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Barber, A.

Publications and source records attributed to Barber, A..

5 recordsLinked to original sources

Glucose Challenge Uncovers Temporal Fungibility of Metabolic Homeostasis Throughout the Day

Rhythmicity is a cornerstone of behavioral and biological processes, especially metabolism, yet the mechanisms behind metabolite cycling remain elusive. This study uncovers a robust oscillation in key metabolite pathways downstream of glucose in humans. A purpose-built 13C6-glucose isotope tracing platform was used to sample Drosophila every 4h and probe these pathways, revealing a striking peak in biosynthesis shortly after lights-on in wild-type flies. A hyperactive mutant (fumin) demonstrates increased Krebs cycle labelling and dawn-specific glycolysis labelling. Surprisingly, neither underlying feeding rhythms nor the presence of food availability explain the rhythmicity of glucose processing across genotypes, suggesting a robust internal mechanism for metabolic control of glucose processing. These results align with clinical data highlighting detrimental effects of mistimed energy intake. Our approach offers a unique insight into the dynamic range of daily metabolic processing and provides a mechanistic foundation for exploring circadian metabolic homeostasis in disease contexts.

systems biology↗

Effects of phase encoding direction on test-retest reliability of human functional connectome

The majority of human connectome studies in the literature based on functional magnetic resonance imaging (fMRI) data use either an anterior-to-posterior (AP) or a posterior-to-anterior (PA) phase encoding direction. However, whether and how phase encoding direction would affect test-retest reliability of functional connectome is unclear. Here, in a sample of healthy subjects with two sessions of fMRI scans separated by 12 weeks (two runs per session, one with AP, the other with PA), we tested the influence of phase encoding direction on global and nodal connectivity in the constructed brain networks. All data underwent the state-of-the-art Human Connectome Project (HCP) pipeline to correct for phase-encoding-related distortions before entering analysis. We found that at the global level, the PA scans showed significantly higher intraclass correlation coefficients (ICCs) for global connectivity compared with AP scans, which was particularly prominent when using the Seitzman-300 atlas (versus the CAB-NP-718 atlas). At the nodal level, regions most strongly affected by phase encoding direction were consistently mapped to the cingulate cortex and temporal lobe, with significantly higher ICCs during PA scans compared with AP scans, regardless of atlas. Further, we demonstrated that the observed reliability differences between phase encoding directions may relate to a similar effect on the reliability of temporal signal-to-noise ratio (tSNR) in the same regions (that PA scans were associated with higher reliability of tSNR than AP scans). Averaging the connectivity outcome from the AP and PA scans could slightly, but overall have limited value to boost the ICCs. These results were largely replicated in an independent, public dataset from the HCP-Early Psychosis (HCP-EP) study with a similar design but a much shorter scan session interval. Our findings suggest that phase encoding direction has significant effects on the reliability of connectomic estimates in fMRI studies. We urge that these effects need to be carefully considered in future neuroimaging designs, especially in longitudinal studies such as those related to neurodevelopment or clinical intervention.

neuroscience↗

Does it pay to pay? A comparison of the benefits of open-access publishing across various sub-fields in Biology

Authors are often faced with the decision of whether to maximize impact or minimize costs when publishing the results of their research. For example, to potentially improve impact via increased accessibility, many subscription-based journals now offer the option of paying a fee to publish open access (i.e., hybrid journals), but this solution excludes authors who lack the capacity to pay to make their research accessible. Here, we tested if paying to publish open access in a subscriptionbased journal benefited authors by conferring more citations relative to closed access articles. We identified 146,415 articles published in 152 hybrid journals in the field of biology from 2013-2018 to compare the number of citations between various types of open access and closed access articles. In a simple generalized linear model analysis of our full dataset, we found that publishing open access in hybrid journals that offer the option confers an average citation advantage to authors of 17.8 citations compared to closed access articles in similar journals. After taking into account the number of authors, journal impact, year of publication, and subject area, we still found that open access generated significantly more citations than closed access (p < 0.0001). However, results were complex, with exact differences in citation rates among access types impacted by these other variables. This citation advantage based on access type was even similar when comparing open and closed access articles published in the same issue of a journal (p < 0.0001). However, by examining articles where the authors paid an article processing charge, we found that cost itself was not predictive of citation rates (p = 0.14). Based on our findings of access type and other model parameters, we suggest that, in most cases, paying for access does confer a citation advantage. For authors with limited budgets, we recommend pursuing open access alternatives that do not require paying a fee as they still yielded more citations than closed access. For authors who are considering where to submit their next article, we offer additional suggestions on how to balance exposure via citations with publishing costs.

scientific communication and education↗

Temperate grass allergy season defined by spatio-temporal shifts in airborne pollen communities

Grass pollen is the worlds most harmful outdoor aeroallergen and sensitivity varies between species. Different species of grass flower at different times, but it is not known how airborne communities of grass pollen change in time and space. Persistence and high mobility of grass pollen could result in increasingly diverse seasonal pollen communities. Conversely, if grass pollen does not persist for an extended time in the air, shifting pollen communities would be predicted throughout the summer months. Here, using targeted high throughput sequencing, we tracked the seasonal progression of airborne Poaceae pollen biodiversity across Britain, throughout the grass allergy season. All grass genera displayed discrete, temporally restricted peaks of pollen incidence which varied with latitude, revealing that the taxonomic composition of grass pollen exposure changes substantially across the allergy season. By developing more refined aeroallergen profiling, we predict that our findings will facilitate the exploration of links between taxon-specific exposure of harmful grass pollen and disease, with concomitant socio-economic benefits.

ecology↗

An assay for de novo kinetochore assembly reveals a key role for the CENP-T pathway in budding yeast

Chromosome segregation depends on the kinetochore, the machine that establishes force-bearing attachments between DNA and spindle microtubules. Kinetochores are formed every cell cycle via a highly regulated process that requires coordinated assembly of multiple subcomplexes on specialized chromatin. To elucidate the underlying mechanisms, we developed an assay to assemble kinetochores de novo using centromeric DNA and budding yeast extracts. Assembly is enhanced by mitotic phosphorylation of the Dsn1 kinetochore protein and generates kinetochores capable of binding microtubules. We used this assay to investigate why kinetochores recruit the microtubule-binding Ndc80 complex via two receptors: the Mis12 complex and CENP-T. Although the CENP-T pathway is non-essential in yeast, we demonstrate that it becomes essential for viability and Ndc80c recruitment when the Mis12 pathway is crippled by defects in Dsn1 phosphorylation. Assembling kinetochores de novo in yeast extracts provides a powerful and genetically tractable method to elucidate critical regulatory events in the future.

biochemistry↗