bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel KCND3 variant in the N‐terminus impairs the ionic current of Kv4.3 and is associated with SCA19/22
Authors: Reis Marlen Colleen , Mandler Laura , Kang Jun‐Suk , Oliver Dominik , Halaszovich Christian , Nolte Dagmar 
Published: August 2024

AbstractSpinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant movement disorders. Among the SCAs associated with impaired ion channel function, SCA19/22 is caused by pathogenic variants in KCND3, which encodes the voltage‐gated potassium channel Kv4.3. SCA19/22 is clinically characterized by ataxia, dysarthria and oculomotor dysfunction in combination with other signs and symptoms, including mild cognitive impairment, peripheral neuropathy and pyramidal signs. The known KCND3 pathogenic variants are localized either in the transmembrane segments, the connecting loops, or the C‐terminal region of Kv4.3. We have identified a novel pathogenic variant, c.455A>G (p.D152G), localized in the N‐terminus of Kv4.3. It is located in the immediate neighbourhood of the T1 domain, which is responsible for multimerization with the β‐subunit KChIP2b and thus for the formation of functional heterooctamers. Electrophysiological studies showed that p.D152G does not affect channel gating, but reduces the ionic current in Kv4.3, even though the variant is not located in the transmembrane domains. Impaired channel trafficking to the plasma membrane may contribute to this effect. In a patient with a clinical picture corresponding to SCA19/22, p.D152G is the first pathogenic variant in the N‐terminus of Kv4.3 to be described to date with an effect on ion channel activity.
Simultaneous effective monitoring of Grapholita molesta and Cydia pomonella (Lepidoptera: Tortricidae) in traps with a dual sex pheromone/kairomone lure plus a UV‐A light
Authors: Knight Alan Lee , Mujica Valentina , Basoalto Esteban , Preti Michele 
Published: August 2024

AbstractStudies of oriental fruit moth (OFM), Grapholita molesta (Busck), and codling moth (CM), Cydia pomonella (L.) (Lepidoptera: Tortricidae), both important pests of pome fruit, evaluated the addition of low‐intensity light‐emitting diode (LED) to delta traps baited with 3 commercial monitoring lures. Studies were conducted in 9 orchards treated with and without sex pheromone mating disruption for one or both species. OFM was monitored with a two‐part pheromone/kairomone lure (OFM Combo Dual), while CM was monitored with either a two‐part kairomone lure (CM Dual 4 K) or a sex pheromone lure (CM PH). Both pests were monitored with or without the addition of three types of a low power LED light with peak intensity at 395 (UV‐A), 458 (blue), and 516 (green) nm. The UV‐A LED was found to be the most effective among the three lights for OFM. Unexpectedly, traps with the OFM Combo Dual lure plus UV‐A LED caught similar numbers of CM as traps baited with the CM Dual 4 K and CM PH lures alone. They also caught other pest species, such as oblique banded leafroller (OBLR), Choristoneura rosaceana (Harris), and peach twig borer (PTB), Anarsia lineatella (Zeller). Interestingly, in different trials the OFM Combo Dual combined with UV‐A LED light caught significantly more OFM and/or CM females compared to the OFM Combo Dual lure without light, opening the perspective for a female‐oriented monitoring and for a “female removal” management approach of these pests. The development of inexpensive, dual‐modality traps adding a light stimulus to a pheromone/kairomone lure may reduce monitoring costs in orchards with multiple moth pests, improving the trapping efficiency.
Metabolomic analysis revealed the inflammatory and oxidative stress regulation in response to Vibrio infection in Plectropomus leopardus
Authors: Wang Jie , Zhang Junwei , Shi Meng , Ma Xinran , Chen Songlin , Zhou Qian , Zhu Chunhua 
Published: August 2024

AbstractFrequent outbreaks of infectious diseases in aquaculture have led to significant economic losses. The leopard coral grouper (Plectropomus leopardus) often suffers from vibriosis. Improving host immunity presents a superior strategy for disease control, with minimal side effects compared to the use of antibiotics, highlighting the necessity of exploring the mechanisms underlying the fish's response to pathogen infections. Here, we conducted a comparative metabolomic analysis on the livers of the P. leopardus infected with Vibrio harveyi. A total of 1124 differential metabolites (DMs) were identified, with 190, 218, 359, and 353 DMs being identified at 6, 12, 24, and 48 h post‐infection (hpi), respectively. Then, based on the time series analysis, we found that the lipid metabolism pathways were modulated in response to the Vibrio infection, with an increase in the quantity of eicosanoids and gycerophospholipids (GPLs), as well as a decrease in the quantity of bile acids (BAs), vitamin D, and sex hormones. Furthermore, 13 enriched pathways involving 31 DMs were identified through KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses. We identified histamine, 15(S)‐HpETE, and anandamide in the transient receptor potential (TRP) channels pathway, as well as (7S,8S)‐DiHODE, 5S,8R‐DiHODE, and 13(S)‐HpODE in the linoleic acid (LA) metabolism pathway. The DM levels increased, which may be attributed to inflammation. The DMs in the thyroid hormone synthesis pathway were identified, and the contents of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) decreased, which may be crucial in antioxidants. Our findings highlighted the dynamic adjustments in lipid metabolism and the response to inflammation and oxidative stress during the infection of V. harveyi in P. leopardus. This study not only deepens our understanding of the metabolic underpinnings of fish immune responses but also lays the groundwork for research into functional metabolomics and mechanisms of disease resistance.
HSP110 is a modulator of amyloid beta (Aβ) aggregation and proteotoxicity
Authors: Montresor Sabrina , Pigazzini Maria Lucia , Baskaran Sudarson , Sleiman Mira , Adhikari Govinda , Basilicata Lukas , Secker Luca , Jacob Natascha , Ehlert Yara , Kelkar Anushree , Kalsi Gurleen Kaur , Kulkarni Niraj , Spellerberg Paul , Kirstein Janine 
Published: August 2024

AbstractChaperones safeguard protein homeostasis by promoting folding and preventing aggregation. HSP110 is a cytosolic chaperone that functions as a nucleotide exchange factor for the HSP70 cycle. Together with HSP70 and a J‐domain protein (JDP), HSP110 maintains protein folding and resolubilizes aggregates. Interestingly, HSP110 is vital for the HSP70/110/JDP‐mediated disaggregation of amyloidogenic proteins implicated in neurodegenerative diseases (i.e., α‐synuclein, HTT, and tau). However, despite its abundance, HSP110 remains still an enigmatic chaperone, and its functional spectrum is not very well understood. Of note, the disaggregation activity of neurodegenerative disease‐associated amyloid fibrils showed both beneficial and detrimental outcomes in vivo. To gain a more comprehensive understanding of the chaperone HSP110 in vivo, we analyzed its role in neuronal proteostasis and neurodegeneration in C. elegans. Specifically, we investigated the role of HSP110 in the regulation of amyloid beta peptide (Aβ) aggregation using an established Aβ‐C. elegans model that mimics Alzheimer's disease pathology. We generated a novel C. elegans model that over‐expresses hsp‐110 pan‐neuronally, and we also depleted hsp‐110 by RNAi‐mediated knockdown. We assessed Aβ aggregation in vivo and in situ by fluorescence lifetime imaging. We found that hsp‐110 over‐expression exacerbated Aβ aggregation and appeared to reduce the conformational variability of the Aβ aggregates, whereas hsp‐110 depletion reduced aggregation more significantly in the IL2 neurons, which marked the onset of Aβ aggregation. HSP‐110 also plays a central role in growth and fertility as its over‐expression compromises nematode physiology. In addition, we found that HSP‐110 modulation affects the autophagy pathway. While hsp‐110 over‐expression impairs the autophagic flux, a depletion enhances it. Thus, HSP‐110 regulates multiple nodes of the proteostasis network to control amyloid protein aggregation, disaggregation, and autophagic clearance.
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Investigating the impact of OCT imaging of the crystalline lens on the accuracy and precision of cataract assessment
Authors: Burke Niamh , Mulholland Pádraig J. , Keane Pearse A. , Little Julie‐Anne 
Published: August 2024

AbstractPurposeTo determine if supplementing standard clinical assessments with Optical Coherence Tomography (OCT) imaging of the crystalline lens improves the accuracy and precision of lens opacity assessment and associated clinical management decisions by optometrists.MethodsFifty optometrists registered in the UK or Éire undertook a clinical vignette study where participants graded lens opacities and made associated clinical management decisions based on the image(s)/information displayed. Three forms of vignettes were presented: (1) Slit‐lamp (SL) images of the lens, (2) SL and OCT images and (3) SL, OCT and visual function measures. Vignettes were constructed using anonymised data from 50 patients with varying cataract severity, each vignette being presented twice in a randomised order (total vignette presentations = 300). The accuracy of opacity and management decisions were evaluated using descriptive statistics and non‐parametric Bland–Altman analysis where assessments from experienced clinicians were the reference. The precision of assessments was examined for each vignette form using non‐parametric Bland–Altman analysis.ResultsAll (n = 50) participants completed the study, with 36 working in primary eyecare (primary eyecare) settings and 14 in hospital eyecare services (HES). Agreement was highest where vignettes contained all clinical data (i.e., SL, OCT and visual function data—grading: 51.0%, management: 50.5%), and systematically reduced with decreasing vignette content (p < 0.001). A larger number of vignettes containing imaging and visual function measures exhibited below reference (i.e., less conservative) grading compared with vignettes containing imaging data alone (all p < 0.05). HES‐based optometrists were more likely to grade lens opacities lower than clinicians working in primary eyecare (p < 0.001). Good measurement precision was evident for all vignettes, with a mean bias close to zero and limits of agreement below one grading step for all conditions.ConclusionsThe addition of anterior segment OCT to SL images improved the accuracy of lens opacity grading. Structural assessment alone yielded more conservative decision making, which reversed once visual functional data was available.
SUBSTANDARD STARCH GRAIN7 regulates starch grain size and endosperm development in rice
Authors: Yan Haigang , Ren Yulong , Zhang Binglei , Jin Jie , Du Feilong , Shan Zhuangzhuang , Fu Yushuang , Zhu Yun , Wang Xin , Zhu Changyuan , Cai Yue , Zhang Jie , Wang Fan , Zhang Xiao , Wang Rongqi , Wang Yongxiang , Xu Hancong , Jiang Ling , Liu Xi , Zhu Shanshan , Lin Qibing , Lei Cailin , Cheng Zhijun , Wang Yihua , Zhang Wenwei , Wan Jianmin 
Published: August 2024

SummaryStarch is synthesized as insoluble, semicrystalline particles within plant chloroplast and amyloplast, which are referred to as starch grains (SGs). The size and morphology of SGs in the cereal endosperm are diverse and species–specific, representing a key determinant of the suitability of starch for industrial applications. However, the molecular mechanisms modulating SG size in cereal endosperm remain elusive. Here, we functionally characterized the rice (Oryza sativa) mutant substandard starch grain7 (ssg7), which exhibits enlarged SGs and defective endosperm development. SSG7 encodes a plant–specific DUF1001 domain‐containing protein homologous to Arabidopsis (Arabidopsis thaliana) CRUMPLED LEAF (AtCRL). SSG7 localizes to the amyloplast membrane in developing endosperm. Several lines of evidence suggest that SSG7 functions together with SSG4 and SSG6, known as two regulators essential for SG development, to control SG size, by interacting with translocon‐associated components, which unveils a molecular link between SG development and protein import. Genetically, SSG7 acts synergistically with SSG4 and appears to be functional redundancy with SSG6 in modulating SG size and endosperm development. Collectively, our findings uncover a multimeric functional protein complex involved in SG development in rice. SSG7 represents a promising target gene for the biotechnological modification of SG size, particularly for breeding programs aimed at improving starch quality.
MdWRKY31‐MdNAC7 regulatory network: orchestrating fruit softening by modulating cell wall‐modifying enzyme MdXTH2 in response to ethylene signalling
Authors: Wang Jia‐Hui , Sun Quan , Ma Chang‐Ning , Wei Meng‐Meng , Wang Chu‐Kun , Zhao Yu‐Wen , Wang Wen‐Yan , Hu Da‐Gang 
Published: August 2024

SummarySoftening in fruit adversely impacts their edible quality and commercial value, leading to substantial economic losses during fruit ripening, long‐term storage, long‐distance transportation, and marketing. As the apple fruit demonstrates climacteric respiration, its firmness decreases with increasing ethylene release rate during fruit ripening and postharvest storage. However, the molecular mechanisms underlying ethylene‐mediated regulation of fruit softening in apple remain poorly understood. In this study, we identified a WRKY transcription factor (TF) MdWRKY31, which is repressed by ethylene treatment. Using transgenic approaches, we found that overexpression of MdWRKY31 delays softening by negatively regulating xyloglucan endotransglucosylase/hydrolases 2 (MdXTH2) expression. Yeast one‐hybrid (Y1H), electrophoretic mobility shift (EMSA), and dual‐luciferase assays further suggested that MdWRKY31 directly binds to the MdXTH2 promoter via a W‐box element and represses its transcription. Transient overexpression of ethylene‐induced MdNAC7, a NAC TF, in apple fruit promoted softening by decreasing cellulose content and increasing water‐soluble pectin content in fruit. MdNAC7 interacted with MdWRKY31 to form a protein complex, and their interaction decreased the transcriptional repression of MdWRKY31 on MdXTH2. Furthermore, MdNAC7 does not directly regulate MdXTH2 expression, but the protein complex formed with MdWRKY31 hinders MdWRKY31 from binding to the promoter of MdXTH2. Our findings underscore the significance of the regulatory complex NAC7–WRKY31 in ethylene‐responsive signalling, connecting the ethylene signal to XTH2 expression to promote fruit softening. This sheds light on the intricate mechanisms governing apple fruit firmness and opens avenues for enhancing fruit quality and reducing economic losses associated with softening.
X and Y Differences in Melanoma Survival Between the Sexes
Authors: Hersey Peter , Tseng Hsin‐Yi , Alavi Sara , Tiffen Jessamy 
Published: August 2024

ABSTRACTMarked differences in survival from melanoma are noted between men and women that cannot be accounted for by behavioral differences. We and others have provided evidence that this difference may be due to increased expression of immune‐related genes from the second X chromosome because of failure of X inactivation. In the present review, we have examined evidence for the contrary view that survival differences are due to weaker immune responses in males. One reason for this may be the loss of Y chromosomes (LOY), particularly in older males. The genes involved may have direct roles in immune responses or be noncoding RNAs that regulate both sex and autosomal genes involved in immune responses or tumor growth. Loss of the KDM6C and KDM5D demethylases appeared to common genes involved. The second factor appears to be the activation of androgen receptors (AR) on melanoma cells that increase their invasiveness and growth. Induction of T‐cell exhaustion by AR that limits immune responses against melanoma appeared a common finding. The development of treatments to overcome effects related to gene loss on Y poses challenges, but several avenues related to AR signaling appear worthy of further study in the treatment of metastatic disease.
Wittgenstein on mathematical facts
Authors: Berg Ásgeir 
Published: August 2024

AbstractThe status of mathematical facts has long been taken to be unclear in Wittgenstein's philosophy of mathematics, and often, it seems that he wants to eliminate mathematical facts in favour of facts about our beliefs or behaviour. In this paper, I argue that by reading Wittgenstein as a radical conventionalist, we can give a reading of the relevant passages according to which Wittgenstein doesn't deny that there are mathematical facts, but rather denies that one needs a metaphysical account of what mathematical facts are and how they relate to the world that goes beyond the minimal claims of radical conventionalism—that empirical facts about how we would find natural to project our training into new cases and the constitution of concepts by our agreement are enough. At the end of the paper, I discuss the implications of this reading on how to understand a rule's determination of its own application.
Providing red blood cells to facilitate organ transplant via normothermic perfusion techniques: A single‐center experience
Authors: Allen Elizabeth S. , Stephens Laura D. , Weber Nesinee , Brubaker Aleah L. , Hudson Ken , Pretorius Victor , Schnickel Gabriel , Kopko Patricia M. 
Published: August 2024

AbstractBackgroundNormothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are organ procurement and transport techniques that can improve organ quality, facilitate longer transport, and reduce postoperative complications, increasing organ availability and improving outcomes. NRP and NMP often require allogeneic red blood cells (RBCs). Our academic transfusion service began providing RBCs to support NRP and NMP for adult heart transplant (HT), orthotopic liver transplant (OLT), and multiorgan transplant (MOT) in August 2020.MethodsThis single‐center, retrospective study describes the implementation process and analyzes the characteristics of RBC support during the first 3 years of the perfusion programs. Timing and quantity of units issued and used, organ recipient demographics, and transplant outcomes were obtained from transfusion service and electronic medical records.ResultsFrom 2020 to 2023, the transfusion service received 233 requests to support NRP and NMP perfusion cases. Of these, 105 cases resulted in RBC use, and units were returned or discarded in 112 cases. A total of 131 patients received perfusion‐facilitated transplants (92 HT, 27 OLT, and 12 MOT). The majority of perfusion‐facilitated HTs utilized NRP (81/92, 88%), whereas most perfusion‐facilitated OLTs utilized NMP (21/27, 78%). Across all 233 requests, a total of 381 RBC units were used to facilitate 131 transplants, averaging 2.91 units/transplant.DiscussionProvision of RBCs for NRP and NMP techniques represents a novel method for transfusion services to support and facilitate life‐saving organ transplants with only modest product use, about three RBC units per organ transplant in this single‐center study.
Intraosseous contrast administration for coelomic computed tomography angiography in green iguanas (Iguana iguana): Preliminary findings show promise as an alternative to the intravenous route
Authors: Erickson Maëva C. M. , Gendron Karine P. , Aguilar Laura A. B. , Wyneken Jeanette , Walth Gregory B. , Gottdenker Nicole L. , Divers Stephen J. 
Published: August 2024

AbstractComputed tomography is commonly used to evaluate the reptile coelom. One challenge in the acquisition of contrast‐enhanced CT studies in reptiles is the difficulty in placing intravenous catheters due to the poor conspicuity of peripheral vessels. To overcome these limitations, intraosseous catheterization of the long bones (humerus, femur, and tibia) can be used. The purpose of this prospective study was to assess the feasibility and diagnostic value of contrast‐enhanced CT of the coelom using a femoral intraosseous route for contrast administration. Twelve healthy juvenile green iguanas were enrolled. In 9 of 12 iguanas, vascular phases were obtained, providing strong, homogeneous enhancement of the arterial and venous tree concurrently. In these nine cases, Phase #1, acquired 60 s after beginning the injection of contrast medium, provided maximal contrast between the hepatic parenchyma and hepatic vasculature. In the remaining three cases, injection failure resulted from intracortical placement of the catheter tip. Histological examination of the liver, kidneys, and femur was performed to determine the pathomorphological correlates of the CT findings; in a third of patients, some degree of contrast‐induced renal toxicity was documented, which in mammalians shows potential for reversibility. Four iguanas had iatrogenic structural damage to the femoral growth plates attributed to intraosseous catheter placement. A femoral intraosseous route can be used in green iguanas for iodinated contrast medium administration for CT angiography. For the greatest contrast between coelomic organs and vascular structures, at least one postcontrast acquisition 60 s after initiation of contrast administration is recommended when using this technique.
On finitely generated Engel branch groups
Authors: Petschick J. Moritz 
Published: August 2024

AbstractWe construct finitely generated Engel branch groups, answering a question of Fernández‐Alcober, Noce and Tracey on the existence of such objects. In particular, the groups constructed are not nilpotent, yielding the second known class of examples of finitely generated non‐nilpotent Engel groups following a construction by Golod from 1969. To do so, we exhibit groups acting on rooted trees with growing valency on which word lengths of elements are contracting very quickly under section maps. Our methods apply in principle to a wider class of iterated identities, of which the Engel words are a special case.