bluuebunny/crossref_metadata_2025 huggingface dataset:
4 SPECIES OF BACTERIA DETERMINISTICALLY FORM A STABLE BIOFILM IN A MILLIFLUIDIC CHANNEL: ASSEMBLY PRINCIPLES
Authors: Monmeyran A. , Benyoussef W. , Thomen P. , Dahmane N. , Baliarda A. , Jules M. , Aymerich S. , Henry N.
Published: April 2021

Abstract

Multispecies microbial adherent communities are widespread in nature and organisms but the principles of their assembly and development remain unclear. Yet, the demand to understand and predict the responses of such living communities to environmental changes is increasing, calling for new approaches. Here, we test the possibility to establish a simplified but relevant model of multispecies biofilm in a laboratory setup enablingin situreal-time monitoring of the community development and control of the environmental parameters in order to decipher the mechanisms underlying the formation of the community. Using video-microscopy and species combinatorial approach, we assess the global and individual species spatiotemporal development in millifluidic channels under constant flow of nutrients. Based on quantitative measurements of expansion kinetics, local dynamics and spatial distribution, we demonstrate that the four chosen species (Bacillus thuringiensis, Pseudomonas fluorescens, Kocuria variansandRhodocyclussp.) form a dynamical community that deterministically reaches its equilibrium after about 30 hours of growth. We evidence the emergence of complexity in this simplified community as reported by spatial heterogeneity rise and non-monotonic developmental kinetics. We find interspecies interactions consisting in competition for resources — in particular oxygen — and both direct and indirect physical interactions but no positive feedback. Thereby, we introduce a model of multispecies adherent community where effective couplings result from individual species quest for fitness optimization in a moving and heterogenous environment. This control and the understanding of this simplified experimental model shall open new avenues to apprehend adherent bacterial communities behavior in a context of rapid global change.
Genomic analysis reveals a polygenic architecture of antler morphology in wild red deer (Cervus elaphus)
Authors: Peters Lucy , Huisman Jisca , Kruuk Loeske E.B. , Pemberton Josephine M. , Johnston Susan E.
Published: April 2021

Sexually-selected traits show large variation and rapid evolution across the animal kingdom, yet genetic variation often persists within populations despite apparent directional selection. A key step in solving this long-standing paradox is to determine the genetic architecture of sexually-selected traits to understand evolutionary drivers and constraints at the genomic level. Antlers are a form of sexual weaponry in male red deer. On the island of Rum, Scotland, males with larger antlers have increased breeding success, yet there has been no response to selection observed at the genetic level. To better understand the underlying mechanisms of this observation, we investigate the genetic architecture of ten antler traits and their principle components using genomic data from >38,000 SNPs. We estimate the heritabilities and genetic correlations of the antler traits using a genomic relatedness approach. We then use genome-wide association and haplotype-based regional heritability to identify regions of the genome underlying antler morphology, and an Empirical Bayes approach to estimate the underlying distributions of allele effect sizes. We show that antler morphology is heritable with a polygenic architecture, highly repeatable over an individual’s lifetime, and that almost all aspects are positively genetically correlated with some loci identified as having pleiotropic effects. Our findings suggest that a large mutational target and pleiotropy with traits sharing similar complex polygenic architectures are likely to contribute to the maintenance of genetic variation in antler morphology in this population.
Co-evolutionary analysis suggests a role for TLR9 in papillomavirus restriction
Authors: King Kelly , Larsen Brendan B. , Gryseels Sophie , Richet Cécile , Kraberger Simona , Jackson Robert , Worobey Michael , Harrison Joseph S. , Varsani Arvind , Doorslaer Koenraad Van
Published: April 2021

A.

Upon infection, DNA viruses can be sensed by pattern recognition receptors (PRRs) leading to the activation of type I and III interferons, aimed at blocking infection. Therefore, viruses must inhibit these signaling pathways, avoid being detected, or both. Papillomavirus virions are trafficked from early endosomes to the Golgi apparatus and wait for the onset of mitosis to complete nuclear entry. This unique subcellular trafficking strategy avoids detection by cytoplasmic PRRs, a property that may contribute to establishment of infection. However, as the capsid uncoats within acidic endosomal compartments, the viral DNA may be exposed to detection by toll-like receptor (TLR) 9. In this study we characterize two new papillomaviruses from bats and use molecular archeology to demonstrate that their genomes altered their nucleotide composition to avoid detection by TLR9, providing evidence that TLR9 acts as a PRR during papillomavirus infection. Furthermore, we demonstrate that TLR9, like other components of the innate immune system, is under evolutionary selection in bats, providing the first direct evidence for co-evolution between papillomaviruses and their hosts.
Design of time-delayed safety switches for CRISPR gene therapy
Authors: Sun Dashan
Published: April 2021

CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. Inspired by previously reported Cas9 self-elimination systems, time-delayed safety switches are designed in this work. Firstly, ultrasensitive relationship is constructed between Cas9-sgRNA (enzyme) and Cas9 plasmids (substrate), which generates the artificial time delay. Then intrinsic time delay in biomolecular activities is revealed by data fitting and utilized in constructing safety switches. The time-delayed safety switches function by separating the gene editing process and self-elimination process, and the tunable delay time may ensure a good balance between gene editing efficiency and side effect minimization. By addressing gene therapy efficiency, off-target effect, immune response and drug accumulation, we hope our safety switches may offer inspiration in realizing safe and efficient gene therapy in humans.
Neutralization of the anthrax toxin by antibody-mediated stapling of its membrane penetrating loop
Authors: Hoelzgen Fabian , Zalk Ran , Alcalay Ron , Schwartz Sagit Cohen , Garau Gianpiero , Shahar Anat , Mazor Ohad , Frank Gabriel A.
Published: April 2021

Anthrax infection is associated with severe illness and high mortality. Protective antigen (PA) is the central component of the anthrax toxin, which is the main virulent factor of anthrax. Upon endocytosis, PA opens a pore in the membranes of endosomes, through which the toxin’s cytotoxic enzymes are extruded. The PA pore is formed by a cooperative conformational change where PA’s membrane-penetrating loops associate, forming a hydrophobic rim that pierces the membrane. Due to its crucial role in anthrax progression, PA is an important target of monoclonal antibodies-based therapy. cAb29 is a highly effective neutralizing antibody against PA. We determined the cryo-EM structure of PA in complex with the Fab portion of cAb29. We found that cAb29 neutralizes the toxin by clamping the membrane-penetrating loop of PA to a static region on PA’s surface, thereby preventing pore formation. Therefore, our results provide the structural basis for the antibody-based neutralization of PA and bring to focus the membrane-penetrating loop of PA as a target for the development of better anti-anthrax vaccines.
Transcriptomic stability or lability explains sensitivity to climate stressors in coralline algae
Authors: Page Tessa M. , McDougall Carmel , Bar Ido , Diaz-Pulido Guillermo
Published: April 2021

Crustose coralline algae (CCA) are a group of calcifying red macroalgae crucial to tropical coral reefs because they form crusts that cement together the reef framework1. Previous research into the responses of CCA to ocean warming (OW) and ocean acidification (OA) have found reductions in calcification rates and survival2,3, with magnitude of effect being species-specific. Responses of CCA to OW and OA could be linked to evolutionary divergence time and/or their underlying molecular biology, the role of either being unknown in CCA. Here we showSporolithon durum, a species from an earlier diverged lineage that exhibits low sensitivity to climate stressors, had little change in metabolic performance and did not significantly alter the expression of any genes when exposed to temperature and pH perturbations. In contrast,Porolithon onkodes, a species from a recently diverged lineage, reduced photosynthetic rates and had over 400 significantly differentially expressed genes in response to experimental treatments, with differential regulation of genes relating to physiological processes. We suggest earlier diverged CCA may be resistant to OW and OA conditions predicted for 2100, whereas taxa from more recently diverged lineages with demonstrated high sensitivity to climate stressors may have limited ability for acclimatisation.
Principles of mRNA targeting via the Arabidopsis m6A-binding protein ECT2
Authors: Arribas-Hernández Laura , Rennie Sarah , Köster Tino , Porcelli Carlotta , Lewinski Martin , Staiger Dorothee , Andersson Robin , Brodersen Peter
Published: April 2021

Specific recognition ofN6-methyladenosine (m6A) in mRNA by RNA-binding proteins containing a YT521-B homology (YTH) domain is important in eukaryotic gene regulation. The Arabidopsis YTH-domain protein ECT2 is thought to bind to mRNA at URU(m6A)Y sites, yet RR(m6A)CH is the canonical m6A consensus site in all eukaryotes and ECT2 functions require m6A binding activity. Here, we apply iCLIP (individual-nucleotide resolution cross-linking and immunoprecipitation) and HyperTRIBE (targets of RNA-binding proteins identified by editing) to define high-quality target sets of ECT2, and analyze the patterns of enriched sequence motifs around ECT2 crosslink sites. Our analyses show that ECT2 does in fact bind to RR(m6A)CH. Pyrimidine-rich motifs are enriched around, but not at m6A-sites, reflecting a preference forN6-adenosine methylation of RRACH/GGAU islands in pyrimidine-rich regions. Such motifs, particularly oligo-U and UNUNU upstream of m6A sites, are also implicated in ECT2 binding via its intrinsically disordered region (IDR). Finally, URUAY-type motifs are enriched at ECT2 crosslink sites, but their distinct properties suggest function as sites of competition between binding of ECT2 and as yet unidentified RNA-binding proteins. Our study provides coherence between genetic and molecular studies of m6A-YTH function in plants, and reveals new insight into the mode of RNA recognition by YTH-domain-containing proteins.
Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Authors: Kruse Thomas , Benz Caroline , Garvanska Dimitriya H. , Lindqvist Richard , Mihalic Filip , Coscia Fabian , Inturi Ravi Teja , Sayadi Ahmed , Simonetti Leandro , Nilsson Emma , Ali Muhammad , Kliche Johanna , Morro Ainhoa Moliner , Mund Andreas , Andersson Eva , McInerney Gerald , Mann Matthias , Jemth Per , Davey Norman E , Överby Anna K , Nilsson Jakob , Ivarsson Ylva
Published: April 2021

Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, current methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a scalable viral peptide discovery approach covering 229 RNA viruses that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction blocks SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
Feeling documents: toward a phenomenology of information seeking
Authors: Keilty Patrick , Leazer Gregory
Published: April 2021

Purpose

The purpose of this paper is to present two models of human cognition. The first narrow model concentrates on the mind as an information-processing apparatus, and interactions with information as altering thought structures and filling gaps in knowledge. A second model incorporates elements of unconsciousness, embodiment and affect. The selection of one model over the other, often done tacitly, has consequences for subsequent models of information seeking and use.

Design/methodology/approach

A close reading of embodied engagements with pornography guided by existential phenomenology.

Findings

The paper develops a phenomenology of information seeking, centered primarily around the work of Merleau-Ponty, to justify a more expansive concept of cognition. The authors demonstrate the roles of affect and embodiment in document assessment and use, with a prolonged example in the realm of browsing pornography.

Originality/value

Models of information seeking and use need to account for diverse kinds of human-document interaction, to include documents such as music, film and comics that engage the emotions or are perceived through a broader band of sensory experience to include visual and auditory components. The authors consider how those human-document engagements form virtual communities based on the similarity of their members’ affective and embodied responses, which in turn inform the arrangements, through algorithms, of the relations of documents to each other. Less instrumental forms of information seeking and use – ones that incorporate elements of embodiment and affect – are characterized as esthetic experiences, following the definition of the esthetic provided by Dewey. Ultimately the authors consider, given the ubiquity of information seeking and its rhythm in everyday life, whether we can meaningfully characterize information seeking as a distinct human process.
Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate in LPS‐induced neutrophil extracellular traps
Authors: Ding Jing , Zhang Zuoman , Huang Weimin , Bi Guangliang
Published: April 2021

Neutrophil extracellular traps (NETs) are beneficial antibacterial defense structures. However, excessive NETs have also been linked to tissue damage and organ dysfunction. LPS and Gram‐negative bacteria induce the formation of reactive oxygen species (ROS)‐dependent NETs via the JNK pathway. It was found previously that knockdown of nicotinamide phosphoribosyltransferase (NAMPT) upregulates surfactant protein B (SFTPB or SP‐B) and attenuates LPS‐induced acute lung injury (ALI) via inhibiting JNK activation. This study investigated the effect of FK866, an intracellular NAMPT inhibitor, on the formation of LPS‐induced NETs in mouse bronchoalveolar lavage (BAL) neutrophils and in differentiated HL‐60 cells. The results show that inhibition of NAMPT by FK866 suppresses NETs formation in BAL neutrophils from the mice exposed to LPS. FK866 also suppresses NETs formation in the differentiated HL‐60 cells stimulated with LPS. Additional data indicate that these effects are mediated by suppressing ROS production at least partly via inhibiting JNK activation and depleting NAD(P)H. The utility of inhibition of intracellular NAMPT may be a potential therapy for LPS‐induced NETs‐related diseases.
Dsk2 involves in conidiation, multi‐stress tolerance and thermal adaptation in Beauveria bassiana
Authors: Wang Dingyi , Lv Chao , Guan Yi , Ni Xiangyin , Wu Fuzhong
Published: April 2021

Dsk2 is a nuclear‐enriched ubiquitin‐like polyubiquitin‐binding protein that regulates protein degradation in yeast but has not been explored yet in filamentous fungi, such as Beauveria bassiana. Here, we report Beauveria bassiana Dsk2 located both in the nucleus and in cytoplasm of hyphal cells. Deletion of Dsk2 resulted in mild growth defect on scant media with various carbon/nitrogen sources and dramatic attenuation in conidiation capability at optimal condition. Compared to the wild‐type, ΔDsk2 strains are much more sensitive to high osmotic and oxidative pressure during vegetative growth. Meanwhile, the mutant strains showed an increased chemical tolerance to Congo red and calcofluor white, two cell wall perturbing agents. The transcriptional changes of genes involved in central development, superoxide dismutase and chitin synthesis pathway indicate that Dsk2 acts as a multi‐functional regulator in adapting to environmental changes. Importantly, Dsk2 negatively regulated the ability of thermal resistance in B. bassiana, which makes it a potential target gene for constructing engineering anti‐thermal strains in the circumstance of global warming. Altogether, our finding highlights novel roles of Dsk2 involved in the asexual cycle, multi‐stress tolerance and pest control potential of B. bassiana.
Oral health self‐care behaviours in serious mental illness: A systematic review and meta‐analysis
Authors: Turner Elizabeth , Berry Katherine , Aggarwal Vishal R. , Quinlivan Leah , Villanueva Timothy , Palmier‐Claus Jasper
Published: April 2021

Aim

To understand the relationship between serious mental illness and oral health self‐care behaviours using meta‐analytic methods and a narrative synthesis of available literature.

Method

The review followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines [PROSPERO reference: CRD42020176779]. Search terms pertaining to serious mental illness and oral health were entered into EMBASE, PsycINFO, Medline and CINAHL. Eligible studies included a sample of people with a serious mental illness and a quantitative measure of an oral health self‐care behaviour (eg dental visits, toothbrushing). The Effective Public Health Practice Project tool was utilised to appraise the quality of the literature. Studies in the meta‐analysis contained a non‐clinical or general population comparator sample.

Results

People with a serious mental illness were significantly less likely to visit the dentist (OR 0.46, 95% CI 0.32–0.065, p > 0.001) or brush their teeth (OR 0.19, 95% CI 0.08–0.42, p < 0.001) when compared to non‐clinical comparator samples. Few studies explored other oral health self‐care behaviours (eg flossing and mouth washing), but uptake was generally low in people with a serious mental illness. The study quality of included studies was variable.

Conclusions

The research showed a reduced uptake of oral health self‐care behaviours in people with a serious mental illness. Suboptimal oral health can negatively impact on physical, social and psychological functioning. Further research is needed to understand the reasons for low rates of oral health self‐care behaviours in this population.
Review Article: Anabolic‐Androgenic Steroids, Violence, and Crime: Two Cases and Literature Review
Authors: Pope Harrison G. , Kanayama Gen , Hudson James I. , Kaufman Marc J.
Published: April 2021

Background and Objectives

Anabolic‐androgenic steroid (AAS) use has become a major worldwide substance use disorder, affecting tens of millions of individuals. Importantly, it is now increasingly recognized that some individuals develop uncharacteristically violent or criminal behaviors when using AAS. We sought to summarize available information on this topic.

Methods

We reviewed the published literature on AAS‐induced behavioral effects and augmented this information with extensive observations from our clinical and forensic experience.

Results

It is now generally accepted that some AAS users develop uncharacteristically violent or criminal behaviors while taking these drugs. Although these behaviors may partially reflect premorbid psychopathology, sociocultural factors, or expectational effects, accumulating evidence suggests that they are also attributable to biological effects of AAS themselves. The mechanism of these effects remains speculative, but preliminary data suggest a possible role for brain regions involved in emotional reactivity, such as the amygdala and regions involved in cognitive control, including the frontal cortex. For unknown reasons, these effects appear idiosyncratic; most AAS users display few behavioral effects, but a minority develops severe effects.

Conclusion and Scientific Significance

Professionals encountering AAS users in clinical or forensic settings should be alert to the possibility of AAS‐induced violence or criminality and should employ strategies to assess whether AAS is indeed a contributory factor in a given case. Further research is needed to elucidate the mechanism of AAS‐induced violence and to explain why only a subset of AAS users appears vulnerable to these effects. (Am J Addict 2021;00:00–00)
Nutrition risk prevalence and associated health and social risk factors in Māori and non‐Māori: Results from the New Zealand Health, Work and Retirement Study
Authors: Tkatch Melaney T. , Towers Andy J. , Keller Heather H. , Wham Carol A.
Published: April 2021

Objective

To determine the nutrition risk prevalence and associated health and social risk factors amongst community‐living Māori and non‐Māori older adults in New Zealand.

Methods

As part of the 2014 Health, Work and Retirement postal survey, 2914 community‐living older adults (749 Māori) aged 49‐87 years completed the Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN II‐AB) to determine nutrition risk status and sociodemographic and health measures.

Results

Half (50.2%) of Māori and 32.7% of non‐Māori were at nutrition risk. Independent risk factors were as follows: for Māori, being unpartnered and rating general health as fair, and for non‐Māori, being unpartnered and rating general health as fair or poor, lower life satisfaction, higher number of health conditions and emotional loneliness.

Conclusions

Findings highlight the need for culturally appropriate intervention strategies, which provide opportunity for older adults to eat with others, especially for those who are unpartnered and lonely.
Sowing the Seeds: Radicalization as a Political Tool
Authors: Lehmann Todd C. , Tyson Scott A.
Published: April 2021

Do radicalized individuals with no logistical assistance from opposition groups generate liabilities or advantages for opposition leaders? To address this question, we develop a theory that articulates a novel strategic channel connecting radicalization, defined as self‐motivation to dissent, to repression targeting an opposition group's operational capacity or its leadership. Our main result shows that targeted repression is strictly decreasing in the proportion of radicalized citizens. We endogenize opposition leaders' decision to radicalize citizens and show that opposition leaders, even absent any direct benefit to radicalize, nevertheless invest effort into radicalization. Thus, radicalization is a political tool to deter repression by decreasing its usefulness. To better understand this strategic consequence, we analyze two common policy interventions—economic and psychological—and show that improving economic conditions reduces both radicalization efforts and dissent, while making individuals psychologically less susceptible to radicalization can sometimes backfire and increase dissent because it increases leaders' radicalization efforts.
Use of non‐insulin antidiabetic drugs in children and young adults – A Scandinavian drug utilization study from 2010–2019
Authors: Jensen Helene K. , Rasmussen Lotte , Furu Kari , Karlstad Øystein , Linder Marie , Cesta Carolyn E. , Pottegård Anton
Published: April 2021

Knowledge on utilization patterns of non‐insulin antidiabetic drugs in childhood and youth is limited. Therefore, we conducted a population‐based drug utilization study using publicly available aggregate data on use of non‐insulin antidiabetics from 2010 to 2019 in Scandinavia (Denmark, Norway and Sweden) in individuals aged up to 24 years. For each non‐insulin antidiabetic drug, we calculated the annual prevalence proportion of users, overall and for specific age groups.

From 2010 to 2019, the prevalence of non‐insulin antidiabetic users in Scandinavia increased 37% from 0.43 to 0.59/1000 individuals. The prevalence proportions were highest among female adolescents and young adults, but the largest relative increase in use was seen among 10–14‐year‐olds (78%). Metformin was by far the most widely used non‐insulin antidiabetic drug with a prevalence proportion of 0.51/1000 in 2019, followed by glucagon‐like peptide‐1 (GLP‐1) analogues, which, however, showed an eight‐fold relative increase during the study period.
Dynamic insulin‐stimulated mTOR/GSK3 signaling in peripheral immune cells: Preliminary evidence for an association with lithium response in bipolar disorder
Authors: Tye Susannah J. , Borreggine Kristin , Price J. Blair , Sutor Shari L. , Cuéllar‐Barboza Alfredo B. , McElroy Susan L. , Biernacka Joanna M. , Frye Mark A.
Published: April 2021

Introduction

A key mechanism of lithium is the inhibition of glycogen synthase kinase‐3β (GSK3β) and activation of mammalian target of rapamycin (mTOR), two contributors to insulin signaling. We explored the relationship between these markers and clinical response to lithium in bipolar disorder (BD).

Methods

Thirty‐four subjects with BD who had been taking lithium for ≥2 years and had a maintenance lithium Alda score defined as either high (≥7; n = 20) or low (≤2; n = 14) were included in the study. Baseline protein expression of GSK3β and mTOR (total and phosphorylated (p)) was obtained from a buffy coat. Peripheral blood mononuclear cells (PBMCs) from a subset of each group (n = 11) were stimulated with insulin (10 µg) and change in protein expression was determined using Western blot.

Results

In buffy coat samples, significantly higher levels of pmTOR were present in subjects with an Alda score ≤2 (lithium non‐responsive), relative to those with scores ≥7 (lithium‐responsive). No differences were observed for pGSK3β. In contrast, functional PBMC responses to 5 min of insulin stimulation demonstrated robust increases in pGSK3β (87.05 ± 43.41%) and pmTOR (105.7 ± 66.48%) in the lithium responsive group only. This contrasted observed decreases in pGSK3β (34.08 ± 16.12%) and pmTOR (37.84 ± 14.39%) 5 mins post‐insulin in non‐responders.

Conclusions

Dynamic increases in pmTOR and pGSK3β post‐insulin stimulation may reflect an immunometabolic state that facilitates lithium response. Further prospective analyses are needed to replicate and extend these preliminary findings and further investigate the role of insulin signaling in lithium response in BD.
Mitochondrial protein import as a quality control sensor
Authors: Maity Sebabrata , Chakrabarti Oishee
Published: April 2021

Mitochondria are organelles involved in various functions related to cellular metabolism and homoeostasis. Though mitochondria contain own genome, their nuclear counterparts encode most of the different mitochondrial proteins. These are synthesised as precursors in the cytosol and have to be delivered into the mitochondria. These organelles hence have elaborate machineries for the import of precursor proteins from cytosol. The protein import machineries present in both mitochondrial membrane and aqueous compartments show great variability in pre‐protein recognition, translocation and sorting across or into it. Mitochondrial protein import machineries also interact transiently with other protein complexes of the respiratory chain or those involved in the maintenance of membrane architecture. Hence mitochondrial protein translocation is an indispensable part of the regulatory network that maintains protein biogenesis, bioenergetics, membrane dynamics and quality control of the organelle. Various stress conditions and diseases that are associated with mitochondrial import defects lead to changes in cellular transcriptomic and proteomic profiles. Dysfunction in mitochondrial protein import also causes over‐accumulation of precursor proteins and their aggregation in the cytosol. Multiple pathways may be activated for buffering these harmful consequences. Here, we present a comprehensive picture of import machinery and its role in cellular quality control in response to defective mitochondrial import. We also discuss the pathological consequences of dysfunctional mitochondrial protein import in neurodegeneration and cancer.
Home ownership, income and oral health of children in Australia—A population‐based study
Authors: Fleitas Alfonzo Ludmila , Bentley Rebecca , Singh Ankur
Published: April 2021

Objective

Income inequalities in children's oral health have been well described. It is plausible that the security of tenure reflected by the ownership status of children's housing dynamically interacts with household income to shape these inequalities. We examined whether housing tenure modifies the known association between household income and oral health.

Methods

Data were analysed on 3344 10‐ to 11‐year‐old children from the Longitudinal Study of Australian Children. Multivariable regression models tested associations between household income and dental caries and tooth loss due to caries. Effect modification by home ownership (yes/no) was tested on the additive and multiplicative scales. Models were adjusted for sex, Indigenous status, main language spoken at home, area of residence, main carer education and family arrangement.

Results

Children in households in the low income group had worse oral health than children in the high group for caries and tooth loss. Models only weakly supported an additive interaction for tooth loss; that is, the relative excess risk due to interaction (RERI) for low household income was −0.903 (−2.38; 0.571) for tooth loss and −0.076 (−0.42; 0.271) for dental decay, although we note that the low proportion of children from low‐income homeowning households (6%) reduces the power to detect interactions. Notably, our models suggest renters in both high‐ and low‐income categories had the highest risk of tooth loss compared to owners (PR for high‐income renters: 2.19 (95% CI: 1.25, 3.85); PR for low‐income renters: 2.11 (95% CI: 1.42, 3.16)).

Conclusion

Our study confirms that children in low‐income households have poorer oral health outcomes than their high‐income counterparts. Our findings additionally suggest that children in rental households may fare the worst of all housing and income combinations considered. Improving the security of housing for families privately renting may have wider health benefits that currently acknowledged.
Thyroid function and dysfunction in preterm infants—Challenges in evaluation, diagnosis and therapy
Authors: Zdraveska Nikolina , Kocova Mirjana
Published: April 2021

Thyroid hormone levels have a crucial role for optimal brain development from gestation through the first 2 postnatal years. However, thyroid hormones vary with gestational age, and their levels vary between term and preterm infants. Preterm newborns are prone to thyroid dysfunction which is now more frequently observed with the advances of neonatal care and improved survival of extremely premature infants. Thus, hypothyroxinaemia of prematurity associated with delayed TSH elevation is very common in low birth weight premature infants most likely due to the immaturity of the hypothalamic‐pituitary thyroid axis. Furthermore, postnatal illness, medications and iodine status may contribute to the thyroid dysfunction or affect the interpretation of the thyroid function tests. Despite available guidelines, timing of screening and optimal treatment of thyroid dysfunction in premature infants remains controversial. Furthermore, it is unknown whether untreated thyroid dysfunction in premature babies affects neurodevelopmental outcome. In the vast majority of preterm infants, hypothyroxinaemia is transient; however, permanent hypothyroidism due to thyroid dysgenesis or enzyme defects might also occur. Therefore, careful monitoring of thyroid function and long‐term follow‐up is needed to assess an appropriate therapeutic approach. This article reviews thyroid physiology in preterm infants, the influences of gestation and other neonatal conditions on thyroid function tests, optimal timing of screening and possible predictors to differentiate transient hypothyroxinaemia from permanent hypothyroidism.
Consider the context: An analysis of personal social networks of caregivers of children participating in a paediatric weight management program
Authors: D'Silva Chelsea , Thompson Bronwyn , Fierheller Dianne , Martel Sara , Yousefi Nooraie Reza , Zenlea Ian
Published: April 2021

Social networks influence the health and well‐being of children and families. This study aimed to identify and understand the social networks of caregivers of children participating in the KidFit Health and Wellness Clinic, a paediatric weight management program. An egocentric social network analysis was used. Caregivers with children enrolled in KidFit participated in semi‐structured interviews by completing a personal network map and discussing the individuals in their social networks and their influence on them and their family. Twenty‐two caregivers (90.9% mothers) completed the interview. Four structural patterns were identified within the networks: existence of a core, star‐shaped network, well‐connected network and existence of multiple clusters. Healthcare providers and family had the most influence within the caregivers' networks. With the exception of healthcare providers, individuals who communicated less frequently with caregivers tended to have less influence on caregivers. Internet resources, activity‐related resources and social media were the top three services, resources or supports that caregivers reported accessing. It is important that practitioners working with children and families within paediatric settings recognize the unique sociocultural context of each family. Reconceptualising a care model that includes community and incorporates services, supports and resources beyond the clinic could enhance treatment.
Clinical study of atherosclerotic plaque in the carotid artery and lower extremities in patients with obstructive sleep apnea‐hypopnea syndrome
Authors: Li Xiaolong , Wang Pu , Huang Li
Published: April 2021

Objective

The present study aimed to explore the relationship between young and middle‐aged patients with obstructive sleep apnea‐hypopnea syndrome (OSAHS) and atherosclerotic plaque of the carotid artery and lower extremities.

Methods

A total of 110 patients diagnosed with OSAHS by polysomnography in the researchers’ hospital from September 2018 to September 2019 were selected as the research objects. The enrolled patients were divided into a mild group (36 cases), a moderate group (38 cases), and a severe group (36 cases). Another 36 healthy subjects were set up as the non‐OSAHS group. All the selected subjects were examined by color Doppler ultrasound of the carotid artery and lower extremity arteries.

Results

The detection rate of atherosclerotic plaque of the carotid artery and/or lower extremities in patients with OSAHS was significantly higher than that in the non‐OSAHS group (P< 0.05), and the incidence of plaque tended to increase along with an increase in the degree of OSAHS.

Conclusion

The findings indicate that OSAHS might be an independent influencing factor for atherosclerosis.
Evaluating Organizational Identity of Zoos to Enhance Conservation
Authors: Maynard Lily , Adams Alison E. , Jacobson Susan K. , Monroe Martha C.
Published: April 2021

Zoos, aquariums, and museums are expanding their identities and efforts to support wildlife conservation, but their impact is unclear. We apply a business theory of organizational identity to assess how conservation identities are created and applied. We examine three foundational and three practical components of identity using semi‐structured interviews with zoo directors and conservation directors at eight institutions. Our qualitative analysis highlights the well‐established organizational identity constructs among zoos and aquariums, while elucidating the constructs with room for further development and application to activate conservation identities. Each organization shared some conservation strategies and successes, yet the leaders also identified gaps and barriers to reaching conservation goals, including how some zoos perceive their conservation identity competes against other organizational identities and goals. This research provides insights into ways museums can build and reinforce their identities when supporting environmental and social causes. Additionally, the organizational identity framework provides an evaluation tool for examining museums’ integrated identities, strategies, and practices.
Time‐related changes in cell morphology and biomarker immunoreactivity for cells stored in a buffer‐based cell medium
Authors: Srebotnik Kirbis Irena , Prosen Lara , Strojan Flezar Margareta
Published: April 2021

Objective

Buffer‐based cell media (BBCM) are a valuable tool in the post‐collection processing of cytology samples, though with poorly defined effects on cell properties. In this study, time‐related changes in cell morphology and biomarker immunoreactivity were evaluated for cells stored at room temperature in a BBCM prepared with bovine serum albumin (BSA) and ethylene diamine tetraacetic acid (EDTA).

Methods

Cytospins were prepared at five consecutive 24‐hour intervals (0, 24, 48, 72, 96) from three human cell lines (MCF7, SK‐MEL‐28, FaDu) suspended and stored in BBCM. Preservation of cell morphology was evaluated on Papanicolaou‐stained cytospins from the percentages of apoptotic cells. Preservation of immunoreactivity was evaluated for cytokeratins, oestrogen receptors, Ki67, and melanoma markers from the percentages of cells positive for the corresponding immunocytochemical reactions.

Results

Cell morphology was well preserved for the majority of cells of the three lines stored for 24 and 48 hours (93%, 97%, 98% and 62%, 81%, 88%, respectively), while the majority of cells were apoptotic after 72 and 96 hours (70%, 47%, 39% and 77%, 70%, 59%, respectively). The immunoreactivity of cytokeratins remained unchanged during the entire 96 hours, while that of melanoma markers (S100, HMB45, Melan‐A) decreased by 27%, 2%, and 3%, respectively. The immunoreactivity of oestrogen receptors and Ki67 decreased by 29% and 17% after the first 24 hours, and was completely lost after 96 hours.

Conclusions

A BBCM with the addition of BSA and EDTA facilitates good preservation of cell morphology and immunoreactivity of biomarkers for up to 48 hours at room temperature.
Usefulness of preoperative site marking with an indocyanine green fluorescent clip for gastrointestinal stromal tumor
Authors: Minoda Yosuke , Hisamatsu Yuichi , Ihara Eikichi
Published: April 2021

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Effect of the use of music on definitional knowledge in an introductory statistics course: Evidence from a Pareto chart activity
Authors: Anderson Jan L. , Krasnozhon Leonid A.
Published: April 2021

The traditional instructional approach combined with standard textbook examples provide a disengaging learning environment for students in introductory statistics courses. This article proposes and examines an experiential music‐based single‐class‐period learning activity for an introductory statistics course. This activity teaches students how to use graphical presentation of descriptive statistics, such as bar, pie, and Pareto charts. Studies in psychology and consumer research demonstrate that the music has positive short‐term effects on spatial‐temporal reasoning and sensorial response. We use a preclass postclass control‐group design to examine how the change of the method of instruction affects learning outcome. We find that the music‐based experiential learning activity has a positive effect on the definitional knowledge acquired by male students and students with higher grade point averages.
An Ecological Framework for Item Responding Within the Context of a Youth Risk and Needs Assessment
Authors: Vo Thao T. , French Brian F.
Published: April 2021

The use and interpretation of educational and psychological test scores are paramount to individual outcomes and opportunities. Methods for detecting differential item functioning (DIF) are imperative for item analysis when developing and revising assessments, particularly as it pertains to fairness across populations, languages, and cultures. We discuss the practical application of third generation of DIF, which proposes an ecological framework for explaining why DIF occurs using sociological, community, and contextual variables as possible explanations of item responding. We examined school district clusters for DIF through a model‐based approach via multilevel logistic regression random‐intercept and random‐coefficient models to detect racial/ethnic DIF on a youth risk and needs assessment. We demonstrate how the use of district‐level administrative data as estimates of student's contextual environments shows promise to understand ecological sources of DIF and DIF variance. The implication of the work progresses DIF research, enhances the approach to understanding item responses, and provides a more accurate understanding of youth development through an ecological framework. Recommendations for practice and future studies are discussed.
Association of HMOX‐1 with sporadic Alzheimer’s disease in southern Han Chinese
Authors: Zhang Bei , Yu Hong‐Xiang , Zhi Nan , Cui Can , Han Ying‐Ying , Hu Min , Shen Hao , Bao Huan , Li Gang
Published: April 2021

Background and purpose

The aim of this study was to discover the associations between HMOX‐1 and Alzheimer's disease (AD).

Methods

A total of 500 AD patients and 500 healthy controls were recruited in this study. Polymer chain reaction was used.

Results

There was a statistically significant difference between AD patients and controls in both the dominant and recessive models of HMOX‐1 rs2071746 after adjustment for age, gender and education (dominant model: p = 0.047, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.00–1.78, adjusted; recessive model: p = 0.049, OR 1.34, 95% CI 1.00–1.80, adjusted). There was also a trend for an association between the dominant model and late‐onset AD after adjustment for age, gender and education (dominant model: p = 0.084, OR 1.37, 95% CI 0.96–1.95, adjusted).

Conclusions

We found an association between the dominant and recessive models of HMOX1 rs2071746 and AD.
Couples Therapists’ Attitudes Toward Online Therapy During the COVID‐19 Crisis
Authors: Machluf Reut , Abba Daleski Michal , Shahar Ben , Kula Ofra , Bar‐Kalifa Eran
Published: April 2021

The measures adopted by governments around the world to control the spread of the COVID‐19 virus (e.g., social distancing) have propelled a rapid transition from face‐to‐face to online therapy. Studies on online individual therapy indicate that therapists often have favorable attitudes toward this modality. To date, there is scant work on couples therapists’ attitudes, despite the fact that the provision of online couples’ therapy poses unique challenges (e.g., dealing with escalating conflict remotely). To provide a snapshot, in real time, as to how therapists experience the transition to online therapy, we surveyed 166 Israeli couples’ therapists during April 2020, when lockdown orders prevented therapists from seeing couples face‐to‐face. A few weeks later, when the stay‐at‐home policy was lifted, a subsample (N = 60) of these therapists completed a follow‐up assessment. The results suggest that couples therapists had limited experience using the online modality prior to COVID. The therapists reported experiencing online couples’ therapy as somewhat successful and that their experience of providing therapy during the COVID‐19 crisis had an overall positive impact on their attitudes toward online work. Establishing a strong therapeutic bond with both partners, dealing with escalating conflict, and treatment dropout were identified as the issues of most concern when conducting online couples therapy. The perceived difficulties with online therapy prospectively predicted lower usage of online couples’ therapy, as well as less intention to continue online treatment once the crisis is over.
Geometric analysis of the calorimetric glass transition and fragility using constant cooling rate cycles
Authors: Mancini Matthew , Sendova Mariana , Mauro John C.
Published: April 2021

A novel calorimetric approach and analytic method were proposed to characterize the glass transition and fragility of glass‐forming systems. Initial characterization of the glass transition temperatures (onset, inflection, and end) was performed by precisely defining these points based on derivative behavior of the total heat flow curve obtained through differential scanning calorimetry (DSC). Geometric representation allowed for consolidation of critical glass transition data into one matrix. This glass transition matrix can be used for automated characterization of the regime, including thermodynamics and kinetics, via programmed computation. Comparison of results to traditional methods revealed excellent agreement with results derived by the novel procedure proposed, and indeed was corroborated by literature values of glass transition temperature, liquid fragility index, and activation energy. The proposed analytic methods establish a significant metrological traceability by development of a robust confidence interval for all targeted measurands, and in so doing provide a highly reproducible and efficient analysis via DSC.
Neuronally expressed a‐series gangliosides are sufficient to prevent the lethal age‐dependent phenotype in GM3‐only expressing mice
Authors: McGonigal Rhona , Barrie Jennifer A. , Yao Denggao , Black Lauren E. , McLaughlin Mark , Willison Hugh J.
Published: April 2021

Gangliosides are expressed on plasma membranes throughout the body and enriched in the nervous system. A critical role for complex a‐ and b‐series gangliosides in central and peripheral nervous system ageing has been established through transgenic manipulation of enzymes in ganglioside biosynthesis. Disrupting GalNAc‐transferase (GalNAc‐T), thus eliminating all a‐ and b‐series complex gangliosides (with consequent over‐expression of GM3 and GD3) leads to an age‐dependent neurodegeneration. Mice that express only GM3 ganglioside (double knockout produced by crossing GalNAc‐T−/− and GD3 synthase−/− mice, Dbl KO) display markedly accelerated neurodegeneration with reduced survival. Degenerating axons and disrupted node of Ranvier architecture are key features of complex ganglioside‐deficient mice. Previously, we have shown that reintroduction of both a‐ and b‐series gangliosides into neurons on a global GalNAcT−/− background is sufficient to rescue this age‐dependent neurodegenerative phenotype. To determine the relative roles of a‐ and b‐series gangliosides in this rescue paradigm, we herein reintroduced GalNAc‐T into neurons of Dbl KO mice, thereby reconstituting a‐series but not b‐series complex gangliosides. We assessed survival, axon degeneration, axo–glial integrity, inflammatory markers and lipid‐raft formation in these Rescue mice compared to wild‐type and Dbl KO mice. We found that this neuronal reconstitution of a‐series complex gangliosides abrogated the adult lethal phenotype in Dbl KO mice, and partially attenuated the neurodegenerative features. This suggests that whilst neuronal expression of a‐series gangliosides is critical for survival during ageing, it is not entirely sufficient to restore complete nervous system integrity in the absence of either b‐series or glial a‐series gangliosides.

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