bluuebunny/crossref_metadata_2025 huggingface dataset:
Parvalbumin interneurons in human ventromedial prefrontal cortex: a comprehensive post-mortem study of myelination and perineuronal nets in neurotypical individuals and depressed suicides with and without a history of child abuse
Authors: Théberge Stéphanie , Belliveau Claudia , Xie Dongyue , Khalaf Roy , Perlman Kelly , Rahimian Reza , Davoli Maria Antonietta , Turecki Gustavo , Mechawar Naguib
Published: May 2024

Cortical parvalbumin interneurons (PV+) are major regulators of excitatory/inhibitory information processing, and their maturation is associated with the opening of developmental critical periods (CP). Recent studies reveal that cortical PV+ axons are myelinated, and that myelination along with perineuronal net (PNN) maturation around PV+ cells is associated with the closures of CP. Although PV+ interneurons are susceptible to early-life stress, their relationship between their myelination and PNN coverage remains unexplored. This study compared the fine features of PV+ interneurons in well-characterized human post-mortem ventromedial prefrontal cortex samples (n = 31) from depressed suicides with or without a history of child abuse (CA) and matched controls. In healthy controls, 81% of all sampled PV+ interneurons displayed a myelinated axon, while a subset (66%) of these cells also displayed a PNN, proposing a relationship between both attributes. Intriguingly, a 3-fold increase in the proportion of unmyelinated PV+ interneurons with a PNN was observed in CA victims, along with greater PV-immunofluorescence intensity in myelinated PV+ cells with a PNN. This study, which is the first to provide normative data on myelination and PNNs around PV+ interneurons in human neocortex, sheds further light on the cellular and molecular consequences of early-life adversity on cortical PV+ interneurons.
Radiomics to Detect Inflammation and Fibrosis on Magnetic Resonance Enterography in Stricturing Crohn’s Disease
Authors: Chirra Prathyush , Sleiman Joseph , Gandhi Namita S , Gordon Ilyssa O , Hariri Mohsen , Baker Mark , Ottichilo Ronald , Bruining David H , Kurowski Jacob A , Viswanath Satish E , Rieder Florian
Published: May 2024

Background and Aims

Non-invasive cross-sectional imaging via magnetic resonance enterography [MRE] offers excellent accuracy for the diagnosis of stricturing complications in Crohn’s disease [CD] but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathological inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE.

Methods

This single-centre, cross-sectional study included 51 CD patients [n = 34 for discovery; n = 17 for validation] with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both were evaluated against histopathology.

Results

Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both the discovery (area under the curve [AUC = 0.69, 0.83] and validation [AUC = 0.67, 0.78] cohorts. Radiologist visual scoring had an AUC = 0.67 for identifying severe inflammation and AUC = 0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation [AUC = 0.79] and modestly improved assessment of severe fibrosis [AUC = 0.79 for severe fibrosis] over individual approaches.

Conclusions

Radiomic features of CD strictures on MRE can accurately identify severe histopathological inflammation and severe histopathological fibrosis, as well as augment performance of the radiologist visual scoring in stricture characterization.
Incentivising Textbooks for Self-Study: Experimental Evidence from the Democratic Republic of the Congo
Authors: Falisse Jean-Benoît , Huysentruyt Marieke , Olofsgård Anders
Published: May 2024

We designed and randomly evaluated the impact of textbooks for a self-study scheme in eastern areas of the Democratic Republic of the Congo targeting student achievement in primary schools. Students in treatment schools were 7 percentage points more likely to pass the national exam, and those who passed obtained higher scores. We also evidence higher scores on a French language test. The effects are primarily driven by student interest in textbooks, frequency of doing homework and motivation to go to school and continue education. Student achievement can thus be improved by intensified and diversified use of existing learning materials in poor and fragile settings.
History of Diversification and Adaptation from North to South Revealed by Genomic Data: Guanacos from the Desert to Sub-Antarctica
Authors: León Fabiola , Pizarro Eduardo J , Noll Daly , Pertierra Luis R , Gonzalez Benito A , Johnson Warren E , Marín Juan Carlos , Vianna Juliana A
Published: May 2024

The increased availability of quality genomic data has greatly improved the scope and resolution of our understanding of the recent evolutionary history of wild species adapted to extreme environments and their susceptibility to anthropogenic impacts. The guanaco (Lama guanicoe), the largest wild ungulate in South America, is a good example. The guanaco is well adapted to a wide range of habitats, including the Sechura Desert, the high Andes Mountains to the north, and the extreme temperatures and conditions of Navarino Island to the south. Guanacos also have a long history of overexploitation by humans. To assess the evolutionary impact of these challenging habitats on the genomic diversity, we analyzed 38 genomes (∼10 to 16×) throughout their extensive latitudinal distribution from the Sechura and Atacama Desert to southward into Tierra del Fuego Island. These included analyses of patterns of unique differentiation in the north and geographic region further south with admixture among L. g. cacsilensis and L. g. guanicoe. Our findings provide new insights on the divergence of the subspecies ∼800,000 yr BP and document two divergent demographic trajectories and to the initial expansion of guanaco into the more southern portions of the Atacama Desert. Patagonian guanacos have experienced contemporary reductions in effective population sizes, likely the consequence of anthropogenic impacts. The lowest levels of genetic diversity corresponded to their northern and western limits of distribution and some varying degrees of genetic differentiation. Adaptive genomic diversity was strongly linked with environmental variables and was linked with colonization toward the south followed by adaptation.
The Mediating Role of Kynurenine Pathway Metabolites on the Relationship Between Inflammation and Muscle Mass in Oldest–Old Men
Authors: Hetherington-Rauth Megan , Johnson Eileen , Migliavacca Eugenia , Langsetmo Lisa , Hepple Russell T , Ryan Terence E , Ferrucci Luigi , Breuillé Denis , Corthesy John , Lane Nancy E , Feige Jérôme N , Napoli Nicola , Tramontana Flavia , Orwoll Eric S , Cawthon Peggy M
Published: May 2024

Tryptophan (TRP) metabolites along the kynurenine (KYN) pathway (KP) have been found to influence muscle. Proinflammatory cytokines are known to stimulate the degradation of TRP down the KP. Given that both inflammation and KP metabolites have been connected with loss of muscle, we assessed the potential mediating role of KP metabolites on inflammation and muscle mass in older men. Five hundred and five men (85.0 ± 4.2 years) from the Osteoporotic Fractures in Men cohort study with measured D3-creatine dilution (D3Cr) muscle mass, KP metabolites, and inflammation markers (C-reactive protein [CRP], alpha-1-acid glycoprotein [AGP] and a subsample [n = 305] with interleukin [IL-6, IL-1β, IL-17A] and tumor necrosis factor-α [TNF-α]) were included in the analysis. KP metabolites and inflammatory markers were measured using liquid chromatography-tandem mass spectrometry and immunoassays, respectively. 23%–92% of the inverse relationship between inflammatory markers and D3Cr muscle mass was mediated by KP metabolites (indirect effect p < .05). 3-hydroxyanthranilic acid (3-HAA), quinolinic acid (QA), TRP, xanthurenic acid (XA), KYN/TRP, 3-hydroxykynurenine (3-HK)/3-HAA, QA/3-HAA, and nicotinamide (NAM)/QA mediated the AGP relationship. 3-HAA, QA, KYN/TRP, 3-HK/XA, HKr ratio, 3-HK/3-HAA, QA/3-HAA, and NAM/QA mediated the CRP. KYN/TRP, 3-HK/XA, and NAM/QA explained the relationship for IL-6 and 3-HK/XA and QA/3-HAA for TNF-α. No mediation effect was observed for the other cytokines (indirect effect p > .05). KP metabolites, particularly higher ratios of KYN/TRP, 3-HK/XA, 3-HK/3-HAA, QA/3-HAA, and a lower ratio of NAM/QA, mediated the relationship between inflammation and low muscle mass. Our preliminary cross-sectional data suggest that interventions to alter D3Cr muscle mass may focus on KP metabolites rather than inflammation per se.
Linking Aging to Cancer: The Role of Chromatin Biology
Authors: Corveleyn Laura , Sen Payel , Adams Peter , Sidoli Simone
Published: May 2024

Epigenetic changes have been established to be a hallmark of aging, which implies that aging science requires collaborating with the field of chromatin biology. DNA methylation patterns, changes in relative abundance of histone post-translational modifications, and chromatin remodeling are the central players in modifying chromatin structure. Aging is commonly associated with an overall increase in chromatin instability, loss of homeostasis, and decondensation. However, numerous publications have highlighted that the link between aging and chromatin changes is not nearly as linear as previously expected. This complex interplay of these epigenetic elements during the lifetime of an organism likely contributes to cellular senescence, genomic instability, and disease susceptibility. Yet, the causal links between these phenomena still need to be fully unraveled. In this perspective article, we discuss potential future directions of aging chromatin biology.
What Does It Mean to “Age Well” Among British and Javanese Older Adults? A Cross-Cultural Qualitative Study
Authors: Sulandari Santi , Coats Rachel O , Taufik Taufik , Johnson Judith
Published: May 2024

Objectives

This study aimed to investigate perceptions of what it means to “age well” and to explore similarities and differences between a Western and non-Western culture (Britain and Java).

Methods

Qualitative interviews explored how Javanese and British older adults defined aging well, establishing the similarities and differences between cultures. Javanese (n = 14) and British (n = 15) adults aged 61–80 (mean age = 68) participated. The data were analyzed using reflexive thematic analysis and organized with NVivo.

Results

Four themes were identified that captured what it means to age well across cultures: (a) good health is a springboard for aging well; (b) holding a positive outlook is a decisive factor in aging well; (c) “having enough” and “feeling safe” provide peace of mind; and (d) spirituality and religiosity provide tranquility. Although both cultures mentioned similar factors, there were variations in the interpretations and emphasis within themes. For example, Javanese participants emphasized the importance of the social environment whereas British participants highlighted the physical environment.

Discussion

Differences between cultures are important for understanding how best to support people as they age. For example, in Java, aging well may be best supported by providing a vibrant social environment. For people in Britain, having a safe and secure physical environment may be more important.
Using Clustering Methods to Map the Experience Profiles of Dementia Caregivers
Authors: Ashida Sato , Lynn Freda B , Thompson Lena , Koehly Laura M , Williams Kristine N , Donohoe Maria S
Published: May 2024

Background and Objectives

Caregivers of persons living with dementia report wide-ranging lived experiences, including feelings of burden and frustration but also positivity about caregiving. This study applies clustering methodology to novel survey data to explore variation in caregiving experience profiles, which could then be used to design and target caregiver interventions aimed at improving caregiver well-being.

Research Design and Methods

The k-means clustering algorithm partitioned a sample of 81 caregivers from the Midwest region of the United States on the basis of 8 variables capturing caregiver emotions, attitudes, knowledge, and network perceptions (adversity: burden, anxiety, network malfeasance; network nonfeasance; positivity: positive aspects of caregiving, preparedness and confidence in community-based care, knowledge about community services for older adults, and network uplift). The experience profile of each segment is described qualitatively and then regression methods were used to examine the association between (a) experience profiles and caregiver demographic characteristics and (b) experience profiles and study attrition.

Results

The clustering algorithm identified 4 segments of caregivers with distinct experience profiles: Thriving (low adversity, high positivity); Struggling with Network (high network malfeasance); Intensely Struggling (high adversity, low positivity); Detached (unprepared, disconnected, but not anxious). Experience profiles were associated with significantly different demographic profiles and attrition rates.

Discussion and Implications

How caregivers respond to support interventions may be contingent on caregivers’ experience profile. Research and practice should focus on identifying public health strategies tailored to fit caregiver experiences.

Clinical Trial Registration

NCT03932812
War-Related Life Course Stress and Late-Life Subjective Age in Northern Vietnam
Authors: Korinek Kim , Young Yvette , Schmidt Jefferson , Toan Tran Khanh , Zimmer Zachary
Published: May 2024

Background and Objectives

The role of early life stressors in subjective aging is weakly understood, especially in low- to middle-income countries. This paper investigated how early life stressors encountered in armed conflict influence subjective age among Vietnamese older adults who experienced war over decades of their early life.

Research Design and Methods

We analyzed survey data from the 2018 Vietnam Health and Aging Study involving 2,447 Vietnamese older adults who encountered diverse war-related stressors in early adulthood. The analytical sample (N = 2,341) included 50.9% women and 49.1% men, with an average age of 69.8. 41.1% are military veterans. We conducted survey-adjusted multinomial logistic regression analyses with mediation to predict the probability of feeling younger or older than one’s chronological age. We examined how childhood adversity (i.e., childhood hunger and low parental SES) and wartime stressors (i.e., war-related violence, malevolent environment, and military service) influenced late-life subjective age, both directly and as mediated by late-life mental, functional, and physical health.

Results

We found significant associations between early adulthood war-related stressors and subjective age. Formal military service significantly lessened the relative risk of feeling subjectively old, and more plentiful wartime violence exposures significantly increased the risk of feeling younger than one’s chronological age. Violence exposure’s effects were both direct and indirect through functional and mental health. Conversely, greater exposure to wartime malevolent conditions (e.g., shortages of clean water and evacuations) and multiple episodes of severe hunger in childhood increased the risk of feeling older, effects both direct and mediated by late-life functional and mental health.

Discussion and Implications

Results suggest wartime stressors, especially war’s malevolent environments and severe childhood hunger, experienced in many conflict-affected populations globally, have the potential to subjectively “age” survivors. Yet, not all war exposures are equal, and some may yield psychological and socioeconomic resources that support healthy aging.
Beclin-mediated Autophagy Drives Dorsal Longitudinal Flight Muscle Histolysis in the Variable Field Cricket, Gryllus lineaticeps
Authors: Diaz Tomás , Treidel Lisa A , Menze Michael A , Williams Caroline M , Lebenzon Jacqueline E
Published: May 2024

Synopsis

Flight muscle histolysis is a widespread strategy used by insects to break down functional flight muscle and modulate the energetic costs associated with flight muscle use and maintenance. The variable field cricket, Gryllus lineaticeps, undergoes histolysis during their transition between dispersal flight and reproduction. Despite the importance of histolysis on insect reproduction and fitness, the molecular mechanisms driving this flight muscle breakdown are not well understood. Here, we show that beclin-mediated autophagy, a conserved lysosomal-dependent degradation process, drives breakdown of dorsal longitudinal flight muscle in female flight-capable G. lineaticeps. We found that female G. lineaticeps activate autophagy in their dorsal longitudinal flight muscle (DLM), but to a greater extent than the neighboring dorsoventral flight muscle (DVM) during histolysis. RNA interference knockdown of beclin, a gene that encodes a critical autophagy initiation protein, delayed DLM histolysis, but did not affect DVM histolysis. This suggests that crickets selectively activate autophagy to break down the DLMs, while maintaining DVM function for other fitness-relevant activities such as walking. Overall, we confirmed that autophagy is a critical pathway used to remodel flight muscle cells during flight muscle histolysis, providing novel insights into the mechanisms underlying a major life history transition between dispersal and reproduction.
High-order Lagrange-Galerkin methods for the conservative formulation of the advection-diffusion equation
Authors: Bermejo Rodolfo , Colera Manuel
Published: May 2024

We introduce in this paper the numerical analysis of high order both in time and space Lagrange-Galerkin methods for the conservative formulation of the advection-diffusion equation. As time discretization scheme we consider the Backward Differentiation Formulas up to order $q=5$. The development and analysis of the methods are performed in the framework of time evolving finite elements presented in C. M. Elliot and T. Ranner, IMA Journal of Numerical Analysis41, 1696–1845 (2021). The error estimates show through their dependence on the parameters of the equation the existence of different regimes in the behavior of the numerical solution; namely, in the diffusive regime, that is, when the diffusion parameter $\mu $ is large, the error is $O(h^{k+1}+\varDelta t^{q})$, whereas in the advective regime, $\mu \ll 1$, the convergence is $O(\min (h^{k},\frac{h^{k+1} }{\varDelta t})+\varDelta t^{q})$. It is worth remarking that the error constant does not have exponential $\mu ^{-1}$ dependence.
Dietary glycine supplementation activates mechanistic target of rapamycin signaling pathway in tissues of pigs with intrauterine growth restriction
Authors: He Wenliang , Posey Erin A , Steele Chandler C , Savell Jeffrey W , Bazer Fuller W , Wu Guoyao
Published: May 2024

The mechanistic target of rapamycin (mTOR) cell signaling pathway serves as the central mechanism for the regulation of tissue protein synthesis and growth. We recently reported that supplementing 1% glycine to corn- and soybean meal-based diets enhanced growth performance between weaning and market weights in pigs with intrauterine growth restriction (IUGR). Results of recent studies have revealed an important role for glycine in activating mTOR and protein synthesis in C2C12 muscle cells. Therefore, the present study tested the hypothesis that dietary glycine supplementation enhanced the mTOR cell signaling pathway in skeletal muscle and other tissues of IUGR pigs. At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to one of the two groups: supplementation with either 1% glycine or 1.19% l-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Tissues were obtained from the pigs within 1 wk after the feeding trial ended at 188 d of age to determine the abundances of total and phosphorylated forms of mTOR and its two major downstream proteins: eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and ribosomal protein S6 kinase-1 (p70S6K). Results showed that IUGR decreased (P < 0.05) the abundances of both total and phosphorylated mTOR, 4EBP1, and p70S6K in the gastrocnemius muscle and jejunum. In the longissimus lumborum muscle of IUGR pigs, the abundances of total mTOR did not differ (P > 0.05) but those for phosphorylated mTOR and both total and phosphorylated 4EBP1 and p70S6K were downregulated (P < 0.05), when compared to NBW pigs. These adverse effects of IUGR in the gastrocnemius muscle, longissimus lumborum muscle, and jejunum were prevented (P < 0.05) by dietary glycine supplementation. Interestingly, the abundances of total or phosphorylated mTOR, 4EBP1, and p70S6K in the liver were not affected (P > 0.05) by IUGR or glycine supplementation. Collectively, our findings indicate that IUGR impaired the mTOR cell signaling pathway in the tissues of pigs and that adequate glycine intake was crucial for maintaining active mTOR-dependent protein synthesis for the growth and development of skeletal muscle.
CCT6A alleviates pulmonary fibrosis by inhibiting HIF-1α-mediated lactate production
Authors: Yan Peishuo , Yang Kun , Xu Mengwei , Zhu Miaomiao , Duan Yudi , Li Wenwen , Liu Lulu , Liang Chenxi , Li Zhongzheng , Pan Xin , Wang Lan , Yu Guoying
Published: May 2024

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive fibrotic lung disease. The development of IPF involves different molecular and cellular processes, and recent studies indicate that lactate plays a significant role in promoting the progression of the disease. Nevertheless, the mechanism by which lactate metabolism is regulated and the downstream effects remain unclear. The molecular chaperone CCT6A performs multiple functions in a variety of biological processes. Our research has identified a potential association between CCT6A and serum lactate levels in IPF patients. Herein, we found that CCT6A was highly expressed in type 2 alveolar epithelial cells (AEC2s) of fibrotic lung tissues and correlated with disease severity. Lactate increases the accumulation of lipid droplets in epithelial cells. CCT6A inhibits lipid synthesis by blocking the production of lactate in AEC2s and alleviates bleomycin-induced pulmonary fibrosis in mice. In addition, our results revealed that CCT6A blocks HIF-1α-mediated lactate production by driving the VHL-dependent ubiquitination and degradation of HIF-1α and further inhibits lipid accumulation in fibrotic lungs. In conclusion, we propose that there is a pivotal regulatory role of CCT6A in lactate metabolism in pulmonary fibrosis, and strategies aimed at targeting these key molecules could represent potential therapeutic approaches for pulmonary fibrosis.
Habitat-specific allocations of elements in Atriplex lentiformis seeds indicate adaptation to metal toxicity
Authors: Murawska-Wlodarczyk Kamila , van der Ent Antony , Wlodarczyk Tomasz , Słomka Aneta , Paterson David J , Brueckner Dennis , Przybyłowicz Wojciech J , Mesjasz-Przybyłowicz Jolanta , Ryan Chris C , Maier Raina M , Babst-Kostecka Alicja
Published: May 2024

Self-sustaining vegetation in metal-contaminated areas is essential for rebuilding ecological resilience and community stability in degraded lands. Metal-tolerant plants originating from contaminated post-mining areas may hold the key to successful plant establishment and growth. Yet, little is known about the impact of metal toxicity on reproductive strategies, metal accumulation, and allocation patterns at the seed stage. Our research focused on the metal tolerant Atriplex lentiformis. Specifically, we examined the effects of toxic metal(loid) concentration in soils on variability in its reproductive strategies, including germination patterns, elemental uptake, and allocation within the seeds. We employed advanced imaging techniques like synchrotron X-ray fluorescence microscopy (2D scans and 3D tomograms) combined with inductively coupled plasma mass spectrometry to reveal significant differences in metal(loid) concentration and distribution within the seed structures of A. lentiformis from contrasting habitats. Exclusive Zn hotspots of high concentrations were found in the seeds of the metallicolous accession, primarily in the sensitive tissues of shoot apical meristems and root zones of the seed embryos. Our findings offer novel insights into phenotypic variability and metal tolerance and accumulation in plants from extreme environments. This knowledge can be applied to enhance plant survival and performance in land restoration efforts.
“Uncertain Thresholds”: An Interview with Carmen Maria Machado
Authors: Milne Leah A
Published: May 2024

This interview with award-winning novelist, essayist, and short story writer Carmen Maria Machado took place shortly after she delivered her reading and keynote address at the 2023 MELUS conference. In the interview, she discusses the complications of her liminal identity as a queer, fat, mixed-race, and white-presenting woman, as well as numerous personal and professional influences influencing her views on race and culture. She also talks about her books, the 2017 short fiction collection Her Body and Other Parties and the 2019 experimental memoir In the Dream House, and discusses the short story that she read at the MELUS conference and that will appear in a forthcoming short story collection, A Brief and Fearful Star. Privilege and the politics of reading and writing across boundaries such as race and nationality form the basis for additional contemplations about the ethics underlying multi-ethnic and mixed-race narratives.
Impacts of the 12C(α, γ)16O reaction rate on 56Ni nucleosynthesis in pair-instability supernovae
Authors: Kawashimo Hiroki , Sawada Ryo , Suwa Yudai , Moriya Takashi J , Tanikawa Ataru , Tominaga Nozomu
Published: May 2024

Nuclear reactions are key to our understanding of stellar evolution, particularly the $^{12}{\rm C}(\alpha ,\gamma)^{16}{\rm O}\,$ rate, which is known to significantly influence the lower and upper ends of the black hole (BH) mass distribution due to pair-instability supernovae (PISNe). However, these reaction rates have not been sufficiently determined. We use the mesa stellar evolution code to explore the impact of uncertainty in the $^{12}{\rm C}(\alpha ,\gamma)^{16}{\rm O}\,$ rate on PISN explosions, focusing on nucleosynthesis and explosion energy by considering the high resolution of the initial mass. Our findings show that the mass of synthesized radioactive nickel (56Ni) and the explosion energy increase with $^{12}{\rm C}(\alpha ,\gamma)^{16}{\rm O}\,$ rate for the same initial mass, except in the high-mass edge region. With a high (about twice the starlib standard value) rate, the maximum amount of nickel produced falls below 70 M⊙, while with a low rate (about half of the standard value) it increases up to 83.9 M⊙. These results highlight that carbon ‘preheating’ plays a crucial role in PISNe by determining core concentration when a star initiates expansion. Our results also suggest that the onset of the expansion, which means the end of compression, competes with collapse caused by helium photodisintegration, and the maximum mass that can lead to an explosion depends on the $^{12}{\rm C}(\alpha ,\gamma)^{16}{\rm O}\,$ reaction rate.
X-ray cool core remnants heated by strong radio AGN feedback
Authors: Liu Wenhao , Sun Ming , Voit G Mark , Lal Dharam Vir , Nulsen Paul , Gaspari Massimo , Sarazin Craig , Ehlert Steven , Zheng Xianzhong
Published: May 2024

Strong AGN heating provides an alternative means for the disruption of cluster cool cores (CCs) to cluster mergers. In this work, we present a systematic Chandra study of a sample of 108 nearby (z < 0.1) galaxy clusters, to investigate the effect of AGN heating on CCs. About 40 per cent of clusters with small offsets between the BCG and the X-ray centre (≤50 kpc) have small CCs. For comparison, 14 of 17 clusters with large offsets have small CCs, which suggests that mergers or sloshing can be efficient in reducing the CC size. Relaxed, small CC clusters generally have weak radio AGNs ($P_{1.4\rm GHz}\lt 10^{23}$ W Hz−1), and they show a lack of systems hosting a radio AGN with intermediate radio power ($2\times 10^{23}\lt P_{1.4\rm GHz}\lt 2\times 10^{24}$ W Hz−1). We found that the strongest circumnuclear (<1 kpc) X-ray emission only exists in clusters with strong radio AGN. The duty cycle of relaxed, small CC clusters is less than half of that for large CC clusters. It suggests that the radio activity of BCGs is affected by the properties of the surrounding gas beyond the central ∼10 kpc, and strong radio AGNs in small X-ray CCs fade more rapidly than those embedded in large X-ray CCs. A scenario is also presented for the transition of large CCs and coronae due to radio AGN feedback. We also present a detailed analysis of galaxy cluster 3C 129.1 as an example of a CC remnant possibly disrupted by radio AGN.
Searching for magnetar binaries disrupted by core-collapse supernovae
Authors: Sherman Myles B , Ravi Vikram , El-Badry Kareem , Sharma Kritti , Ocker Stella Koch , Kosogorov Nikita , Connor Liam , Faber Jakob T
Published: May 2024

Core-collapse supernovae (CCSNe) are considered the primary magnetar formation channel, with 15 magnetars associated with supernova remnants (SNRs). A large fraction of these should occur in massive stellar binaries that are disrupted by the explosion, meaning that $\sim 45~{{\ \rm per\ cent}}$ of magnetars should be nearby high-velocity stars. Here, we conduct a multiwavelength search for unbound stars, magnetar binaries, and SNR shells using public optical (uvgrizy bands), infrared (J, H, K, and Ks bands), and radio (888 MHz, 1.4 GHz, and 3 GHz) catalogues. We use Monte Carlo analyses of candidates to estimate the probability of association with a given magnetar based on their proximity, distance, proper motion, and magnitude. In addition to recovering a proposed magnetar binary, a proposed unbound binary, and 13 of 15 magnetar SNRs, we identify two new candidate unbound systems: an OB star from the Gaia catalogue we associate with SGR J1822.3−1606, and an X-ray pulsar we associate with 3XMM J185246.6 + 003317. Using a Markov Chain Monte Carlo simulation that assumes all magnetars descend from CCSNe, we constrain the fraction of magnetars with unbound companions to $5\lesssim f_u \lesssim 24~{{\ \rm per\ cent}}$, which disagrees with neutron star population synthesis results. Alternate formation channels are unlikely to wholly account for the lack of unbound binaries as this would require $31\lesssim f_{nc} \lesssim 66~{{\ \rm per\ cent}}$ of magnetars to descend from such channels. Our results support a high fraction ($48\lesssim f_m \lesssim 86~{{\ \rm per\ cent}}$) of pre-CCSN mergers, which can amplify fossil magnetic fields to preferentially form magnetars.
Metabolomics reveals the implication of acetoacetate and ketogenic diet therapy in radioiodine-refractory differentiated thyroid carcinoma
Authors: Wang Jiaqi , Xu Qianqian , Xuan Ziyang , Mao Yuting , Tang Xi , Yang Ke , Song Fahuan , Zhu Xin
Published: May 2024

Objective

Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC; RAIR-DTC) have a poor prognosis. The aim of this study was to provide new insights and possibilities for the diagnosis and treatment of RAIR-DTC.

Methods

The metabolomics of 24 RAIR-DTC and 18 non-radioiodine-refractory (NonRAIR) DTC patients samples were analyzed by liquid chromatograph-mass spectrometry. Cellular radioiodine uptake was detected with γ counter. Sodium iodide symporter (NIS) expression and thyroid stimulating hormone receptor (TSHR) were measured by Western blot analysis. CCK8 and colony formation assays were used to measure cellular proliferation. Scratch and transwell assays were performed to assess cell migration and invasion. Annexin V/PI staining was used to detect cell apoptosis. Cell growth in vivo was evaluated by a tumor xenograft model. The acetoacetate (AcAc) level was measured by ELISA. Pathological changes, Ki67, NIS, and TSHR expression were investigated by immunohistochemistry.

Results

The metabolite profiles of RAIR could be distinguished from those of NonRAIR, with AcAc significantly lower in RAIR. The significantly different metabolic pathway was ketone body metabolism. AcAc increased NIS and TSHR expression and improved radioiodine uptake. AcAc inhibited cell proliferation, migration, and invasion, and as well promoted cell apoptosis. Ketogenic diet (KD) elevated AcAc levels and significantly suppressed tumor growth, as well as improved NIS and TSHR expression.

Conclusion

Significant metabolic differences were observed between RAIR and NonRAIR, and ketone body metabolism might play an important role in RAIR-DTC. AcAc improved cellular iodine uptake and had antitumor effects for thyroid carcinoma. KD might be a new therapeutic strategy for RAIR-DTC.
Individual foraging site fidelity persists within and across stopover seasons in a migratory shorebird, Numenius phaeopus (Whimbrel)
Authors: Handmaker Maina C , Sanders Felicia J , Smith Adam D , Shealy Ethan P , Fontaine Natasza , Kaplin Madelyn B , Thibault Janet M , Martin Mary Catherine , Duquet Camille , Sterling Abby V , Senner Nathan R
Published: May 2024

Site fidelity—returning repeatedly to the same site—can help many migratory species reduce uncertainty in their environment, especially when migratory stopover periods leave little time to explore and evaluate new habitat. Avian taxa, though, have shown wide variation in their levels of site fidelity during migration, and few studies have been able to examine individual-level fidelity at fine spatiotemporal scales. We used a high-resolution GPS tracking dataset of Numenius phaeopus (Whimbrel), a long-distance migratory shorebird, to assess levels of fidelity to specific foraging and roosting sites during migration, both within and between stopover seasons. We found that individuals are almost exclusively faithful to one shared roost site at night, but disperse to individual foraging territories during the day that overlap with each other by <20%. Individuals remain faithful to these distinct territories over time, on average shifting the center of their daily home ranges by <1.5 km within a single season, and overlapping with their previous season’s home range by 70% when they return during subsequent stopovers. Our findings reveal for the first time that a shorebird species exhibits fine-scale, individual foraging site fidelity during and between migratory stopovers—an important insight to inform effective conservation and management action.
Low nitrate under waterlogging triggers exodermal suberization to form a barrier to radial oxygen loss in rice roots
Authors: Shiono Katsuhiro , Ejiri Masato , Sawazaki Yuto , Egishi Yuka , Tsunoda Tomonori
Published: May 2024

To acclimate to hypoxic waterlogged conditions, the roots of wetland plants form a radial oxygen loss (ROL) barrier that can promote oxygen diffusion to the root tips. We hypothesized that the low-nitrate concentrations that occur after molecular oxygen is consumed in waterlogged soils are an environmental trigger for ROL barrier formation in rice (Oryza sativa). We previously identified 128 tissue-specific up/downregulated genes during rice ROL barrier formation. The RiceXPro database showed that many of these genes were differentially regulated in response to nitrogen deficiency. Therefore, we assessed changes in the concentrations of ionic species of nitrogen under stagnant conditions, i.e. in a nutrient solution that mimics waterlogged soil conditions, and examined the effects of an increase or decrease of nitrate in the nutrient solution on ROL barrier formation and exodermal suberization. Preventing nitrate deficiency in the stagnant nutrient solution suppressed the formation of an ROL barrier. Conversely, a decrease in nitrate strongly induced ROL barrier formation, even under aerated conditions. In parallel with ROL barrier formation, suberin lamellae formed at the exodermis. Nitrate deficiency also promoted aerenchyma formation and the enlargement of root diameters. These findings suggest that the severe decline of nitrates under waterlogged conditions is an environmental cue for exodermal suberization to form an ROL barrier in rice roots.
Tissue-specific deposition, speciation and transport of antimony in rice
Authors: Huang Hengliang , Yamaji Naoki , Ma Jian Feng
Published: May 2024

Rice (Oryza sativa) as a staple food is a potential intake source of antimony (Sb), a toxic metalloid. However, how rice accumulates this element is still poorly understood. Here, we investigated tissue-specific deposition, speciation, and transport of Sb in rice. We found that Sb(III) is the preferential form of Sb uptake in rice, but most Sb accumulates in the roots, resulting in a very low root-to-shoot translocation (less than 2%). Analysis of Sb deposition with laser ablation-inductively coupled plasma-mass spectrometry showed that most Sb deposits at the root exodermis. Furthermore, we found that Sb is mainly present as Sb(III) in the root cell sap after uptake. Further characterization showed that Sb(III) uptake is mediated by Low silicon rice 1 (Lsi1), a Si permeable transporter. Lsi1 showed transport activity for Sb(III) rather than Sb(V) in yeast (Saccharomyces cerevisiae). Knockout of Lsi1 resulted in a significant decrease in Sb accumulation in both roots and shoots. Sb concentration in the root cell sap of two independent lsi1 mutants decreased to less than 3% of that in wild-type rice, indicating that Lsi1 is a major transporter for Sb(III) uptake. Knockout of Lsi1 also enhanced rice tolerance to Sb toxicity. However, knockout of Si efflux transporter genes, including Lsi2 and Lsi3, did not affect Sb accumulation. Taken together, our results showed that Sb(III) is taken up by Lsi1 localized at the root exodermis and is deposited at this cell layer due to lack of Sb efflux transporters in rice.
Research impact assessment: Developing and applying a viable model for the social sciences
Authors: Wood Thomaz , Wilner Adriana
Published: May 2024

Prompted by research funding agencies and regulatory bodies, universities need to demonstrate and manage the impact of their research. Therefore, models for evaluating research impacts that can be applied quickly and at a reasonable cost are needed. However, the development of these models presents considerable challenges: research impact is multidimensional and can occur over time because of multiple interactions between different agents. Furthermore, impact assessment can demand substantial time and resources. Considering this challenging context, this study proposes a research impact assessment model capable of optimizing benefits and costs. The model was based on a multidimensional impact perspective and an application-oriented way of generating and transmitting knowledge. It was applied to a large teaching and research institution with a predominant role in the social sciences. The assessment involved a survey of the leaders of 133 research projects. The main findings of the application of the assessment model were as follows: first, knowledge production is transitioning from a traditional mode (aimed to impact science) to a new mode (aimed to impact multiple stakeholders); second, project leaders still perceive the prevalence of scientific impact over other types of impact; and third, the survey revealed how certain characteristics of the knowledge production mode relate to (perceived) impact. The viable research impact assessment model was demonstrated to be useful and cost-effective; thus, with adaptations and improvements, it may be used by other institutions, particularly those with internal research funding programs. This article also presents the model’s limitations, suggesting directions for future research.
The influence of the cardiac cycle on the halo sign and its impact on the ultrasound diagnosis of giant cell arteritis
Authors: Fernández-Fernández Elisa , Brugarolas Emma , Monjo-Henry Irene , Novella-Navarro Marta , Balsa Alejandro , De Miguel Eugenio
Published: May 2024

Objectives

To investigate whether hypoechoic wall thickness is influenced by the systole or diastole moment in the cardiac cycle and if this can influence US assessments of GCA.

Methods

US videos of 100 consecutive patients (50 with GCA, 50 without) performed between January 2021 and June 2023 were reviewed. Intima-media thickness (IMT) of temporal (including common trunk, frontal and parietal branches), axillary and subclavian arteries were measured at two different time points, at systolic peak (SP) and at the end-diastole (ED). Differences between SP IMT and ED IMT, as well as in the halo count (HC) and in the OMERACT GCA Ultrasonography Score (OGUS) between these two times, were analysed.

Results

IMT was significantly higher (4.8–5%) at ED in all arteries, in both GCA and non-GCA groups. HC and OGUS were also higher in ED in both groups. In four non-GCA patients (8%), the HC was positive in ED and negative in SP; in all of them the HC in ED was 1. In the GCA group, the timing of the cardiac cycle did not influence the final US diagnosis; however, it did modify the HC in 14 patients (28%).

Conclusion

IMT can fluctuate during the cardiac cycle, with higher measurements occurring at ED. This variability could potentially impact the accuracy of US diagnoses and assessments of GCA. If further research corroborates these findings, it may be imperative to revise the guidelines for employing US in diagnosing GCA in order to incorporate these nuanced aspects.
Analysis of the molecular structure of hydroxychavicol, a promising oral antibacterial
Authors: Vandyarto Rannod R , Domingues Aaron P , Cornwall Richard G
Published: May 2024

Objectives

In order to better understand hydroxychavicol’s effectiveness as an oral antibacterial, its structural components were analyzed with respect to minimum inhibitory concentrations and minimum bactericidal concentrations against various oral bacteria. These structural components include the free hydroxy groups and allyl chain connected to hydroxychavicol’s benzene core.

Methods

Six structural analogs of hydroxychavicol were tested against a range of oral bacteria using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. MIC results were obtained using serial microdilution techniques in 96-well plates with resazurin dye as a colorimetric indicator. Aliquots within each MIC concentration range were then placed on appropriate agar medium, and the minimum bactericidal concentration was determined as the lowest concentration with no observed colony growth.

Key findings

A synergistic interaction was observed between the allyl chain and hydroxy groups on the benzene core of hydroxychavicol, which resulted in lower MICs against the tested oral bacteria. It was also found that a hydroxy group para to the allyl chain on the benzene ring resulted in more effective inhibition, with a MIC of <50 μg/ml against R. dentocariosa. Additionally, analytes possessing free hydroxy groups ortho to one another on the benzene ring resulted in MICs of 200–300 μg/ml or lower, whereas analytes with free hydroxy groups meta to one another on the benzene ring exhibited MICs of >1000 μg/ml.

Conclusions

This study helps elucidate the structural components responsible for hydroxychavicol’s effectiveness as an oral antibacterial. The findings herein help to understand the mechanism of hydroxychavicol’s antibacterial properties and will be helpful in the design and synthesis of more effective oral antibacterial treatments.
The HH-GLI2-CKS1B network regulates the proliferation-to-maturation transition of cardiomyocytes
Authors: Waldron Christina J , Kelly Lauren A , Stan Nicholas , Kawakami Yasuhiko , Abrahante Juan E , Magli Alessandro , Ogle Brenda M , Singh Bhairab N
Published: May 2024

Cardiomyocyte (CM) proliferation and maturation are highly linked processes, however, the extent to which these processes are controlled by a single signaling axis is unclear. Here, we show the previously undescribed role of Hedgehog (HH)-GLI2-CKS1B cascade in regulation of the toggle between CM proliferation and maturation. Here we show downregulation of GLI-signaling in adult human CM, adult murine CM, and in late-stage hiPSC-CM leading to their maturation. In early-stage hiPSC-CM, inhibition of HH- or GLI-proteins enhanced CM maturation with increased maturation indices, increased calcium handling, and transcriptome. Mechanistically, we identified CKS1B, as a new effector of GLI2 in CMs. GLI2 binds the CKS1B promoter to regulate its expression. CKS1B overexpression in late-stage hiPSC-CMs led to increased proliferation with loss of maturation in CMs. Next, analysis of datasets of patients with heart disease showed a significant enrichment of GLI2-signaling in patients with ischemic heart failure (HF) or dilated-cardiomyopathy (DCM) disease, indicating operational GLI2-signaling in the stressed heart. Thus, the Hh-GLI2-CKS1B axis regulates the proliferation-maturation transition and provides targets to enhance cardiac tissue engineering and regenerative therapies.
Israel: Recognition of foundations and foreign trusts in Israel
Authors: Kaplan Alon , Eyal Lyat
Published: May 2024

Recognition of foreign trusts and foundations has been an issue in Israel for many years. Having immigrants from many countries speaking foreign languages and having a legacy of foreign laws and cultures has contributed to the extensive use of foreign trusts in Israel. The Trust Law, and later the Tax Ordinance, as revised in connection with trusts, have endorsed the use of foreign trusts and foundations by non-Israelis investing and doing business in Israel and by Israeli families investing overseas with a requirement for tax and estate planning. In this article, the authors explore the recognition and use of foreign trusts in Israel and give an overview of the respective taxation of trusts.
Social marketing and the challenges of participant recruitment
Authors: Baranowski Tom , O’Connor Teresia M , Jimenez-Garcia John A , Radhakrishnan Kavita , Arredondo Elva M , Thompson Debbe
Published: May 2024

Recruitment of research participants often has not obtained a desired sample size, thereby becoming a major problem inhibiting investigators’ ability to adequately test the specified hypotheses. Social marketing with its four Ps, originally developed by the business world to sell products and adapted for public health initiatives, is proposed as a dynamic comprehensive conceptual framework to apply marketing principles and practices to enhance participant recruitment. Applying a social marketing approach to research recruitment would require initial investigation to understand the motivations of the target audience in regard to research participation, and continued research throughout the main project to adapt the recruitment efforts as limitations arise. Additional funding would be needed for successful social marketing research recruitment programs to be systematically implemented and evaluated as part of research projects. In this paper, we define social marketing concepts, briefly review the available literature supporting social marketing applied to recruitment for research studies, and consider ethical issues that may arise when using a social marketing approach.
VThe Early Sixteenth Century
Authors: Smith Edward
Published: May 2024

This chapter has six sections: 1. General: Prose; 2. General: Verse; 3. More; 4. Skelton; 5. Surrey; 6. Wyatt