bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion approximations in population genetics and the rate of Muller’s ratchet
Authors: Bräutigam Camila , Smerlak Matteo
Published: November 2021

The Wright-Fisher binomial model of allele frequency change is often approximated by a scaling limit in which selection, mutation and drift all decrease at the same 1/N rate. This construction restricts the applicability of the resulting “Wright-Fisher diffusion equation” to the weak selection, weak mutation regime of evolution. We argue that diffusion approximations of the Wright-Fisher model can be used more generally, for instance in cases where genetic drift is much weaker than selection. One important example of this regime is Muller’s ratchet phenomenon, whereby deleterious mutations slowly but irreversibly accumulate through rare stochastic fluctuations. Using a modified diffusion equation we derive improved analytical estimates for the mean click time of the ratchet.
Cryo-EM structure of the Smc5/6 holo-complex
Authors: Hallett Stephen T. , Harry Isabella Campbell , Schellenberger Pascale , Zhou Lihong , Cronin Nora B. , Baxter Jonathan , Etheridge Thomas J. , Murray Johanne M. , Oliver Antony W.
Published: November 2021

The Smc5/6 complex plays an essential role in the resolution of recombination intermediates formed during mitosis or meiosis, or as a result of the cellular response to replication stress. It also functions as a restriction factor preventing viral integration. Here, we report the cryo-EM structure of the six-subunit budding yeast Smc5/6 holo-complex, reconstituted from recombinant proteins expressed in insect cells – providing a full overview of the complex in its apo / non-liganded form, and revealing how the Nse1/3/4 subcomplex binds to the hetero-dimeric SMC protein core. In addition, we demonstrate that a region within the head domain of Smc5, equivalent to the ‘W-loop’ of Smc4 or ‘F-loop’ of Smc1, mediates an essential interaction with Nse1. Taken together, these data confirm a degree of functional equivalence between the structurally unrelated KITE and HAWK accessory subunits associated with SMC complexes.
Lipid droplets control mitogenic lipid mediator production in human cancer cells
Authors: Jarc Jovičić Eva , Pucer Janež Anja , Eichmann Thomas O. , Koren Špela , Brglez Vesna , Jordan Paul M. , Gerstmeier Jana , Lainšček Duško , Golob-Urbanc Anja , Jerala Roman , Lambeau Gérard , Werz Oliver , Zimmermann Robert , Petan Toni
Published: November 2021

Polyunsaturated fatty acids (PUFAs) are components of membrane phospholipids and precursors of bioactive lipid mediators. Here, we investigated the crosstalk of three pathways providing PUFAs for lipid mediator production: (i) secreted group X phospholipase A2(GX sPLA2) and (ii) cytosolic group IVA PLA2(cPLA2α), which both mobilize PUFAs from phospholipids, and (iii) adipose triglyceride lipase (ATGL), which breaks down triacylglycerols (TAGs) stored in lipid droplets (LDs). Combining lipidomic and functional analyses, we demonstrate that lipid mediator production depends on TAG turnover. GX sPLA2directs PUFAs into TAGs and ATGL is required for their entry into lipid mediator biosynthetic pathways. ATGL also promotes the incorporation of LD-derived PUFAs into phospholipids representing substrates for cPLA2α. Additionally, inhibition of TAG synthesis mediated by acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) reduces the levels of mitogenic lipid signals and compromises tumour growth. This study expands the paradigm of PLA2-driven lipid mediator signalling and identifies LDs as central lipid mediator production hubs.
In silico analysis and in planta production of recombinant ccl21/IL1β protein and characterization of its in vitro anti-tumor and immunogenic activity
Authors: Marashi Hasan , Beihaghi Maria , Khaksar Samad
Published: November 2021

CCL21 has an essential role in anti-tumor immune activity. Epitopes of IL1β have adjuvant activity without causing inflammatory responses. CCR7 and its ligands play a vital role in the immune balance; specifically, in transport of T lymphocytes and antigen-presenting cells such as dendritic cells to the lymph nodes. This study aimed to produce epitopes of CCL21 and IL1β as a recombinant protein and characterize it’s in vitro anti-tumor and immunogenic activity. A codon-optimized ccl21/IL1β gene was designed and synthesized from human genes. Stability and binding affinity of CCL21/IL1β protein and CCR7 receptor were examined through in silico analyses. The construct was introduced into N. tabacum to produce this recombinant protein and the structure and function of CCL21/IL1β were examined. Purified protein from transgenic leaves generated a strong signal in SDS PAGE and western blotting assays. FTIR measurement and MALDI-TOF/TOF mass spectrography showed that ccl21/IL-1β was correctly expressed in tobacco plants. Potential activity of purified CCL21/IL1β in stimulating the proliferation and migration of MCF7CCR7+ cancer cell line was investigated using the wound healing method. The results demonstrated a decrease in survival rate and metastasization of cancer cells in the presence of CCL21/IL1β, and IC50 of CCL21 on MCF7 cells was less than that of non-recombinant protein. Agarose assay on PBMCsCCR7+ showed that CCL21/IL1β has biological activity and there is a distinguishable difference between chemokinetic (CCL21) and chemotactic (FBS) movements. Overall, the results suggest that CCL21/IL1β could be considered an effective adjuvant in future in vivo and clinical tests.
Development of a novel glycoengineering platform for the rapid production of conjugate vaccines
Authors: Abouelhadid Sherif , Atkins Elizabeth , Kay Emily , Passmore Ian , North Simon J , Lehri Burhan , Hitchen Paul , Bakke Eirik , Rahman Mohammed , Bosse Janine , Li Yanwen , Terra Vanessa S. , Langford Paul , Dell Anne , Wren Brendan W , Cuccui Jon
Published: November 2021

Antimicrobial resistance (AMR) is threatening the lives of millions worldwide. Antibiotics which once saved countless lives, are now failing, ushering in vaccines development as a current global imperative. Conjugate vaccines produced either by chemical synthesis or biologically in Escherichia coli cells, have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccines assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel method that overcomes the limitations of the current conjugate vaccine design method(s). We demonstrate at least 2-fold increase in glycoconjugate yield via MAGIC when compared to conventional bioconjugate method(s). Furthermore, the modularity of the MAGIC platform also allowed us to perform glycoengineering in genetically intractable bacterial species other than E. coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against bacteria, especially AMR pathogens, and could be applied for biopreparedness.
Using crystallography tools to improve vaccine formulations
Authors: Fantini Márcia Carvalho de Abreu , Oliveira Cristiano Luis Pinto , Lopes José Luiz de Souza , Martins Tereza da Silva , Akamatsu Milena Apetito , Trezena Aryene Góes , Franco Milene Tino-De- , Botosso Viviane Fongaro , Sant'Anna Osvaldo Augusto Brazil Esteves , Kardjilov Nikolay , Rasmussen Martin Kjaerulf , Bordallo Heloísa Nunes
Published: November 2021

This article summarizes developments attained in oral vaccine formulations based on the encapsulation of antigen proteins inside porous silica matrices. These vaccine vehicles show great efficacy in protecting the proteins from the harsh acidic stomach medium, allowing the Peyer's patches in the small intestine to be reached and consequently enhancing immunity. Focusing on the pioneering research conducted at the Butantan Institute in Brazil, the optimization of the antigen encapsulation yield is reported, as well as their distribution inside the meso- and macroporous network of the porous silica. As the development of vaccines requires proper inclusion of antigens in the antibody cells, X-ray crystallography is one of the most commonly used techniques to unveil the structure of antibody-combining sites with protein antigens. Thus structural characterization and modelling of pure antigen structures, showing different dimensions, as well as their complexes, such as silica with encapsulated hepatitis B virus-like particles and diphtheria anatoxin, were performed using small-angle X-ray scattering, X-ray absorption spectroscopy, X-ray phase contrast tomography, and neutron and X-ray imaging. By combining crystallography with dynamic light scattering and transmission electron microscopy, a clearer picture of the proposed vaccine complexes is shown. Additionally, the stability of the immunogenic complex at different pH values and temperatures was checked and the efficacy of the proposed oral immunogenic complex was demonstrated. The latter was obtained by comparing the antibodies in mice with variable high and low antibody responses.
Designing and implementing performance measurement systems based on enterprise engineering guidelines
Authors: Moura Louisi Francis , Pinheiro de Lima Edson , Deschamps Fernando , Etzion Dror , Gouvea da Costa Sergio E.
Published: November 2021

Purpose

This conceptual paper presents a proposal for improving a performance measurement (PM) system implementation process based on enterprise engineering (EE) guidelines, which gives the process a sense of completeness.

Design/methodology/approach

This paper analyzes a well-known process for PM systems implementation organized in two phases: identifying, designing and implementing the top-level performance measures; and cascading the top-level measures and identify appropriate lower-level performance measures. The proposed improvements to the studied process derive from the EE guidelines, which establish a basis for the structure of an organizational management system, the formalization and synchronization of processes, performance expectations, exception handling and change management.

Findings

The study reveals that not all EE guidelines are covered by the analyzed process, with four of them having no evidence of being adopted: involvement of people in process design and implementation; ensuring interoperability between different systems in the information structure; addressing of all possible exceptions; coherence and consistency of semantics across all processes.

Originality/value

By the lens of EE guidelines, this paper advances a how-to-guide. This paper can support managers and researchers on PM system design and implementation, given the importance and relevance of EE recommendations having a consistent and well-structured procedure.
WOW, the make-up AR app is impressive: a comparative study between China and South Korea
Authors: Butt Asad , Ahmad Hassan , Muzaffar Asif , Ali Fayaz , Shafique Nouman
Published: November 2021

Purpose

Consumers today actively participate in online purchasing experiences. As a result, it is critical to comprehend the behavioral aspects of novel technology usage, such as augmented reality (AR). AR apps enable beauty companies to create and design more immersive experience services. This study aims to highlight consumers’ perspectives on their continued desire to use AR app services.

Design/methodology/approach

A comparative study between China and South Korea was conducted with sample sizes of 458 and 315, respectively. Smart PLS was used for analysis.

Findings

The findings suggest that AR apps influence innovative consumers in China and South Korea to be satisfied with and continue to use such services. Previous research on technology acceptance model, information system success, AR and artificial intelligence (AI)-context-specific variables supported the findings.

Practical implications

This study contributes to the development of AR apps for beauty brands, as such technology revolutionizes how beauty brands work and grow. As a result, AR apps can pave the way for brands to provide an immersive experience to their customers.

Originality/value

The current study contributes to AR and AI drivers in the context of beauty brands by using novel technologies such as AR. AR integration with AI-context-specific variables indicates that consumers in China and South Korea are innovative and accept such technologies when purchasing beauty products online.
Sustainability performance and social media: an explorative analysis
Authors: Russo Sarah , Schimperna Federico , Lombardi Rosa , Ruggiero Pasquale
Published: November 2021

Purpose

This paper aims to present a deep understanding of how social media affects organisations’ sustainability performance, using environmental, social and governance (ESG) factors. Particularly, this paper assumes the existence of a causal relationship between organisations’ sustainability performance and the use of their social media profile (i.e. Twitter).

Design/methodology/approach

The authors used a multivariate regression with an explorative approach. Using Thomson Reuters Eikon, the authors composed a sample of 115 public EU companies with a headquarter in Europe operating in the “energy” and “utilities” sectors. The authors collected ESG-related, financial and Twitter-related data covering the period 2016–2019.

Findings

The study findings emphasise the existence of a statistically significant and positive relationship between social media profiles (i.e. Twitter) and companies’ sustainability performance. Findings show that ESG-oriented companies use their Twitter profile more as a tool for achieving a higher level of legitimation rather than for managing their sustainability strategy and related performance. Therefore, social media contribute more to the construction of companies’ CSR identity than the management of analytic aspects of sustainability performance. The longevity of companies’ profiles is the variable mostly showing a causal relationship not only with the general measure of companies’ sustainability performance but also with its pillars and sub-pillars.

Originality/value

This research is original in showing academics, practitioners and policymakers results on the impact of different modalities of interaction (retweets, replies, likes and quotes) between organisations and stakeholders by using social media on sustainability performance.
Traders' perceptions of environmental quality as tools in improving public space: a study of markets in Ile-Ife, Nigeria
Authors: Taiwo Amos Oluwole , Fajoye Oluwafemi Samson
Published: November 2021

Purpose

The purpose of this paper is to provide insights into traders' perceptions of and responses to environmental quality in markets of Ile-Ife, Nigeria.

Design/methodology/approach

Primary data were collected from 445 traders in five different markets (Odo-Ogbe, Olorunsogo Oja-Ife, Bonfo and Urban day) in Ile-Ife through questionnaire administration. Physical observations were also carried out for holistic and detailed assessment of the environment.

Findings

Results showed that most of the traders were married (64.6%), females (74.5%), who were young adults within the age bracket of 31–45 years (39.8%) while over half of them had secondary school education (55.2%) and spent between 8 and 9 h in the market on a daily basis. Using what is termed “Facility Condition Index” (FCI), it was shown that public toilet (FCI = 2.11), health centre (FCI = 1.76) and electricity supply (FCI = 1.43) were the three most deplorable facilities in the markets. Findings further showed that flooding, pollution and blocked drain, each with 22.1%, were the most common environmental problems.

Originality/value

The study extends the existing literature by examining traders' perceptions of environmental quality of open spaces (markets), which could be used as tools in proffering solution to the varying environmental problems of the markets by policymakers.
Physiochemical properties and sensory characteristics of resistant starch enriched cookies
Authors: Rojhani Arezoo , Naranjo Joshua , Ouyang Ping
Published: November 2021

Purpose

The purpose of this study was to examine sensory attributes, physiochemical characteristics and consumer preference of drop sugar cookies prepared using high-amylose maize resistant starch (HAMRS) as a replacement for 10%, 20% and 30% of all-purpose (AP) flour as compared to a control made with 100% AP flour.

Design/methodology/approach

A balanced complete block experimental design was used to evaluate the eating quality of the resistant starch enriched cookies using a consumer panel. Consumer preference for the appearance, flavor, texture, moistness and overall acceptability of cookies was assessed. Diameter, height, spread ratio, hardness, moisture, pH, density, surface color and nutrient composition of cookies were analyzed.

Findings

Compared with the control cookies, the HAMRS cookies had lower diameters, higher, heights, reduced spreads, reduced % moisture losses and lower densities (p < 0.001). TA.XT Plus Texture Analyzer showed the HAMRS cookies had a softer texture than the control cookies (p < 0.0001). Evaluation of surface color showed no significant difference in lightness between the control and the HAMRS cookies. The HAMRS cookies were preferred over the control for appearance, texture and moistness in sensory evaluation with 42.5% of panelists choosing the 20% HAMRS replaced cookies as their overall preference. The 20% and 30% HAMRS replaced cookies qualify to be labeled as a “good source” and “excellent source” of fiber, respectively.

Practical implications

This data demonstrates that replacement of up to 30% of AP flour with HAMRS improves eating quality and dietary fiber content of sugar cookies. Our results show that HAMRS has good potential for developing high fiber cookies with minimal adverse impact on physical characteristics and notable improvements in sensory attributes and nutritional value.

Originality/value

To the best of the authors’ knowledge, this is the first study that has reported on the functionality, consumer preference and nutritional value of cookies enriched with a HAMRS that is available to consumers in the form of flour.
The role of citizens and transformation of energy, water, and waste infrastructure for an intelligent, sustainable environment in cities
Authors: Rodrigues Margarida , Franco Mário
Published: November 2021

Purpose

This study aims to list indicators to allow construction of a ranking for environmental sustainability in towns and cities, in relation to energy and water consumption and the prevention, production and management of waste. A systematization of theoretical and empirical indices was elaborated, focused on this dimension.

Design/methodology/approach

The results allow presentation of a ranking supported by multivariate statistical techniques – Exploratory Factor Analysis and Principal Component Analysis – confirming its scientific quality and robustness, with this being the main contribution of the study.

Findings

The analysis of the ranking revealed the great heterogeneity of towns and cities in Portugal, with the city of Lisbon and the town of Sardoal in the Top 20, suggesting that the achievement of the goal of environmental sustainability is proactively associated with the ability to articulate resources with infrastructure and the strategic and political will applied, being essential the appeal to the individual awareness of each citizen, even if the design of green infrastructures does not depend on citizens’ behavior. This means that redesigned green infrastructures may exist, but their success depends. In addition, cities are increasingly moving toward a circular economy articulated holistically with open and participatory governance.

Practical implications

The empirical evidence obtained in the Portuguese context provides some implications for practice, by showing it is possible to counteract the negative effects of rapid urban growth and its environmental consequences in urban and non-urban areas.

Originality/value

The main contribution and innovation of this study lie in the presentation of empirical evidence that the population density of a city or town does not have a cause–effect relationship with its level of environmental sustainability.
Estimation of porosity and gas hydrate saturation by inverting 2D seismic data using very fast simulated Annealing in the Krishna Godavari offshore basin, India
Authors: Joshi Anju K , Ojha Maheswar
Published: November 2021

Gas hydrate saturation and porosity are the two essential parameters for characterizing a gas hydrate reservoir. Generally, porosities determined at the well locations are interpolated and extrapolated over the seismic volume, which is not so appropriate to get an estimate of gas hydrate saturation. Here, we propose a method to predict both porosity and gas hydrate saturation directly by inverting seismic data using a global optimization technique known as Very Fast Simulated Annealing. Acoustic impedance, as a function of water saturation and porosity, is defined by a second‐degree polynomial equation used as a forward problem. These are used as the primary model parameters. Acoustic impedance derived from these values is then used to compute synthetic seismograms that are compared against observed traces. We demonstrate our approach on a 23.5 km two‐dimensional seismic line crossing four wells in the Krishna Godavari Basin, eastern Indian offshore. First, the proposed method is tested on well log data and then applied on post‐stack seismic data. The posterior probability density function and the correlation matrix between the model parameters (gas hydrate saturation and porosity) are calculated to measure the associated uncertainty in prediction. Inversion results illustrate that the approach can be efficiently used for the prediction of porosity and gas hydrate saturation directly from the seismic data.
Desire over damage: Epistemological shifts and anticolonial praxis from an indigenous‐led community health project
Authors: Smith Shelda‐Jane , Penados Filiberto , Gahman Levi
Published: November 2021

This article offers an overview of an Indigenous‐led participatory research project, The Future We Dream, co‐developed by rural land defenders in Central America and the Caribbean. To engage in recent dialectics concerning complicity and decolonising methodologies, we centre Indigenous Maya conceptions of health, wellbeing and what ‘living well’ means to community members. For context, The Future We Dream responds to the 2015 landmark ruling made by the Caribbean Court of Justice affirming the land rights of the Maya people of Southern Belize. Amidst tensions with the state that followed the ruling, an autonomous movement composed of grassroots organisers turned their attention towards imagining and constructing a self‐determined future. In turn, the communities initiated a research exercise inspired by desire‐based methodologies (Tuck, 2009) to articulate a collective vision of a healthful Maya future outside of colonial‐liberal worldviews, and notably, formulating Maya visions of healthful, sustainable worlds. In reporting on this one example of grassroots, anticolonial health research that departs from the hierarchal knowledge production practices of liberal academia, this paper details the collaborative process/project; the complexities/complicities of research involving Indigenous communities; and how Indigenous epistemologies are generative vis‐a‐vis unsettling conventional knowledge production practices in the contentious field of global health research.
Analysis of histomorphometric variables: Proposal and validation of osteon definitions
Authors: Crowder Christian , Dominguez Victoria M. , Heinrich Jarred , Pinto Deborrah , Mavroudas Sophia
Published: November 2021

Histological analysis of bone tissue has been used to explore a variety of questions relating to age‐at‐death, habitual behaviors, health, and nutritional stress. Identification of intact and fragmentary osteons is of key interest to many researchers in these studies, yet the definitions of these features vary between researchers making cross‐study comparisons problematic. Furthermore, histological variable definitions are often ambiguous or require subjective classifications by the observer. As a result, and as indicated by previous studies, observer error and misclassification of certain variables, namely intact and fragmentary osteons, can be significant. This study proposes new definitions for intact and fragmentary osteons that are designed to limit observer subjectivity and also explore efficacy of combining osteon types into one variable. A sample of 30 6th rib cross‐sections from a modern forensic population was used to test the validity of the proposed definitions. Observations of intact osteon population density (OPD(I)) and fragmentary osteon population density (OPD(F)) were made by three observers for each cross‐section. These observations were used to explore the interobserver error associated with the proposed definitions and determine if combining variables into one variable (OPD) mitigates persisting classification difficulties. Results indicate that the proposed definitions significantly reduce interobserver error and misclassification of intact and fragmentary osteons. However, the interobserver error associated with fragmentary osteons is still high. Evaluation of the variables independently indicates that combining variables has potential to reduce the predictive strength of an age estimation model and the ability to interpret age‐related bone remodeling.
Spatial distribution of synanthropic cockroaches found in Quetta, Pakistan and antibiotic‐resistant bacteria strains found in Shelfordella lateralis (Walker, 1868) (Blattodea: Blattidae)
Authors: Kamran Kashif , Schapheer Constanza , Ali Abid , Kamran Taj Muhammad , Siddiqui Saima , Maldonado Ana Karina , Iqbal Asim , Arif Sana , Villagra Cristian
Published: November 2021

Synanthropic cockroaches are a public health concern, because they can carry pathogens and allergens. These insects inhabit urban spaces and must be constantly monitored in order to assess the pest emergence outbreaks. Here, we combined spatial population monitoring with microbiological testing to survey the main pest cockroach species found inside residences of the city of Quetta, Pakistan. We evaluated the distribution of pest cockroaches at two scales: landscape (neighborhood) and patch (inside houses). We found at least one of the following pest species in the 73.2% of the total residences surveyed (n = 112): Shelfordella lateralis 37.1%, Periplaneta americana 23%, Blatella germanica 16.7%, Blatta orientalis 13.4% and Polyphaga aegyptiaca 9.8%. At landscape scale, the most common was S. lateralis, presenting a clustered distribution in two sampled zones, also heavily urbanized. At indoor scale, S. lateralis were most frequently found in kitchens. When we studied the bacterial loads in this species, we found that S. lateralis carried several pathogenic bacteria. Susceptibility tests tested on these strains against 10 common formulations showed antibiotic resistance for some bacteria. For instance, Pasteurella spp was susceptible towards six antibiotics tested, while Helicobacter spp showed resistance against eight antibiotics tested. Our evidence suggests that S. lateralis have the potential to displace main cosmopolitan pests and, most concerning, also carry antibiotic‐resistant pathogenic bacteria. Considering that this emergent Asian‐native pest is now present in Europe and America, it may correspond to a relevant urban pest deserving further international public health attention.
Dual ecological functions of scatter‐hoarding rodents: pollinators and seed dispersers of Mucuna sempervirens (Fabaceae)
Authors: XIAO Zhishu
Published: November 2021

Double mutualism, that is, pollination and seed dispersal of the same plant species mediated by the same animal partners, is important but remains elusive in nature. Recently, rodent species were found as key pollinators (i.e. explosive openers) for some Mucuna species in (sub)tropical Asia, but no evidence has shown whether and how these rodents could also act as legitimate seed dispersers via scatter‐hoarding for those producing large seeds. Here, my aim was to test the hypothesis that scatter‐hoarding rodents could act as double mutualists for both pollination and seed dispersal of the same Mucuna species, that is, Mucuna sempervirens (Fabaceae). Based on camera‐trapping survey at 2 locations with or without squirrel presence in the Dujiangyan subtropical forests, Southwest China, 7 mammals and birds were identified as explosive openers for M. sempervirens flowers, but Leopoldamys edwardsi (rats) and Paguma larvata (civets) were the main pollinators at the squirrel‐absent site, while Callosciurus erythraeus (squirrels) were the main pollinators at the squirrel‐present site. By tracking the fate of individually‐tagged seeds over 5 years at each site, I provide the first evidence for seed‐eating rodents as legitimate seed dispersers via scatter‐hoarding of seeds in this world‐wide plant genus, although dispersal services were slightly reduced at squirrel‐absent site. More importantly, the dual roles of scatter‐hoarding rodents as key pollinators and seed dispersers for the same Mucuna species have shown a clear relationship of double mutualism, and their key services may be essential for population conservation of these Mucuna species in human‐disturbed landscapes.
Evaluation of apical clips placed during axillary dissection demonstrates potential under‐coverage of axillary radiation therapy target volumes during breast cancer regional nodal irradiation
Authors: Hsieh Michael Ti , Aherne Noel J , Ross William , Salindera Shehnarz , Westhuyzen Justin , Winkley Lauren , Shakespeare Thomas P
Published: November 2021

Introduction

Evidence‐based Australian guidelines (eviQ) recommend adjuvant supraclavicular fossa irradiation after axillary lymph node dissection (ALND) in node‐positive breast cancer patients. Disparity between surgically determined versus computed tomography (CT) determined nodal volumes may result in discontiguous nodal volumes and untreated nodal tissue. We examine the extent of untreated nodal tissue in women with breast cancer post‐level II or III ALND and adjuvant radiation therapy (RT) using ESTRO contouring guidelines.

Methods

Female breast cancer patients who underwent level II and III ALND with apical clip placement from 2016 to 2020 and CT simulated in supine position were included. CT‐defined axillary level II‐IV volumes were contoured using ESTRO guidelines. The distance between the apical clip and RT nodal volumes was measured to indicate extent of untreated tissue.

Results

Of 34 eligible patients treated by 7 surgeons, 76% had level II ALND and 24% level III ALND. Only 5.9% of clips entirely encompassed the corresponding RT nodal volumes. 55.9% of clips fell within and 44.1% fell inferolaterally outside the corresponding RT nodal volumes. A median 3.6 cm (range 0–7.5 cm) of undissected nodal tissue would not be included within standard RT target volumes following eviQ recommendations.

Conclusion

There is a disparity between surgically determined versus CT determined axillary nodal volumes, leading to discontiguous nodal volumes and untreated axillary nodal tissue, despite following standard radiation contouring guidelines. Intraoperatively placed apical axillary clips may assist radiation oncologists to accurately delineate undissected nodal tissues at risk.
Sequence coverage required for accurate genotyping by sequencing in polyploid species
Authors: Wang Lin , Yang Jixuan , Zhang Hong , Tao Qin , Zhang Yuxin , Dang Zhenyu , Zhang Fengjun , Luo Zewei
Published: November 2021

Polyploidy plays an important role in the evolution of eukaryotes, especially for flowering plants. Many of ecologically or agronomically important plant or crop species are polyploids, including sycamore maple (tetraploid), the world second and third largest food crops wheat (hexaploid) and potato (tetraploid) as well as economically important aquaculture animals such as Atlantic salmon and trout. The next generation sequencing data enables to allocate genotype at a sequence variant site, known as genotyping by sequencing (GBS). GBS has stimulated enormous interests in population based genomics studies in almost all diploid and many polyploid organisms. DNA sequence polymorphisms are codominant and thus fully informative about the underlying genotype at the polymorphic site, making GBS a straightforward task in diploids. However, sequence data may usually be uninformative in polyploid species, making GBS a far more challenging task in polyploids. This paper presents novel and rigorous statistical methods for predicting the number of sequence reads needed to ensure accurate GBS at a polymorphic site bared by the reads in polyploids and shows that a dozen of reads can ensure a probability of 95% to recover all constituent alleles of any tetraploid genotype but several hundreds of reads are needed to accurately uncover the genotype with probability confidence of 90%, subverting the proposition of GBS using low coverage sequence data in the literature. The theoretical prediction was tested by use of RAD‐seq data from tetraploid potato cultivars. The paper provides polyploid experimentalists with theoretical guides and methods for designing and conducting their sequence‐based studies.
Integration of Sequence Stratigraphic Analysis and 3D Geostatistical Modeling of Pliocene–Pleistocene Delta, F3 Block, Netherlands
Authors: KHAN Haris Ahmed , SHAHID Ali Asghar , KHAN Muhammad Jahangir , ZOUAGHI Taher , ALVAREZ Maria Dolores , NAQVI Syed Danial Mehdi
Published: November 2021

This research is focused on the analysis of the sequence stratigraphic units of F3 Block, within a wave‐dominated delta of Plio–Pleistocene age. Three wells of F3 block and a 3D seismic data, are utilized in this research. The conventional techniques of 3D seismic interpretation were utilized to mark the 11 surfaces on the seismic section. Integration of seismic sequence stratigraphic interpretation, using well logs, and subsequent 3D geostatistical modeling, using seismic data, aided to evaluate the shallow hydrocarbon traps. The resulting models were obtained using System Tract and Facies models, which were generated by using sequential stimulation method and their variograms made by spherical method, moreover, these models are validated via histograms. The CDF curve generated from upscaling of well logs using geometric method, shows a good relation with less percentage of errors (1 to 2 for Facies and 3 to 4 for System Tract models) between upscaled and raw data that complements the resulted models. These approaches help us to delineate the best possible reservoir, lateral extent of system tracts (LST and/or HST) in the respective surface, and distribution of sand and shale in the delta. The clinoform break points alteration observed on seismic sections, also validates the sequence stratigraphic interpretation. The GR log‐based Facies model and sequence stratigraphy‐based System Tract model of SU‐04‐2 showed the reservoir characteristics, presence of sand bodies and majorly LST, respectively, mainly adjacent to the main fault of the studied area. Moreover, on the seismic section, SU‐04‐2 exhibits the presence of gas pockets at the same location that also complements the generated Facies and System Tract models. The generated models can be utilized for any similar kind of study and for the further research in the F3 block reservoir characterization.
Geochemistry and Petrogenesis of Late Cretaceous–Paleocene Granites from the Tengchong Block, Western Yunnan: Implications for Angle‐switching of Subducting Slab
Authors: CHEN Xijie , MENG Yuanku , CAI Zhihui , LI Huaqi , LIU Xiaojia
Published: November 2021

The Cenozoic geological hallmark of Western Yunnan is the characteristic voluminous Late Cretaceous‐Eocene granites; however, their geological background and petrogenesis have not been well constrained and elucidated. In this study, we present new zircon U‐Pb dating, along with geochemical and Sr‐Nd‐Hf isotopic data for granites from the Tengchong–Lianghe granitoid belt (as abbreviated to Tengliang belt) and West Yingjiang batholiths from the Tengchong block. The mineralogical and geochemical features of the Tengliang granites and the West Yingjiang batholiths are ascribed to aluminous S‐type granites and weak peraluminous I‐type, respectively. Zircon U‐Pb analyses yielded consistent ages ranging from 67.5 Ma, 68.4 Ma and 66.2 Ma from the Tengliang granitoid belt and 50.4 Ma to 60.8 Ma for three samples from the west Yingjiang batholiths. The Tengliang granites were emplaced during the Late Cretaceous (68–66 Ma) and demonstrate negative εHf(t) values (–24 to –4) and initial 87Sr/86Sr ratios of 0.7101–0.7139 and significant negative εNd(t) values from –8.91 to –13.2, indicating a Proterozoic sedimentary source or enriched components. The hornblende‐bearing I‐type granites from West Yingjiang are characterized by lower initial 87Sr/86Sr ratios of 0.7076–0.7106, compared to Tengliang granite and negative whole‐rock εNd(t) values from –4.0 to –11.9. The early Eocene west Yingjiang gneissic granites show wide ranges of εHf(t) values from +7.4 to –8.5 and T2DM of 1.30–0.65 Ga, indicating partial melting of ancient crust with contributions of depleted mantle materials. In combination with the regional background and previous studies, we propose that such a spatio‐temporal distribution of the Tengchong granitoid belt might be related to the rollback or angle‐switching of the Neo‐Tethyan subducting slab. This study sheds new light on the evolutionary history of the Tengchong block.
Associations between radiographic features, clinical features and ultrasound of thumb‐base osteoarthritis: A secondary analysis of the COMBO study
Authors: Shi Ying , Fu Kai , Oo Win Min , Deveza Leticia A. , Wang Xia , Duong Vicky , Robbins Sarah R. , Hunter David J.
Published: November 2021

Aim

To investigate the associations of ultrasound and radiographic features of thumb‐base osteoarthritis (OA) with thumb‐base pain and hand function at baseline and 12 weeks.

Method

Data from a randomized controlled trial conducted in participants with symptomatic radiographic thumb‐base OA were analyzed. Participants who finished follow up were included in this secondary analysis. Pain and hand function were assessed using self‐reported measures. All participants underwent ultrasound examinations for synovitis, power Doppler signal (PDS), and osteophytes, and underwent radiography for osteophytes, joint space narrowing (JSN), and subchondral bone sclerosis at baseline. Hand pain and function were reassessed after the 12‐week follow up. The associations of ultrasound and radiographic findings with clinical features were further evaluated, using linear regression analyses, after adjustment for relevant confounding factors.

Results

A total of 166 participants (average age 66.2 years; 76.5% female) were included. At baseline, radiographic JSN and subchondral bone sclerosis were associated with hand function. There was a significant association between ultrasound‐detected PDS and patient's global assessment (PGA) at baseline. Baseline radiographic JSN was significantly associated with the changes in stiffness and PGA from baseline to 12 weeks. There was no association between ultrasound features and changes in the clinical outcomes over 12 weeks.

Conclusion

This study indicates that radiographic features significantly correlate with hand function, and ultrasound PDS is closely related to the PGA at baseline in thumb‐base OA. Radiographic JSN may be a predictor for stiffness and PGA in thumb‐base OA.
An Overview of the Literature on Upper Echelons*
Authors: Liu Ming , Ji Duan
Published: November 2021

This paper reviews the literature pertaining to the effects of the characteristics of top executives on firms' decisions and outcomes. We focus particularly on research related to executives' individual characteristics, including their demographic, psychological, and other characteristics. Thereafter, we discuss the literature related to the relationship among executives, particularly the CEO and the CFO, which may affect corporate performance and accounting outcomes. Finally, we identify the gaps in the literature and provide directions for future research.
Nogo receptor impairs the clearance of fibril amyloid‐β by microglia and accelerates Alzheimer’s‐like disease progression
Authors: Wang Jianing , Qin Xiaoying , Sun Hao , He Meijun , Lv Qunyu , Gao Congcong , He Xinran , Liao Hong
Published: November 2021

Alzheimer's disease (AD) is characterized by the progressive accumulation of β‐amyloid (Aβ)‐containing amyloid plaques, and microglia play a critical role in mediating Aβ clearance. Mounting evidence has confirmed that the ability of microglia in clearing Aβ decreased with aging and AD progress, but the underlying mechanisms are unclear. Previously, we have demonstrated that Nogo receptor (NgR), a receptor for three axon growth inhibitors associated with myelin, can decrease adhesion and migration of microglia to fibrils Aβ with aging. However, whether NgR expressed on microglia affect microglia phagocytosis of fibrils Aβ with aging remains unclear. Here, we found that aged but not young microglia showed increased NgR expression and decreased Aβ phagocytosis in APP/PS1 transgenic mice. NgR knockdown APP/PS1 mice showed simultaneous reduced amyloid burden and improved spatial learning and memory, which were associated with increased Aβ clearance. Importantly, Nogo‐P4, an agonist of NgR, enhanced the protein level of p‐Smad2/3, leading to a significant transcriptional inhibition of CD36 gene expression, which in turn decreased the microglial phagocytosis of Aβ. Moreover, ROCK accounted for Nogo‐P4‐induced activation of Smad2/3 signaling. Finally, the decreasing effect of NgR on microglial Aβ uptake was confirmed in a mouse model of intra‐hippocampal fAβ injection. Our findings suggest that NgR may play an important role in the regulation of Aβ homeostasis, and has potential as a therapeutic target for AD.
Phenotype correlations reveal the relationships of physiological systems underlying human ageing
Authors: Hao Meng , Zhang Hui , Hu Zixin , Jiang Xiaoyan , Song Qi , Wang Xi , Wang Jiucun , Liu Zuyun , Wang Xiaofeng , Li Yi , Jin Li
Published: November 2021

Ageing is characterized by degeneration and loss of function across multiple physiological systems. To study the mechanisms and consequences of ageing, several metrics have been proposed in a hierarchical model, including biological, phenotypic and functional ageing. In particular, phenotypic ageing and interconnected changes in multiple physiological systems occur in all ageing individuals over time. Recently, phenotypic age, a new ageing measure, was proposed to capture morbidity and mortality risk across diverse subpopulations in US cohort studies. Although phenotypic age has been widely used, it may overlook the complex relationships among phenotypic biomarkers. Considering the correlation structure of these phenotypic biomarkers, we proposed a composite phenotype analysis (CPA) strategy to analyse 71 biomarkers from 2074 individuals in the Rugao Longitudinal Ageing Study. CPA grouped these biomarkers into 18 composite phenotypes according to their internal correlation, and these composite phenotypes were mostly consistent with prior findings. In addition, compared with prior findings, this strategy exhibited some different yet important implications. For example, the indicators of kidney and cardiovascular functions were tightly connected, implying internal interactions. The composite phenotypes were further verified through associations with functional metrics of ageing, including disability, depression, cognitive function and frailty. Compared to age alone, these composite phenotypes had better predictive performances for functional metrics of ageing. In summary, CPA could reveal the hidden relationships of physiological systems and identify the links between physiological systems and functional ageing metrics, thereby providing novel insights into potential mechanisms underlying human ageing.
Persistent myelin abnormalities in a third trimester‐equivalent mouse model of fetal alcohol spectrum disorder
Authors: Newville Jessie , Howard Tamara A. , Chavez Glenna J. , Valenzuela Carlos Fernando , Cunningham Lee Anna
Published: November 2021

Background

Abnormal diffusion within white matter (WM) tracts has been linked to cognitive impairment in children with fetal alcohol spectrum disorder. Whether changes to myelin organization and structure underlie the observed abnormal diffusion patterns remains unknown. Using a third trimester‐equivalent mouse model of alcohol exposure, we previously demonstrated acute loss of oligodendrocyte lineage cells with persistent loss of myelin basic protein and lower fractional anisotropy (FA) in the corpus callosum (CC). Here, we tested whether these WM deficits are accompanied by changes in: (i) axial diffusion (AD) and radial diffusion (RD), (ii) myelin ultrastructure, or (iii) structural components of the node of Ranvier.

Methods

Mouse pups were exposed to alcohol or air vapor for 4 h daily from postnatal day (P)3 to P15 (BEC: 160.4 ± 12.0 mg/dl; range = 128.2 to 185.6 mg/dl). Diffusion tensor imaging (DTI) and histological analyses were performed on brain tissue isolated at P50. Diffusion parameters were measured with Paravision™ 5.1 software (Bruker) following ex vivo scanning in a 7.0 T MRI. Nodes of Ranvier were identified using high‐resolution confocal imaging of immunofluorescence for Nav1.6 (nodes) and Caspr (paranodes) and measured using Imaris™ imaging software (Bitplane). Myelin ultrastructure was evaluated by calculating the G‐ratio (axonal diameter/myelinated fiber diameter) on images acquired using transmission electron microscopy.

Results

Consistent with our previous study, high resolution DTI at P50 showed lower FA in the CC of alcohol‐exposed mice (p = 0.0014). Here, we show that while AD (diffusion parallel to CC axons) was similar between treatment groups (p = 0.30), RD (diffusion perpendicular to CC axons) in alcohol‐exposed subjects was significantly higher than in controls (p = 0.0087). In the posterior CC, where we identified the highest degree of abnormal diffusion, node of Ranvier length did not differ between treatment groups (p = 0.41); however, the G‐ratio of myelinated axons was significantly higher in alcohol‐exposed animals than controls (p = 0.023).

Conclusions

High resolution DTI revealed higher RD at P50 in the CC of alcohol‐exposed animals, suggesting less myelination of axons, particularly in the posterior regions. In agreement with these findings, ultrastructural analysis of myelinated axons in the posterior CC showed reduced myelin thickness in alcohol‐exposed animals, evidenced by a higher G‐ratio.