bluuebunny/crossref_metadata_2025 huggingface dataset:
Sports and US Foreign Relations
Authors: Dichter Heather L.
Published: January 2024

Against the long-standing claim that sport and politics should remain separate, the United States has long included sport within its broader foreign relations efforts. During the second half of the 19th century, American businessmen, members of the military, and missionaries all taught local populations how to play sports like baseball and basketball because they viewed their actions as part of the “civilizing mission” of Americans abroad.

With the onset of the Cold War, the government began incorporating sport into its formal programs to promote the United States overseas, using athletes as a large part of its public diplomacy efforts. Federal programs related to physical education were implemented to improve American health in the interest of fighting the Soviet Union. Sport thus served a role in the global competition of the Cold War as well as contributing to building bridges with other states. In the 21st century, the government formalized the use of sport within public diplomacy efforts with the establishment of a bureaucracy focused solely on sport.

Sport also provided an avenue to spread American culture overseas as a model for organizing events and the approach to marketing and sponsorship. Both the 1984 Los Angeles Olympic Games and Nike’s contract with basketball player Michael Jordan established new forms of cultural capitalism. American professional teams have capitalized on their global interest by holding exhibition and regular-season games overseas, bringing an American sport experience to international audiences while simultaneously expanding marketing opportunities.
Islamic Bioethics: Bioethics in Egypt
Authors: Dupret Baudouin , El Bernoussi Zaynab
Published: January 2024

Continuous technical developments in medicine prompt different actors to think about morality, biology, and the legitimacy of scientific progress in different societies. In Muslim-majority countries, religious institutions provide a trusted source of guidance on bioethical issues for believers. Meanwhile, in Egypt, the Napoleonic colonial legacy has granted more authority to the state in ruling over the individual’s body. There are increasing demands for pluralism within Muslim-majority countries and the notion of pan-Muslim events as important venues to discuss pressing bioethics issues, such as contraception, abortion, and population control.
SPANN: annotating single-cell resolution spatial transcriptome data with scRNA-seq data
Authors: Yuan Musu , Wan Hui , Wang Zihao , Guo Qirui , Deng Minghua
Published: January 2024

Motivation

The rapid development of spatial transcriptome technologies has enabled researchers to acquire single-cell-level spatial data at an affordable price. However, computational analysis tools, such as annotation tools, tailored for these data are still lacking. Recently, many computational frameworks have emerged to integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics datasets. While some frameworks can utilize well-annotated scRNA-seq data to annotate spatial expression patterns, they overlook critical aspects. First, existing tools do not explicitly consider cell type mapping when aligning the two modalities. Second, current frameworks lack the capability to detect novel cells, which remains a key interest for biologists.

Results

To address these problems, we propose an annotation method for spatial transcriptome data called SPANN. The main tasks of SPANN are to transfer cell-type labels from well-annotated scRNA-seq data to newly generated single-cell resolution spatial transcriptome data and discover novel cells from spatial data. The major innovations of SPANN come from two aspects: SPANN automatically detects novel cells from unseen cell types while maintaining high annotation accuracy over known cell types. SPANN finds a mapping between spatial transcriptome samples and RNA data prototypes and thus conducts cell-type-level alignment. Comprehensive experiments using datasets from various spatial platforms demonstrate SPANN’s capabilities in annotating known cell types and discovering novel cell states within complex tissue contexts.

Availability

The source code of SPANN can be accessed at https://github.com/ddb-qiwang/SPANN-torch.

Contact

dengmh@math.pku.edu.cn.
Identification, characterization and expression analysis of circRNA encoded by SARS-CoV-1 and SARS-CoV-2
Authors: Niu Mengting , Wang Chunyu , Chen Yaojia , Zou Quan , Xu Lei
Published: January 2024

Virus-encoded circular RNA (circRNA) participates in the immune response to viral infection, affects the human immune system, and can be used as a target for precision therapy and tumor biomarker. The coronaviruses SARS-CoV-1 and SARS-CoV-2 (SARS-CoV-1/2) that have emerged in recent years are highly contagious and have high mortality rates. In coronaviruses, little is known about the circRNA encoded by the SARS-CoV-1/2. Therefore, this study explores whether SARS-CoV-1/2 encodes circRNA and characteristics and functions of circRNA. Based on RNA-seq data of SARS-CoV-1 and SARS-CoV-2 infections, we used circRNA identification tools (circRNA_finder, find_circ and CIRI2) to identify circRNAs. The number of circRNAs encoded by SARS-CoV-1 and SARS-CoV-2 was identified as 151 and 470, respectively. It can be found that SARS-CoV-2 shows more prominent circRNA encoding ability than SARS-CoV-1. Expression analysis showed that only a few circRNAs encoded by SARS-CoV-1/2 showed high expression levels, and the positive strand produced more abundant circRNAs. Then, based on the identified SARS-CoV-1/2-encoded circRNAs, we performed circRNA identification and characterization using the previously developed CirRNAPL. Finally, target gene prediction and functional enrichment analysis were performed. It was found that viral circRNA is closely related to cancer and has a potential role in regulating host cell functions. This study studied the characteristics and functions of viral circRNA encoded by coronavirus SARS-CoV-1/2, providing a valuable resource for further research on the function and molecular mechanism of coronavirus circRNA.
Benchmarking of computational methods for m6A profiling with Nanopore direct RNA sequencing
Authors: Maestri Simone , Furlan Mattia , Mulroney Logan , Coscujuela Tarrero Lucia , Ugolini Camilla , Dalla Pozza Fabio , Leonardi Tommaso , Birney Ewan , Nicassio Francesco , Pelizzola Mattia
Published: January 2024

N6-methyladenosine (m6A) is the most abundant internal eukaryotic mRNA modification, and is involved in the regulation of various biological processes. Direct Nanopore sequencing of native RNA (dRNA-seq) emerged as a leading approach for its identification. Several software were published for m6A detection and there is a strong need for independent studies benchmarking their performance on data from different species, and against various reference datasets. Moreover, a computational workflow is needed to streamline the execution of tools whose installation and execution remains complicated. We developed NanOlympicsMod, a Nextflow pipeline exploiting containerized technology for comparing 14 tools for m6A detection on dRNA-seq data. NanOlympicsMod was tested on dRNA-seq data generated from in vitro (un)modified synthetic oligos. The m6A hits returned by each tool were compared to the m6A position known by design of the oligos. In addition, NanOlympicsMod was used on dRNA-seq datasets from wild-type and m6A-depleted yeast, mouse and human, and each tool’s hits were compared to reference m6A sets generated by leading orthogonal methods. The performance of the tools markedly differed across datasets, and methods adopting different approaches showed different preferences in terms of precision and recall. Changing the stringency cut-offs allowed for tuning the precision-recall trade-off towards user preferences. Finally, we determined that precision and recall of tools are markedly influenced by sequencing depth, and that additional sequencing would likely reveal additional m6A sites. Thanks to the possibility of including novel tools, NanOlympicsMod will streamline the benchmarking of m6A detection tools on dRNA-seq data, improving future RNA modification characterization.
Revolutionizing immune research with organoid-based co-culture and chip systems
Authors: Papp Diana , Korcsmaros Tamas , Hautefort Isabelle
Published: January 2024

The intertwined interactions various immune cells have with epithelial cells in our body require sophisticated experimental approaches to be studied. Due to the limitations of immortalized cell lines and animal models, there is an increasing demand for human in vitro model systems to investigate the microenvironment of immune cells in normal and in pathological conditions. Organoids, which are self-renewing, 3D cellular structures that are derived from stem cells, have started to provide gap-filling tissue modelling solutions. In this review, we first demonstrate with some of the available examples how organoid-based immune cell co-culture experiments can advance disease modelling of cancer, inflammatory bowel disease, and tissue regeneration. Then, we argue that to achieve both complexity and scale, organ-on-chip models combined with cutting-edge microfluidics-based technologies can provide more precise manipulation and readouts. Finally, we discuss how genome editing techniques and the use of patient-derived organoids and immune cells can improve disease modelling and facilitate precision medicine. To achieve maximum impact and efficiency, these efforts should be supported by novel infrastructures such as organoid biobanks, organoid facilities, as well as drug screening and host-microbe interaction testing platforms. All these together or in combination can allow researchers to shed more detailed, and often patient-specific, light on the crosstalk between immune cells and epithelial cells in health and disease.
Bugs in our pockets: the risks of client-side scanning
Authors: Abelson Harold , Anderson Ross , Bellovin Steven M , Benaloh Josh , Blaze Matt , Callas Jon , Diffie Whitfield , Landau Susan , Neumann Peter G , Rivest Ronald L , Schiller Jeffrey I , Schneier Bruce , Teague Vanessa , Troncoso Carmela
Published: January 2024

Our increasing reliance on digital technology for personal, economic, and government affairs has made it essential to secure the communications and devices of private citizens, businesses, and governments. This has led to pervasive use of cryptography across society. Despite its evident advantages, law enforcement and national security agencies have argued that the spread of cryptography has hindered access to evidence and intelligence. Some in industry and government now advocate a new technology to access targeted data: client-side scanning (CSS). Instead of weakening encryption or providing law enforcement with backdoor keys to decrypt communications, CSS would enable on-device analysis of data in the clear. If targeted information were detected, its existence and, potentially, its source would be revealed to the agencies; otherwise, little or no information would leave the client device. Its proponents claim that CSS is a solution to the encryption versus public safety debate: it offers privacy—in the sense of unimpeded end-to-end encryption—and the ability to successfully investigate serious crime. In this paper, we argue that CSS neither guarantees efficacious crime prevention nor prevents surveillance. Indeed, the effect is the opposite. CSS by its nature creates serious security and privacy risks for all society, while the assistance it can provide for law enforcement is at best problematic. There are multiple ways in which CSS can fail, can be evaded, and can be abused.
The Select Council of Philip I: A Spanish Institution in Tudor England, 1555–1558
Authors: Velasco Berenguer Gonzalo
Published: January 2024

Traditional interpretations of the reign of Philip and Mary in England and Ireland (1554–58) have tended to investigate this short-lived episode from a strongly Anglocentric perspective. Such an approach has often hindered interpretations of crucial aspects of the reign that have wider implications for the study of Britain, Spain and Europe in an increasingly globalised world. Philip’s creation of a new consultative body in 1555, the select council (consejo escogido), is a case in point. Conventionally viewed as a superfluous body that only worsened the alleged ungovernability of Mary’s privy council—from which, it was claimed, it was never truly separate—it has been assumed that the select council was allowed to function nominally for a while to sustain Philip’s ego. In fact, the creation of the select council responded to the deeply rooted conciliar traditions of Spain and England (based on Aristotelian notions of ‘political friendship’) and its actual level of activity disproves previous assumptions about its role and viability. The diplomatic negotiations undertaken by the English select councillors and their Spanish and Flemish counterparts place England firmly within the conciliar framework of the Spanish Monarchy and provide an invaluable window from which to explore the role of England as a fully integrated member of a composite monarchy extending from Naples and Oran to Lima and Mexico City.
Facultative symbiont virulence determines horizontal transmission rate without host specificity in Dictyostelium discoideum social amoebas
Authors: Noh Suegene , Peck Ron F , Larson Emily R , Covitz Rachel M , Chen Anna , Roy Prachee , Hamilton Marisa C , Dettmann Robert A
Published: January 2024

In facultative symbioses, only a fraction of hosts are associated with symbionts. Specific host and symbiont pairings may be the result of host–symbiont coevolution driven by reciprocal selection or priority effects pertaining to which potential symbiont is associated with a host first. Distinguishing between these possibilities is important for understanding the evolutionary forces that affect facultative symbioses. We used the social amoeba, Dictyostelium discoideum, and its symbiont, Paraburkholderia bonniea, to determine whether ongoing coevolution affects which host–symbiont strain pairs naturally cooccur within a facultative symbiosis. Relative to other Paraburkholderia, including another symbiont of D. discoideum, P. bonniea features a reduced genome size that indicates a significant history of coevolution with its host. We hypothesized that ongoing host–symbiont coevolution would lead to higher fitness for naturally cooccurring (native) host and symbiont pairings compared to novel pairings. We show for the first time that P. bonniea symbionts can horizontally transmit to new amoeba hosts when hosts aggregate together during the social stage of their life cycle. Here we find evidence for a virulence–transmission trade-off without host specificity. Although symbiont strains were significantly variable in virulence and horizontal transmission rate, hosts and symbionts responded similarly to associations in native and novel pairings. We go on to identify candidate virulence factors in the genomes of P. bonniea strains that may contribute to variation in virulence. We conclude that ongoing coevolution is unlikely for D. discoideum and P. bonniea. The system instead appears to represent a stable facultative symbiosis in which naturally cooccurring P. bonniea host and symbiont pairings are the result of priority effects.
RADseq data reveal widespread historical introgression in four familiar North American songbirds
Authors: Lait Linda A , Enciso-Romero Juan , Lekamlage Thilini T M , Veale Aaron , Abeyrama Dilini K , Burg Theresa M
Published: January 2024

Population genetic structure is influenced by a combination of contemporary and historical events; however, this structure can be complicated by ongoing gene flow. While it is well known that contemporary hybridization occurs frequently among many closely related species, it often remains uncertain as to which populations are involved in introgression events, and this can be even more difficult to infer when introgression is historical. Here we use restriction-site associated DNA sequencing to look at the level of introgression among four species of songbirds in North America: the black-capped, mountain, boreal, and chestnut-backed chickadee. Samples from both sympatric and allopatric sites across the species’ ranges supported limited ongoing mixing among the four species with Bayesian clustering and principal component analyses. In contrast, f4-statistics and admixture graphs revealed extensive historical introgression among geographically structured populations. Almost all historical admixture events were among populations west of the Rocky Mountains, and almost all populations west of the Rocky Mountains, excluding island and coastal populations, showed evidence of historical admixture. The inclusion of all four chickadee species proved crucial in differentiating which species were involved in hybridization events to avoid erroneous conclusions. Taken together, the results suggest a complex pattern of divergence with gene flow.
Effects of selfing on the evolution of sexual reproduction
Authors: Xu Kuangyi
Published: January 2024

Plants exhibit diverse breeding systems, with populations capable of outcrossing, selfing, and/or asexual reproduction. However, interactions between the three reproductive pathways remain not fully clear. Sexual reproduction introduces segregation and recombination, but incurs several costs. Selfing can affect the relative costs and benefits of sexual vs. asexual reproduction. Building population genetic models, I explore how selfing affects the evolution of a sexual reproduction rate modifier via (a) indirect selection due to segregation, (b) indirect selection from changes in recombination rates, and (c) selection from the cost of meiosis and mate limitation. The dominant selective force mediating the evolution of sex is found to vary with the rate of sexual reproduction and selfing, but selective force (a) and (c) are generally stronger than selective force (b). A modifier enhancing sexual reproduction tends to be favored by indirect selection generated by partially recessive, small-effect deleterious mutations, while hindered by highly recessive lethal mutations. Overall, evolution toward higher sexual reproduction is hindered at low sexual reproduction rates and intermediate selfing rates, but favored under high selfing rates. The results suggest that asexual reproduction may precede the evolution of selfing and offer insights into the evolution of mechanisms reducing geitonogamy in partially clonal populations.
Primary care physicians’ perspectives on the identification and management of postnatal mental health problems
Authors: Liow Yiyang , Lazarus Monica , Loh Victor , Shorey Shefaly , Chee Cornelia , Young Doris , Valderas Jose M
Published: January 2024

Background

Postnatal mental health problems (PMHPs) are prevalent and negatively affect mothers, children, and society. International and local guidelines recommend that Singapore primary care physicians (PCP) screen, assess, and manage mothers with PMHPs. However, little is known about their experiences and views.

Methods

We conducted semi-structured interviews with 14 PCPs in Singapore. Interview questions elicited perspectives on the identification and management of mothers with PMHPs. The interview guide was developed from a conceptual framework incorporating the knowledge-attitudes-practices, self-efficacy, and socio-ecological models. Interviews were audio-recorded and transcribed. Thematic analysis was used to identify emergent themes.

Results

Singapore PCPs viewed themselves as key providers of first-contact care to mothers with PMHPs. They believed mothers preferred them to alternative providers because of greater accessibility and trust. In detection, they were vigilant in identifying at-risk mothers and favoured clinical intuition over screening tools. PCPs were confident in diagnosing common PMHPs and believed that mothers not meeting diagnostic criteria must be readily recognized and supported. In managing PMHPs, PCPs expressed varying confidence in prescribing antidepressants, which were viewed as second-line to supportive counselling and psychoeducation. Impeding physician factors, constraining practice characteristics and health system limitations were barriers. Looking forward, PCPs aspired to leverage technology and multidisciplinary teams to provide comprehensive, team-based care for the mother-child dyad.

Conclusion

Singapore PCPs are key in identifying and managing mothers with PMHPs. To fully harness their potential in providing comprehensive care, PCPs need greater multidisciplinary support and technological solutions that promote remote disclosure and enhanced preparation for their role.
Calcineurin contributes to RNAi-mediated transgene silencing and small interfering RNA production in the human fungal pathogen Cryptococcus neoformans
Authors: Yadav Vikas , Mohan Riya , Sun Sheng , Heitman Joseph
Published: January 2024

Adaptation to external environmental challenges at the cellular level requires rapid responses and involves relay of information to the nucleus to drive key gene expression changes through downstream transcription factors. Here, we describe an alternative route of adaptation through a direct role for cellular signaling components in governing gene expression via RNA interference-mediated small RNA production. Calcium–calcineurin signaling is a highly conserved signaling cascade that plays central roles in stress adaptation and virulence of eukaryotic pathogens, including the human fungal pathogen Cryptococcus neoformans. Upon activation in C. neoformans, calcineurin localizes to P-bodies, membraneless organelles that are also the site for RNA processing. Here, we studied the role of calcineurin and its substrates in RNAi-mediated transgene silencing. Our results reveal that calcineurin regulates both the onset and the reversion of transgene silencing. We found that some calcineurin substrates that localize to P-bodies also regulate transgene silencing but in opposing directions. Small RNA sequencing in mutants lacking calcineurin or its targets revealed a role for calcineurin in small RNA production. Interestingly, the impact of calcineurin and its substrates was found to be different in genome-wide analysis, suggesting that calcineurin may regulate small RNA production in C. neoformans through additional pathways. Overall, these findings define a mechanism by which signaling machinery induced by external stimuli can directly alter gene expression to accelerate adaptative responses and contribute to genome defense.
Examining the Role of Frailty on Treatment Patterns and Complications Among Older Women Undergoing Procedure-Based Treatment for Urinary Incontinence
Authors: Parker-Autry Candace Y , Bauer Scott , Ford Cassie , Gregory W Thomas , Badlani Gopal , Scales Charles D
Published: January 2024

Background

Aging beyond 65 years is associated with increased prevalence of urinary incontinence (UI), frailty, and increased complication rate with UI treatments. To investigate this relationship, we examined frailty as a predictor of procedure-based UI treatment patterns and urologic complications in Medicare-eligible women.

Methods

We identified women undergoing procedures for UI between 2011 and 2018 in the 5% limited Medicare data set. A claims-based frailty index (CFI) using data from the 12 months prior to the index procedure defined frailty (CFI ≥0.25). Urologic complications were assessed during the 12 months following the index procedure. We used unadjusted logistic regression models to calculate odds of having a specific type of UI procedure based on frailty status. Odds of postprocedure urologic complications were examined with logistic regression adjusted for age and race.

Results

We identified 21 783 women who underwent a procedure-based intervention for UI, of whom 3 826 (17.5%) were frail. Frail women with stress UI were 2.6 times more likely to receive periurethral bulking (95% confidence interval [CI] 2.26–2.95), compared to nonfrail. Conversely, frailty was associated with lower odds of receiving a Sling or Burch colposuspension. Among women with urgency UI or overactive bladder, compared to nonfrail, frailty was associated with higher odds of both sacral neuromodulation (odds ratio [OR] = 1.21, 95% CI: 1.11–1.33) and intravesical Botox (OR = 1.16, 95% CI: 1.06–1.28), but lower odds of receiving posterior tibial nerve stimulation. Frailty was associated with higher odds of postprocedure urologic complications (OR = 1.64, 95% CI: 1.47–1.81).

Conclusions

Frailty status may influence treatment choice for treatment of stress or urgency UI symptoms and increase the odds of postprocedural complications in older women.
Parent–Child Relationships Following Gray Divorce: Stronger Ties With Mothers, Weaker Ties With Fathers
Authors: Buyukkececi Zafer , Leopold Thomas
Published: January 2024

Objectives

With rising gray divorce rates, older individuals face heightened risk of social isolation, highlighting the significance of adult children as a vital source of solidarity in the absence of a spouse. Simultaneously, gray divorce may undermine parent–adult child relationships and weaken the core of the family safety net of older persons. This study examined the consequences of gray divorce for parent–child relationships.

Methods

We used longitudinal data from the German Family Panel (Pairfam), a large-scale panel study collecting detailed information about family relationships and family structure. We focused on adult children aged 18–49 (n = 9,092) whose parents were married at first observation. During an observation period spanning up to 13 years (2008–2020), 606 individuals experienced parental divorce. Using fixed-effects models, we estimated changes in contact frequency, emotional closeness, and instrumental and emotional support provided to parents.

Results

Consequences of gray divorce varied strongly between mothers and fathers. Adult–child solidarity intensified for mothers but eroded for fathers. This impact was strongest for changes in contact frequency, moderate for changes in emotional closeness, and smaller for changes in support. The persistence of gender role differentiation was evident, as daughters displayed closer ties and provided greater support to their mothers following a gray divorce.

Discussion

Divorce alters relationships with adult children. A gray divorce tilts adult–child solidarity toward mothers and puts fathers at a higher risk of social isolation. Moreover, the observed gender dynamics underscore the continued influence of gender roles on family dynamics in the aftermath of gray divorce.
FAIR data retrieval for sensitive clinical research data in Galaxy
Authors: Ouwerkerk Jasper , Rasche Helena , Spalding John D , Hiltemann Saskia , Stubbs Andrew P
Published: January 2024

Background

In clinical research, data have to be accessible and reproducible, but the generated data are becoming larger and analysis complex. Here we propose a platform for Findable, Accessible, Interoperable, and Reusable (FAIR) data access and creating reproducible findings. Standardized access to a major genomic repository, the European Genome-Phenome Archive (EGA), has been achieved with API services like PyEGA3. We aim to provide a FAIR data analysis service in Galaxy by retrieving genomic data from the EGA and provide a generalized “omics” platform for FAIR data analysis.

Results

To demonstrate this, we implemented an end-to-end Galaxy workflow to replicate the findings from an RD-Connect synthetic dataset Beyond the 1 Million Genomes (synB1MG) available from the EGA. We developed the PyEGA3 connector within Galaxy to easily download multiple datasets from the EGA. We added the gene.iobio tool, a diagnostic environment for precision genomics, to Galaxy and demonstrate that it provides a more dynamic and interpretable view for trio analysis results. We developed a Galaxy trio analysis workflow to determine the pathogenic variants from the synB1MG trios using the GEMINI and gene.iobio tool. The complete workflow is available at WorkflowHub, and an associated tutorial was created in the Galaxy Training Network, which helps researchers unfamiliar with Galaxy to run the workflow.

Conclusions

We showed the feasibility of reusing data from the EGA in Galaxy via PyEGA3 and validated the workflow by rediscovering spiked-in variants in synthetic data. Finally, we improved existing tools in Galaxy and created a workflow for trio analysis to demonstrate the value of FAIR genomics analysis in Galaxy.
Toward genome assemblies for all marine vertebrates: current landscape and challenges
Authors: de Jong Emma , Parata Lara , Bayer Philipp E , Corrigan Shannon , Edwards Richard J
Published: January 2024

Marine vertebrate biodiversity is fundamental to ocean ecosystem health but is threatened by climate change, overharvesting, and habitat degradation. High-quality reference genomes are valuable foundational scientific resources that can inform conservation efforts. Consequently, global consortia are striving to produce reference genomes for representatives of all life. Here, we summarize the current landscape of available marine vertebrate reference genomes, including their phylogenetic diversity and geographic hotspots of production. We discuss key logistical and technical challenges that remain to be overcome if we are to realize the vision of a comprehensive reference genome library of all marine vertebrates.
OPA1 mutation affects autophagy and triggers senescence in autosomal dominant optic atrophy plus fibroblasts
Authors: Zanfardino Paola , Amati Alessandro , Doccini Stefano , Cox Sharon N , Tullo Apollonia , Longo Giovanna , D’Erchia Annamaria , Picardi Ernesto , Nesti Claudia , Santorelli Filippo M , Petruzzella Vittoria
Published: January 2024

In several cases of mitochondrial diseases, the underlying genetic and bioenergetic causes of reduced oxidative phosphorylation (OxPhos) in mitochondrial dysfunction are well understood. However, there is still limited knowledge about the specific cellular outcomes and factors involved for each gene and mutation, which contributes to the lack of effective treatments for these disorders. This study focused on fibroblasts from a patient with Autosomal Dominant Optic Atrophy (ADOA) plus syndrome harboring a mutation in the Optic Atrophy 1 (OPA1) gene. By combining functional and transcriptomic approaches, we investigated the mitochondrial function and identified cellular phenotypes associated with the disease. Our findings revealed that fibroblasts with the OPA1 mutation exhibited a disrupted mitochondrial network and function, leading to altered mitochondrial dynamics and reduced autophagic response. Additionally, we observed a premature senescence phenotype in these cells, suggesting a previously unexplored role of the OPA1 gene in inducing senescence in ADOA plus patients. This study provides novel insights into the mechanisms underlying mitochondrial dysfunction in ADOA plus and highlights the potential importance of senescence in disease progression.
Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice
Authors: McCallum-Loudeac Jeremy , Moody Edward , Williams Jack , Johnstone Georgia , Sircombe Kathleen J , Clarkson Andrew N , Wilson Megan J
Published: January 2024

Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2%–5.2% of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to understand better its contribution to AIS, which we named AIS_CRMΔ. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not only Lbx1 but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region and contribute to our understanding of the underlying causes of this debilitating disease.
Mitochondrial protein synthesis quality control
Authors: Koludarova Lidiia , Battersby Brendan J
Published: January 2024

Human mitochondrial DNA is one of the most simplified cellular genomes and facilitates compartmentalized gene expression. Within the organelle, there is no physical barrier to separate transcription and translation, nor is there evidence that quality control surveillance pathways are active to prevent translation on faulty mRNA transcripts. Mitochondrial ribosomes synthesize 13 hydrophobic proteins that require co-translational insertion into the inner membrane of the organelle. To maintain the integrity of the inner membrane, which is essential for organelle function, requires responsive quality control mechanisms to recognize aberrations in protein synthesis. In this review, we explore how defects in mitochondrial protein synthesis can arise due to the culmination of inherent mistakes that occur throughout the steps of gene expression. In turn, we examine the stepwise series of quality control processes that are needed to eliminate any mistakes that would perturb organelle homeostasis. We aim to provide an integrated view on the quality control mechanisms of mitochondrial protein synthesis and to identify promising avenues for future research.
Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis
Authors: Ouahed Jodie D , Griffith Alexandra , Collen Lauren V , Snapper Scott B
Published: January 2024

Monogenic causes of inflammatory bowel diseases (IBD) are increasingly being discovered. To date, much attention has been placed in those resulting from inborn errors of immunity. Therapeutic efforts have been largely focused on offering personalized immune modulation or curative bone marrow transplant for patients with IBD and underlying immune disorders. To date, less emphasis has been placed on monogenic causes of IBD that pertain to impairment of the intestinal epithelial barrier. Here, we provide a comprehensive review of monogenic causes of IBD that result in impaired intestinal epithelial barrier that are categorized into 6 important functions: (1) epithelial cell organization, (2) epithelial cell intrinsic functions, (3) epithelial cell apoptosis and necroptosis, (4) complement activation, (5) epithelial cell signaling, and (6) control of RNA degradation products. We illustrate how impairment of any of these categories can result in IBD. This work reviews the current understanding of the genes involved in maintaining the intestinal barrier, the inheritance patterns that result in dysfunction, features of IBD resulting from these disorders, and pertinent translational work in this field.
Reconceptualizing Advocacy through the Women, Peace and Security Agenda: Embodiment, Relationality, and Power
Authors: Achilleos-Sarll Columba
Published: January 2024

This article critically examines the embodied and relational politics of networked advocacy in the case of the Women, Peace and Security (WPS) agenda in the United Kingdom. Moving beyond liberal framings that position WPS advocacy as an attempt to overcome gender exclusion from peace and security policymaking, this article is concerned instead with the gendered, racialized, and classed logics and hierarchies (re)produced through the practice of WPS advocacy. Toward this end, this article conceptualizes advocacy as an embodied, relational practice where WPS meanings are shaped, power is negotiated, and individuals are interpolated into subject positions. This conceptual claim is substantiated through an initial, exploratory analysis of interviews conducted with UK NGO professionals and government officials. Examining the figures of the “critical friends” and the “shouty NGOs,” I demonstrate how modes of advocating for WPS are ascribed and inscribed to certain bodies, which, in turn, reproduce power relations that affect the possibilities of the agenda. By reconceptualizing advocacy, the article contributes not only to WPS scholarship on civil society and advocacy but to wider debates within international political sociology around embodiment, relationality, and power. Additionally, it contributes empirically by highlighting how NGOs advocate for the WPS agenda.
Boundary Work, Overlapping Identities, and Liminality in Communities of Practice: Diplomacy within and beyond ASEAN
Authors: Glas Aarie , Martel Stéphanie
Published: January 2024

Communities of practice (CoPs) are important sites of social interaction and are of growing concern in international relations. Much attention has been devoted to examining the existence and effect of these communities, and the kinds of practices and identities they coalesce around. Relatively less attention has been afforded to the relations between a CoP and what lies outside of it. In this article we examine encounters at the boundaries of CoPs. Empirically, we examine the boundaries and interactions of a community of diplomatic practice in the context of the Association of Southeast Asian Nations (ASEAN) as regional officials engage with extra-regional diplomats and “dialogue partners” operating within and alongside the organization. We find that the “boundary work” of these interactions are important sites of social interaction that constitute communities in important ways and make possible meaningful changes in identity and behavior. More broadly, we show that ASEAN’s unique position as a hub of a multilateral architecture that extends to a wider state membership provides prime terrain to inquire about what happens in liminal spaces of encounter between social agents of varied communities. To advance our claims, we draw on sixty-one semi-structured interviews with regional and extra-regional officials in Jakarta and elsewhere in the region, alongside analysis of public statements from diplomatic practitioners.
An Emergent Community of Cyber Sovereignty: The Reproduction of Boundaries?
Authors: Qiao-Franco Guangyu
Published: January 2024

This research probes the boundary-work of Communities of Practice (CoP) by examining China’s active efforts in advancing a state-centric approach in managing cyberspace in the international arena. Boundaries separating the Global North and South are reproduced in the expansion of what I call the “community of cyber sovereignty.” This phenomenon points to the CoP literature’s omission of the proactive aspects of boundary-work undertaken by core members and its surrounding and confounding historical contexts. I argue that boundary reproduction arises from both deliberate and unreflective moves in cultivating CoP. First, emerging from reflexivity in interacting with the external environment, practitioners in CoPs that are vigorously contested will likely replicate historically successful boundary drawing to acquire or maintain credibility. Second, CoP members engage in the habitual selection of strategies, anchoring the community toward sustaining relationships with actors that its members traditionally associate with. These proactive boundary-work dynamics are enabled by inclusive and exclusive mechanisms such as “brokering” varied practices to include potential members and “gatekeeping” others. My analysis suggests that scholarship must attend to actors’ proactive efforts to establish communities preferentially as well as their linkages with prevailing social structures.
Total metagenomes outperform viromes in recovering viral diversity from sulfuric soils
Authors: Bi Li , He Ji-Zheng , Hu Hang-Wei
Published: January 2024

Recent metagenomic advancements have offered unprecedented insights into soil viral ecology. However, it remains a challenge to select the suitable metagenomic method for investigating soil viruses under different environmental conditions. Here, we assessed the performance of viral size-fraction metagenomes (viromes) and total metagenomes in capturing viral diversity from hypersulfidic soils with neutral pH and sulfuric soils with pH <3.3. Viromes effectively enhanced the sequencing coverage of viral genomes in both soil types. Viomes of hypersulfidic soils outperformed total metagenomes by recovering a significantly higher number of viral operational taxonomic units (vOTUs). However, total metagenomes of sulfuric soils recovered ~4.5 times more vOTUs than viromes on average. Altogether, our findings suggest that the choice between viromes and total metagenomes for studying soil viruses should be carefully considered based on the specific environmental conditions.
Mammography Screening Should Begin at Age 40 Years
Authors: Hendrick R Edward , Monticciolo Debra L
Published: January 2024

The 2023 U.S. Preventive Services Task Force draft recommendation statement on screening for breast cancer recommends lowering the starting age for biennial screening with mammography to age 40 years from 50 years, the age of screening initiation that the Task Force had previously recommended since 2009. A recent Perspective article in the New England Journal of Medicine by Woloshin et al contends that this change will provide no additional benefit and is unjustified. This article reviews the main ideas presented by Woloshin et al and provides substantial evidence not considered by those authors in support of screening mammography in U.S. women starting at age 40 years.
Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study
Authors: Dhaliwal Ruban , Kendler David , Saag Kenneth , Ing Steven W , Singer Andrea , Adler Robert A , Pearman Leny , Wang Yamei , Mitlak Bruce
Published: January 2024

Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80 μg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12 mo and/or a shift in T-score category (based on LS and TH T-scores) at 12 mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], P = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], P < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], P < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12 mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study.
What Might Future Rights-Based Climate Litigation Look Like in Indonesia? A Preliminary Analysis
Authors: Cornelius Conrado M
Published: January 2024

While there has been some climate litigations in Indonesia, a rights-based climate case has yet to emerge. On the other hand, several rights-based environmental cases have seen the light of day before the Indonesian courts, although with more failures than successes. This note explores the prospects and challenges for future rights-based climate litigation in Indonesia by reflecting on previous climate and rights-based environmental cases. At the same time, with reference to Urgenda, this note recognizes a growing global discourse on transnational climate litigation, unveiling the possibility of replicating successful climate litigation strategies from one jurisdiction to another. This note inquires into what potential plaintiffs can learn from Urgenda and previous Indonesian climate and rights-based environmental litigation to strategize future rights-based climate lawsuits before Indonesian courts.
Release the hens: a study on the complexities of guinea fowl as tick control
Authors: White Alexis L , Cumbie Alexandra , Brinkerhoff R Jory , Hynes Wayne L , Gaff Holly D
Published: January 2024

Established tick control strategies often involve methods that can be damaging to existing environmental conditions or natural host ecology. To find more environmentally friendly methods, biological controls, like predators of ticks, have been suggested. There are natural predators of ticks, but most are generalists and not expected to control tick populations. Helmeted guinea fowl (Numida meleagris (L.) (Galliformes: Numididae)) have been suggested to be biological controls of ticks, and therefore, tick-borne pathogens, but their potential role as hosts for ticks complicates the relationship. A study was conducted to assess whether guinea fowl reduces the abundance of lone star ticks, Amblyomma americanum (L.) (Acari: Ixodidae), or whether they are hosts of ticks. Using mark–recapture techniques, painted lone star ticks were placed into 3 different treatments: penned, excluded, and free range. The recapture rates of painted ticks were compared. There was a significant difference between excluded and free-range treatments, but not between excluded and penned or between free range and penned. To investigate the role of guinea fowl as hosts of ticks, coop floors were examined for engorged ticks. Engorged lone star nymphs that had fed on guinea fowl were found. Lastly, ticks collected were tested to identify the potential reduction in risk of tick-borne pathogens. This study found no evidence that guinea fowl are an effective biological control of lone star ticks or tick-borne pathogens, but they are hosts of lone star nymphs. Future studies are needed to assess the complex ecology of a biological control of ticks that is also a host.