bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic effect of ion-releasing fillers on the remineralization and mechanical properties of resin–dentin bonding interfaces
Authors: Xie Yimeng , Chen Ruhua , Yao Wei , Ma Liang , Li Bing
Published: October 2023

In modern restorative dentistry, adhesive resin materials are vital for achieving minimally invasive, esthetic, and tooth-preserving restorations. However, exposed collagen fibers are found in the hybrid layer of the resin-dentin bonding interface due to incomplete resin penetration. As a result, the hybrid layer is susceptible to attack by internal and external factors such as hydrolysis and enzymatic degradation, and the durability of dentin bonding remains limited. Therefore, efforts have been made to improve the stability of the resin-dentin interface and achieve long-term clinical success. New ion-releasing adhesive resin materials are synthesized by introducing remineralizing ions such as calcium and phosphorus, which continuously release mineral ions into the bonding interface in resin-bonded restorations to achieve dentin biomimetic remineralization and improve bond durability. As an adhesive resin material capable of biomimetic mineralization, maintaining excellent bond strength and restoring the mechanical properties of demineralized dentin is the key to its function. This paper reviews whether ion-releasing dental adhesive materials can maintain the mechanical properties of the resin-dentin bonding interface by supplementing the various active ingredients required for dentin remineralization from three aspects: phosphate, silicate, and bioactive glass.
Hidden convexity in the heat, linear transport, and Euler’s rigid body equations: A computational approach
Authors: Kouskiya Uditnarayan , Acharya Amit
Published: October 2023

A finite element based computational scheme is developed and employed to assess a duality based variational approach to the solution of the linear heat and transport PDE in one space dimension and time, and the nonlinear system of ODEs of Euler for the rotation of a rigid body about a fixed point. The formulation turns initial-(boundary) value problems into degenerate elliptic boundary value problems in (space)-time domains representing the Euler-Lagrange equations of suitably designed dual functionals in each of the above problems. We demonstrate reasonable success in approximating solutions of this range of parabolic, hyperbolic, and ODE primal problems, which includes energy dissipation as well as conservation, by a unified dual strategy lending itself to a variational formulation. The scheme naturally associates a family of dual solutions to a unique primal solution; such ‘gauge invariance’ is demonstrated in our computed solutions of the heat and transport equations, including the case of a transient dual solution corresponding to a steady primal solution of the heat equation. Primal evolution problems with causality are shown to be correctly approximated by noncausal dual problems.
Clinicopathologic characterization of cutaneous adult T-cell leukemia/lymphoma: A single tertiary care center experience in the United States
Authors: Modi Mitul B , Kiszluk Alexandra , Chai Jiani N , Edema Ukuemi , Ma Maxwell Y , Sica R Alejandro , Wang Yanhua , Shi Yang
Published: October 2023

Objectives

Adult T-cell leukemia/lymphoma (ATLL) is a rare aggressive T-cell leukemia/lymphoma associated with human T lymphotropic virus type 1 infection. The patients might present with skin rash before, at, or after the diagnosis. The dermatopathologic finding might be diagnostically very challenging.

Methods

We retrospectively identified 110 patients with ATLL at a single institution in a 19-year period, with 19 patients having skin biopsies. Clinical, dermatopathologic, immunophenotypic, and molecular findings were studied.

Results

The cohort included 13 skin-first (5 acute, 5 lymphomatous, 2 chronic, 1 smoldering), 6 skin-second (4 acute, 1 lymphomatous, 1 smoldering), and 91 patients without skin biopsy. Some nonphotoprotected areas of body such as the forearm and lower lip were also seen. Skin manifestations included papular (5), erythroderma (1), nodulotumoral (3), plaques (1), patches (1), and a combination of skin rashes (2). Histopathologic findings included large pleomorphic cells, angiocentrism, epidermal infiltration with large Pautrier-like microabscesses, and folliculotropism. Fifteen (78.9%) cases showed CD4+/CD7–/CD25+. Next-generation sequencing study was conducted on 5 patients using either blood or bone marrow samples, revealing multiple genetic mutations across multiple signaling pathways.

Conclusions

Pleomorphic large, atypical cells with CD4+/CD25+/CD7– immunophenotype from a non–“bathing trunk” location, especially in a patient from endemic regions, raise suspicion for ATLL. T-cell receptor gene rearrangement is almost always positive, and the neoplasm usually demonstrates multiple mutations by next-generation sequencing study.
Characterizing Imbalance in the Tails of the Propensity Score Distribution
Authors: DiPrete Bethany L , Girman Cynthia J , Mavros Panagiotis , Breskin Alexander , Brookhart M Alan
Published: October 2023

Understanding characteristics of patients with propensity scores in the tails of the propensity score (PS) distribution has relevance for inverse-probability-of-treatment–weighted and PS-based estimation in observational studies. Here we outline a method for identifying variables most responsible for extreme propensity scores. The approach is illustrated in 3 scenarios: 1) a plasmode simulation of adult patients in the National Ambulatory Medical Care Survey (2011–2015) and 2) timing of dexamethasone initiation and 3) timing of remdesivir initiation in patients hospitalized for coronavirus disease 2019 from February 2020 through January 2021. PS models were fitted using relevant baseline covariates, and tails of the PS distribution were defined using asymmetric first and 99th percentiles. After fitting of the PS model in each original data set, values of each key covariate were permuted and model-agnostic variable importance measures were examined. Visualization and variable importance techniques were helpful in identifying variables most responsible for extreme propensity scores and may help identify individual characteristics that might make patients inappropriate for inclusion in a study (e.g., off-label use). Subsetting or restricting the study sample based on variables identified using this approach may help investigators avoid the need for trimming or overlap weights in studies.
Cooperation of an external carbonic anhydrase and HCO3– transporter supports underwater photosynthesis in submerged leaves of the amphibious plant Hygrophila difformis
Authors: Horiguchi Genki , Oyama Ryoma , Akabane Tatsuki , Suzuki Nobuhiro , Katoh Etsuko , Mizokami Yusuke , Noguchi Ko , Hirotsu Naoki
Published: October 2023

Background and Aims

HCO3– can be a major carbon resource for photosynthesis in underwater environments. Here we investigate the underlying mechanism of uptake and membrane transport of HCO3– in submerged leaves of Hygrophila difformis, a heterophyllous amphibious plant. To characterize these mechanisms, we evaluated the sensitivity of underwater photosynthesis to an external carbonic anhydrase (CA) inhibitor and an anion exchanger protein inhibitor, and we attempted to identify components of the mechanism of HCO3– utilization.

Methods

We evaluated the effects of the external CA inhibitor and anion exchanger protein inhibitor on the NaHCO3 response of photosynthetic O2 evolution in submerged leaves of H. difformis. Furthermore, we performed a comparative transcriptomic analysis between terrestrial and submerged leaves.

Key Results

Photosynthesis in the submerged leaves was decreased by both the external CA inhibitor and anion exchanger protein inhibitor, but no additive effect was observed. Among upregulated genes in submerged leaves, two α-CAs, Hdα-CA1 and Hdα-CA2, and one β-carbonic anhydrase, Hdβ-CA1, were detected. Based on their putative amino acid sequences, the α-CAs are predicted to be localized in the apoplastic region. Recombinant Hdα-CA1 and Hdβ-CA1 showed dominant CO2 hydration activity over HCO3– dehydration activity.

Conclusions

We propose that the use of HCO3– for photosynthesis in submerged leaves of H. difformis is driven by the cooperation between an external CA, Hdα-CA1, and an unidentified HCO3– transporter.
Capsaicin indirectly regulates TRPA1 via the arachidonic acid cascade, resulting in TJ opening
Authors: Kanda Yusuke , Mukaiyama Minagi , Yamasaki Yohei , Usui Takeo , Nagumo Yoko
Published: October 2023

Capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. We previously revealed that TRPA1 is involved in the capsaicin-induced Ca2+ influx and TJ permeability increase, although there are no reports that capsaicin directly activates TRPA1. In this study, we investigated the upstream factors of TRPA1 using RNA-seq analysis, and found that the cyclooxygenase 2 (COX2) gene was upregulated by capsaicin. Cyclooxygenase 2 converts arachidonic acid (AA), a metabolite by phospholipase A2 (PLA2), to prostaglandins. Prostaglandin E2 (PGE2) production was stimulated by capsaicin, and capsaicin-induced Ca2+ influx was effectively inhibited by PLA2 and COX2 inhibitors. The AA-induced TJ permeability increase was inhibited by a TRPA1 antagonist, but the capsaicin- and AA-induced TJ permeability increases were hardly inhibited by a COX2 inhibitor. These results suggest that capsaicin-induced PLA2 activation and AA production are the important steps for the TJ permeability increase.
Evolution of Skipper (SK), a family of DD34E/Tc1 transposons, in animals
Authors: Wang Saisai , Guan Zhongxia , Diaby Mohamed , Asare Emmanuel , Ullah Numan , Jia Wenzhu , Gao Bo , Yu Duonan , Song Chengyi
Published: October 2023

High diversity and differential evolution profiles have been observed for DD34E/Tc1 transposons; several families originating from these groups, such as DD34E/ZB, DD34E/SB, DD35E/TR, DD36E/IC, and DD38E/IT, have been well defined. Even though Frisky, Tiang, Tsessebe, and Topi transposons have been identified in Anopheles gambiae, their taxonomic distribution and phylogenetic relationship in nature remain largely unknown. The evolutionary profiles of Frisky, Tiang, Tsessebe, and Topi homology transposons were investigated in the current study. In total, 254 homology transposons of Frisky, Tiang, Hob, Tsessebe, and Topi were obtained in 200 species by data mining. The phylogenetic tree revealed that these transposons were classified into five main clades (Frisky, Tiang, Hob, Tsessebe, and Topi) forming a monophyletic clade with 98% bootstrap support, belonging to the DD34E/Tc1 group, and named as Skipper (SK). SK transposons show a wide distribution in animals; however, differential taxonomic distribution patterns were observed for the subfamilies of Frisky, Tiang, Hob, Tsessebe, and Topi; extensive invasion of Frisky in animals was found, whereas Tiang, Hob, Tsessebe, and Topi were mainly detected in Diptera. SK elements share a similar structural organization and display high sequence identities across subfamilies. Evolutionary dynamics and structural analysis revealed that SKs in some species, such as Bombyx mori, Lordiphosa magnipectinata, Carassius gibelio, Triplophysa dalaica, and Silurus glanis, have recently evolved and present as intact copies, indicating that SKs in these genomes may be active. Together, these observations improve our understanding of the diversity of DD34E/Tc1 transposons and their impacts on genome evolution in animals.
Value Compatibility: Work–Family Conflict, Psychological Ownership, Person–Organisation Value Congruence and Turnover Intention amongst Chinese Social Workers
Authors: Chen Yutian , Liang Zurong
Published: October 2023

Chinese social work has experienced a sharp rise in staff turnover. Work–family conflict is a key risk factor for employees’ turnover intention. Whilst the relationship between work–family conflict and turnover intention has been widely documented, little is known about its mediating and moderating mechanisms, especially amongst social workers in China. This study explored the mediating role of job-based and collective psychological ownership and the moderating role of person–organisation value congruence. The study drew on data from the China Social Work Longitudinal Study 2019, a nationally representative sample of 1,421 Chinese social workers (79.73 per cent female; mean age = 28.9 years old). We performed a moderated mediation analysis combining a simple slope test and the Johnson–Neyman technique. Both job-based psychological ownership and collective psychological ownership were found to mediate the association between work–family conflict and turnover intention. Person–organisation value congruence moderated the indirect relationship between work–family conflict and turnover intention via collective psychological ownership. This study enhances understanding of the impact of the psychological mechanisms of work–family conflict on Chinese social workers’ turnover intention. Specific strategies should be adopted to establish a work environment that supports psychological ownership, enhance social workers’ identification with and attachment to their organisations, and thus reduce their turnover intention.
Increased presynaptic excitability in a migraine with aura mutation
Authors: Suryavanshi Pratyush , Sawant-Pokam Punam , Clair Sarah , Brennan K C
Published: October 2023

Migraine is a common and disabling neurological disorder. The headache and sensory amplifications of migraine are attributed to hyperexcitable sensory circuits, but a detailed understanding remains elusive. A mutation in casein kinase 1 delta (CK1δ) was identified in non-hemiplegic familial migraine with aura and advanced sleep phase syndrome. Mice carrying the CK1δT44A mutation were more susceptible to spreading depolarization (the phenomenon that underlies migraine aura), but mechanisms underlying this migraine-relevant phenotype were not known. We used a combination of whole-cell electrophysiology and multiphoton imaging, in vivo and in brain slices, to compare CK1δT44A mice (adult males) to their wild-type littermates.

We found that despite comparable synaptic activity at rest, CK1δT44A neurons were more excitable upon repetitive stimulation than wild-type, with a reduction in presynaptic adaptation at excitatory but not inhibitory synapses. The mechanism of this adaptation deficit was a calcium-dependent enhancement of the size of the readily releasable pool of synaptic vesicles, and a resultant increase in glutamate release, in CK1δT44A compared to wild-type synapses. Consistent with this mechanism, CK1δT44A neurons showed an increase in the cumulative amplitude of excitatory post-synaptic currents, and a higher excitation-to-inhibition ratio during sustained activity compared to wild-type.

At a local circuit level, action potential bursts elicited in CK1δT44A neurons triggered an increase in recurrent excitation compared to wild-type, and at a network level, CK1δT44A mice showed a longer duration of ‘up state’ activity, which is dependent on recurrent excitation. Finally, we demonstrated that the spreading depolarization susceptibility of CK1δT44A mice could be returned to wild-type levels with the same intervention (reduced extracellular calcium) that normalized presynaptic adaptation.

Taken together, these findings show a stimulus-dependent presynaptic gain of function at glutamatergic synapses in a genetic model of migraine, that accounts for the increased spreading depolarization susceptibility and may also explain the sensory amplifications that are associated with the disease.
The Orbits of Folded Crossed Cubes
Authors: Liu Jia-Jie
Published: October 2023

Two vertices $u$ and $v$ in a graph $G=(V,E)$ are in the same orbit if there exists an automorphism $\phi $ of $G$ such that $\phi (u)=v$. The orbit number of a graph $G$, denoted by $Orb(G)$, is the smallest number of orbits, which form a partition of $V(G)$, in $G$. All vertex-transitive graphs $G$ are with $Orb(G)=1$. Since the $n$-dimensional hypercube, denoted by $Q_{n}$, is vertex-transitive, it follows that $Orb(Q_{n})=1$ for $n\geq 1$. Pai, Chang, and Yang proved that the $n$-dimensional folded crossed cube, denoted by $FCQ_{n}$, is vertex-transitive if and only if $n\in \{1,2,4\}$, namely $Orb(FCQ_{1})=Orb(FCQ_{2})=Orb(FCQ_{4})=1$. In this paper, we prove that $Orb(FCQ_{n})=2^{\lceil \frac{n}{2}\rceil -2}$ if $n\geq 6$ is even and $Orb(FCQ_{n}) = 2^{\lceil \frac{n}{2}\rceil -1}$ if $n\geq 3$ is odd.
Successful treatment of frequent premature ventricular contractions and non-sustained ventricular tachycardia with verapamil and flecainide in RYR1-related myopathy: a case report
Authors: Maruo Yuji , Saito Yoshihiko , Nishino Ichizo , Takeda Atsuhito
Published: October 2023

Background

Ryanodine receptor 1 (RYR1)-related myopathies are a group of congenital muscle diseases caused by RYR1 mutations. These mutations may cause centronuclear myopathy, a congenital neuromuscular disorder characterized by clinical muscle weakness and pathological presence of centrally placed nuclei on muscle biopsy. Mutations in RYR2 cause ventricular arrhythmias that can be treated with flecainide; however, reports of ventricular arrhythmias in RYR1-related myopathies are rare. Herein we report a case of centronuclear myopathy with RYR1 mutations who exhibited frequent premature ventricular contractions (PVCs) and non-sustained ventricular tachycardia (NSVT), which was successfully treated with verapamil and flecainide.

Case summary

At 7 months, the patient presented neurological manifestations of hypotonia and delayed motor development. A skeletal muscle biopsy performed at age 4 years led to the diagnosis of centronuclear myopathy. At age 15 years, frequent PVCs and NSVT were identified on the electrocardiogram and 24 h Holter monitoring. Treatment with verapamil was initiated; however, it was not beneficial. Therefore, flecainide was added to the treatment, decreasing the frequency of PVCs and NSVT. Non-sustained ventricular tachycardia disappeared at the age of 21, and PVCs almost disappeared at the age of 22. Genetic testing revealed c.13216delG (p.E4406Rfs*35), c.14874G>C (p.K4958N), and c.9892G>A (p.A3298T) in RYR1, and the compound heterozygosity of variants was confirmed by analysis of the parents.

Discussion

This is the first report of ventricular arrhythmia associated with RYR1-related myopathy that was successfully treated with verapamil and flecainide. The combination of verapamil and flecainide may be a useful treatment option for ventricular arrhythmias in patients with RYR1-related myopathies.
Adult height improved over decades in patients with X-linked hypophosphatemia: a cohort study
Authors: Boros Emese , Ertl Diana-Alexandra , Berkenou Jugurtha , Audrain Christelle , Lecoq Anne Lise , Kamenicky Peter , Briot Karine , Amouroux Cyril , Zhukouskaya Volha , Gueorguieva Iva , Mignot Brigitte , Girerd Barbara , Porquet Bordes Valerie , Salles Jean Pierre , Edouard Thomas , Coutant Régis , Bacchetta Justine , Linglart Agnès , Rothenbuhler Anya
Published: October 2023

Objectives

The aim of this study is to analyze height after cessation of growth (final height [FH]) and its evolution over the last decades in X-linked hypophosphatemia (XLH) patients in France, as the data on natural history of FH in XLH are lacking.

Design

We performed a retrospective observational study in a large cohort of French XLH patients with available data on FH measurements.

Materials and methods

We divided patients into 3 groups according to their birth year: group 1 born between 1950 and 1974, group 2 born between 1975 and 2000, and group 3 born between 2001 and 2006, respectively, and compared their FHs.

Results

A total of 398 patients were included. Mean FHs were the following: for group 1, −2.31 ± 1.11 standard deviation score (SDS) (n = 127), 156.3 ± 9.7 cm in men and 148.6 ± 6.5 cm in women; for group 2, −1.63 ± 1.13 SDS (n = 193), 161.6 ± 8.5 cm in men and 153.1 ± 7.2 cm in women; and for group 3, −1.34 ± 0.87 SDS (n = 78), 165.1 ± 5.5 cm in men and 154.7 ± 6 cm in women. We report a significant increase in mean FH SDS over 3 generations of patients, for both men and women (P < .001). Final height SDS in male (−2.08 ± 1.18) was lower than in female (−1.70 ± 1.12) (P = .002).

Conclusion

The FH of XLH patients in France increased significantly over the last decades. Even though men's FHs improved more than women's, men with XLH remain shorter reflecting a more severe disease phenotype. While the results are promising, most patients with XLH remain short leaving room for improvement.
AlexandrusPS: A User-Friendly Pipeline for the Automated Detection of Orthologous Gene Clusters and Subsequent Positive Selection Analysis
Authors: Ceron-Noriega Alejandro , Schoonenberg Vivien A C , Butter Falk , Levin Michal
Published: October 2023

The detection of adaptive selection in a system approach considering all protein-coding genes allows for the identification of mechanisms and pathways that enabled adaptation to different environments. Currently, available programs for the estimation of positive selection signals can be divided into two groups. They are either easy to apply but can analyze only one gene family at a time, restricting system analysis; or they can handle larger cohorts of gene families, but require considerable prerequisite data such as orthology associations, codon alignments, phylogenetic trees, and proper configuration files. All these steps require extensive computational expertise, restricting this endeavor to specialists. Here, we introduce AlexandrusPS, a high-throughput pipeline that overcomes technical challenges when conducting transcriptome-wide positive selection analyses on large sets of nucleotide and protein sequences. The pipeline streamlines 1) the execution of an accurate orthology prediction as a precondition for positive selection analysis, 2) preparing and organizing configuration files for CodeML, 3) performing positive selection analysis using CodeML, and 4) generating an output that is easy to interpret, including all maximum likelihood and log-likelihood test results. The only input needed from the user is the CDS and peptide FASTA files of proteins of interest. The pipeline is provided in a Docker image, requiring no program or module installation, enabling the application of the pipeline in any computing environment. AlexandrusPS and its documentation are available via GitHub (https://github.com/alejocn5/AlexandrusPS).
Assessment of Physical Resilience Using Residual Methods and Its Association With Adverse Outcomes in Older Adults
Authors: Zhang Hui , Hao Meng , Li Yi , Hu Zixin , Liu Zuyun , Jiang Shuai , Jin Li , Wang Xiaofeng
Published: October 2023

Background and Objectives

Physical resilience (PR) is recognized as the ability to recover from the adverse effects of a stressor. However, there is a lack of consensus on how to optimally measure PR in older adults in general. We aimed to measure PR using residuals from regression analyses and investigated its association with adverse outcomes in older adults.

Research Design and Methods

A total of 6 508 older adults were included from the National Health and Aging Trends Study, which was a population-based prospective cohort study. PR was assessed using residual methods from a linear model regressing the short physical performance battery on clinical diseases, age, sex, race/ethnicity, and health condition. Adverse outcomes included all-cause mortality, falls, and overnight hospitalization.

Results

The mean age was 77.48 (7.84) years. Increased PR was associated with a lower risk of all-cause mortality (hazard ratio [HR] = 0.85, 95% confidence interval [CI]: 0.83–0.87). Compared to participants with reduced PR, those with normal PR had a lower risk for mortality (HR = 0.51, 95% CI: 0.46–0.56). Specifically, restricted cubic spline regression revealed a dose–response relationship between PR and all-cause mortality (p-overall < .0001, p-nonlinear = .011). Additionally, we also found significant associations of increased PR with lower risks of falls (HR = 0.98, 95% CI: 0.96–0.99) and overnight hospitalization (HR = 0.98, 95% CI: 0.97–1.00).

Discussion and Implications

PR, measured by residual methods, was robustly and independently associated with all-cause mortality, falls, and overnight hospitalization. Our findings provide evidence that this approach may be a simple and feasible strategy to assess PR.
The haplotype-resolved T2T genome of teinturier cultivar Yan73 reveals the genetic basis of anthocyanin biosynthesis in grapes
Authors: Zhang Kekun , Du Mengrui , Zhang Hongyan , Zhang Xiaoqian , Cao Shuo , Wang Xu , Wang Wenrui , Guan Xueqiang , Zhou Penghui , Li Jin , Jiang Wenguang , Tang Meiling , Zheng Qiuling , Cao Muming , Zhou Yongfeng , Chen Keqin , Liu Zhongjie , Fang Yulin
Published: October 2023

Teinturier grapes are characterized by the typical accumulation of anthocyanins in grape skin, flesh, and vegetative tissues, endowing them with high utility value in red wine blending and nutrient-enriched foods developing. However, due to the lack of genome information, the mechanism involved in regulating teinturier grape coloring has not yet been elucidated and their genetic utilization research is still insufficient. Here, the cultivar ‘Yan73’ was used for assembling the telomere-to-telomere (T2T) genome of teinturier grapes by combining the High Fidelity (HiFi)， Hi-C and ultralong Oxford Nanopore Technologies (ONT) reads. Two haplotype genomes were assembled, at the sizes of 501.68 Mb and 493.38 Mb, respectively. In the haplotype 1 genome, the transposable elements (TEs) contained 32.77% of long terminal repeats (LTRs), while in the haplotype 2 genome, 31.53% of LTRs were detected in TEs. Furthermore, obvious inversions were identified in chromosome 18 between the two haplotypes. Transcriptome profiling suggested that the gene expression patterns in ‘Cabernet Sauvignon’ and ‘Yan73’ were diverse depending on tissues, developmental stages, and varieties. The transcription program of genes in the anthocyanins biosynthesis pathway between the two cultivars exhibited high similarity in different tissues and developmental stages, whereas the expression levels of numerous genes showed significant differences. Compared with other genes, the expression levels of VvMYBA1 and VvUFGT4 in all samples, VvCHS2 except in young shoots and VvPAL9 except in the E-L23 stage of ‘Yan73’ were higher than those of ‘Cabernet Sauvignon’. Further sequence alignments revealed potential variant gene loci and structure variations of anthocyanins biosynthesis related genes and a 816 bp sequence insertion was found in the promoter of VvMYBA1 of ‘Yan73’ haplotype 2 genome. The ‘Yan73’ T2T genome assembly and comparative analysis provided valuable foundations for further revealing the coloring mechanism of teinturier grapes and the genetic improvement of grape coloring traits.
Partitioning genetic effects on birthweight at classical human leukocyte antigen loci into maternal and fetal components, using structural equation modelling
Authors: Wang Geng , Warrington Nicole M , Evans David M
Published: October 2023

Background

Single nucleotide polymorphisms in the human leukocyte antigen (HLA) region in both maternal and fetal genomes have been robustly associated with birthweight (BW) in previous genetic association studies. However, no study to date has partitioned the association between BW and classical HLA alleles into maternal and fetal components.

Methods

We used structural equation modelling (SEM) to estimate the maternal and fetal effects of classical HLA alleles on BW. Our SEM leverages the data structure of the UK Biobank (UKB), which includes ∼270 000 participants’ own BW and/or the BW of their firstborn child.

Results

We show via simulation that our model yields asymptotically unbiased estimates of the maternal and fetal allelic effects on BW and appropriate type I error rates, in contrast to simple regression models. Asymptotic power calculations show that we have sufficient power to detect moderate-sized maternal or fetal allelic effects of common HLA alleles on BW in the UKB. Applying our SEM to imputed classical HLA alleles and own and offspring BW from the UKB replicated the previously reported association at the HLA-C locus and revealed strong evidence for maternal (HLA-A*03:01, B*35:01, B*39:06, P <0.001) and fetal allelic effects (HLA-B*39:06, P <0.001) of non-HLA-C alleles on BW.

Conclusions

Our model yields asymptotically unbiased estimates, appropriate type I error rates and appreciable power to estimate maternal and fetal effects on BW. These novel allelic associations between BW and classical HLA alleles provide insight into the immunogenetics of fetal growth in utero.
Deformations of Pairs of Kleinian Singularities
Authors: Klyuev Daniil
Published: October 2023

Kleinian singularities, that is, the varieties corresponding to the algebras of invariants of Kleinian groups are of fundamental importance for Algebraic geometry, Representation theory, and Singularity theory. The filtered deformations of these algebras of invariants were classified by Brieskorn (the commutative case) and Losev (the general case). To an inclusion of Kleinian groups, there is the corresponding inclusion of algebras of invariants. We classify deformations of these inclusions when the smaller subgroup is normal in the larger.
Comparative anatomy of venom glands suggests a role of maternal secretions in gall induction by cynipid wasps (Hymenoptera: Cynipidae)
Authors: Guiguet Antoine , Tooker John F , Deans Andrew R , Mikó István , Ning Gang , Schwéger Szabina , Hines Heather M
Published: October 2023

Many herbivorous insect species are capable of hijacking plant development to induce novel plant organs called galls. In most groups of galling insects, the insect organs and molecular signals involved in gall induction are poorly understood. We focused on gall wasps (Hymenoptera:Cynipidae), the second largest clade of gall inducers (~1,400 spp.), for which the developmental stages and organs responsible for gall development are unclear. We investigated the female metasomal anatomy of 69 gall-inducing and 29 non-gall-inducing species across each of the major lineages of Cynipoidea, to test relationships between this lifestyle and the relative size of secretory organs. We confirmed that the venom apparatus in gall-inducing species is greatly expanded, although gall-inducing lineages vary in the relative size of these glands. Among these gallers, we measured the largest venom gland apparatus relative to body size ever recorded in insects. Non-galling inquiline species are accompanied by a reduction of this apparatus. Comparative microscopic analysis of venom glands suggests varying venom gland content across the lineages. Some oak gallers also had enlarged accessory glands, a lipid-rich organ whose function remains unclear, and which has not been previously studied in relation to gall formation. Together, the massive expansion of secretory organs specifically in gall-inducing species suggests a role of these secretions in the process of gall formation, and the variance in size of venom glands, accessory glands, and the contents of these glands among gallers, suggests that gall formation across this clade is likely to employ a diversity of molecular strategies.
Evaluation of phenotypical and genotypical methods for the identification and typing of Stenotrophomonas maltophilia isolated from a pharmaceutical facility
Authors: de Miranda Rebeca Vitória da Silva Lage , Monteiro Giovanna Merrelho , da Costa Luciana Veloso , dos Santos Milena Cristina Silva , dos Reis Cristhiane Moura Falavina , Braga Lygia Maria Paulo da Silva , Forsythe Stephen James , Villas Bôas Maria Helena Simões , Brandão Marcelo Luiz Lima
Published: October 2023

Aims

Evaluate methods for identification and typing of Stenotrophomonas maltophilia isolated from a pharmaceutical facility.

Methods and results

From 270 S. maltophilia strains identified by VITEK®2, 40 were selected and submitted to MALDI TOF-MS, 16S and 23S rRNA gene analysis, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), and an antimicrobial susceptibility profile. 16S rRNA sequencing was able to identify 39 (97.5%) strains as Stenotrophomonas spp. and one (2.5%) as Luteimonas huabeiensis. MALDI TOF-MS identified 37 (92.5%) strains as S. maltophilia, and three (7.5%) were not identified. PCR targeting 23S rRNA yielded a positive result for 39 (97.5%) strains. However, after sequencing, two strains were identified as Stenotrophomonas rhizophila, showing false-positive results. The confirmed S. maltophilia strains (n = 37) showed 35 distinct ERIC-PCR profiles and exhibited sensitivity to minocycline and levofloxacin, and six (16.3%) showed intermediate resistance to sulfamethoxazole-trimethoprim.

Conclusion

Matrix-assisted laser desorption lonization-time of flight mass spectrometry (MALDI-TOF MS) was a satisfactory methodology for the identification of S. maltophilia, but expansion of the database is necessary for the identification of other species. 16S rDNA sequencing showed low resolution for Stenotrophomonas species differentiation. PCR targeting 23S rRNA could not differentiate S. maltophilia from S. rhizophila. ERIC-PCR was shown to be a useful tool for the microbial source tracking of S. maltophilia.
Presidential Address 2023: The Beauty of Uncertainty: The Rise of Insurance Contracts and Markets in Medieval Europe
Authors: Botticini Maristella , Buri Pietro , Marinacci Massimo
Published: October 2023

Maritime insurance developed in medieval Europe is the ancestor of all forms of insurance that appeared subsequently. We address the question of why modern insurance was first invented in medieval Europe, and neither earlier nor elsewhere. Drawing from insights from the literature on uncertainty aversion, we show that medieval merchants had to bear more frequently natural risks (they traveled longer distances) and new human risks with unknown probabilities (they faced unpredictable attacks by corsairs due to increased political fragmentation and commercial competition in Europe). The increased demand for protection in medieval seaborne trade met the supply of protection by a small group of wealthy merchants with a broad information network who could pool risks and profit from selling protection through a novel business device: the insurance contract. A new market—the market for insurance—was then born. Next, analyzing more than 7,000 insurance contracts redacted by notaries and about 100 court proceedings housed in the archives of Barcelona, Florence, Genoa, Palermo, Prato, and Venice, we study the main features of medieval trade, the type of risks faced by merchants, and the characteristics of insurance contracts and markets from 1340 to 1500.The empirical analysis delivers two main findings. First, risks related to human activities (e.g., attacks by corsairs) seem to have had a relatively greater impact on insurance premia compared to natural risks (proxied by seasonal risks). Second, distance mattered but the route seems to have had a greater impact on insurance premia. Specific routes (e.g., in the Tyrrhenian and the western Mediterranean) were more plagued by human risks, which were harder to avoid for the majority of merchants who did not have a broad information network compared to the few wealthy merchants, who became the key players in selling insurance in the early stages of the development of insurance markets.
The Zoom city: working from home, urban productivity and land use
Authors: Kyriakopoulou Efthymia , Picard Pierre M
Published: October 2023

This article investigates the impact of working from home (WFH) on the emergence and structure of monocentric cities. In the long run, WFH raises urban productivity only in sufficiently large cities. Business land rents fall while residential land rents decrease near the business district. Workers have incentives to adopt inefficiently high WFH schemes. In the short run, WFH yields mixed benefits for commuters and firms, which corroborates the low WFH adoption before the pandemic. Advances in digital technology increase the welfare benefits of WFH. Calibration exercises on European capital cities shed light on the quantitative impact of WFH.
Collecting antiquities in wartime
Authors: Donaldson James , Asmussen Brit , McWilliam Janette , Parkhill David
Published: October 2023

During the First World War (1914–1918), many service personnel collected souvenirs from the countries in which they served, but the collection of antiquities by service personnel remains a neglected area of research. Between 2019 and 2021, the R. D. Milns Antiquities Museum at the University of Queensland and the Queensland Museum collaborated in a research partnership to learn more about the antiquities collecting activities of First World War personnel from Queensland, Australia. In addition to reporting on the preliminary results of that pilot study, this paper also begins to address the question of why antiquities appealed to service personnel. Most artefacts in this study are from the private collections donated to the Queensland Museum and from three privately owned collections. Artefacts are mostly small ‘curios’ such as scarabs, figurines, coins and fragments of monuments collected in various theatres of the war.
The hybrid work of public sector data scientists
Authors: Lorenz Lukas
Published: October 2023

As algorithms play an increasingly important role in public organizations, we see a rise in the number of public sector data scientists. Even though the relevance and risks of algorithms in the public sector are broadly discussed, our current academic knowledge of public sector data scientists and their work is limited. To develop an understanding of their work practices, data scientists have been studied in two Dutch government organizations. In a core period of 5 months per organization, I conducted in-depth qualitative research into the work of the data scientists, their role in the organization, and their relationship with other actors at two regulatory agencies in the Netherlands. The analysis shows that data scientists integrate Silicon Valley and engineering, domain, as well as political–administrative logics in their work practices. Thus, the work of the data scientists is hybrid. However, even though the organizational contexts are very similar, hybrid work takes very different forms both across organizations and over time. This dynamic hybridity is linked to different algorithmization processes and outcomes in the two organizations. The results suggest that hybridity in public sector data scientists’ work should be adapted to organizational and technological aspects of transformation processes and aspired outcomes.
Ultrasound-mediated delivery of Pik3cb shRNA using magnetic nanoparticles for the treatment of in-stent restenosis in a rat balloon-injured model
Authors: Wang Yuhao , Li Miao , Sheng Zongxiang , Ran Hong , Dong Jing , Fang Lingling , Zhang Pingyang
Published: October 2023

The aim of the present work was to examine the effect of polyethylene glycol (PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles carrying Pik3cb short hairpin RNA (shRNA) in the prevention of restenosis with the aid of ultrasound and a magnetic field. SPIO is a type of contrast agent used in medical imaging to enhance the visibility of specific tissues or organs. It consists of tiny iron oxide nanoparticles that can be targeted to specific areas of interest in the body. PEG-coated SPIO nanoparticles carrying Pik3cb shRNA (SPIO-shPik3cb) were prepared, and the particle size and zeta potential of PEG-coated SPIO nanoparticles with and without Pik3cb shRNA were examined. After a right common artery balloon-injured rat model was established, the rats were randomly divided into four groups, and the injured arteries were transfected with SPIO-shPik3cb, saline, SPIO-shcontrol and naked shRNA Pik3cb. During the treatment, each group was placed under a magnetic field and was transfected with the aid of ultrasound. Rats were sacrificed, and the tissue was harvested for analysis after 14 days. The results suggested that the mean particle size and zeta potential of SPIO-shPik3cbs were 151.45 ± 11 nm and 10 mV, respectively. SPIO-shPik3cb showed higher transfection efficiency and significantly inhibited the intimal thickening compared with naked Pik3cb shRNA in vascular smooth muscle cells (VSMCs) (*P < 0.05). Moreover, SPIO-shPik3cb could also significantly downregulate the expression of pAkt protein compared with naked Pik3cb shRNA. According to the results, SPIO-shPik3cb can remarkably inhibit the intimal thickening under a combination of magnetic field exposure and ultrasound.
Effect of Liraglutide on Osteoporosis in a Rat Model of Type 2 Diabetes Mellitus: A Histological, Immunohistochemical, and Biochemical Study
Authors: Fathy Maha Abdelhamid , Anbaig Amal , Aljafil Raja , El-Sayed Sherein F , Abdelnour Hanim Magdy , Ahmed Mona Mostafa , Abdelghany Eman M A , Alnasser Sulaiman Mohammed , Hassan Shaimaa Mohamed Abdelfattah , Shalaby Amany Mohamed
Published: October 2023

Diabetic osteoporosis (DOP) is a diabetic complication associated with a significant disability rate. Liraglutide, a glucagon-like peptide-1 receptor agonist, is a promising and innovative drug for type 2 diabetes mellitus (T2DM), with potential therapeutic implications for bone disorders. This investigation examined the impact of liraglutide on osteoporosis in rats with T2DM and studied the influence of vitamin D receptor Bsm1 polymorphism on liraglutide-induced outcomes. Thirty rats were divided into control, T2DM induced by a combination of a high-fat diet and 25 mg/kg streptozotocin, and T2DM-liraglutide (T2DM treated with 0.4 mg/kg/day liraglutide) groups. After 8 weeks of liraglutide treatment, femurs and blood samples were obtained from all rats for subsequent investigations. Diabetes induced a remarkable rise in the serum levels of receptor activator of nuclear factor kappa B ligand (RANKL) and C-telopeptide of type I collagen (CTX-1) associated with a remarkable decline in osteocalcin and osteoprotegerin (OPG). Impaired bone architecture was also demonstrated by light and scanning electron microscopic study. The immune expression of OPG was down-regulated, while RANKL was up-regulated. Interestingly, the administration of liraglutide ameliorated the previous changes induced by diabetes mellitus. In conclusion, liraglutide can prevent DOP, mostly due to liraglutide's ability to increase bone growth, while inhibiting bone resorption.
Evaluating Stage Motion for Automated Electron Microscopy
Authors: Fiedler Kevin R , Olszta Matthew J , Yano Kayla H , Doty Christina , Hopkins Derek , Akers Sarah , Spurgeon Steven R
Published: October 2023

Precise control is an essential and elusive quality of emerging self-driving transmission electron microscopes (TEMs). It is widely understood these instruments must be capable of performing rapid, high-volume, and arbitrary movements for practical self-driving operation. However, stage movements are difficult to automate at scale, owing to mechanical instability, hysteresis, and thermal drift. Such difficulties pose major barriers to artificial intelligence-directed microscope designs that require repeatable, precise movements. To guide design of emerging instruments, it is necessary to understand the behavior of existing mechanisms to identify rate limiting steps for full autonomy. Here, we describe a general framework to evaluate stage motion in any TEM. We define metrics to evaluate stage degrees of freedom, propose solutions to improve performance, and comment on fundamental limits to automated experimentation using present hardware.
The orbital period of the recurrent nova V2487 Oph revealed
Authors: Rodríguez-Gil Pablo , Corral-Santana Jesús M , Elías-Rosa N , Gänsicke Boris T , Hernanz Margarita , Sala Gloria
Published: October 2023

We present the first reliable determination of the orbital period of the recurrent nova V2487 Oph (Nova Oph 1998). We derived a value of 0.753 ± 0.016 d (18.1 ± 0.4 h) from the radial velocity curve of the intense He ii λ4686 emission line as detected in time-series X-shooter spectra. The orbital period is significantly shorter than earlier claims, but it makes V2487 Oph one of the longest period cataclysmic variables known. The spectrum of V2487 Oph is prolific in broad Balmer absorptions that resemble a white dwarf spectrum. However, we show that they come from the accretion disc viewed at low inclination. Although highly speculative, the analysis of the radial velocity curves provides a binary mass ratio q ≈ 0.16 and a donor star mass M2 ≈ 0.21 M⊙, assuming the reported white dwarf mass M1 = 1.35 M⊙. A subgiant M-type star is tentatively suggested as the donor star. We were lucky to inadvertently take some of the spectra when V2487 Oph was in a flare state. During the flare, we detected high-velocity emission in the Balmer and He ii λ4686 lines exceeding −2000 km s−1 at close to orbital phase 0.4. Receding emission up to 1200 km s−1 at about phase 0.3 is also observed. The similarities with the magnetic cataclysmic variables may point to magnetic accretion on to the white dwarf during the repeating flares.
QUIJOTE Scientific Results – XVII. Studying the anomalous microwave emission in the Andromeda Galaxy with QUIJOTE-MFI
Authors: Fernández-Torreiro M , Génova-Santos R T , Rubiño-Martín J A , López-Caraballo C H , Peel M W , Arce-Tord C , Rebolo R , Artal E , Ashdown M , Barreiro R B , Casas F J , de la Hoz E , Guidi F , Herranz D , Hoyland R , Lasenby A , Martínez-Gonzalez E , Piccirillo L , Poidevin F , Ruiz-Granados B , Tramonte D , Vansyngel F , Vielva P , Watson R A
Published: October 2023

The Andromeda Galaxy (M31) is the Local Group galaxy that is most similar to the Milky Way (MW). The similarities between the two galaxies make M31 useful for studying integrated properties common to spiral galaxies. We use the data from the recent QUIJOTE-MFI Wide Survey, together with new raster observations focused on M31, to study its integrated emission. The addition of raster data improves the sensitivity of QUIJOTE-MFI maps by almost a factor 3. Our main interest is to confirm if anomalous microwave emission (AME) is present in M31, as previous studies have suggested. To do so, we built the integrated spectral energy distribution of M31 between 0.408 and 3000 GHz. We then performed a component separation analysis taking into account synchrotron, free–free, AME, and thermal dust components. AME in M31 is modelled as a log-normal distribution with maximum amplitude, AAME, equal to 1.03 ± 0.32 Jy. It peaks at ${\nu _{\rm AME}}=17.2\pm 3.2{\rm \, GHz}{}$ with a width of WAME = 0.58 ± 0.16. Both the Akaike and Bayesian information criteria find the model without AME to be less than 1 per cent as probable as the one taking AME into consideration. We find that the AME emissivity per 100 $\mu$m intensity in M31 is ${\epsilon _{\rm AME}^{\rm 28.4\, GHz}}=9.6\pm 3.1\,\mu$K MJy−1 sr, similar to that of the MW. We also provide the first upper limits for the AME polarization fraction in an extragalactic object. M31 remains the only galaxy where an AME measurement has been made of its integrated spectrum.