bluuebunny/crossref_metadata_2025 huggingface dataset:
The small RNA biogenesis in rice is regulated by MAP kinase‐mediated OsCDKD phosphorylation
Authors: Singh Dhanraj , Verma Neetu , Rengasamy Balakrishnan , Banerjee Gopal , Sinha Alok Krishna
Published: September 2024

CDKs are the master regulator of cell division and their activity is controlled by the regulatory subunit cyclins and phosphorylation by the CAKs. However, the role of MAP kinases in regulating plant cell cycle or CDKs have not been explored.

Here, we report that the MAP kinases OsMPK3, OsMPK4, and OsMPK6 physically interact and phosphorylate OsCDKD and its regulatory subunit OsCYCH in rice. MAP kinases phosphorylate CDKD at Ser‐168 and Thr‐235 residues in OsCDKD. The MAP kinase‐mediated phosphorylation of OsCDKD is required for its activation to control the small RNA biogenesis. The phosphodead version of OsCDKD fails to activate the C‐terminal domain of RNA Polymerase II, thereby negatively impacting small RNA transcription.

Further, the overexpression lines of wild‐type (WT) OsCDKD and phosphomimic OsCDKD show increased root growth, plant height, tiller number, panicle number, and seed number in comparison to WT, phosphodead OsCDKD‐OE, and kinase‐dead OsCDKD‐OE plants.

In a nutshell, our study establishes a novel regulation of OsCDKD by MAPK‐mediated phosphorylation in rice. The phosphorylation of OsCDKD by MAPKs imparts a positive effect on rice growth and development by regulating miRNAs transcription.
Predicting soil hydraulic conductivity using random forest, SVM, and LSSVM models
Authors: Farasati Masumeh , Seyedian Morteza , Fathaabadi Abolhasan
Published: September 2024

Understanding the hydraulic properties of soil is essential to solve many management problems in agriculture and the environment. Water quality affects soil hydraulic conductivity. Soil hydraulic properties play an important role in nature's water cycle and are used as basic information in designing irrigation and drainage systems, hydrological issues, and soil quality assessment. In the current study, soil sampling is performed from different areas and its hydraulic conductivity was measured using the drop load method and then predicted using support vector machine (SVM) and least‐squares support vector machine (LSSVM) models. The model inputs were: soil texture (percentage of sand, silt, and clay particles), salinity (electrical conductivity), pH, sodium adsorption ratio, soil porosity, and bulk density and the output was soil hydraulic conductivity. Correlation coefficient, root mean square error (RMSE), mean bias error (MBE), and Nash–Sutcliffe efficiency (NSE) were used to evaluate the models and compare them. Based on evaluation criteria the best performance was obtained for random forest (RF) (R = 0.89, RMSE = 0.53, mean absolute error (MAE) = 0.54, and NSE = 0.72). Following RF, the SVM with (R = 0.69, RMSE = 1.32, MAE = 0.69, and NSE = 0.48) performed better than LSSVM model.
Exploring Plant Diversity Through Enzyme‐Mediated Analysis Using Electro‐Carbon Sensors
Authors: Rachappanavar Vinaykumar
Published: September 2024

This review explores the application of enzyme‐mediated analysis using electro‐carbon sensors to investigate plant diversity. Precision plant genotype fingerprinting (PPGF) represents a paradigm shift in agricultural science, merging the fields of phyto‐enzyme identification and quantification with cutting‐edge electro‐sensor technology. PPGF acts as a powerful tool for dissecting the genetic makeup of plant species by meticulously examining their unique phyto‐enzyme signatures. Electro‐sensor technology emerges as a pioneering force, utilizing electro‐analytical methods to precisely measure and differentiate these markers. Enzyme‐based sensors are capable of detecting plant metabolites even at low concentrations, enabling highly precise and accurate measurements. Furthermore, they are generally more eco‐friendly because they use fewer hazardous chemicals and produce less waste. These sensors can function under gentle conditions and can be miniaturized, making them highly suitable for field applications. This synergistic approach between PPGF and electro‐sensor technology ushers in a transformative era, offering unprecedented insights into plant genomics and paving the way for novel avenues for PPGF. Overall, enzyme‐based electrochemical sensors contribute to improving the efficiency and effectiveness of plant fingerprinting, thereby facilitating more comprehensive and precise plant phenotyping and research endeavours.
Tyrosylprotein Sulfotransferase Positively Regulates Symbiotic Nodulation and Root Growth
Authors: Zhang Danping , Di Qi , Gui Jinshan , Li Qiong , Mysore Kirankumar S. , Wen Jiangqi , Luo Li , Yu Liangliang
Published: September 2024

Posttranslational tyrosine sulfation of peptides and proteins is catalysed by tyrosylprotein sulfotransferases (TPSTs). In Arabidopsis, tyrosine sulfation is essential for the activities of peptide hormones, such as phytosulfokine (PSK) and root meristem growth factor (RGF). Here, we identified a TPST‐encoding gene, MtTPST, from model legume Medicago truncatula. MtTPST expression was detected in all organs, with the highest level in root nodules. A promoter:GUS assay revealed that MtTPST was highly expressed in the root apical meristem, nodule primordium and nodule apical meristem. The loss‐of‐function mutant mttpst exhibited a stunted phenotype with short roots and reduced nodule number and size. Application of both of the sulfated peptides PSK and RGF3 partially restored the defective root length of mttpst. The reduction in symbiotic nodulation in mttpst was partially recovered by treatment with sulfated PSK peptide. MtTPST‐PSK module functions downstream of the Nod factor signalling to promote nodule initiation via regulating accumulation and/or signalling of cytokinin and auxin. Additionally, the small‐nodule phenotype of mttpst, which resulted from decreased apical meristematic activity, was partially complemented by sulfated RGF3 treatment. Together, these results demonstrate that MtTPST, through its substrates PSK, RGF3 and other sulfated peptide(s), positively regulates nodule development and root growth.
Wittgenstein's critical Philosophy of Mathematical Practice
Authors: Scheppers Frank
Published: September 2024

On the one hand, I show that the later Wittgenstein's practice‐based approach to meaning, including the idea that the meaningfulness of mathematics ultimately is rooted in the everyday ‘applications’ it emerged from, as well as his insistence on the variability in and contingency of mathematical and mathematics‐like practices, foreshadows more recent work in Philosophy of Mathematical Practice (PMP), although Wittgenstein's approach was more radically practice‐based than what is prevalent in present‐day PMP. On the other hand, I also show that Wittgenstein's work on mathematics is driven by a pervasive critical attitude towards some key characteristics (monism, foundationalism and exceptionalism) of mainstream philosophical discourse about mathematics (then and now), which is mostly absent from present‐day PMP, and I argue that this aspect of Wittgenstein's work on mathematics could inspire present‐day practitioners of PMP to rethink the identity of their discipline.
Non‐ideal epistemic rationality
Authors: Hughes Nick
Published: September 2024

I develop a broadly reliabilist theory of non‐ideal epistemic rationality and argue that if it is correct we should reject the recently popular idea that the standards of non‐ideal epistemic rationality are mere social conventions.
Gratitude and believing in someone
Authors: Lewis Max
Published: September 2024

I aim to vindicate the claim that we can owe someone gratitude for believing in us and to show how this seemingly prosaic fact has important upshots for the normativity of gratitude. I start by sketching a novel account of what it is to believe in someone according to which it consists in holding an affective attitude of confident optimism toward their general ability in some domain(s). I then argue that people can deserve gratitude for holding this attitude. I close by showing how the possibility of being gratitudeworthy for believing in someone casts down on three commonplaces about when gratitude is owed.
Emotions and the phenomenal grasping of epistemic blameworthiness
Authors: Magalotti Tricia
Published: September 2024

In this paper, I consider the potential implications of the observation that epistemic judgment seems to be less emotional than moral judgment. I argue that regardless of whether emotions are necessary for blame, blaming emotions do play an important epistemic role in the moral domain. They allow us to grasp propositions about moral blameworthiness and thereby to appreciate their significance in a special way. Further, I argue that if we generally lack blaming emotions in the epistemic domain, then we are unable to grasp propositions about epistemic blameworthiness. As a result, regardless of one's theory of epistemic blame, there emerges a tension between the claims that we are epistemically blameworthy for our epistemic failings and the claim that we do not feel epistemic blaming emotions.
Blaming the victim
Authors: Sliwa Paulina
Published: September 2024

Feminists critique acts and practices as victim‐blaming. Victim‐blaming is a moral phenomenon: to call a communicative act victim blaming is to criticise it. It is also a political phenomenon. As feminists point out, it plays a important role in perpetuating oppression. But what makes a communicative act an act of victim‐blaming? I propose that victim‐blaming communicative acts attribute responsibility to the victim for the wrong in contexts in which such attributions are morally improper. Attributions of responsibility can be morally imporoper in virtue of what they make salient in a conversation. Making salient the victim's conduct and backgrounding the conduct of the perpetrator can run afoul of the duties we have to the victim: including the duty to listen to the victim, to support her, and to hold the perpetrator responsible.
Life cycle and molecular phylogeny of Vaucheria piloboloides (Vaucheriales, Xanthophyceae) from Sado Island, Japan
Authors: Hoshino Masakazu , Tadokoro Satoru , Akita Shingo , Uwai Shinya
Published: September 2024

The siphonous, yellow–green alga Vaucheria piloboloides (Vaucheriales, Xanthophyceae) is the type species of the section Piloboloideae and is widely reported worldwide. Despite its taxonomic importance and broad range distribution, its detailed life cycle and molecular phylogenetic position are unknown. In the present study, we established culture strains of V. piloboloides collected from Sado Island, Niigata Prefecture, Japan, and examined its morphology, life cycle and phylogenetic position based on rbcL sequences. The morphology of the gametangia and aplanosporangia (asexual sporangia) of our samples, along with their monoecious nature, resembled that of V. piloboloides from the Atlantic coast, including the type locality. The rbcL phylogenetic analysis demonstrated that our sample formed a clade with other Piloboloideae species, supporting the current sectional scheme of Vaucheria. Under culture conditions, our samples exhibited a monophasic life cycle. Development of gametangia was observed in any culture conditions, whereas development of aplanosporangia could be induced by low salinity (salinity = 24).
Impacts of “Reef Star” coral restoration on multiple metrics of habitat complexity
Authors: Vida Rindah Talitha , Razak Tries B. , Mogg Andrew O. M. , Roche Ronan , Lynch Jason , Williams Ben ,   Mars Coral Restoration Project Monitoring Team, Alisa Cut Aja Gita , Subhan Beginer , Agus Syamsul B. , Graham Nicholas A. J. , Lamont Timothy A. C.
Published: September 2024

Coral reefs face threats from climate change and local pressures that lead to reductions in their physical structure, impacting biodiversity by limiting habitat availability. Despite many efforts to actively restore damaged reefs, few projects provide thorough evaluations of their success. This study measured the success of the “Reef Star” method at the Mars Coral Reef Restoration Project in Indonesia in reestablishing the physical structure of reef habitats that were destroyed by blast fishing. We used photogrammetry surveys to measure the physical habitat structure of 17 large sites (1000 m2 each), calculating three complementary measures of small‐ and large‐scale habitat complexity across degraded, restored, and naturally healthy coral reefs. We demonstrate that the restoration efforts have successfully restored small‐scale habitat complexity, as described by surface complexity metrics (3.22 ± 0.27 on restored reefs; 2.85 ± 0.26 on healthy reefs) and fractal dimension (2.27 ± 0.02 on restored reefs; 2.24 ± 0.02 on healthy reefs). This demonstrates the capacity for restored reefs to recover important ecosystem functions that are lost in degradation. However, while restoration has delivered some increases in large‐scale habitat complexity compared to degraded reefs, restored reefs still exhibit lower values of maximum vertical relief than healthy reefs, due to a lack of large physical structures. This lack of available large‐scale habitat might impact fish populations, meaning that restored reefs with limited large‐scale complexity may only support a restricted range of ecosystem functions. Effective reef restoration strategies must use a mixture of different methods that target the recovery of structural complexity at multiple scales.
Governing the European Union's recovery and resilience facility: National ownership and performance‐based financing in theory and practice
Authors: Zeitlin Jonathan , Bokhorst David , Eihmanis Edgars
Published: September 2024

The Recovery and Resilience Facility (RRF) adopted in response to the COVID‐19 pandemic marks an important departure in European Union (EU) governance, as it introduces an innovative “demand‐driven, performance‐based” model aimed at overcoming the limitations of past policies seeking to promote national reforms. In this study, we set out the theoretical assumptions underlying the RRF governance model, and assess its practical effectiveness and legitimacy by analyzing the drafting, implementation, and monitoring of National Recovery and Resilience Plans in eight member states. The study concludes by assessing the strengths and weaknesses of the RRF's governance model, relating them to theoretical expectations derived from previous international experience with similar approaches elsewhere, and considers the implications for future EU policy. Our core argument is that while the RRF's governance design has reinforced national ownership and commitment to reform and investment objectives, its performance‐based financing system leads to a mechanical focus on formal verification of predetermined milestones and targets, with negative consequences for both effectiveness and legitimacy. Addressing these problems would require a redesign of the RRF's complete contracting approach, giving member states greater flexibility on the means for achieving agreed commitments, as well as for revising them, not only in response to unanticipated changes in objective circumstances, but also to lessons learned during the implementation process.
On recognizing the real: Beauty and affliction in Simone Weil
Authors: Thomas Christopher
Published: September 2024

If the guiding question of ethics is “how should I live?,” then the guiding question of aesthetics might be “what is beauty?” For Simone Weil, these two questions have intertwined answers that turn on a like conceptual apparatus. Focussing on Weil's foremost ethical problem, the plight of the afflicted (malheur), this article offers an account of the philosophical basis to Weil's claim that, when truly recognized, beauty and affliction motivate the same form of experience. I argue that, for Weil, both the aesthetic and moral disposition are grounded in an experience of the real, an experience that both requires and compels the subject to the same attentive state. Finally, I address the charges that might be leveled at Weil for suggesting that our experience of beauty is the same as our experience of affliction, specifically arguing that rather than this experience leading to a form of passive aesthetic arrest, as the experience of beauty has typically been theorized to lead to, Weil understands the experience of beauty and affliction as fundamentally motivational toward the Good.
Attitudes toward abortion legality and abortion regulation: Insights from a nationally representative study
Authors: Jozkowski Kristen N. , Crawford Brandon L. , Hawbaker Amelia , Parker Erik , Golzarri Arroyo Lilian , Turner Ronna C.
Published: September 2024

Objective

National public opinion polls and surveys use different questions from one another to assess people's abortion attitudes. We included commonly asked abortion attitude items on a single survey to examine people's attitudes toward abortion legality and abortion restriction to create profiles of people which we then compared across state groups. Concurrently assessing attitudes toward both abortion legality and restrictions is important given the changing abortion legislative climate in the United States.

Method

We administered an online survey to U.S. adults (n = 919) via Ipsos probability panel and used latent class analysis to identify classes of participants. Then, we used multinominal logistic regression to make state‐level comparisons.

Results

We identified three classes: (1) 35.0 percent—abortion should be illegal/more restricted, (2) 35.1 percent—abortion should be legal/laws should reflect the status quo, and (3) 29.9 percent—abortion should be legal/more available. Trigger‐law states comprise the largest proportion of people who think abortion should be illegal/more restricted, whereas states without trigger laws comprise similar proportions of people from all three classes.

Conclusion

Concurrently measuring whether people believe abortion should be legal and the extent it should be restricted can provide a more comprehensive understanding of people's attitudes and demonstrates important state‐level nuances in attitudes.
Region‐specific diversification dynamics and biogeographic history of one of the most diverse families of insects
Authors: Ghanavi Hamid Reza , Chazot Nicolas , Sanmartín Isabel , Murillo‐Ramos Leidys , Duchêne Sebastián , Sihvonen Pasi , Brehm Gunnar , Wahlberg Niklas
Published: September 2024

A long‐standing question in evolutionary biology is how historical biogeographic processes have shaped the current diversity of organisms, especially for highly diverse groups. We study the diversification dynamics and biogeographic processes of one of the most diverse families of Lepidoptera, Geometridae, with over 24,000 described species and a worldwide distribution. Despite the cosmopolitan distribution of the family, most species of Geometridae have limited distribution ranges. We present the largest historical biogeography and diversification study on the current diversity patterns and distribution ranges of Geometridae. We use a multi‐locus dataset of 1200 taxa to estimate the historical biogeography of Geometridae, implementing a Bayesian approach of the Dispersal‐Extinction‐Cladogenesis (DEC) model that incorporates palaeographic‐based dispersal graphs with uncertainty in geological ages in RevBayes. We also implement a Bayesian time‐variable, episodic birth–death model and a model that allows branch‐specific speciation rates to estimate the diversification dynamics in the family. Our results suggest that the most recent common ancestor of Geometridae was distributed in the New World, with the Neotropics being the most likely ancestral area. An increase in diversification rates occurred circa 30–40 million years ago (Mya), coinciding with a time of a major global climate cooling in the Eocene. Clade‐specific shifts in speciation rates also occurred around 10–15 Mya, coincident with another period of major climate change in the Oligocene. Our results point to different biogeographical and evolutionary histories per area to show the differences of the diversification rates in different biogeographical regions through time, showing the relative importance of each region in the diversification history of Geometridae.
The development and evanescence of red blood cell antibodies after transfusion: A multi‐institutional prospective study in Japan
Authors: Yamada Chiaki , Ono Takaaki , Ino Kaede , Nemoto Naoki , Shinba Takahito , Furumaki Hiroaki , Shibata Hiroki , Ishizuka Keiko , Yamada Naotomo , Matsuura Hideaki , Izuhara Yumiko , Fujihara Harumi , Minamiguchi Hitoshi
Published: September 2024

Background

Despite several reports on red blood cell (RBC) alloimmunization, the actual prevalence and factors contributing to RBC alloimmunization in transfused patients remain poorly investigated. We examined the association between clinical factors and the development and evanescence of RBC antibodies after transfusion.

Study Design and Methods

Each participating institution performed antibody screens before and after RBC transfusion. A survey including patient characteristics, results of antibody screen and identification, antibody screen methods, total amount of RBC transfused, and adverse reactions, was conducted.

Results

Between October 2018 and March 2023, 1194 patients were registered at five institutions. Overall, 958 patients underwent at least one follow‐up RBC antibody screen after transfusion, revealing new antibody development in 44 (4.6%). Anti‐E was identified in 25 patients, anti‐Jka in 5, and anti‐c in 4. The number of RBC units transfused was significantly associated with antibody development after transfusion (p < .001). Among 55 patients in whom antibodies were identified after transfusion, including historical antibodies, antibodies evanesced in 18 (33%); anti‐E in 7, anti‐Jka in 4, and anti‐Lea in 2. Evanescent antibodies were identified more frequently by saline and/or enzyme methods than persistent antibodies (p = .012).

Discussion

The number of RBC units transfused can impact antibody development, and antibodies identified only by saline and/or enzyme methods, deemed clinically insignificant, are likely to have a high evanescence rate. Antibody screen should be carefully performed, especially in those receiving a large number of RBC units. Confirming previous antibody screen results should be performed to prevent omitting evanesced antibodies regardless of clinical relevance.
A Retrospective Study Evaluating the Outcomes of Conventionally Fractionated Radiation Therapy as a Treatment for Infiltrative Lipomas in Twenty‐One Dogs
Authors: Hauser Adam , Thorsen Lily , Boss Mary‐Keara , Martin Tiffany W.
Published: September 2024

Infiltrative lipomas represent a subcategorisation of rarer, potentially more aggressive, lipoma‐related neoplasms. Twenty‐one dogs treated with conventionally fractionated radiotherapy (CFRT) for infiltrative lipomas were included in this retrospective study. One patient had no prior surgical excision, 11 patients had one prior surgery and 9 patients had two or more surgeries prior to CFRT. Five patients (24%) had microscopic disease and 16 patients (76%) had macroscopic disease prior to treatment. A complete response or no regrowth was seen in 10 patients (48%), stable disease in 6 patients (29%) and progressive disease or regrowth in 5 patients (24%). Response to treatment of macroscopic tumours was significantly different between dogs that had one prior surgery versus two or more (p = 0.01). Dogs with a single surgery were most likely to result in stable disease compared with dogs with two or more surgeries resulting in a complete response. The dog without surgery developed progressive disease at 211 days, dogs with one surgery had a median progression or recurrence at 1369 days and dogs with two or more surgeries developed progression or recurrence at 826 days (p = 0.04). Twelve dogs were alive at the time of analysis. Overall median survival time (MST) was 1694 days. The prior number of surgeries did not significantly affect MST. While survival time is comparable to previous reports, the number of patients with progressive disease or recurrence of previous microscopic disease requires more investigation into the most appropriate protocol, dose and treated field size.
Impact of regression modeling on the assessment and harmonization of a point‐of‐care analyzer and commercial laboratory analyzer for feline plasma biochemistry testing
Authors: Baral Randolph M. , Flatland Bente , Jaensch Susan M. , Hayward Douglas A. , Freeman Kathleen P.
Published: September 2024

Background

Regression describes the relationship of results from two analyzers, and the generated equation can be used to harmonize results. Point‐of‐care (POC) analyzers cannot be calibrated by the end user, so regression offers an opportunity for calculated harmonization. Harmonization (uniformity) of laboratory results facilitates the use of common reference intervals and medical decision thresholds.

Objective

Our aims were to characterize the relationship of results for multiple biochemistry analytes on a POC and a commercial laboratory analyzer (CL) with three regression techniques and to use regression equations to harmonize the POC results with those of the CL. Harmonized results were assessed by recognized quality goals. We used harmonized results to assess the regression techniques.

Methods

After analyzer imprecision assessments, paired clinical samples were assessed with one dataset to calculate regression parameters that were applied to a second dataset. Three regression techniques were performed, and each was used to harmonize the POC results with those from the CL. POC results were assessed for bias and the number of results reaching quality goals before and after harmonization.

Results

All regression techniques could be used to harmonize most analytes so that 95% of results were within ASVCP TEa guidelines. Harmonization could be further improved with alternate regression techniques or exclusions.

Conclusions

Regression offers a means to harmonize POC and CL analyzers. Further work is needed to assess how few samples can reliably be used and to assess likely species differences. No regression technique reliably describes the relationship between methods when correlation is poor.
Lattice reduced and complete convex bodies
Authors: Codenotti Giulia , Freyer Ansgar
Published: September 2024

The purpose of this paper is to study convex bodies for which there exists no convex body of the same lattice width. Such bodies will be called ‘lattice reduced’, and they occur naturally in the study of the flatness constant in integer programming, as well as other problems related to lattice width. We show that any simplex that realizes the flatness constant must be lattice reduced and prove structural properties of general lattice reduced convex bodies: they are polytopes with at most vertices and their lattice width is attained by at least independent directions. Strongly related to lattice reduced bodies are the ‘lattice complete bodies’, which are convex bodies for which there exists no such that has the same lattice diameter as . Similar structural results are obtained for lattice complete bodies. Moreover, various construction methods for lattice reduced and complete convex bodies are presented.
Integrated care for adults with chronic musculoskeletal disorders: a scoping review protocol
Authors: Chala Mulugeta Bayisa , Elliott Jacobi , Baker G. Ross , Walton David M. , Steele Micheline , Schabrun Siobhan
Published: September 2024

Objective:

The objective of this scoping review is to describe the current evidence exploring integrated care for people with chronic musculoskeletal disorders.

Introduction:

The integrated model of care is an emerging approach to delivering person-centered care. Integrated care supports the management of people with major chronic health conditions; however, the evidence behind its use to support people with chronic musculoskeletal disorders is scant. This scoping review will synthesize how integrated care is conceptualized, delivered, and evaluated for people with chronic musculoskeletal disorders. The review will also synthesize the attributes, components, elements, goals, frequently evaluated outcomes, theories/frameworks, and facilitators and barriers to delivering this model among people with musculoskeletal disorders.

Inclusion criteria:

Studies conducted on the delivery and/or evaluation of integrated care for people with chronic musculoskeletal disorders in any health care setting (eg, primary, secondary, tertiary) and/or geographical location (countries, cultures) will be considered.

Methods:

The review will follow the JBI scoping review methodology. Databases such as MEDLINE (Ovid), CINAHL (EBSCOhost), Scopus, Embase (Ovid), PsycINFO (Ovid), the JBI EBP Database, PEDRO, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and Web of Science, as well as sources of gray literature, will be thoroughly searched. Papers published in all languages will be considered. Two reviewers will independently review the selected articles and extract data using a data extraction tool developed for this scoping review. The analysis will involve numerical and descriptive summaries of the selected articles and will be presented using graphs and tables, in line with Preferred Reported Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).
Lipopolysaccharide accelerates peristalsis by stimulating glucagon‐like peptide‐1 release from L cells in the rat proximal colon
Authors: Nakamori Hiroyuki , Niimi Atsuko , Mitsui Retsu , Hashitani Hikaru
Published: September 2024

Upon epithelial barrier dysfunction, lipopolysaccharide (LPS) stimulates glucagon‐like peptide‐1 (GLP‐1) secretion from enteroendocrine L cells by activating Toll‐like receptor 4 (TLR4). Because GLP‐1 accelerates peristalsis in the proximal colon, the present study aimed to explore whether LPS facilitates colonic peristalsis by stimulating L cell‐derived GLP‐1 release. In isolated segments of rat proximal colon that were serosally perfused with physiological salt solution and luminally perfused with 0.9% saline, peristaltic wall motion was video recorded and converted into spatio‐temporal maps. Fluorescence immunohistochemistry was also carried out. Intraluminal administration of LPS (100 or 1 µg mL−1 but not 100 ng mL−1) increased the frequency of oro‐aboral propagating peristaltic contractions. The LPS‐induced acceleration of colonic peristalsis was blocked by TAK‐242 (the TLR4 antagonist), exendin‐3 (the GLP‐1 receptor antagonist) or BIBN4096 (the calcitonin gene‐related peptide receptor antagonist). GLP‐1‐positive epithelial cells co‐expressed TLR4 immunoreactivity. In aspirin‐pretreated preparations where epithelial barrier function had been impaired, a lower dose of LPS (100 ng mL−1) became capable of accelerating peristalsis. By contrast, luminally applied dimethyl sulphoxide, a reactive oxygen species scavenger that protects epithelial integrity, attenuated the prokinetic effects of a higher dose of LPS (100 µg mL−1). In colonic segments of a stress rat model leading to a leaky gut, LPS induced more pronounced prokinetic effects. Colonic L cells may well sense luminal LPS via TLR4 triggering the release of GLP‐1 that stimulates calcitonin gene‐related peptide‐containing neurons. The resultant acceleration of peristalsis would facilitate excretion of Gram‐negative bacteria from the intestine, and thus L cells may have a protective role against intestinal bacterial infections.

image

Key points

Colonic epithelial cells form a barrier against bacterial invasion but also may contribute more actively to the exclusion of luminal pathogen by stimulating colonic motility.

Luminal lipopolysaccharide (LPS) accelerated colonic peristalsis by stimulating calcitonin gene‐related peptide‐containing neurons.

The prokinetic effect of LPS was mediated by the secretion of glucagon‐like peptide‐1 from enteroendocrine L cells in which Toll‐like receptor 4 was expressed.

The LPS‐mediated acceleration of peristalsis depended on epithelial barrier integrity.

L cells have a defensive role against Gram‐negative bacterial infections by facilitating faecal excretion, and could be a potential therapeutic target for gastrointestinal infections.
ISOLATION OF THE EXOSOMES FROM hUC-MSCs
Authors: Sekenova A.Ye. , Ogay V.B.
Published: September 2024

The studies on the potential application of exosomes isolated from stem cells are expanding every year. Researchers and medical clinics are interested in them in the regard that exosomes contain different molecules that have therapeutic and regeneration potential. This study aimed to investigate the exosomes of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs).
The hUC-MSCs were isolated from the human umbilical cord using the standard protocol. Obtained cells were cultivated till 3rd passage. Then, the conditioned medium (CM) was collected, centrifuged and ultracentrifuged using the standard protocol for exosome isolation. The isolated exosomes were identified in 63 x magnification in the inverted microscope and the concentration of DNA and RNA was measured by nanodrope equipment.
The obtained hUC-MSCs showed typical morphology of MSCs. We isolated exosomes from the CM of UC-MSCs. The obtained exosomes were round-shaped and had a distinct border. The DNA concentration and RNA concentration in obtained exosomes were 13.4 ng/ml and 17.0 ng/ml, respectively.
Our hUC-MSCs-derived exosomes demonstrated the initial characteristics of normal exosomes and also contained DNA and RNA. Further study is needed to determine their functional properties.
Monaural and binaural masking release with speech-like stimuli
Authors: Kim Hyojin , Ratkute Viktorija , Epp Bastian
Published: September 2024

The relevance of comodulation and interaural phase difference for speech perception is still unclear. We used speech-like stimuli to link spectro-temporal properties of formants with masking release. The stimuli comprised a tone and three masker bands centered at formant frequencies F1, F2, and F3 derived from a consonant-vowel. The target was a diotic or dichotic frequency-modulated tone following F2 trajectories. Results showed a small comodulation masking release, while the binaural masking level difference was comparable to previous findings. The data suggest that factors other than comodulation may play a dominant role in grouping frequency components in speech.
Expanding the Realms of Sport Psychology in Esports: An Epilogue
Authors: Swettenham Laura , Leis Oliver , Birch Phil , Price David
Published: September 2024

In this epilogue to the special issue, we provide a summary of four case studies in esports. Specifically, we draw attention to (1) interventions with teams and esports athletes, (2) coach support and development, and (3) practitioner development. We explore these areas in relation to the case studies presented in the special issue, providing a structured analysis and discussion of the experiences shared in these case studies and shedding light on how sport psychology is applied in esports. Lastly, we offer future research and practice opportunities for those intending to practice or currently practicing in the realm of esports.
Gentamicin and clindamycin antibiotic-eluting depot technology eradicates
S. aureus
in an implant-associated osteomyelitis pig model without systemic antibiotics
Authors: Henriksen Nicole L. , Serrano-Chávez Elizabeth , Fuglsang-Madsen Albert , Jensen Louise K. , Gottlieb Hans , Bue Mats , Andresen Thomas L. , Henriksen Jonas R. , Hansen Anders E.
Published: September 2024

The therapeutic challenges of orthopedic device-related infections and emerging antimicrobial resistance have attracted attention to drug delivery technologies. This study evaluates the preclinical efficacy of local single- and dual-antibiotic therapy against implant-associated osteomyelitis (IAO) using a drug-eluting depot technology, CarboCell, that provides sustained release of high-dose antibiotics and allows for strategic
in situ
placement in relation to infectious lesions. Clindamycin and gentamicin were formulated in CarboCell compositions. One-stage-revision of tibial
Staphylococcus aureus
IAO was conducted in 19 pigs. Pigs were treated locally with CarboCell containing either gentamicin alone for 1 week or a co-formulation of gentamicin and clindamycin for 1 or 3 weeks. Bone, soft tissue, and antibiotic depots were collected for microbiology, histology, and HPLC analyses. Supporting
in vivo
release studies of CarboCell formulations were performed on mice. Both single- and dual-antibiotic CarboCell formulations were developed and capable of eradicating the infectious bacteria in bone and preventing colonization of implants inserted at revision. Eradication in soft tissue was observed in all pigs after 3 weeks and in 6/9 pigs after 1 week of treatment. Neutrophil counts in bone tissue were below the infection cut-off in all pigs receiving the dual-antibiotic therapies, but above in all pigs receiving the single-antibiotic therapy. Histological signs of active bone reorganization and healing were observed at 3 weeks. In conclusion, all CarboCell formulations demonstrated strong therapeutic activity against IAO, eradicating
S. aureus
in bone tissue and preventing colonization of implants even without the addition of systemic antibiotic therapy.
Sporadic phage defense in epidemic
Vibrio cholerae
mediated by the toxin-antitoxin system DarTG is countered by a phage-encoded antitoxin mimic
Authors: Patel Kishen M. , Seed Kimberley D.
Published: September 2024

Bacteria and their viral predators (phages) are constantly evolving to subvert one another. Many bacterial immune systems that inhibit phages are encoded on mobile genetic elements that can be horizontally transmitted to diverse bacteria. Despite the pervasive appearance of immune systems in bacteria, it is not often known if these immune systems function against phages that the host encounters in nature. Additionally, there are limited examples demonstrating how these phages counter-adapt to such immune systems. Here, we identify clinical isolates of the global pathogen
Vibrio cholerae
harboring a novel genetic element encoding the bacterial immune system DarTG and reveal the immune system’s impact on the co-circulating lytic phage ICP1. We show that DarTG inhibits ICP1 genome replication, thus preventing ICP1 plaquing. We further characterize the conflict between DarTG-mediated defense and ICP1 by identifying an ICP1-encoded protein that counters DarTG and allows ICP1 progeny production. Finally, we identify this protein, AdfB, as a functional antitoxin that abrogates the toxin DarT likely through direct interactions. Following the detection of the DarTG system in clinical
V. cholerae
isolates, we observed a rise in ICP1 isolates with the functional antitoxin. These data highlight the use of surveillance of
V. cholerae
and its lytic phages to understand the co-evolutionary arms race between bacteria and their phages in nature.

IMPORTANCE

The global bacterial pathogen
Vibrio cholerae
causes an estimated 1 to 4 million cases of cholera each year. Thus, studying the factors that influence its persistence as a pathogen is of great importance. One such influence is the lytic phage ICP1, as once infected by ICP1,
V. cholerae
is destroyed. To date, we have observed that the phage ICP1 shapes
V. cholerae
evolution through the flux of anti-phage bacterial immune systems. Here, we probe clinical
V. cholerae
isolates for novel anti-phage immune systems that can inhibit ICP1 and discover the toxin-antitoxin system DarTG as a potent inhibitor. Our results underscore the importance of
V. cholerae
and ICP1 surveillance to elaborate novel means by which
V. cholerae
can persist in both the human host and aquatic reservoir in the face of ICP1.
SIRT7 remodels the cytoskeleton
via
RAC1 to enhance host resistance to
Mycobacterium tuberculosis
Authors: Li Fuxiang , Zhang Ximeng , Xu Jinjin , Zhang Yue , Li Guo , Yang Xirui , Deng Guofang , Dai Youchao , Liu Baohua , Kosan Christian , Chen Xinchun , Cai Yi
Published: September 2024

Phagocytosis of
Mycobacterium tuberculosis
(
Mtb
) followed by its integration into the matured lysosome is critical in the host defense against tuberculosis. How
Mtb
escapes this immune attack remains elusive. In this study, we unveiled a novel regulatory mechanism by which SIRT7 regulates cytoskeletal remodeling by modulating RAC1 activation. We discovered that SIRT7 expression was significantly reduced in CD14
+
monocytes of TB patients.
Mtb
infection diminished SIRT7 expression by macrophages at both the mRNA and protein levels. SIRT7 deficiency impaired actin cytoskeleton-dependent macrophage phagocytosis, LC3II expression, and bactericidal activity. In a murine tuberculosis model, SIRT7 deficiency detrimentally impacted host resistance to
Mtb
, while
Sirt7
overexpression significantly increased the host defense against
Mtb
, as determined by bacterial burden and inflammatory–histopathological damage in the lung. Mechanistically, we demonstrated that SIRT7 limits
Mtb
infection by directly interacting with and activating RAC1, through which cytoskeletal remodeling is modulated. Therefore, we concluded that SIRT7, in its role regulating cytoskeletal remodeling through RAC1, is critical for host responses during
Mtb
infection and proposes a potential target for tuberculosis treatment.

IMPORTANCE

Tuberculosis (TB), caused by
Mycobacterium tuberculosis
(
Mtb
), remains a significant global health issue. Critical to macrophages’ defense against
Mtb
is phagocytosis, governed by the actin cytoskeleton. Previous research has revealed that
Mtb
manipulates and disrupts the host’s actin network, though the specific mechanisms have been elusive. Our study identifies a pivotal role for SIRT7 in this context:
Mtb
infection leads to reduced SIRT7 expression, which, in turn, diminishes RAC1 activation and consequently impairs actin-dependent phagocytosis. The significance of our research is that SIRT7 directly engages with and activates Rac Family Small GTPase 1 (RAC1), thus promoting effective phagocytosis and the elimination of
Mtb
. This insight into the dynamic between host and pathogen in TB not only broadens our understanding but also opens new avenues for therapeutic development.
Gut microbiota-derived butyrate improved acute leptospirosis in hamster
via
promoting macrophage ROS mediated by HDAC3 inhibition
Authors: Chen Xi , Xie Xufeng , Sun Ni , Liu Xin , Liu Jiuxi , Zhang Wenlong , Cao Yongguo
Published: September 2024

Leptospirosis is a re-emerging worldwide zoonotic disease. Infected patients and animals often exhibit intestinal symptoms. Mounting evidence suggests that host immune responses to bacterial infection are closely associated with intestinal homeostasis. Our previous research has shown that the gut microbiota can protect the host from acute leptospirosis, while the specific bacterial metabolic mediators participating in the pathogenesis remain to be identified. Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota that play a role in immune regulation. However, whether SCFAs are the key to protecting the host against leptospirosis and the underlying regulatory mechanisms are unknown. In this study, our results showed that the SCFA butyrate is involved in ameliorating leptospirosis. The depletion of SCFAs by antibiotic cocktail treatment reduced survival time after
Leptospira
infection while supplementation with butyrate but not acetate or propionate significantly amelioration of leptospirosis.
In vitro
experiments showed that butyrate treatment enhanced the intracellular bactericidal activity mediated by reactive oxygen species (ROS) production. Mechanistically, butyrate functions as a histone deacetylase 3 inhibitor (HDAC3i) to promote ROS production
via
monocarboxylate transporter (MCT). The protection of butyrate against acute leptospirosis mediated by ROS was also proven
in vivo
. Collectively, our data provide evidence that the butyrate-MCT-HDAC3i-ROS signaling axis is a potential therapeutic target for acute leptospirosis. Our work not only interprets the microbial metabolite signaling involved in transkingdom interactions between the host and gut microbiota but also provides a possible target for developing a prevention strategy for acute leptospirosis.

IMPORTANCE

Leptospirosis is a worldwide zoonotic disease caused by
Leptospira
. An estimated 1 million people are infected with leptospirosis each year. Studies have shown that healthy gut microbiota can protect the host against leptospirosis but the mechanism is not clear. This work elucidated the mechanism of gut microbiota protecting the host against acute leptospirosis. Here, we find that butyrate, a metabolite of gut microbiota, can improve the survival rate of hamsters with leptospirosis by promoting the bactericidal activity of macrophages. Mechanistically, butyrate upregulates reactive oxygen species (ROS) levels after macrophage infection with
Leptospira
by inhibiting HDAC3. This work confirms the therapeutic potential of butyrate in preventing acute leptospirosis and provides evidence for the benefits of the macrophage-HDAC3i-ROS axis.
Reconceptualizing transcriptional slippage in plant RNA viruses
Authors: Valli Adrian A. , Domingo-Calap María Luisa , González de Prádena Alfonso , García Juan Antonio , Cui Hongguang , Desbiez Cécile , López-Moya Juan José
Published: September 2024

RNA viruses have evolved sophisticated strategies to exploit the limited encoded information within their typically compact genomes. One of them, named transcriptional slippage (TS), is characterized by the appearance of indels in nascent viral RNAs, leading to changes in the open reading frame (ORF). Although members of unrelated viral families express key proteins via TS, the available information about this phenomenon is still limited. In potyvirids (members of the
Potyviridae
family), TS has been defined by the insertion of an additional A at A
n
motifs (
n
≥ 6) in newly synthesized transcripts at a low frequency, modulated by nucleotides flanking the A-rich motif. Here, by using diverse experimental approaches and a collection of plant/virus combinations, we discover cases not following this definition. In summary, we observe (i) a high rate of single-nucleotide deletions at slippage motifs, (ii) overlapping ORFs acceded by slippage at an U
8
stretch, and (iii) changes in slippage rates induced by factors not related to cognate viruses. Moreover, a survey of whole-genome sequences from potyvirids shows a widespread occurrence of species-specific A
n
/U
n
(
n
≥ 6) motifs. Even though many of them, but not all, lead to the production of truncated proteins rather than access to overlapping ORFs, these results suggest that slippage motifs appear more frequently than expected and play relevant roles during virus evolution. Considering the potential of this phenomenon to expand the viral proteome by acceding to overlapping ORFs and/or producing truncated proteins, a re-evaluation of TS significance during infections of RNA viruses is required.

IMPORTANCE

Transcriptional slippage (TS) is used by RNA viruses as another strategy to maximize the coding information in their genomes. This phenomenon is based on a peculiar feature of viral replicases: they may produce indels in a small fraction of newly synthesized viral RNAs when transcribing certain motifs and then produce alternative proteins due to a change of the reading frame or truncated products by premature termination. Here, using plant-infecting RNA viruses as models, we discover cases expanding on previously established features of plant virus TS, prompting us to reconsider and redefine this expression strategy. An interesting conclusion from our study is that TS might be more relevant during RNA virus evolution and infection processes than previously assumed.