bluuebunny/crossref_metadata_2025 huggingface dataset:
Capturing excited-state structural snapshots of evolutionary green-to-red photochromic fluorescent proteins
Authors: Krueger Taylor D. , Henderson J. Nathan , Breen Isabella L. , Zhu Liangdong , Wachter Rebekka M. , Mills Jeremy H. , Fang Chong
Published: December 2023

Photochromic fluorescent proteins (FPs) have proved to be indispensable luminous probes for sophisticated and advanced bioimaging techniques. Among them, an interplay between photoswitching and photoconversion has only been observed in a limited subset of Kaede-like FPs that show potential for discovering the key mechanistic steps during green-to-red photoconversion. Various spectroscopic techniques including femtosecond stimulated Raman spectroscopy (FSRS), X-ray crystallography, and femtosecond transient absorption were employed on a set of five related FPs with varying photoconversion and photoswitching efficiencies. A 3-methyl-histidine chromophore derivative, incorporated through amber suppression using orthogonal aminoacyl tRNA synthetase/tRNA pairs, displays more dynamic photoswitching but greatly reduced photoconversion versus the least-evolved ancestor (LEA). Excitation-dependent measurements of the green anionic chromophore reveal that the varying photoswitching efficiencies arise from both the initial transient dynamics of the bright cis state and the final trans-like photoswitched off state, with an exocyclic bridge H-rocking motion playing an active role during the excited-state energy dissipation. This investigation establishes a close-knit feedback loop between spectroscopic characterization and protein engineering, which may be especially beneficial to develop more versatile FPs with targeted mutations and enhanced functionalities, such as photoconvertible FPs that also feature photoswitching properties.
Development of primer-probe sets to rapidly distinguish single nucleotide polymorphisms in SARS-CoV-2 lineages
Authors: Ealand Christopher S. , Gordhan Bhavna G. , Machowski Edith E. , Kana Bavesh D.
Published: December 2023

Ongoing SARS-CoV-2 infections are driven by the emergence of various variants, with differential propensities to escape immune containment. Single nucleotide polymorphisms (SNPs) in the RNA genome result in altered protein structures and when these changes occur in the S-gene, encoding the spike protein, the ability of the virus to penetrate host cells to initiate an infection can be significantly altered. As a result, vaccine efficacy and prior immunity may be diminished, potentially leading to new waves of infection. Early detection of SARS-CoV-2 variants using a rapid and scalable approach will be paramount for continued monitoring of new infections. In this study, we developed minor groove-binding (MGB) probe-based qPCR assays targeted to specific SNPs in the S-gene, which are present in variants of concern (VOC), namely the E484K, N501Y, G446S and D405N mutations. A total of 95 archived SARS-CoV-2 positive clinical specimens collected in Johannesburg, South Africa between February 2021 and March 2022 were assessed using these qPCR assays. To independently confirm SNP detection, Sanger sequencing of the relevant region in the S-gene were performed. Where a PCR product could be generated and sequenced, qPCR assays were 100% concordant highlighting the robustness of the approach. These assays, and the approach described, offer the opportunity for easy detection and scaling of targeted detection of variant-defining SNPs in the clinical setting.
Obstacles shape the way we walk at home
Authors: Sannier Mélodie , Janaqi Stefan , Dray Gérard , Slangen Pierre , Bardy Benoît G.
Published: December 2023

Introduction

Walking indoors, particularly at home, presents a distinct experience compared to the conventional pedestrian walking classically described. Our homes encompass intricate, confined, and cluttered architectural spaces that necessitate a predominantly curvilinear walking pattern. Despite the growing interest in studying our home, spurred by successive COVID-19 lockdowns, there remains a dearth of information regarding our walking behaviors inside homes, yet rich in data on the physical and sensory links between humans and their daily interior environment.

Methods

This study presents the outcomes of a controlled experiment conducted in an apartment in Montpellier, France. Participants were tasked with traversing the living room at a natural pace, encountering two natural obstacles-a large dining table and a small coffee table. They then walked back in opposite direction, circumnavigating the same two obstacles. To examine walking behavior within a pseudo-natural context, three conditions were tested: a controlled condition and two conditions that perturbed the natural curvilinear trajectory perceptually, by imposing an unpleasant sound, or physically, by suddenly displacing the coffee table between conditions. Twenty participants performed 30 trials in each condition. We approximated the position of their center of mass and computed various metrics related to their trajectories, including walking speed, obstacle clearance distance, its adaptation over time, and inter-trial trajectory variability.

Results

Findings revealed a greater visual clearance distance for the dining table compared to the coffee table, a difference reduced by the perturbation caused by displacing the coffee table. This clearing distance diminished with repetitions, showing that over time we tend to walk closer to obstacles around us. These adaptations were clearly the result of an active visuo-motor regulation, as evidenced by the reduced trajectory variability at, or just before, the location of the obstacles.

Discussion

Collectively, these results demonstrate that walking at home is a flexible behavior necessitating continuous perceptual adaptations in our daily trajectories. These findings could contribute to a detailed analysis of walking indoors under natural conditions, and the investigated metrics could serve as a baseline for comparing the embodiment of physical and mental health in walking patterns, for instance during lockdowns. Furthermore, our findings have consequences for safer mediated human architecture interaction.
Hypertension among adolescents in sub-Saharan Africa: a systematic review
Authors: Nsanya Mussa K. , Abramson Rachel , Kisigo Godfrey A. , Hickner Andy , Nyanza Elias C. , Peck Robert N. , Kapiga Saidi H.
Published: December 2023

Introduction

Hypertension (HTN) among adolescents is common in high-income countries, and leads to increased premature cardiovascular diseases (CVD). In sub-Saharan Africa (SSA), the prevalence of HTN among adolescents, associated risk factors and CVD complications are not well-described. Such data is needed for planning public health programs to prevent premature CVD in SSA.

Methods

We systematically searched 5 databases (MEDLINE, Embase, Google Scholar, Web of Science, and African Index Medicus) from their establishment to December 2021. Key search terms were: adolescent, arterial hypertension, and names of the 48 countries in SSA. We used Covidence® to manage the search results. The review was registered in the Open Science Framework (OSF) https://osf.io/p5sbt/.

Results

We identified 4,008 articles out of which we screened 3,088 abstracts, and reviewed 583 full-text articles. We finally included 92 articles that were published between 1968 to December 2021. The majority were cross-sectional studies (80%) and conducted in school settings (78%). The risk of bias was low for 59 studies (64.1%), moderate for 29 studies (31.5%), and high for 4 studies (4.3%). Overall, the prevalence of HTN varied widely from 0.18% to 34.0% with a median (IQR) of 5.5% (3.1%, 11.1%). It was relatively higher in studies using automated blood pressure (BP) devices, and in studies defining HTN using thresholds based on percentile BP distribution for one's height, age, and sex. In addition, the prevalence of HTN was significantly higher in studies from Southern Africa region of SSA and positively correlated with the year of publication. Across studies, traditional risk factors such as age, sex, body mass index, and physical inactivity, were commonly found to be associated with HTN. In contrast, non-traditional risk factors related to poverty and tropical diseases were rarely assessed. Only three studies investigated the CVD complications related to HTN in the study population.

Conclusion

The prevalence of HTN among adolescents in SSA is high indicating that this is a major health problem. Data on non-traditional risk factors and complications are scarce. Longitudinal studies are needed to clearly define the rates, causes, and complications of HTN.

Systematic Review Registration

https://osf.io/p5sbt/, identifier (10.17605/OSF.IO/P5SBT).
The effects of physiological and injurious hydrostatic pressure on murine ex vivo articular and growth plate cartilage explants: an RNAseq study
Authors: Bourne Lucie E. , Hesketh Andrew , Sharma Aikta , Bucca Giselda , Bush Peter G. , Staines Katherine A.
Published: December 2023

Introduction

Chondrocytes are continuously exposed to loads placed upon them. Physiological loads are pivotal to the maintenance of articular cartilage health, while abnormal loads contribute to pathological joint degradation. Similarly, the growth plate cartilage is subject to various loads during growth and development. Due to the high-water content of cartilage, hydrostatic pressure is considered one of the main biomechanical influencers on chondrocytes and has been shown to play an important role in the mechano-regulation of cartilage.

Methods

Herein, we conducted RNAseq analysis of ex vivo hip cap (articular), and metatarsal (growth plate) cartilage cultures subjected to physiological (5 MPa) and injurious (50 MPa) hydrostatic pressure, using the Illumina platform (n = 4 replicates).

Results

Several hundreds of genes were shown to be differentially modulated by hydrostatic pressure, with the majority of these changes evidenced in hip cap cartilage cultures (375 significantly upregulated and 322 downregulated in 5 MPa versus control; 1022 upregulated and 724 downregulated in 50 MPa versus control). Conversely, fewer genes were differentially affected by hydrostatic pressure in the metatarsal cultures (5 significantly upregulated and 23 downregulated in 5 MPa versus control; 7 significantly upregulated and 19 downregulated in 50 MPa versus control). Using Gene Ontology annotations for Biological Processes, in the hip cap data we identified a number of pathways that were modulated by both physiological and injurious hydrostatic pressure. Pathways upregulated in response to 50 MPa versus control, included those involved in the generation of precursor metabolites and cellular respiration. Biological processes that were downregulated in this tissue included ossification, connective tissue development, and chondrocyte differentiation.

Discussion

Collectively our data highlights the divergent chondrocyte phenotypes in articular and growth plate cartilage. Further, we show that the magnitude of hydrostatic pressure application has distinct effects on gene expression and biological processes in hip cap cartilage explants. Finally, we identified differential expression of a number of genes that have previously been identified as osteoarthritis risk genes, including Ctsk, and Chadl. Together these data may provide potential genetic targets for future investigations in osteoarthritis research and novel therapeutics.
Association between the triglyceride glucose index and diabetic retinopathy in type 2 diabetes: a meta-analysis
Authors: Zhou Jianlong , Zhu Lv , Li Yadi
Published: December 2023

The triglyceride-glucose (TyG) index is an accessible and reliable surrogate indicator of insulin resistance and is strongly associated with diabetes. However, its relationship with diabetic retinopathy (DR) remains controversial. This meta-analysis aimed to assess the relationship between the TyG index and the prevalence of DR. Initial studies were searched from PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) electronic databases. The retrieval time range was from the establishment of the database to June 2023. Pooled estimates were derived using a random-effects model and reported as odds ratio (OR) with 95% confidence intervals (CIs). Two researchers independently assessed the methodological quality of the included studies. The Newcastle-Ottawa Quality Scale (NOS) was utilized to assess cohort studies or case-control studies. The Agency for Healthcare Research and Quality (AHRQ) methodology checklist was applied to assess cross-sectional studies. Ten observational studies encompassing 13716 patients with type 2 diabetes were included in the meta-analysis. The results showed that a higher TyG index increased the risk of DR compared with a low TyG index (OR: 2.34, 95% CI: 1.31-4.19, P < 0.05). When the index was analyzed as a continuous variable, consistent results were observed (OR: 1.48, 95% CI: 1.12-1.97, P < 0.005). There was no significant effect on the results of the sensitivity analyses excluding one study at a time (P all < 0.05). A higher TyG index may be associated with an increased prevalence of DR in patients with type 2 diabetes. However, high-quality cohort or case-control studies are needed to further substantiate this evidence.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432747.
The science of rural human settlements: a comprehensive overview
Authors: Liu Junyou , Zheng Bohong , Tang Haifang
Published: December 2023

In the process of rapid urbanization in the world, many villages are facing a series of problems such as depopulation, population ageing, insufficient infrastructure, and public service facilities. In order for better rural development and full implementation of the 2030 sustainable development goals, we should hammer at improving the rural human settlements. Based on the science of human settlements proposed by Constantinos Doxiadis, bibliometric analysis was made on studies related to rural human settlements in the last 25 years. Through analysis, we believe that the number of related studies will gradually increase. Currently, the improvement of the rural ecological environment and the creation of a healthy rural human settlement environment are two hot topics. It is very likely that these topics will also be highly focused in the following decades. With the gradual development of rural areas and the improvement of the material lives of people, more and more scholars will pay attention to higher-level demands such as rural cultural environment and self-realization of villagers. By reviewing literature related to rural human settlements, we can comprehensively consider different aspects in rural human settlements. This is quite beneficial for the comprehensive development of rural human settlements. Scholars in different countries have similar focuses related to rural human settlements. However, because of different country conditions, the focuses of researchers have some obvious differences. Relevant literature contributes to the development of the science of human settlements.
Monastic silviculture legacies and current old-growthness of silver fir (Abies alba) forests in the northern Apennines (Italy)
Authors: Motta Renzo , Garbarino Matteo , Berretti Roberta , Bono Alessia , Curovic Milic , Dukić Vojislav , Nola Paola
Published: December 2023

Species-rich mixed silver fir (Abies alba Mill.) forests dominated in the northern Apennines, but climate and, mainly, anthropogenic land use provoked a sharp silver fir decline approximately 5000 years bp. The conservation of the silver fir in this region was mainly due to the establishment of monastic orders that preserved and even planted silver fir for its spiritual and economic value. In 1993, the best silver fir stands were included in the Parco Nazionale delle Foreste Casentinesi (FCNP), Monte Falterona e Campigna, and have been submitted to low-intensive management or strict protection regardless of past land use and cultural history. In this study, we have (1) analyzed the current structure of three silver fir forests that have had different ownership histories and (2) compared the structure of the three Italian forests among them and with two old-growth forests from the Dinaric Alps as a reference of naturalness. The results show that the current structures of the three Italian forests are very different among them and are strictly related to past land use and, mainly, to monastic legacies. Even if the Italian forests have experienced decades of low-intensity management or strict protection, they are currently structurally very different from Dinaric old-growth forests. Developing an old-growth structure in these forests can be very slow and, in some ways, unpredictable. The results also highlight the importance of recognizing protected areas as cultural landscapes that host an important biocultural diversity. The current risk is that by applying almost exclusive biodiversity-centered management and setting difficult or impossible-to-achieve biodiversity goals, total diversity will decrease, and biocultural diversity, the greatest richness of most European parks, will be lost.
Age-related changes in human bone marrow mesenchymal stromal cells: morphology, gene expression profile, immunomodulatory activity and miRNA expression
Authors: Massaro Fulvio , Corrillon Florent , Stamatopoulos Basile , Dubois Nathan , Ruer Achille , Meuleman Nathalie , Bron Dominique , Lagneaux Laurence
Published: December 2023

Introduction

Mesenchymal stromal cells (MSC) are one of the main cellular components of bone marrow (BM) microenvironment. MSC play a key role in tissue regeneration, but they are also capable of immunomodulating activity. With host aging, MSC undergo age-related changes, which alter these functions, contributing to the set-up of “inflammaging”, which is known to be the basis for the development of several diseases of the elderly, including cancer. However, there’s few data investigating this facet of MSC, mainly obtained using murine models or replicative senescence. The aim of this research was to identify morphological, molecular and functional alterations of human bone marrow-derived MSC from young (yBM-MSC) and old (oBM-MSC) healthy donors.

Methods

MSC were identified by analysis of cell-surface markers according to the ISCT criteria. To evaluate response to inflammatory status, MSC were incubated for 24h in the presence of IL-1β, IFN-α, IFN-ɣ and TNF-α. Macrophages were obtained by differentiation of THP-1 cells through PMA exposure. For M1 polarization experiments, a 24h incubation with LPS and IFN-ɣ was performed. MSC were plated at the bottom of the co-culture transwell system for all the time of cytokine exposure. Gene expression was evaluated by real-time PCR after RNA extraction from BM-MSC or THP-1 culture. Secreted cytokines levels were quantitated through ELISA assays.

Results

Aging MSC display changes in size, morphology and granularity. Higher levels of β-Gal, reactive oxygen species (ROS), IL-6 and IL-8 and impaired colony-forming and cell cycle progression abilities were found in oBM-MSC. Gene expression profile seems to vary according to subjects’ age and particularly in oBM-MSC seem to be characterized by an impaired immunomodulating activity, with a reduced inhibition of macrophage M1 status. The comparative analysis of microRNA (miRNA) expression in yBM-MSC and oBM-MSC revealed a significant difference for miRNA known to be involved in macrophage polarization and particularly miR-193b-3p expression is strongly increased after co-culture of macrophages with yBM-MSC.

Conclusion

There are profound differences in terms of morphology, gene and miRNA expression and immunomodulating properties among yBM-MSC and oBM-MSC, supporting the critical role of aging BM microenvironment on senescence, immune-mediated disorders and cancer pathogenesis.
Biomaterial-assisted local oxygenation safeguards the prostimulatory phenotype and functions of human dendritic cells in hypoxia
Authors: Bhatt Khushbu , Nukovic Alexandra , Colombani Thibault , Bencherif Sidi A.
Published: December 2023

Dendritic cells (DCs), professional antigen-presenting cells, function as sentinels of the immune system. DCs initiate and fine-tune adaptive immune responses by presenting antigenic peptides to B and T lymphocytes to mount an effective immune response against cancer and pathogens. However, hypoxia, a condition characterized by low oxygen (O2) tension in different tissues, significantly impacts DC functions, including antigen uptake, activation and maturation, migration, as well as T-cell priming and proliferation. In this study, we employed O2-releasing biomaterials (O2-cryogels) to study the effect of localized O2 supply on human DC phenotype and functions. Our results indicate that O2-cryogels effectively mitigate DC exposure to hypoxia under hypoxic conditions. Additionally, O2-cryogels counteract hypoxia-induced inhibition of antigen uptake and migratory activity in DCs through O2 release and hyaluronic acid (HA) mediated mechanisms. Furthermore, O2-cryogels preserve and restore DC maturation and co-stimulation markers, including HLA-DR, CD86, and CD40, along with the secretion of proinflammatory cytokines in hypoxic conditions. Finally, our findings demonstrate that the supplemental O2 released from the cryogels preserves DC-mediated T-cell priming, ultimately leading to the activation and proliferation of allogeneic CD3+ T cells. This work emphasizes the potential of local oxygenation as a powerful immunomodulatory agent to improve DC activation and functions in hypoxia, offering new approaches for cancer and infectious disease treatments.
Comparative analysis of contemporary anti-double stranded DNA antibody assays for systemic lupus erythematosus
Authors: Bauer Claus-Juergen , Karakostas Pantelis , Weber Nadine , Behning Charlotte , Stoffel-Wagner Birgit , Brossart Peter , Dolscheid-Pommerich Ramona , Schäfer Valentin Sebastian
Published: December 2023

Objective

Elevated double-stranded DNA (dsDNA) antibody levels in blood serum are considered a disease-specific marker in systemic lupus erythematosus (SLE), correlate with disease activity and the incidence of lupus nephritis, and can be detected in up to 86% of all SLE cases. Despite the high clinical relevance, the variety of dsDNA antibody testing methods with heterogenous performance in clinical use remains challenging. This study is the first to prospectively investigate the performance of two of today’s most commonly applied anti-dsDNA testing methods head-to-head under real-world conditions, as well as their correlation with other clinical and serological disease parameters in SLE patients.

Methods

In this prospective study, all SLE patients undergoing treatment at the Department of Rheumatology at the University Hospital Bonn within a 13-months period (n=41) and control patients without connective-tissue disease (n=51) were consecutively enrolled and examined. For all study participants’ serum samples both anti-dsDNA-NcX enzyme-linked immunoassay testing EUROIMMUN, Luebeck, Germany) and the fluorescence immunoassay ELiA dsDNA (Thermo Fisher Scientific, Waltham, USA) were performed. In addition, demographic data, further laboratory values and disease activity parameters were recorded. Clinical disease activity was assessed by SLEDAI-2K.

Results

Both assays showed high specificity (anti-dsDNA-NcX ELISA: 0.9, ELiA dsDNA: 0.959), but there were notable differences in sensitivity (anti-dsDNA-NcX ELISA: 0.51, ELiA dsDNA: 0.38). Pearsons’s correlation yielded a positive correlation between anti-dsDNA concentrations and CRP concentrations for the anti-dsDNA-NcX ELISA (R=0.22; p=0.038) and a mild-to-moderate inverse correlation between concentrations of anti-dsDNA and complement C4 for the ELiA dsDNA test (R=-0.22; p=0.045) when SLE and control patients were considered together. Other than, no significant correlation between anti-dsDNA concentrations and clinical or laboratory findings was found for either test procedure.

Conclusion

Both anti-dsDNA antibody assays represent reliable examination methods with high specificity for the diagnosis of SLE that fulfill EULAR/ACR requirements. However, the anti-dsDNA-NcX ELISA showed superior sensitivity and significant correlation with disease activity (as measured by CRP concentrations).
Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury
Authors: Liu Yi , Wang Rong , Song Congkuan , Ding Song , Zuo Yifan , Yi Ke , Li Ning , Wang Bo , Geng Qing
Published: December 2023

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated death, occurring during or within 6 hours after transfusion. Reports indicate that TRALI can be categorized as having or lacking acute respiratory distress syndrome (ARDS) risk factors. There are two types of TRALI in terms of its pathogenesis: antibody-mediated and non-antibody-mediated. The key initiation steps involve the priming and activation of neutrophils, with neutrophil extracellular traps (NETs) being established as effector molecules formed by activated neutrophils in response to various stimuli. These NETs contribute to the production and release of reactive oxygen species (ROS) and participate in the destruction of pulmonary vascular endothelial cells. The significant role of NETs in TRALI is well recognized, offering a potential pathway for TRALI treatment. Moreover, platelets, macrophages, endothelial cells, and complements have been identified as promoters of NET formation. Concurrently, studies have demonstrated that the storage of platelets and concentrated red blood cells (RBC) can induce TRALI through bioactive lipids. In this article, recent clinical and pre-clinical studies on the pathophysiology and pathogenesis of TRALI are reviewed to further illuminate the mechanism through which NETs induce TRALI. This review aims to propose new therapeutic strategies for TRALI, with the hope of effectively improving its poor prognosis.
Spatial diversity and habitat characteristics of seagrass meadows with management recommendations in the Andaman and Nicobar Islands, India
Authors: Gole Swapnali , Prajapati Sumit , Prabakaran Nehru , Das Himansu , Kuppusamy Sivakumar , Johnson Jeyaraj Antony
Published: December 2023

The Andaman and Nicobar Islands, India, a geographically remote region, harbor a diverse island ecosystem. Limited exploration has hindered our understanding of marine floral biodiversity in this area. To address this gap, we investigated seagrass meadows in the Andaman and Nicobar Islands to understand their spatial distribution, species composition, and habitat characteristics. We assessed 66 seagrass meadows, including 32 newly discovered ones, filling data gaps in the region’s seagrass coldspots. Seagrasses were found across a wide range of depths, with the majority occurring in shallow subtidal waters (< 8 m). Large-sized species such as Thalassia hemprichii, Enhalus acoroides, Cymodocea rotundata, Cymodocea serrulata, and Syringodium isoetifolium dominated the littoral and shallow subtidal zones, while smaller species such as Halophila spp. and Halodule spp. exhibited broader depth distributions. H. beccarii and H. decipiens were strictly intertidal and subtidal species, respectively. Water depth significantly influenced seagrass occurrence (p < 0.0001), cover (β = -0.2759; SE = 0.02471; p < 0.0001), shoot densities (β = -0.3556; SE = 0.1231; p = 0.005), and biomass (β = -0.3526; SE = 0.1159; p = 0.003). Sand availability emerged as the second significant predictor of seagrass distribution, cover, and biomass (p values < 2e-16, < 2e-16, and 0.01, respectively). Habitat heterogeneity decreased with increasing water depth, and seagrass species exhibited strong preferences for specific substrata, resulting in spatial niche partitioning. Our study provides novel insights into the seagrass spatial diversity, habitat characteristics, and seagrass-environment relationship in the Andaman and Nicobar Islands. Further, it highlights the importance of water depth, habitat characteristics, and substratum heterogeneity in seagrass distribution and growth. Lastly, our findings imply that any change to the benthic profile of the meadows will influence the seagrass species distribution and growth. Understanding these factors is crucial for seagrass conservation and management in the region, aiding the development of targeted strategies to protect these valuable marine habitats and associated biodiversity.
mtDNA data reveal disparate population structures and High Arctic colonization patterns in three intertidal invertebrates with contrasting life history traits
Authors: Csapó Hedvig , Jabłońska Aleksandra , Węsławski Jan Marcin , Mieszkowska Nova , Gantsevich Michael , Dahl-Hansen Ida , Renaud Paul , Grabowski Michał
Published: December 2023

Introduction

Post-glacial climate variation is known to have influenced the distribution of marine species in the North Atlantic. In particular, the Atlantic side of the Arctic has experienced strong fluctuations in both atmospheric and sea surface temperature, as well as seasonal ice coverage since the last glacial maximum (LGM). Here, we aim to unveil the phylogeography and historical demography of three rocky intertidal marine invertebrates showing a trans-Atlantic distribution and presently inhabiting the Arctic: Gammarus oceanicus, Littorina saxatilis and Semibalanus balanoides.

Methods

We used a large amount of mitochondrial DNA barcode data, both newly-obtained and stored in public databases. We performed phylogeographic and demographic analyses on 1119 G. oceanicus, 205 L. saxatilis, and 884 S. balanoides sequences.

Results

Our results show that all three of these boreal species have expanded their effective population sizes in the high Arctic Svalbard Archipelago since the LGM. Analyses investigating the origin of all these populations point to the eastern Atlantic.

Discussion

Based on our results we conclude that the expansion of these boreal species to the Arctic possibly happened during an earlier warm cycle of the Holocene era, and is probably not the result of the recent ‘Atlantification’ of the Arctic. We also discuss the effects of dispersal potential on population structure as an important aspect of comparative biogeographical studies.
A real-world study on the safety profile of extended-interval dosing of immune checkpoint inhibitors for melanoma: a single-center analysis in Japan
Authors: Ito Takamichi , Kaku-Ito Yumiko , Ohno Fumitaka , Nakahara Takeshi
Published: December 2023

Background

Anti-programmed death-1 (PD-1) antibodies are the mainstay for the treatment of unresectable or high-risk melanoma. However, real-world data on the safety profile of their extended-interval doses (EDs) are limited, particularly in Asian patients with melanoma.

Materials and methods

In this single-center retrospective study, we analyzed the risks of immune-related adverse events (irAEs) among 71 Japanese patients (36 males; mean age, 65.0 years) who received anti-PD-1 monotherapy for melanoma at our institute. Patients who were administered ipilimumab prior to anti-PD-1 monotherapy were excluded. Patients were divided into three groups: canonical-interval dose (CD) group (n = 50, body weight-based dosing or 240 mg Q2W for nivolumab and body weight-based dosing or 200 mg Q3W for pembrolizumab), ED group (n = 14, 480 mg Q4W for nivolumab and 400 mg Q6W for pembrolizumab), and dose-switch (DS) group (n = 7, upfront CD followed by ED).

Results

The CD group received nivolumab more frequently in the metastatic setting. There were no significant differences in baseline characteristics among the three groups, including in sex, age, primary tumor site, tumor subtype, and follow-up period. irAEs occurred in 36.6% (26 patients) of all patients (32.0% of the CD group, 35.7% of the ED group, and 71.4% of the DS group), while severe (grade ≥ 3) irAEs occurred in only two patients, both of whom were in the CD group. Most of the irAEs occurred during the first 6 months of anti-PD-1 therapy and, interestingly, all of the irAEs in the DS group occurred before the switch (during the CD). There was no significant difference among the three groups in the probability of irAE estimated by the Kaplan–Meier method.

Conclusion

These findings may highlight the safety of ED of anti-PD-1 monotherapy in the treatment of Asian patients with melanoma.
Multimodal imaging study of hepatic perivascular epithelioid cell tumors: a case report
Authors: Yang Wenbi , Sun Quanlin , Shang Maocai , Li Song , Hu Xiao , Hu Xianwen
Published: December 2023

Hepatic perivascular epithelioid cell tumors (PEComas) are rare interstitial tumors that are often misdiagnosed as hepatocellular carcinomas due to their unique vascular enhancement patterns. Herein, we present a case of a 61-year-old man who was incidentally found to have a lesion in the left medial segment of the liver during a chest computed tomography (CT) examination performed 4 days prior to his presentation for chest discomfort. Imaging revealed solid components with density similar to that of normal liver tissue and areas of low-density adipose tissue within the lesion. The solid components exhibited increased uptake of fluorine-18 fluorodeoxyglucose on positron emission tomography/CT. Magnetic resonance imaging demonstrated areas with unevenly high signal intensity in both T1-weighted imaging (T1WI) in-phase and T2-weighted imaging (T2WI) sequences, while T2WI in the opposite phase displayed areas with unevenly low signal intensity, indicating the presence of fatty components. Contrast-enhanced T1WI displayed a “fast in and fast out” enhancement pattern. These distinct imaging features contribute to the diagnosis of hepatic PEComas and distinguish it from hepatocellular carcinoma.
Improvement in gravel-mulched land soil nutrient and bacterial community diversity with Lonicera japonica
Authors: Wang Xing , Ma Bin , Liu Hua , Bao Yangmei , Li Ming , McLaughlin Neil B. , Guo Lanping
Published: December 2023

Gravel-mulched land in China suffers from poor natural resources and fragile ecological environment, posing a challenge to effective restoration of ecological function. Lonicera japonica, a traditional Chinese herb used for treating human diseases, is a highly adaptable and resilient plant species, can effectively improve the soil properties, and may have important implications for the ecology and economy of gravel-mulched land. A study was conducted in a gravel-mulched field to measure the impact of planting the L. japonica (including control (CK), 1-year, 2-year, and 4-year cultivation of plants) on (i) dynamic changes in soil nutrient and enzyme activity properties, and (ii) soil rhizosphere microbial community structure characteristics. We found that the concentration of soil organic carbon, available nitrogen, available phosphorus and available potassium in L. japonica soil after cultivation for 1–4 years increased by 11–409%. The urease, phosphatase and catalase activities were increased by 11–560%, with the highest nutrient concentration and enzyme activity in 4-year plants. The pH value gradually decreased after cultivation. The improved soil environments increased soil bacterial community diversity. Planting L. japonica significantly increased the bacterial ACE, Chao1 index, Simpson index, and Shannon-Wiener index. The Firmicutes, Proteobacteria and Bacteroidetes were observed in dominant phyla. The relative abundance of eight genera, including Streptococcus, Veillonella and Rothia, was significantly reduced by more than 1%. Taken together, these soil indicators suggest that planting L. japonica in the short term would be a cost-effective strategy to combat soil degradation in a gravel-mulched ecosystem.
Fluorescence-based primary productivity estimates are influenced by non-photochemical quenching dynamics in Arctic phytoplankton
Authors: Sezginer Yayla , Campbell Douglas , Pillai Sacchinandan , Tortell Philippe
Published: December 2023

Chlorophyll fluorescence-based estimates of primary productivity typically include dark or low-light pre-treatments to relax non-photochemical quenching (NPQ), a process that influences the relationship between PSII photochemistry and fluorescence yields. The time-scales of NPQ relaxation vary significantly between phytoplankton taxa and across environmental conditions, creating uncertainty in field-based productivity measurements derived from fluorescence. To address this practical challenge, we used fast repetition rate fluorometry to characterize NPQ relaxation kinetics in Arctic Ocean phytoplankton assemblages across a range of hydrographic regimes. Applying numerical fits to our data, we derived NPQ relaxation life times, and determined the relative contributions of various quenching components to the total NPQ signature across the different assemblages. Relaxation kinetics were best described as a combination of fast-, intermediate- and slow-relaxing processes, operating on time-scales of seconds, minutes, and hours, respectively. Across sampling locations and depths, total fluorescence quenching was dominated by the intermediate quenching component. Our results demonstrated an average NPQ relaxation life time of 20 ± 1.9 min, with faster relaxation among high light acclimated surface samples relative to lowlight acclimated sub-surface samples. We also used our results to examine the influence of NPQ relaxation on estimates of photosynthetic electron transport rates (ETR), testing the commonly held assumption that NPQ exerts proportional effects on light absorption (PSII functional absorption cross section, σPSII) and photochemical quantum efficiency (FV/FM). This assumption was violated in a number of phytoplankton assemblages that showed a significant decoupling of σPSII and FV/FM during NPQ relaxation, and an associated variability in ETR estimates. Decoupling of σPSII and FV/FM was most prevalent in samples displaying symptoms photoinhibition. Our results provide insights into the mechanisms and kinetics of NPQ in Arctic phytoplankton assemblages, with important implications for the use of FRRF to derive non-invasive, high-resolution estimates of photosynthetic activity in polar marine waters.
Adolescent social housing protects against adult emotional and cognitive deficits and alters the PFC and NAc transcriptome in male and female C57BL/6J mice
Authors: Lodha Jyoti , Brocato Emily R. , Nash McKenzie , Marcus Madison M. , Pais A. Chris , Pais Alex B. , Miles Michael F. , Wolstenholme Jennifer Theresa
Published: December 2023

Introduction

Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome.

Methods

Adolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis.

Results

As adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex.

Discussion

The behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens.
Exosomal microRNAs: implications in the pathogenesis and clinical applications of subarachnoid hemorrhage
Authors: Liao Lishang , Wang Haoran , Wei Deli , Yi Mingliang , Gu Yingjiang , Zhang Mingwei , Wang Li
Published: December 2023

Subarachnoid hemorrhage (SAH) is a severe acute neurological disorder with a high fatality rate. Early brain injury (EBI) and cerebral vasospasm are two critical complications of SAH that significantly contribute to poor prognosis. Currently, surgical intervention and interventional therapy are the main treatment options for SAH, but their effectiveness is limited. Exosomes, which are a type of extracellular vesicles, play a crucial role in intercellular communication and have been extensively studied in the past decade due to their potential influence on disease progression, diagnosis, and treatment. As one of the most important components of exosomes, miRNA plays both direct and indirect roles in affecting disease progression. Previous research has found that exosomal miRNA is involved in the development of various diseases, such as tumors, chronic hepatitis, atherosclerosis, diabetes, and SAH. This review focuses on exploring the impact of exosomal miRNA on SAH, including its influence on neuronal apoptosis, inflammatory response, and immune activation following SAH. Furthermore, this review highlights the potential clinical applications of exosomal miRNA in the treatment of SAH. Although current research on this topic is limited and the clinical application of exosomal miRNA has inherent limitations, we aim to provide a concise summary of existing research progress and offer new insights for future research directions and trends in this field.
Online monitoring the hydrolysis of uranium hexafluoride for intermediates by cryogenic layering and FTIR
Authors: McNamara Louis E. , Kelly John T. , Waldron Abigail M. , Villa-Aleman Eliel , Strange Fessler K. Alicia
Published: December 2023

Uranium hexafluoride (UF6) is a commonly utilized material feedstock in uranium enrichment processes due to its high vapor pressure and ease of sublimation. When exposed to air, UF6 undergoes spontaneous hydrolysis to form uranyl fluoride (UO2F2) particulates which are utilized for the detection of undeclared nuclear activities by nuclear safeguards organizations. The kinetics of the hydrolysis reaction and how they relate to particle morphology of the product are still debated in the literature. Here, we report the direct, in situ observation of UF6 reaction intermediates by cooling the reaction to cryogenic temperatures to significantly reduce the rate of hydrolysis. The reaction is then observable by Fourier transform infrared (FTIR) spectroscopy. The conversion of UF6 to UOF4 is observed as well as several other bands associated with possible long lived intermediate complexes. Chemometrics are used to further elucidate the reaction pathway from UF6 to UO2F2.
New tools and recommendations for a better management of harmful algal blooms under the European Marine Strategy Framework Directive
Authors: Sagarminaga Yolanda , Garcés Esther , Francé Janja , Stern Rowena , Revilla Marta , Magaletti Erika , Bresnan Eileen , Tsirtsis George , Jakobsen Hans Henrik , Sampedro Nagore , Reñé Albert , Camp Jordi , Borja Ángel , Rodríguez José Germán , Spada Emanuela , Pagou Kalliopi , De Angelis Roberta , Lanzén Anders , Ferrer Luis , Borrello Patrizia , Boicenco Laura , Kobos Justyna , Mazaris Antonios , Katsanevakis Stelios
Published: December 2023

Marine harmful algal blooms (HABs), caused by various aquatic microalgae, pose significant risks to ecosystems, some socio-economic activities and human health. Traditionally managed as a public health issue through reactive control measures such as beach closures, seafood trade bans or closure of mollusc production areas, the multifaceted linkages of HABs with environmental and socio-economic factors require more comprehensive ecosystem-based management approach tools to support policies. This study promotes a coordinated understanding and implementation of HAB assessment and management under the Marine Strategy Framework Directive (MSFD), targeting the achievement of Good Environmental Status (GES) in European marine waters. We introduce two novel tools: GES4HABs (GES for HABs) decision tree, and MAMBO (environMental mAtrix for the Management of BlOoms), a decision support matrix. These tools aim to streamline HABs reporting and prioritize resource allocation and management interventions. The GES4HABs decision tree defines a sequence of decision steps to identify HAB management strategies according to their state (evaluated against predefined baselines) and causes (anthropic or natural). MAMBO is proposed to address different HABs and their interaction with human and environmental pressures. The matrix utilizes two axes: natural trophic status and level of human influence, capturing major aspects such as nutrient supply. While acknowledging the limitations of this simplified framework, MAMBO categorizes marine regions into quadrants of varying management viability. Regions with high human influence and eutrophic conditions are identified as most suitable for effective management intervention, whereas regions with minimal or mixed human influence are deemed less amenable to active management. In addition, we explore and describe various indicators, monitoring methods and initiatives that may be relevant to support assessments of HAB status and associated pressures and impacts in the MSFD reporting. Finally, we provide some recommendations to promote the consideration of HABs in ecosystem-based management strategies, intensify efforts for harmonizing and defining best practices of analysis, monitoring and assessment methodologies, and foster international and cross-sectoral coordination to optimize resources, efforts and roles.
Hemangiosarcoma in dogs as a potential non-rodent animal model for drug discovery research of angiosarcoma in humans
Authors: Heishima Kazuki , Aketa Naohiko , Heishima Mizuki , Kawachi Asuka
Published: December 2023

Since the domestication of dogs 10,000 years ago, they have shared their living environment with humans and have co-evolved. The breeding process that dogs have undergone in only a few centuries has led to a significant accumulation of specific genetic alterations that could induce particular diseases in certain breeds. These canine diseases are similar to what is found in humans with several differences; therefore, comparing such diseases occurring in humans and dogs can help discover novel disease mechanisms, pathways, and causal genetic factors. Human angiosarcoma (AS) and canine hemangiosarcoma (HSA), which are sarcomas originating from endothelium, are examples of diseases shared between humans and dogs. They exhibit similar characteristics and clinical behaviors, although with some critical differences resulting from evolution. In this review, we will describe the similarities and differences in terms of clinical and molecular characteristics between human AS and canine HSA, and discuss how these similarities and differences can be applied to advance the treatment of these diseases.