bluuebunny/crossref_metadata_2025 huggingface dataset:
Description of three new species of Gyrodactylus von Nordmann, 1832 (Monopisthocotylea: Gyrodactylidae) on Triplophysa species (Nemacheilidae) from Qinghai-Tibet Plateau
Authors: Jin X. , Li M. , Zhang D. , Zou H. , Cai J. , Amoah K. , Wang G.T. , Li W.X.
Published: November 2024

Three new species of Gyrodactylus were identified from the body surface of the Triplophysa species from the Qinghai-Tibet Plateau, Gyrodactylus triplorienchili n. sp. on Triplophysa orientalis in northern Tibet, G. yellochili n. sp. on T. sellaefer and T. scleroptera and G. triplsellachili n. sp. on T. sellaefer and T. robusta in Lanzhou Reach of the Yellow River. The three newly identified species share the nemachili group species’ characteristic of having inturning hamulus roots. Gyrodactylus triplorienchili n. sp. shared a quadrate sickle heel and a thin marginal hook sickle, two morphological traits that set them apart from G. yellochili n. sp. However, they may be identified by the distinct shapes of the sickle base and marginal hook sickle point. Gyrodactylus triplsellachili n. sp. had much larger opisthaptoral hard part size than the other two species. The three new species show relatively low interspecific differences of 2.9–5.3% p-distance for ITS1-5.85-ITS2 rDNA sequences. Phylogenetic analysis indicated that the three new species formed a well-supported monophyletic group (bp = 99) with the other nemachili group species.
Diabetes prevention after gestational diabetes: challenges and opportunities
Authors: Dunne Pauline , Sherry Deirbhile , O’Reilly Sharleen L.
Published: November 2024

Gestational diabetes mellitus (GDM) poses significant health concerns for women and their offspring, with implications that extend beyond pregnancy. While GDM often resolves postpartum, a diagnosis of GDM confers a greater risk of future type 2 diabetes (T2D) and other chronic illnesses. Furthermore, the intergenerational impact of GDM predisposes offspring to increased chronic disease risk. Despite the awareness of the short- and long-term consequences of GDM, translating this knowledge into prevention strategies remains challenging. Challenges arise from a lack of clarity among health professionals regarding roles and responsibilities in chronic disease prevention and women’s lack of awareness of the magnitude of associated health risks. These challenges are compounded by changes in the circumstances of new mothers as they adjust to balance the demands of infant and family care with their own needs. Insights into behaviour change strategies, coupled with advances in technology and digital healthcare delivery options, have presented new opportunities for diabetes prevention among women with a history of GDM. Additionally, there is growing recognition of the benefits of adopting an implementation science approach to intervention delivery, which seeks to enhance the effectiveness and scalability of interventions. Effective prevention of T2D following GDM requires a comprehensive person-centred approach that leverages technology, targeted interventions and implementation science methodologies to address the complex needs of this population. Through a multifaceted approach, it is possible to improve the long-term health outcomes of women with prior GDM.
Evaluation of CD1a immunostaining in the diagnosis of cutaneous leishmaniasis caused by Leishmania donovani in Sri Lanka
Authors: Riyal Hasna , Samaranayake Nilakshi , Amarathunga Priyani , Munidasa Deepani , Karunaweera Nadira
Published: November 2024

Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease, routinely diagnosed by direct light microscopy. The sensitivity of this method is dependent on the number of parasites present in the lesion. Immunoexpression of CD1a surface antigen by Leishmania amastigotes and its application as a diagnostic tool has been recently demonstrated in several species including Leishmania major, Leishmania tropica and Leishmania infantum. Leishmania donovani is the only reported species in Sri Lanka primarily causing CL and its CD1a status remains unexplored. We studied CD1a expression by amastigotes of L. donovani in skin biopsies from 116 patients with suspected CL. The biopsy sections were stained with CD1a clones O10 and MTB1 separately. Slit skin smear (SSS) results were considered the gold standard for diagnosis of CL. 103 cases were confirmed through SSS where 73 of them showed positive parasite staining for CD1a clone MTB1 with 70.9% sensitivity. Positivity was seen mostly in parasites closer to the epidermis. CD1a clone O10 failed to detect any amastigotes. Test sensitivity improved to 74.1% when the analysis was applied only to patients with low/no discernible Leishman-Donovan (LD) bodies in histology. Our findings show that CD1a clone MTB1 successfully stains amastigotes of L. donovani species and can be used as a supplementary diagnostic tool in detecting CL, especially when LD bodies are low in number. This method could be validated to detect other forms of leishmaniasis caused by L. donovani in Indian and sub-Saharan regions.
Ecology and phenology of the bat tick Argas (Carios) dewae (Acari: Argasidae)
Authors: Godinho Lisa , van Lieshout Emile , Griffiths Stephen , Kwak Mackenzie L.
Published: November 2024

Although 12 soft tick species (Argasidae) are native to Australia, the ecology of most is poorly known. Argas dewae parasitizes several insectivorous bat species and has been recorded on humans. Therefore, understanding its ecology is crucial for wildlife health management and public health preparedness. To address this knowledge gap, A. dewae populations were monitored from 2 bat hosts (Chalinolobus gouldii and Austronomus australis) using bat boxes at 3 sites in Victoria, Australia, for 28 months (July 2005–December 2007). A phenological profile undertaken for A. dewae revealed that tick load on bat hosts increased throughout winter and peaked in the first month of spring, before collapsing and remaining low throughout the drier late spring and summer periods. There was also further investigation of the relationship between 2 response variables (tick infestation risk and tick load) and a range of explanatory variables (body condition index, sex, age class, bioseason, site, bat density per nest box). In C. gouldii, site was the only significant predictor of A. dewae infestation risk, while load was correlated with several variables including age class, sex, bioseason, roost density and body condition index. This paper also reports the first records of A. dewae from 6 bat species in 3 bat families (Miniopteridae: Miniopterus australis; Molossidae: A. australis; Vespertilionidae: Chalinolobus morio, Myotis Macropus, Vespadelus darlingtonia, Vespadelus regulus) and a second record of A. dewae from a human. The first distribution records are presented for A. dewae in South Australia, the Australian Capital Territory and Queensland.
Rhipicephalus simus ticks: new hosts for phleboviruses
Authors: Munjita Samuel Munalula , Mubemba Benjamin , Tembo John , Bates Mathew , Munsaka Sody
Published: November 2024

Ticks are widespread arthropods that transmit microorganisms of veterinary and medical significance to vertebrates, including humans. Rhipicephalus simus, an ixodid tick frequently infesting and feeding on humans, may play a crucial role in transmitting infectious agents across species. Despite the known association of many Rhipicephalus ticks with phleboviruses, information on R. simus is lacking. During a study in a riverine area in Lusaka Zambia, ten R. simus ticks were incidentally collected from the grass and bushes and subjected to metagenomic next generation sequencing (mNGS) in 2 pools of 5. Analysis detected a diverse microbial profile, including bacteria 82% (32/39), fungi 15.4% (6/39), and viruses 2.6% (1/39). Notably, viral sequence LSK-ZM-102022 exhibited similarity to tick phleboviruses, sharing 74.92% nucleotide identity in the RdRp gene and 72% in the NP gene with tick-borne phlebovirus (TBPV) from Greece and Romania, respectively. Its RNA-dependent RNA polymerase (RdRp) encoding region carried conserved RdRp and endonuclease domains characteristic of phenuiviridae viruses. Phylogenetic analysis positioned LSK-ZM-102022 in a distinct but lone lineage within tick phleboviruses basal to known species like brown dog tick phlebovirus and phlebovirus Antigone. Pair-wise genetic distance analysis revealed similar findings. This study emphasizes the urgency of further research on the ecology, transmission dynamics, and pathogenic potential of LSK-ZM-102022 and related TBPVs, crucial for local and global preparedness against emerging tick-borne diseases.
The lost message of Nils Strindberg: Re-examining an 1897 Andrée balloon expedition mystery
Authors: Lantz Björn , Uusma Bea , Tjernström Michael
Published: November 2024

During the ill-fated 1897 Andrée balloon expedition, Nils Strindberg allegedly dropped a small tin containing a last message for his fiancée onto the island Fuglesongen in northwestern Svalbard, as the expedition crew passed over it in their hydrogen balloon, Örnen. Despite at least one lengthy search on Fuglesongen, the tin has never been found. This paper investigates the hypothesis that the tin was accidentally dropped onto Klovningen, a neighbouring island similar in size and shape, situated approximately 2.4 km east of Fuglesongen. A re-analysis of Strindberg’s original handwritten notes from the balloon flight, along with other primary sources and meteorological analyses, suggests that a targeted search for the tin on Klovningen could be a promising next step in solving this enduring mystery.
Electroretinographic responses to periodic stimuli in primates and the relevance for visual perception and for clinical studies
Authors: Kremers Jan , Huchzermeyer Cord
Published: November 2024

Currently, electroretinograms (ERGs) are mainly recorded while using flashes as stimuli. In this review, we will argue that strong flashes are not ideal for studying visual information processing. ERG responses to periodic stimuli may be more strongly associated with the activity of post-receptoral neurons (belonging to different retino-geniculate pathways) and, therefore, be more relevant for visual perception. We will also argue that the use of periodic stimuli may be an attractive addition to clinically available retinal electrophysiological methods.
The Sequence Argument Against the Procreation Asymmetry
Authors: Adelstein Matthew
Published: November 2024

The procreation asymmetry is a widely held view in ethics, claiming that one should make existing people happy but has no reason to make happy people. Here, I shall present a new objection demonstrating from modest premises that one has a reason to take a sequence of actions that simply creates a happy person; yet this judgment in combination with plausible principles about sequences of actions entails that one has some reason to simply create a happy person. Additionally, I will argue that one's reasons to create a happy person are quite strong.
Variation in the management and treatment of children with giant coronary artery aneurysm following Kawasaki disease
Authors: Chen Mia , Dionne Audrey , Choueiter Nadine F. , Harahsheh Ashraf S. , Tierney Seda , Navarro Castellanos Iñaki , Dahdah Nagib
Published: November 2024

Objectives:

Giant coronary artery aneurysms are rare but potentially fatal complications of Kawasaki disease. The lack of evidence-based recommendations on their management and treatment cause guidelines and practices to differ. We aimed to assess these variations.

Methods:

An anonymous online survey regarding surveillance, imaging, pharmacological management, and interventional practices was distributed among 134 physicians attending to Kawasaki disease patients worldwide. A p-value of <0.05 was deemed significant.

Results:

The majority (60%) of respondents were general paediatric cardiologists, and 29% interventional specialists. The average years in practice was 15 ± 9.6. Physicians from Asia had the most experience with giant coronary artery aneurysms. American practitioners preferred combining anticoagulants with aspirin. Beta-blockers and statins were more likely used in teenagers versus younger children. Cardiac catheterisation was most (52%) chosen for coronary surveillance in patients with echocardiogram anomalies, followed by Coronary CT-angiography. The indications for coronary intervention were split among respondents, regardless of geographic region or experience. The preferred treatment of coronary stenosis was percutaneous intervention (69%) versus bypass surgery. For thrombosis, thrombolytics (50%) were preferred over percutaneous (39%) and surgical (11%) interventions. Most (92%) preferred intervening in young children in a paediatric facility but were split between a paediatric and adult facility for older children. Most chose combined management by adult and paediatric specialists for either age-scenarios (70, 82%).

Conclusion:

As identified by our study, the lack of large studies and evidence-based recommendations cause uncertainty and ambivalence towards certain treatments. International collaborative efforts are needed to provide more robust evidence in the management of these patients.
Isolated very low QRS voltage in at least one frontal lead is associated with vasovagal syncope in children
Authors: Gao Yumeng , Xu Yanyan , Sun Yan , Zhang Qingyou
Published: November 2024

Objective:

To assess whether isolated very low QRS voltage of ≤0.3 mV in the frontal leads might be a marker for diagnosing paediatric vasovagal syncope and the risk of recurrence.

Methods:

We included 118 children with vasovagal syncope, comprising 70 males and 48 females in our retrospective analysis. All patients underwent head-up tilt test and supine 12-lead electrocardiography. Furthermore, the QRS voltage was measured from each one of the 12 leads on basal electrocardiography. Patients were followed up for 6–24 months (average, 16 months).

Results:

Eighty-six patients (73%) patients displayed isolated very low QRS voltage in frontal leads. Furthermore, the patients were classified into two groups based on the presence or absence of isolated very low QRS voltage. Enhanced syncopic spells over the past 6 months, and the positive rates of head-up tilt test were observed in patients having isolated very low QRS voltage in the frontal leads than those without isolated very low QRS voltage (p < 0.05). The single factor and time-to-event analyses also showed an increased syncope recurrence rate in patients with isolated very low QRS voltage in frontal leads when compared with those without isolated very low QRS voltage (p < 0.01).

Conclusions:

Isolated very low QRS voltage in frontal leads is correlated with the positive response of the head-up tilt test in children who experience syncope and its recurrence post-treatment. Hence, isolated very low QRS voltage in frontal leads might become a novel diagnostic indicator and a risk factor for syncope recurrence in children with vasovagal syncope.
Working memory multicomponent model outcomes in individuals with traumatic brain injury: Critical review and meta-analysis
Authors: Lambez Bar , Vakil Eli , Azouvi Philippe , Vallat-Azouvi Claire
Published: November 2024

Objective:

Traumatic Brain Injury (TBI) often leads to cognitive impairments, particularly regarding working memory (WM). This meta-analysis aims to examine the impact of TBI on WM, taking into account moderating factors which has received little attention in previous research, such as severity of injury, the different domains of Baddeley’s multi-component model, and the interaction between these two factors, as well as the interaction with other domains of executive functions.

Method:

Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic review and meta-analysis searched Google Scholar, PubMed, and PsycNET for studies with objective WM measures. Multiple meta-analyses were performed to compare the effects of TBI severity on different WM components. Twenty-four English, peer-reviewed articles, mostly cross-sectional were included.

Results:

TBI significantly impairs general WM and all Baddeley’s model components, most notably the Central Executive (d’ = 0.74). Severity categories, mild-moderate and moderate-severe, were identified. Impairment was found across severities, with “moderate-severe” demonstrating the largest effect size (d’ = 0.81). Individuals with moderate-severe TBI showed greater impairments in the Central Executive and Episodic Buffer compared to those with mild-moderate injury, whereas no such differences were found for the Phonological Loop and Visuospatial Sketchpad.

Conclusions:

These findings enhance our understanding of WM deficits in varying severities of TBI, highlighting the importance of assessing and treating WM in clinical practice and intervention planning.
AN EXAMPLE OF THE JANTZEN FILTRATION OF A D-MODULE
Authors: BOHUN SIMON , ROMANOV ANNA
Published: November 2024

We compute the Jantzen filtration of a

$\mathcal {D}$

-module on the flag variety of

$\operatorname {\mathrm {SL}}_2(\mathbb {C})$

. At each step in the computation, we illustrate the

$\mathfrak {sl}_2(\mathbb {C})$

-module structure on global sections to give an algebraic picture of this geometric computation. We conclude by showing that the Jantzen filtration on the

$\mathcal {D}$

-module agrees with the algebraic Jantzen filtration on its global sections, demonstrating a famous theorem of Beilinson and Bernstein.
THE PRODUCT OF A GENERALIZED QUATERNION GROUP AND A CYCLIC GROUP
Authors: DU SHAOFEI , LUO WENJUAN , YU HAO
Published: November 2024

Let
$X=GC$
be a group, where C is a cyclic group and G is either a generalized quaternion group or a dihedral group such that
$C\cap G=1$
. In this paper, X is characterized and, moreover, a complete classification for
$X$
is given, provided that G is a generalized quaternion group and C is core-free.
Wer Viewership and Queer Imag(in)ing: Thai Soap Opera Shadow of Love and Boys Love Media
Authors: Chao Shi-Yan , Chunsaengchan Palita , Chaochuti Thosaeng
Published: November 2024

This article brings film/media theory into Southeast Asian research through a revisionist queer approach. It contains two goals: addressing some recent developments about queer imag(in)ing in Thai media whilst reappraising the fundamental question of spectatorship via screen theory. Taking into account the more general issue of media specificity and the particular textual device of identity/gender-switch in several recent Thai television serials, we propose the notion of wer viewership: a mode of viewing practice that features viewer-text interaction through the perceptual-cognitive processes, and is characterised by wer/excessive aesthetics, multiple meanings, and diverse pleasures. Resonant with camp reading, wer viewership underlines how the viewer actively makes sense of the ambiguities about gender, particularly those along the extra-/diegetic interface. We use Thai soap opera Shadow of Love to illuminate the wer/excessive aesthetics rendered through its identity/gender play bordering on the extra-/diegetic divide, and the enhanced pleasures and meanings thus available to its extradiegetic active viewers. We stress, though, the expanded queer imag(in)ing in Shadow is not of total free interpretation, but is animated in relation to both the evolving discourses about gender/sexuality in Thailand, and the popularising homoerotic Boys Love (BL) media across Asia in recent years.
Persönlichkeitspsychologie
Authors: Kuhl Julius , Quirin Markus
Published: November 2024

Bei diesem Lehrbuch handelt es sich um die 2., vollständig überarbeitete Auflage des „Lehrbuchs der Persönlichkeitspsychologie“ von Julius Kuhl. Es beschreibt verschiedene traditionelle Sichtweisen und Ansätze aus der Persönlichkeits- und Motivationspsychologie sowie ihre wichtigsten Forschungsbefunde. Dies geschieht in einer Weise, dass ein integratives Verständnis der menschlichen Persönlichkeit und somit vernetztes Denken erleichtert wird. Die Kapitel sind nicht nach vorherrschenden theoretischen Ansätzen (Schulen) oder Forschungsthemen geordnet, sondern systematisch nach sieben psychischen Prozessebenen: Gewohnheiten, Temperament, Affekt, Stressbewältigung, Motive, komplexe Kognition und Selbststeuerung. Persönlichkeit lässt sich demnach als die für das Individuum typische Art und Weise beschreiben, wie das Zusammenwirken der verschiedenen Prozessebenen das Erleben und Handeln steuert.
Nach einem einleitenden Kapitel widmet sich jedes Kapitel des Lehrbuchs einer Prozessebene, behandelt theoretisch-historische Ansätze und stellt aktuelle Befunde vor. Das Lehrbuch schließt mit theoretischen und empirischen Entwicklungen, die das Zusammenwirken verschiedener Prozessebenen beleuchten, und einer Darstellung der Theorie der Persönlichkeits-System-Interaktionen. Zahlreiche Kästen mit Zusammenfassungen, Definitionen und Beispielen gliedern den Text und erleichtern das Lernen. Reflexions- und Übungsaufgaben dienen der Prüfungsvorbereitung.
Dynamic Coupling Between Intensified Physical Erosion and Asian Dust Activity Under Late Cenozoic Global Cooling
Authors: Wang Shuwen , Zan Jinbo , Heller Friedrich , Fang Xiaomin , Liu Xiaoming
Published: November 2024

Distinguishing the independent contributions of tectonic denudation and climate‐driven erosion on the production and supply of clastic materials of Chinese eolian deposits is important in understanding the dynamic links between global climate changes, tectonics, and Asian dust emission. Here, multi‐proxy rock magnetic records of detrital fractions of Chinese eolian deposits since ∼6 Ma, combined with further comparison with dust accumulation rates and geochemical data, suggest that limited production and supply of clastic materials of Chinese eolian deposits were observed between 5.6 and 4.4 Ma in a warmer climate, and thereafter an increasing trend is evident during a cooler world. We propose that intense physical erosion under cooler conditions caused increasing production of fresh detrital components, exerting dominant influences on the sediment supply to Asian eolian deposits. This study provides direct evidence of dynamic coupling between intensified physical erosion and Asian dust activity under late Cenozoic global cooling.
Quantifying the Mesoscale Contribution to FACs During a Magnetospheric Substorm
Authors: Gasparini S. , Kepko L. , Laundal K. M.
Published: November 2024

Mesoscales, which couple small to large scales, and vice‐versa, are critical to the magnetosphere‐ionosphere coupling. Optical and radar measurements indicate that dynamical mesoscale features are present in the ionosphere, however quantifying their contribution to the overall dynamics remains a challenge. We use a new ionospheric data assimilation technique, Lompe (Local mapping of the polar ionospheric electrodynamics), to specify ionospheric electrodynamics using a wide variety of input data and a priori assumptions about the physical nature of the ionospheric electric field. We isolate the terms of the ionospheric Ohm's law and find that mesoscale structures in the FACs are driven by Hall gradients, while the larger scale patterns are associated with the divergence of the electric field. We calculate the relative contribution of mesoscales to the overall FAC patterns during a magnetospheric substorm, and find that in the nightside, mesoscale FACs contribute up to 60% of the total.
Tectonic Implications of Early Permian Arc Rocks and Their Cretaceous to Early Cenozoic Reworking in Southern Lhasa Terrane, Tibet
Authors: Ding Huixia , Kohn Matthew J. , Zhang Zeming , Niu Zhixiang
Published: November 2024

The Lhasa terrane in southern Tibet occupies a central position in Asian tectonics, yet its pre‐Mesozoic petrologic and tectonic evolution is poorly constrained, especially the Southern Lhasa subterrane (SLS). Here, new zircon U–Pb ages, zircon trace element and Hf isotopic compositions, and whole‐rock geochemical data for mafic meta‐igneous rocks from the SLS distinguish three tectono‐thermal events at ∼290 Ma, ∼126 Ma and ∼49 Ma. Whole‐rocks and zircons with ages of the two older events have arc magma geochemistry, but Hf isotopes are distinct from Mesozoic Gangdese arc magmas. Zircon cores and, arguably, whole rocks instead derive from ∼290 Ma magma formed during southward subduction of Paleo‐Tethys beneath the SLS. These rocks later underwent Early Cretaceous (∼126 Ma) remelting and early Cenozoic (∼49 Ma) metamorphism with P–T conditions of ~800°C and 15.3 kbar, and record a retrograde P–T path characterized by exhumation with cooling, consistent with a collisional origin. These data suggest Permian igneous rocks underwent reworking during both the Early Cretaceous and the early Cenozoic, reaching crustal thicknesses of at least ~50 km during the early Eocene. Combined with regional data, Paleo‐Tethys evidently experienced early Permian double‐sided subduction within the Lhasa terrane, with back arc basins forming between the SLS and the Indian margin to the south. These back arc basins ultimately widened to form the Neo‐Tethys Ocean, which then subducted during the Mesozoic, leading to Cretaceous arc magmatism and overprinting, followed by early Cenozoic metamorphism and final reworking during collision with India.
Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics
Authors: Ye Ziyang , Li Genpeng , Lei Jianyong
Published: November 2024

Immune checkpoint proteins (ICPs) serve as critical regulators of the immune system, ensuring protection against damage due to overly activated immune responses. However, within the tumor environment, excessive ICP activation weakens antitumor immunity. Despite the development of numerous immune checkpoint blockade (ICB) drugs in recent years, their broad application has been inhibited by uncertainties about their clinical efficacy. A thorough understanding of ICP regulation in the tumor microenvironment is essential for advancing the development of more effective and safer ICB therapies. Extracellular vesicles (EVs), which are pivotal mediators of cell–cell communication, have been extensively studied and found to play key roles in the functionality of ICPs. Nonetheless, a comprehensive review summarizing the current knowledge about the crosstalk between EVs and ICPs in the tumor environment is lacking. In this review, we summarize the interactions between EVs and several widely studied ICPs as well as their potential clinical implications, providing a theoretical basis for further investigation of EV-related ICB therapeutic approaches.
Bessel beam optical coherence microscopy enables multiscale assessment of cerebrovascular network morphology and function
Authors: Glandorf Lukas , Wittmann Bastian , Droux Jeanne , Glück Chaim , Weber Bruno , Wegener Susanne , El Amki Mohamad , Leitgeb Rainer , Menze Bjoern , Razansky Daniel
Published: November 2024

Understanding the morphology and function of large-scale cerebrovascular networks is crucial for studying brain health and disease. However, reconciling the demands for imaging on a broad scale with the precision of high-resolution volumetric microscopy has been a persistent challenge. In this study, we introduce Bessel beam optical coherence microscopy with an extended focus to capture the full cortical vascular hierarchy in mice over 1000 × 1000 × 360 μm3 field-of-view at capillary level resolution. The post-processing pipeline leverages a supervised deep learning approach for precise 3D segmentation of high-resolution angiograms, hence permitting reliable examination of microvascular structures at multiple spatial scales. Coupled with high-sensitivity Doppler optical coherence tomography, our method enables the computation of both axial and transverse blood velocity components as well as vessel-specific blood flow direction, facilitating a detailed assessment of morpho-functional characteristics across all vessel dimensions. Through graph-based analysis, we deliver insights into vascular connectivity, all the way from individual capillaries to broader network interactions, a task traditionally challenging for in vivo studies. The new imaging and analysis framework extends the frontiers of research into cerebrovascular function and neurovascular pathologies.
Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway
Authors: Huang Guichuan , Yang Xiangsheng , Yu Qingyang , Luo Qun , Ju Chunrong , Zhang Bangyan , Chen Yijing , Liang Zihan , Xia Shu , Wang Xiaohua , Xiang Dong , Zhong Nanshan , Tang Xiao Xiao
Published: November 2024

Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.
Bone loss with aging is independent of gut microbiome in mice
Authors: You Xiaomeng , Yan Jing , Herzog Jeremy , Nobakhti Sabah , Campbell Ross , Hoke Allison , Hammamieh Rasha , Sartor R. Balfour , Shefelbine Sandra , Kacena Melissa A. , Chakraborty Nabarun , Charles Julia F.
Published: November 2024

Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors’ age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.
PRMT1-mediated methylation of ME2 promotes hepatocellular carcinoma growth by inhibiting ubiquitination
Authors: Zhang Shuai , Zhang Shuling , Xia Baijuan , Li Xueying , Jiang Hongyu , Feng Su , Xiang Yang , Qiu Ya , Zhou Shi , Luo Peng
Published: November 2024

The mitochondrial malic enzyme 2 (ME2), which is frequently elevated during carcinogenesis and may be a target for cancer therapy, catalyzes the conversion of malate to pyruvate. The processes controlling ME2 activity, however, remain largely unclear. In this work, we show that human hepatocellular carcinoma (HCC) tissues contain high levels of ME2 and that the methylation of ME2 stimulates the growth and migration of HCC cells. Furthermore, we observed that ME2 interacts with protein arginine methyltransferase 1 (PRMT1) and that ME2 enzymatic activity is activated by mutation of ME2 at lysine 67. Mitochondrial respiration was markedly increased by activated ME2, which promoted cell division and carcinogenesis. Furthermore, a negative prognosis for patients was strongly linked with the expression levels of PRMT1 and ME2 R67K in HCC tissues. These findings imply that hepatocellular carcinoma growth is aided by PRMT1-mediated ME2 methylation, that is an essential signaling event that cancer cells need to continue mitochondrial respiration.
ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases
Authors: Lobanova Evgeniia , Zhang Yu P. , Emin Derya , Brelstaff Jack , Kahanawita Lakmini , Malpetti Maura , Quaegebeur Annelies , Triantafilou Kathy , Triantafilou Martha , Zetterberg Henrik , Rowe James B. , Williams-Gray Caroline H. , Bryant Clare Elizabeth , Klenerman David
Published: November 2024

Immunotherapeutic strategies for Alzheimer’s and Parkinson’s disease would be facilitated by better measures of inflammation. Here we established an ultra-sensitive single-molecule pull-down immunoassay combined with direct stochastic optical reconstruction microscopy (dSTORM) to measure the number, size and shape of individual extracellular inflammasome ASC specks. We assayed human post-mortem brain, serum and cerebrospinal fluid of patients with Parkinson’s and Alzheimer’s as well as healthy elderly. The number of ASC specks increased and showed altered morphology in the blood of early-stage Parkinson’s and Alzheimer’s patients compared to controls, mimicking those found in the brain and cerebrospinal fluid. In serum samples we also measured the number of Aβ, p-tau and α-syn aggregates and formed a composite biomarker of (ASC + p-tau)/Aβ and (ASC + α-syn)/Aβ ratios that distinguished age-matched healthy controls from patients with early-stage Alzheimer’s with AUC of 92% and early-stage Parkinson’s with AUC of 97%. Our findings confirm ASC specks as a fluid candidate biomarker of inflammation for neurodegenerative diseases with blood being the main focus for further development as convenient sample for diagnostics and clinical trials.
A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation
Authors: Bertran M. Teresa , Walmsley Robert , Cummings Thomas , Aramburu Iker Valle , Benton Donald J. , Mora Molina Rocio , Assalaarachchi Jayalini , Chasampalioti Maria , Swanton Tessa , Joshi Dhira , Federico Stefania , Okkenhaug Hanneke , Yu Lu , Oxley David , Walker Simon , Papayannopoulos Venizelos , Suga Hiroaki , Christophorou Maria A. , Walport Louise J.
Published: November 2024

Peptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune responses and cellular reprogramming, although the full extent of its physiological roles is unexplored. Despite detailed molecular knowledge of PADI4 activation in vitro, we lack understanding of its regulation within cells, largely due to a lack of appropriate systems and tools. Here, we develop and apply a set of potent and selective PADI4 modulators. Using the mRNA-display-based RaPID system, we screen >1012 cyclic peptides for high-affinity, conformation-selective binders. We report PADI4_3, a cell-active inhibitor specific for the active conformation of PADI4; PADI4_7, an inert binder, which we functionalise for the isolation and study of cellular PADI4; and PADI4_11, a cell-active PADI4 activator. Structural studies with PADI4_11 reveal an allosteric binding mode that may reflect the mechanism that promotes cellular PADI4 activation. This work contributes to our understanding of PADI4 regulation and provides a toolkit for the study and modulation of PADI4 across (patho)physiological contexts.
Evasion of antiviral bacterial immunity by phage tRNAs
Authors: Azam Aa Haeruman , Kondo Kohei , Chihara Kotaro , Nakamura Tomohiro , Ojima Shinjiro , Nie Wenhan , Tamura Azumi , Yamashita Wakana , Sugawara Yo , Sugai Motoyuki , Cui Longzhu , Takahashi Yoshimasa , Watashi Koichi , Kiga Kotaro
Published: November 2024

Retrons are bacterial genetic elements that encode a reverse transcriptase and, in combination with toxic effector proteins, can serve as antiphage defense systems. However, the mechanisms of action of most retron effectors, and how phages evade retrons, are not well understood. Here, we show that some phages can evade retrons and other defense systems by producing specific tRNAs. We find that expression of retron-Eco7 effector proteins (PtuA and PtuB) leads to degradation of tRNATyr and abortive infection. The genomes of T5 phages that evade retron-Eco7 include a tRNA-rich region, including a highly expressed tRNATyr gene, which confers protection against retron-Eco7. Furthermore, we show that other phages (T1, T7) can use a similar strategy, expressing a tRNALys, to counteract a tRNA anticodon defense system (PrrC170).
Interferometry of quantum correlation functions to access quasiprobability distribution of work
Authors: Hernández-Gómez Santiago , Isogawa Takuya , Belenchia Alessio , Levy Amikam , Fabbri Nicole , Gherardini Stefano , Cappellaro Paola
Published: November 2024

The Kirkwood-Dirac quasiprobability distribution, intimately connected with the quantum correlation function of two observables measured at distinct times, is becoming increasingly relevant for fundamental physics and quantum technologies. This quasiprobability distribution can take non-positive values, and its experimental reconstruction becomes challenging when expectation values of incompatible observables are involved. Here, we use an interferometric scheme aided by an auxiliary system to reconstruct the Kirkwood-Dirac quasiprobability distribution. We experimentally demonstrate this scheme in an electron-nuclear spin system associated with a nitrogen-vacancy center in diamond. By measuring the characteristic function, we reconstruct the quasiprobability distribution of work and analyze the behavior of its first and second moments. Our results clarify the physical meaning of the work quasiprobability distribution in the context of quantum thermodynamics. Finally, we study the uncertainty of measuring the Hamiltonian of the system at two times, via the Robertson-Schrödinger uncertainty relation, for different initial states.
Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models
Authors: Dudášová Julie , Valenta Zdeněk , Sachs Jeffrey R.
Published: November 2024

Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models. The method is applied to two datasets from immunogenicity sub-studies of vaccine phase 3 clinical trials for zoster and dengue vaccines. Results show that using immunogenicity-based estimation of efficacy in subgroups using time-to-event models is more precise than the standard estimation. Incorporating immune correlate data in time-to-event models improves precision in estimating efficacy (i.e., yields narrower confidence intervals), which can assist vaccine developers and public health authorities in making informed decisions.
Mechanism for Vipp1 spiral formation, ring biogenesis, and membrane repair
Authors: Naskar Souvik , Merino Andrea , Espadas Javier , Singh Jayanti , Roux Aurelien , Colom Adai , Low Harry H.
Published: November 2024

The ESCRT-III-like protein Vipp1 couples filament polymerization with membrane remodeling. It assembles planar sheets as well as 3D rings and helical polymers, all implicated in mitigating plastid-associated membrane stress. The architecture of Vipp1 planar sheets and helical polymers remains unknown, as do the geometric changes required to transition between polymeric forms. Here we show how cyanobacterial Vipp1 assembles into morphologically-related sheets and spirals on membranes in vitro. The spirals converge to form a central ring similar to those described in membrane budding. Cryo-EM structures of helical filaments reveal a close geometric relationship between Vipp1 helical and planar lattices. Moreover, the helical structures reveal how filaments twist—a process required for Vipp1, and likely other ESCRT-III filaments, to transition between planar and 3D architectures. Overall, our results provide a molecular model for Vipp1 ring biogenesis and a mechanism for Vipp1 membrane stabilization and repair, with implications for other ESCRT-III systems.
Structural basis of the mechanism and inhibition of a human ceramide synthase
Authors: Pascoa Tomas C. , Pike Ashley C. W. , Tautermann Christofer S. , Chi Gamma , Traub Michael , Quigley Andrew , Chalk Rod , Štefanić Saša , Thamm Sven , Pautsch Alexander , Carpenter Elisabeth P. , Schnapp Gisela , Sauer David B.
Published: November 2024

Ceramides are bioactive sphingolipids crucial for regulating cellular metabolism. Ceramides and dihydroceramides are synthesized by six ceramide synthase (CerS) enzymes, each with specificity for different acyl-CoA substrates. Ceramide with a 16-carbon acyl chain (C16 ceramide) has been implicated in obesity, insulin resistance and liver disease and the C16 ceramide-synthesizing CerS6 is regarded as an attractive drug target for obesity-associated disease. Despite their importance, the molecular mechanism underlying ceramide synthesis by CerS enzymes remains poorly understood. Here we report cryo-electron microscopy structures of human CerS6, capturing covalent intermediate and product-bound states. These structures, along with biochemical characterization, reveal that CerS catalysis proceeds through a ping-pong reaction mechanism involving a covalent acyl–enzyme intermediate. Notably, the product-bound structure was obtained upon reaction with the mycotoxin fumonisin B1, yielding insights into its inhibition of CerS. These results provide a framework for understanding CerS function, selectivity and inhibition and open routes for future drug discovery.
Novel BMI cutoff points for obesity diagnosis in older Hispanic adults
Authors: Esparza-Hurtado Natalia , Martagon Alexandro J. , Hart-Vazquez Delia Patricia , Rodríguez-Tadeo Alejandra , González-Arellanes Rogelio
Published: November 2024

Current body mass index (BMI) cutoff points (≥ 30 kg/m2) underestimate obesity prevalence in older adults. The aim of the present study was to propose new BMI cutoff points for identifying obesity in older Hispanic adults. In this study, new internally derived (ID) BMI cutoff point for obesity in older Hispanic adults was developed by analyzing data from the National Health and Nutrition Survey of 2018–2019 from Mexico. To evaluate the performance/validation of this newly proposed cutoff point, data from the "Study of the 1000", conducted in Northern Mexico, was utilized. Sensitivity, and negative predictive value (NPV) were assessed using receiver operating characteristic analysis, with obesity defined by fat mass index (FMI; ≥ 9.0 kg/m2 for men and ≥ 12.0 kg/m2 for women) as the reference method. The newly proposed ID BMI cutoff point was ≥ 27.2 kg/m2 which demonstrated high sensitivity (≥ 99.4%) and NPV (≥ 99.5%) in the total sample. Furthermore, the prevalence of obesity estimated by the new BMI cutoff point was comparable to that estimated by the FMI. The newly proposed BMI cutoff point provides a more accurate identification of obesity in older Hispanic adults. These findings have implications for improving obesity diagnosis and management in this population.
Solvent and additive-controlled supramolecular isomerism in zinc coordination polymers
Authors: Khorshidi Ghazale , Notash Behrouz
Published: November 2024

A new series of Zn(II) supramolecular isomers containing ditopic 1,3-di(pyridin-4-yl)urea (4bpu) ligand were synthesized and characterized by infrared analysis, elemental analysis and TGA as well as single-crystal X-ray diffraction analysis. Four solvent-induced pseudopolymorphic zinc (II) coordination polymers (CPs), namely, {[Zn(4bpu)(OAc)2](CH3OH)}n (1), {[Zn(4bpu)(OAc)2](C2H5OH)}n (2), {[Zn(4bpu)(OAc)2](HOCH2CH2OH)}n (3), and {[Zn(4bpu)(OAc)2](0.5H2O)}n (4), were prepared by the reaction of Zn(OAc)2.2H2O and 4bpu via self-assembly under varying solvent systems. Also, a pair of polymorphic coordination polymers namely, {[Zn(4bpu)(OAc)2](CH3OH)}n (1α) and {[Zn3(4bpu)3(OAc)6](CH3OH)2}n(1β), was prepared in the presence of different organic additives. Single-crystal X-ray diffraction confirmed that 1−4 and 1α display 1D polymeric zig-zag chains and 1β exhibits 1D triple-stranded ladders that were self-assembled through various supramolecular interactions. In addition, a series of dissolution-recrystallization structural transformations (DRST) were performed on these supramolecular isomers.
Expression profile of tsRNAs in white adipose tissue of vitamin D deficiency young male mice with or without obesity
Authors: Jia Qiaowei , Zhao Yan
Published: November 2024

The expression of tsRNA in white adipose tissue (WAT) of VD deficiency male mice with obesity has not been reported. The healthy male C57BL/6J mice aged 4-6 weeks were divided into 4 groups according to the VD3 and fat energy supplement in daily diets. The qPCR verification further demonstrated that tRF5-20-HisGTG-3 were significantly up-regulated and mt-tRF3a-ProTGG was significantly down-regulated not only in HFVDD vs HFVDS, but aslo in HFVDD vs ConVDS. tRF5-22-CysGCA-27 were significantly up-regulated and mt-5'tiRNA-32-SerTGA, mt-5'tiRNA-33-SerTGA and mt-5'tiRNA-33-AlaTGC was significantly down-regulated only in HFVDD vs ConVDS. Enrichment analysis of the qPCR verified DE tsRNAs showed that the 3 up-regulated tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−Oxocarboxylic acid metabolism, Autophagy-animal, Glucagon and insulin signaling pathway, while 4 down-regulated tsRNA seemed to be associated with cell communication, primary metabolic process, metabolic process, response to stimulus, multicellular organismal process, cellular metabolic process, cellular process and biological regulation. The tsRNAs were differentially expressed in VD deficiency with obesity, especially tRF5-20-HisGTG-3, tRF5-22-CysGCA-27, tRF3a-GlyGCC-1, mt-5'tiRNA-33-AlaTGC, mt-5'tiRNA-33-SerTGA, mt-5'tiRNA-32-SerTGA and mt-tRF3a-ProTGG. These tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−oxocarboxylic acid metabolism, autophagy, glucagon and insulin signaling pathway, metabolic process and biological regulation.