bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma
Authors: Labidi Soumaya , Meti Nicholas , Barua Reeta , Li Mengqi , Riromar Jamila , Jiang Di Maria , Fallah-Rad Nazanin , Sridhar Srikala S. , del Rincon Sonia V. , Pezo Rossanna C. , Ferrario Cristiano , Cheng Susanna , Sacher Adrian G. , Rose April A. N.
Published: October 2023

Background

Anti-PD-1/L1 immune checkpoint inhibitors (ICI) are indicated for metastatic urothelial cancer (mUC), however, only a minority of patients will derive therapeutic benefit. Strong predictive and prognostic factors are lacking. We investigated if clinical variables were associated with ICI outcomes in mUC.

Methods

We performed a multi-center retrospective cohort study of patients with mUC who received anti-PD-1/L1 ICI for metastatic disease between 2016-2021 at 3 Canadian cancer centres. Clinical characteristics, including demographics, BMI, metastatic sites, neutrophil-to-lymphocyte ratio (NLR), objective response, and survival were abstracted from chart review. ICI treatment response was determined by investigator assessment of clinical and radiologic parameters. Fisher’s exact test was used to assess differences in response rates between groups. Log rank and Cox regression models were used to assess overall survival (OS).

Results

We identified 135 patients with mUC who received anti-PD1/L1 ICI. A BMI ≥ 25 was significantly correlated to a higher overall response rate (ORR) to ICI (45.4% vs 16.3%, P = 0.020). After a median follow-up of 14.5 months, patients with BMI ≥ 30 experienced significant longer median OS 24.8 months vs. 14.4 months for 25 ≤ BMI < 30 and 8.5 months for BMI < 25 (P = 0.012). The ORR was significantly less in the presence of bone metastasis 16% vs 41% P = 0.006, and liver metastasis 16% vs 39% P = 0.013. Conversely, the presence of metastatic lymph nodes was significantly correlated with higher ORR 40% vs 20% P = 0.032. The median OS for patients with bone metastasis was 7.3 months vs 18 months in the absence of bone metastasis (P < 0.001). Patients with liver metastasis had a median OS of 8.6 months compared to 15 months for those without liver metastasis (P = 0.006). For lung metastasis, median OS was 8.7 months compared to 17.3 months (P = 0.004). No statistical difference was shown in OS for lymph nodes metastasis, with a median of 13.5 months vs 12.7 months (P = 0.175). Patients with NLR ≥ 4 had a significant worse OS (8.2 months vs 17.7 months P = 0.0001). In multivariate analysis, BMI ≥ 30, bone metastasis and NLR ≥ 4 were independent prognosis factor for OS.

Conclusions

Our data identified BMI and bone metastasis as novel, independent, clinical biomarkers that were strongly and independently associated with ICI response and survival in mUC. External validation of these data in a larger study and investigations into the mechanisms behind these findings are warranted.
Cell-to-cell heterogeneity drives host-virus coexistence in a bloom-forming alga
Authors: Joffe Nir , Kuhlisch Constanze , Schleyer Guy , Ahlers Nadia Samira , Shemi Adva , Vardi Assaf
Published: October 2023

Algal blooms drive global biogeochemical cycles of key nutrients in the oceans and serve as hotspots for biological interactions. The massive spring blooms of the cosmopolitan coccolithophoreEmiliania huxleyi (E. huxleyi)are often infected by the lyticEmiliania huxleyispecific virus (EhV) which is a major mortality agent triggering bloom demise. Nonetheless, the multi-annual “boom and bust” pattern ofE. huxleyisuggests that mechanisms of coexistence are essential for these host-virus dynamics. To investigate host-virus coexistence, we developed a new model system from anE. huxleyiculture which recovered from viral infection. The recovered population coexists with the virus, as host cells continue to grow in parallel to viral production. By applying a single-molecule fluorescencein situhybridization (smFISH) approach to quantify the fraction of infected cells and assessing infection-specific lipid biomarkers, we identified a small subpopulation (5-7% of cells) that was infected and produced new virions, whereas the majority of the host population could resist infection. To further assess population heterogeneity, we generated monoclonal strain collections using single-cell sorting and subsequently phenotyped their susceptibility to EhV infection. This unraveled a substantial cell-to-cell heterogeneity across a continuum of susceptibility to resistance, suggesting that infection outcomes may vary depending on the individual cell. These results add a new dimension to our understanding of the complexity of host-virus interactions that are commonly assessed in bulk and described by binary definitions of resistance or susceptibility. We propose that phenotypic heterogeneity drivesE. huxleyi-EhV coexistence and may potentially provide the coexisting strain an ecological advantage by killing competing susceptible strains.
CRISPR Screening in Tandem with Targeted mtDNA Damage Reveals WRNIP1 Essentiality
Authors: Sack Tanja , Dhavarasa Piriththiv , Szames Daniel , O’Brien Siobhan , Angers Stephane , Kelley Shana O.
Published: October 2023

A major impediment to the characterization of mtDNA repair mechanisms, in comparison to nuclear DNA repair mechanisms, is the difficulty of specifically addressing mitochondrial damage. Using a mitochondria-penetrating peptide, we can deliver DNA-damaging agents directly to mitochondria, bypassing the nuclear compartment. Here, we describe the use of a mtDNA-damaging agent in tandem with CRISPR/Cas9 screening for the genome-wide discovery of factors essential for mtDNA damage response. Using mitochondria-targeted doxorubicin (mtDox) we generate mtDNA double-strand breaks (mtDSBs) specifically in this organelle. Combined with an untargeted Dox screen, we identify genes with significantly greater essentiality during mitochondrial versus nuclear DNA damage. We characterize the essentially of our top hit - WRNIP1 - observed here for the first time to respond to mtDNA damage. We further investigate the mitochondrial role of WRNIP1 in innate immune signaling and nuclear genome maintenance, outlining a model that experimentally supports mitochondrial turnover in response to mtDSBs.
MFSD7c functions as a transporter of choline at the blood-brain barrier
Authors: Nguyen Xuan T.A. , Le Thanh Nha Uyen , Ha Hoa Thi Thuy , Nguyen Toan Q. , Artati Anna , Leong Nancy C.P. , Nguyen Dat T. , Lim Pei Yen , Susanto Adelia Vicanatalita , Qianhui Huang , Ling Fam , Ngah Leong Lo , Bonne Isabelle , Lee Angela , Gooch Catherine , Luque Jorge Luis Granadillo De , Yu Dejie , Hua Huang , Soong Tuck Wah , Chang Matthew Wook , Wenk Markus R. , Adamski Jerzy , Cazenave-Gassiot Amaury , Nguyen Long N.
Published: October 2023

Mutations of MFSD7c (also known asFlvcr2), which is an orphan transporter, are linked to Fowler syndrome1, 2. Here, we useMfsd7cknockout mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood-brain barrier (BBB). We performed comprehensive metabolomics and detected differential changes of metabolites in the brains and livers ofMfsd7cknockout (Mfsd7c−/−) embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers ofMfsd7c−/−embryos. Thus, we hypothesized that MFSD7c regulates the levels of choline in the brain. Indeed, expression of humanMFSD7cin cells significantly increased choline uptake. Interestingly, we showed that choline uptake byMFSD7cis greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch-clamp showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c is conserved in vertebrates, but not in yeasts. We show that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. Employing our transport assays, we showed that several missense mutations of humanMFSD7cfrom Fowler patients had abolished or reduced choline transport activity. Mice lackingMfsd7cin the CNS endothelial cells suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c is required for exporting choline derived from lysophosphatidylcholine (LPC) in the brain. Collectively, our work identifies MFSD7c as a choline transporter at the BBB. This study suggests that defective export of choline in the brain may be a cause of Fowler syndrome.
Virological characteristics correlating with SARS-CoV-2 spike protein fusogenicity
Authors: Begum MST Monira , Ichihara Kimiko , Takahashi Otowa , Nasser Hesham , Jonathan Michael , Tokunaga Kenzo , Yoshida Isao , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Sato Kei , Ikeda Terumasa
Published: October 2023

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike (S) protein is essential in mediating membrane fusion of the virus with the target cells. Several reports demonstrated that SARS-CoV-2 S protein fusogenicity is reportedly closely associated with the intrinsic pathogenicity of the virus determined using hamster models. However, the association between S protein fusogenicity and other virological parameters remains elusive. In this study, we investigated the virological parameters of eleven previous variants of concern (VOCs) and variants of interest (VOIs) correlating with S protein fusogenicity. S protein fusogenicity was found to be strongly correlated with S1/S2 cleavage efficiency and plaque size formed by clinical isolates. However, S protein fusogenicity was less associated with pseudoviral infectivity, pseudovirus entry efficiency, and viral replication kinetics. Taken together, our results suggest that S1/S2 cleavage efficiency and plaque size could be potential indicators to predict the intrinsic pathogenicity of newly emerged SARS-CoV-2 variants.
Engineering ofSalmonellaphages into novel antimicrobial Tailocins
Authors: Woudstra Cedric , Sørensen Anders Nørgaard , Brøndsted Lone
Published: October 2023

Due to the extensive use of antibiotics, the increase of infections caused by antibiotic resistant bacteria are now a global health concern. Phages have proven useful for treating bacterial infections and represent a promising alternative or complement to antibiotic treatment. Yet, other alternative exists, such as bacteria-produced non-replicative protein complexes that can kill their targeted bacteria by puncturing their membrane (Tailocins). To expand the repertoire of Tailocins available, we suggest a new approach transforming phages into Tailocins. Here we genetically engineered the virulentAckermannviridaephage S117, as well as temperate phages Fels-1, -2 and Gifsy-1 and -2 targeting the food pathogenSalmonella, by deleting theportal vertexormajor capsidgene using CRISPR-Cas9. We report the production of Tailocin particles from engineered virulent and temperate phages able to kill their native host. Our work represents a steppingstone to tape into the huge diversity of phages and transform them into versatile puncturing new antimicrobials.
Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium
Authors: Ohigashi Izumi , White Andrea J. , Yang Mei-Ting , Fujimori Sayumi , Tanaka Yu , Jacques Alison , Kiyonari Hiroshi , Matsushita Yosuke , Turan Sevilay , Kelly Michael C. , Anderson Graham , Takahama Yousuke
Published: October 2023

Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla. Both self-antigen-displaying and thymocyte-attracting mTEC subsets are essential for self-tolerance. Here we identify a developmental pathway by which mTECs gain their diversity in functionally distinct subsets. We show that CCL21-expressing mTECs arise early during thymus ontogeny. Fate-mapping analysis reveals that self-antigen-displaying mTECs, including Aire-expressing mTECs and thymic tuft cells, are derived from CCL21-expressing cells. The differentiation capability of CCL21-expressing embryonic mTECs is verified in reaggregate thymus experiments. These results indicate that CCL21-expressing embryonic mTECs carry a developmental potential to give rise to self-antigen-displaying mTECs, revealing that the sequential conversion of thymocyte-attracting subset into self-antigen-displaying subset serves to assemble functional diversity in the thymus medulla epithelium.
Targeting the Hippo pathway in cancers via ubiquitination dependent TEAD degradation
Authors: Pham Trang H. , Pahuja Kanika Bajaj , Hagenbeek Thijs J. , Zbieg Jason , Noland Cameron L. , Pham Victoria C. , Yao Xiaosai , Rose Christopher M. , Browder Kristen C. , Lee Ho-June , Yu Mamie , Liang-Chu May , Martin Scott , Verschueren Erik , Li Jason , Kubala Marta H. , Fong Rina , Lorenzo Maria , Beroza Paul , Hsu Peter , Paul Sayantanee , Villemure Elisia , Lee Wendy , Cheung Tommy K. , Clausen Saundra , Lacap Jennifer , Liang Yuxin , Cheng Jason , Schmidt Steve , Modrusan Zora , Cohen Michael , Crawford James , Jasper Heinrich , Ashworth Alan , Lill Jennie R. , Malek Shiva , Rudolph Joachim , Wertz Ingrid E. , Chang Matthew T. , Ye Xin , Dey Anwesha
Published: October 2023

The Hippo pathway is among the most frequently altered key signaling pathways in cancer. TEAD1-4 are essential transcription factors and key downstream effectors in the Hippo pathway in human cells. Here, we identified RNF146 as a ubiquitin ligase (E3) of TEADs, which negatively regulates their stability in cells through proteasome-mediated degradation. We show that RNF146-mediated TEAD ubiquitination is dependent on the TEAD PARylation state. We further validated the genetic interaction between RNF146 and the Hippo pathway in cancer cell lines and the model organismDrosophila melanogaster.Despite the RNF146 and proteasome-mediated degradation mechanisms, TEADs are stable proteins with a long half-life in cells. We demonstrate that degradation of TEADs can be greatly enhanced pharmacologically with heterobifunctional chemical inducers of protein degradation (CIDEs). These TEAD-CIDEs can effectively suppress activation of YAP/TAZ target genes in a dose-dependent manner and exhibit significant anti-proliferative effects in YAP/TAZ-dependent tumor cells, thus phenocopying the effect of genetic ablation of TEAD protein. Collectively, this study demonstrates that the ubiquitin-proteasome system plays an important role in regulating TEAD functions and provides a proof-of-concept demonstration that pharmacologically induced TEAD ubiquitination could be leveraged to target YAP/TAZ-driven cancers.
Programming dynamic division of labor using horizontal gene transfer
Authors: Hamrick Grayson S. , Maddamsetti Rohan , Son Hye-In , Wilson Maggie L. , Davis Harris M. , You Lingchong
Published: October 2023

The metabolic engineering of microbes has broad applications, including in biomanufacturing, bioprocessing, and environmental remediation. The introduction of a complex, multi-step pathway often imposes a substantial metabolic burden on the host cell, restraining the accumulation of productive biomass and limiting pathway efficiency. One strategy to alleviate metabolic burden is division of labor (DOL), in which different subpopulations carry out different parts of the pathway and work together to convert a substrate into a final product. However, the maintenance of different engineered subpopulations is challenging due to competition and convoluted inter-strain population dynamics. Through modeling, we show that dynamic division of labor (DDOL) mediated by horizontal gene transfer (HGT) can overcome these limitations and enable the robust maintenance of burdensome, multi-step pathways. We also use plasmid genomics to uncover evidence that DDOL is a strategy utilized by natural microbial communities. Our work suggests that bioengineers can harness HGT to stabilize synthetic metabolic pathways in microbial communities, enabling the development of robust engineered systems for deployment in a variety of contexts.
Backbone extension acyl rearrangements enable cellular synthesis of proteins with internal β2-peptide linkages
Authors: Roe Leah T. , Schissel Carly K. , Dover Taylor L. , Shah Bhavana , Hamlish Noah X. , Zheng Shuai , Dilworth Diondra A. , Wong Nicole , Zhang Zhongqi , Chatterjee Abhishek , Francis Matthew B. , Miller Scott J. , Schepartz Alanna
Published: October 2023

Proteins and polypeptides containing extended backbone monomers embody highly desirable structures and functions, but they cannot yet be biosynthesized in cells. There are two challenges at work. First is the ribosome, whose ability to promote rapid bond-forming reactions to and from anything other than an α-amino acid or α-hydroxy acid is unknown. The second challenge is the absence of orthogonal enzymes that acylate tRNA with extended backbone monomers. Here we describe a general approach to the programmed cellular synthesis of proteins containing extended backbone monomers that circumvents both of these challenges. Rather than relying on direct and uncharacterized reactions of non-α-amino acid monomers within the ribosomal PTC, we develop a proximity-guided intramolecular rearrangement that effectively edits the protein backbone post-translationally. The method relies on the ability of PylRS-like aminoacyl-tRNA synthetase enzymes to accept diverse α-hydroxy acid monomers, including those whose side chains contain masked nucleophiles. Introduction of such an α-hydroxy acid monomer into a protein translatedin vivo, followed by nucleophile unmasking, sets up a thermodynamically favored and quantitative intramolecular Backbone Extension Acyl Rearrangement (BEAR) reaction that edits the protein backbone to install an extended backbone monomer. In the examples described here, the intramolecular rearrangement converts an α-peptide backbone directly into a β-backbone. As far as we know, this report represents the first example in which a much-desired expanded backbone β-amino acid linkage has been introduced site-selectively into a protein in a cell.
A dual-pathway architecture enables chronic stress to disrupt agency and promote habit formation
Authors: Giovanniello Jacqueline R. , Paredes Natalie , Wiener Anna , Ramírez-Armenta Kathia , Oragwam Chukwuebuka , Uwadia Hanniel O. , Yu Abigail L. , Lim Kayla , Pimenta Jenna S. , Vilchez Gabriela E. , Nnamdi Gift , Wang Alicia , Sehgal Megha , Reis Fernando MCV , Sias Ana C. , Silva Alcino J. , Adhikari Avishek , Malvaez Melissa , Wassum Kate M.
Published: October 2023

Chronic stress can change how we learn and, thus, how we make decisions. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted systems neuroscience approach in male and female mice, we reveal a dual pathway, amygdala-striatal neuronal circuit architecture by which a recent history of chronic stress disrupts the action-outcome learning underlying adaptive agency and promotes the formation of inflexible habits. We found that the basolateral amygdala projection to the dorsomedial striatum is activated by rewarding events to support the action-outcome learning needed for flexible, goal-directed decision making. Chronic stress attenuates this to disrupt action-outcome learning and, therefore, agency. Conversely, the central amygdala projection to the dorsomedial striatum mediates habit formation. Following stress this pathway is progressively recruited to learning to promote the premature formation of inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to disrupt agency and promote habit. These data provide neuronal circuit insights into how chronic stress shapes learning and decision making, and help understand how stress can lead to the disrupted decision making and pathological habits that characterize substance use disorders and mental health conditions.
A DRP-like pseudoenzyme coordinates with MICOS to promote cristae architecture
Authors: Kumar Abhishek , Gok Mehmet Oguz , Nguyen Kailey N. , Reese Michael L. , Wideman Jeremy G. , Muñoz-Gómez Sergio A. , Friedman Jonathan R.
Published: October 2023

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial inner membrane-localized MICOS complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae shaping factors, has not been fully determined. Here, we examine the MICOS complex inSchizosaccharomyces pombe, a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS complexes to promote normal mitochondrial morphology and respiratory function. Bioinformatic analyses reveal that Mmc1 is a distant relative of the Dynamin-Related Protein (DRP) family of GTPases, which are well established to shape and remodel membranes. We find that, like DRPs, Mmc1 self-associates and forms high molecular weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting it does not dynamically remodel membranes. These data are consistent with a model in which Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans.
Uterine secretome initiates growth of gynecologic tissues in ectopic locations
Authors: Sunde Jan , Wasickanin Morgan , Katz Tiffany A , Bidadi Sanam , O’Neil Derek , Burney Richard O , Pennington Kathleen A
Published: October 2023

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Post-ovulatory endometrium was induced hormonally in donor tdT and wild-type (WT) female mice. tdT oviductal cells and WT endometrium were harvested for intraperitoneal injection into synchronized recipient WT mice. Ectopic lesions were identified using fluorescence in-vivo imaging and then harvested for histological evaluation. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. In conclusion, endometrial derived implantation factors are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.
Direct and indirect effects of fire on parasites in an African savanna
Authors: Donaldson Jason E. , Holdo Ricardo M. , Anderson T. Michael , Morrison Thomas A. , Hopcraft J. Grant C. , McIntyre Jennifer , Devaney Eileen , Hempson Gareth , Senso Basil , Trentinus Aidan , Ezenwa Vanessa O.
Published: October 2023

Fires in grassy ecosystems consume vegetation and initiate high‐quality regrowth, which results in pyric herbivory when mammalian grazers concentrate feeding in recent burns. For environmentally transmitted parasites with transmission mechanisms linked to vegetation structure, fire should exert direct effects on parasites, as well as indirect effects resulting from subsequent enhanced herbivory, which can affect parasite input and exposure to environmental conditions.

We combined an experimental manipulation with observational data in the Serengeti National Park to investigate the direct and indirect effects of fire on parasites. We assessed the direct effects of fire by measuring changes in parasitic nematode larvae in the grass layer before and after fire on paired experimental burned and control plots. To investigate indirect effects linked to pyric herbivory, we sampled herbivore dung, grass biomass, ground temperature and larval densities every month for 5 months following fire in seven pairs of burned and unburned monitoring plots. Finally, to assess if fire‐driven changes to larval densities affected host infection burdens, we collected faecal samples from a key host, Grant's gazelle (Nanger granti), each month for 5 months to estimate within‐host parasite burdens.

Fire killed all larvae and increased grazer dung inputs by 40% for 2 months following fire. Dung inputs after fire led to larval parasite recolonization of burned patches, but intense herbivory kept grass short and larval densities were associated with changes in ground temperature linked to grass biomass and ambient temperature. Grant's gazelles had lower parasite burdens when sampled in areas with higher compared to lower burned area fraction.

Fire and pyric herbivory change the densities of larval parasites in the environment and divide the landscape into burned and unburned regions with distinct infection risks for local herbivores.

The indirect effects quantified here represent a novel finding with major implications for all grazing systems impacted by fire.
A Girls’ Army of Vengeance?: Perceptions of Sexual Violence against Children in post‐1905 Russia
Authors: Oberländer Alexandra
Published: October 2023

This article offers a microhistorical reading of a criminal case of sexual violence in 1908 St Petersburg. It traces the re‐interpretation of underage girls from innocent victims to potential prostitutes and carriers of debauchery and disease. Furthermore, after this case, the perceptions shifted from pitied victim to source of threatening vengeance. This discursive shift took place in newspapers, court procedures but also in charity organisations encountering victims of sexual violence. While vengeance is usually reserved as a trope for framing the actions of adult victims of sexual violence, here it was explicitly applied to underage girls, thereby rendering victims of sexual violence a threat to Russian society.
Luxembourg: Political Developments and Data in 2022
Authors: DUMONT PATRICK , KIES RAPHAEL
Published: October 2023

Luxembourg politics in 2022 was marked by the economic consequences of Russia's war against Ukraine. The government responded through policy packages negotiated with social partners. The decade‐long process of revamping the Constitution finally came to an end, and new measures were taken to allow for greater participation of foreign residents in local politics. The year 2022 was indeed a pre‐electoral year, as both local and national elections are scheduled for 2023. Parties started to prepare for these important deadlines through personnel movements.
Finite element stress analysis of dental cement application on endocrown and onlay restoration
Authors: Wicaksono Satrio , Prasetia Wandi , Muryani Anna , Dirgantara Tatacipta , Mahyuddin Andi Isra
Published: October 2023

The aim of the study was to evaluate the influence of resin cement material types on tooth with endocrown and onlay restorations. The first molar was scanned using Micro‐CT and underwent a modelling process to obtain the 3D model for computational simulation. Eight models were simulated in the current study with two loading conditions (720N vertical load and 200N oblique load), two types of restoration (onlay and endocrown restorations), and two resin cement variants (dual‐cure resin cement and light‐cure resin cement). The tooth with onlay restoration showed a significant stress reduction (up to 70%) when using light‐cure resin cement compared to dual‐cure resin cement. In contrast, types of cement did not affect stress distribution in the tooth with endocrown restoration. The current study found that dual‐cure resin cement was preferable in Endocrown and Onlay restorations, due to dual‐cure resin cement provided better bond strength compared to light‐cure resin cement.
Detection of genomic variations and selection signatures in Wagyu using whole‐genome sequencing data
Authors: Shi Lulu , Hu Mingyue , Lai Weining , Yi Wenfeng , Liu Zhengxi , Sun Hao , Li Feng , Yan Shouqing
Published: October 2023

Wagyu is recognized for producing marbled beef with high nutritional value and flavor. Reportedly, Wagyu has been widely used to improve the meat quality of local breeds around the world. However, studies on the genetic mechanism of meat quality in Wagyu at the whole‐genome level are rarely reported. Here, whole‐genome sequencing data of 11 Wagyu and 115 other individuals were used to explore the genomic variations and genes under selection pressure in Wagyu. A total of 31 349 non‐synonymous variants and 53 102 synonymous variants were identified in Wagyu. The population structure analysis showed that Wagyu had the closest genetic relationship with Mishima–Ushi cattle and was apparently separated from other cattle breeds. Then, composite likelihood ratio (CLR), integrated haplotype score, fixation index and cross‐population composite likelihood ratio (XP‐CLR) tests were performed to identify the candidate genes under positive selection in Wagyu. In total, 770 regions containing 312 genes were identified by at least three methods. Among them, 97 regions containing 27 genes were detected by all four methods. We specifically illustrate a list of interesting genes, including LRP2BP, GAA, CACNG6, CXADR, GPCPD1, KLF2, KLF13, SOX5, MYBPC1, SLC25A10, ATP8A1 and MYH15, which are associated with lipid metabolism, fat deposition, muscle development, bone development, feed intake and growth traits in Wagyu. This is the first study to explore the genomic variations and selection signatures of Wagyu at the whole‐genome level. These results will provide significant help to beef cattle improvement and breeding.
Distributions and expressions of Aquaporin‐5 and 7 in the testes of developing male chicks
Authors: Kara Hülya , Tekiner Deniz
Published: October 2023

Aquaporins (AQPs) are integral membrane proteins that act as water channels for which a total of 13 orthologs of AQP genes in birds have been reported. Tissue expression and cellular or subcellular localization of AQPs have been poorly investigated in the male reproductive system of birds. We aimed to determine the distribution and localization of AQP5 and AQP7 proteins by immunocytochemistry in testicular tissues obtained from developing chicks (14, 21, 28, 35 and 42 days old). Totally 175 male chicks (Ross 308) were used in the study from which testicular tissue was removed, fixed in 10% formaldehyde solution, then embedded in paraffin blocks. Five μm sections were cut, mounted on poly‐L‐lysine slides, dried in an oven, then dehydrated using standard immunohistochemistry staining protocol. The sections were imaged with a Nikon Eclipse 50i trinocular light microscope. Immunohistochemical evaluation of the immune reactivity of AQP5 revealed a positive immune reaction in spermatocytes and interstitial areas of the testes in 14‐day‐old chicks. Testicular tissue AQP5 immune reactivity was observed in the tubule and the interstitial regions of 21‐, 28‐, 35‐ and 42‐day‐old chicks. AQP7 immune reactions were determined in the tubule and interstitial areas testes of developing chicks' testis tissue, with increasing positivity corresponding to older age. The expression of AQP5 and AQP7 appears to be species‐specific due to differences in localization and expression in male chicks compared with studies of other mammals, which is likely to play an important role in regulating fluid and sperm volume. This research can serve as a base for future studies that will contribute to the understanding of the male genital system of AQPs.
Prostaglandins as local regulators of ovarian physiology in ruminants
Authors: Berisha Bajram , Thaqi Granit , Sinowatz Fred , Schams Dieter , Rodler Daniela , Pfaffl Michael W.
Published: October 2023

Prostaglandins are synthesized from arachidonic acid through the catalytic activities of cyclooxygenase, while the production of different prostaglandin types, prostaglandin F2 alpha (PGF) and prostaglandin E2 (PGE), are regulated by specific prostaglandin synthases (PGFS and PGES). Prostaglandin ligands (PGF and PGE) bind to specific high‐affinity receptors and initiate biologically distinct signalling pathways. In the ovaries, prostaglandins are known to be important endocrine regulators of female reproduction, in addition to maintaining local function through autocrine and/or paracrine effect. Many research groups in different animal species have already identified a variety of factors and molecular mechanisms that are responsible for the regulation of prostaglandin functions. In addition, prostaglandins stimulate their intrafollicular and intraluteal production via the pathway of prostaglandin self‐regulation in the ovary. Therefore, the objective of the review article is to discuss recent findings about local regulation patterns of prostaglandin ligands PGF and PGE during different physiological stages of ovarian function in domestic ruminants, especially in bovine. In conclusion, the discussed local regulation mechanisms of prostaglandins in the ovary may stimulate further research activities in different methodological approaches, especially during final follicle maturation and ovulation, as well as corpus luteum formation and function.
Adult children and older people's demand for community care services in urban China
Authors: Zhou Junshan , Walker Alan
Published: October 2023

Objectives

This paper has two objectives. First, it assesses whether the existing informal care provided by adult children has an impact on older people's propensity to demand community care services. Second, it compares the different statuses of sons and daughters in the formal/informal support trade‐off.

Methods

The paper is based on an analysis of data from the 2018 wave of the China Longitudinal Ageing Social Survey, within the framework of a revised version of Andersen's model, and applies multilevel models to analyse the effects of adult children's gender, numbers and the quality of their support, on older people's willingness to purchase community care services.

Results

Older people who had sons as well as daughters demanded fewer services, while the number of sons increased service demand. Regarding sons, community care services compensated for economic support, daily life care and spiritual consolation, but did so only in respect of daily life care from daughters.

Conclusions

Many families have only one son or one daughter as a result of the one‐child policy and therefore often require support from formal care services. Moreover, there is a distinct gender division and an influential filial culture governing the impact of services on the support provided by adult children. Because ageing in place depends on both informal family support and formal services, this key policy goal is at risk if the latter provides insufficient support to the former.
Ecological worldview moderates the mediation of implementation‐intentions found in the relationship between ecological concerns and pro‐environmental behaviour
Authors: Mishra Navneet , Mishra Ankita , Singh Parwinder
Published: October 2023

Even after adopting various measures, recent years have witnessed a surge in environment‐related issues such as pollution and climate change. These issues have been considered anthropogenic, and it is a well‐received notion that changing human behaviour is crucial for sustainable development. Promoting pro‐environmental behaviour (PEB) requires understanding of associations among relevant factors; the present study aimed to explore the same among a few less‐explored constructs, which, along with other factors, may significantly explain pro‐environmental behaviour. The study examined the direct relationship of PEB with ecological intelligence (EI) and self‐transcendent values. Also, it explored the mediating effects of implementation‐intentions and the moderating effect of the “new ecological paradigm” (NEP) on PEB. The data were obtained from 400 adult participants using a set of standardized questionnaires. The results showed significant direct and indirect associations among EI, self‐transcendent values, implementation‐intentions, the NEP and PEB. Implementation‐intentions significantly mediated the relationship of EI and values with PEB, and the mediation was moderated by the NEP. Individuals low on EI but endorsing the NEP showed implementation‐intentions similar to those with high EI. Knowledge of the interplay among these factors can be utilized to design interventions for promoting PEB.
Do you trust the rumors? Examining the determinants of health‐related misinformation in India
Authors: Kapoor Hansika , Gurjar Swanaya , Mahadeshwar Hreem , Mehta Nikita , Puthillam Arathy
Published: October 2023

Rumors, conspiracies, and health‐related misinformation have gone hand‐in‐hand with the global COVID‐19 pandemic, making it hard to obtain reliable and accurate information. Against this background, this study examined the different psychosocial predictors of believing in conspiratorial information related to general health in India. Indian participants (N = 826) responded to measures related to conspiratorial thinking, trust, moral emotions, political ideology, bullshit receptivity, and belief in conspiratorial information in an online survey. Exploratory and confirmatory factor analyses were used to determine the validity of the instruments used with an Indian sample. Results revealed that lower subjective socioeconomic status, lower trust in political institutions, greater negative moral emotions, greater conspiratorial thinking, and right‐leaning political ideology predicted beliefs in health‐related conspiratorial information. In highlighting these potential psychosocial determinants of conspiratorial beliefs, we can move toward combating conspiracies effectively and developing necessary interventions for the same. Future work can focus on assessing the moderating effects of political ideology on conspiratorial beliefs in India.
Reject bias: A dialectical perspective on the relationship between bottom‐line mentality and unethical pro‐organizational behaviour
Authors: Zhang Guiqing , Zhou Shenbei , Li Yibin , Duan Yeqing , Liu Longjun
Published: October 2023

There is a “positive–negative” debate on the development of the bottom‐line mentality (BLM) concept. Previous research showed a relationship between BLM and unethical pro‐organizational behaviour (UPB) and revealed that BLM positively affected UPB. This research aims to challenge this partial view and calls for a more balanced and comprehensive view of the BLM concept by revealing the potential negative influencing mechanism between BLM and UPB. Drawing from social information processing theory, we construct a moderated‐mediation model to test the mediating mechanism through different individual‐level processes in the Chinese context. Findings indicate that team BLM positively affects member UPB via state performance‐prove goal orientation and perceived insider status and negatively affects member UPB via state performance‐avoid goal orientation. These results confirm the overall positive relationship between team BLM and member UPB but also document the possible inhibitory mechanism of BLM on UPB. This study is the first to acknowledge the potential negative relationship between BLM and UPB, which deserves attention. This research also presents a complete picture of the BLM literature. The findings of this work have significant implications in enabling organizations to appropriately handle BLM and its relationship with UPB dynamically.
Fuzzy borders
Authors: Raheja Natasha
Published: October 2023

In the western Indian city of Jodhpur, computer typists provide migration brokerage services to Pakistani Hindu refugee‐migrants and Indian immigration officers. Such encounters and their interpretations contrast with the Indian state's emphasis on governmental proximity and immediate state‐subject relations. Though computer typists—who I am calling brokers—are essential mediators, their acts of mediation are underrecognized. Immigration officers’ strategies of mediation, such as intermittently acknowledging typists, implicate brokerage as both part of and distinct from the everyday bureaucratic workings of the state. I argue that through their acts of mediation, brokers are essential to bureaucratic work and have come to embody the fuzziness surrounding where the state begins and ends.
Development of diabetic macular oedema shows associations with systemic medication – An epidemiological study
Authors: Loukovaara Sirpa , Korhonen Ani , Niskanen Leo , Haukka Jari
Published: October 2023

Purpose

To identify associations between systemic drugs and the incidence of diabetic macular oedema (DME). Of interest was to find beneficial and/or deleterious associations of used drugs.

Methods

A historic cohort design based on administrative data. Study population consisted of 150 353 individuals with diabetes. Endpoint event was the development of DME (ICD‐10 H36.01), censoring events were death or study end December 2017. The follow‐up started between 1997 and 2010. The systemic medication consisted of 95 substances. We constructed a nested case–control study design comparing 2630 cases with DME to 13 144 age‐ and sex‐matched controls without DME. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) based on conditional logistic regression models.

Results

Incidence rate for DME was 1.80 per 1000 person‐years (95% CI 1.73–1.87). In all, we observed a lower incidence rate of DME in females (IRR 0.57; 95% CI 0.52–0.62) compared to males. Exposure to hormone replacement therapy estradiol (OR 0.42; 0.25–0.68), temazepam (0.23; 0.08–0.62) and allopurinol (0.61; 0.43–0.86) were associated with lower risk of DME, while use of insulin or insulin analogue (3.30; 2.99–3.64), sulfonylureas (1.21; 1.05–1.40), diuretic furosemide (1.90; 1.61–2.24), calcium channel blocker amlodipine (1.53; 1.34–1.75), ACE inhibitors ramipril (1.66; 1.46–1.89) and enalapril (1.38; 1.16–1.64) were associated with an increased risk of DME.

Conclusions

Large‐scale studies examining the incidence of DME are lacking. Our findings suggest that associations of systemic medications with the incidence of DME may shed light on the pathogenesis of complex DME, encouraging further studies.
Local or imported? The origin of the raw material used in manufacturing bricks from castles of the Teutonic knights in north‐central Poland and their significance to our understanding of medieval construction techniques
Authors: Wiewióra Marcin , Bartz Wojciech , Łukaszewicz Jadwiga , Witkowska Karolina , Jóźwiak Sławomir , Molewski Paweł
Published: October 2023

This article presents the results of research on bricks from medieval castles in north‐central Poland. They were characterised based on petrographic analyses of thin section and mutually complementary instrumental methods. The bricks came from the oldest parts of the castles preserved to this day, or from castles not preserved but examined and excavated during archaeological research. The data obtained allowed for the identification of building materials that shared similar material and technical properties and that can be associated with different phases of the castles. Based on the results, it was found that the Pleistocene tills commonly found around the castles were not used in the manufacturing of the bricks. Small local deposits of fatty clays were used—Pleistocene varved clays or Miocene variegated clays. The buildings differed in the composition and texture of their bricks, indicating that the local clay raw material was extracted for each building separately. The share of raw material brought in from larger exposures further afield was small. Analyses of brick samples indicate the use of a fatty clay raw material that was improved by the addition of clastic material (quartz sand or a mixture of sand and quartz silt of various fractions).
The impact of anxiety and intolerance of uncertainty on climate change distress, policy support, and pro‐environmental behaviour
Authors: Goldwert Danielle , Dev Amelia S. , Broos Hannah C. , Broad Kenneth , Timpano Kiara R.
Published: October 2023

Objectives

As the threat of climate change continues to grow, bolstering individual‐level support for climate change initiatives is crucial. More research is needed to better understand how individual difference factors, such as climate change anxiety and intolerance of uncertainty (IU), may shape how people perceive climate change and respond to climate change messaging. To date, the majority of published studies have not taken these individual difference factors into consideration, and IU has been particularly neglected in the climate change literature. This study examined the independent effects of climate change anxiety and IU on three climate change‐related outcomes: climate‐related distress, support for climate change policies, and behavioural engagement.

Methods

Participants were Florida residents (N = 441) who completed an online survey, including measures of climate change anxiety and IU. Participants then watched a video describing climate change consequences and completed three outcome measures: post‐video distress, climate change policy support, and behavioural engagement.

Results

Controlling for demographic covariates, both climate change anxiety (β = .43, p < .001) and IU (β = .27, p < .001) were associated with greater post‐video distress, but only IU independently predicted greater policy support (β = .10, p = .034) and behavioural engagement (β = .12, p = .017).

Conclusions

Our findings suggest that IU may be an important factor in promoting pro‐environmental behaviour and policy support, but climate change anxiety may increase emotional distress without boosting meaningful behaviours or support. Our findings highlight the potential influence of cognitive factors on climate change engagement and suggest that invoking uncertainty rather than anxiety may be more effective in catalysing effective environmental engagement.