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Funnell, D. L., and Pedersen, J. F. 2006. Reaction of sorghum lines genetically modified for reduced lignin content to infection by Fusarium and Alternaria spp. Plant Dis. 90:331-338. Two genes conferring the brown midrib (bmr) trait had been backcrossed into six elite sorghum lines, resulting in reduced lignin in the bmr lines when compared with the wild-type parent. Seed and leaf tissue from field-grown plants, planted at two locations, were screened for Alternaria spp. and Fusarium spp. on semi-selective media. The results suggest that bmr lines do not have increased susceptibility to colonization by Alternaria spp. However, significantly fewer colonies of Fusarium spp., including Fusarium moniliforme, were recovered from seed of reduced lignin lines from two genetic backgrounds. That the bmr trait in some genetic backgrounds might enable increased resistance to colonization by F. moniliforme was further supported by greenhouse experiments in which peduncles of developing heads were inoculated with F. moniliforme. Mean lesion measurements on bmr lines were significantly lower than those resulting from inoculations on wild-type lines. Analysis of near-isogenic lines revealed that mean lesion lengths on bmr lines were significantly less than those produced on their wild-type counterparts in four of the six genetic backgrounds. These results suggest that reduced lignin lines exhibit, in some cases, increased resistance to Fusarium spp., including F. moniliforme. Additional keywords: bmr-6, bmr-12, Fusarium verticillioides, grain mold

The impacts of microplastic particulates in benthic freshwater organisms have been largely unexplored despite abundant plastic accumulation in the sediments of these systems. We investigated the uptake of plastic particles by benthic filter feeding quagga mussels (Dreissena bugensis) and associated toxicity exhibited through impacts on mortality, filtration rate, reproduction and oxygen consumption. Matrix Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI-IMS) technology was used to assess the microplastic inclusion. For this purpose, quagga mussels were exposed to four treatments ranging from 0.0 to 0.8 g/L of a high density fluorescent red polyethylene powder in the size range of 10–45 μm for 24-h, and the targeted endpoints were quantified. Identification of several micrograms of microplastics in the digestive tract suggests rapid clearance from the water column by filtering. At the higher concentrations, about 95% of the microplastics ingested remained in the mussels after 24-h. Microplastics were found in the gills which correlated with decreasing filtration rate at higher microplastic concentrations. Despite large-scale ingestion, plastic exposure did not affect survivorship, reproduction rates, or oxygen consumption in the period examined. MALDI-IMS identified unique mass spectra that correlated with microplastic inclusion. This research suggests that microplastics can impair feeding through decreased filtration rates of filter feeding organisms, potentially resulting in a reduction of overall fitness over time and that MALDI-IMS may have the potential to identify microplastics and changes in tissue at the borders of plastic inclusion.

The contribution of large molecular size organic nitrogen (N) to plant N uptake is unclear. Soils with and without maize, at three pH levels, were treated with (carbon-14 and -13 (14C, 13C), 15N) triple-labelled ' 100 kDa organic N. After 48 h, soil and maize were sampled for bulk and compound specific isotope analysis to study the turnover in soil and plant 13C and 15N uptake. Mineralization of ' 100 kDa organic N increased with higher pH only in soil without maize. The ' 100 kDa organic N disappeared rapidly in soils with and without maize, but surprisingly more ' 100 kDa organic N derived amino acids remained in soil with than without maize – most likely in the microbial biomass. Total 15N uptake in maize increased with higher soil pH. The organic N uptake was estimated to account for 20–30% of the total 15N uptake. Organic N uptake was confirmed by the presence of 13C-labelled amino acids in maize roots. The study suggests that the importance of plant organic N uptake increases when N is derived from complex molecules such as proteins compared to studies using single amino acids as N source, and that rhizosphere microorganisms increase anabolic utilization of organic N compared to microorganisms in the bulk soil.

Mecanismes de la malaltia; Càncer de mama Mecanismos de la enfermedad; Cáncer de mama Disease Mechanisms; Breast Cancer The HER2 oncogene and its truncated form p95HER2 play central roles in breast cancer. Here, we show that although HER2 and p95HER2 generally elicit qualitatively similar changes in miRNA profile in MCF-7 breast cancer cells, a subset of changes are distinct and p95HER2 shifts the miRNA profile towards the basal breast cancer subtype. High-throughput miRNA profiling was carried out 15, 36 and 60 h after HER2 or p95HER2 expression and central hits validated by RT-qPCR. miRNAs strongly regulated by p95HER2 yet not by HER2, included miR-221, miR-222, miR-503, miR-29a, miR-149, miR-196 and miR-361. Estrogen receptor-α (ESR1) expression was essentially ablated by p95HER2 expression, in a manner recapitulated by miR-221/-222 mimics. c-Myb family transcription factors MYB and MYBL1, but not MYBL2, were downregulated by p95HER2 and by miR-503 or miR-221/-222 mimics. MYBL1 3′UTR inhibition by miR-221/222 was lost by deletion of a single putative miR-221/222 binding sites. p95HER2 expression, or knockdown of either MYB protein, elicited upregulation of tissue inhibitor of matrix metalloprotease-2 (TIMP2). miR-221/222 and -503 mimics increased, and TIMP2 knockdown decreased, cell migration and invasion. A similar pathway was operational in T47D- and SKBr-3 cells. This work reveals important differences between HER2- and p95HER2- mediated miRNA changes in breast cancer cells, provides novel mechanistic insight into regulation of MYB family transcription factors by p95HER2, and points to a role for a miR-221/222– MYB family–TIMP2 axis in regulation of motility in breast cancer cells. This work was supported by the Danish Council for Independent Research (grants no. 12-126942 and 12-127290 to SFP), by the Hartmann foundation (SFP), Fondation Juchum (SFP), Kirsten og Freddy Johansens Fond (SFP), the Breast Cancer Research Foundation (BCRF-17-008) (JA), Instituto de Salud Carlos III (PI16/00253) (JA) and the Harboe foundation (SFP). Katrine Franklin Mark is gratefully acknowledged for excellent technical assistance. We are grateful to Pascal Pineau from Institut Pasteur, France for the MYBL1 3′UTR/psiCHECK2 construct.

Speed is a major killer in traffic. This paper presents the DriveLaB telematics platform that monitors drivers in real-Time and provides feedback if they are speeding. The platform has been developed in collaboration with a major Danish insurance company and used in three larger field trials. The platform uses an Android/iOS smartphone app at the client side and does all data processing at the server-side, e.g., map-matching. The paper first provides an overview of the entire platform and then focuses on three major technical challenges: 1) A trip scoring algorithm that allows for comparison of scores across trip length. 2) A notification system that provides both positive and negative real-Time feedback to the drivers, without leading the drivers' attention away from traffic. 3) Auto start of the cross-platform app to make it convenient for drivers to participate in the field trials. Three field trials, with 32 participants driving 57,933 km has been conducted. The results of these trials validates that trip scores can be compared across trip length. Further, we demonstrate that doing all data-processing on the server side is a viable approach also for real-Time notifications and that drivers are notified with reasonable delays. Finally, we show that the client auto start is fast, robust, and convenient.

Factorial calculations indicate that energy requirement of sows in late gestation is relatively constant, while there is a marked increase in protein requirement. Thus, the objective was to investigate plasma nutrient metabolites and determine the yield and composition of colostrum in sows fed different energy levels and proportions of standardized ileal digestible protein relative to metabolizable energy for two weeks prior to parturition. A total of 28 sows were either fed a high energy level and a fixed protein supply (HE-FP); a high energy level with a daily increase in the proportion of protein (HE-IP); a low energy level and a fixed protein supply (LE-FP) or a low energy level with a daily increase in the proportion of protein (LE-IP) from day 101 in gestation to day 2 in lactation. Sows were fed combinations of: (1) a basic diet, formulated to match recommendations for gestating sows, and (2) a supplement diet, high in protein, to fulfill requirements for colostrum, mammary growth, fetuses, placenta and uterus. Blood was collected on day 105 and 112 of gestation by jugular vein venipuncture four hours after feeding. Colostrum was collected at 0, 12, and 24 h relative to birth of the first piglet. Colostrum yield was estimated based on piglets’ birth weight, weight gain, and the duration the individual piglet had access to the udder. A daily increase in the protein to energy ratio, increased plasma urea and glucose concentrations on day 112 of gestation in sows fed a low energy level (P < 0.05). A positive relationship between glucose and urea in plasma and the dietary protein to energy ratio was observed (P < 0.05). Colostrum fat concentration at 0 h tended to be greater in sows fed LE-IP than in sows fed LE-FP with HE-IP and HE-FP being intermediate (P = 0.06). Moreover, a positive relationship between plasma glucose on day 112 of gestation and colostrum fat at 0 h was observed (P = 0.01), suggesting that an increase in plasma glucose was used by the mammary gland for fat synthesis of the colostrum synthesized pre-partum. No evidence of impact of dietary energy or protein to energy ratio was found for sow colostrum yield (P > 0.10). In conclusion, except for sow BW gain, no direct effects of energy or protein supply on farrowing length, birth interval and litter gain were observed, whereas dietary protein to energy ratio influenced energy and protein metabolism and tended to increase colostrum fat synthesized pre-partum.

Key points: Exogenous Na + /H + exchanger 1 (NHE1) expression stimulated the collective migration of epithelial cell sheets Stimulation with epidermal growth factor, a key morphogen, primarily increased migration of the front row of cells, whereas NHE1 increased that of submarginal cell rows, and the two stimuli were additive Accordingly, NHE1 localized not only to the leading edges of leader cells, but also in cryptic lamellipodia in submarginal cell rows NHE1 expression disrupted the morphology of epithelial cell sheets and three-dimensional cysts. Abstract: Collective cell migration plays essential roles in embryonic development, in normal epithelial repair processes, and in many diseases including cancer. The Na + /H + exchanger 1 (NHE1, SLC9A1) is an important regulator of motility in many cells and has been widely studied for its roles in cancer, although its possible role in collective migration of normal epithelial cells has remained unresolved. In the present study, we show that NHE1 expression in MDCK-II kidney epithelial cells accelerated collective cell migration. NHE1 localized to the leading edges of leader cells, as well as to cryptic lamellipodia in submarginal cell rows. Epidermal growth factor, a kidney morphogen, increased displacement of the front row of collectively migrating cells and reduced the number of migration fingers. NHE1 expression increased the number of migration fingers and increased displacement of submarginal cell rows, resulting in additive effects of NHE1 and epidermal growth factor. Finally, NHE1 expression resulted in disorganized development of MDCK-II cell cysts. Thus, NHE1 contributes to collective migration and epithelial morphogenesis, suggesting roles for the transporter in embryonic and early postnatal development.

Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na + ,HCO 3 – -cotransporter NBCn1 (Slc4a7) to intracellular acid–base regulation in ErbB2-induced breast cancer tissue and the consequences of NBCn1 knockout for breast tumor development and growth. We demonstrate an approximately 2-fold increase of NBCn1 protein abundance in ErbB2-induced breast cancer tissue compared to normal breast tissue despite a 4-fold decrease in the NBCn1 mRNA level. In congruence, we show that NBCn1 facilitates net acid extrusion and elevates steady-state intracellular pH in breast cancer tissue. Disruption of NBCn1 expression delayed ErbB2-induced breast carcinogenesis from a median tumor-free survival of 9.5 months in wild-type mice to 12 months in NBCn1-knockout mice and decelerated the tumor growth rate by approximately 1/3. Glycolytic metabolism—evaluated based on the interstitial concentrations of lactate and glucose measured in microdialysates—was increased in breast cancer tissue compared to normal breast tissue, but was unaffected by NBCn1 knockout. Disruption of NBCn1 expression inhibited cell proliferation—evaluated by staining for the proliferative marker Ki67—particularly in central tumor areas with predicted increase in acid loading from glycolytic metabolism. In conclusion, NBCn1 regulates intracellular pH in ErbB2-induced breast cancer tissue by providing a pathway for cellular uptake of HCO 3 – , which can neutralize metabolic acidic waste products. Disrupting NBCn1 expression delays ErbB2-induced breast cancer development, inhibits cancer cell proliferation, and decelerates tumor growth.

Precise acid-base homeostasis is essential for maintaining normal cell proliferation and growth. Conversely, dysregulated acid-base homeostasis, with increased acid extrusion and marked extracellular acidification, is an enabling feature of solid tumors, yet the mechanisms through which intra- and extracellular pH (pH(i), pH(e)) impact proliferation and growth are incompletely understood. The aim of this study was to determine the impact of pH, and specifically of the Na(+)/H(+) exchanger NHE1 and Na(+), HCO(3)(−) transporter NBCn1, on cell cycle progression and its regulators in human breast cancer cells. Reduction of pH(e) to 6.5, a common condition in tumors, significantly delayed cell cycle progression in MCF-7 human breast cancer cells. The NHE1 protein level peaked in S phase and that of NBCn1 in G2/M. Steady state pH(i) changed through the cell cycle, from 7.1 in early S phase to 6.8 in G2, recovering again in M phase. This pattern, as well as net acid extrusion capacity, was dependent on NHE1 and NBCn1. Accordingly, knockdown of either NHE1 or NBCn1 reduced proliferation, prolonged cell cycle progression in a manner involving S phase prolongation and delayed G2/M transition, and altered the expression pattern and phosphorylation of cell cycle regulatory proteins. Our work demonstrates, for the first time, that both NHE1 and NBCn1 regulate cell cycle progression in breast cancer cells, and we propose that this involves cell cycle phase-specific pH(i) regulation by the two transporters.

For corn grown on two light-textured soils, leaf P and N concentrations at the six-leaf stage represented their respective concentrations in shoots. At the seven/eight-leaf stage, the P concentration was higher in leaves than in shoots. Biomass at the seven/eight-leaf stage is linked to the N to P ratio in leaves and shoots at the six-leaf stage.

The article Cattle slurry acidification and application method can improve initial phosphorus availability for maize, written by Ingeborg F. Pedersen, Gitte H. Rubaek and Peter Sorensen, was originally published Online First without open access.

The volume-regulated anion channel (VRAC), also known as the volume-sensitive outwardly rectifying (VSOR) anion channel or the volume-sensitive organic osmolyte/anion channel (VSOAC), is essential for cell volume regulation after swelling in most vertebrate cell types studied to date. In addition to its role in cell volume homeostasis, VRAC has been implicated in numerous other physiological and pathophysiological processes, including cancer, ischemic brain edema, cell motility, proliferation, angiogenesis, programmed cell death, and excitotoxic glutamate release. Although VRAC has been extensively biophysically, pharmacologically, and functionally characterized, its molecular identity was highly controversial until the recent identification of the leucine-rich repeats containing 8A (LRRC8A) protein as essential for the VRAC current in multiple cell types and a likely pore-forming subunit of VRAC. Members of this distantly pannexin-1-related protein family form heteromers, and in addition to LRRC8A, at least another LRRC8 family member is required for the formation of a functional VRAC. This review summarizes the biophysical and pharmacological properties of VRAC, highlights its main physiological functions and pathophysiological implications, and outlines the search for its molecular identity.

TGFβ-induced expression of the NADPH oxidase Nox4 is essential for fibroblast-myofibroblast transition. Rho has been implicated in Nox4 regulation, but the underlying mechanisms are largely unknown. Myocardin-related transcription factor (MRTF), a Rho/actin polymerization-controlled coactivator of serum response factor, drives myofibroblast transition from various precursors. We have shown that TGFβ is necessary but insufficient for epithelial-myofibroblast transition in intact epithelia; the other prerequisite is the uncoupling of intercellular contacts, which induces Rho-dependent nuclear translocation of MRTF. Because the Nox4 promoter harbors a serum response factor/MRTF cis-element (CC(A/T)6GG box), we asked if MRTF (and thus cytoskeleton organization) could regulate Nox4 expression. We show that Nox4 protein is robustly induced in kidney tubular cells exclusively by combined application of contact uncoupling and TGFβ. Nox4 knockdown abrogates epithelial-myofibroblast transition-associated reactive oxygen species production. Laser capture microdissection reveals increased Nox4 expression in the tubular epithelium also during obstructive nephropathy. MRTF down-regulation/inhibition suppresses TGFβ/contact disruption-provoked Nox4 protein and mRNA expression, Nox4 promoter activation, and reactive oxygen species production. Mutation of the CC(A/T)6GG box eliminates the synergistic activation of the Nox4 promoter. Jasplakinolide-induced actin polymerization synergizes with TGFβ to facilitate MRTF-dependent Nox4 mRNA expression/promoter activation. Moreover, MRTF inhibition prevents Nox4 expression during TGFβ-induced fibroblast-myofibroblast transition as well. Although necessary, MRTF is insufficient; Nox4 expression also requires TGFβ-activated Smad3 and TAZ/YAP, two contact- and cytoskeleton-regulated Smad3-interacting coactivators. Down-regulation/inhibition of TAZ/YAP mitigates injury-induced epithelial Nox4 expression in vitro and in vivo. These findings uncover new MRTF- and TAZ/YAP-dependent mechanisms, which link cytoskeleton remodeling and redox state and impact epithelial plasticity and myofibroblast transition.

BACKGROUND: The cardiovascular burden and consequences of peripheral atherosclerosis appear to differ between men and women. Data regarding long-term outcomes, including the impact of medical prophylactic treatment, are insufficient. This study examined long-term outcomes according to sex following primary vascular surgery, adjusted for multiple variables as well as recommended medical prophylaxis.METHODS: All Danish patients who underwent peripheral vascular surgery from January 2000 to December 2007 were stratified into five procedural groups: (a) aorto-iliac bypass or thromboendarterectomy, (b) femoro-femoral crossover, (c) thromboendarterectomy of the femoral arteries, (d) infrainguinal bypass, or (e) axillo- uni-, and bifemoral bypass. Data were analyzed according to sex for differences in myocardial infarction, stroke, and death, individually and combined, after surgery.RESULTS: A total of 11,234 patients were included: 6,289 males and 4,945 females. The overall adjusted hazard ratio for male patients compared with female patients for death was 1.11 (95% CI 1.06-1.17), for MI was 1.16 (95% CI 1.04-1.29), for stroke was 0.99 (95% CI 0.89-1.11), and for any major adverse cardiovascular event was 1.10 (95% CI 1.05-1.16).CONCLUSIONS: These findings show that, despite indication, severity, and concomitant medical treatment of peripheral artery disease, men have a higher risk of mortality and adverse cardiovascular events following surgery for peripheral arterial disease.

Continental margin sediments are commonly studied using trace metal enrichments as proxies for characterizing their modern redox conditions and tracking past changes in bottom water ventilation and marine primary productivity. Currently little is known about the sedimentary redox history of the continental shelf west of the Antarctic Peninsula. Yet, environmental conditions in the Antarctic Peninsula region have changed rapidly in recent decades in response to global warming. Paleoclimate archives including bulk sediment trace metal enrichments can provide insight into both past and future environmental changes in this climatically sensitive region, and characterization of redox conditions in surface (modern) sediments is essential for establishing a framework for paleoredox interpretations. In this study we measured concentrations of trace metals (Ag, Cd, Re, and Mo) and productivity proxies (total Ba, organic carbon, and biogenic silica) in surface sediments from the Marguerite Bay, Gerlache Strait, and Bransfield Strait areas. Proxy concentrations suggest that sediments are generally suboxic due to seasonally high export of organic carbon from surface waters. Comparison of West Antarctic Peninsula trace metal/Al ratios to trace metal data from continental margins outside the Antarctic region demonstrates that although the West Antarctic Peninsula water column differs from other locations (e.g., it lacks a strong oxygen minimum zone), sedimentary redox chemistry is similarly controlled by organic matter decomposition, through slow recycling of highly seasonal export production falling through a cold water column.

Solute carriers (SLCs) are one of the largest groups of multi-spanning membrane proteins in mammals and include ubiquitously expressed proteins as well as proteins with highly restricted tissue expression. A vast number of studies have addressed the function and organization of SLCs as well as their posttranslational regulation, but only relatively little is known about the role of SLC glycosylation. Glycosylation is one of the most abundant posttranslational modifications of animal proteins and through recent advances in our understanding of protein-glycan interactions, the functional roles of SLC glycosylation are slowly emerging. The purpose of this review is to provide a concise overview of the aspects of glycobiology most relevant to SLCs, to discuss the roles of glycosylation in the regulation and function of SLCs, and to outline the major open questions in this field, which can now be addressed given major technical advances in this and related fields of study in recent years.

We report manufacture of fully printed and coated polymer solar cells on a small scale roll-to-roll coater representing the intermediate scale between laboratory and pilot scale. We highlight the enormous span in scale between the laboratory scale and the intended industrial scale by a factor of >100.000 and detail how this enormous scale must be covered by equipment that follow the scale. Especially the intermediate scale between equipment that can fit inside a fume cupboard and the typical pilot equipment with a footprint having the size of a large room presents a challenge that comprises some of the most critical steps in the scaling process. We describe the development of such a machine that comprise web guiding, tension control and surface treatment in a compact desk size that is easily moved around and also detail the development of a small cassette based flexographic unit for back electrode printing that is parsimonious in terms of ink usage and more gentle than laboratory scale flexo units where the foil transport is either driven by the flexo unit or the flexo unit is driven by the foil transport. We demonstrate fully operational flexible polymer solar cell manufacture using this new roll and roll-to-roll (R3) approach and compare with the existing methods.

A high-resolution sedimentary record of dinoflagellate cysts from Ocean Drilling Program Hole 1017E (off Point Conception, California margin) reflects how marine primary productivity has changed in response to major shifts in climate and ocean circulation along the California margin over the past 42 kyr. Throughout the studied sequence, dinoflagellate cyst assemblages are dominated by upwelling-related taxa, signifying the continued presence of coastal upwelling on the margin during the late Quaternary. The cyst record suggests that marine primary productivity was enhanced during the Holocene and Bolling, and to a lesser extent, during the late glacial and most Dansgaard-Oeschger events, while an apparent reduction in primary productivity can be seen during the Younger Dryas. The best analogue technique, based on a modern dinoflagellate cyst assemblage database from the northeast Pacific, was used for quantitative reconstruction of past sea surface conditions. It points to dynamic changes in annual marine primary productivity (~235–331 g C m−2 yr−1) and sea surface temperature (~10.1–12.6°C in winter; ~13.1–14.3°C in summer), while sea surface salinity appears to be confined to a narrower range (~32.9–33.4 in summer). Our results also indicate noticeable climate variability during the Holocene in this region.

Loss of function mutations in waxy, encoding granule bound starch synthase (GBSS) that synthesizes amylose, results in starch granules containing mostly amylopectin. Low amylose grain with altered starch properties has increased usability for feed, food, and grain-based ethanol. In sorghum, two classes of waxy (wx) alleles had been characterized for absence or presence of GBSS: wxa (GBSS−) and wxb (GBSS+, with reduced activity). Field-grown grain of wild-type; waxy, GBSS−; and waxy, GBSS+ plant introduction accessions were screened for fungal infection. Overall, results showed that waxy grains were not more susceptible than wild-type. GBSS− and wild-type grain had similar infection levels. However, height was a factor with waxy, GBSS+ lines: short accessions (wxb allele) were more susceptible than tall accessions (undescribed allele). In greenhouse experiments, grain from accessions and near-isogenic wxa, wxb, and wild-type lines were inoculated with Alternaria sp., Fusarium thapsinum, and Curvularia sorghina to analyze germination and seedling fitness. As a group, waxy lines were not more susceptible to these pathogens than wild-type, supporting field evaluations. After C. sorghina and F. thapsinum inoculations most waxy and wild-type lines had reduced emergence, survival, and seedling weights. These results are valuable for developing waxy hybrids with resistance to grain-infecting fungi.

Grain sorghum [Sorghum bicolor (L.) Moench] is an important crop for rainfed production systems with 2.7 million ha grown in the United States in 2013. The brown-midrib (bmr) mutations, especially bmr-12, have resulted in low stover lignin and high fiber digestibility without reducing grain yield in some sorghum lines. However, the effect of the bmr trait on beef cattle (Bos taurus) performance when grazing crop residue is unknown. Our objectives were to validate previous small-plot results reporting no grain yield difference between near-isogenic bmr-12 (BMR) and wild-type control (CON) A Wheatland × R Tx430 sorghum hybrids in a field-scale experiment and to determine if BMR stover enhances beef production in a grazing experiment. Four replicated paddocks (2.3 ha) were planted in 2006 and 2008 near Mead, NE. Crossbred yearling steers (240 ± 17 kg hd⁻¹) grazed (2.6 steers ha⁻¹) paddocks following grain harvest for 72 d in 2006 and 61 d in 2008. Forage was sampled 4, 30, and 60 d after grazing began. Grain yield of BMR was 6% less (P = 0.01) than CON with no difference in stover neutral detergent fiber (NDF) content, but BMR stover had higher in vitro NDF digestibility (IVNDFD) (31%; P < 0.0001), steer average daily gain (ADG; 0.18 kg hd⁻¹ d⁻¹; P = 0.001), and body weight (BW) gain (29 kg ha⁻¹; P = 0.002), resulting in an estimated increase in net return of $133.84 ha⁻¹ due to BMR. Results suggest that the A Wheatland × R Tx430 bmr-12 hybrid is an effective dual-purpose sorghum crop for both grain and beef production.

Metabolic acid production challenges cellular pH homeostasis in solid cancer tissue, and mechanisms of net acid extrusion represent promising new targets for breast cancer therapy. Here, we used genetically engineered mice to investigate the contribution of the Na

The Na+;HCO3− co-transporter NBCn1 (SLC4A7) is a major regulator of intracellular pH yet its trafficking and turnover are essentially unstudied. Here, we used MDCK-II and MCF-7 cells to investigate these processes in epithelial cells. GFP-NBCn1 membrane localization was abolished by truncation of the full NBCn1 C-terminal tail (C-tail) yet did not require the C-terminal PDZ-binding motif (ETSL). Glutathione-S-Transferase-pulldown of the C-tail followed by mass spectrometry analysis revealed putative interactions with multiple sorting-, degradation- and retention factors, including the scaffolding protein RACK1. Pulldown of FLAG-tagged deletion constructs mapped the RACK1 interaction to the proximal NBCn1 C-tail. Proximity Ligation Assay and co-immunoprecipitation confirmed that native NBCn1 interacts with RACK1 in a cellular context. Consistent with a functional role of this complex, RACK1 knockdown reduced NBCn1 membrane localization without affecting total NBCn1 expression. Notably, only non-confluent cells exhibited detectable NBCn1-RACK1 plasma membrane co-localization, suggesting that RACK1 regulates the trafficking of NBCn1 to the membrane. Whereas total NBCn1 degradation was slow, with a half-life of more than 24 h, one-third of surface NBCn1 was constitutively endocytosed from the basolateral membrane within 60 min. This suggests that a fraction of NBCn1 exhibits recycling between the basolateral membrane and intracellular compartment(s). Our findings have important implications for understanding NBCn1 regulation as well as its dysregulation in disease.

A high-resolution, 55 kyr long record of chalcophile and redox-sensitive trace element accumulation (Ag, Cd, Re, and Mo) from MD02-2515, western Guaymas Basin, is investigated in conjunction with patterns in stratigraphy and productivity. High opal concentrations (~59 wt. %), representing increased diatom production, coincide with laminated sediments and dilute the concentrations of organic carbon (Corg) and metals. A similarity between opal and normalized Corg, Ag, and Cd concentrations suggests delivery to the sediments by diatom export production, while patterns in normalized Re and Mo accumulation suggest a different emplacement mechanism. Although Mo enrichment in organic-rich, laminated sediments typically represents anoxic conditions at other locations, Mo (and Re) in Guaymas Basin is enriched in nonlaminated and bioturbated sediments that are representative of oxygenated conditions. Adsorption onto Fe- and/or Mn-oxyhydroxide surfaces during oxygenation inadequately explains both the Re and Mo enrichments. Thus, recently published mechanisms invoking direct Re and Mo removal from the water column and bioturbation-assisted irrigation of Re into the sediments are used to explain the counterintuitive observations in Guaymas Basin. The MD02-2515 stratigraphic and proxy records are also different from other records in the northeast Pacific in that there is little correspondence with Greenland Dansgaard-Oeschger interstadials. There is some correlation with Heinrich events, suggesting that ventilation of intermediate waters and/or reduced productivity may be important in controlling stratigraphy and trace element accumulation. The results question whether MD02-2515 records can be compared to northeast Pacific open-margin records, especially before 17 kyr B.P.

Cellular antennas having a mutual coupling can be isolated by the generation of an additional current path along a ground plane. A first antenna element can resonate at a resonance that interferes with and is mutually coupled to a second antenna element operating in a same frequency range, such as a low band frequency range. One or more parasitic scattering elements can generate the additional current path between the two antennas and isolate the two antennas from one another. A parasitic scattering element can comprise two capacitors that alter a radiation pattern of one of the antennas and decrease a correlation between both antennas.

Monitoring needs of spacecraft are rapidly increasing due to new and more challenging missions, along with demands to reduce launching costs by minimizing the manufacture, assembly, integration and test time and employing new low weight materials balanced by the need for maximizing system lifetime while maintaining good reliability. Conventional electronic sensors are characterized by their low multiplexing capability and their EMI/RF susceptibility and it is in this scenario that Fiber Optic Sensors (FOS) in general, and more specifically Fiber Bragg Grating (FBG) technology offers important benefits, improving in various ways the already deployed sensing subsystems (e.g. reducing the weight associated with sensor cabling, increasing the number of sensing points) and enabling new monitoring applications that were not possible by using conventional sensing technologies. This work presents the activities performed and the lessons learnt in the frame of ESA's ARTES-5 project "Fiber Optic Sensing Subsystem for Spacecraft Health Monitoring in Telecommunication Satellites". This project finished in July 2009, with the implementation and testing of two different demonstrators employing FBG sensor technology: FBG sensors for temperature monitoring in high voltage environments, and in particular in several parts of electric propulsion subsystems [1], and FBG sensors for thermal monitoring of array-antennas during RF testing [2]. In addition, the contacts performed with different actors within the space community allowed the identification of a special area of interest for the substitution of regular thermocouple instrumentation by FBG technology for thermal vacuum ground testing of satellites. Sin financiación No data (2017) UEM

Precise spatiotemporal regulation of intracellular pH (pHi ) is a prerequisite for normal cell function, and changes in pHi or pericellular pH (pHe ) exert important signalling functions. It is well established that proliferation of mammalian cells is dependent on a permissive pHi in the slightly alkaline range (7.0-7.2). It is also clear that mitogen signalling in nominal absence of HCO3- is associated with an intracellular alkalinization (~0.3 pH unit above steady-state pHi ), which is secondary to activation of Na+ /H+ exchange. However, it remains controversial whether this increase in pHi is part of the mitogenic signal cascade leading to cell cycle entry and progression, and whether it is relevant under physiological conditions. Furthermore, essentially all studies of pHi in mammalian cell proliferation have focused on the mitogen-induced G0-G1 transition, and the regulation and roles of pHi during the cell cycle remain poorly understood. The aim of this review is to summarize and critically discuss the possible roles of pHi and pHe in cell cycle progression. While the focus is on the mammalian cell cycle, important insights from studies in lower eukaryotes are also discussed. We summarize current evidence of links between cell cycle progression and pHi and discuss possible pHi - and pHe sensors and signalling pathways relevant to mammalian proliferation control. The possibility that changes in pHi during cell cycle progression may be an integral part of the checkpoint control machinery is explored. Finally, we discuss the relevance of links between pH and proliferation in the context of the perturbed pH homoeostasis and acidic microenvironment of solid tumours.

The high precious metal loading and high overpotential of the oxygen evolution reaction (OER) prevents the widespread utilization of polymer electrolyte membrane (PEM) water electrolyzers. Herein we explore the OER activity and stability in acidic electrolyte of a combined IrO

Herein we present surface sensitive operando XAS L-edge measurements on IrO

The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows. A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used. Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet). The enzyme applied was a mono-component xylanase dosed at 200 enzyme unit (FXU) per kg of feed, which corresponds to 200 g per ton of feed. The diets were fed until weaning at day 28 of lactation. On day 2 of lactation, litter size of each sow was adjusted to 14 piglets within treatment. Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured. Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition. Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments. Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments. The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from −13.6 to −5.2 kg (P = 0.04) with xylanase addition when compared to control sows. The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation. Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04). In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.

Several Fusarium spp. cause sorghum (Sorghum bicolor) grain mold, resulting in deterioration and mycotoxin production in the field and during storage. Fungal isolates from the air (2005 to 2006) and from leaves and grain from wild-type and brown midrib (bmr)-6 and bmr12 plants (2002 to 2003) were collected from two locations. Compared with the wild type, bmr plants have reduced lignin content, altered cell wall composition, and different levels of phenolic intermediates. Multilocus maximum-likelihood analysis identified two Fusarium thapsinum operational taxonomic units (OTU). One was identified at greater frequency in grain and leaves of bmr and wild-type plants but was infrequently detected in air. Nine F. graminearum OTU were identified: one was detected at low levels in grain and leaves while the rest were only detected in air. Wright’s F statistic (FST) indicated that Fusarium air populations differentiated between locations during crop anthesis but did not differ during vegetative growth, grain development, and maturity. FST also indicated that Fusarium populations from wild-type grain were differentiated from those in bmr6 or bmr12 grain at one location but, at the second location, populations from wild-type and bmr6 grain were more similar. Thus, impairing monolignol biosynthesis substantially effected Fusarium populations but environment had a strong influence.

Naturally ventilated dairy cattle buildings are one of the major sources for ammonia and greenhouse gas emissions to the atmosphere. Generally it is difficult to clean the air from naturally ventilated buildings. In order to reduce the emissions, a hybrid ventilation system, which is natural ventilation combining with mechanical partial pit ventilation, has been developed. By full-scale measurement, this study was to quantify ammonia and methane emissions and to investigate the impacts of climate parameters on gaseous emissions, air exchange rate (ACH) and concentrations at sampling locations in a dairy cattle building with hybrid ventilation. The results revealed that 64–83% of ammonia emissions were collected by partial pit ventilation while 10–50% of methane emission was collected. The results showed that ammonia emission through natural ventilation was around 60% lower than the value found in literatures. ACH was significantly influenced by wind speed and wind direction (wind angle in the range of 135–270°) in summer. The ACH increased generally with wind speed in winter while it hardly changed with wind speed when the windows opening ratio was 6% and even lower. The paper further investigated the impact of wind speed and outdoor temperature on ammonia emissions.

Sorghum lines were bred for reduced lignin for cellulosic bioenergy uses, through the incorporation of brown midrib (bmr)6 or -12 into two backgrounds (RTx430 and Wheatland) as either single or double-mutant lines. When these lines were assessed for resistance to Fusarium thapsinum stalk rot, a cause of lodging, they were as resistant to F. thapsinum as the near-isogenic wild type. Peduncles of newly identified bmr lines from an ethyl-methanesulfonate-mutagenized population, inoculated with F. thapsinum, were as resistant as the wild-type line, BTx623. One bmr line (1107) had significantly smaller mean lesion lengths than BTx623, suggesting that a mutation is associated with reduced susceptibility. Growing F. thapsinum on medium with ferulic, vanillic, sinapic, syringic, and caffeic acids (phenolic compounds derived from the lignin pathway and elevated in different bmr lines) indicated that F. thapsinum was tolerant to these compounds. When eight other sorghum fungi were tested for response to the presence of these compounds, ferulic acid inhibited these fungi. Most of the phenolics inhibited F. verticillioides and F. proliferatum. Accumulation of phenolic metabolites in bmr plants may inhibit growth of some sorghum pathogens, while other factors such as aromatic phytoalexins or salicylic acid may be involved in resistance to F. thapsinum.

Reducing lignin concentration in lignocellulosic biomass can increase forage digestibility for ruminant livestock and saccharification yields of biomass for bioenergy. In sorghum (Sorghum bicolor (L.) Moench) and several other C4 grasses, brown midrib (bmr) mutants have been shown to reduce lignin concentration. Putative bmr mutants isolated from an EMS-mutagenized population were characterized and classified based on their leaf midrib phenotype and allelism tests with the previously described sorghum bmr mutants bmr2, bmr6, and bmr12. These tests resulted in the identification of additional alleles of bmr2, bmr6, and bmr12, and, in addition, six bmr mutants were identified that were not allelic to these previously described loci. Further allelism testing among these six bmr mutants showed that they represented four novel bmr loci. Based on this study, the number of bmr loci uncovered in sorghum has doubled. The impact of these lines on agronomic traits and lignocellulosic composition was assessed in a 2-yr field study. Overall, most of the identified bmr lines showed reduced lignin concentration of their biomass relative to wild-type (WT). Effects of the six new bmr mutants on enzymatic saccharification of lignocellulosic materials were determined, but the amount of glucose released from the stover was similar to WT in all cases. Like bmr2, bmr6, and bmr12, these mutants may affect monolignol biosynthesis and may be useful for bioenergy and forage improvement when stacked together or in combination with the three previously described bmr alleles.

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival rates of all cancers. ANO1 (TMEM16A) is a recently identified Ca2+-activated Cl− channel (CaCC) that is upregulated in several tumors. Although ANO1 was subject to extensive studies in the recent years, its pathophysiological function has only been poorly understood. The aim of the present study is to establish the significance of ANO1 in PDAC behavior and demarcate its roles in PDAC from those of the volume-regulated anion channel (VRAC). We performed qPCR and Western blot measurements on different PDAC cell lines (Panc-1, Mia PaCa 2, Capan-1, AsPC-1, BxPC-3) and compared the results to those obtained in a human pancreatic ductal epithelium (HPDE) cell line. All cancer cell lines showed an upregulation of ANO1 on mRNA and protein levels. Whole-cell patch-clamp recordings identified large Ca2+ and voltage-dependent Cl− currents in PDAC cells. Using siRNA knockdown of ANO1 and three ANO1 inhibitors (T16Ainh-A01, CaCCinh-A01, and NS3728), we found that ANO1 is the main constituent of CaCC current in PDAC cells. We further characterized these three inhibitors and found that they had unspecific effects on the free intracellular calcium concentration. Functional studies on PDAC behavior showed that surprisingly inhibition of ANO1 did not influence cellular proliferation. On the other hand, we found ANO1 channel to be pivotal in PDAC cell migration as assessed in wound healing experiments. Electronic supplementary material The online version of this article (doi:10.1007/s00424-014-1598-8) contains supplementary material, which is available to authorized users.

Deglacial sediments in piston core JT96-02 from the continental slope off western Canada contain numerous centimeter-thick, iron sulfide-rich layers. Major and minor element chemistry, as well as C and N isotopic data suggest that these layers represent background hemipelagic sedimentation. Intervening gray silty clay layers, each of which exhibits a fining-upward trend, are distal turbidites. The iron sulfides precipitated in response to the emplacement of each turbidite, which slowed oxygen diffusion into the sediment allowing anoxic conditions to develop in the underlying relatively organic-rich deposits. Resulting sulfate reduction and precipitation of Fe-sulfide fostered Mo enrichment (> 2 μg/g). It may also explain Ni, Cr, V, and Co enrichments, although differences in detrital mineralogy cannot be ruled out, particularly for Ni and Cr. Rhenium is also enriched, albeit slightly, within the sulfide layers, but low Re/Mo ratios (~ 0.78 ng/g/μg/g) suggest that anoxic conditions developed very rapidly. Metals with high lithogenic concentrations (Cd and U) are not obviously enriched in the sulfide layers because there was insufficient time for noticeable authigenic accumulation before deposition of the next turbidite which severed diffusive communication with overlying seawater, the primary source of metals. Silver is also slightly higher in the sulfide layers, possibly linked to higher marine organic matter content. In summary, the pulsed character of sedimentation during the deglaciation led to episodic enrichment of Mo and occurred independently of changes in bottom water oxygen or organic carbon content. This observation potentially complicates the use of Mo as a paleo-proxy in some continental margin environments.

Background and objective During forced expiration, alveolar pressure (PALV) increases and intrathoracic gas is compressed. Thus, 1-s forced expiratory volume measured by spirometry (FEV1-sp) is smaller than 1-s forced expiratory volume measured by plethysmography (FEV1-pl). Thoracic gas compression volume (TGCV) depends on the amount of gas within the lung when expiratory flow limitation occurs in the airways. We therefore tested the hypothesis that bronchoconstrictor and bronchodilator responses using FEV1-sp are biased by height and gender, which are major determinants of lung volume. Methods We studied 54 asthmatics during methacholine challenge and 55 subjects with airway obstruction (FEV1-sp increase >200 mL and >12% after salbutamol) measuring at the same time FEV1-sp or FEV1-pl. Results During methacholine challenge, TGCV increased more in males than females, correlated with PALV, total lung capacity (TLC) and height, and the provocative dose was lower using FEV1-sp than FEV1-pl. With salbutamol, FEV1-pl increased

Background and Purpose Endothelins act via two receptor subtypes, ETA and ETB. Under physiological conditions in coronary arteries, ETA receptors expressed in smooth muscle cells mediate vasoconstriction whereas ETB receptors mainly found in endothelial cells mediate vasorelaxation. However, under pathophysiological conditions, ETB receptors may also be expressed in vascular smooth muscle cells mediating vasoconstriction. Here, we have investigated whether vasoconstrictor ETB receptors are up-regulated in coronary arteries after experimental myocardial ischaemia in rats. Experimental Approach Male Sprague-Dawley rats were subjected to either heart ischaemia–reperfusion (15 min ischaemia and 22 h reperfusion), permanent ischaemia (22 h) by ligation of the left anterior descending coronary artery, or sham operation. Using wire myography, the endothelin receptor subtypes mediating vasoconstriction were examined in isolated segments of the left anterior descending and the non-ligated septal coronary arteries. Endothelin receptor-mediated vasoconstriction was examined with cumulative administration of sarafotoxin 6c (ETB receptor agonist) and endothelin-1 (with or without ETA or ETB receptor blockade). The distribution of ETB receptors was localized with immunohistochemistry and quantified by Western blot. Key Results Endothelin ETB receptor-mediated vasoconstriction and receptor protein levels were significantly augmented in coronary arteries situated downstream of the occlusion after ischaemia–reperfusion compared with non-ischaemic arteries. In contrast, the ETA receptor-mediated vasoconstriction was unaltered in all groups. Conclusions and Implications Ischaemia–reperfusion induced local up-regulation of ETB receptors in the smooth muscle cells of coronary arteries in the post-ischaemic area. In contrast, in non-ischaemic areas, ETB receptor function was unaltered.

Cadmium (Cd) is a micronutrient and a tracer of biological productivity and circulation in the ocean. The correlation between dissolved Cd and the major algal nutrients in seawater has led to the use of Cd preserved in microfossils to constrain past ocean nutrient distributions. However, linking Cd to marine biological processes requires constraints on marine sources and sinks of Cd. Here, we show a decoupling between Cd and major nutrients within oxygen-deficient zones (ODZs) in both the Northeast Pacific and North Atlantic Oceans, which we attribute to Cd sulfide (CdS) precipitation in euxinic microenvironments around sinking biological particles. We find that dissolved Cd correlates well with dissolved phosphate in oxygenated waters, but is depleted compared with phosphate in ODZs. Additionally, suspended particles from the North Atlantic show high Cd content and light Cd stable isotope ratios within the ODZ, indicative of CdS precipitation. Globally, we calculate that CdS precipitation in ODZs is an important, and to our knowledge a previously undocumented marine sink of Cd. Our results suggest that water column oxygen depletion has a substantial impact on Cd biogeochemical cycling, impacting the global relationship between Cd and major nutrients and suggesting that Cd may be a previously unidentified tracer for water column oxygen deficiency on geological timescales. Similar depletions of copper and zinc in the Northeast Pacific indicate that sulfide precipitation in ODZs may also have an influence on the global distribution of other trace metals.