bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased miscarriage rate is associated with at least four components of metabolic syndrome in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycle
Authors: Dai Ziyi , Chen Yufeng , Liu Chang
Published: September 2024

Aim

This study aimed to investigate the association between the components of metabolic syndrome (MetS) and reproductive outcomes in women with polycystic ovary syndrome (PCOS) undergoing their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) embryo transfer cycle.

Methods

This is a retrospective study that included 720 women with PCOS from January 2018 to December 2021. Anthropometric, biochemical, and reproductive data of the study subjects were collected from electronic medical record. Women with PCOS met <3, 3, and >3 criteria of MetS were classified in group 1, 2, and 3, respectively.

Results

The miscarriage rate in women with MetS was significantly higher than that in non‐MetS group (23.2% vs. 14.2%, p = 0.03). There was a significant increasing trend in miscarriage rate from group 1 to group 3 (p for trend <0.05). The miscarriage rate in group 3 was significantly higher than that in group 1 (29.3% vs. 14.2%, p < 0.05). Logistic regression analyses showed that women with at least four components of MetS (group 3) were independently associated with a high risk of miscarriage, with the odds ratios and 95% confidence intervals for group 2 and 3 versus group 1 were 1.38 (0.67–2.82) and 2.46 (1.06–5.74), respectively (p for trend = 0.04).

Conclusions

PCOS women accompanied with at least four diagnostic criteria of MetS is independently associated with increased miscarriage rate when undergoing their first IVF or ICSI cycle.
Diagnostic accuracy of Ages and Stages Questionnaire, Third Edition to identify abnormal or delayed gross motor development in high‐risk infants
Authors: Danks Marcella T , Gray Peter H , Hurrion Elizabeth M
Published: September 2024

Aim

To investigate the diagnostic accuracy of parent‐completed Ages and Stages Questionnaire, Third Edition (ASQ‐3) to identify abnormal or delayed gross motor development in infants born less than 1000 g or less than 28 weeks gestation.

Methods

Prospective cohort study of high‐risk infants comparing ASQ‐3 as the index test with concurrent score on Alberta Infant Motor Scale (AIMS) as the reference standard, at 4‐, 8‐ and 12‐month corrected (post‐term) age. Reference standard positivity cut‐offs were ‘Abnormal motor development’ (AIMS Clinical Range) and ‘Motor delay’ (AIMS score >1 SD below mean, not captured in Clinical Range).

Results

Participating infants (n = 191) had mean gestational age (95% confidence interval (CI)) 26.8 weeks (26.6–27.1) and mean birthweight (95% CI) 870 g (844–896). AIMS rated 51%, 31% and 23% of infants as having ‘Abnormal motor development’ and 12%, 28% and 13% with ‘Motor delay’, at 4, 8 and 12 months, respectively. Diagnostic accuracy of ASQ‐3 to identify abnormal motor development was acceptable for older infants only if ‘Monitor’ cut‐off was used: sensitivity (95% CI) 33% (23–44), 86% (73–95) and 80% (63–92) and specificity (95% CI) 84% (74–92), 76% (66–84), and 76% (67–83) at 4, 8 and 12 months, respectively. ASQ‐3 sensitivity to identify motor delay was low.

Conclusions

ASQ‐3 has poor sensitivity to identify abnormal or delayed motor development at 4 months. Using the ‘Monitor’ cut‐off improves the diagnostic accuracy of ASQ‐3 for identification of older infants with abnormal motor development who are at high risk of motor disability. However, ASQ‐3 has poor sensitivity to identify motor delay. Clinical motor assessment of high‐risk infants is recommended, particularly in early infancy.
Multiparametric Cranberry (Vaccinium macrocarpon Ait.) Fruit Textural Trait Development for Harvest and Postharvest Evaluation in Representative Cultivars
Authors: Lopez‐Moreno Hector , Phillips Matthew , Diaz‐Garcia Luis , Torres‐Meraz Maria , Jarquin Diego , Loarca Jenyne , Ikeda Shinya , Giongo Lara , Grygleski Edward , Iorizzo Massimo , Zalapa Juan
Published: September 2024

Fruit texture is a priority trait that guarantees the long‐term economic sustainability of the cranberry industry through value‐added products such as sweetened dried cranberries (SDCs). To develop a standard methodology to measure texture, we conducted a comparative analysis of 22 textural traits using five different methods under both harvest and postharvest conditions in 10 representative cranberry cultivars. A set of textural traits from the 10%‐strain compression and puncture methods were identified that differentiate between cultivars primarily based on hardness/stiffness and elasticity properties. The complementary use of both methodologies allowed for a detailed evaluation by capturing the effect of key texture‐determining factors such as structure, flesh, and skin. Furthermore, the high effectiveness of this approach in different conditions and its ability to capture high phenotypic variation in cultivars highlights its great potential for applicability in various areas of the value chain and research. Therefore, this study provides an informed reference for unifying future efforts to enhance cranberry fruit texture and quality.
Cosmogenic radionuclides in meteorites from the Otway Massif blue ice area, Antarctica: An unusual, well‐preserved H5 chondrite strewn field
Authors: Welten Kees C. , Caffee Marc W. , Kress Monika E. , Giscard Marlene D. , Jull A. J. Timothy , Harvey Ralph P. , Schutt John
Published: September 2024

The US Antarctic Search for Meteorites (ANSMET) discovered a dense cluster of 88 ordinary chondrites with a total mass of more than 100 kg on a blue ice area (BIA) of 1.6 × 0.3 km2 near the Otway Massif, Grosvenor Mountains, Antarctica. The larger masses (weighing up to 29 kg) were found at one end of an oval‐shaped pattern and the smaller masses (50–200 g) at the other end. We measured concentrations of the cosmogenic radionuclides 10Be (half‐life—1.36 × 106 year) and 36Cl (3.01 × 105 year) in the metal fraction of 17 H chondrites, including 14 fragments of this cluster, to verify the hypothesis that this meteorite cluster on the Otway Massif BIA represents a meteorite strewn field produced by the atmospheric breakup of a single meteoroid. The 10Be and 36Cl concentrations confirm that 10 out of 14 H chondrites from different locations within this small area are paired fragments of the same meteorite fall, while the four other H chondrites represent two additional—smaller—falls. The radionuclides suggest a pre‐atmospheric mass of 200–400 kg for the large pairing group, suggesting that 25%–50% of the meteoroid survived atmospheric entry. Based on the distribution of the paired H chondrites and evidence of their common cosmic‐ray exposure history in space, we conclude that most of the 88 meteorites within this small area represent a meteorite strewn field. The small size of the strewn field suggests that the meteoroid entered at a steep angle (>60°), while the low amount of fusion crust on most meteorite surfaces most likely indicates atmospheric break up at low altitude, while additional fragmentation of a large surviving fragment may have occurred during impact on the ice. This well‐documented strewn field provides a good opportunity to apply model simulations of the atmospheric fragmentation of this object as a function of entry angle, velocity, and meteoroid strength. Cosmogenic 14C analyses in two members of the Otway Massif pairing group yield a terrestrial age of 15.5 ± 1.5 kyr, which represents the time elapsed since this meteorite fell on Earth. The excellent preservation of an Antarctic meteorite strewn field suggests that the Otway Massif BIA represents a relatively stagnant blue ice field.
Editorial comment on “Current options in the management of tree nut allergy: A systematic review and narrative synthesis”
Authors: Bognanni Antonio , Eigenmann Philippe , Upton Julia E. M.
Published: September 2024

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Multi‐omics integration analysis reveals the molecular mechanisms of drought adaptation in homologous tetraploid alfalfa(Medicago sativa ‘Xinjiang‐Daye’)
Authors: Qi Jianwei , Luo Yongzhong , Lu Songsong , Liu Hui , Huang Haixia , Qiu Yingde , Zhou Xiaotong , Ma Chao
Published: September 2024

Drought stress is a predominant abiotic factor leading to decreased alfalfa yield. Genomic ploidy differences contribute to varying adaptation mechanisms of different alfalfa cultivars to drought conditions. This study employed a multi‐omics approach to characterize the molecular basis of drought tolerance in a tetraploid variant of alfalfa (Medicago sativa, Xinjiang‐Daye). Under drought treatment, a total of 4446 genes, 859 proteins, and 524 metabolites showed significant differences in abundance. Integrative analysis of the multi‐omics data revealed that regulatory modules involved in flavonoid biosynthesis, plant hormone signalling transduction, linoleic acid metabolism, and amino acid biosynthesis play crucial roles in alfalfa adaptation to drought stress. The severity of drought led to the substantial accumulation of flavonoids, plant hormones, free fatty acids, amino acids, and their derivatives in the leaves. Genes such as PAL, 4CL, CHI, CHS, PP2C, ARF_3, and AHP_4 play pivotal regulatory roles in flavonoid biosynthesis and hormone signalling pathways. Differential expression of the LOX gene emerged as a key factor in the elevated levels of free fatty acids. Upregulation of P5CS_1 and GOT1/2 contributed significantly to the accumulation of Pro and Phe contents. ERF19 emerged as a principal positive regulator governing the synthesis of the aforementioned compounds. Furthermore, observations suggest that Xinjiang‐Daye alfalfa may exhibit widespread post‐transcriptional regulatory mechanisms in adapting to drought stress. The study findings unveil the critical mechanisms by which Xinjiang‐Daye alfalfa adapts to drought stress, offering novel insights for the improvement of alfalfa germplasm resources.
Copper Homeostasis and Its Impact on Innate Immunity in Crustaceans
Authors: Chen Hejia , Huang Xi , Tayyab Muhammad , Zhao Mingming , Yao Defu , Zheng Zhihong , Zhao Xianliang , Zhao Yongzhen , Chen Xiuli , Zhang Bobo , Yang Qiongqiong , Zhang Yueling , Lin Zhongyang
Published: September 2024

Copper, an essential micronutrient in crustaceans, plays vital roles in enzymatic processes, oxygen transport, pigmentation, and structural protein synthesis, including collagen and elastin. Recent research has elucidated its pivotal role in innate immunity of crustaceans, enhancing the immune response by promoting phagocytic activity, antimicrobial peptide production, and modulation of immune gene expression. Copper ions exhibit antimicrobial effects by disrupting cell membranes and inhibiting microbial proliferation. Furthermore, copper governs antioxidant defense mechanisms, protecting crustaceans against oxidative stress and infection. However, excessive copper can lead to toxicity, highlighting the need for strict maintenance of copper homeostasis. This review explores the complex processes of copper homeostasis in crustaceans, detailing transport mechanisms, storage proteins, and detoxification pathways. It emphasizes copper's critical physiological and immunological functions, contributing to a comprehensive understanding of its multifaceted roles in crustaceans and laying groundwork for further exploration of copper homeostasis as a strategy for boosting crustacean immunity. Aquaculture practices significantly influence copper levels in crustaceans. Effective copper management, including monitoring techniques, water treatment strategies, and regulatory frameworks, is crucial for both crustacean welfare and environmental sustainability.
Community engagement in coral reef restoration in the Seaflower MPA, Colombia
Authors: Uribe‐Castañeda Natalia , Morales Nia , Loizzo Jamie , Patterson Joshua , Main Martin
Published: September 2024

Community engagement has been identified as a key component for successful conservation efforts. According to community members, key stakeholders, and coral reef restoration practitioners in the Seaflower Marine Protected Area (MPA), the most effective way to engage communities in coral reef restoration is by building local capacity. We used a mixed‐methods approach including interviews, strengths, weaknesses, opportunities, and threats analysis, and surveys to assess strategies employed in the Seaflower MPA to involve local communities in coral reef restoration and the motivations and possible barriers that hinder community engagement. The community residing in the Seaflower MPA demonstrated awareness of the importance of coral reefs and their role in their livelihoods. They identified the main challenges to restoration as social dysfunctionality, administrative barriers, and environmental threats, along with a lack of opportunities for the community to participate in coral reef restoration. Our findings identified building trust, promoting equity, transparency, and accountability, fostering collaboration, and improving communication as essential to overcoming these challenges. Empowering local communities through capacity‐building initiatives such as educational programs, economic incentives, equity and inclusion measures, formal certifications, and local leadership would enhance support for coral reef restoration in the Seaflower MPA. In addition to building local capacity, our research identified the need for strategic planning, budgeting, and effective policies for enhancing community efforts in coral reef restoration.
Two‐phase magma flow with phase exchange: Part I. Physical modeling of a volcanic conduit
Authors: Narbona‐Reina Gladys , Bresch Didier , Burgisser Alain , Collombet Marielle
Published: September 2024

In a review paper in this same volume, we present the state of the art on modeling of compressible viscous flows ranging from single‐phase to two‐phase systems. It focuses on mathematical properties related to weak stability because they are important for numerical resolution and on the homogenization process that leads from a microscopic description of two separate phases to an averaged two‐phase model. This review serves as the foundation for Parts I and II, which present averaged two‐phase models with phase exchange applicable to magma flow during volcanic eruptions. Here, in Part I, after introducing the physical processes occurring in a volcanic conduit, we detail the steps needed at both microscopic and macroscopic scales to obtain a two‐phase transient conduit flow model ensuring: (1) mass and volatile species conservation, (2) disequilibrium degassing considering both viscous relaxation and volatile diffusion, and (3) dissipation of total energy. The resulting compressible/incompressible system has eight transport equations on eight unknowns (gas volume fraction and density, dissolved water content, liquid pressure, and the velocity and temperature of both phases) as well as algebraic closures for gas pressure and bubble radius. We establish valid sets of boundary conditions such as imposing pressures and stress‐free conditions at the conduit outlet and either velocity or pressure at the inlet. This model is then used to obtain a drift‐flux system that isolates the effects of relative velocities, pressures, and temperatures. The dimensional analysis of this drift‐flux system suggests that relative velocities can be captured with a Darcy equation and that gas–liquid pressure differences partly control magma acceleration. Unlike the vanishing small gas–liquid temperature differences, bulk magma temperature is expected to vary because of gas expansion. Mass exchange being a major control of flow dynamics, we propose a limit case of mass exchange by establishing a relaxed system at chemical equilibrium. This single‐velocity, single‐temperature system is a generalization of an existing volcanic conduit flow model. Finally, we compare our full compressible/incompressible system to another existing volcanic conduit flow model where both phases are compressible. This comparison illustrates that different two‐phase systems may be obtained depending on the governing unknowns chosen. Part II presents a 1.5D version of the model established herein that is solved numerically. The numerical outputs are compared to those of another steady‐state, equilibrium degassing, isothermal model under conditions typical of an effusive eruption at an andesitic volcano.
Not exactly twins: Authoritarians and populists differ in their attitudes toward trust in government, elitism, pluralism, political identification, and identity fusion
Authors: Jami Waleed A.
Published: September 2024

Introduction

Authoritarianism and populism are used regularly to describe the individuals responsible for anti‐democratic action. These two constructs share some similarities with regard to how they hinder democracy and at times have been used interchangeably to describe such issues. However, authoritarians and populists may differ with regard to their political identification, as well as how they view the government and the existing establishment.

Objectives

With a US college sample, this study's goal was to examine how authoritarianism and populist attitudes influence views on pluralism, elitism, trust in government, identity fusion, and political identification (identification with American political parties).

Results

The findings indicated that right‐wing authoritarians trusted the government, endorsed elitist attitudes, but were low on pluralism; this pattern was the opposite for those high on populist attitudes. Left‐wing authoritarianism was related only to low pluralism. Moreover, low trust in the government partially mediated the link between populist attitudes and pluralism. Results also indicated that right‐wing and left‐wing authoritarians identified with the Republican and Democratic parties, respectively, whereas political identification was unrelated to populist attitudes. Furthermore, identity fusion partially mediated the link between right‐wing authoritarianism and identification with the Republican Party.

Conclusion

Authoritarianism and populist attitudes may explain different motivations for anti‐democratic thought and behaviors. This study contributes to ongoing debates found in contemporary populism and authoritarianism research as well as different solutions to addressing their rise in mainstream politics.
“Fiddler on the Roof ” as a Tool for Teaching About How Religions Change Through Time
Authors: Wilson Liz
Published: September 2024

This article reflects on the difficulty that many students have in appreciating that religions change over time. It describes an assignment that can be used to teach this important religious literacy skill. The assignment focuses on changing norms on courtship, marriage, and family formation in Jewish communities at two different times and two different places. Students reflect on norms in the Pale of Settlement of Imperial Russia at the turn‐of‐the century using the film version of the musical Fiddler on the Roof. They then view a documentary about the making and reception of the musical that centers the social movements of 1960s America, and they also read secondary literature on changing marriage norms in turn‐of‐the century Jewish communities in Eastern Europe and in 20th century Jewish communities in America. The assignment turns on concepts of tradition and innovation, showing how often innovation plays a role in things deemed “traditional”.
СТРАТЕГИЯ СОЗДАНИЯ ПРИРОДОПОДОБНЫХ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ НОВОГО ПОКОЛЕНИЯ ЧЕРЕЗ ПРИЗМУ МИКРОБИОМ
Authors: Даниленко В.Н.
Published: September 2024

Успехи и достижения науки о жизни в последние десятилетия позволили сделать прорыв в создании лекарственных препаратов по различным направлениям, в том числе в области онкологии, кардиологии и других. Вместе с тем существующими подходами не удается решить проблему множественной лекарственную устойчивости и создания новых эффективных антибактериальных препаратов, создание препаратов нового поколения для лечения неврологических и нейродепрессивных состояний. Требуются новые подходы для создания препаратов, снимающих побочные действия при лучевой, химиотерапии и иммунотерапии, онкозаболеваний. Природоподобные технологии, открывают новые горизонты создания лекарственных средств нового поколения, адаптированных к организму человека. Микробиота кишечника является резервуаром полезных бактерий, функциональных генов, сигнальных молекул и метаболитов, определяющих позитивный гомеостаз организма, и служащая их источником для создания новых биотерапевтических препаратов различной направленности. Сегодня микробиота кишечника является источником фармабиотиков и постбиотиков (метабиотиков) с нейромодулирующими, иммуномодулирующими и противовоспалительными свойствами с установленными механизмами действия, биологически активными ингредиентами, их определяющими. В лаборатории генетики микроорганизмов ИОГен РАН проводятся работы по созданию фармабиотиков и постбиотиков на основе штаммов: L. brevis 47f для снятия побочных эффектов мукозитной природы при лучевой терапии, L.fermentum U21 для комбинированного лечения пневмонии, B.longum GT15 и B.adolescentis в комбинированной терапии депрессивных состояний. Для каждого из предложенных кандидатов в препараты осуществлён большой комплекс исследований, в том числе основанных на омиксных и геномных технологиях, а также определенный цикл доклинических исследований по их эффективности и безопасности. В ИОГен РАН разработан алгоритм поиска генов и бактерий, их содержащих, с заданными свойствами. Разработаны методы экспрессии скрининга среди коллекции штаммов с заданными свойствами. Для отобранных кандидатов препараты проводится изучение их свойств на адекватных моделях культур клеток, грызунов. Конечной целью является создание препаратов фармабиотиков для лечения заболеваний различной этиологии.
ИЗУЧЕНИЕ ВОПРОСОВ БИОБЕЗОПАСНОСТИ ПРИ ПОДГОТОВКЕ СПЕЦИАЛИСТОВ ДЛЯ БИОТЕХНОЛОГИЧЕСКИХ ФАРМПРОИЗВОДСТВ
Authors: Сулейменов М. К. , Албаева Ж. Т. , Сулейменова Д. М.
Published: September 2024

Учитывая важность вопросов биобезопасности, впервые в Казахстане 21 мая  2022 года принят закон № 122-VII ЗРК «О биологической безопасности Республики Казахстан». Он определил правовые основы государственного регулирования в области биологической безопасности Республики Казахстан и направлен на предотвращение биологических угроз.
 Закон, создав правовые основы государственного регулирования вопросов биобезопас­ности при появлении в Казах­стане патогенных биологических агентов, позволит сформировать единую основу для ее обеспечения в сфере здравоохранения, санитарно-эпидемиологической службы, экологической, ветеринарной, фитосанитарной безопасности, гражданской защиты и, конечно, для развития науки.
Осознавая перспективы развития биотехнологии и рост производства биотехнологических препаратов, вакцин, диагностических средств, в Школе Фармации КазНМУ имени С.Д.Асфендиярова в августе 2022 года создана кафедра биотехнологии и общей химической технологии (ОХТ). В образовательные программы по специальности «Технология фармацевтического производства» включена обязательная дисциплина «Основы биологической безопасности на фармацевтическом производстве».
Целью дисциплины является формирование у студентов мышления по вопросам биобезопасности при проектировании и эксплуатации фармацевтического производства на основе изучения действующей правовой документации и законодательства. Программа дисциплины и силлабус интегрированы и разработаны совместно с Санкт-Петербургским химико-фармацевтическим университетом. При подготовке специалистов для биотехнологических фармпроизводств большое значение имеет сотрудничество ВУЗа и  научно-исследовательских организаций, предприятий. КазНМУ имени С.Д. Асфендиярова наладил сотрудничество  с НИИ проблем биологической безопасности, ННЦ особо опасных инфекций имени Масгута Айкимбаева, ТОО «OtarBioPharm», Карагандинским фармацевтическим комплексом, ТОО НПП «Антиген», ТОО «КАЗ-ДИА-ТЕСТ». Рассматриваются планы сотрудничества в научной сфере, подготовке магистрантов, докторантов. Учитывая рост в Казахстане фармацевтических предприятий,  выпускающих биотехнологические препараты, вакцины, диагностикумы, тест-системы, изучение  дисциплины «Основы биологической безопасности на фармацевтическом производстве» в медицинских ВУЗах Казахстана представляется важным и актуальным.
В связи с увеличением в перспективе числа фармацевтических производств в Казахстане, выпускающих биотехнологические препараты, вакцины необходимо больше видеоматериалов и информации о казахстанских предприятиях, выпускающих такую продукцию. Целесообразно также прохождение тренинга или курсов повышения квалификации по биологической безопасности для преподавателей, обучающих студентов по дисциплине «Основы биологической безопасности на фармацевтическом производстве», с получением соответствующего сертификата.
Development of a Method for Shape Optimization for a Gas Turbine Fuel Injector Design Using Metal-Additive Manufacturing
Authors: Jalui Sagar , Xuan Yuan , Manogharan Guha , O'Connor Jacqueline
Published: September 2024

Adjoint shape optimization has enabled physics-based optimal designs for aerodynamic surfaces. Additive manufacturing (AM) makes it possible to manufacture complex shapes. However, there has been a gap between optimal and manufacturable surfaces due to the inherent limitations of commercial computational fluid dynamics (CFD) codes to implement geometric constraints during adjoint computation. In such cases, the design sensitivities are exported and used to perform constrained shape modifications using parametric information stored in computer aided design (CAD) files to satisfy manufacturability constraints. However, modifying the design using adjoint methods in CFD solvers and performing constrained shape modification in CAD can lead to inconsistencies due to different shape parameterization schemes. This paper describes a method to enable the simultaneous optimization of the fluid domain and impose AM manufacturability constraints, resolving one of the key issues of geometry definition for isogeometric analysis. Similar to a grid convergence study, the proposed method verifies the consistencies between shape parameterization techniques present within commercial CAD and CFD software during mesh movement as a part of the adjoint shape optimization routine. By identifying the appropriate parameters essential to a shape optimization study, the error metric between the different parameterization techniques converges to demonstrate sufficient consistencies for justifiable exchange of data between CAD and CFD. For the identified shape optimization parameters, the error metric to measure the deviation between the two parameterization schemes lies within the AM laser-powder bed fusion (L-PBF) process tolerance. Additionally, comparison for subsequent objective function calculations between iterations of the optimization loop showed acceptable differences within 1% variation between the modified geometries obtained using the two parameterization schemes. This method provides justification for the use of multiphysics guided adjoint design sensitivities computed in CFD software to perform shape modifications in CAD to incorporate AM manufacturability constraints during the shape optimization loop such that optimal designs are also additively manufacturable.
Insulating electromagnetic-shielding silicone compound enables direct potting electronics
Authors: Zhou Xinfeng , Min Peng , Liu Yue , Jin Meng , Yu Zhong-Zhen , Zhang Hao-Bin
Published: September 2024

Traditional electromagnetic interference–shielding materials are predominantly electrically conductive, posing short-circuit risks when applied in highly integrated electronics. To overcome this dilemma, we propose a microcapacitor-structure model comprising conductive fillers as polar plates and intermediate polymer as a dielectric layer to develop insulating electromagnetic interference–shielding polymer composites. The electron oscillation in plates and dipole polarization in dielectric layers contribute to the reflection and absorption of electromagnetic waves. Guided by this, the synergistic nonpercolation densification and dielectric enhancement enable our composite to combine high resistivity, shielding performance, and thermal conductivity. Its insulating feature allows for direct potting into the crevices among assembled components to address electromagnetic compatibility and heat-accumulation issues.
Anti-echinococcal effect of metformin in advanced experimental cystic echinococcosis: reprogrammed intermediary carbon metabolism in the parasite
Authors: Loos Julia A. , Negro Perla S. , Ortega Hugo H. , Salinas Facundo J. , Arán Martín , Pellizza Leonardo , Salerno Graciela L. , Cumino Andrea C.
Published: September 2024

Metformin, a safe biguanide derivative with antiproliferative properties, has shown antiparasitic efficacy against the
Echinococcus
larval stage. Hence, we assessed the efficacy of a dose of 250 mg kg
−1
day
−1
in experimental models of advanced CE, at 6 and 12 months post-infection with oral and intraperitoneal administration, respectively. At this high dose, metformin reached intracystic concentrations between 0.7 and 1.7 mM and triggered Eg-TOR inhibition through AMPK activation by AMP-independent and -dependent mechanisms, which are dependent on drug dose. Cystic metformin uptake was controlled by increased expression of organic cation transporters in the presence of the drug. In both experimental models, metformin reduced the weight of parasite cysts, altered the ultrastructural integrity of their germinal layers, and reduced the intracystic availability of glucose, limiting the cellular carbon and energy charge and the proliferative capacity of metacestodes. This glucose depletion in the parasite was associated with a slight increase in cystic uptake of 2-deoxiglucose and the transcriptional induction of GLUT genes in metacestodes. In this context, drastic glycogen consumption led to increased lactate production and altered intermediary metabolism in treated metacestodes. Specifically, the fraction of reducing soluble sugars decreased twofold, and the levels of non-reducing soluble sugars, such as sucrose and trehalose, were modified in both cystic fluid and germinal cells. Taken together, our findings highlight the relevance of metformin as a promising candidate for CE treatment and warrant further research to improve the therapeutic conditions of this chronic zoonosis in humans.
Transcriptomic analyses of bacterial growth on fungal necromass reveal different microbial community niches during degradation
Authors: Novak Jessica K. , Kennedy Peter G. , Gardner Jeffrey G.
Published: September 2024

Bacteria are major drivers of organic matter decomposition and play crucial roles in global nutrient cycling. Although the degradation of dead fungal biomass (necromass) is increasingly recognized as an important contributor to soil carbon (C) and nitrogen (N) cycling, the genes and metabolic pathways involved in necromass degradation are less characterized. In particular, how bacteria degrade necromass containing different quantities of melanin, which largely control rates of necromass decomposition
in situ
, is largely unknown. To address this gap, we conducted a multi-timepoint transcriptomic analysis using three Gram-negative, bacterial species grown on low or high melanin necromass of
Hyaloscypha bicolor
. The bacterial species,
Cellvibrio japonicus, Chitinophaga pinensis
, and
Serratia marcescens
, belong to genera known to degrade necromass
in situ
. We found that while bacterial growth was consistently higher on low than high melanin necromass, the CAZyme-encoding gene expression response of the three species was similar between the two necromass types. Interestingly, this trend was not shared for genes encoding nitrogen utilization, which varied in
C. pinensis
and
S. marcescens
during growth on high vs low melanin necromass. Additionally, this study tested the metabolic capabilities of these bacterial species to grow on a diversity of C and N sources and found that the three bacteria have substantially different utilization patterns. Collectively, our data suggest that as necromass changes chemically over the course of degradation, certain bacterial species are favored based on their differential metabolic capacities.

IMPORTANCE

Fungal necromass is a major component of the carbon (C) in soils as well as an important source of nitrogen (N) for plant and microbial growth. Bacteria associated with necromass represent a distinct subset of the soil microbiome and characterizing their functional capacities is the critical next step toward understanding how they influence necromass turnover. This is particularly important for necromass varying in melanin content, which has been observed to control the rate of necromass decomposition across a variety of ecosystems. Here we assessed the gene expression of three necromass-degrading bacteria grown on low or high melanin necromass and characterized their metabolic capacities to grow on different C and N substrates. These transcriptomic and metabolic studies provide the first steps toward assessing the physiological relevance of up-regulated CAZyme-encoding genes in necromass decomposition and provide foundational data for generating a predictive model of the molecular mechanisms underpinning necromass decomposition by soil bacteria.
Virulence and transmission biology of the widespread, ecologically important pathogen of zooplankton,
Spirobacillus cienkowskii
Authors: Wale Nina , Freimark Claire B. , Ramirez Justin , Dziuba Marcin K. , Kafri Ahmad Y. , Bilich Rebecca , Duffy Meghan A.
Published: September 2024

Spirobacillus cienkowskii
(
Spirobacillus,
hereafter) is a widely distributed bacterial pathogen that has significant impacts on the population dynamics of zooplankton (
Daphnia spp
.)
,
particularly in months when
Daphnia
are asexually reproducing. However, little is known about
Spirobacillus’
virulence, transmission mode, and dynamics. As a result, we cannot explain the dynamics of
Spirobacillus
epidemics in nature or use
Spirobacillus
as a model pathogen, despite
Daphnia’s
tractability as a model host. Here, we work to fill these knowledge gaps experimentally. We found that
Spirobacillus
is among the most virulent of
Daphnia
pathogens, killing its host within a week and reducing host fecundity. We further found that
Spirobacillus
did not transmit horizontally among hosts unless the host died or was destroyed (i.e., it is an “obligate killer”). In experiments aimed at quantifying the dynamics of horizontal transmission among asexually reproducing
Daphnia
, we demonstrated that
Spirobacillus
transmits poorly in the laboratory. In mesocosms,
Spirobacillus
failed to generate epidemics; in experiments wherein individual
Daphnia
were exposed,
Spirobacillus’
transmission success was low. In the (limited) set of conditions we considered,
Spirobacillus’
transmission success did not change with host density or pathogen dose and declined following environmental incubation. Finally, we conducted a field survey of
Spirobacillus’
prevalence within egg cases (ephippia) made by sexually reproducing
Daphnia
. We found
Spirobacillus
DNA in ~40% of ephippia, suggesting that, in addition to transmitting horizontally among asexually reproducing
Daphnia
,
Spirobacillus
may transmit vertically from sexually reproducing
Daphnia
. Our work fills critical gaps in the biology of
Spirobacillus
and illuminates new hypotheses vis-à-vis its life history.

IMPORTANCE

Spirobacillus cienkowskii
is a bacterial pathogen of zooplankton, first described in the 19
th
century and recently placed in a new family of bacteria, the
Silvanigrellaceae
.
Spirobacillus
causes large epidemics in lake zooplankton populations and increases the probability that zooplankton will be eaten by predators. However, little is known about how
Spirobacillus
transmits among hosts, to what extent it reduces host survival and reproduction (i.e., how virulent it is), and what role virulence plays in
Spirobacillus
’ life cycle. Here, we experimentally quantified
Spirobacillus’
virulence and showed that
Spirobacillus
must kill its host to transmit horizontally. We also found evidence that
Spirobacillus
may transmit vertically via
Daphnia’
s seed-like egg sacks. Our work will help scientists to (i) understand
Spirobacillus
epidemics, (ii) use
Spirobacillus
as a model pathogen for the study of host-parasite interactions, and (iii) better understand the unusual group of bacteria to which
Spirobacillus
belongs.
PRRSV non-structural protein 5 inhibits antiviral innate immunity by degrading multiple proteins of RLR signaling pathway through FAM134B-mediated ER-phagy
Authors: Wang Jing , Sun Huiqin , Li Rui , Xu Shixuan , Guo Junqing , Xing Guangxu , Jia Bin , Qiao Songlin , Chen Xin-xin , Zhang Gaiping
Published: September 2024

Viruses employ various evasion strategies to establish prolonged infection, with evasion of innate immunity being particularly crucial. Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen in swine industry, characterized by reproductive failures in sows and respiratory distress in pigs of all ages, leading to substantial economic losses globally. In this study, we found that the non-structural protein 5 (Nsp5) of PRRSV antagonizes innate immune responses via inhibiting the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs), which is achieved by degrading multiple proteins of RIG-I-like receptor (RLR) signaling pathway (RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7). Furthermore, we showed that PRRSV Nsp5 is located in endoplasmic reticulum (ER), where it promotes accumulation of RLR signaling pathway proteins. Further data demonstrated that Nsp5 activates reticulophagy (ER-phagy), which is responsible for the degradation of RLR signaling pathway proteins and IFN-I production. Mechanistically, Nsp5 interacts with one of the ER-phagy receptor family with sequence similarity 134 member B (FAM134B), promoting the oligomerization of FAM134B. These findings elucidate a novel mechanism by which PRRSV utilizes FAM134B-mediated ER-phagy to elude host antiviral immunity.

IMPORTANCE

Innate immunity is the first line of host defense against viral infections. Therefore, viruses developed numerous mechanisms to evade the host innate immune responses for their own benefit. PRRSV, one of the most important endemic swine viruses, poses a significant threat to the swine industry worldwide. Here, we demonstrate for the first time that PRRSV utilizes its non-structural protein Nsp5 to degrade multiple proteins of RLR signaling pathways, which play important roles in IFN-I production. Moreover, FAM134B-mediated ER-phagy was further proved to be responsible for the protein’s degradation. Our study highlights the critical role of ER-phagy in immune evasion of PRRSV to favor replication and provides new insights into the prevention and control of PRRSV.
Genetic characteristics of human parainfluenza viruses 1–4 associated with acute lower respiratory tract infection in Chinese children, during 2015–2021
Authors: Zhu Yun , Sun Yun , Li Changchong , Lu Gen , Jin Rong , Xu Baoping , Shang Yunxiao , Ai Junhong , Wang Ran , Duan Yali , Chen Xiangpeng , Xie Zhengde
Published: September 2024

Human parainfluenza viruses (HPIVs) are a significant cause of acute lower respiratory tract infections (ALRTIs) among young children and elderly individuals worldwide. The four types of HPIVs (HPIV1–4) can cause recurrent infections and pose a significant economic burden on health care systems globally. However, owing to the limited availability of complete genome sequences, the genetic evolution of these viruses and the development of vaccines and antiviral treatments are hampered. To address this issue, this study utilized next-generation sequencing to obtain 156 complete genome sequences of HPIV1–4, which were isolated from hospitalized children with ALRTIs in six regions of China between 2015 and 2021. This study revealed multiple clades, lineages, or sublineages of HPIVs circulating in mainland China, with a novel clade D of HPIV1 identified as geographically restricted to China. Moreover, this study identified the endemic dominant genotype of HPIV3, lineage C3, which has widely spread and continuously circulated in China. Bioinformatic analysis of the genome sequences revealed that the proteins of HPIV3 possessed the most variable sites, with the P protein showing more diversity than the other proteins among all types of HPIVs. The HN proteins of HPIV1–3 are all under negative/purifying selection, and two amino acid substitutions in the HN proteins correspond to known mAb neutralizing sites in the two HPIV3 strains. These findings provide crucial insights into the genetic diversity and evolutionary dynamics of HPIVs circulating among children in China and may facilitate research on the molecular diagnosis, vaccine development, and surveillance of HPIVs.

IMPORTANCE

Phylogenetic analysis revealed the prevalence of multiple clades, lineages, or sublineages of human parainfluenza viruses (HPIVs) circulating in mainland China. Notably, a unique evolutionary branch of HPIV1 containing only Chinese strains was identified and designated clade D. Furthermore, in 2023, HPIV3 strains from Pakistan and Russia formed a new lineage within clade C, named C6. The first HPIV4b sequence obtained in this study from China belongs to lineage C2. Evolutionary rate assessments revealed that both the HN and whole-genome sequences of HPIV3 presented the lowest evolutionary rates compared with those of the other HPIV types, with rates of 6.98E−04 substitutions/site/year (95% HPD: 5.87E−04 to 8.25E−03) and 5.85E−04 substitutions/site/year (95% HPD: 5.12E−04 to 6.62E−04), respectively. Recombination analysis revealed a potential recombination event in the F gene of an HPIV1 strain in this study. Additionally, all the newly obtained HPIV1–3 strains exhibited negative selection pressure, and two mutations were identified in the HN protein of two HPIV3 strains at monoclonal antibody-binding sites.
Exploring pangenomic diversity and CRISPR-Cas evasion potential in jumbo phages: a comparative genomics study
Authors: Magar Sharayu , Kolte Vaishnavi , Sharma Gaurav , Govindarajan Sutharsan
Published: September 2024

Jumbo phages are characterized by their remarkably large-sized genome and unique life cycles. Jumbo phages belonging to Chimalliviridae family protect the replicating phage DNA from host immune systems like CRISPR-Cas and restriction-modification system through a phage nucleus structure. Several recent studies have provided new insights into jumbo phage infection biology, but the pan-genome diversity of jumbo phages and their relationship with CRISPR-Cas targeting beyond Chimalliviridae are not well understood. In this study, we used pan-genome analysis to identify orthologous gene families shared among 331 jumbo phages with complete genomes. We show that jumbo phages lack a universally conserved set of core genes but identified seven “soft-core genes” conserved in over 50% of these phages. These genes primarily govern DNA-related activities, such as replication, repair, or nucleotide synthesis. Jumbo phages exhibit a wide array of accessory and unique genes, underscoring their genetic diversity. Phylogenetic analyses of the soft-core genes revealed frequent horizontal gene transfer events between jumbo phages, non-jumbo phages, and occasionally even giant eukaryotic viruses, indicating a polyphyletic evolutionary nature. We categorized jumbo phages into 11 major viral clusters (VCs) spanning 130 sub-clusters, with the majority being multi-genus jumbo phage clusters. Moreover, through the analysis of hallmark genes related to CRISPR-Cas targeting, we predict that many jumbo phages can evade host immune systems using both known and yet-to-be-identified mechanisms. In summary, our study enhances our understanding of jumbo phages, shedding light on their pan-genome diversity and remarkable genome protection capabilities.

IMPORTANCE

Jumbo phages are large bacterial viruses known for more than 50 years. However, only in recent years, a significant number of complete genome sequences of jumbo phages have become available. In this study, we employed comparative genomic approaches to investigate the genomic diversity and genome protection capabilities of the 331 jumbo phages. Our findings revealed that jumbo phages exhibit high genetic diversity, with only a few genes being relatively conserved across jumbo phages. Interestingly, our data suggest that jumbo phages employ yet-to-be-identified strategies to protect their DNA from the host immune system, such as CRISPR-Cas.
Radiolarian-based stratigraphic reconstruction along the western Yarlung-Tsangpo suture zone, southern Tibet, and its implication for Neo-Tethyan late-stage evolution
Authors: Cheng Jianbo , Li Yalin , Li Xin , Xiao Siqi , Li Shuai , Bi Wenjun , He Zhihao , Ma Xingduo , Li Zijian , Zhou Rui
Published: September 2024

Mélange complexes and continental marginal deposits along suture zones can provide crucial insights into the subduction-accretion processes of oceanic lithosphere and continent-continent collisions. Herein, moderately to well-preserved Late Jurassic–Early Cretaceous and late Paleocene radiolarian assemblages, including 86 species within 52 genera, were identified in the Jiangmuna mélange and the adjacent Tethyan Himalayan sedimentary strata along the western Yarlung-Tsangpo suture zone, southern Tibet. Reconstruction of the ocean plate stratigraphy revealed that the Jiangmuna mélange represents the products of fragmentation and mixing of Early Jurassic–Late Cretaceous ocean plate materials originally accumulated in different portions of the central Neo-Tethyan domain. The bottom-up lithological transition and the southward-younger seamount system indicate that the Neo-Tethyan oceanic lithosphere was subducted northward beneath the Zhongba microterrane, and then the Jiangmuna mélange was accreted one unit after another along the southern margin of the Zhongba microterrane during the Late Cretaceous. The adjacent Tethyan Himalayan sedimentary strata were originally deposited in a continental slope-basin environment along the northern margin of the Indian plate since the Middle Jurassic. The occurrence of Selandian–Thanetian radiolarian assemblages implies that deep-water sedimentation persisted along the northern margin of the Indian plate until at least the late Paleocene. Our findings, combined with previously published data, indicate that the Neo-Tethys Ocean existed at least from the Early Jurassic to late Paleocene, and the Neo-Tethyan late-stage evolution involved at least two subduction-accretion systems along the southern margins of the Lhasa block and the Zhongba microterrane, respectively, prior to the two-stage India-Eurasia collision.
NovelABCC8mutation in the genetic diagnosis of familial hyperinsulinaemic hypoglycaemia
Authors: Kattamanchi Deepthi , Maralusiddappa Pradeep Gejjegenahalli Channabasapp , Manne Veerabhadraiah Krithika , Mangalgi Sharanabasavesh
Published: September 2024

Familial hyperinsulinaemic hypoglycaemia-1 arises from mutations within the genes of pancreatic beta cells, resulting in unregulated insulin secretion from pancreatic beta cells. A 4.06 kg female neonate, born to a second-degree consanguineously married couple, presented with repeated asymptomatic hypoglycaemia. There was a significant history of a previous sibling’s death from nesidioblastosis. Despite treatment with intravenous glucose, diazoxide, hydrochlorothiazide and octreotide, she continued to experience hypoglycaemic episodes. Despite efforts to manage sepsis, including antibiotics, antifungals and intravenous immunoglobulin/granulocyte-macrophage colony‐stimulated factor, her condition worsened. She succumbed on day 34. This case underscores the complexities of managing congenital hyperinsulinaemic hypoglycaemia, especially in the context of concurrent infections and the need for multidisciplinary care. Early genetic diagnosis proved invaluable in facilitating timely and effective treatment. Furthermore, the genetic results enabled us to counsel the parents regarding the recurrence risk in subsequent pregnancies and the necessity for antenatal diagnosis.