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Fulltext Four products from Escherichia coli pseudogenes increase hydrogen production

Mohd Yusoff MZ, Hashiguchi Y, Maeda T, Wood TK

Biochem Biophys Res Commun, 2013 Oct 4;439(4):576-9.
PMID: 24025676 DOI: 10.1016/j.bbrc.2013.09.016

Pseudogenes are considered to be nonfunctional genes that lack a physiological role. By screening 3985 Escherichia coli mutants using chemochromic membranes, we found four pseudogenes involved in hydrogen metabolism. Knockouts of pseudogenes ydfW and ypdJ had a defective hydrogen phenotype on glucose and formate, respectively. Also, the knockout of pseudogene yqiG formed hydrogen from formate but not from glucose. For the yqiG mutant, 100% hydrogen recovery was obtained by the complementation of YqiG via a plasmid. The knockout of pseudogene ylcE showed hydrogen deficiency in minimal media which suggested that the role of YlcE is associated with cell growth. Hence, the products of these four pseudogenes play an important physiological role in hydrogen production in E. coli.
Two-week test-retest reliability of the Polar® RS800CX™ to record heart rate variability

Williams DP, Jarczok MN, Ellis RJ, Hillecke TK, Thayer JF, Koenig J

Clin Physiol Funct Imaging, 2017 Nov;37(6):776-781.
PMID: 26815165 DOI: 10.1111/cpf.12321

Recently, research has validated the use of Polar® heart rate monitors as a tool to index heart rate variability (HRV). In the current investigation, we sought to evaluate the test-retest reliability of both time and frequency domain measures of HRV using the Polar® RS800CX™ . Continuous HRV data were collected as 60 nominally healthy adults underwent a resting and orthostatic stress test. We evaluated reproducibility by means of the interclass correlation coefficient for absolute agreement and consistency, and the standard error of measurement. We found moderate reliable 2-week test-retest reliability of HRV using the Polar® RS800CX™ , results that are in line with previous studies that have validated the stability of HRV using other methods of measurement (e.g. electrocardiogram). Additionally, when examining different methods of spectral density estimation, we found that using the auto-regressive transformation method provides the most stable indices of HRV. Taken together, our results suggest that the Polar® RS800CX™ is not only a valid method to record HRV, but also a reliable one, particularly when using the auto-regressive transformation method.
Fulltext Pseudogene product YqiG is important for pflB expression and biohydrogen production in Escherichia coli BW25113

Zakaria MA, Mohd Yusoff MZ, Zakaria MR, Hassan MA, Wood TK, Maeda T

3 Biotech, 2018 Oct;8(10):435.
PMID: 30306004 DOI: 10.1007/s13205-018-1461-2

Pseudogenes in the Escherichia coli genome are assumed to be non-functional. In this study, Keio collection BW25113∆yqiG and YqiG-producing strain (BW25113/pCA24N-YqiG) were used to evaluate the importance of pseudogene yqiG in hydrogen metabolism. Our results show pseudogene protein YqiG was identified as an essential protein in the production of biohydrogen from glucose. The mutant yqiG decreased biohydrogen production from 37 µmol mg-1 protein to 6 µmol mg-1 protein compared to the wild-type strain, and glucose consumption was reduced by 80%. Through transcriptional analysis, we found that the yqiG mutation represses pflB transcription tenfold; pflB encodes pyruvate-formate lyase, one of the key enzymes in the anaerobic metabolism of E. coli. Moreover, production of YqiG stimulated glycolysis and increased biohydrogen productivity 1.5-fold compared to that of the wild-type strain. Thus, YqiG is important for the central glycolysis reaction and is able to influence hydrogen metabolism activity in E. coli.
Fulltext Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor

Wei GZ, Martin KA, Xing PY, Agrawal R, Whiley L, Wood TK, et al.

Proc Natl Acad Sci U S A, 2021 Jul 06;118(27).
PMID: 34210797 DOI: 10.1073/pnas.2021091118

While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.
Fulltext Phylogenomic resolution of the root of Panpulmonata, a hyperdiverse radiation of gastropods: new insight into the evolution of air breathing

Krug PJ, Caplins SA, Algoso K, Thomas K, Valdés ÁA, Wade R, et al.

Proc Biol Sci, 2022 Apr 13;289(1972):20211855.
PMID: 35382597 DOI: 10.1098/rspb.2021.1855

Transitions to terrestriality have been associated with major animal radiations including land snails and slugs in Stylommatophora (>20 000 described species), the most successful lineage of 'pulmonates' (a non-monophyletic assemblage of air-breathing gastropods). However, phylogenomic studies have failed to robustly resolve relationships among traditional pulmonates and affiliated marine lineages that comprise clade Panpulmonata (Mollusca, Gastropoda), especially two key taxa: Sacoglossa, a group including photosynthetic sea slugs, and Siphonarioidea, intertidal limpet-like snails with a non-contractile pneumostome (narrow opening to a vascularized pallial cavity). To clarify the evolutionary history of the panpulmonate radiation, we performed phylogenomic analyses on datasets of up to 1160 nuclear protein-coding genes for 110 gastropods, including 40 new transcriptomes for Sacoglossa and Siphonarioidea. All 18 analyses recovered Sacoglossa as the sister group to a clade we named Pneumopulmonata, within which Siphonarioidea was sister to the remaining lineages in most analyses. Comparative modelling indicated shifts to marginal habitat (estuarine, mangrove and intertidal zones) preceded and accelerated the evolution of a pneumostome, present in the pneumopulmonate ancestor along with a one-sided plicate gill. These findings highlight key intermediate stages in the evolution of air-breathing snails, supporting the hypothesis that adaptation to marginal zones played an important role in major sea-to-land transitions.
Complex multiple introductions drive fall armyworm invasions into Asia and Australia

Rane R, Walsh TK, Lenancker P, Gock A, Dao TH, Nguyen VL, et al.

Sci Rep, 2023 Jan 12;13(1):660.
PMID: 36635481 DOI: 10.1038/s41598-023-27501-x

The fall armyworm (FAW) Spodoptera frugiperda is thought to have undergone a rapid 'west-to-east' spread since 2016 when it was first identified in western Africa. Between 2018 and 2020, it was recorded from South Asia (SA), Southeast Asia (SEA), East Asia (EA), and Pacific/Australia (PA). Population genomic analyses enabled the understanding of pathways, population sources, and gene flow in this notorious agricultural pest species. Using neutral single nucleotide polymorphic (SNP) DNA markers, we detected genome introgression that suggested most populations in this study were overwhelmingly C- and R-strain hybrids (n = 252/262). SNP and mitochondrial DNA markers identified multiple introductions that were most parsimoniously explained by anthropogenic-assisted spread, i.e., associated with international trade of live/fresh plants and plant products, and involved 'bridgehead populations' in countries to enable successful pest establishment in neighbouring countries. Distinct population genomic signatures between Myanmar and China do not support the 'African origin spread' nor the 'Myanmar source population to China' hypotheses. Significant genetic differentiation between populations from different Australian states supported multiple pathways involving distinct SEA populations. Our study identified Asia as a biosecurity hotspot and a FAW genetic melting pot, and demonstrated the use of genome analysis to disentangle preventable human-assisted pest introductions from unpreventable natural pest spread.
Spread of drug-resistant Streptococcus pneumoniae in Asian countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study

Song JH, Lee NY, Ichiyama S, Yoshida R, Hirakata Y, Fu W, et al.

Clin Infect Dis, 1999 Jun;28(6):1206-11.
PMID: 10451154

Antimicrobial susceptibility of 996 isolates of Streptococcus pneumoniae from clinical specimens was investigated in 11 Asian countries from September 1996 to June 1997. Korea had the greatest frequency of nonsusceptible strains to penicillin with 79.7%, followed by Japan (65.3%), Vietnam (60.8%), Thailand (57.9%), Sri Lanka (41.2%), Taiwan (38.7%), Singapore (23.1%), Indonesia (21.0%), China (9.8%), Malaysia (9.0%), and India (3.8%). Serotypes 23F and 19F were the most common. Pulsed-field gel electrophoresis (PFGE) of 154 isolates from Asian countries showed several major PFGE patterns. The serotype 23F Spanish clone shared the same PFGE pattern with strains from Korea, Japan, Singapore, Taiwan, Thailand, and Malaysia. Fingerprinting analysis of pbp1a, pbp2x, and pbp2b genes of 12 strains from six countries also showed identical fingerprints of penicillin-binding protein genes in most strains. These data suggest the possible introduction and spread of international epidemic clones into Asian countries and the increasing problems of pneumococcal drug resistance in Asian countries for the first time.
Fulltext Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial

Peters MJ, Gould DW, Ray S, Thomas K, Chang I, Orzol M, et al.

Lancet, 2024 Jan 27;403(10424):355-364.
PMID: 38048787 DOI: 10.1016/S0140-6736(23)01968-2

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care.
METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439).
FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group.
INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs.
FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.
Fulltext Child and Adolescent Health From 1990 to 2015: Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2015 Study

Global Burden of Disease Child and Adolescent Health Collaboration, Kassebaum N, Kyu HH, Zoeckler L, Olsen HE, Thomas K, et al.

JAMA Pediatr, 2017 Jun 01;171(6):573-592.
PMID: 28384795 DOI: 10.1001/jamapediatrics.2017.0250

IMPORTANCE: Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.
OBJECTIVE: To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.
EVIDENCE REVIEW: Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.
FINDINGS: Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3% (95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.
CONCLUSIONS AND RELEVANCE: Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.