased levels of oleic acid (18:1n-9) and an increase in the unsaturation index of fatty acids in the plasma membrane, resulting in higher tolerance to acetic, formic and levulinic acid, while this change was found to be detrimental to cells exposed to lipophilic cinnamic acid.[br/] Conclusions: Comparison of lipid profiles revealed different remodeling of lipids, FAs and the unsaturation index of the FAs in the cell membrane in response of S. cerevisiae to acetic, formic, levulinic and cinnamic acid, depending on the properties of the acid. In future work, it will be necessary to combine lipidome and transcriptome analysis to gain a better understanding of the underlying regulation network and interactions between central carbon metabolism (e.g., glycolysis, TCA cycle) and lipid biosynthesis

Engineering of the glycerol decomposition pathway and cofactor regulation in an industrial yeast improves ethanol production

Glycerol is a major by-product of industrial ethanol production and its formation consumes up to 4 % of the sugar substrate. This study modified the glycerol decomposition pathway of an industrial strain of Saccharomyces cerevisiae to optimize the consumption of substrate and yield of ethanol. This study is the first to couple glycerol degradation with ethanol formation, to the best of our knowledge. The recombinant strain overexpressing GCY1 and DAK1, encoding glycerol dehydrogenase and dihydroxyacetone kinase, respectively, in glycerol degradation pathway, exhibited a moderate increase in ethanol yield (2.9 %) and decrease in glycerol yield (24.9 %) compared to the wild type with the initial glucose concentration of 15 % under anaerobic conditions. However, when the mhpF gene, encoding acetylating NAD(+)-dependent acetaldehyde dehydrogenase from Escherichia coli, was co-expressed in the aforementioned recombinant strain, a further increase in ethanol yield by 5.5 % and decrease in glycerol yield by 48 % were observed for the resultant recombinant strain GDMS1 when acetic acid was added into the medium prior to inoculation compared to the wild type. The process outlined in this study which enhances glycerol consumption and cofactor regulation in an industrial yeast is a promising metabolic engineering strategy to increase ethanol production by reducing the formation of glycerol

Engineering of the glycerol decomposition pathway and cofactor regulation in an industrial yeast improves ethanol production

Glycerol is a major by-product of industrial ethanol production and its formation consumes up to 4 % of the sugar substrate. This study modified the glycerol decomposition pathway of an industrial strain of Saccharomyces cerevisiae to optimize the consumption of substrate and yield of ethanol. This study is the first to couple glycerol degradation with ethanol formation, to the best of our knowledge. The recombinant strain overexpressing GCY1 and DAK1, encoding glycerol dehydrogenase and dihydroxyacetone kinase, respectively, in glycerol degradation pathway, exhibited a moderate increase in ethanol yield (2.9 %) and decrease in glycerol yield (24.9 %) compared to the wild type with the initial glucose concentration of 15 % under anaerobic conditions. However, when the mhpF gene, encoding acetylating NAD(+)-dependent acetaldehyde dehydrogenase from Escherichia coli, was co-expressed in the aforementioned recombinant strain, a further increase in ethanol yield by 5.5 % and decrease in glycerol yield by 48 % were observed for the resultant recombinant strain GDMS1 when acetic acid was added into the medium prior to inoculation compared to the wild type. The process outlined in this study which enhances glycerol consumption and cofactor regulation in an industrial yeast is a promising metabolic engineering strategy to increase ethanol production by reducing the formation of glycerol

How does the extent of fibrosis in adenomyosis lesions contribute to heavy menstrual bleeding?

Abstract Purpose To investigate how the extent of fibrosis in adenomyosis lesions contributes to heavy menstrual bleeding (HMB). Methods We recruited 57 women with histologically confirmed adenomyosis, 29 of whom reported moderate/heavy bleeding (MHB) (menstrual blood loss (MBL) ≥20 but <100 mL) and the remaining 28, excessive MBL (EXB; ≥100 mL). Lesional stiffness was measured by transvaginal elastosonography. Full‐thickness uterine tissue columns containing the lesion and its neighboring endometrial‐myometrial interface (EMI) and endometrial tissues were evaluated for tissue fibrosis and immunohistochemical analysis of HIF‐1α, COX‐2, EP2, and EP4. Results The lesional stiffness in the EXB group was significantly higher than that of MHB, and consistently, the extent of lesional fibrosis and the extent of tissue fibrosis in both EMI and eutopic endometrium were also significantly higher. In adenomyotic lesions and their neighboring EMI and eutopic endometrial tissues, the immunostaining of HIF‐1α, COX‐2, EP2, and EP4 was significantly reduced. The extent of fibrosis and the immunostaining levels of HIF‐1α, COX‐2, EP2, and EP4 were negatively correlated in all tissues. Conclusions Lesional fibrosis begets stiffening matrix, propagating fibrosis to neighboring EMI and eutopic endometrium, resulting in reduced PGE2 and HIF‐1α signaling, and thus likely reduced hypoxia necessary for endometrial repair, leading to HMB