Oligosaccharyltransferase (OST) catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum. Mammals express two distinct OST complexes that act in a ...cotranslational (OST-A) or posttranslocational (OST-B) manner. Here, we present high-resolution cryo-electron microscopy structures of human OST-A and OST-B. Although they have similar overall architectures, structural differences in the catalytic subunits STT3A and STT3B facilitate contacts to distinct OST subunits, DC2 in OST-A and MAGT1 in OST-B. In OST-A, interactions with TMEM258 and STT3A allow ribophorin-I to form a four-helix bundle that can bind to a translating ribosome, whereas the equivalent region is disordered in OST-B. We observed an acceptor peptide and dolichylphosphate bound to STT3B, but only dolichylphosphate in STT3A, suggesting distinct affinities of the two OST complexes for protein substrates.
Ecosystems worldwide are receiving increasing amounts of reactive nitrogen (N) via anthropogenic activities with the added N having potentially important impacts on microbially mediated belowground ...carbon dynamics. However, a comprehensive understanding of how elevated N availability affects soil microbial processes and community dynamics remains incomplete. The mechanisms responsible for the observed responses are poorly resolved and we do not know if soil microbial communities respond in a similar manner across ecosystems. We collected 28 soils from a broad range of ecosystems in North America, amended soils with inorganic N, and incubated the soils under controlled conditions for 1 year. Consistent across nearly all soils, N addition decreased microbial respiration rates, with an average decrease of 11% over the year‐long incubation, and decreased microbial biomass by 35%. High‐throughput pyrosequencing showed that N addition consistently altered bacterial community composition, increasing the relative abundance of Actinobacteria and Firmicutes, and decreasing the relative abundance of Acidobacteria and Verrucomicrobia. Further, N‐amended soils consistently had lower activities in a broad suite of extracellular enzymes and had decreased temperature sensitivity, suggesting a shift to the preferential decomposition of more labile C pools. The observed trends held across strong gradients in climate and soil characteristics, indicating that the soil microbial responses to N addition are likely controlled by similar wide‐spread mechanisms. Our results support the hypothesis that N addition depresses soil microbial activity by shifting the metabolic capabilities of soil bacterial communities, yielding communities that are less capable of decomposing more recalcitrant soil carbon pools and leading to a potential increase in soil carbon sequestration rates.
Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic ...modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this problem, new semisynthetic aminoglycosides were developed in the 70s. The most widely used semisynthetic aminoglycoside is amikacin, which is refractory to most aminoglycoside modifying enzymes. Amikacin was synthesized by acylation with the l-(-)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A. The main amikacin resistance mechanism found in the clinics is acetylation by the aminoglycoside 6'-
-acetyltransferase type Ib AAC(6')-Ib, an enzyme coded for by a gene found in integrons, transposons, plasmids, and chromosomes of Gram-negative bacteria. Numerous efforts are focused on finding strategies to neutralize the action of AAC(6')-Ib and extend the useful life of amikacin. Small molecules as well as complexes ionophore-Zn
or Cu
were found to inhibit the acetylation reaction and induced phenotypic conversion to susceptibility in bacteria harboring the
gene. A new semisynthetic aminoglycoside, plazomicin, is in advance stage of development and will contribute to renewed interest in this kind of antibiotics.
How early media exposure may affect cognitive function Christakis, Dimitri A.; Ramirez, Julian S.Benedikt; Ferguson, Susan M. ...
Proceedings of the National Academy of Sciences - PNAS,
10/2018, Letnik:
115, Številka:
40
Journal Article
Recenzirano
Odprti dostop
Attention deficit hyperactivity disorder (ADHD) is now among the most commonly diagnosed chronic psychological dysfunctions of childhood. By varying estimates, it has increased by 30% in the past 20 ...years. Environmental factors that might explain this increase have been explored. One such factor may be audiovisual media exposure during early childhood. Observational studies in humans have linked exposure to fast-paced television in the first 3 years of life with subsequent attentional deficits in later childhood. Although longitudinal and well controlled, the observational nature of these studies precludes definitive conclusions regarding a causal relationship. As experimental studies in humans are neither ethical nor practical, mouse models of excessive sensory stimulation (ESS) during childhood, akin to the enrichment studies that have previously shown benefits of stimulation in rodents, have been developed. Experimental studies using this model have corroborated that ESS leads to cognitive and behavioral deficits, some of which may be potentially detrimental. Given the ubiquity of media during childhood, these findings in human-sand rodents perhaps have important implications for public health.
Summary
Pre‐operative anaemia in patients undergoing major surgical procedures has been linked to poor outcomes. Therefore, early detection and treatment of pre‐operative anaemia is recommended. ...However, to effectively implement a pre‐operative anaemia management protocol, an estimation of its prevalence and main causes is needed. We analysed data from 3342 patients (44.5% female) scheduled for either: elective orthopaedic surgery (n = 1286); cardiac surgery (n = 691); colorectal cancer resection (n = 735); radical prostatectomy (n = 362); gynaecological surgery (n = 203) or resection of liver metastases (n = 122). For both sexes, anaemia was defined by a haemoglobin level < 130 g.l−1; absolute iron deficiency by ferritin < 30 ng.ml−1 (< 100 ng.ml−1, if transferrin saturation < 20% or C‐reactive protein > 5 mg.l−1); iron sequestration by transferrin saturation < 20% and ferritin > 100 ng.ml−1; and low iron stores by transferrin saturation > 20% and ferritin 30–100 ng.ml−1. The overall prevalence of anaemia was 36%, with differences according to the type of surgery. Laboratory parameters allowing classification of iron status were available for 2884 patients. Among those with anaemia (n = 986), 677 (69%) were women, 608 (62%) presented with absolute iron deficiency, 101 (10%) with iron sequestration; and 150 (5%) with low iron stores. Iron status alterations were similar in women with haemoglobin < 130 g.l−1 or < 120 g.l−1. For those who were not anaemic (n = 1898), corresponding figures were 656 (35%), 621 (33%), 165 (9%) and 518 (27%), respectively. Anaemia was present in one‐third of patients undergoing major elective procedures. Over two‐thirds of anaemic patients presented with absolute iron deficiency or iron sequestration. Over half of non‐anaemic patients presented with absolute iron deficiency or low iron stores. We consider these data useful for planning pre‐operative management of patients scheduled for major elective surgery.
☛ CPD available at http://www.learnataagbi.org
Abstract
Motivated by the proof of Rump of a conjecture of Gateva–Ivanova on the decomposability of square-free solutions to the Yang–Baxter equation, we present several other decomposability ...theorems based on the cycle structure of a certain permutation associated with the solution.
In the first part, we focus on indecomposable involutive solutions of the Yang-Baxter equation whose permutation group forces them to be uniconnected. Indecomposable involutive solutions with a ...permutation group isomorphic to a dihedral group or a minimal non-cyclic group are studied in detail. In the last part, we study the Dehornoy class of involutive solutions (not necessarily indecomposable) and its link with left braces. As an application, we give an upper bound for several families of indecomposable involutive solutions and we compute the precise value in some other cases.
•Technical knowledge to study hydrocracking of heavy oil with dispersed catalysts is summarized.•Experimental setups, operation modes and reactors for conducting heavy oil hydrocracking are ...reviewed.•A description of catalyst precursors and analytical techniques for sample characterization is provided.•Procedures for pretreatment of feed, catalyst dispersion and sulfurization of catalyst precursors are presented.
This paper summarizes the technical knowledge necessary to study the hydrocracking of heavy oil with dispersed catalysts. Chemical kinetics aspects of the hydrocracking of heavy oil reaction are reviewed. The discussion also includes a description of the experimental setups, operation modes and suitable reactors for conducting heavy oil hydrocracking experiments. Reactors and their hydrodynamics are described in order to establish the more appropriate operating conditions to perform the experiments. The most common catalyst precursors used in the reaction are listed as well as the analytical techniques employed in characterizing and quantifying gas, liquid and solid samples. Procedures for pretreatment of feed, catalyst dispersion and sulfurization of catalyst precursors are also presented
Although numerous studies have investigated changes in soil microbial communities across space, questions about the temporal variability in these communities and how this variability compares across ...soils have received far less attention. We collected soils on a monthly basis (May to November) from replicated plots representing three land-use types (conventional and reduced-input row crop agricultural plots and early successional grasslands) maintained at a research site in Michigan, USA. Using barcoded pyrosequencing of the 16S rRNA gene, we found that the agricultural and early successional land uses harbored unique soil bacterial communities that exhibited distinct temporal patterns. α-Diversity, the numbers of taxa or lineages, was significantly influenced by the sampling month with the temporal variability in α-diversity exceeding the variability between land-use types. In contrast, differences in community composition across land-use types were reasonably constant across the 7-month period, suggesting that the time of sampling is less important when assessing β-diversity patterns. Communities in the agricultural soils were most variable over time and the changes were significantly correlated with soil moisture and temperature. Temporal shifts in bacterial community composition within the successional grassland plots were less predictable and are likely a product of complex interactions between the soil environment and the more diverse plant community. Temporal variability needs to be carefully assessed when comparing microbial diversity across soil types and the temporal patterns in microbial community structure can not necessarily be generalized across land uses, even if those soils are exposed to the same climatic conditions.
Pathogen recognition by plants results in the activation of signaling pathways that induce defense reactions. There is growing evidence indicating that epigenetic mechanisms directly participate in ...plant immune memory. Here, we discuss current knowledge of diverse epigenomic processes and elements, such as noncoding RNAs, DNA and RNA methylation, histone post-translational modifications, and chromatin remodeling, that have been associated with the regulation of immune responses in plants. Furthermore, we discuss the currently limited evidence of transgenerational inheritance of pathogen-induced defense priming, together with its potentials, challenges, and limitations for crop improvement and biotechnological applications.
To defend against microbial pathogens, plants have developed a sophisticated immune system. Upon recognition of external microbe-associated molecular patterns (MAMPs) or internal microbial effectors that are delivered into the host cells, signal transduction events are triggered, leading to rapid defense responses that include massive transcriptional reprogramming. These events are followed by the systemic activation of defense programs at distant, nonchallenged sites, a process termed ‘systemic acquired resistance’ (SAR) and linked to priming, whereby plants memorize previous attacks and can respond more robustly to subsequent pathogen challenges.
Recent evidence demonstrates that plant defense gene expression also involves epigenetic mechanisms, such as DNA methylation and histone modifications, that are closely linked to the dynamical chromatin states.
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