bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in a Drosophila model of ALS
Authors: Karagas Nicholas E. , Tan Kai Li , Bellen Hugo J. , Venkatachalam Kartik , Wong Ching-On
Published: December 2021

Mutations in the gene encoding VAPB (vesicle-associated membrane protein B) cause a familial form of Amyotrophic Lateral Sclerosis (ALS). Expression of an ALS-related variant of vapb (vapbP58S) in Drosophila motor neurons results in morphological changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphological changes, a mechanism for the loss of presynaptic microtubules has been lacking. Here, we demonstrate the suppression of vapbP58S- induced changes in NMJ morphology by either the loss of ER Ca2+ release channels or the inhibition Ca2+/calmodulin (CaM)-activated kinase II (CaMKII). These data suggest a model in which decreased stability of presynaptic microtubules at vapbP58S NMJs result from hyperactivation of CaMKII due to elevated cytosolic [Ca2+]. We attribute the Ca2+ dyshomeostasis to delayed extrusion of cytosolic Ca2+ stemming from a paucity of activity-induced mitochondrial ATP production coupled with elevated rates of ATP consumption. Taken together, our data point to bioenergetic dysfunction as the root cause for the synaptic defects in vapbP58S-expressing Drosophila motor neurons.

Significance Statement

Rates of ATP production and consumption are tightly synchronized in healthy neurons. Whether this synchrony is lost in models of neurodegenerative diseases remains poorly understood. Here, we find that expression of a gene encoding an ALS-causing variant of an ER membrane protein, VAPB, decouples mitochondrial ATP production from neuronal activity. Due to a combination of diminished ATP production and elevated ATP consumption — established outcomes in ALS neurons — the levels of ATP in vapbP58S neurons are unable to keep up with the bioenergetic burden of depolarization. The resulting paucity of ATP and attendant decrease in the activity of Ca2+ ATPases results in diminished extrusion of cytosolic Ca2+ in vapbP58S-expressing motor neurons. The accumulation of residual Ca2+ in vapbP58S-expressing neurons underlies paired-pulse facilitation of synaptic vesicle release, and the changes in bouton development at the NMJ. In summary, our findings point to bioenergetic dysfunction due to the loss of activity-induced ATP production as being the cause of the synaptic defects observed in a Drosophila model of ALS.
A framework for research into continental ancestry groups of the UK Biobank
Authors: Constantinescu Andrei-Emil , Mitchell Ruth E. , Zheng Jie , Bull Caroline J. , Timpson Nicholas J. , Amulic Borko , Vincent Emma E. , Hughes David A.
Published: December 2021

Background

The UK Biobank is a large prospective cohort, based in the United Kingdom, that has deep phenotypic and genomic data on roughly a half a million individuals. Included in this resource are data on approximately 78,000 individuals with “non-white British ancestry”. Whilst most epidemiology studies have focused predominantly on populations of European ancestry, there is an opportunity to contribute to the study of health and disease for a broader segment of the population by making use of the UK Biobank’s “non-white British ancestry” samples. Here we present an empirical description of the continental ancestry and population structure among the individuals in this UK Biobank subset.

Results

Reference populations from the 1000 Genomes Project for Africa, Europe, East Asia, and South Asia were used to estimate ancestry for each individual. Those with at least 80% ancestry in one of these four continental ancestry groups were taken forward (N=62,484). Principal component and K-means clustering analyses were used to identify and characterize population structure within each ancestry group. Of the approximately 78,000 individuals in the UK Biobank that are of “non-white British” ancestry, 50,685, 6,653, 2,782, and 2,364 individuals were associated to the European, African, South Asian, and East Asian continental ancestry groups, respectively. Each continental ancestry group exhibits prominent population structure that is consistent with self-reported country of birth data and geography.

Conclusions

Methods outlined here provide an avenue to leverage UK Biobank’s deeply phenotyped data allowing researchers to maximise its potential in the study of health and disease in individuals of non-white British ancestry.
Considerable escape of SARS-CoV-2 variant Omicron to antibody neutralization
Authors: Planas Delphine , Saunders Nell , Maes Piet , Guivel-Benhassine Florence , Planchais Cyril , Buchrieser Julian , Bolland William-Henry , Porrot Françoise , Staropoli Isabelle , Lemoine Frederic , Péré Hélène , Veyer David , Puech Julien , Rodary Julien , Baela Guy , Dellicour Simon , Raymenants Joren , Gorissen Sarah , Geenen Caspar , Vanmechelen Bert , Wawina-Bokalanga Tony , Martí-Carrerasi Joan , Cuypers Lize , Sève Aymeric , Hocqueloux Laurent , Prazuck Thierry , Rey Félix , Simon-Lorrière Etienne , Bruel Timothée , Mouquet Hugo , André Emmanuel , Schwartz Olivier
Published: December 2021

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1,2. It has in the meantime spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the Spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a traveller returning from Egypt. We examined its sensitivity to 9 monoclonal antibodies (mAbs) clinically approved or in development3, and to antibodies present in 90 sera from COVID-19 vaccine recipients or convalescent individuals. Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 5 to 31 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies.
Using Piecewise Regression to Identify Biological Phenomena in Biotelemetry Datasets
Authors: Wolfson David W. , Andersen David E. , Fieberg John R.
Published: December 2021

Technological advances in the field of animal tracking have greatly expanded the potential to remotely monitor animals, opening the door to exploring how animals shift their behavior over time or respond to external stimuli. A wide variety of animal-borne sensors can provide information on an animal’s location, movement characteristics, external environmental conditions, and internal physiological status. Here, we demonstrate how piecewise regression can be used to identify the presence and timing of potential shifts in a variety of biological responses using GPS telemetry and other biologging data streams. Different biological latent states can be inferred by partitioning a time-series into multiple segments based on changes in modeled responses (e.g., their mean, variance, trend, degree of autocorrelation) and specifying a unique model structure for each interval. We provide five example applications highlighting a variety of taxonomic species, data streams, timescales, and biological phenomena. These examples include a short-term behavioral response (flee and return) by a trumpeter swan (Cygnus buccinator)immediately following a GPS collar deployment; remote identification of parturition based on movements by a pregnant moose (Alces alces); a physiological response (spike in heart-rate) in a black bear (Ursus americanus) to a stressful stimulus (presence of a drone); a mortality event of a trumpeter swan signaled by changes in collar temperature and Overall Dynamic Body Acceleration; and an unsupervised method for identifying the onset, return, duration, and staging use of sandhill crane (Antigone canadensis) migration. We implement analyses using the mcp package in R, which provides functionality for specifying and fitting a wide variety of user-defined model structures in a Bayesian framework and methods for assessing and comparing models using information criterion and cross-validation measures. This approach uses simple modeling approaches that are accessible to a wide audience and is a straightforward means of assessing a variety of biologically relevant changes in animal behavior.
Scalable, ultra-fast, and low-memory construction of compacted de Bruijn graphs with Cuttlefish 2
Authors: Khan Jamshed , Kokot Marek , Deorowicz Sebastian , Patro Rob
Published: December 2021

The de Bruijn graph is a key data structure in modern computational genomics, and construction of its compacted variant resides upstream of many genomic analyses. As the quantity of genomic data grows rapidly, this often forms a computational bottleneck.

We present Cuttlefish 2, significantly advancing the state-of-the-art for this problem. On a commodity server, it reduces the graph construction time for 661K bacterial genomes, of size 2.58Tbp, from 4.5 days to 17–23 hours; and it constructs the graph for 1.52Tbp white spruce reads in ∼10 hours, while the closest competitor requires 54–58 hours, using considerably more memory.
Protocol for a cluster randomised trial to evaluate a community-level complementary-food safety and hygiene and nutrition intervention in Mali: The MaaCiwara study
Authors: Watson Samuel I , Asamane E , Lilford RJ , Hemming K , Sidibe Cheick , Rego Ryan T. , Bensassi Sami , Diarra Ayouba , Diarra Youssouf , Diop Samba , Gautam Om Prasad , Islam Mohammad Sirajul , Jackson Louise , Jolly Kate , Kayentao Kassoum , Koita Ousmane , Manjang Buba , Tebbs Susan , Gale Nicola , Griffiths Paula , Cairncross Sandy , Toure Ousmane , Manaseki-Holland Semira
Published: December 2021

Background

Diarrheal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. This article describes a protocol for a cluster randomized trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition.

Methods

We will conduct a mixed-methods, parallel cluster randomised controlled trial with baseline measures. 120 clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. Participants will be mother-child dyads (27 per cluster period) with children aged 6 to 24 months. Data collection will comprise a day of observation and interviews with each participating mother-child pair and will take place at baseline and four and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutritional content of meals, and child anthropometry. A secondary structural equation analysis will be conducted to examine the causal relationships between the different outcomes.

Conclusions

The trial will provide evidence on the effectiveness of community-based behavioural change and educational interventions designed to reduce the burden of diarrhoeal disease in the under fives, and how effectiveness varies across different contexts.
Exome-wide analysis of copy number variation shows association of the human leukocyte antigen region with asthma in UK Biobank
Authors: Fawcett Katherine A. , Demidov German , Shrine Nick , Paynton Megan L , Ossowski Stephan , Sayers Ian , Wain Louise V. , Hollox Edward J.
Published: December 2021

Background

The role of copy number variants (CNVs) in susceptibility to asthma is not well understood. This is, in part, due to the difficulty of accurately measuring CNVs in large enough sample sizes to detect associations. The recent availability of whole-exome sequencing (WES) in large biobank studies provides an unprecedented opportunity to study the role of CNVs in asthma.

Methods

We called common CNVs in 49,953 individuals in the first release of UK Biobank WES using ClinCNV software. CNVs were tested for association with asthma in a stage 1 analysis comprising 7,098 asthma cases and 36,578 controls from the first release of sequencing data. Nominally-associated CNVs were then meta-analysed in stage 2 with an additional 17,280 asthma cases and 115,562 controls from the second release of UK Biobank exome sequencing, followed by validation and fine-mapping.

Results

Five of 189 CNVs were associated with asthma in stage 2, including a deletion overlapping the HLA-DQA1 and HLA-DQB1 genes, a duplication of CHROMR/PRKRA, deletions within MUC22 and TAP2, and a duplication in FBRSL1. The HLA-DQA1, HLA-DQB1, MUC22 and TAP2 genes all reside within the human leukocyte antigen (HLA) region on chromosome 6. In silico analyses demonstrated that the deletion overlapping HLA-DQA1 and HLA-DQB1 is likely to be an artefact arising from under-mapping of reads from non-reference HLA haplotypes, and that the CHROMR/PRKRA and FBRSL1 duplications represent presence/absence of pseudogenes within the HLA region. Bayesian fine-mapping of the HLA region suggested that there are two independent asthma association signals. The variants with the largest posterior inclusion probability in the two credible sets were an amino acid change in HLA-DQB1 (glutamine to histidine at residue 253) and a multi-allelic amino acid change in HLA-DRB1 (presence/absence of serine, glycine or leucine at residue 11).

Conclusions

At least two independent loci characterised by amino acid changes in the HLA-DQA1, HLA-DQB1 and HLA-DRB1 genes are likely to account for association of SNPs and CNVs in this region with asthma. The high divergence of haplotypes in the HLA can give rise to spurious CNVs, providing an important, cautionary tale for future large-scale analyses of sequencing data.
A prospective validation of nomograms based on BC-116 and BC-106 urine peptide biomarker panels for bladder cancer diagnostics and monitoring
Authors: Mengual Lourdes , Frantzi Maria , Mokou Marika , Ingelmo-Torres Mercedes , Vlaming Michiel , Merseburger Axel S. , Roesch Marie C. , Culig Zoran , Alcaraz Antonio , Vlahou Antonia , Mischak Harald , Van der Heijden Antoine G.
Published: December 2021

Purpose

Non-invasive urine-based biomarkers for bladder cancer (BC) diagnosis and surveillance can potentially improve current diagnostic and monitoring protocols by guiding cystoscopy. Here, we aim to access the diagnostic performance of nomograms based on published biomarker panels for BC detection (BC-116) and monitoring of recurrence (BC-106) in combination with cytology, in two prospectively collected patient cohorts.

Experimental Design

602 recruited patients were screened for presence of BC, out of which 551 were found eligible for further analysis. For the primary setting, urine samples from 73 eligible patients were analyzed from those diagnosed with primary BC (n=27) and benign urological disorders (n=46). For the surveillance setting, 478 eligible patients were considered (83 BC recurrences; 395 negative for recurrence). Urine samples were analyzed with capillary electrophoresis coupled to mass spectrometry and the biomarker score was estimated via a support vector machine-based software.

Results

Validation of the BC-116 biomarker panel resulted in 89% sensitivity and 67% specificity (AUCBC-116=0.82), similar to the published estimates. The nomogram based on cytology and BC-116 resulted in good (AUCNom116=0.85) but not significantly better performance than the BC-116 alone (P=0.5672). BC-106 biomarker panel showed 89% sensitivity and 32% specificity for surveillance, while improved performance was achieved when a nomogram including BC-106 and cytology was evaluated (AUCNom106=0.82), significantly outperforming both cytology (AUCcyt=0.72;P=0.0022) and BC-106 alone (AUCBC-106=0.67;P=0.0012).

Conclusions

BC-116 biomarker panel is a useful test for detecting primary BC. BC-106 classifier integrated with cytology and showing >95% negative predictive value, might be useful for decreasing the number of cystoscopies during surveillance.
Racial disparity in distant recurrence-free survival in localized breast cancer patients: A pooled analysis of NSABP trials
Authors: Kim Gina , Pastoriza Jessica M. , Qin Jiyue , Lin Juan , Karagiannis George S. , Condeelis John S. , Yothers Greg , Anderson Stewart , Julian Thomas , Entenberg David , Rohan Thomas E. , Xue Xiaonan , Sparano Joseph A. , Oktay Maja H.
Published: December 2021

Background

Black race is associated with worse outcome in patients with breast cancer. We evaluated distant relapse-free survival (DRFS) between Black and White women with localized breast cancer who participated in NCI-sponsored clinical trials.

Methods

We analyzed pooled data from eight National Surgical Adjuvant Breast and Bowel Project (NSABP) trials including 9,702 women with localized breast cancer treated with adjuvant chemotherapy (AC, n=7,485) or neoadjuvant chemotherapy (NAC, n=2,217), who self-reported as Black (n=1,070) or White (n=8,632). The association between race and DRFS was analyzed using log-rank tests and multivariate Cox regression.

Results

After adjustment for covariates including age, tumor size, nodal status, body mass index and taxane use, and treatment (AC vs. NAC), Black race was associated with an inferior DRFS in ER-positive (HR 1.24 [95% CI 1.05-1.46], p=0.01), but not in ER-negative disease (HR 0.97 [95% CI 0.83-1.14], p=0.73), and significant interaction between race and ER status was observed (p=0.03). There was no racial disparity in DRFS among patients with pathologic complete response (pCR) (Log-rank p =0.8). For patients without pCR, black race was associated with worse DRFS in ER-positive (HR 1.67 [95% CI 1.14-2.45], p=0.01), but not in ER-negative disease (HR 0.91 [95% CI 0.65-1.28], p=0.59).

Conclusion

Black race was associated with significantly inferior DRFS in ER-positive localized breast cancer treated with AC or NAC, but not in ER-negative disease. In the NAC group, racial disparity was also observed in patients with residual ER-positive breast cancer at surgery, but not in those who had a pathologic complete response.

Lay Summary

Black women with breast cancer have worse outcome compared to White women. We investigated if this held true in the context of clinical trials which provide controlled treatment setting. Black women with cancer containing estrogen receptors (ER) had worse outcome than White women. If breast cancers did not contain ER there was no racial disparity in outcome. Moreover, we observed racial disparity in women who received chemotherapy before their cancer was removed, but only if they had cancer with ER and residual disease upon completion of treatment. If cancer disappeared upon pre-surgical chemotherapy, there was no racial disparity.
Antigenic and virological properties of an H3N2 variant that will likely dominate the 2021-2022 Northern Hemisphere influenza season
Authors: Bolton Marcus J. , Ort Jordan T. , McBride Ryan , Swanson Nicholas J. , Wilson Jo , Awofolaju Moses , Greenplate Allison R. , Drapeau Elizabeth M. , Pekosz Andrew , Paulson James C. , Hensley Scott E.
Published: December 2021

Influenza viruses have circulated at very low levels during the COVID-19 pandemic, and population immunity against these viruses is low. Influenza virus cases have been increasing in the Northern Hemisphere involving an H3N2 strain (3C.2a1b.2a2) with a hemagglutinin (HA) that has several substitutions relative to the 2021-2022 H3N2 vaccine strain. Here, we show that one of these substitutions eliminates a key glycosylation site on HA and alters sialic acid binding. Using glycan array profiling, we show that the 3C.2a1b.2a2 H3 maintains binding to an extended bi-antennary sialoside and replicates to high titers in human airway cells. We found that antibodies elicited by the 2021-2022 Northern Hemisphere influenza vaccine poorly neutralize the new H3N2 strain. Together, these data indicate that 3C.2a1b.2a2 H3N2 viruses efficiently replicate in human cells and could potentially cause an antigenic mismatch if they continue to circulate at high levels during the 2021-2022 influenza season.
Development and Validation of Suspicious Liver Lesion Deep Learning Algorithm for Computed Tomography
Authors: Johnson Jacob , Senevirathne Kaneel , Ngo Lawrence
Published: December 2021

In this work, we report the results of a deep-learning based liver lesion detection algorithm. While several liver lesion segmentation and classification algorithms have been developed, none of the previous work has focused on detecting suspicious liver lesions. Furthermore, their generalizability remains a pitfall due to their small sample size and sample homogeneity. Here, we developed and validated a highly generalizable deep-learning algorithm for detection of suspicious liver lesions. The algorithm was trained and tested on a diverse dataset containing CT exams from over 2,000 hospital sites in the United States. Our final model achieved an AUROC of 0.84 with a specificity of 0.99 while maintaining a sensitivity of 0.33.
Spindle pole body-associated Atg11, an autophagy-related protein, regulates microtubule dynamics essential for high-fidelity chromosome segregation
Authors: Reza Md. Hashim , Aggarwal Rashi , Verma Jigyasa , Podh Nitesh Kumar , Chowdhury Ratul , Mehta Gunjan , Manjithaya Ravi , Sanyal Kaustuv
Published: December 2021

Emerging studies hint at the roles of autophagy-related proteins in various cellular processes in a eukaryotic cell. To understand if autophagy-related proteins influence genome stability, we examined a cohort of 35 autophagy mutants inSaccharomyces cerevisiae.We observed cells lacking Atg11 show poor mitotic stability of minichromosomes. Atg11 molecules dynamically localize to the spindle pole bodies (SPBs). Loss of Atg11 leads to a delayed cell cycle progression. Such cells accumulate at metaphase at an elevated temperature that is relieved when the spindle assembly checkpoint is inactivated. Indeed,atg11Δ cells have stabilized securin levels, that prevent anaphase onset, confirming chromosome biorientation defects associated with the mutant. Atg11 functions in the Kar9-dependent spindle positioning pathway and maintains Kar9 asymmetry by facilitating proper dynamic instability of astral microtubules (aMTs). Taken together, this study uncovers a non-canonical role of Atg11 in facilitating MT dynamics crucial for chromosome segregation.
Spatial effects in parasite induced marine diseases of immobile hosts
Authors: Giménez-Romero Alex , Vazquez Federico , López Cristóbal , Matias Manuel A.
Published: December 2021

Marine infectious diseases are more prevalent in recent times due to climate change and other anthropogenic pressures, posing a substantial threat to marine ecosystems and the conservation of their biodiversity. An important subset of marine organisms are sessile, for which the most common mechanism for disease transmission is direct contact with waterborne parasites. Only recently, some deterministic compartmental models have been proposed to describe this kind of epidemics, being these models based on non-spatial descriptions where space is homogenised and parasite mobility is not explicitly accounted for. However, in realistic situations, epidemic transmission is conditioned by the spatial distribution of hosts and the parasites mobility patterns. Thus, the interplay between these factors is expected to have a crucial effect in the evolution of the epidemic, so calling for a explicit description of space. In this work we develop a spatially-explicit individual-based model to study disease transmission by waterborne parasites in sessile marine populations. We investigate the impact of spatial disease transmission, performing extensive numerical simulations and analytical approximations. Specifically, the effects of parasite mobility into the epidemic threshold and the temporal evolution of the epidemic are assessed. We show that larger values of pathogen mobility have two main implications: more severe epidemics, as the number of infections increases, and shorter time-scales to extinction. Moreover, an analytical expression for the basic reproduction number of the spatial model,, is derived as function of the non-spatial counterpart,R0, which characterises a transition between a disease-free and a propagation phase, in which the disease propagates over a large fraction of the system. This allows to determine a phase diagram for the epidemic model as function of the parasite mobility and the basic reproduction number of the non-spatial model.
Discovery of lipid-mediated protein-protein interactions in living cells using metabolic labeling with photoactivatable clickable probes
Authors: Fedoryshchak Roman O. , Gorelik Andrii , Shen Mengjie , Shchepinova Maria M. , Pérez-Dorado Inmaculada , Tate Edward W.
Published: December 2021

Protein-protein interactions (PPIs) are essential and pervasive regulatory elements in cell biology. Despite development of a range of techniques to probe PPIs in living systems, there is a dearth of approaches to capture interactions driven by specific post-translational modifications (PTMs). Myristoylation is a lipid PTM added to more than 200 human proteins, where it may regulate membrane localization, stability or activity. Here we report design and synthesis of a panel of novel photocrosslinkable and clickable myristic acid analog probes, and their characterization as efficient substrates for human N-myristoyltransferases NMT1 and NMT2, both biochemically and through X-ray co-crystallography. We demonstrate metabolic incorporation of probes to label NMT substrates in cell culture and in situ intracellular photoactivation to form a covalent crosslink between modified proteins and their interactors, capturing a snapshot of interactions driven by the presence of the lipid PTM. Proteomic analyses revealed both known and multiple novel interactors of a series of myristoylated proteins, including ferroptosis suppressor protein FSP1 and spliceosome-associated RNA helicase DDX46. The concept exemplified by these probes offers an efficient approach for exploring the PTM-specific interactome, which may prove broadly applicable to other PTMs.
The MyLo CRISPR-Cas9 Toolkit: A Markerless Yeast Localization and Overexpression CRISPR-Cas9 Toolkit
Authors: Bean Björn D.M. , Whiteway Malcolm , Martin Vincent J.J.
Published: December 2021

The genetic tractability of the yeast Saccharomyces cerevisiae has made it a key model organism for basic research and a target for metabolic engineering. To streamline the introduction of tagged genes and compartmental markers with powerful CRISPR-Cas9-based genome editing tools we constructed a Markerless Yeast Localization and Overexpression (MyLO) CRISPR-Cas9 toolkit with three components: (i) a set of optimized S. pyogenes Cas9-guide RNA (gRNA) expression vectors with five selectable markers and the option to either pre-clone or co-transform the gRNAs; (ii) vectors for the one-step construction of integration cassettes expressing an untagged or GFP/RFP/HA-tagged gene of interest at one of three levels, supporting localization and overexpression studies; and (iii) integration cassettes containing moderately expressed GFP- or RFP-tagged compartmental markers for colocalization experiments. These components allow rapid, high efficiency genomic integrations and modifications with only transient selection for the Cas9 vector, resulting in markerless transformations. To demonstrate the ease of use, we applied our complete set of compartmental markers to co-label all target subcellular compartments with GFP and RFP. Thus, the MyLO toolkit packages CRISPR-Cas9 technology into a flexible, optimized bundle to simplify yeast research.
Seed sourcing for climate-resilient grasslands: the role of seed source diversity during early restoration establishment
Authors: Lindstrom Jessica , Ahlering Marissa , Hamilton Jill
Published: December 2021

Restoration often advocates for the use of local seed in restoration, however increasingly new strategies have been proposed to incorporate diverse sources to maintain evolutionary potential within seed mixes. Increasing seed sources per species within a seed mix should increase genetic variation, however, few empirical studies have evaluated how seed source diversity impacts plant community composition following restoration. Thus, the goal of this research was to compare the use of single or multi-source seed mix treatments to plant community diversity following restoration. Using 14 species commonly applied in grassland restoration, we examined plant community diversity following restoration comparing seed mixes with either one or five sources per species across two restoration sites in Minnesota and South Dakota, United States. Following seeding, species establishment and abundance were recorded to calculate plant diversity for each seed mix treatment. There were no major effects of seed mix treatment on community emergence and diversity observed, with the majority of plant establishment reflecting non-seeded species. However, site-specific differences were observed. Heterogeneous land-use history associated with the Minnesota site likely contributed to differences across the restoration treatments. In contrast, community diversity at the South Dakota site was homogeneous across seed mix treatments with changes in plant community influenced solely by early season species establishment. This suggests land-use history irrespective of seed mix treatment influences establishment and persistence, particularly in the first year following restoration. Future monitoring across seasons will be needed to evaluate if community diversity changes in response to seed mix treatment.
Genome size distributions in bacteria and archaea are strongly linked to phylogeny
Authors: Martinez-Gutierrez Carolina A. , Aylward Frank O.
Published: December 2021

The evolutionary forces that determine genome size in bacteria and archaea have been the subject of intense debate over the last few decades. Although the preferential loss of genes observed in prokaryotes is explained through the deletional bias, factors promoting and preventing the fixation of such gene losses remain unclear. Moreover, statistical analyses on this topic have typically been limited to a narrow diversity of bacteria and archaea without considering the potential bias introduced by the shared recent ancestry of many lineages. In this study, we used a phylogenetic generalized least-squares (PGLS) analysis to evaluate the effect of different factors on the genome size of a broad diversity of bacteria and archaea. We used dN/dS to estimate the strength of purifying selection, and 16S copy number as a proxy for ecological strategy, which have both been postulated to play a role in shaping genome size. After model fit, Pagel’s lambda indicated a strong phylogenetic signal in genome size, suggesting that the diversification of this trait is strongly influenced by shared evolutionary histories. As a predictor variable, dN/dS showed a poor predictability and non-significance when phylogeny was considered, consistent with the view that genome reduction can occur under either weak or strong purifying selection depending on the ecological context. Copies of 16S rRNA showed poor predictability but maintained significance when accounting for non-independence in residuals, suggesting that ecological strategy as approximated from 16S rRNA copies might play a minor role in genome size variation. Altogether, our results indicate that genome size is a complex trait that is not driven by any singular underlying evolutionary force, but rather depends on lineage- and niche-specific factors that will vary widely across bacteria and archaea.

Author Summary

The evolutionary forces driving genome size in bacteria and archaea have been subject to debate during the last decades. Independent comparative analyses have suggested that unique variables, such as the strength of selection, environmental complexity, and mutation rate, are the main drivers of this trait, which complicates generalizations across the Tree of Life. Here, we applied a phylogeny-based statistical approach to assess how tightly genome size is linked to evolutionary history in bacteria and archaea. Moreover, we also evaluated the predictability of genome size from the strength of purifying selection and ecological strategy on a broad diversity of bacteria and archaea genomes. Our approach indicates that genome size in prokaryotes is strongly dependent on phylogenetic history, and that genome size is the result of the interaction of variables like past events, current selection regimes, and environmental complexity that are clade dependent.
Loss of Cohesin regulator PDS5A reveals repressive role of Polycomb loops
Authors: Bsteh Daniel , Moussa Hagar F. , Michlits Georg , Yelagandula Ramesh , Wang Jingkui , Elling Ulrich , Bell Oliver
Published: December 2021

Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. In addition, a subset of PRC1/PRC2 targets engage in long-range interactions whose functions in gene silencing are poorly understood. Using a CRISPR screen in mouse embryonic stem cells, we identified that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not associated with loss of repressive Polycomb chromatin modifications. Instead, loss of PDS5A leads to aberrant cohesin activity, ectopic insulation sites and specific reduction of ultra-long Polycomb loops. We infer that these loops are important for robust silencing at a subset of Polycomb target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.
Decreased retinal vascular complexity is an early biomarker of MI supported by a shared genetic control
Authors: Villaplana-Velasco Ana , Engelmann Justin , Rawlik Konrad , Canela-Xandri Oriol , Tochel Claire , Lona-Durazo Frida , Krishnan Mookiah Muthu Rama , Doney Alex , Parra Esteban J. , Trucco Emanuele , MacGillivray Tom , Rannikmae Kristiina , Tenesa Albert , Pairo-Castineira Erola , Bernabeu Miguel O.
Published: December 2021

There is increasing evidence that the complexity of the retinal vasculature (measured as fractal dimension, Df) might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present here a genome-wide association study (GWAS) aimed to elucidate the genetic component of Df and to analyse its relationship with CAD. To this end, we obtained Df from retinal fundus images and genotyping information from ∼38,000 white-British participants in the UK Biobank. We discovered 9 loci associated with Df, previously reported in pigmentation, retinal width and tortuosity, hypertension, and CAD studies. Significant negative genetic correlation estimates endorse the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD fatal outcomes. This strong association motivated us to developing a MI predictive model combining clinical information, Df, a CAD polygenic risk score and using a random forest algorithm. Internal cross validation evidenced a considerable improvement in the area under the curve (AUC) of our predictive model (AUC=0.770) when comparing with an established risk model, SCORE, (AUC=0.719). Our findings shed new light on the genetic basis of Df, unveiling a common control with CAD, and highlights the benefits of its application in individualised MI risk prediction.
Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity
Authors: Kaise Takashi , Fukui Masahiro , Sueda Risa , Piao Wenhui , Yamada Mayumi , Kobayashi Taeko , Imayoshi Itaru , Kageyama Ryoichiro
Published: December 2021

The regenerative potential of neural stem cells (NSCs) declines during aging, leading to cognitive dysfunctions. This decline involves up-regulation of senescence-associated genes, but inactivation of such genes failed to reverse aging of hippocampal NSCs. Because many genes are up-regulated or down-regulated during aging, manipulation of single genes would be insufficient to reverse aging. Here we searched for a gene combination that can rejuvenate NSCs in the aged mouse brain from nuclear factors differentially expressed between embryonic and adult NSCs and their modulators. We found that a combination of inducing the zinc finger transcription factor genePlagl2and inhibitingDyrk1a, a gene associated with Down syndrome (a genetic disorder known to accelerate aging), rejuvenated aged hippocampal NSCs, which already lost proliferative and neurogenic potential. Such rejuvenated NSCs proliferated and produced new neurons continuously at the level observed in juvenile hippocampi, leading to improved cognition. Epigenome, transcriptome, and live-imaging analyses indicated that this gene combination induces up-regulation of embryo-associated genes and down-regulation of age-associated genes by changing their chromatin accessibility, thereby rejuvenating aged dormant NSCs to function like juvenile active NSCs. Thus, aging of NSCs can be reversed to induce functional neurogenesis continuously, offering a way to treat age-related neurological disorders.
Three-dimensional grain resolved strain mapping using laboratory X-ray diffraction contrast tomography: theoretical analysis
Authors: Lindkvist Adam , Zhang Yubin
Published: December 2021

Laboratory diffraction contrast tomography (LabDCT) is a recently developed technique to map crystallographic orientations of polycrystalline samples in three dimensions non-destructively using a laboratory X-ray source. In this work, a new theoretical procedure, named LabXRS, expanding LabDCT to include mapping of the deviatoric strain tensors on the grain scale, is proposed and validated using simulated data. For the validation, the geometries investigated include a typical near-field LabDCT setup utilizing Laue focusing with equal source-to-sample and sample-to-detector distances of 14 mm, a magnified setup where the sample-to-detector distance is increased to 200 mm, a far-field Laue focusing setup where the source-to-sample distance is also increased to 200 mm, and a near-field setup with a source-to-sample distance of 200 mm. The strain resolution is found to be in the range of 1–5 × 10−4, depending on the geometry of the experiment. The effects of other experimental parameters, including pixel binning, number of projections and imaging noise, as well as microstructural parameters, including grain position, grain size and grain orientation, on the strain resolution are examined. The dependencies of these parameters, as well as the implications for practical experiments, are discussed.
Exploring the attitude towards the adoption of a sustainable diet: a cross-country comparison
Authors: Pucci Tommaso , Casprini Elena , Sogari Giovanni , Zanni Lorenzo
Published: December 2021

Purpose

Understanding the determinants that influence consumers' attitude to adopt sustainable diets represents an important area of research to promote sustainable food consumption. The aim of this study is to investigate how (1) the individual openness to new foods (ONFs), (2) the involvement in food trends (IFTs) and (3) the social media use (SMU) can potentially impact the attitude towards the adoption of a sustainable diet (ATSD).

Design/methodology/approach

The authors conducted a structured survey in eight countries: Italy, Germany, Poland, USA, Brazil, Japan, Korea and China. The final sample of 5,501 individuals was analysed applying a structural equation model.

Findings

The main results show that attitude towards the ATSD is influenced differently by the antecedents investigated in each country. In particular, the ONF positively influences the ATSD only in Italy, USA and Germany. IFT positively influences the ATSD only in Italy, Poland and USA, while negatively in Germany. SMU has a positive influence on the ATSD only in Japan, USA and Germany, while a negative one in Brazil and Korea.

Originality/value

This study presents a cross-country comparison about the antecedents of attitude towards the ATSD, thus providing evidence for the need of ad hoc marketing strategies by companies and policies by institutions at single country level.
Comparative analyses of electrical circuits with conventional and revisited definitions of circuit elements: a fractional conformable calculus approach
Authors: Banchuin Rawid
Published: December 2021

Purpose

The purpose of this paper is to comparatively analyze the electrical circuits defined with the conventional and revisited time domain circuit element definitions in the context of fractional conformable calculus and to promote the combined usage of conventional definitions, fractional conformable derivative and conformable Laplace transform.

Design/methodology/approach

The RL, RC, LC and RLC circuits described by both conventional and revisited time domain circuit element definitions has been analyzed by means of the fractional conformable derivative based differential equations and conformable Laplace transform. The comparison among the obtained results and those based on the methodologies adopted in the previous works has been made.

Findings

The author has found that the conventional definitions-based solution gives a physically reasonable result unlike its revisited definitions-based counterpart and the solutions based on those previous methodologies. A strong agreement to the time domain state space concept-based solution can be observed. The author has also shown that the scalar valued solution can be directly obtained by singularity free conformable Laplace transform-based methodology unlike such state space concept based one.

Originality/value

For the first time, the revisited time domain definitions of resistance and inductance have been proposed and applied together with the revisited definition of capacitance in electrical circuit analyses. The advantage of the combined usage of conventional time definitions, fractional conformable derivative and conformable Laplace transform has been suggested and the impropriety of applying the revisited definitions in circuit analysis has been pointed out.
Carbon emissions management in construction operations: a systematic review
Authors: Joseph Verona Ramas , Mustaffa Nur Kamaliah
Published: December 2021

Purpose

The demand to reduce carbon emissions has become an increasingly important social factor due to the unprecedented impacts of climate change. However, most existing publications have focused on minimizing emissions during the operational phase of buildings. At the same time, there is a lack of comprehensive research conducted on carbon emissions, specifically during the construction phase. The purpose of this paper is to identify, review and classify current practices related to carbon emissions management in construction operations to gain greater insight into how to reduce and mitigate emissions and achieve more sustainable solutions.

Design/methodology/approach

This study reviewed the published literature on carbon emissions from construction. A total of 198 bibliographic records were extracted from the Scopus collection database and analyzed using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). PRISMA is used as a basis for reporting possible trends, research methods and strategies used in published literatures. A total of 99 papers related to carbon emissions in the construction operations were further reviewed and analyzed. This review paper draws on existing research and identifies current carbon management patterns in construction projects.

Findings

Data indicated an upward trend in the number of publications in carbon emissions research during the last few years, particularly in 2015, 2017 and 2019. The most significant contributions to the domain were reported from China, Europe and the USA. This paper found that most studies conduct the Life Cycle Assessment (LCA) method to estimate carbon emissions. This paper found that the primary studies have focused on construction machinery and equipment emissions. The strategies such as establishing uniform standards for carbon emissions policies and regulations, equipment and logistic planning and low carbon design material will potentially impact carbon emissions reductions.

Practical implications

This paper provides information that will be beneficial for the construction industry to design and manage construction operations. It will also be of interest to those looking to reduce or manage construction emissions.

Originality/value

Although there is a diversity of current thinking related to the practical estimation and management of carbon emissions in construction projects, there is no consolidated set of keys of standardized carbon emissions management in practice. By assessing the existing paradigms of carbon assessment methods and tactics in the construction industry, this study contributed to the existing knowledge base by providing insights into current techniques in the construction sector for monitoring and mitigating emissions.
Information and material delays effect on price setting, operating contribution margins and cash conversion cycles in feed ingredients supply chain
Authors: Fraiha Marcos
Published: December 2021

Purpose

The purpose of this report was to evaluate the effectiveness and practicality of system dynamics modeling in integrating econometric equations to describe the effects of supply chain material and information delays on pricing decisions and consequent financial results in an animal feed export business.

Design/methodology/approach

An empirical dynamic model, loaded with econometric theory of price effect on competitive demand, was used to describe the input data.

Findings

The model simulation outputs proved themselves relevant in analyzing the complex interconnections of multiple variables affecting the profitability in a commercial routine, supporting the decision process among sales managers. The impact of information delay on price decisions and business financial results were estimated using the model proposed.

Originality/value

This paper describes an empirical model, based on system dynamics, that predicts operating contribution margins and cash conversion cycles based on estimation of information and material delays in a supply chain. The method is pragmatic and simple for business routine implementation.