bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep-learning-based approach for strain estimation in phase-sensitive optical coherence elastography
Authors: Dong Bo , Huang Naixing , Bai Yulei , Xie Shengli
Published: November 2021

In this Letter, a deep-learning-based approach is proposed for estimating the strain field distributions in phase-sensitive optical coherence elastography. The method first uses the simulated wrapped phase maps and corresponding phase-gradient maps to train the strain estimation convolution neural network (CNN) and then employs the trained CNN to calculate the strain fields from measured phase-difference maps. Two specimens with different deformations, one with homogeneous and the other with heterogeneous, were measured for validation. The strain field distributions of the specimens estimated by different approaches were compared. The results indicate that the proposed deep-learning-based approach features much better performance than the popular vector method, enhancing the SNR of the strain results by 21.6 dB.
In-line hollow-core fiber-optic bandpass filter
Authors: Xiong Daiqi , Wu Xu , Abu Hassan Muhammad Rosdi , Gavara Trivikramarao , Chang Wonkeun
Published: November 2021

We present an antiresonant hollow-core fiber-based bandpass optical filter. The device is realized by tapering down a section of tubular hollow-core fiber to a ratio of less than 0.5. Sweeping of the tube wall thickness-induced resonant bands in the down- and up-transition sections of the taper suppresses the blue side of the spectrum, while the red side filtering exploits the increased confinement loss at the taper waist that depends sharply on the wavelength-to-core-diameter ratio. These working principles of the filter make it possible to customize the location and width of the passband by tailoring the fiber design and taper profile. We achieve a 350-nm-wide bandpass filter with the minimum insertion loss of 1.3 dB in the passband and up to 40 dB suppression in the lossbands. We anticipate the filter to become one of the essential components in all-hollow-core fiberized optical systems.
Computational redesign of a fluorogen activating protein with Rosetta
Authors: Bozhanova Nina G. , Harp Joel M. , Bender Brian J. , Gavrikov Alexey S. , Gorbachev Dmitry A. , Baranov Mikhail S. , Mercado Christina B. , Zhang Xuan , Lukyanov Konstantin A. , Mishin Alexander S. , Meiler Jens
Published: November 2021

The use of unnatural fluorogenic molecules widely expands the pallet of available genetically encoded fluorescent imaging tools through the design of fluorogen activating proteins (FAPs). While there is already a handful of such probes available, each of them went through laborious cycles of in vitro screening and selection. Computational modeling approaches are evolving incredibly fast right now and are demonstrating great results in many applications, including de novo protein design. It suggests that the easier task of fine-tuning the fluorogen-binding properties of an already functional protein in silico should be readily achievable. To test this hypothesis, we used Rosetta for computational ligand docking followed by protein binding pocket redesign to further improve the previously described FAP DiB1 that is capable of binding to a BODIPY-like dye M739. Despite an inaccurate initial docking of the chromophore, the incorporated mutations nevertheless improved multiple photophysical parameters as well as the overall performance of the tag. The designed protein, DiB-RM, shows higher brightness, localization precision, and apparent photostability in protein-PAINT super-resolution imaging compared to its parental variant DiB1. Moreover, DiB-RM can be cleaved to obtain an efficient split system with enhanced performance compared to a parental DiB-split system. The possible reasons for the inaccurate ligand binding pose prediction and its consequence on the outcome of the design experiment are further discussed.
RESCRIPt: Reproducible sequence taxonomy reference database management
Authors: Robeson Michael S. , O’Rourke Devon R. , Kaehler Benjamin D. , Ziemski Michal , Dillon Matthew R. , Foster Jeffrey T. , Bokulich Nicholas A.
Published: November 2021

Nucleotide sequence and taxonomy reference databases are critical resources for widespread applications including marker-gene and metagenome sequencing for microbiome analysis, diet metabarcoding, and environmental DNA (eDNA) surveys. Reproducibly generating, managing, using, and evaluating nucleotide sequence and taxonomy reference databases creates a significant bottleneck for researchers aiming to generate custom sequence databases. Furthermore, database composition drastically influences results, and lack of standardization limits cross-study comparisons. To address these challenges, we developed RESCRIPt, a Python 3 software package and QIIME 2 plugin for reproducible generation and management of reference sequence taxonomy databases, including dedicated functions that streamline creating databases from popular sources, and functions for evaluating, comparing, and interactively exploring qualitative and quantitative characteristics across reference databases. To highlight the breadth and capabilities of RESCRIPt, we provide several examples for working with popular databases for microbiome profiling (SILVA, Greengenes, NCBI-RefSeq, GTDB), eDNA and diet metabarcoding surveys (BOLD, GenBank), as well as for genome comparison. We show that bigger is not always better, and reference databases with standardized taxonomies and those that focus on type strains have quantitative advantages, though may not be appropriate for all use cases. Most databases appear to benefit from some curation (quality filtering), though sequence clustering appears detrimental to database quality. Finally, we demonstrate the breadth and extensibility of RESCRIPt for reproducible workflows with a comparison of global hepatitis genomes. RESCRIPt provides tools to democratize the process of reference database acquisition and management, enabling researchers to reproducibly and transparently create reference materials for diverse research applications. RESCRIPt is released under a permissive BSD-3 license at https://github.com/bokulich-lab/RESCRIPt.
The H3.3K27M oncohistone affects replication stress outcome and provokes genomic instability in pediatric glioma
Authors: Bočkaj Irena , Martini Tosca E. I. , de Camargo Magalhães Eduardo S. , Bakker Petra L. , Meeuwsen-de Boer Tiny G. J. , Armandari Inna , Meuleman Saskia L. , Mondria Marin T. , Stok Colin , Kok Yannick P. , Bakker Bjorn , Wardenaar René , Seiler Jonas , Broekhuis Mathilde J. C. , van den Bos Hilda , Spierings Diana C. J. , Ringnalda Femke C. A. , Clevers Hans , Schüller Ulrich , van Vugt Marcel A. T. M. , Foijer Floris , Bruggeman Sophia W. M.
Published: November 2021

While comprehensive molecular profiling of histone H3.3 mutant pediatric high-grade glioma has revealed extensive dysregulation of the chromatin landscape, the exact mechanisms driving tumor formation remain poorly understood. Since H3.3 mutant gliomas also exhibit high levels of copy number alterations, we set out to address if the H3.3K27M oncohistone leads to destabilization of the genome. Hereto, we established a cell culture model allowing inducible H3.3K27M expression and observed an increase in mitotic abnormalities. We also found enhanced interaction of DNA replication factors with H3.3K27M during mitosis, indicating replication defects. Further functional analyses revealed increased genomic instability upon replication stress, as represented by mitotic bulky and ultrafine DNA bridges. This co-occurred with suboptimal 53BP1 nuclear body formation after mitosis in vitro, and in human glioma. Finally, we observed a decrease in ultrafine DNA bridges following deletion of the K27M mutant H3F3A allele in primary high-grade glioma cells. Together, our data uncover a role for H3.3 in DNA replication under stress conditions that is altered by the K27M mutation, promoting genomic instability and potentially glioma development.
Ploidy and recombination proficiency shape the evolutionary adaptation to constitutive DNA replication stress
Authors: Fumasoni Marco , Murray Andrew W.
Published: November 2021

In haploid budding yeast, evolutionary adaptation to constitutive DNA replication stress alters three genome maintenance modules: DNA replication, the DNA damage checkpoint, and sister chromatid cohesion. We asked how these trajectories depend on genomic features by comparing the adaptation in three strains: haploids, diploids, and recombination deficient haploids. In all three, adaptation happens within 1000 generations at rates that are correlated with the initial fitness defect of the ancestors. Mutations in individual genes are selected at different frequencies in populations with different genomic features, but the benefits these mutations confer are similar in the three strains, and combinations of these mutations reproduce the fitness gains of evolved populations. Despite the differences in the selected mutations, adaptation targets the same three functional modules in strains with different genomic features, revealing a common evolutionary response to constitutive DNA replication stress.
Signaling via the FLP-14/FRPR-19 neuropeptide pathway sustains nociceptive response to repeated noxious stimuli in C. elegans
Authors: Marques Filipe , Falquet Laurent , Vandewyer Elke , Beets Isabel , Glauser Dominique A.
Published: November 2021

In order to thrive in constantly changing environments, animals must adaptively respond to threatening events. Noxious stimuli are not only processed according to their absolute intensity, but also to their context. Adaptation processes can cause animals to habituate at different rates and degrees in response to permanent or repeated stimuli. Here, we used a forward genetic approach in Caenorhabditis elegans to identify a neuropeptidergic pathway, essential to prevent fast habituation and maintain robust withdrawal responses to repeated noxious stimuli. This pathway involves the FRPR-19A and FRPR-19B G-protein coupled receptor isoforms produced from the frpr-19 gene by alternative splicing. Loss or overexpression of each or both isoforms can impair withdrawal responses caused by the optogenetic activation of the polymodal FLP nociceptor neuron. Furthermore, we identified FLP-8 and FLP-14 as FRPR-19 ligands in vitro. flp-14, but not flp-8, was essential to promote withdrawal response and is part of the same genetic pathway as frpr-19 in vivo. Expression and cell-specific rescue analyses suggest that FRPR-19 acts both in the FLP nociceptive neurons and downstream interneurons, whereas FLP-14 acts from interneurons. Importantly, genetic impairment of the FLP-14/FRPR-19 pathway accelerated the habituation to repeated FLP-specific optogenetic activation, as well as to repeated noxious heat and harsh touch stimuli. Collectively, our data suggest that well-adjusted neuromodulation via the FLP-14/FRPR-19 pathway contributes to promote nociceptive signals in C. elegans and counteracts habituation processes that otherwise tend to rapidly reduce aversive responses to repeated noxious stimuli.
The effects of introgression across thousands of quantitative traits revealed by gene expression in wild tomatoes
Authors: Hibbins Mark S. , Hahn Matthew W.
Published: November 2021

It is now understood that introgression can serve as powerful evolutionary force, providing genetic variation that can shape the course of trait evolution. Introgression also induces a shared evolutionary history that is not captured by the species phylogeny, potentially complicating evolutionary analyses that use a species tree. Such analyses are often carried out on gene expression data across species, where the measurement of thousands of trait values allows for powerful inferences while controlling for shared phylogeny. Here, we present a Brownian motion model for quantitative trait evolution under the multispecies network coalescent framework, demonstrating that introgression can generate apparently convergent patterns of evolution when averaged across thousands of quantitative traits. We test our theoretical predictions using whole-transcriptome expression data from ovules in the wild tomato genusSolanum. Examining two sub-clades that both have evidence for post-speciation introgression, but that differ substantially in its magnitude, we find patterns of evolution that are consistent with histories of introgression in both the sign and magnitude of ovule gene expression. Additionally, in the sub-clade with a higher rate of introgression, we observe a correlation between local gene tree topology and expression similarity, implicating a role for introgressedcis-regulatory variation in generating these broad-scale patterns. Our results reveal a general role for introgression in shaping patterns of variation across many thousands of quantitative traits, and provide a framework for testing for these effects using simple model-informed predictions.
Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle
Authors: Bengtsen Mads , Winje Ivan Myhre , Eftestøl Einar , Landskron Johannes , Sun Chengyi , Nygård Kamilla , Domanska Diana , Millay Douglas P. , Meza-Zepeda Leonardo A. , Gundersen Kristian
Published: November 2021

Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.
Health literacy and associated factors among undergraduates: A university-based cross-sectional study in Nepal
Authors: Bhusal Sandesh , Paudel Rajan , Gaihre Milan , Paudel Kiran , Adhikari Tara Ballav , Pradhan Pranil Man Singh
Published: November 2021

Health literacy is one of the most critical aspects of health promotion. Limited health literacy is also accounted for adverse health outcomes and a huge financial burden on society. However, a gap exists in the level of health literacy, especially among undergraduates. This study aimed to assess the levels of health literacy and its socio-demographic determinants among undergraduate students of Tribhuvan University, Nepal. A web-based cross-sectional survey was conducted among 469 undergraduate students from five institutes of Tribhuvan University, Nepal. The 16-item short version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16) was used to measure students’ health literacy levels. Associated factors were examined using Chi-square tests followed by multivariate logistic regression analyses at the level of significance of 0.05. Nearly 61% of students were found to have limited health literacy (24.5% had “inadequate” and 36.3% had “problematic” health literacy). Female students (aOR = 1.6, 95% CI: 1.1–2.5), students from non-health related majors (aOR = 1.9, 95% CI: 1.2–3.0), students with unsatisfactory health status (aOR = 2.8, 95% CI: 1.7–4.5), students with poor financial status (aOR = 2.9, 95% CI: 1.2–6.8) and students with low self-esteem (aOR = 2.5, 95% CI: 1.5–4.1) were significantly more likely to have limited health literacy. The majority of the undergraduates were found to have limited health literacy. Gender, sector of study, self-rated health status, self-rated financial status, and self-esteem were significantly associated with limited health literacy. This study indicates university students should not be assumed to be health-literate and interventions to improve students’ health literacy especially for those whose majors are not health-related should be implemented. Further studies using a longer version of the health literacy survey questionnaire and qualitative methods to explore more on determinants of health literacy are recommended.
Evaluation of GeneXpert vanA/vanB in the early diagnosis of vancomycin-resistant enterococci infection
Authors: Li Zhuo-Lei , Luo Qi-Bing , Xiao Shan-Shan , Lin Ze-Hong , Liu Ye-Ling , Han Meng-Yi , Zhong Jing-Hua , Ji Tian-Xing , Guo Xu-Guang
Published: November 2021

Purpose

Vancomycin-resistant enterococci infection is a worrying worldwide clinical problem. To evaluate the accuracy of GeneXpert vanA/vanB in the diagnosis of VRE, we conducted a systematic review in the study.

Methods

Experimental data were extracted from publications until May 03 2021 related to the diagnostic accuracy of GeneXpert vanA/vanB for VRE in PubMed, Embase, Web of Science and the Cochrane Library. The accuracy of GeneXpert vanA/vanB for VRE was evaluated using summary receiver to operate characteristic curve, pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio.

Results

8 publications were divided into 3 groups according to two golden standard references, vanA and vanB group, vanA group, vanB group, including 6 researches, 5 researches and 5 researches, respectively. The pooled sensitivity and specificity of group vanA and vanB were 0.96 (95% CI, 0.93–0.98) and 0.90 (95% CI, 0.88–0.91) respectively. The DOR was 440.77 (95% CI, 37.92–5123.55). The pooled sensitivity and specificity of group vanA were 0.86 (95% CI, 0.81–0.90) and 0.99 (95% CI, 0.99–0.99) respectively, and those of group vanB were 0.85 (95% CI, 0.63–0.97) and 0.82 (95% CI, 0.80–0.83) respectively.

Conclusion

GeneXpert vanA/vanB can diagnose VRE with high-accuracy and shows greater accuracy in diagnosing vanA.
Return of individual research results from genomic research: A systematic review of stakeholder perspectives
Authors: Vears Danya F. , Minion Joel T. , Roberts Stephanie J. , Cummings James , Machirori Mavis , Blell Mwenza , Budin-Ljøsne Isabelle , Cowley Lorraine , Dyke Stephanie O. M. , Gaff Clara , Green Robert , Hall Alison , Johns Amber L. , Knoppers Bartha M. , Mulrine Stephanie , Patch Christine , Winkler Eva , Murtagh Madeleine J.
Published: November 2021

Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders’ perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants.
New insights into the Upper Palaeolithic of the Caucasus through the study of personal ornaments. Teeth and bones pendants from Satsurblia and Dzudzuana caves (Imereti, Georgia)
Authors: Tejero José-Miguel , Bar-Oz Guy , Bar-Yosef Ofer , Meshveliani Tengiz , Jakeli Nino , Matskevich Zinovi , Pinhasi Ron , Belfer-Cohen Anna
Published: November 2021

The region of western Georgia (Imereti) in the Southern Caucasus has been a major geographic corridor for human migrations during the Middle and Upper Paleolithic. Data of recent research and excavations in this region display its importance as a possible route for the dispersal of anatomically modern humans (AMH) into northern Eurasia. Nevertheless, within the local research context, bone-working and personal ornaments have yet contributed but little to the Upper Palaeolithic (UP) regional sequence’s characterization. Here we present an archaeozoological, technological and use-wear study of pendants from two local UP assemblages, originating in the Dzudzuana Cave and Satsurblia Cave. The ornaments were made mostly of perforated teeth, though some specimens were made on bone. Both the manufacturing marks made during preparation and use-wear traces indicate that they were personal ornaments, used as pendants or attached to garments. Detailed comparison between ornament assemblages from northern and southern Caucasus reveal that they are quite similar, supporting the observation of cultural bonds between the two regions, demonstrated previously through lithic techno-typological affinities. Furthermore, our study highlights the importance attributed to red deer (Cervus elaphus) by the UP societies of the Caucasus in sharing aesthetic values and/or a symbolic sphere.
Development of a real-time PCR assay to detect the single nucleotide polymorphism causing Warmblood Fragile Foal Syndrome
Authors: Flanagan Sharon , Rowe Áine , Duggan Vivienne , Markle Erin , O’Brien Maureen , Barry Gerald
Published: November 2021

Warmblood Fragile Foal syndrome (WFFS) is an autosomal recessive condition that affects the maturation of collagen in affected foals. Foals affected with the disease typically die or are euthanised shortly after birth. WFFS is caused by a single nucleotide change at position 2032 of the equine PLOD1 gene, causing an impairment of the wild-type enzyme. A commercial test for the causative genetic mutation is currently available from companies operating under licence from Cornell University but it has limitations. This test requires amplification of a region of the PLOD1 gene encompassing the site of interest, followed by Sanger sequencing of that region and computational analysis. We describe here the development of an alternative, real-time PCR based assay that rapidly and reliably differentiates between the wild-type and WFFS associated nucleotides without the need for sequencing, thus increasing the potential for high throughput analysis of large numbers of samples in a cost-effective manner.
Unbiased high-content screening reveals Aβ- and tau-independent synaptotoxic activities in human brain homogenates from Alzheimer’s patients and high-pathology controls
Authors: Jiang Hao , Esparza Thomas J. , Kummer Terrance T. , Brody David L.
Published: November 2021

Alzheimer’s disease (AD) is tightly correlated with synapse loss in vulnerable brain regions. It is assumed that specific molecular entities such as Aβ and tau cause synapse loss in AD, yet unbiased screens for synaptotoxic activities have not been performed. Here, we performed size exclusion chromatography on soluble human brain homogenates from AD cases, high pathology non-demented controls, and low pathology age-matched controls using our novel high content primary cultured neuron-based screening assay. Both presynaptic and postsynaptic toxicities were elevated in homogenates from AD cases and high pathology non-demented controls to a similar extent, with more modest synaptotoxic activities in homogenates from low pathology normal controls. Surprisingly, synaptotoxic activities were found in size fractions peaking between the 17–44 kDa size standards that did not match well with Aβ and tau immunoreactive species in these homogenates. The fractions containing previously identified high molecular weight soluble amyloid beta aggregates/”oligomers” were non-toxic in this assay. Furthermore, immunodepletion of Aβ and tau did not reduce synaptotoxic activity. This result contrasts with previous findings involving the same methods applied to 3xTg-AD mouse brain extracts. The nature of the synaptotoxic species has not been identified. Overall, our data indicates one or more potential Aβ and tau independent synaptotoxic activities in human AD brain homogenates. This result aligns well with the key role of synaptic loss in the early cognitive decline and may provide new insight into AD pathophysiology.
Birth-related retinal hemorrhages: The Soonchunhyang University Cheonan Hospital universal newborn eye screening (SUCH-NES) study
Authors: Cho In Hwan , Kim Min Seong , Heo Nam Hun , Kim So Young
Published: November 2021

Purpose

To report the prevalence, related factors, and characteristics of birth-related retinal hemorrhages (RHs) according to their severity in healthy newborns using a telemedicine network and wide-field digital retinal imaging (WFDRI).

Methods

Newborns who underwent WFDRI at 61 obstetrics/gynecology hospitals between January 2017 and December 2019 were enrolled. Demographics and related factors were compared among newborns with and without RHs. The newborns’ eyes were divided into the minimal, mild, moderate, and severe groups according to the number of RHs, and characteristics like bilaterality, laterality, involved retinal layer, involved zone, macular and/or optic nerve (ON) involvement were compared.

Results

Among 56247 newborns, 13026 had birth-related RHs (23.2%). Normal spontaneous vaginal delivery (NSVD) showed the highest association with RHs (odds ratio, 19.774; 95% confidence interval, 18.277–21.393; P < 0.001) on multivariate analysis. Bilateral RHs (8414/13026; 64.59%) were more common than unilateral RHs (4612/13026; 35.41%); however, unilateral RHs (2383/4217; 56.51%) were more common than bilateral RHs (1834/4217; 43.49%) in the minimal group. RHs showed no laterality differences between the two eyes (P = 0.493). Most RHs were intraretinal (18678/21440; 87.12%), and 2328 (31.65%) eyes with preretinal hemorrhage were observed in the severe group. Zone I RHs were common in the minimal (7072/7090; 99.75%), mild (4953/4960; 99.86%), and moderate (2013/2035; 98.92%) groups; zone I and II RHs were common in the severe group (4843/7355; 65.85%); and RHs in zone III were rare (7/21440; 0.03%). Most RHs showed no macular and/or ON involvement in the minimal and mild group; however, this was common in the severe group (7111/7355; 96.68%).

Conclusions

Birth-related RHs were common in healthy newborns and were significantly associated with NSVD. RHs were usually bilateral, intraretinal, and distributed posterior to the retina, but severe RHs had unique characteristics. Future long-term and longitudinal studies are required to elucidate the prognosis of severe RHs.
Down in the pond: Isolation and characterization of a new Serratia marcescens strain (LVF3) from the surface water near frog’s lettuce (Groenlandia densa)
Authors: Friedrich Ines , Bodenberger Bernhard , Neubauer Hannes , Hertel Robert , Daniel Rolf
Published: November 2021

Serratia marcescensis a species that belongs to the family ofYersiniaceae. This family comprises taxa representing opportunistic human- and phytopathogens but also plant growth-promoting rhizobacteria (PGPR). This study describes a novel Gram-negative strain (LVF3R) of the speciesSerratia marcescens. The strain was characterized genomically, morphologically, and physiologically. In addition, the potential of the isolate to act as a host strain to assess the diversity ofSerratiaassociated phages in environmental samples was explored. Average nucleotide identity analysis revealed that LVF3Rbelongs to the speciesSerratia marcescens.In silicoanalysis and ProphageSeq data resulted in the identification of one prophage, which is capable of viral particle formation. Electron microscopy showed cells of a rod-shaped, flagellated morphotype. The cells revealed a length and width of 1–1.6 μm and 0.8 μm, respectively. LVF3Rshowed optimal growth at 30 C and in the presence of up to 2% (w/v) NaCl. It exhibited resistances to ampicillin, erythromycin, oxacillin, oxytetracycline, rifampicin, tetracycline, and vancomycin. Genome data indicate that strainS.marcescensLVF3Ris a potential PGPR strain. It harbors genes coding for indole acetic acid(IAA) biosynthesis, siderophore production, plant polymer degradation enzymes, acetoin synthesis, flagellar proteins, type IV secretion system, chemotaxis, phosphorous solubilization, and biofilm formation.
Genomic regions associated with physiological, biochemical and yield-related responses under water deficit in diploid potato at the tuber initiation stage revealed by GWAS
Authors: Díaz Paula , Sarmiento Felipe , Mathew Boby , Ballvora Agim , Mosquera Vásquez Teresa
Published: November 2021

Water deficit, which is increasing with climate change, is a serious threat to agricultural sustainability worldwide. Dissection of the genetic architecture of water deficit responses is highly desirable for developing water-deficit tolerant potato cultivars and enhancing the resilience of existing cultivars. This study examined genetic variation in response to water deficit in a panel of diploid potato and identified the QTL governing this trait via a genome-wide association study (GWAS). A panel of 104 diploid potato accessions were evaluated under both well-watered and water deficit treatments at tuber initiation stage. Drought stress index (DTI) was calculated to assess tolerance of the diploid potato genotypes to water deficit. The GWAS was conducted using a matrix of 47K single nucleotide polymorphisms (SNP), recently available for this population. We are reporting 38 QTL, seven for well-watered conditions, twenty-two for water deficit conditions and nine for DTI which explain between 12.6% and 44.1% of the phenotypic variance. A set of 6 QTL were found to be associated with more than one variable. Marker WDP-9.21 was found associated with tuber fresh weigh under WD and gene annotation analysis revealed co-localization with theGlucan/water dikinase(GWD) gene. Of the nine QTL detected from DTI on chromosomes 2,3,5,8,10 and 12, three candidate genes with a feasible role in water deficit response were identified. The findings of this study can be used in marker-assisted selection (MAS) for water- deficit tolerance breeding in potato.
Species-specific quantification of circulating ebolavirus burden using VP40-derived peptide variants
Authors: Shu Qingbo , Kenny Tara , Fan Jia , Lyon Christopher J. , Cazares Lisa H. , Hu Tony Y.
Published: November 2021

Six ebolavirus species are reported to date, including human pathogens Bundibugyo virus (BDBV), Ebola virus (EBOV), Sudan virus (SUDV), and Taï Forest virus (TAFV); non-human pathogen Reston virus (RESTV); and the plausible Bombali virus (BOMV). Since there are differences in the disease severity caused by different species, species identification and viral burden quantification are critical for treating infected patients timely and effectively. Here we developed an immunoprecipitation-coupled mass spectrometry (IP-MS) assay for VP40 antigen detection and quantification. We carefully selected two regions of VP40, designated as peptide 8 and peptide12 from the protein sequence that showed minor variations among Ebolavirus species through MS analysis of tryptic peptides and antigenicity prediction based on available bioinformatic tools, and generated high-quality capture antibodies pan-specific for these variant peptides. We applied this assay to human plasma spiked with recombinant VP40 protein from EBOV, SUDV, and BDBV and virus-like particles (VLP), as well as EBOV infected NHP plasma. Sequence substitutions between EBOV and SUDV, the two species with highest lethality, produced affinity variations of 2.6-fold for p8 and 19-fold for p12. The proposed IP-MS assay differentiates four of the six known EBV species in one assay, through a combination of p8 and p12 data. The IP-MS assay limit of detection (LOD) using multiple reaction monitoring (MRM) as signal readout was determined to be 28 ng/mL and 7 ng/mL for EBOV and SUDV respectively, equivalent to ~1.625–6.5×105 Geq/mL, and comparable to the LOD of lateral flow immunoassays currently used for Ebola surveillance. The two peptides of the IP-MS assay were also identified by their tandem MS spectra using a miniature MALDI-TOF MS instrument, greatly increasing the feasibility of high specificity assay in a decentralized laboratory.
The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo
Authors: Flores-Garcia Yevel , Wang Lawrence T. , Park Minah , Asady Beejan , Idris Azza H. , Kisalu Neville K. , Muñoz Christian , Pereira Lais S. , Francica Joseph R. , Seder Robert A. , Zavala Fidel
Published: November 2021

Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria.
ΔNp63α promotes Epstein-Barr virus latency in undifferentiated epithelial cells
Authors: Van Sciver Nicholas , Ohashi Makoto , Nawandar Dhananjay M. , Pauly Nicholas P. , Lee Denis , Makielski Kathleen R. , Bristol Jillian A. , Tsao Sai Wah , Lambert Paul F. , Johannsen Eric C. , Kenney Shannon C.
Published: November 2021

Epstein-Barr virus (EBV) is a human herpesvirus that causes infectious mononucleosis and contributes to both B-cell and epithelial-cell malignancies. EBV-infected epithelial cell tumors, including nasopharyngeal carcinoma (NPC), are largely composed of latently infected cells, but the mechanism(s) maintaining viral latency are poorly understood. Expression of the EBV BZLF1 (Z) and BRLF1 (R) encoded immediate-early (IE) proteins induces lytic infection, and these IE proteins activate each other’s promoters. ΔNp63α (a p53 family member) is required for proliferation and survival of basal epithelial cells and is over-expressed in NPC tumors. Here we show that ΔNp63α promotes EBV latency by inhibiting activation of the BZLF1 IE promoter (Zp). Furthermore, we find that another p63 gene splice variant, TAp63α, which is expressed in some Burkitt and diffuse large B cell lymphomas, also represses EBV lytic reactivation. We demonstrate that ΔNp63α inhibits the Z promoter indirectly by preventing the ability of other transcription factors, including the viral IE R protein and the cellular KLF4 protein, to activate Zp. Mechanistically, we show that ΔNp63α promotes viral latency in undifferentiated epithelial cells both by enhancing expression of a known Zp repressor protein, c-myc, and by decreasing cellular p38 kinase activity. Furthermore, we find that the ability of cis-platinum chemotherapy to degrade ΔNp63α contributes to the lytic-inducing effect of this agent in EBV-infected epithelial cells. Together these findings demonstrate that the loss of ΔNp63α expression, in conjunction with enhanced expression of differentiation-dependent transcription factors such as BLIMP1 and KLF4, induces lytic EBV reactivation during normal epithelial cell differentiation. Conversely, expression of ΔNp63α in undifferentiated nasopharyngeal carcinoma cells and TAp63α in Burkitt lymphoma promotes EBV latency in these malignancies.
Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption
Authors: Ren Wenlin , Lan Jun , Ju Xiaohui , Gong Mingli , Long Quanxin , Zhu Zihui , Yu Yanying , Wu Jianping , Zhong Jin , Zhang Rong , Fan Shilong , Zhong Guocai , Huang Ailong , Wang Xinquan , Ding Qiang
Published: November 2021

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike protein. However, the functional properties of these “Cluster 5” mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs ofMustelaspecies without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution inMustelaspecies and other susceptible hosts in order to prevent future outbreaks.
Suppression of inflammatory arthritis by the parasitic worm product ES-62 is associated with epigenetic changes in synovial fibroblasts
Authors: Corbet Marlene , Pineda Miguel A. , Yang Kun , Tarafdar Anuradha , McGrath Sarah , Nakagawa Rinako , Lumb Felicity E. , Suckling Colin J. , Harnett William , Harnett Margaret M.
Published: November 2021

ES-62 is the major secreted protein of the parasitic filarial nematode, Acanthocheilonema viteae. The molecule exists as a large tetramer (MW, ~240kD), which possesses immunomodulatory properties by virtue of multiple phosphorylcholine (PC) moieties attached to N-type glycans. By suppressing inflammatory immune responses, ES-62 can prevent disease development in certain mouse models of allergic and autoimmune conditions, including joint pathology in collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). Such protection is associated with functional suppression of “pathogenic” hyper-responsive synovial fibroblasts (SFs), which exhibit an aggressive inflammatory and bone-damaging phenotype induced by their epigenetic rewiring in response to the inflammatory microenvironment of the arthritic joint. Critically, exposure to ES-62 in vivo induces a stably-imprinted CIA-SF phenotype that exhibits functional responses more typical of healthy, Naïve-SFs. Consistent with this, ES-62 “rewiring” of SFs away from the hyper-responsive phenotype is associated with suppression of ERK activation, STAT3 activation and miR-155 upregulation, signals widely associated with SF pathogenesis. Surprisingly however, DNA methylome analysis of Naïve-, CIA- and ES-62-CIA-SF cohorts reveals that rather than simply preventing pathogenic rewiring of SFs, ES-62 induces further changes in DNA methylation under the inflammatory conditions pertaining in the inflamed joint, including targeting genes associated with ciliogenesis, to programme a novel “resolving” CIA-SF phenotype. In addition to introducing a previously unsuspected aspect of ES-62’s mechanism of action, such unique behaviour signposts the potential for developing DNA methylation signatures predictive of pathogenesis and its resolution and hence, candidate mechanisms by which novel therapeutic interventions could prevent SFs from perpetuating joint inflammation and destruction in RA. Pertinent to these translational aspects of ES-62-behavior, small molecule analogues (SMAs) based on ES-62’s active PC-moieties mimic the rewiring of SFs as well as the protection against joint disease in CIA afforded by the parasitic worm product.
COGNITIVE PERFORMANCE DOES NOT LIMIT PHYSICAL ACTIVITY PARTICIPATION IN THE LIFESTYLE INTERVENTIONS AND INDEPENDENCE FOR ELDERS PILOT STUDY (LIFE-P)
Authors: Reid K.F. , Walkup M.P. , Katula J.A. , Sink K.M. , Anton, S. , Axtell R. , Kerwin, D.R. , King, A.C. , Kramer, A.F. , Miller M.E. , Myers, V. , Rosano C. , Studenski S.A. , Lopez O.L. , Verghese J. , Fielding R.A. , Williamson J.
Published: November 2021

Objectives: We examined whether multiple domains of baseline cognitive performance were associated with prospective physical activity (PA) adherence in the Lifestyle Interventions and Independence for Elders Pilot study (LIFE-P). Design, Setting, Participants: The LIFE-P study was a single-blind, multicenter, randomized controlled trial of a PA intervention compared to a successful aging educational intervention in sedentary, mobility-limited older adults. Intervention: A 12-month structured, moderate-intensity, multi-modal PA program that included walking, resistance training, and flexibility exercises. For the first 2 months (adoption), 3 center-based exercise sessions (40–60 min) / week were conducted. During the next 4 months (transition), center-based sessions were conducted 2 times / week. The subsequent maintenance phase consisted of optional once-to-twice-per-week center-based sessions and home-based PA. Measurements: Tests of executive and global cognitive functioning, working memory and psychomotor speed were administered at baseline. Median test scores were used to dichotomize participants into low or high cognitive performance groups. Results: 52 mobility-limited older adults (age: 76.9 ±5 yrs) were randomized to the PA arm of LIFE-P. Compared to participants with high cognitive performance, participants with low performance had similar PA adherence rates (all P ≥ 0.34). Furthermore, weak and non-significant univariate relationships were elicited between all measures of cognition and overall PA adherence levels (r values ranged: -0.20 to 0.12, P ≥ 0.12). Conclusion: These data suggest that cognitive performance does not limit long-term PA adherence in mobility-limited older adults. Additional studies in larger cohorts are warranted to verify these findings.
ANTIOXIDANTS IN THE DIET AND COGNITIVE FUNCTION: WHICH ROLE FOR THE MEDITERRANEAN LIFE-STYLE?
Authors: Vassalle C. , Sabatino L. , Pingitore A. , Chatzianagnostou K. , Mastorci F. , Ceravolo R.
Published: November 2021

This review aims to focus on main antioxidants- abundantly contained in the diet- as well as of the whole Mediterranean diet and life-style and their relationship with cognitive function, especially critical in two phases of life, in children until adolescence and oldness. The role of emerging biochemical and molecular biomarkers as opportunity to estimate more accurately nutritional assumption and requirement, in terms of cognitive preservation and disease risk, will be also discussed. The cluster of factors within the Mediterranean pattern -which include not only nutritional, but also physical, social, and stimulating aspects- is still largely understudied as a whole, but it is proposed as attractive research area and tool for public health planning of prevention and intervention.
ALBUMIN, HEMOGLOBIN, AND THE TRAJECTORY OF COGNITIVE FUNCTION IN COMMUNITY-DWELLING OLDER JAPANESE: A 13-YEAR LONGITUDINAL STUDY
Authors: Murayama H. , Shinkai S. , Nishi M. , Taniguchi Y. , Amano H. , Seino S. , Yokoyama Y. , Yoshida H. , Fujiwara Y. , Ito H.
Published: November 2021

Background: Cognitive function can substantially decline over a long period, and understanding the trajectory of cognitive function is important. However, little is known about the linkage between nutritional biomarkers and long-term cognitive change. Objectives: We analyzed 13-year longitudinal data for older Japanese to examine the associations of serum albumin and hemoglobin levels with the trajectory of cognitive function. Design: Longitudinal study. Setting: Community-based. Participants: A total of 1,744 community-dwelling adults aged 65 years or older who participated in annual health examinations in Kusatsu town, Gunma Prefecture, Japan, from 2002–2014. Measurements: Cognitive function was assessed annually by the Mini-Mental State Examination (MMSE). Albumin and hemoglobin levels at baseline (the year when a respondent first participated in the health examination) were divided into quartiles. Hierarchical linear modeling was used to analyze intrapersonal and interpersonal differences in cognitive function. Results: Participants’ MMSE scores decreased at an accelerated rate over the 13-year period. Participants with the lowest baseline albumin level (below the first quartile line) showed a greater accelerated decline in MMSE scores over time, compared with those with the highest level (above the third quartile line). Moreover, MMSE scores in participants with a lower hemoglobin level and lower MMSE score at baseline tended to decline faster over time at an accelerated rate. Conclusions: These findings yield new insights about the complex and diverse roles of these nutritional biomarkers on the trajectory of cognitive function in old age.