bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of the antibody-dependent respiratory burst assay for assessing protective immune responses to malaria
Authors: Mansourou Annick , Joos Charlotte , Niass Oumy , Diouf Babacar , Tall Adama , Perraut Ronald , Niang Makhtar , Toure-Balde Aissatou
Published: March 2022

The antibody-dependent respiratory burst (ADRB) assay is a sensitive isoluminol-based chemiluminescence (CL) functional assay designed to assess the capacity of opsonizing antibodies against merozoites to induce neutrophil respiratory burst. ADRB was shown to measure protective immunity against malaria in endemic areas, but the assay needed further improvement to ensure better sensitivity and reproducibility. Here, we adjusted parameters such as the freezing–thawing procedure of merozoites, merozoites's concentration and the buffer solution's pH, and we used the improved assay to measure ADRB activity of 207 sera from 97 and 110 individuals living, respectively, in Dielmo and Ndiop villages with differing malaria endemicity. The improvement led to increased CL intensity and assay sensitivity, and a higher reproducibility. In both areas, ADRB activity correlated with malaria endemicity and individual's age discriminated groups with and without clinical malaria episodes, and significantly correlated with
in vivo
clinical protection from
Plasmodium falciparum
malaria. Our results demonstrate that the improved ADRB assay can be valuably used to assess acquired immunity during monitoring by control programmes and/or clinical trials.
Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review
Authors: Jha Niraj Kumar , Chen Wei-Chih , Kumar Sanjay , Dubey Rajni , Tsai Lung-Wen , Kar Rohan , Jha Saurabh Kumar , Gupta Piyush Kumar , Sharma Ankur , Gundamaraju Rohit , Pant Kumud , Mani Shalini , Singh Sandeep Kumar , Maccioni Ricardo B. , Datta Tirtharaj , Singh Sachin Kumar , Gupta Gaurav , Prasher Parteek , Dua Kamal , Dey Abhijit , Sharma Charu , Mughal Yasir Hayat , Ruokolainen Janne , Kesari Kavindra Kumar , Ojha Shreesh
Published: March 2022

Developmental signalling pathways such as Wnt/β-catenin, Notch and Sonic hedgehog play a central role in nearly all the stages of neuronal development. The term ‘embryonic’ might appear to be a misnomer to several people because these pathways are functional during the early stages of embryonic development and adulthood, albeit to a certain degree. Therefore, any aberration in these pathways or their associated components may contribute towards a detrimental outcome in the form of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke. In the last decade, researchers have extensively studied these pathways to decipher disease-related interactions, which can be used as therapeutic targets to improve outcomes in patients with neurological abnormalities. However, a lot remains to be understood in this domain. Nevertheless, there is strong evidence supporting the fact that embryonic signalling is indeed a crucial mechanism as is manifested by its role in driving memory loss, motor impairments and many other processes after brain trauma. In this review, we explore the key roles of three embryonic pathways in modulating a range of homeostatic processes such as maintaining blood–brain barrier integrity, mitochondrial dynamics and neuroinflammation. In addition, we extensively investigated the effect of these pathways in driving the pathophysiology of a range of disorders such as Alzheimer's, Parkinson's and diabetic neuropathy. The concluding section of the review is dedicated to neurotherapeutics, wherein we identify and list a range of biological molecules and compounds that have shown enormous potential in improving prognosis in patients with these disorders.
Functional characterization of the human Cdk10/Cyclin Q complex
Authors: Düster Robert , Ji Yanlong , Pan Kuan-Ting , Urlaub Henning , Geyer Matthias
Published: March 2022

Cyclin-dependent kinases (CDKs) are key players in cell cycle regulation and transcription. The CDK-family member Cdk10 is important for neural development and can act as a tumour suppressor, but the underlying molecular mechanisms are largely unknown. Here, we provide an in-depth analysis of Cdk10 substrate specificity and function. Using recombinant Cdk10/CycQ protein complexes, we characterize RNA pol II CTD, c-MYC and RB1 as
in vitro
protein substrates. Using an analogue-sensitive mutant kinase, we identify 89 different Cdk10 phosphosites in HEK cells originating from 66 different proteins. Among these, proteins involved in cell cycle, translation, stress response, growth signalling, as well as rRNA, and mRNA transcriptional regulation, are found. Of a set of pan-selective CDK- and Cdk9-specific inhibitors tested, all inhibited Cdk10/CycQ at least five times weaker than their proposed target kinases. We also identify Cdk10 as an
in vitro
substrate of Cdk1 and Cdk5 at multiple sites, allowing for a potential cross-talk between these CDKs. With this functional characterization, Cdk10 adopts a hybrid position in both cell cycle and transcriptional regulation.
Rescued back from extinction in the wild: past, present and future of the genetics of the Arabian oryx in Oman
Authors: Al Rawahi Qais , Mijangos Jose Luis , Khatkar Mehar S. , Al Abri Mohammed A. , AlJahdhami Mansoor H. , Kaden Jennifer , Senn Helen , Brittain Katherine , Gongora Jaime
Published: March 2022

The Arabian oryx was the first species to be rescued from extinction in the wild by the concerted efforts of captive programmes in zoos and private collections around the world. Reintroduction efforts have used two main sources: the ‘World Herd’, established at the Phoenix Zoo, and private collections in Saudi Arabia. The breeding programme at the Al-Wusta Wildlife Reserve (WWR) in Oman has played a central role in the rescue of the oryx. Individuals from the ‘World Herd’ and the United Arab Emirates have been the main source for the WWR programme. However, no breeding strategies accounting for genetic diversity have been implemented. To address this, we investigated the diversity of the WWR population and historical samples using mitochondrial DNA (mtDNA) and single nucleotide polymorphisms (SNPs). We found individuals at WWR contain 58% of the total mtDNA diversity observed globally. Inference of ancestry and spatial patterns of SNP variation shows the presence of three ancestral sources and three different groups of individuals. Similar levels of diversity and low inbreeding were observed between groups. We identified individuals and groups that could most effectively contribute to maximizing genetic diversity. Our results will be valuable to guide breeding and reintroduction programmes at WWR.
Instant pH sensor based on the functionalized cellulose for detecting strong acid leaks
Authors: Jeong Hoseong , Jung Byung Jun , Kim Jae Hyun , Choi Seung-Ho , Lee Yoon Jung , Kim Kang Su
Published: March 2022

Acid spills cause large-scale environmental damage and casualties. To respond to such incidents, a sensor capable of detecting acid leaks is required. Cellulose is a useful substrate material for the fast detection of acid leaks because it has high hydrophilicity and porosity. On the other hand, methods of manufacturing cellulose-based sensors are still complicated or time-consuming. Thus, in this study, a simple and rapid synthesis method for a cellulose-based pH sensor was proposed. The functionalization of α-cellulose was achieved via chloroacetyl chloride, and Congo red was covalently immobilized to the functionalized cellulose for detecting strong acids. The manufacturing process was composed of two steps as above and finished within 8 h. The developed sensor exhibited absorbance changes in the pH range of 0.2 to 3.0, and response time was shorter than 1 s. A prototype system using this sensor was manufactured and tested, and it detected acid leaks easily and quickly.
Non-pharmaceutical intervention levels to reduce the COVID-19 attack ratio among children
Authors: David Jummy , Bragazzi Nicola Luigi , Scarabel Francesca , McCarthy Zachary , Wu Jianhong
Published: March 2022

The attack ratio in a subpopulation is defined as the total number of infections over the total number of individuals in this subpopulation. Using a methodology based on an age-stratified transmission dynamics model, we estimated the attack ratio of COVID-19 among children (individuals 0–11 years) when a large proportion of individuals eligible for vaccination (age 12 and above) are vaccinated to contain the epidemic among this subpopulation, or the
effective
herd immunity (with additional physical distancing measures). We describe the relationship between the attack ratio among children, the time to remove infected individuals from the transmission chain and the children-to-children daily contact rate while considering the increased transmissibility of virus variants (using the Delta variant as an example). We illustrate the generality and applicability of the methodology established by performing an analysis of the attack ratio of COVID-19 among children in the population of Canada and in its province of Ontario. The clinical attack ratio, defined as the number of symptomatic infections over the total population, can be informed from the attack ratio and both can be reduced substantially via a combination of reduced social mixing and rapid testing and isolation of the children.
Modulation theory for soliton resonance and Mach reflection
Authors: Ryskamp Samuel J. , Hoefer Mark A. , Biondini Gino
Published: March 2022

Resonant Y-shaped soliton solutions to the Kadomtsev–Petviashvili II (KPII) equation are modelled as shock solutions to an infinite family of modulation conservation laws. The fully two-dimensional soliton modulation equations, valid in the zero dispersion limit of the KPII equation, are demonstrated to reduce to a one-dimensional system. In this same limit, the rapid transition from the larger Y soliton stem to the two smaller legs limits to a travelling discontinuity. This discontinuity is a multivalued, weak solution satisfying modified Rankine–Hugoniot jump conditions for the one-dimensional modulation equations. These results are applied to analytically describe the dynamics of the Mach reflection problem, V-shaped initial conditions that correspond to a soliton incident upon an inward oblique corner. Modulation theory results show excellent agreement with direct KPII numerical simulation.
Targeted Sanger sequencing to recover key mutations in SARS-CoV-2 variant genome assemblies produced by next-generation sequencing
Authors: Singh Lavanya , San James E. , Tegally Houriiyah , Brzoska Pius M. , Anyaneji Ugochukwu J. , Wilkinson Eduan , Clark Lindsay , Giandhari Jennifer , Pillay Sureshnee , Lessells Richard J. , Martin Darren Patrick , Furtado Manohar , Kiran Anmol M. , de Oliveira Tulio
Published: March 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is adaptively evolving to ensure its persistence within human hosts. It is therefore necessary to continuously monitor the emergence and prevalence of novel variants that arise. Importantly, some mutations have been associated with both molecular diagnostic failures and reduced or abrogated next-generation sequencing (NGS) read coverage in some genomic regions. Such impacts are particularly problematic when they occur in genomic regions such as those that encode the spike (S) protein, which are crucial for identifying and tracking the prevalence and dissemination dynamics of concerning viral variants. Targeted Sanger sequencing presents a fast and cost-effective means to accurately extend the coverage of whole-genome sequences. We designed a custom set of primers to amplify a 401 bp segment of the receptor-binding domain (RBD) (between positions 22698 and 23098 relative to the Wuhan-Hu-1 reference). We then designed a Sanger sequencing wet-laboratory protocol. We applied the primer set and wet-laboratory protocol to sequence 222 samples that were missing positions with key mutations K417N, E484K, and N501Y due to poor coverage after NGS sequencing. Finally, we developed SeqPatcher, a Python-based computational tool to analyse the trace files yielded by Sanger sequencing to generate consensus sequences, or take preanalysed consensus sequences in fasta format, and merge them with their corresponding whole-genome assemblies. We successfully sequenced 153 samples of 222 (69 %) using Sanger sequencing and confirmed the occurrence of key beta variant mutations (K417N, E484K, N501Y) in the S genes of 142 of 153 (93 %) samples. Additionally, one sample had the Y508F mutation and four samples the S477N. Samples with RT-PCR C
t scores ranging from 13.85 to 37.47 (mean=25.70) could be Sanger sequenced efficiently. These results show that our method and pipeline can be used to improve the quality of whole-genome assemblies produced using NGS and can be used with any pairs of the most used NGS and Sanger sequencing platforms.
What have molecular simulations contributed to understanding of Gram-negative bacterial cell envelopes?
Authors: Khalid Syma , Schroeder Cyril , Bond Peter J. , Duncan Anna L.
Published: March 2022

Bacterial cell envelopes are compositionally complex and crowded and while highly dynamic in some areas, their molecular motion is very limited, to the point of being almost static in others. Therefore, it is no real surprise that studying them at high resolution across a range of temporal and spatial scales requires a number of different techniques. Details at atomistic to molecular scales for up to tens of microseconds are now within range for molecular dynamics simulations. Here we review how such simulations have contributed to our current understanding of the cell envelopes of Gram-negative bacteria.
Phytochemical profiles of Citrus hybrid
kanpei and Citrus reticulata natsumi :
Analysis of volatile and non-volatile components
Authors: Kim Sang Suk , Park Suk Man , Park YoSup , Joa Jae-Ho , Kim Misun , Yun Seok Kyu , Han Seung Gab
Published: March 2022

For analyzing the useful components in kanpei and
natsumi, volatile as well as non-volatile components were
analyzed using HPLC and GC/MS. Kanpei and
natsumi juices contain free sugars and organic acids which
are involved in imparting sweet and sour flavors. Analysis of the free sugar
content revealed that the sucrose content was 6.53±0.31 g/100 g and
7.36±0.28 g/100 g in kanpei and
natsumi, respectively. The content of citric acid, which is an
organic acid, in kanpei and natsumi was
0.99±0.04 g/100 g and 0.87±0.06 g/100g, respectively. The analysis
of 20 different free amino acids revealed that arginine was the most abundant at
65.27 mg/100 g and 38.09 mg/100 g, respectively. Essential amino acids contents
were 13.59 mg/100 g and 17.93 mg/100 g, accounting for 5.95% and 14.3% of the
total amino acids for kanpei and natsumi,
respectively. Narirutin and hesperidin were identified as the major flavonoids
in the juice and peel. Furthermore, nobiletin and tangeretin, which are present
only in citrus species, were identified in the peels. The analysis of volatile
components revealed that kanpei and natsumi
had a high content of limonene>γ-terpinene>linalool, while
natsumi was characterized by the abundance of
limonene>γ-terpinene>β-myrcene.
As a result of this study, many functional components were found in large
amounts in kanpei and natsumi. This result can
be used as cultivar characteristics evaluation.
Analyses of microbial community and quality characteristics of
nuruk
Authors: Park So-Young , Jeong Seok-Tae , Kim Chan Woo , Yun Sun-Il , Kang Ji-Eun , Kang Heui-Yun , Lim Bora
Published: March 2022

Nuruk is a traditional Korean fermentation starter containing
various microbes; it is utilized for the synthesis of alcoholic beverage. In
this study, the changes in the quality characteristics and microbial community
during the cultivation period of nuruk were analyzed. The
results indicated that the fungal richness, expressed as Chao 1, from 70.0 to
19.3 on day 10 and subsequently increased to 35.0 on day 30 of cultivation. The
content ratio of Aspergillus sp., Rhizopus sp.
and Saccharomycopsis sp. increased with the progress of
cultivation. Among the fungi, the content of the Aspergillus
genus increased from 0.01% before cultivation to 70.4 %. Among the bacteria, the
content of the Pantoea genus increased to 69.76% on day 7 and
decreased to 44.80% on day 14. Considering the enzyme activity, saccharogenic
power, α-amylase and carboxy peptidase exhibited the highest activity on
day 7 while lipase exhibited the highest activity on day 14. Considering only
the enzyme activity, the results indicated that it would be appropriate to
terminate cultivation before day 14. The traditional cultivation period of
nuruk is approximately 14 days; However, it is necessary to
determine a suitable cultivation period for the application of
nuruk as enzyme source.
Quality characteristics and antioxidant activity of onion vinegar
and black onion vinegar
Authors: Kim Mi Suk , Kim Ji Hyun , Gwon Geon Hyeong , Kim Nan Kyung , Lee Ah Young , Seo Weon Taek , Kim Hyun Young
Published: March 2022

In this study, we investigated the physicochemical characteristics and
antioxidant activity of fermented vinegar using onion and black onion. When the
onion and black onion were fermented in alcohol for 8 days, the alcohol content
in both onion vinegar (OV) and black onion vinegar (BV) increased, whereas their
sugar content decreased. The alcohol content was higher in OV than that in BV.
When the onion and black onion were fermented in acetic acid for 20 days, the pH
of both OV and BV decreased, whereas their total acidity increased. After
fermentation, the main free sugars of OV and BV were fructose and glucose, and
they were higher in BV than in OV. The major organic acids in OV and BV were
acetic acid and malic acid, and the content of acetic acid was higher in BV than
that in OV. In addition, OV and BV increased 1,1’-diphenyl-2-picrylhydrazyl
(DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid
(ABTS+) radical scavenging activities in a dose-dependent manner.
Furthermore, DPPH and ABTS+ radical scavenging activities were
greater in black onion juice than in onion juice. The BV showed a higher DPPH
and ABTS+ radical scavenging activities than OV. Therefore, BV is the
more suitable antioxidant functional vinegar through radical scavenging
activity.
Comparison of physicochemical properties and flavor content of
yuja (Citrus junos) powders prepared
by different homogenization and drying methods
Authors: Jung Seo A , Yoon Ji-young , Kim Jun Tae , Shin Gye Hwa
Published: March 2022

We prepared various types of yuja powders from
yuja juice, fruit, and seed (to maintain the unique
yuja flavor) by using different homogenization and drying
methods and investigated their physicochemical properties. To this end,
ultrasonic homogenization and high-pressure homogenization, were carried out to
obtain the yuja mixtures. These mixtures were subjected to via
spray-drying, freeze-drying, and microwave vacuum-drying to obtain spray-dried,
freeze-dried, and microwave vacuum-dried yuja powders,
respectively. The moisture content of the spray-dried yuja
powder was lower than that of the other two types: however, this powder had the
smallest particle size, with the average particle size ranging from 4.11
μm to 15.19 μm. The
freeze-dried and microwave vacuum-dried yuja powders exhibited
irregular amorphous structures, whereas the spray-dried yuja
powder exhibited a spherical shape, as revealed by scanning electron microscopy
analysis. Moreover, the maximum electron-donating ability indicated by the DPPH
test was 80% for the microwave vacuum-dried yuja powder, and
the maximum ABTS radical scavenging ability was 74% for the freeze-dried
yuja powder. The D-limonene content of the
yuja powders ranged from 4.67 μg/g
to 4.82 μg/g, with the maximum amount present in the
freeze-dried yuja powder treated by ultrasonic
homogenization.
Testing microbiome associations with censored survival outcomes at both the community and individual taxon levels
Authors: Hu Yingtian , Li Yunxiao , Satten Glen A. , Hu Yi-Juan
Published: March 2022

Background

Finding microbiome associations with possibly censored survival times is an important problem, especially as specific taxa could serve as biomarkers for disease prognosis or as targets for therapeutic interventions. The two existing methods for survival outcomes, MiRKAT-S and OMiSA, are restricted to testing associations at the community level and do not provide results at the individual taxon level. An ad hoc approach testing each taxon with a survival outcome using the Cox proportional hazard model may not perform well in the microbiome setting with sparse count data and small sample sizes.

Methods

We have previously developed the linear decomposition model (LDM) that unifies community-level and taxon-level tests into one framework. Here we extend the LDM to test survival outcomes. We propose to use the Martingale residuals or the deviance residuals obtained from the Cox model as continuous covariates in the LDM. We further construct tests that combine the results of analyzing each set of residuals separately. Finally, we extend PERMANOVA, the most commonly used distance-based method for testing community-level hypotheses, to handle survival outcomes in a similar manner.

Results

Using simulated data, we showed that the LDM-based tests preserved the false discovery rate for testing individual taxa and had good sensitivity. The LDM-based community-level tests and PERMANOVA-based tests had comparable or better power than MiRKAT-S and OMiSA. An analysis of data on the association of the gut microbiome and the time to acute graft-versus-host disease revealed several dozen associated taxa that would not have been achievable by any community-level test, as well as improved community-level tests by the LDM and PERMANOVA over those obtained using MiRKAT-S and OMiSA.

Availability and Implementation

The new methods described here have been added to our R packageLDM, which is available on GitHub athttps://github.com/yijuanhu/LDM.
Honeycomb crystallography: comb formation under geometric frustrations
Authors: Gharooni Fard Golnar , Jimenez Francisco Lopez , Peleg Orit
Published: March 2022

As honeybees build their nests in pre-existing tree cavities, they must deal with dealing with the presence of geometric constraints, resulting in non-regular hexagons and topological defects in the comb. In this work, we study how bees adapt to their environment in order to regulate the comb structure. Specifically, we identify the irregularities in honeycomb structure in the presence of various geometric frustrations. We 3D-print experimental frames with a variety of constraints imposed on the imprinted foundations. The combs constructed by the bees show clear evidence of reoccurring patterns built by bees in response to specific geometric frustrations on these starter frames. Furthermore, using an experimental-modeling framework, we demonstrate that these patterns can be successfully modeled and replicated through a simulated annealing process, in which the minimized potential is a variation of the Lennard-Jones potential that only considers first-neighbor interactions according to a Delaunay triangulation. Our simulation results not only confirm the connection between honeycomb structures and other crystal systems such as graphene, but also show that irregularities in the honeycomb structure can be explained as the result of local interactions between honeybees and their immediate surroundings, leading to emergent global order. Additionally, our computational model can be used to describe specific strategies that bees use to effectively solve each geometric mismatch problem while minimizing cost of comb building.
FGF10 triggers de novo alveologenesis in a BPD model: impact on the resident mesenchymal niche cells
Authors: Taghizadeh Sara , Chao Cho-Ming , Guenther Stefan , Glaser Lea , Gersmann Luisa , Michel Gabriela , Kraut Simone , Goth Kerstin , Koepke Janine , Heiner Monika , Vazquez-Armendariz Ana Ivonne , Herold Susanne , Samakovolis Christos , Weissmann Norbert , Ricci Francesca , Aquila Giorgio , Boyer Laurent , Ehrhardt Harald , Minoo Parviz , Bellusci Saverio , Rivetti Stefano
Published: March 2022

Bronchopulmonary dysplasia (BPD) is a neonatal lung disease developing in premature babies characterized by arrested alveologenesis and associated with decreased Fibroblast growth factor 10 (FGF10) expression. One-week hyperoxia (HYX) exposure of newborn mice leads to a permanent arrest in alveologenesis. To test the role of Fgf10 signaling to promote de novo alveologenesis following hyperoxia, we used transgenic mice allowing inducible expression of Fgf10 and recombinant FGF10 (rFGF10) protein delivered intraperitoneally. We carried out morphometry analysis, and IF on day 45. Alveolospheres assays were performed co-culturing AT2s from normoxia (NOX) with FACS-isolated Sca1Pos resident mesenchymal cells (rMC) from animals exposed to NOX, HYX+PBS, or HYX+FGF10. scRNAseq between rMC-Sca1Pos isolated from NOX and HYX+PBS were also carried out. Transgenic overexpression of Fgf10 and rFGF10 administration rescued the alveologenesis defects following HYX. Alveolosphere assays indicate that the activity of rMC-Sca1Pos is negatively impacted by HYX and partially rescued by rFGF10 treatment. Analysis by IF demonstrates a significant impact of rFGF10 on the activity of resident mesenchymal cells. scRNAseq results identified clusters expressing Fgf10, Fgf7, Pdgfra, and Axin2, which could represent the rMC niche cells for the AT2 stem cells. In conclusion, we demonstrate that rFGF10 administration is able to induce de-novo alveologenesis in a BPD mouse model and identified subpopulations of rMC-Sca1Pos niche cells potentially representing its cellular target.
Cellular redox metabolism is modulated by the distinct localization of cyclic nucleotide phosphodiesterase 5A isoforms
Authors: Cardarelli Silvia , Miele Adriana Erica , Campolo Federica , Massimi Mara , Mancini Patrizia , Biagioni Stefano , Naro Fabio , Giorgi Mauro , Saliola Michele
Published: March 2022

3’-5’ cyclic nucleotide phosphodiesterases (PDEs) are a family of evolutionary conserved cAMP and/or cGMP hydrolysing enzymes, components of transduction pathways regulating crucial aspects of cell life. Among them, cGMP-specific PDE5, being a regulator of vascular smooth muscle contraction, is the molecular target of several drugs used to treat erectile dysfunction and pulmonary hypertension.

Production of full-length murine PDE5A isoforms in the milk-yeast Kluyveromyces lactis showed that the quaternary assembly of MmPDE5A1 is a mixture of dimers and tetramers, while MmPDE5A2 and MmPDE5A3 only assembled as dimers. We showed that the N-terminal peptide is responsible for the tetramer assembly of MmPDE5A1, while that of MmPDE5A2 for its mitochondrial localization.

Overexpression of the three isoforms alters at different levels the cAMP/cGMP equilibrium as well as the NAD(P)+/NAD(P)H balance and induces a metabolic switch from oxidative to fermentative. In particular, the mitochondrial localization of MmPDE5A2 unveiled the existence of a cAMP-cGMP signaling cascade in this organelle, for which we propose a metabolic model that could explain the role of PDE5 in some cardiomyopathies and some of the side effects of its inhibitors.
Protein prediction models support widespread post-transcriptional regulation of protein abundance by interacting partners
Authors: Srivastava Himangi , Lippincott Michael J. , Currie Jordan , Canfield Robert , Lam Maggie P. Y. , Lau Edward
Published: March 2022

Protein and mRNA levels correlate only moderately. The availability of proteogenomics data sets with protein and transcript measurements from matching samples is providing new opportunities to assess the degree to which protein levels in a system can be predicted from mRNA information. Here we examined the contributions of input features in protein abundance prediction models. Using large proteogenomics data from 8 cancer types within the Clinical Proteomic Tumor Analysis Consortium (CPTAC) data set, we trained models to predict the abundance of over 13,000 proteins using matching transcriptome data from up to 958 tumor or normal adjacent tissue samples each, and compared predictive performances across algorithms, data set sizes, and input features. Over one-third of proteins (4,648) showed relatively poor predictability (elastic net r ≤ 0.3) from their cognate transcripts. Moreover, we found widespread occurrences where the abundance of a protein is considerably less well explained by its own cognate transcript level than that of one or more trans locus transcripts. The incorporation of additional trans-locus transcript abundance data as input features increasingly improved the ability to predict sample protein abundance. Transcripts that contribute to non-cognate protein abundance primarily involve those encoding known or predicted interaction partners of the protein of interest, including not only large multi-protein complexes as previously shown, but also small stable complexes in the proteome with only one or few stable interacting partners. Network analysis further shows a complex proteome-wide interdependency of protein abundance on the transcript levels of multiple interacting partners. The predictive model analysis here therefore supports that protein-protein interaction including in small protein complexes exert post-transcriptional influence on proteome compositions more broadly than previously recognized. Moreover, the results suggest mRNA and protein co-expression analysis may have utility for finding gene interactions and predicting expression changes in biological systems.
Contribution of Mendelian disorders in a population-based pediatric neurodegeneration cohort
Authors: Guo Rose , Mentch Frank D. , Li Dong , Will Erin E. , Ahrens-Nicklas Rebecca C. , Bhoj Elizabeth J.
Published: March 2022

Objectives

To evaluate Mendelian causes of neurodegenerative disorders in a cohort of pediatric patients as pediatric neurodegenerative disorders are a rare, diverse group of diseases. As molecular testing has advanced, many children can be diagnosed, but the relative contribution of various disorders is unclear.

Study Design

Patients enrolled in the Center for Applied Genomics (CAG) Biobank at the Children’s Hospital of Philadelphia with neurodegenerative symptoms were identified using an algorithm that consisted of including and excluding selected ICD9 and ICD10 codes. A manual chart review was then performed to abstract detailed clinical information.

Results

Out of approximately 100,000 patients enrolled in the CAG Biobank, 76 had a neurodegenerative phenotype. Following chart review, 7 patients were excluded. Of the remaining 69 patients, 42 had a genetic diagnosis (60.9%) and 27 were undiagnosed (39.1%). There were 32 unique disorders. Common diagnoses included Rett syndrome, mitochondrial disorders and neuronal ceroid lipofuscinoses.

Conclusions

The disorders encountered in our cohort demonstrate the diverse diseases and pathophysiology that contribute to pediatric neurodegeneration. Establishing a diagnosis often informed clinical management, although curative treatment options are lacking. Many patients who underwent genetic evaluation remained undiagnosed, highlighting the importance of continued research efforts in this field.
Defining the genes required for survival of Mycobacterium bovis in the bovine host offers novel insights into the genetic basis of survival of pathogenic mycobacteria
Authors: Gibson Amanda J , Stiens Jennifer , Passmore Ian J , Faulkner Valwynne , Miculob Josephous , Willcocks Sam , Coad Michael , Berg Stefan , Werling Dirk , Wren Brendan W , Nobeli Irene , Villarreal-Ramos Bernardo , Kendall Sharon L
Published: March 2022

Tuberculosis has severe impacts in both humans and animals. Understanding the genetic basis of survival of both Mycobacterium tuberculosis, the human adapted species, and Mycobacterium bovis, the animal adapted species is crucial to deciphering the biology of both pathogens. There are several studies that identify the genes required for survival of M. tuberculosis in vivo using mouse models, however, there are currently no studies probing the genetic basis of survival of M. bovis in vivo. In this study we utilise transposon insertion sequencing in M. bovis to determine the genes required for survival in cattle. We identify genes encoding established mycobacterial virulence functions such as the ESX-1 secretion system, PDIM synthesis, mycobactin synthesis and cholesterol catabolism that are required in vivo. We show that, as in M. tuberculosis, phoPR is required by M. bovis in vivo despite the known defect in signalling through this system. Comparison to studies performed in glycerol adapted species such as M. bovis BCG and M. tuberculosis suggests that there are differences in the requirement for genes involved in cholesterol import (mce4 operon), oxidation (hsd) and detoxification (cyp125). We report good correlation with existing mycobacterial virulence functions, but also find several novel virulence factors, including genes involved in protein mannosylation, aspartate metabolism and glycerol-phosphate metabolism. These findings further extend our knowledge of the genetic basis of survival in vivo in bacteria that cause tuberculosis and provide insight for the development of novel diagnostics and therapeutics.

Importance

This is the first report of the genetic requirements of an animal adapted member of the MTBC in a natural host. M. bovis has devastating impacts in cattle and bovine tuberculosis is a considerable economic, animal welfare and public health concern. The data highlight the importance of mycobacterial cholesterol catabolism and identifies several new virulence factors. Additionally, the work informs the development of novel differential diagnostics and therapeutics for TB in both human and animal populations.
Halophilic bacteria Bacillus altitudinis MIM2 producing bioactive melanin isolated from Mundra port, Kutch, Gujarat, India
Authors: Gordhanbhai Pankhaniya Mira , Jigna Chavda , Kurian Noble K
Published: March 2022

Melanins are ubiquitous black or brown color pigments exhibiting a wide variety of bioactivities. They are stable and insoluble in nature. Melanin are industrially important pigment currently used in cosmetics, medicine and pharmaceuticals, industries. Bacteria mainly produce three types of melanin namely, Eumelanin, pheomelanin and pyomelanin which is usually extracellularly secreted. This makes the downstream processing of bacterial melanin easier. Stress conditions like salt stress, radiation stress etc. triggers the bacteria to produce melanin and several bacterial species were found to produce melanin under different stress induced conditions. In this present study we had isolated melanin producing bacteria from saline sediment sample of Mundra port, Kutch region of Gujarat state of India. The melanin producing bacteria was characterized using staining, biochemical and molecular methods. The melanin produced was extracted and analyzed using physicochemical techniques. The extracted melanin had shown good anti-bacterial and radical scavenging activity. To our knowledge, this is the first report on Bacillus altitudinis producing melanin.
Graph deep learning reveals multiple signal pathways activated in anti-citrullinated protein antibodies stimulated synoviocytes
Authors: Sun Meng , Chen Yang , Brodin Petter , Catrina Anca I
Published: March 2022

We present a study of anti-citrullinated protein antibodies stimulated fibroblast-like synoviocytes from patients with rheumatoid arthritis, which is powered by a novel graph deep learning framework applied to single-cell mRNA expression data. This new analytical framework discovered dominant pathways that suggest IL1-IL1R mediated signaling, a novel signal transduction response to ACPA-stimulation, and comfirmed our previous finding of PI3K/AKT activation in response of ACPA-stimulation as well. The study demonstrated the capability of graph deep learning framework on signaling pathway analysis. The findings suggest that ACPAs contribute to distinct pathogenic events through activating multiple signaling pathways.
A Unique Cellular Organization of Human Distal Airways and Its Disarray in Chronic Obstructive Pulmonary Disease
Authors: Rustam Samir , Hu Yang , Mahjour Seyed Babak , Randell Scott H. , Rendeiro Andre F. , Ravichandran Hiranmayi , Urso Andreacarola , D’Ovidio Frank , Martinez Fernando J. , Richmond Bradley , Polosukhin Vasiliy , Kropski Jonathan A. , Blackwell Timothy S. , Elemento Olivier , Shaykhiev Renat
Published: March 2022

In the human lung, terminal bronchioles (TBs), the most distal conducting airways, open to respiratory bronchioles (RBs) that lead to the alveolar region where gas exchange takes place. This transition occurs in pulmonary lobules, lung tissue units supplied by pre-TBs, which give rise to TBs. Accumulating evidence suggests that remodeling and loss of pre-TBs and TBs underlies progressive airflow limitation in chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. Understanding the nature of these changes at the single-cell level has so far been limited by poor accessibility of pre-TBs and TBs. Here, we introduce a novel method of region-precise airway dissection, which enables capture of the entire anatomical continuum of peripheral airways, from pre-TBs to RBs, and the associated alveolar region within the lobule. This approach allowed us to identify terminal airway-enriched secretory cells (TASCs), a unique epithelial cell population of distal airways expressing secretoglobin 3A2 (SCGB3A2) and/or surfactant protein B (SFTPB). TASCs were enriched in TBs, particularly, in areas of TB-RB transition and exhibited an intermediate, broncho-alveolar molecular pattern. TASC frequency was markedly decreased in pre-TBs and TBs of COPD patients compared to those in non-diseased lungs, accompanied by changes in cellular composition of vascular and immune microenvironments. In vitro regeneration assays identified basal cells (BCs) of pre-TBs and TBs as a cellular origin of TASCs in the human lung. Generation of TASCs by these region-specific progenitors was suppressed by IFN-γ signaling that was augmented in distal airways of COPD patients. Thus, altered maintenance of region-specific cellular organization of pre-TBs and TBs represents a key component of distal airway pathology in COPD.
‘Merging of ventral fibers at adhesions drives the remodeling of cellular contractile systems in fibroblasts.’
Authors: Narasimhan Shwetha , Holmes William R. , Kaverina Irina
Published: March 2022

Ventral stress fibers (VSFs) are contractile actin fibers present in the ventral plane of the cell and existing in a dynamic attachment with cell-matrix focal adhesions. VSFs are critical in cellular mechanobiological functions such as traction force production, cell polarization, and migration. VSF within their intracellular network vary from short, thinner fibers that are randomly oriented to long, thick fibers that span along the whole long axis of a cell.De novoVSF formation was shown to occur by condensation from the cortical actin mesh or by crosslinking of other stress fiber subtypes (dorsal stress fibers and transverse arcs) at the cell front. However, formation of long VSFs that extend across the whole cell axis is not well understood. Here, we report a novel phenomenon of VSF merging in migratory fibroblast cells, which is guided by mechanical force balance and contributes to VSF alignment along the long cell axis. The mechanism of VSF merging involves two steps: connection of two ventral fibers by an emerging myosin II bridge at an intervening adhesion and intervening adhesion dissolution to form a cohesive, contractile VSF. Our data indicate that these two steps are interdependent, since under conditions where adhesion disassembly is slowed, formation of the myosin bridge is slowed as well. Cellular data and computational modeling show that the angle of contact between merging fibers decides successful merging, with angles closer to 180 yielding merging events and shallower angles leading to merge failure. Our data and modeling further show that merging increases the share of uniformly aligned long VSFs, which would contribute to directional traction force production. Thus, we thoroughly characterize merging as process for dynamic reorganization of VSFs in steady state, investigating the steps and variants of the process as well as its functional significance in migratory cells.
Dose-efficient multimodal microscopy of human tissue at a hard X-ray nanoprobe beamline
Authors: Sala Simone , Zhang Yuhe , De La Rosa Nathaly , Dreier Till , Kahnt Maik , Langer Max , Dahlin Lars B. , Bech Martin , Villanueva-Perez Pablo , Kalbfleisch Sebastian
Published: March 2022

X-ray fluorescence microscopy performed at nanofocusing synchrotron beamlines produces quantitative elemental distribution maps at unprecedented resolution (down to a few tens of nanometres), at the expense of relatively long measuring times and high absorbed doses. In this work, a method was implemented in which fast low-dose in-line holography was used to produce quantitative electron density maps at the mesoscale prior to nanoscale X-ray fluorescence acquisition. These maps ensure more efficient fluorescence scans and the reduction of the total absorbed dose, often relevant for radiation-sensitive (e.g. biological) samples. This multimodal microscopy approach was demonstrated on human sural nerve tissue. The two imaging modes provide complementary information at a comparable resolution, ultimately limited by the focal spot size. The experimental setup presented allows the user to swap between them in a flexible and reproducible fashion, as well as to easily adapt the scanning parameters during an experiment to fine-tune resolution and field of view.
Indigenous practices of accounting on the ground: a Bourdieusian perspective
Authors: Fukofuka Peni , Scobie Matthew , Finau Glenn
Published: March 2022

Purpose

This study explores accounting practice in an Indigenous organization. This organization is embedded within a rural Aboriginal community in the country currently known as Australia. In doing so, this study illustrates the intertwining of accounting practice, practitioners, organizations and social/cultural context, while recognizing that the cultural embeddedness of accounting is not uniform.

Design/methodology/approach

Empirical materials were collected as part of a qualitative field study with an Indigenous organization. Specific methods include interviews, informal conversations, documentary reviews and participant observations. These materials were analysed through a Bourdieusian perspective.

Findings

By working with Indigenous Peoples on the ground, rather than relying on secondary materials, this study highlights how the values of a community challenge and reorient accounting practice towards community aspirations. This study illustrates how fields beyond the organization influence accounting practice, including in budgeting and assurance.

Originality/value

Exploring Indigenous practices of accounting maintains Indigenous agency and opens up space for alternative understandings and practices of accounting. By illustrating how a community can influence the accounting practice of an organization, this study has implications for wider understandings of the cultural embeddedness of mainstream accounting and possible alternatives.
Vibration response analysis and hoop layout optimization of spatial pipeline under random excitation
Authors: Wang Donghai , Sun Wei , Gao Zhihui , Li Hui
Published: March 2022

Purpose

In many cases, the external pipelines of aero-engine are subjected to random excitation. The purpose of this paper is to reduce the vibration response of the pipeline system effectively by adjusting the hoop layout.

Design/methodology/approach

In this paper, a spatial pipeline supported by multi-hoops is taken as the object, the methods of solution of the vibration response of the pipeline system by using pseudo excitation and hoop layouts optimization with amplitude reduction of vibration response as the goal are presented. First, the finite element model of the spatial pipeline system is presented. Then, an optimization model spatial pipeline is established. Finally, a case study is carried out to prove the rationality of the random vibration response analysis of the pipeline system. Furthermore, the proposed optimization model and genetic algorithm are applied to optimize the hoop layout.

Findings

The results show that the maximum response variance after optimization is reduced by 32.8%, which proves the rationality of the developed hoop layout optimization method.

Originality/value

The pseudo excitation method is used to solve the vibration response of aero-engine pipeline system, and the optimization of the hoop layout for aero-engine spatial pipelines under random excitation to reduce random vibration response is studied systematically.
Inter-organizational relationships in agri-food sector: a bibliometric review and future directions
Authors: Vesperi Walter , Coppolino Raffaella
Published: March 2022

Purpose

The current competitive system, complex and rapidly changing, knowledge represents one of the main strategic resources for organizations. Agri-food organizations, traditionally characterized by low-knowledge management (KM) practices, are facing several challenges that require new knowledge to improve performance and their ability to survive. Since agri-food organizations are low-propensity R&D, they are forced into a collaborative approach and the creation of inter-organizational relationships (IORs) for knowledge transfer. The purpose of this study is to offer an overview of the academic literature on knowledge transfer within scientific institutions and agri-food organizations.

Design/methodology/approach

This study is based on a systematic literature review. In particular, two international and multidisciplinary databases (Scopus and WoS) were considered. Subsequently, the scientific documents were selected following the PRISMA guidelines. In addition, a scientific landscape visualization was created through VOSviewer software.

Findings

The study offers interesting reflections and suggestions on the management of inter-organizational relations in the agri-food sector. In particular, it highlights the importance of the “knowledge” resource in IORs. For this reason, IORs and KM represent a challenge for agri-food organizations.

Originality/value

The main limitation lies in its criteria for collecting and selecting articles. The study is based on the analysis of articles contained only in two scientific databases (Scopus and WoS) and refined by “Business, Management and Accounting”, “Social Sciences” and “Economics, Econometrics and Finance” areas.