Effects of fertilization on soil CH4 and N2O fluxes in young Norway spruce stands

Climate change mitigation strategies have increased the demand for wood products, resulting in an urgent need to increase wood production. One approach is to fertilize forest land, but this can influence greenhouse gas (GHG) fluxes within the ecosystem. The aim of this study was to examine the effects of forest N fertilization on soil CH4 and N2O fluxes in young Norway spruce (Picea abies (L.) Karst.) stands in southern Sweden. The gas fluxes were measured using flow-through non-steady-state dark chambers. In the first, long-term, experiment, half of the stand was fertilized twice (once in 2014 and once in 2016) with 150 kg ha(-1) of N, and gas flux measurements were taken throughout 2014-2017. In the second, dose, experiment, 0, 150, 300, or 450 kg ha(-1) of N was added to the stand in April 2016, and gas flux measurements were taken during April-December 2016. The dose experiment showed that the sink strength of CH4 decreased with increasing amounts of N; the long-term experiment indicated that repeated fertilization decreased the CH4 sink strength over time. Additionally, the long-term experiment indicated that, while significantly higher N2O emissions were recorded in the fertilization years, this was not detected in subsequent years, suggesting the effect to be short-lived. In the dose experiment, fertilization tended to increase the N2O emissions relative to the amount of fertilizer. However, despite the significant effects of fertilization on these GHGs, the summed fluxes were a fraction of the net uptake of C at the sites, as recorded in another study. These findings suggest that fertilizing forest land with commercial NP or NPK fertilizers corresponding to 150 kg ha(-1) of N, the level used in operational forestry in Sweden today, can be conducted without changing CH4 and N2O fluxes to any great extent

IGFBP3 Colocalizes with and Regulates Hypocretin (Orexin)

Background: The sleep disorder narcolepsy is caused by a vast reduction in neurons producing the hypocretin (orexin) neuropeptides. Based on the tight association with HLA, narcolepsy is believed to result from an autoimmune attack, but the cause of hypocretin cell loss is still unknown. We performed gene expression profiling in the hypothalamus to identify novel genes dysregulated in narcolepsy, as these may be the target of autoimmune attack or modulate hypocretin gene expression. Methodology/Principal Findings: We used microarrays to compare the transcriptome in the posterior hypothalamus of (1) narcoleptic versus control postmortem human brains and (2) transgenic mice lacking hypocretin neurons versus wild type mice. Hypocretin was the most downregulated gene in human narcolepsy brains. Among many additional candidates, only one, insulin-like growth factor binding protein 3 (IGFBP3), was downregulated in both human and mouse models and coexpressed in hypocretin neurons. Functional analysis indicated decreased hypocretin messenger RNA and peptide content, and increased sleep in transgenic mice overexpressing human IGFBP3, an effect possibly mediated through decrease

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Liquid chromatography and electron-capture dissociation in Fourier transform ion cyclotron resonance mass spectrometry

Liq. sepn. methods in combination with electrospray mass spectrometry as well as the recently introduced fragmentation method electron capture dissocn. (ECD) have become powerful tools in proteomics research. This paper presents the results of the first successful attempts to combine liq. chromatog. (LC) and Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS) with ECD in the anal. of a mixt. of std. peptides and of a bovine serum albumin tryptic digest. A novel electron injection system provided conditions for ECD sufficient to yield extensive sequence information for the most abundant peptides in the mixts. on the time-scale of the chromatog. sepn. The results suggest that LC/ECD-FTICRMS can be employed in the characterization of peptides in enzymic digests of proteins or protein mixts. and identify and localize posttranslational modifications. [on SciFinder (R)

Peptide and protein characterization by high-rate electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry

A review. The anal. utility of the electron capture dissocn. (ECD) technique, developed by McLafferty and co-workers, has substantially improved peptide and protein characterization using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). The limitations of the first ECD implementations on com. instruments were eliminated by the employment of low-energy electron-injection systems based on indirectly heated dispenser cathodes. In particular, the ECD rate and reliability were greatly increased, enabling the combination of ECD/FTICR-MS with online liq. sepn. techniques. Further technique development allowed the combination of two rapid fragmentation techniques, high-rate ECD and IR multiphoton dissocn. (IRMPD), in a single exptl. configuration. Simultaneous and consecutive irradiations of trapped ions with electrons and photons extended the possibilities for ion activation/dissocn. and led to improved peptide and protein characterization. The application of high-rate ECD/FTICR-MS has demonstrated its power and unique capabilities in top-down sequencing of peptides and proteins, including characterization of post-translational modifications, improved sequencing of peptides with multiple disulfide bridges and secondary fragmentation (w-ion formation). Anal. of peptide mixts. has been accomplished using high-rate ECD in bottom-up mass spectrometry based on mixt. sepn. by liq. chromatog. and capillary electrophoresis. This paper summarizes the current impact of high-rate ECD/FTICR-MS for top-down and bottom-up mass spectrometry of peptides and proteins. [on SciFinder (R)

Peptide and protein characterization by high-rate electron capture dissociation Fourier transform ion cyclotron resonance mass spectrometry. [Erratum to document cited in CA142:280385]

A review. On page 723, the equation should read: [M + zH](z-1)+.bul.: [M + zH]Z+ + e -> [M + zH](z-1)+.bul. (+6 eV) -> [M + (z - 1)H](z-1)+ + H.* -> fragments. [on SciFinder (R)

Ionization energies of multiply protonated polypeptides obtained by tandem ionization in Fourier transform mass spectrometers

Ionization energies (IE) of [M + zH]z+ (z+) electrospray-produced polypeptides were detd. by electron ionization in a Penning cell of 4.7 and 9.4 .T Fourier transform mass spectrometers. For z = 1+ and substance P, the found IE value of 11.0+-0.4 eV is in agreement with that obtained earlier for ions generated with matrix-assisted laser desorption/ionization. For higher z, the following values were found: 11.7+-0.3 eV for 2+ of [Arg-8]-vasopressin, 11.1+-0.6 eV for 2+ of substance P, 12.2+-0.7 eV for 2+ of renin substrate, 13.3+-0.4 eV for 3+ of B-chain of insulin and 14.6+-0.6 eV for 4+ and 15.1+-0.4 eV for 5+ of melittin. It was found that 90% of existing IE data on polypeptides in the 1.0-3.5 kDa mass range are described with ? 0.5 eV uncertainty by the empirical equation IE(z) = 9.8+1.1z. The av. IE increase of 1.1 eV/charge is attributed to Coulombic repulsion. The deduced ionization energy of a neutral polypeptide mol., 9.8+-0.3 eV, is consistent with literature expectations. [on SciFinder (R)

Combined infrared multiphoton dissociation and electron capture dissociation with a hollow electron beam in Fourier transform ion cyclotron resonance mass spectrometry

An electron injection system based on an indirectly heated ring-shaped dispenser cathode was developed and installed in a 7 T Fourier transform ICR (FTICR) mass spectrometer. This new hardware design allows high-rate electron capture dissocn. (ECD) to be carried out by a hollow electron beam coaxial with the ICR trap. IR multiphoton dissocn. (IRMPD) can also be performed with an on-axis IR-laser beam passing through a hole at the center of the dispenser cathode. Electron and photon irradn. times of the order of 100 ms are required for efficient ECD and IRMPD, resp. As ECD and IRMPD generate fragments of different types (mostly c, z and b, y, resp.), complementary structural information that improves the characterization of peptides and proteins by FTICR mass spectrometry can be obtained. The developed technique enables the consecutive or simultaneous use of the ECD and IRMPD methods within a single FTICR exptl. sequence and on the same ensemble of trapped ions in multistage tandem (MS/MS/MS or MSn) mass spectrometry. Flexible changing between ECD and IRMPD should present advantages for the anal. of protein digests sepd. by liq. chromatog. prior to FTICRMS. Also, ion activation by either electron or laser irradn. prior to, as well as after, dissocn. by IRMPD or ECD increases the efficiency of ion fragmentation, including the w-type fragment ion formation, and improves sequencing of peptides with multiple disulfide bridges. The developed instrumental configuration is essential for combined ECD and IRMPD on FTICR mass spectrometers with limited access into the ICR trap. [on SciFinder (R)