Methanogenesis on Early Stages of Life: Ancient but Not Primordial.

Orig Life Evol Biosph. 2019 Jan 05;:

Authors: Muñoz-Velasco I, García-Ferris C, Hernandez-Morales R, Lazcano A, Peretó J, Becerra A

Abstract
Of the six known autotrophic pathways, the Wood-Ljungdahl pathway (WL) is the only one present in both the acetate producing Bacteria (homoacetogens) and the methane producing Archaea (hydrogenotrophic methanogens), and it has been suggested that WL is one of the oldest metabolic pathways. However, only the so-called carbonyl branch is shared by Archaea and Bacteria, while the methyl branch is different, both in the number of reactions and enzymes, which are not homologous among them. In this work we show that some parts of the methyl branch of archaeal Wood-Ljungdahl pathway (MBWL) are present in bacteria as well as in non-methanogen archaea, although the tangled evolutionary history of MBWL cannot be traced back to the Last Common Ancestor. We have also analyzed the different variants of methanogenesis (hydrogenotrophic, acetoclastic and methylotrophic pathways), and concluded that each of these pathways, and every different enzyme or subunit (in the case of multimeric enzymes), has their own intricate evolutionary history. Our study supports the scenario of hydrogenotrophic methanogenesis being older than the other variants, albeit not old enough to be present in the last archaeal common ancestor.

PMID: 30612264 [PubMed - as supplied by publisher]

Profiling Single Cancer Cells with Volatolomics Approach.

iScience. 2018 Dec 14;11:178-188

Authors: Serasanambati M, Broza YY, Marmur A, Haick H

Abstract
Single-cell analysis is a rapidly evolving to characterize molecular information at the individual cell level. Here, we present a new approach with the potential to overcome several key challenges facing the currently available techniques. The approach is based on the identification of volatile organic compounds (VOCs), viz. organic compounds having relatively high vapor pressure, emitted to the cell's headspace. This concept is demonstrated using lung cancer cells with various p53 genetic status and normal lung cells. The VOCs were analyzed by gas chromatography combined with mass spectrometry. Among hundreds of detected compounds, 18 VOCs showed significant changes in their concentration levels in tumor cells versus control. The composition of these VOCs was found to depend, also, on the sub-molecular structure of the p53 genetic status. Analyzing the VOCs offers a complementary way of querying the molecular mechanisms of cancer as well as of developing new generation(s) of biomedical approaches for personalized screening and diagnosis.

PMID: 30612036 [PubMed - as supplied by publisher]

Childhood Socioeconomic Status Predicts Cognitive Outcomes Across Adulthood Following Traumatic Brain Injury.

Neuropsychologia. 2019 Jan 03;:

Authors: Cohen-Zimerman S, Kachian ZR, Krueger F, Gordon B, Grafman J

Abstract
OBJECTIVE: To examine the association between childhood socioeconomic status (SES) and the level and rate of change in intelligence scores throughout adulthood following traumatic brain injury (TBI).
METHODS: In this longitudinal study we tested 186 patients with TBI and 54 healthy controls from the Vietnam Head Injury Study. Childhood SES was determined for each participant based on parental educational attainment and occupational prestige. General intelligence was initially assessed pre-injury upon induction into the military, and again 15, 35 and 40+ years post-injury. We examined whether childhood SES, total brain volume loss and lesion laterality can predict post injury intelligence scores and the rate of change in those scores between study phases.
RESULTS: For both participants with and without TBI, childhood SES accounted for a significant portion of the variance in intelligence scores pre-injury and in all three post-injury evaluations, however, it was not associated with the rate of cognitive change. Lastly, childhood SES predicted cognitive outcome among patients with left hemisphere damage better than it did for right hemisphere damage patients.
CONCLUSIONS: These findings provide the first evidence indicating the persistent effects of childhood SES on intelligence scores later in adulthood following a TBI. Childhood SES should be considered when predicting and assessing cognitive recovery following TBI, even when the injury occurred in adulthood.

PMID: 30611733 [PubMed - as supplied by publisher]

Combining Evolutionary Covariance and NMR Data for Protein Structure Determination.

Methods Enzymol. 2019;614:363-392

Authors: Huang YJ, Brock KP, Ishida Y, Swapna GVT, Inouye M, Marks DS, Sander C, Montelione GT

Abstract
Accurate protein structure determination by solution-state NMR is challenging for proteins greater than about 20kDa, for which extensive perdeuteration is generally required, providing experimental data that are incomplete (sparse) and ambiguous. However, the massive increase in evolutionary sequence information coupled with advances in methods for sequence covariance analysis can provide reliable residue-residue contact information for a protein from sequence data alone. These "evolutionary couplings (ECs)" can be combined with sparse NMR data to determine accurate 3D protein structures. This hybrid "EC-NMR" method has been developed using NMR data for several soluble proteins and validated by comparison with corresponding reference structures determined by X-ray crystallography and/or conventional NMR methods. For small proteins, only backbone resonance assignments are utilized, while for larger proteins both backbone and some sidechain methyl resonance assignments are generally required. ECs can be combined with sparse NMR data obtained on deuterated, selectively protonated protein samples to provide structures that are more accurate and complete than those obtained using such sparse NMR data alone. EC-NMR also has significant potential for analysis of protein structures from solid-state NMR data and for studies of integral membrane proteins. The requirement that ECs are consistent with NMR data recorded on a specific member of a protein family, under specific conditions, also allows identification of ECs that reflect alternative allosteric or excited states of the protein structure.

PMID: 30611430 [PubMed - in process]

Bifunctional Chloroplastic DJ-1B from Arabidopsis thaliana is an Oxidation-Robust Holdase and a Glyoxalase Sensitive to H₂O₂.

Antioxidants (Basel). 2019 Jan 01;8(1):

Authors: Lewandowska A, Vo TN, Nguyen TH, Wahni K, Vertommen D, Van Breusegem F, Young D, Messens J

Abstract
Members of the DJ-1 protein family are multifunctional enzymes whose loss increases the susceptibility of the cell to oxidative stress. However, little is known about the function of the plant DJ-1 homologs. Therefore, we analyzed the effect of oxidation on the structure and function of chloroplastic AtDJ-1B and studied the phenotype of T-DNA lines lacking the protein. In vitro oxidation of AtDJ-1B with H₂O₂ lowers its glyoxalase activity, but has no effect on its holdase chaperone function. Remarkably, upon oxidation, the thermostability of AtDJ-1B increases with no significant alteration of the overall secondary structure. Moreover, we found that AtDJ-1B transcript levels are invariable, and loss of AtDJ-1B does not affect plant viability, growth and stress response. All in all, two discrete functions of AtDJ-1B respond differently to H₂O₂, and AtDJ-1B is not essential for plant development under stress.

PMID: 30609642 [PubMed]

Federated electronic health records research technology to support clinical trial protocol optimization: Evidence from EHR4CR and the InSite platform.

J Biomed Inform. 2019 Jan 02;:

Authors: Claerhout B, Kalra D, Mueller C, Singh G, Ammour N, Meloni L, Blomster J, Hopley M, Kafatos G, Garvey A, Kuhn P, Lewi M, Vannieuwenhuyse B, Marchal B, Patel K, Schindler C, Sundgren M

Abstract
OBJECTIVE: To determine if inclusion/exclusion (I/E) criteria of clinical trial protocols can be represented as structured queries and executed using a secure federated research platform (InSite) on hospital electronic health records (EHR) systems, to estimate the number of potentially eligible patients.
METHODS: Twenty-three clinical trial protocols completed during 2011-2017 across diverse disease areas were analyzed to construct queries that were executed with InSite using EHR records from 24 European hospitals containing records of >14 million patients. The number of patients matching I/E criteria of each protocol was estimated.
RESULTS: All protocols could be formalized to some extent into a medical coding system (e.g. ICD-10CM, ATC, LOINC, SNOMED) and mapped to local hospital coding systems. The median number of I/E criteria of protocols tested was 29 (range: 14-47). A median of 55% (range 38-89%) of I/E criteria in each protocol could be transformed into a computable format. The median number of eligible patients identified was 26 per hospital site (range: 1-134).
CONCLUSION: Clinical trial I/E eligibility criteria can be structured computationally and executed as queries on EHR systems to estimate the patient recruitment pool at each site. The results further suggest that an increase in structured coded information in EHRs would increase the number of I/E criteria that could be evaluated. Additional work is needed on broader deployment of federated platforms such as InSite.

PMID: 30611012 [PubMed - as supplied by publisher]

Ionic stress enhances ER-PM connectivity via phosphoinositide-associated SYT1 contact site expansion in Arabidopsis.

Proc Natl Acad Sci U S A. 2019 Jan 04;:

Authors: Lee E, Vanneste S, Pérez-Sancho J, Benitez-Fuente F, Strelau M, Macho AP, Botella MA, Friml J, Rosado A

Abstract
The interorganelle communication mediated by membrane contact sites (MCSs) is an evolutionary hallmark of eukaryotic cells. MCS connections enable the nonvesicular exchange of information between organelles and allow them to coordinate responses to changing cellular environments. In plants, the importance of MCS components in the responses to environmental stress has been widely established, but the molecular mechanisms regulating interorganelle connectivity during stress still remain opaque. In this report, we use the model plant Arabidopsis thaliana to show that ionic stress increases endoplasmic reticulum (ER)-plasma membrane (PM) connectivity by promoting the cortical expansion of synaptotagmin 1 (SYT1)-enriched ER-PM contact sites (S-EPCSs). We define differential roles for the cortical cytoskeleton in the regulation of S-EPCS dynamics and ER-PM connectivity, and we identify the accumulation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the PM as a molecular signal associated with the ER-PM connectivity changes. Our study highlights the functional conservation of EPCS components and PM phosphoinositides as modulators of ER-PM connectivity in eukaryotes, and uncovers unique aspects of the spatiotemporal regulation of ER-PM connectivity in plants.

PMID: 30610176 [PubMed - as supplied by publisher]

Native mass spectrometry reveals the conformational diversity of the UVR8 photoreceptor.

Proc Natl Acad Sci U S A. 2019 Jan 04;:

Authors: Camacho IS, Theisen A, Johannissen LO, Díaz-Ramos LA, Christie JM, Jenkins GI, Bellina B, Barran P, Jones AR

Abstract
UVR8 is a plant photoreceptor protein that regulates photomorphogenic and protective responses to UV light. The inactive, homodimeric state absorbs UV-B light, resulting in dissociation into monomers, which are considered to be the active state and comprise a β-propeller core domain and intrinsically disordered N- and C-terminal tails. The C terminus is required for functional binding to signaling partner COP1. To date, however, structural studies have only been conducted with the core domain where the terminal tails have been truncated. Here, we report structural investigations of full-length UVR8 using native ion mobility mass spectrometry adapted for photoactivation. We show that, while truncated UVR8 photoconverts from a single conformation of dimers to a single monomer conformation, the full-length protein exists in numerous conformational families. The full-length dimer adopts both a compact state and an extended state where the C terminus is primed for activation. In the monomer the extended C terminus destabilizes the core domain to produce highly extended yet stable conformations, which we propose are the fully active states that bind COP1. Our results reveal the conformational diversity of full-length UVR8. We also demonstrate the potential power of native mass spectrometry to probe functionally important structural dynamics of photoreceptor proteins throughout nature.

PMID: 30610174 [PubMed - as supplied by publisher]

Another gun Dismantled: ABSCISIC ACID INSENSITIVE4 Is Not a Target of Retrograde Signaling.

Plant Physiol. 2019 Jan;179(1):13-14

Authors: Mhamdi A, Gommers CMM

PMID: 30610130 [PubMed - in process]

Impact of early events and lifestyle on the gut microbiota and metabolic phenotypes in young school-age children.

Microbiome. 2019 Jan 04;7(1):2

Authors: Zhong H, Penders J, Shi Z, Ren H, Cai K, Fang C, Ding Q, Thijs C, Blaak EE, Stehouwer CDA, Xu X, Yang H, Wang J, Wang J, Jonkers DMAE, Masclee AAM, Brix S, Li J, Arts ICW, Kristiansen K

Abstract
BACKGROUND: The gut microbiota evolves from birth and is in early life influenced by events such as birth mode, type of infant feeding, and maternal and infant antibiotics use. However, we still have a gap in our understanding of gut microbiota development in older children, and to what extent early events and pre-school lifestyle modulate the composition of the gut microbiota, and how this impinges on whole body metabolic regulation in school-age children.
RESULTS: Taking advantage of the KOALA Birth Cohort Study, a long-term prospective birth cohort in the Netherlands with extensive collection of high-quality host metadata, we applied shotgun metagenomics sequencing and systematically investigated the gut microbiota of children at 6-9 years of age. We demonstrated an overall adult-like gut microbiota in the 281 Dutch school-age children and identified 3 enterotypes dominated by the genera Bacteroides, Prevotella, and Bifidobacterium, respectively. Importantly, we found that breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in the children at school age. The correlations between pre-school dietary lifestyle and metabolic phenotypes exhibited a striking enterotype dependency. Thus, an inverse correlation between high dietary fiber consumption and low plasma insulin levels was only observed in individuals with the Bacteroides and Prevotella enterotypes, but not in Bifidobacterium enterotype individuals in whom the gut microbiota displayed overall lower microbial gene richness, alpha-diversity, functional potential for complex carbohydrate fermentation, and butyrate and succinate production. High total fat consumption and elevated plasma free fatty acid levels in the Bifidobacterium enterotype are associated with the co-occurrence of Streptococcus.
CONCLUSIONS: Our work highlights the persistent effects of breastfeeding duration and pre-school dietary lifestyle in affecting the gut microbiota in school-age children and reveals distinct compositional and functional potential in children according to enterotypes. The findings underscore enterotype-specific links between the host metabolic phenotypes and dietary patterns, emphasizing the importance of microbiome-based stratification when investigating metabolic responses to diets. Future diet intervention studies are clearly warranted to examine gut microbe-diet-host relationships to promote knowledge-based recommendations in relation to improving metabolic health in children.

PMID: 30609941 [PubMed - in process]

Toxic Indole Diterpenes from Endophyte-Infected Perennial Ryegrass Lolium perenne L.: Isolation and Stability.

Toxins (Basel). 2019 Jan 03;11(1):

Authors: Reddy P, Deseo MA, Ezernieks V, Guthridge K, Spangenberg G, Rochfort S

Abstract
The most potent of the indole diterpenes, lolitrem B, is found in perennial ryegrass (Lolium perenne L.) infected with the endophyte Epichloë festucae var. lolii (also termed LpTG-1). Ingestion causes a neurological syndrome in grazing livestock called ryegrass staggers disease. To enable the rapid development of new forage varieties, the toxicity of lolitrem B and its biosynthetic intermediates needs to be established. However, most of these indole diterpenes are not commercially available; thus, isolation of these compounds is paramount. A concentrated endophyte-infected perennial ryegrass seed extract was subjected to silica flash chromatography followed by preparative HPLC and purification by crystallization resulting in lolitrem B and the intermediate compounds lolitrem E, paspaline and terpendole B. The four-step isolation and purification method resulted in a 25% yield of lolitrem B. After isolation, lolitrem B readily degraded to its biosynthetic intermediate, lolitriol. We also found that lolitrem B can readily degrade depending on the solvent and storage conditions. The facile method which takes into consideration the associated instability of lolitrem B, led to the purification of indole diterpenes in quantities sufficient for use as analytical standards for identification in pastures, and/or for toxicity testing in pasture development programs.

PMID: 30609849 [PubMed - in process]

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Effect of Age on the Protein Profile of Healthy Malay Adults and its Association with Cognitive Function Competency.

J Alzheimers Dis. 2018 Dec 26;:

Authors: Abu Bakar ZH, Damanhuri HA, Makpol S, Wan Kamaruddin WMA, Abdul Sani NF, Amir Hamzah AIZ, Nor Aripin KN, Rani MDM, Azila Noh N, Razali R, Mazlan M, Abdul Hamid H, Mohamad M, Wan Ngah WZ

Abstract
BACKGROUND: Many studies on biochemical and psychological variables have aimed to elucidate the association between aging and cognitive function. Demographic differences and protein expression have been reported to play a role in determining the cognitive capability of a population.
OBJECTIVE: This study aimed to determine the effect of age on the protein profile of Malay individuals and its association with cognitive competency.
METHODS: A total of 160 individuals were recruited and grouped accordingly. Cognitive competency of each subject was assessed with several neuropsychological tests. Plasma samples were collected and analyzed with Q Exactive HF Orbitrap. Proteins were identified and quantitated with MaxQuant and further analyzed with Perseus to determine differentially expressed proteins. PANTHER, Reactome, and STRING were applied for bioinformatics output.
RESULTS: Our data showed that the Malay individuals are vulnerable to the deterioration of cognitive function with aging, and most of the proteins were differentially expressed in concordance. Several physiological components and pathways were shown to be involved, giving a hint of a promising interpretation on the induction of aging toward the state of the Malays' cognitive function. Nevertheless, some proteins have shown a considerable interaction with the generated protein network, which provides a direction of focus for further investigation.
CONCLUSION: This study demonstrated notable changes in the expression of several proteins as age increased. These changes provide a promising platform for understanding the biochemical factors affecting cognitive function in the Malay population. The exhibited network of protein-protein interaction suggests the possibility of implementing regulatory intervention in ameliorating Malay cognitive function.

PMID: 30594926 [PubMed - as supplied by publisher]