JURNAL AGROTEKNOLOGI
Not a member yet
63896 research outputs found
Sort by
Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease
No full textARH3/ADPRHL2 and PARG are the primary enzymes reversing ADP-ribosylation in vertebrates, yet their functions in vivo remain unclear. ARH3 is the only hydrolase able to remove serine-linked mono(ADP-ribose) (MAR) but is much less efficient than PARG against poly(ADP-ribose) (PAR) chains in vitro. Here, by using ARH3-deficient cells, we demonstrate that endogenous MARylation persists on chromatin throughout the cell cycle, including mitosis, and is surprisingly well tolerated. Conversely, persistent PARylation is highly toxic and has distinct physiological effects, in particular on active transcription histone marks such as H3K9ac and H3K27ac. Furthermore, we reveal a synthetic lethal interaction between ARH3 and PARG and identify loss of ARH3 as a mechanism of PARP inhibitor resistance, both of which can be exploited in cancer therapy. Finally, we extend our findings to neurodegeneration, suggesting that patients with inherited ARH3 deficiency suffer from stress-induced pathogenic increase in PARylation that can be mitigated by PARP inhibition
Systematic review and meta-analysis of the relationship between the heartbeat-evoked potential and interoception
No full textThe Heartbeat Evoked Potential (HEP) has been proposed as a neurophysiological marker of interoceptive processing. Despite its use to validate interoceptive measures and to assess interoceptive functioning in clinical groups, the empirical evidence for a relationship between HEP amplitude and interoceptive processing, including measures of such processing, is scattered across several studies with varied designs. The aim of this systematic review and meta-analysis was to examine the body of HEP-interoception research, and consider the associations the HEP shows with various direct and indirect measures of interoception, and how it is affected by manipulations of interoceptive processing. Specifically, we assessed the effect on HEP amplitude of manipulating attention to the heartbeat; manipulating participants’ arousal; the association between the HEP and behavioural measures of cardiac interoception; and comparisons between healthy and clinical groups. Following database searches and screening, 45 studies were included in the systematic review and 42 in the meta-analyses. We noted variations in the ways individual studies have attempted to address key confounds, particularly the cardiac field artefact. Meta-analytic summaries indicated there were moderate to large effects of attention, arousal, and clinical status on the HEP, and a moderate association between HEP amplitude and behavioural measures of interoception. Problematically, the reliability of the meta-analytic effects documented here remain unknown, given the lack of standardised protocols for measuring the HEP. Thus, it is possible effects are driven by confounds such as cardiac factors or somatosensory effects
Real world SOF/VEL/VOX retreatment outcomes and viral resistance analysis for HCV patients with prior failure to DAA therapy
No full textSustained viral response (SVR) rates for Direct Acting Antiviral (DAA) therapy for hepatitis C virus (HCV) infection routinely exceed 95%. However, a small number of patients require retreatment. Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is a potent DAA combination primarily used for the retreatment of patients failed by DAA therapies. Here we evaluate retreatment outcomes and the effects of resistance associated substitutions (RAS) in a real-world cohort, including a large number of genotype (GT)3 infected patients. 144 patients from the UK were retreated with SOF/VEL/VOX following virologic failure with first-line DAA treatment regimens. Full-length HCV genome sequencing was performed prior to retreatment with SOF/VEL/VOX. HCV subtypes were assigned and RAS relevant to each genotype were identified. GT1a and GT3a each made up 38% (GT1a n=55, GT3a n=54) of the cohort. 40% (n=58) of patients had liver cirrhosis of whom 7% (n=4) were decompensated, 10% (n=14) had hepatocellular carcinoma (HCC) and 8% (n=12) had received a liver transplant prior to retreatment. The overall re-treatment SVR12 rate was 90% (129/144). On univariate analysis, GT3 infection (50/62; SVR=81%, p=0.009), cirrhosis (47/58; SVR=81% , p=0.01) and prior treatment with SOF/VEL(12/17; SVR=71%, p=0.02) or SOF+DCV (14/19; SVR=74%, p=0.012) were significantly associated with retreatment failure, but existence of pre retreatment RAS was not when viral genotype was taken into account. Retreatment with SOF/VEL/VOX is very successful for non-GT3-infected patients. However, for GT3-infected patients, particularly those with cirrhosis and failed by initial SOF/VEL treatment, SVR rates were significantly lower and alternative retreatment regimens should be considered
Extracting economic signals from Central Bank speeches
No full textEstimating the effects of monetary policy is one of the fundamental research questions in monetary economics. Many economies are facing ultra-low interest rate environments ever since the global financial crisis of 2007-9. The Covid pandemic recently reinforced this situation. In the US and Europe, interest rates are close to (or even below) zero, which limits the scope of traditional monetary policy measures for central banks. Dedicated central bank communication has hence become an increasingly important tool to steer and control market expectations these days. However, incorporating central bank language directly as features into economic models is still a very nascent research area. In particular, the content and effect of central bank speeches has been mostly neglected from monetary policy modelling so far. With our paper, we aim to provide to the research community a novel, monetary policy shock series based on central bank speeches. We use a supervised topic modeling approach that can deal with text as well as numeric covariates to estimate a monetary policy signal dispersion index along three key economic dimensions: GDP, CPI and unemployment. This “dispersion shock” series is not only more frequent than series that classically focus on policy announcement dates, it also opens up the possibility of answering new questions that have up until now been difficult to analyse. For example, do markets form different expectations when facing a “cacophony of policy voices”? Our initial findings for the US point towards the fact that more dispersed or incongruent monetary policy stance communication in the build up to Federal Open Market Committee (FOMC) meetings might be associated with stronger subsequent market surprises at FOMC policy announcement time
The anticipatory and task-driven nature of visual perception
No full textHumans have a remarkable capacity to arrange and rearrange perceptual input according to different categorisations. This begs the question whether the categorisation is exclusively a higher visual or amodal process, or whether categorisation processes influence early visual areas. To investigate this we scanned healthy participants in a magnetic resonance imaging scanner during a conceptual decision task in which participants had to answer questions about upcoming images of animals. Early visual cortices (V1 and V2) contained information about the current visual input, about the granularity of the forthcoming categorical decision, as well as perceptual expectations about the upcoming visual stimulus. The middle temporal gyrus, the anterior temporal lobe, and the inferior frontal gyrus were also involved in the categorical decision, constituting an attention and control network that modulates perceptual processing. These findings provide further evidence that early visual areas process visual input according to conceptual expectations and task demands
Targeted capture and sequencing of Orientia tsutsugamushi genomes from chiggers and humans
No full textScrub typhus is a febrile disease caused by Orientia tsutsugamushi, transmitted by larval stage Trombiculid mites (chiggers), whose primary hosts are small mammals. The phylogenomics of O. tsutsugamushi in chiggers, small mammals and humans remains poorly understood. To combat the limitations imposed by the low relative quantities of pathogen DNA in typical O. tsutsugamushi clinical and ecological samples, along with the technical, safety and cost limitations of cell culture, a novel probe-based target enrichment sequencing protocol was developed. The method was designed to capture variation among conserved genes and facilitate phylogenomic analysis at the scale of population samples. A whole-genome amplification step was incorporated to enhance the efficiency of sequencing by reducing duplication rates. This resulted in on-target capture rates of up to 93% for a diverse set of human, chigger, and rodent samples, with the greatest success rate in samples with real-time PCR Ct values below 35. Analysis of the best-performing samples revealed phylogeographic clustering at local, provincial and international scales. Applying the methodology to a comprehensive set of samples could yield a more complete understanding of the ecology, genomic evolution and population structure of O. tsutsugamushi and other similarly challenging organisms, with potential benefits in the development of diagnostic tests and vaccines
Cytoplasmic CPSF6 regulates HIV-1 capsid trafficking and infection in a cyclophilin A-dependent manner
No full textHuman immunodeficiency virus type 1 (HIV-1) capsid binds host proteins during infection, including cleavage and polyadenylation specificity factor 6 (CPSF6) and cyclophilin A (CypA). We observe that HIV-1 infection induces higher-order CPSF6 formation, and capsid-CPSF6 complexes cotraffic on microtubules. CPSF6-capsid complex trafficking is impacted by capsid alterations that reduce CPSF6 binding or by excess cytoplasmic CPSF6 expression, both of which are associated with decreased HIV-1 infection. Higher-order CPSF6 complexes bind and disrupt HIV-1 capsid assemblies in vitro. Disruption of HIV-1 capsid binding to CypA leads to increased CPSF6 binding and altered capsid trafficking, resulting in reduced infectivity. Our data reveal an interplay between CPSF6 and CypA that is important for cytoplasmic capsid trafficking and HIV-1 infection. We propose that CypA prevents HIV-1 capsid from prematurely engaging cytoplasmic CPSF6 and that differences in CypA cellular localization and innate immunity may explain variations in HIV-1 capsid trafficking and uncoating in CD4+ T cells and macrophages
Let's buy: Some Cordial Balm of Gilead
No full textExamines advertising, persuasion, and social history of the Cordial Balm of Gilea
Observations of Mars with ALMA: potential for future constraints of global circulation models
No full textValidation of global climate models (GCMs) for planets in our solar system requires observational data, but observations from the orbit of Mars and its surface are limited in number and are constrained by their orbit or landing site. Ground-based observations of Mars can help by providing data across the entire Martian hemisphere, yet historically, ground-based observations at submillimeter wavelengths have been limited to disk-average, or at best, a few resolution elements across Mars. We used Atacama Large Millimeter/submillimeter Array (ALMA) observations of Mars to determine the spatial distribution of carbon monoxide in the Martian atmosphere, which can be related to the atmospheric temperature. ALMA’s comparably high spatial and spectral resolutions in the submillimeter wavelengths could allow the mapping of abundances and temperature profiles, and the comparison of these data to simulations generated by the Laboratoire de Météorologie Dynamique (LMD) Mars GCM. However, the long baselines associated with the high spatial resolution of ALMA introduced systematic errors that resulted in radiative transfer modeling degeneracies. We serve to provide insight to facilitate proposed ALMA observations of Mars in the future so that the systematic errors encountered within these observations might be avoided
Explaining crossmodal correspondences between colours and tastes
No full textFor centuries, if not millennia, people have associated the basic tastes (e.g., sweet, bitter, salty, and sour) with specific colours. While the range of tastes may have changed, and the reasons for wanting to connect the senses in this rather surprising way have undoubtedly differed, there would nevertheless appear to be a surprisingly high degree of consistency regarding this crossmodal mapping among non-synaesthetes that merits further consideration. Traditionally, colour–taste correspondences have often been considered together with odour–colour and flavour–colour correspondences. However, the explanation for these various correspondences with the chemical senses may turn out to be qualitatively different, given the presence of identifiable source objects in the case of food aromas/flavours, but not necessarily in the case of basic tastes. While the internalization of the crossmodal statistics of the environment provides one appealing account for the existence of colour–taste correspondences, emotional mediation may also be relevant. Ultimately, while explaining colour–taste correspondences is of both theoretical and historical interest, the growing awareness of the robustness of colour–taste correspondences would currently seem to be of particular relevance to those working in the fields of design and multisensory experiential marketing