Appreciating interconnectivity between habitats is key to Blue Carbon management

We welcome the recent synthesis by Howard et al. (2017), which drew attention to the role of marine systems and natural carbon sequestration in the oceans as a fundamental aspect of climate-change mitigation. The importance of long-term carbon storage in marine habitats (ie “blue carbon”) is rapidly gaining recognition and is increasingly a focus of national and international attempts to mitigate rising atmospheric emissions of carbon dioxide. However, effectively managing blue carbon requires an appreciation of the inherent connectivity between marine populations and habitats. More so than their terrestrial counterparts, marine ecosystems are “open”, with high rates of transfer of energy, matter, genetic material, and species across regional seascapes (Kinlan and Gaines 2003). We suggest that policy frameworks, and the science underpinning them, should focus not only on carbon sink habitats but also on carbon source habitats, which play critical roles in marine carbon cycling and natural carbon sequestration in the oceans

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Heavy Higgs signal-background interference in gg → VV in the Standard Model plus real singlet

For the Standard Model extended with a real scalar singlet field, the modification of the heavy Higgs signal due to interference with the continuum background and the off-shell light Higgs contribution is studied for gg --> ZZ, WW --> 4 lepton processes at the Large Hadron Collider. Interference effects can range from O(10%) to O(1) effects for integrated cross sections. Despite a strong cancellation between the heavy Higgs-continuum and the heavy Higgs-light Higgs interference, the full interference is clearly non-negligible and modifies the heavy Higgs line shape. A |M_VV - M_h2| < Gamma_h2 cut mitigates interference effects to O(10%) or less. A public program that allows to simulate the full interference is presented.Comment: 22 pages, 15 figures, 9 tables; added results and references, improved discussion, corrected v2 results (heavy top approximation was inadvertently active, results deviate by less than 5%), conclusions unchanged, updated gg2VV code, version to appear in EPJ

Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients

Abstract Baricitinib, is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently hypothesized, using artificial intelligence (AI)-algorithms, to be useful for the treatment of COVID-19 infection via a proposed anti-cytokine effects and as an inhibitor of host cell viral propagation1,2. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids, which express hAAK1 and hGAK. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection. In a case series of patients with bilateral COVID-19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS-CoV-2 viral load, inflammatory markers, and IL-6 levels. This represents an important example of an AI-predicted treatment showing scientific and clinical promise during a global health crisis. Collectively, these data support further evaluation of the AI-derived hypothesis on anti-cytokine and anti-viral activity and supports its assessment in randomized trials in hospitalized COVID-19 patients.</jats:p

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

Episodic Memory and Appetite Regulation in Humans

Psychological and neurobiological evidence implicates hippocampal-dependent memory processes in the control of hunger and food intake. In humans, these have been revealed in the hyperphagia that is associated with amnesia. However, it remains unclear whether 'memory for recent eating' plays a significant role in neurologically intact humans. In this study we isolated the extent to which memory for a recently consumed meal influences hunger and fullness over a three-hour period. Before lunch, half of our volunteers were shown 300 ml of soup and half were shown 500 ml. Orthogonal to this, half consumed 300 ml and half consumed 500 ml. This process yielded four separate groups (25 volunteers in each). Independent manipulation of the 'actual' and 'perceived' soup portion was achieved using a computer-controlled peristaltic pump. This was designed to either refill or draw soup from a soup bowl in a covert manner. Immediately after lunch, self-reported hunger was influenced by the actual and not the perceived amount of soup consumed. However, two and three hours after meal termination this pattern was reversed - hunger was predicted by the perceived amount and not the actual amount. Participants who thought they had consumed the larger 500-ml portion reported significantly less hunger. This was also associated with an increase in the 'expected satiation' of the soup 24-hours later. For the first time, this manipulation exposes the independent and important contribution of memory processes to satiety. Opportunities exist to capitalise on this finding to reduce energy intake in humans

The genetic organisation of prokaryotic two-component system signalling pathways

<p>Abstract</p> <p>Background</p> <p>Two-component systems (TCSs) are modular and diverse signalling pathways, involving a stimulus-responsive transfer of phosphoryl groups from transmitter to partner receiver domains. TCS gene and domain organisation are both potentially informative regarding biological function, interaction partnerships and molecular mechanisms. However, there is currently little understanding of the relationships between domain architecture, gene organisation and TCS pathway structure.</p> <p>Results</p> <p>Here we classify the gene and domain organisation of TCS gene loci from 1405 prokaryotic replicons (>40,000 TCS proteins). We find that 200 bp is the most appropriate distance cut-off for defining whether two TCS genes are functionally linked. More than 90% of all TCS gene loci encode just one or two transmitter and/or receiver domains, however numerous other geometries exist, often with large numbers of encoded TCS domains. Such information provides insights into the distribution of TCS domains between genes, and within genes. As expected, the organisation of TCS genes and domains is affected by phylogeny, and plasmid-encoded TCS exhibit differences in organisation from their chromosomally-encoded counterparts.</p> <p>Conclusions</p> <p>We provide here an overview of the genomic and genetic organisation of TCS domains, as a resource for further research. We also propose novel metrics that build upon TCS gene/domain organisation data and allow comparisons between genomic complements of TCSs. In particular, '<it>percentage orphaned TCS genes</it>' (or 'Dissemination') and '<it>percentage of complex loci</it>' (or 'Sophistication') appear to be useful discriminators, and to reflect mechanistic aspects of TCS organisation not captured by existing metrics.</p

Laparoscopic sacrocolpopexy with bone anchor fixation: short-term anatomic and functional results

Contains fulltext : 108485.pdf (publisher's version ) (Open Access)INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate short-term anatomic and functional outcomes and safety of laparoscopic sacrocolpopexy with bone anchor fixation. METHODS: A prospective cohort study of women undergoing laparoscopic sacrocolpopexy between 2004 and 2009. Anatomic outcome was assessed using the pelvic organ prolapse quantification score (POP-Q). Functional outcomes were assessed using the Urogenital Distress Inventory, Defecatory Distress Inventory, and the Incontinence Impact Questionnaire preoperatively and at 6 months postoperatively. The Wilcoxon signed rank test was used to test differences between related samples. RESULTS: Forty-nine women underwent laparoscopic sacrocolpopexy. The objective success rate in the apical compartment was 98%, subjective success rate was 79%. One mesh exposure (2%) was found. One conversion was necessary due to injury to the ileum. CONCLUSIONS: Laparoscopic sacrocolpopexy with bone anchor fixation is a safe and efficacious treatment for apical compartment prolapse. It provides excellent apical support and good functional outcome 6 months postoperatively.1 april 201

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

RATIONALE: The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. OBJECTIVES: The aim of this study was to examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. METHODS: Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. RESULTS: mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. CONCLUSIONS: The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs