bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological and clinical appraisal of factor XI inhibitor drugs
Authors: Occhipinti Giovanni , Laudani Claudio , Spagnolo Marco , Finocchiaro Simone , Mazzone Placido Maria , Faro Denise Cristiana , Mauro Maria Sara , Rochira Carla , Agnello Federica , Giacoppo Daniele , Ammirabile Nicola , Landolina Davide , Imbesi Antonino , Sangiorgio Giuseppe , Greco Antonio , Capodanno Davide
Published: January 2024

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.
Comparison of ductus stent versus surgical systemic-to-pulmonary shunt as initial palliation in patients with univentricular heart
Authors: Grozdanov Dimitrij , Osawa Takuya , Borgmann Kristina , Schaeffer Thibault , Staehler Helena , Di Padua Chiara , Heinisch Paul Philipp , Piber Nicole , Georgiev Stanimir , Hager Alfred , Ewert Peter , Hörer Jürgen , Ono Masamichi
Published: January 2024

OBJECTIVES

In this study, we aimed to compare infants with univentricular hearts who underwent an initial ductus stenting to those receiving a surgical systemic-to-pulmonary shunt (SPS).

METHODS

All infants with univentricular heart and ductal-dependent pulmonary blood flow who underwent initial palliation with either a ductus stenting or a surgical SPS between 2009 and 2022 were reviewed. Outcomes were compared after ductus stenting or SPS including survival, probability of re-interventions and the probability to reach stage II palliations.

RESULTS

A total of 130 patients were evaluated, including 49 ductus stenting and 81 SPSs. The most frequent primary diagnosis was tricuspid atresia in 27, followed by pulmonary atresia with intact ventricular septum in 19 patients. There was comparable hospital mortality (2.0% stent vs 3.7% surgery, P = 0.91) between the groups, but shorter intensive care unit stay (median 1 vs 7 days, P < 0.01) and shorter hospital stay (median 7 vs 17 days, P < 0.01) were observed in patients with initial ductus stenting, compared to those with SPS. However, acute procedure-related complications were more frequently observed in patients with ductus stenting, compared with those with SPS (20.4 vs 6.2%, P = 0.01), and 10 patients needed a shunt procedure after the initial ductus stent. The cumulative incidence of reaching stage II was similar between ductus stenting and SPS (88.0 vs 90.6% at 12 months, P = 0.735). Pulmonary artery (PA) index (median 194 vs 219 mm2/m2, P = 0.93) at stage II was similar between patients with ductus stenting and SPS. However, the ratio of the left to the right PA index [0.69 (0.45–0.95) vs 0.86 (0.51–0.84), P = 0.015] was higher in patients who reached stage II with surgical shunt physiology, compared with patients with ductus stent physiology.

CONCLUSIONS

After initial ductus stenting in infants with univentricular heart, survival is comparable and post-procedural recovery shorter, but more acute stent dysfunctions and lower development of left PA are observed, compared to acute shunt dysfunctions. The less invasive procedure and shorter hospital stay are at the expense of more stent reinterventions.
Up-regulated small-conductance calcium-activated potassium currents contribute to atrial arrhythmogenesis in high-fat feeding mice
Authors: Tsai Wei-Chung , Lin Yi-Hsiung , Kuo Chia-Hao , Jhuo Shih-Jie , Shih Ruo-Yun , Wu Chun-Chieh , Liu I Hsin , Huang Tien-Chi , Liu Ren-Ming , Lin Tsung-Hsien , Su Ho-Ming , Lai Wen-Ter , Lee Chien-Hung , Wu Bin-Nan , Lin Shien-Fong , Lee Hsiang-Chun
Published: January 2024

Aims

Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodelling. The small-conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS.

Methods and results

Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodelling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK current density. The SK current density is higher in atrial myocytes from HFD than in CTL mice (P ≤ 0.037). The RNA and protein expression of SK channels are increased in HFD mice (P ≤ 0.041 and P ≤ 0.011, respectively). Action potential duration is shortened in HFD compared with CTL (P ≤ 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (P ≤ 0.043). Compared with CTL, CaTD is greater in HFD atria (P ≤ 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (P = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (P ≤ 0.043), along with higher inducibility and longer duration of AF in HFD (P ≤ 0.023).

Conclusion

Up-regulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.
Parent perceptions of school meals and how perceptions differ by race and ethnicity
Authors: Zuercher Monica D , Cohen Juliana F W , Ohri-Vachaspati Punam , Hecht Christina A , Hecht Kenneth , Polacsek Michele , Olarte Deborah A , Read Margaret , Patel Anisha I , Schwartz Marlene B , Chapman Leah E , Orta-Aleman Dania , Ritchie Lorrene D , Gosliner Wendi
Published: January 2024

Parental perceptions of school meals can affect student participation and overall support for school meal policies. Little is known about parental school meal perceptions under universal free school meals (UFSM) policies. We assessed California parents' perceptions of school meals during the COVID-19 emergency response with federally funded UFSM and whether perceptions differed by race/ethnicity. Among 1110 California parents of K–12 students, most reported school meals benefit their families, saving them money (81.6%), time (79.2%), and stress (75.0%). Few reported that their child would be embarrassed to eat school meals (11.7%), but more parents of White students than Hispanic students reported this. Many parents reported that their child likes to eat lunch to be with friends (64.7%); about half felt their child has enough time to eat (54.2%). Fewer parents perceived school lunches to be of good quality (36.9%), tasty (39.6%), or healthy (44.0%). Parents of Hispanic and Asian students had less favorable perceptions of school meal quality, taste, and healthfulness than parents of White students. Parents report that school meals benefit their families, but policy efforts are needed to ensure schools have the resources needed to address cultural appropriateness. Schools should address parental perceptions of meals to optimize participation, nutrition security, and health.
Identification of a Spike-Specific CD8+ T-Cell Epitope Following Vaccination Against the Middle East Respiratory Syndrome Coronavirus in Humans
Authors: Harrer Caroline E , Mayer Leonie , Fathi Anahita , Lassen Susan , Ly My L , Zinser Madeleine E , Wolf Timo , Becker Stephan , Sutter Gerd , Dahlke Christine , Addo Marylyn M ,   for the MVA-MERS-S Study Group, Bartels Etienne , Friedrich Monika , Weskamm Leonie M , Grundlach Swantje , Poetsch Joseph H , Koch Till , Schmiedel Stefan , Haagmanns Bart , Hesterkamp Thomas , Krähling Verena , Volz Asisa , Ditt Vanessa A , Kessler Melanie
Published: January 2024

Licensed vaccines against the Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging pathogen of concern, are lacking. The modified vaccinia virus Ankara vector-based vaccine MVA-MERS-S, expressing the MERS-CoV-spike glycoprotein (MERS-S), is one of 3 candidate vaccines in clinical development and elicits robust humoral and cellular immunity. Here, we identified for the first time a MERS-S–specific CD8+ T-cell epitope in an HLA-A*03:01/HLA-B*35:01-positive vaccinee using a screening assay, intracellular cytokine staining, and in silico epitope prediction. As evidence from MERS-CoV infection suggests a protective role of long-lasting CD8+ T-cell responses, the identification of epitopes will facilitate longitudinal analyses of vaccine-induced T-cell immunity.
Host species and geography impact bee-associated RNA virus communities with evidence for isolation by distance in viral populations
Authors: Robinson Chris R P , Dolezal Adam G , Newton Irene L G
Published: January 2024

Virus symbionts are important mediators of ecosystem function, yet we know little of their diversity and ecology in natural populations. The alarming decline of pollinating insects in many regions of the globe, especially the European honey bee, Apis mellifera, has been driven in part by worldwide transmission of virus pathogens. Previous work has examined the transmission of known honey bee virus pathogens to wild bee populations, but only a handful of studies have investigated the native viromes associated with wild bees, limiting epidemiological predictors associated with viral pathogenesis. Further, variation among different bee species might have important consequences in the acquisition and maintenance of bee-associated virome diversity. We utilized comparative metatranscriptomics to develop a baseline description of the RNA viromes associated with wild bee pollinators and to document viral diversity, community composition, and structure. Our sampling includes five wild-caught, native bee species that vary in social behavior as well as managed honey bees. We describe 26 putatively new RNA virus species based on RNA-dependent RNA polymerase phylogeny and show that each sampled bee species was associated with a specific virus community composition, even among sympatric populations of distinct host species. From 17 samples of a single host species, we recovered a single virus species despite over 600 km of distance between host populations and found strong evidence for isolation by distance in associated viral populations. Our work adds to the small number of studies examining viral prevalence and community composition in wild bees.
Metagenome-assembled genomes of deep-sea sediments: changes in microbial functional potential lag behind redox transitions
Authors: Schauberger Clemens , Thamdrup Bo , Lemonnier Clarisse , Trouche Blandine , Poulain Julie , Wincker Patrick , Arnaud-Haond Sophie , Glud Ronnie N , Maignien Lois
Published: January 2024

Hadal sediments are hotspots of microbial activity in the deep sea and exhibit strong biogeochemical gradients. But although these gradients are widely assumed to exert selective forces on hadal microbial communities, the actual relationship between biogeochemistry, functional traits, and microbial community structure remains poorly understood. We tested whether the biogeochemical conditions in hadal sediments select for microbes based on their genomic capacity for respiration and carbohydrate utilization via a metagenomic analysis of over 153 samples from the Atacama Trench region (max. depth = 8085 m). The obtained 1357 non-redundant microbial genomes were affiliated with about one-third of all known microbial phyla, with more than half belonging to unknown genera. This indicated that the capability to withstand extreme hydrostatic pressure is a phylogenetically widespread trait and that hadal sediments are inhabited by diverse microbial lineages. Although community composition changed gradually over sediment depth, these changes were not driven by selection for respiratory or carbohydrate degradation capability in the oxic and nitrogenous zones, except in the case of anammox bacteria and nitrifying archaea. However, selection based on respiration and carbohydrate degradation capacity did structure the communities of the ferruginous zone, where aerobic and nitrogen respiring microbes declined exponentially (half-life = 125–419 years) and were replaced by subsurface communities. These results highlight a delayed response of microbial community composition to selective pressure imposed by redox zonation and indicated that gradual changes in microbial composition are shaped by the high-resilience and slow growth of microbes in the seafloor.
Development of a rapid and highly accurate method for 13C tracer-based metabolomics and its application on a hydrogenotrophic methanogen
Authors: Fukuyama Yuto , Shimamura Shigeru , Sakai Sanae , Michimori Yuta , Sumida Tomomi , Chikaraishi Yoshito , Atomi Haruyuki , Nunoura Takuro
Published: January 2024

Microfluidic capillary electrophoresis-mass spectrometry (CE-MS) is a rapid and highly accurate method to determine isotopomer patterns in isotopically labeled compounds. Here, we developed a novel method for tracer-based metabolomics using CE-MS for underivatized proteinogenic amino acids. The method consisting of a ZipChip CE system and a high-resolution Orbitrap Fusion Tribrid mass spectrometer allows us to obtain highly accurate data from 1 μl of 100 nmol/l amino acids comparable to a mere 1 $\times$ 104–105 prokaryotic cells. To validate the capability of the CE-MS method, we analyzed 16 protein-derived amino acids from a methanogenic archaeon Methanothermobacter thermautotrophicus as a model organism, and the mass spectra showed sharp peaks with low mass errors and background noise. Tracer-based metabolome analysis was then performed to identify the central carbon metabolism in M. thermautotrophicus using 13C-labeled substrates. The mass isotopomer distributions of serine, aspartate, and glutamate revealed the occurrence of both the Wood–Ljungdahl pathway and an incomplete reductive tricarboxylic acid cycle for carbon fixation. In addition, biosynthesis pathways of 15 amino acids were constructed based on the mass isotopomer distributions of the detected protein-derived amino acids, genomic information, and public databases. Among them, the presence of alternative enzymes of alanine dehydrogenase, ornithine cyclodeaminase, and homoserine kinase was suggested in the biosynthesis pathways of alanine, proline, and threonine, respectively. To our knowledge, the novel 13C tracer-based metabolomics using CE-MS can be considered the most efficient method to identify central carbon metabolism and amino acid biosynthesis pathways and is applicable to any kind of isolated microbe.
Genome-wide assessment of genetic diversity and transcript variations in 17 accessions of the model diatom Phaeodactylum tricornutum
Authors: Chaumier Timothée , Yang Feng , Manirakiza Eric , Ait-Mohamed Ouardia , Wu Yue , Chandola Udita , Jesus Bruno , Piganeau Gwenael , Groisillier Agnès , Tirichine Leila
Published: January 2024

Diatoms, a prominent group of phytoplankton, have a significant impact on both the oceanic food chain and carbon sequestration, thereby playing a crucial role in regulating the climate. These highly diverse organisms show a wide geographic distribution across various latitudes. In addition to their ecological significance, diatoms represent a vital source of bioactive compounds that are widely used in biotechnology applications. In the present study, we investigated the genetic and transcriptomic diversity of 17 accessions of the model diatom Phaeodactylum tricornutum including those sampled a century ago as well as more recently collected accessions. The analysis of the data reveals a higher genetic diversity and the emergence of novel clades, indicating an increasing diversity within the P. tricornutum population structure, compared to the previous study and a persistent long-term balancing selection of genes in old and newly sampled accessions. However, the study did not establish a clear link between the year of sampling and genetic diversity, thereby, rejecting the hypothesis of loss of heterozygoty in cultured strains. Transcript analysis identified novel transcript including noncoding RNA and other categories of small RNA such as PiwiRNAs. Additionally, transcripts analysis using differential expression as well as Weighted Gene Correlation Network Analysis has provided evidence that the suppression or downregulation of genes cannot be solely attributed to loss-of-function mutations. This implies that other contributing factors, such as epigenetic modifications, may play a crucial role in regulating gene expression. Our study provides novel genetic resources, which are now accessible through the platform PhaeoEpiview (https://PhaeoEpiView.univ-nantes.fr), that offer both ease of use and advanced tools to further investigate microalgae biology and ecology, consequently enriching our current understanding of these organisms.
Rich diversity and active spatial–temporal dynamics ofThalassiosiraspecies revealed by time-series metabarcoding analysis
Authors: Liu Kuiyan , Liu Shuya , Cui Zongmei , Zhao Yongfang , Chen Nansheng
Published: January 2024

Thalassiosira is a species-rich genus in Bacillariophyta that not only contributes positively as primary producer, but also poses negative impacts on ecosystems by causing harmful algal blooms. Although taxonomical studies have identified a large number of Thalassiosira species, however, the composition of Thalassiosira species and their geographical distribution in marine ecosystems were not well understood due primarily to the lack of resolution of morphology-based approaches used previously in ecological expeditions. In this study, we systematically analyzed the composition and spatial–temporal dynamic distributions of Thalassiosira in the model marine ecosystem Jiaozhou Bay by applying metabarcoding analysis. Through analyzing samples collected monthly from 12 sampling sites, 14 Thalassiosira species were identified, including five species that were not previously reported in Jiaozhou Bay, demonstrating the resolution and effectiveness of metabarcoding analysis in ecological research. Many Thalassiosira species showed prominent temporal preferences in Jiaozhou Bay, with some displaying spring–winter preference represented by Thalassiosira tenera, while others displaying summer–autumn preference represented by Thalassiosira lundiana and Thalassiosira minuscula, indicating that the temperature is an important driving factor in the temporal dynamics. The application of metabarcoding analysis, equipped with appropriate molecular markers with high resolution and high specificity and databases of reference molecular marker sequences for potential all Thalassiosira species, will revolutionize ecological research of Thalassiosira species in Jiaozhou Bay and other marine ecosystems.
Diversity of Bathyarchaeia viruses in metagenomes and virus-encoded CRISPR system components
Authors: Duan Changhai , Liu Yang , Liu Ying , Liu Lirui , Cai Mingwei , Zhang Rui , Zeng Qinglu , Koonin Eugene V , Krupovic Mart , Li Meng
Published: January 2024

Bathyarchaeia represent a class of archaea common and abundant in sedimentary ecosystems. Here we report 56 metagenome-assembled genomes of Bathyarchaeia viruses identified in metagenomes from different environments. Gene sharing network and phylogenomic analyses led to the proposal of four virus families, including viruses of the realms Duplodnaviria and Adnaviria, and archaea-specific spindle-shaped viruses. Genomic analyses uncovered diverse CRISPR elements in these viruses. Viruses of the proposed family “Fuxiviridae” harbor an atypical Type IV-B CRISPR-Cas system and a Cas4 protein that might interfere with host immunity. Viruses of the family “Chiyouviridae” encode a Cas2-like endonuclease and two mini-CRISPR arrays, one with a repeat identical to that in the host CRISPR array, potentially allowing the virus to recruit the host CRISPR adaptation machinery to acquire spacers that could contribute to competition with other mobile genetic elements or to inhibit host defenses. These findings present an outline of the Bathyarchaeia virome and offer a glimpse into their counter-defense mechanisms.
Wild plant species with broader precipitation niches exhibit stronger host selection in rhizosphere microbiome assembly
Authors: Ma Haikun , Liu Jinming , Mo Lidong , Arias-Giraldo Luisa M , Xiang Meichun , Liu Xingzhong
Published: January 2024

Plants actively recruit microbes from the soil, forming species-specific root microbiomes. However, their relationship with plant adaptations to temperature and precipitation remains unclear. Here we examined the host-selected and conserved microbiomes of 13 native plant species in the Xilingol steppe, Inner Mongolia, a semi-arid region in China. By calculating the global precipitation and temperature niches of these plants, considering plant phylogenetic distances, and analyzing functional traits, we found that these factors significantly influenced the rhizosphere microbiome assembly. We further quantified the strength of host selection and observed that plants with wider precipitation niches exhibited greater host selection strength in their rhizosphere microbiome assembly and higher rhizosphere bacterial diversity. In general, the rhizosphere microbiome showed a stronger link to plant precipitation niches than temperature niches. Haliangium exhibited consistent responsiveness to host characteristics. Our findings offer novel insights into host selection effects and the ecological determinants of wild plant rhizosphere microbiome assembly, with implications for steering root microbiomes of wild plants and understanding plant-microbiome evolution.
Novel order-level lineage of ammonia-oxidizing archaea widespread in marine and terrestrial environments
Authors: Zheng Yue , Wang Baozhan , Gao Ping , Yang Yiyan , Xu Bu , Su Xiaoquan , Ning Daliang , Tao Qing , Li Qian , Zhao Feng , Wang Dazhi , Zhang Yao , Li Meng , Winkler Mari-K H , Ingalls Anitra E , Zhou Jizhong , Zhang Chuanlun , Stahl David A , Jiang Jiandong , Martens-Habbena Willm , Qin Wei
Published: January 2024

Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant archaea on Earth, widely distributed in marine, terrestrial, and geothermal ecosystems. However, the genomic diversity, biogeography, and evolutionary process of AOA populations in subsurface environments are vastly understudied compared to those in marine and soil systems. Here, we report a novel AOA order Candidatus (Ca.) Nitrosomirales which forms a sister lineage to the thermophilic Ca. Nitrosocaldales. Metagenomic and 16S rRNA gene-read mapping demonstrates the abundant presence of Nitrosomirales AOA in various groundwater environments and their widespread distribution across a range of geothermal, terrestrial, and marine habitats. Terrestrial Nitrosomirales AOA show the genetic capacity of using formate as a source of reductant and using nitrate as an alternative electron acceptor. Nitrosomirales AOA appear to have acquired key metabolic genes and operons from other mesophilic populations via horizontal gene transfer, including genes encoding urease, nitrite reductase, and V-type ATPase. The additional metabolic versatility conferred by acquired functions may have facilitated their radiation into a variety of subsurface, marine, and soil environments. We also provide evidence that each of the four AOA orders spans both marine and terrestrial habitats, which suggests a more complex evolutionary history for major AOA lineages than previously proposed. Together, these findings establish a robust phylogenomic framework of AOA and provide new insights into the ecology and adaptation of this globally abundant functional guild.
Declines in ice cover are accompanied by light limitation responses and community change in freshwater diatoms
Authors: Zepernick Brittany N , Chase Emily E , Denison Elizabeth R , Gilbert Naomi E , Truchon Alexander R , Frenken Thijs , Cody William R , Martin Robbie M , Chaffin Justin D , Bullerjahn George S , McKay R Michael L , Wilhelm Steven W
Published: January 2024

The rediscovery of diatom blooms embedded within and beneath the Lake Erie ice cover (2007–2012) ignited interest in psychrophilic adaptations and winter limnology. Subsequent studies determined the vital role ice plays in winter diatom ecophysiology as diatoms partition to the underside of ice, thereby fixing their location within the photic zone. Yet, climate change has led to widespread ice decline across the Great Lakes, with Lake Erie presenting a nearly “ice-free” state in several recent winters. It has been hypothesized that the resultant turbid, isothermal water column induces light limitation amongst winter diatoms and thus serves as a competitive disadvantage. To investigate this hypothesis, we conducted a physiochemical and metatranscriptomic survey that spanned spatial, temporal, and climatic gradients of the winter Lake Erie water column (2019–2020). Our results suggest that ice-free conditions decreased planktonic diatom bloom magnitude and altered diatom community composition. Diatoms increased their expression of various photosynthetic genes and iron transporters, which suggests that the diatoms are attempting to increase their quantity of photosystems and light-harvesting components (a well-defined indicator of light limitation). We identified two gene families which serve to increase diatom fitness in the turbid ice-free water column: proton-pumping rhodopsins (a potential second means of light-driven energy acquisition) and fasciclins (a means to “raft” together to increase buoyancy and co-locate to the surface to optimize light acquisition). With large-scale climatic changes already underway, our observations provide insight into how diatoms respond to the dynamic ice conditions of today and shed light on how they will fare in a climatically altered tomorrow.
Specialized digestive mechanism for an insect-bacterium gut symbiosis
Authors: Lee Junbeom , Jeong Bohyun , Kim Jeongtae , Cho Jae H , Byeon Jin H , Lee Bok L , Kim Jiyeun K
Published: January 2024

In Burkholderia-Riptortus symbiosis, the host bean bug Riptortus pedestris harbors Burkholderia symbionts in its symbiotic organ, M4 midgut, for use as a nutrient source. After occupying M4, excess Burkholderia symbionts are moved to the M4B region, wherein they are effectively digested and absorbed. Previous studies have shown that M4B has strong symbiont-specific antibacterial activity, which is not because of the expression of antimicrobial peptides but rather because of the expression of digestive enzymes, mainly cathepsin L protease. However, in this study, inhibition of cathepsin L activity did not reduce the bactericidal activity of M4B, indicating that there is an unknown digestive mechanism that renders specifically potent bactericidal activity against Burkholderia symbionts. Transmission electron microscopy revealed that the lumen of symbiotic M4B was filled with a fibrillar matter in contrast to the empty lumen of aposymbiotic M4B. Using chromatographic and electrophoretic analyses, we found that the bactericidal substances in M4B existed as high-molecular-weight (HMW) complexes that were resistant to protease degradation. The bactericidal HMW complexes were visualized on non-denaturing gels using protein- and polysaccharide-staining reagents, thereby indicating that the HMW complexes are composed of proteins and polysaccharides. Strongly stained M4B lumen with Periodic acid–Schiff (PAS) reagent in M4B paraffin sections confirmed HMW complexes with polysaccharide components. Furthermore, M4B smears stained with Periodic acid–Schiff revealed the presence of polysaccharide fibers. Therefore, we propose a key digestive mechanism of M4B: bacteriolytic fibers, polysaccharide fibers associated with digestive enzymes such as cathepsin L, specialized for Burkholderia symbionts in Riptortus gut symbiosis.
Genome reduction occurred in early Prochlorococcus with an unusually low effective population size
Authors: Zhang Hao , Hellweger Ferdi L , Luo Haiwei
Published: January 2024

In the oligotrophic sunlit ocean, the most abundant free-living planktonic bacterial lineages evolve convergently through genome reduction. The cyanobacterium Prochlorococcus responsible for 10% global oxygen production is a prominent example. The dominant theory known as “genome streamlining” posits that they have extremely large effective population sizes (Ne) such that selection for metabolic efficiency acts to drive genome reduction. Because genome reduction largely took place anciently, this theory builds on the assumption that their ancestors’ Ne was similarly large. Constraining Ne for ancient ancestors is challenging because experimental measurements of extinct organisms are impossible and alternatively reconstructing ancestral Ne with phylogenetic models gives large uncertainties. Here, we develop a new strategy that leverages agent-based modeling to simulate the changes in the genome-wide ratio of radical to conservative nonsynonymous nucleotide substitution rate (dR/dC) in a possible range of Ne in ancestral populations. This proxy shows expected increases with decreases of Ne only when Ne falls to about 10 k − 100 k or lower, magnitudes characteristic of Ne of obligate endosymbiont species where drift drives genome reduction. Our simulations therefore strongly support a scenario where the primary force of Prochlorococcus genome reduction is drift rather than selection.
Flexible genomic island conservation across freshwater and marine Methylophilaceae
Authors: Layoun Paul , López-Pérez Mario , Haro-Moreno Jose M , Haber Markus , Thrash J Cameron , Henson Michael W , Kavagutti Vinicius Silva , Ghai Rohit , Salcher Michaela M
Published: January 2024

The evolutionary trajectory of Methylophilaceae includes habitat transitions from freshwater sediments to freshwater and marine pelagial that resulted in genome reduction (genome-streamlining) of the pelagic taxa. However, the extent of genetic similarities in the genomic structure and microdiversity of the two genome-streamlined pelagic lineages (freshwater “Ca. Methylopumilus” and the marine OM43 lineage) has so far never been compared. Here, we analyzed complete genomes of 91 “Ca. Methylopumilus” strains isolated from 14 lakes in Central Europe and 12 coastal marine OM43 strains. The two lineages showed a remarkable niche differentiation with clear species-specific differences in habitat preference and seasonal distribution. On the other hand, we observed a synteny preservation in their genomes by having similar locations and types of flexible genomic islands (fGIs). Three main fGIs were identified: a replacement fGI acting as phage defense, an additive fGI harboring metabolic and resistance-related functions, and a tycheposon containing nitrogen-, thiamine-, and heme-related functions. The fGIs differed in relative abundances in metagenomic datasets suggesting different levels of variability ranging from strain-specific to population-level adaptations. Moreover, variations in one gene seemed to be responsible for different growth at low substrate concentrations and a potential biogeographic separation within one species. Our study provides a first insight into genomic microdiversity of closely related taxa within the family Methylophilaceae and revealed remarkably similar dynamics involving mobile genetic elements and recombination between freshwater and marine family members.
Strain-level diversity in sulfonamide biodegradation: adaptation of Paenarthrobacter to sulfonamides
Authors: Huang Yue , Pan Anxin , Song Ying , Deng Yu , Wu Alnwick Long-Hei , Lau Colin Shiu-Hay , Zhang Tong
Published: January 2024

The widespread occurrence of sulfonamides raises significant concerns about the evolution and spread of antibiotic resistance genes. Biodegradation represents not only a resistance mechanism but also a clean-up strategy. Meanwhile, dynamic and diverse environments could influence the cellular function of individual sulfonamide-degrading strains. Here, we present Paenarthrobacter from different origins that demonstrated diverse growth patterns and sulfonamide-degrading abilities. Generally, the degradation performance was largely associated with the number of sadA gene copies and also relied on its genotype. Based on the survey of sad genes in the public database, an independent mobilization of transposon-borne genes between chromosome and plasmid was observed. Insertions of multiple sadA genes could greatly enhance sulfonamide-degrading performance. Moreover, the sad gene cluster and sadA transposable element showed phylogenetic conservation currently, being identified only in two genera of Paenarthrobacter (Micrococcaceae) and Microbacterium (Microbacteriaceae). Meanwhile, Paenarthrobacter exhibited a high capacity for genome editing to adapt to the specific environmental niche, opening up new opportunities for bioremediation applications.
PSVII-30 Effect of mineral mixture containing HMTBa in hay-based substrate on methane production.
Authors: Figueiredo Cibelle Borges , Ferreira Reginaldo Nassar , Ubeda Emanuely Zequim , Nunes Gabriela Vitória Pinto , Miranda Matheus Alves , Filho Edson Martins Ribeiro
Published: January 2024

In grazing systems, cattle produce a high molar ratio of acetate, resulting in greater methane production and greater energy loss via gas production. Thus, the objective of this study was to evaluate in vitro gas production and methane concentration using a mineral mixture containing 0.4% HMTBa in a Tifton hay-based substrate. The experiment was carried out under anaerobic conditions using ANKOM Gas Pressure Monitor bottles kept at 39 ºC containing artificial saliva, ruminal fluid, and two grams of a substrate from each treatment: (FE) Control, 1.75 g of Tifton hay and 0.25 g of mineral mixture; and (FM) 1.75 g of Tifton hay and 0.25 g of Suplemax mineral mixture (Suplemento Nutrição Animal) containing 0.4% of HMTBa. Duplicate substrates and duplicate blanks were fermented for each treatment in two runs, with a total of four repetitions per treatment. The accumulated pressure resulting from the fermentation was measured automatically over 48 hours using the Gas Monitor software connected to the ANKOM modules of each bottle. The conversion of pressure to gas volume was calculated as follows: Volume (mL) = 2.3932 + 3.4053 × pressure (R2 = 0.9146; n = 1.151). At the end of each run, a gas sample was collected from each bottle to measure methane concentration using gas chromatography. To obtain the methane production for every 100 mL of gas produced, the total volume of methane produced was multiplied by 100 and divided by the total gas production. Data were analyzed in a completely randomized design using analysis of variance (ANOVA) at α = 0.05. Gas production was not affected by the inclusion of HMTBa (P = 0.3938), with an average of 54.14 mL (Table 1). There was a reduction in methane production from 25.41 to 20.05 mL with the addition of HMTBa (P = 0.0034), representing a decrease of 21.09%. There was a tendency to reduce methane production for each 100 mL of gas produced from 46.01 to 37.86 mL (P = 0.0889). Although HMTBa reduces the molar proportion of propionate, it is considered to be one of the main hydrogen users. In environments with a high concentration of H2 (above 1 mmol) and the presence of an anti-methanogen, the most favored path for using hydrogen is acetogenesis, which reduces methane production. Thus, the use of a mineral mixture containing 0.4% HMTBa in a Tifton-hay-based substrate reduced methane production in an in vitro assay.
Prevalence and Trend of Depression in Burn Survivors: A Single Center Cohort Study
Authors: Ranganath V S , Segu Smitha , Girish B S , Johns Joel M , Meghana C S
Published: January 2024

Burn injuries are frequently disastrous catastrophes that can cause significant skin damage and frequently result in hypertrophic scarring. Recovery from burn injury includes 3 domains—medical, functional, and psychiatric. Psychological concerns affect both the quality of life and the disease recovery. This study assesses the prevalence of major depression or clinically significant symptoms of depression among patients hospitalized for acute burn injury, as well as their persistence once diagnosed. It is a prospective cohort that was studied in 1%-40% of patients with body surface area burn, where the Beck Depression Inventory was used as a depressive symptom measure. A total of 108 patients were included in the study, out of which 42 (38.8%) exhibited depressive symptoms. Type of burn did not affect the prevalence of depression, whereas total body surface area had an impact on prevalence rate. The Beck Depression Inventory score assessment during the study revealed that 8.4% of participants exhibited worsening of scores during the study period and only 3.4% showed improvement throughout the study. Patients with mild depressive symptoms at admission were likely to recover, whereas those with severe depressive symptoms were less likely to recover from the psychological state. To conclude, depression was more prevalent among burn survivors from the Indian community.
Factors Predicting Burn Surgery Operative Time in a Middle-Income Country Regional Burn Service
Authors: Marais Marlé , Wall Shelley , Smith Michelle , Allorto Nikki
Published: January 2024

Access to theater is essential for the surgical management of deep burns. This is a scarce resource in low-middle-income countries. It underpins the importance of optimizing theater time. We sought to look at specific factors and their influence on operative time in minor to moderate burn surgery. This knowledge can assist teams where theater planning and optimization may be beneficial in resource-limited settings. Operative records between January and December 2018 at the Regional Hospital were analyzed. Data fields included age, gender, TBSA of burn, surface area burn operated on, intraoperative position change, seniority of surgeon, presence of an assistant, inclusion of special areas, predicted operative time, and actual operative time. Operative records for 265 patients were analyzed, with a median operative time of 40 minutes (interquartile range 25-64). Overall factors that predict longer operating time are larger total body surface area burn, larger surface area burn operated on, an operation involving at least one special area, number of special areas operated on, position change, presence of an assistant, and longer predicted operative time. Total percentage burn, operated percentage, special areas to be operated, and position change are overall factors to be considered when planning a burns list for the nonspecialist burn surgeon. This knowledge may be useful for an inexperienced surgeon to understand and aid in the effective utilization of limited operative time available for the surgical management of deep burns in resource-limited settings.
Morals in Multi-Unit Markets
Authors: Ziegler Andreas G B , Romagnoli Giorgia , Offerman Theo
Published: January 2024

We examine how the erosion of morals, norms, and norm compliance in markets depends on the market power of individual traders. Previously studied markets allow traders to exchange at most one unit and provide market power to individual traders by de-activating two forces: (i) the replacement logic, whereby immoral trading is justified by the belief that others would trade otherwise and (ii) market selection, by which the least moral trader determines aggregate quantities. In an experiment, we compare single-unit to (more common) multi-unit markets, which may activate these forces. Multi-unit markets, in contrast to single-unit markets, lead to a complete erosion of morals. This is associated primarily with a deterioration in norm compliance: the observed level of immoral trade is in contrast with the prevailing social norm. The replacement logic is the main mechanism driving this finding.
Human Rights-based Approaches and the Right to Health: A Systematic Literature Review
Authors: Patterson David
Published: January 2024

The term ‘human rights-based approach’ is common in rights and international development literature. Yet there is no single, universally agreed definition of a human rights-based approach, let alone its application to the right to health. This article uses a PRISMA-informed systematic literature review to address the question, ‘What is the current status of the human rights-based approach to health in international law?’ Previous reviews have described how international organizations and development donors have tackled human rights-based approaches to development generally and discussed prominent works on human rights-based approaches to health. However, this is the first review to sample the peer-reviewed literature systematically. The study revealed that authors use the terms ‘human rights’, ‘human rights-based approach’ and ‘right to health’ to import a raft of legal implications, or none at all. Similarly, readers may assign legal meanings to these terms, or none at all. Confusion arises because although these terms often have different meanings for authors and readers from different disciplines, this is not commonly acknowledged, and authors rarely clarify their perspectives. The author concludes that scholars should seek co-authors with human rights law or public health qualifications, as relevant. Most academic institutions research and teach health and law separately; interdisciplinary centres of excellence in health, law and human rights offer an opportunity to overcome these historical obstacles to interdisciplinary dialogue and understanding. The study and its conclusions will be of interest to legal researchers, human rights advocates, public health scholars, and advocates from other disciplines.
When the Dragon comes Home to Roost: Chinese Investments in the EU, National Security, and Investor–State Arbitration
Authors: Gáspár-Szilágyi Szilárd
Published: January 2024

The gradual rise of China as an economic, normative, and lending power has resulted in more protectionist measures in areas of the world that traditionally championed economic liberalization. Currently, 21 out of 27 European Union (EU) Member States have national laws or measures in place for the screening or review of foreign investments. However, such restrictive national measures can result in investment treaty-based arbitration under the existing bilateral investment treaties concluded by 26 EU Member States with China, as evidenced by the recent arbitration initiated by Huawei against Sweden. Therefore, this article assesses whether EU Member States are likely to see a spike in investor–State arbitral claims initiated by Chinese investors as a result of the former’s investment screening measures. To achieve this aim, the article first looks at the bilateral investment treaties (BIT)-level variables that can influence the initiation of arbitration against EU Member States, such as the presence and type of investor–State arbitration (ISA) clauses, the types of investments being made, the coverage of the pre- and/or post-establishment phases, or the inclusion of ‘non-precluded measures’ clauses. This is then followed by a look at other variables, such as the decreasing number of Chinese foreign direct investment into EU countries, the treatment of Chinese investors in recent high-profile cases, and the importance of security alliances. The article concludes that those EU States are at a higher risk of being respondents in arbitrations initiated by Chinese investors whose BITs with China include modern ISA clauses, cover the pre-establishment phase, and lack non-precluded measures clauses. However, EU States should wait for the outcome of the Huawei v Sweden arbitration before deciding whether the amendment or termination of the existing BITs with China is needed.
Perceptions of Tree Diseases in Indigenous Communities: Native Alaskan and Hawaiian Insights
Authors: Roy Kylle , Frankel Susan J , Oakes Lauren E , Francisco Kainana S , Kealiʻikanakaʻoleohaililani Kekuhi , Sitz Rachael A , Huff Emily S , Schelhas John
Published: January 2024

Concern for tree mortality and damage, and preferences for management interventions, reflect people’s values and cultures. We examine perceptions of tree diseases in two Indigenous communities to provide examples of the types of distress and attitudes that arise when tree diseases significantly damage cultural values. Summaries of yellow-cedar decline as perceived by Tlingit and Haida Alaska Natives and rapid ʻōhiʻa death (ROD) and Native Hawaiian culture underscore the interconnections between local people and local forests and the ways forest diseases can impart a loss of culture and connections to ancestors. The complex relationships between Indigenous people, ecosystems, and tree diseases highlight the importance of the inclusion of diverse viewpoints to inform natural resource planning and management so that it may be conducted equitably and ethically.

Study Implications: Consideration of cultural and social impacts as criteria for prioritization of forest disease management requires knowledge of the types and intensity of impacts that forest diseases have on Indigenous and Western culture. A greater understanding of the diversity of perspectives toward forest diseases is needed to inform natural resource planning and management so that it may be conducted in an ecologically sound and inclusive manner.
Digital Rights and the State of Exception. Internet Shutdowns from the Perspective of Just Securitization Theory
Authors: Thumfart Johannes
Published: January 2024

Addressing cases from Cameroon, Egypt, Ethiopia, India, Indonesia, Iran, Nigeria, Pakistan, Spain, Togo, the United Kingdom, the United States, and Zimbabwe, this article discusses the global phenomenon of internet shutdowns (ISs) from the normative perspective of Just Securitization Theory (JST). It focuses on the conflict between arguments used to justify ISs and the negative impact of ISs regarding fundamental and human rights. This article develops strict criteria for when ISs might be legitimate as extraordinary security measures in emergency situations. Following JST, these criteria are based on citizens’ right to physical integrity, the expectation of reasonable success, proportionality, harm minimization, and specificity. I argue that it is not legitimate to use ISs to enact collective punishment, preemptive censorship, or hamper legitimate political protests. While denying the legitimacy of the vast majority of ISs on these grounds, I sketch four exceptional scenarios (“WhatsApp lynchings,” “US Capitol 2021,” “Computer virus,” and “False alarm”) in which ISs can be legitimate. JST also includes states’ duty to desecuritize once a threat has been neutralized. In this way, a balanced discussion of ISs as an exceptional measure from the perspective of JST contributes to the establishment of a customary positive human right to digital connectivity in the normal situation.