bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Tobacco Cessation Readiness in OPMD Patients Using the Transtheoretical Model in a tertiary care setting in Northeast India
Authors: Borah Pallabi , Talukdar Alpana , Pathak Bahni Shikha , Barbhuiya Maruf Hussain , Talukdar Bhaskarjyoti , Gogoi Antarika
Published: November 2024

Background: Oropharyngeal cancers pose significant global health challenges and addressing public awareness, early symptoms, and risk factors, alongside promoting tobacco cessation among individuals with potentially malignant oral disorders, is crucial for reducing the disease burden.Objective: Evaluating the degree of public knowledge of oral malignancy & OPMD, initial signs & risk factors amongst patients going to a dental college in North East India, as well as readiness to quit tobacco amongst OPMD patient.Methods: This cross-sectional investigation was undertaken at the Department of Public Health Dentistry, Tertiary care Hospital in Guwahati. 200 participants aged 15-65 years who consented were surveyed using a self-administered questionnaire. Collected data underwent thorough checks for completeness and accuracy. To determine the odd's ratio (OR) and to summarise the data, descriptive & inferential statistics were used. To test the relationship, data were dichotomised. Oral lesions present or absent; behavioural phases were divided into two categories: (preparation + action) & (precontemplation + contemplation). P < 0.05 was used as the statistical significance threshold.Results: Most participants were in the contemplation stage regarding tobacco's risks, neglecting other risk factors like alcohol & inadequate dental hygiene for oral malignancy/OPMD development.Conclusions: The lack of knowledge of oral malignancy & potentially malignant disorders (OPMDs) amongst North Eastern Indian communities, underscores the immediate demand for targeted education and health promotion campaigns. Emphasizing early symptom recognition, risk factors, and prevention measures, tailored to diverse communication preferences, is crucial.
The Reflection of Self in Postmodern Labyrinth: An inquisitive Study in Stephen king’s The Mist and Misery
Authors: Sharma Anjali , Rana Dr. Meenakshi
Published: November 2024

This paper investigates Stephen King’s postmodern books Misery and The Mist, emphasizing how they examine the self in connection to literature and reality from a postmodern perspective. Misery lacks supernatural themes, in contrast to previous King works, and instead presents a conventional story that is chamber play-like in its suspense and restraint. Both the books challenge conventional ideas of authenticity, uniqueness, and authority in writing and reading by highlighting the power struggles and tensions between the individual and the community through a variety of techniques. Misery and The Mist present opposing perspectives on the nature of the ego, its place in the postmodern maze of crises and uncertainties, and the moral ramifications of one's decisions and deeds through their stories.
Mitigating Developed Persistent Threats (APTs) through Machine Learning-Based Intrusion Detection Systems: A Comprehensive Analysis
Authors: Bin Shibghatullah Abdul Samad
Published: November 2024

Persistent threats (APTs) pose a significant challenge to cybersecurity due to their incredible evasive nature. Identification systems often fail to recognize APTs, resulting in significant data breaches and lost revenue. This study aims to solve this problem by developing a machine learning based intrusion detection system (IDS) specifically designed for APT detection This study aims to evaluate the performance of different machine learning algorithms for APT detection, IDS integration of these algorithms are efficient. The system includes integration and evaluation of system performance under real-world conditions. A major contribution of this research includes a comprehensive investigation of machine learning methods for APT recognition, IDS reprogramming, extensive empirical validation using real-world data Findings show that the proposed IDS greatly improves detection accuracy while reducing false positives for.
Cybersecurity Challenges in Autonomous Vehicles: Threats, Vulnerabilities, and Mitigation Strategies
Authors: Sarsam Samer Muthana
Published: November 2024

As autonomous vehicles (AVs) become an integral part of modern transportation, their complex systems face increasing cybersecurity threats. This review examines the critical cybersecurity challenges posed by AVs, focusing on external and internal threats including hackers, cybercriminals, and software vulnerabilities Denial of service (DoS); including AVs that rely on sophisticated communications networks, sensor systems, and artificial intelligence (AI), are highly susceptible to cyberattacks such as counterfeiting and remote control abuse. The problem statement identifies this threat as a serious threat to vehicle safety and the broader transportation system, and highlights the need for robust cybersecurity measures. The purpose of this study is to classify cybersecurity vulnerabilities in AV systems, assess potential risks, and propose effective mitigation measures The study investigates technical vulnerabilities in software, communication systems, sensors, . AI algorithms, as well as systematic challenges and regulatory gaps in AV delivery. In response, the study provides comprehensive mitigation strategies, with policy recommendations to develop effective global cybersecurity standards and regulatory frameworks including encryption, intrusion detection systems , secure software updates, and integrating post-quantum cryptography to address future threats from quantum computer programming. The results highlight the need for a multilevel cybersecurity strategy that incorporates both technical and legal solutions. The findings suggest that a holistic approach is needed to secure AV systems, addressing not only implementation can significantly reduce the risk of cyberattacks, and ensure that autonomous vehicles operate safely and reliably in a highly connected world.
The Evolution of Cybersecurity Threats and Strategies for Effective Protection. A review
Authors: Salman Hasan Ahmed , Alsajri Abdulazeez
Published: November 2024

Cybersecurity has become an increasingly crucial priority for individuals, organizations, and governments due to the growing reliance on technology and internet connectivity. This paper explores the various threats posed by cyber-attacks, such as malware, ransomware, and phishing, that exploit security vulnerabilities to access sensitive information or disrupt systems. It emphasizes the need for comprehensive defense strategies to safeguard digital systems and ensure the continuity of vital processes. The paper also highlights the evolution of cyber-attacks, from simple viruses to sophisticated state-sponsored attacks, and outlines key elements for enhancing cybersecurity, including threat protection, incident response, and user awareness. The paper concludes by advocating for a proactive approach to cybersecurity through technological advancements, legal frameworks, and collaborative efforts at national and international levels.
Sqwa:la (Hope Slough) watershed: Water quality report for the 2023 wet season
Authors: Ross Peter , Scott Samantha , Noel Marie , Kooistra Roxanne
Published: November 2024

Water is essential for life, and steps are needed to understand, protect and restore its health in fish habitat throughout British Columbia. The Raincoast Healthy Waters program was launched in 2023 to establish community-oriented water pollution monitoring in select BC watersheds. Two Healthy Waters sampling events take place every year in each watershed, the first in the dry season (summer), and the second being in the wet season (winter). This report highlights results from the first wet (winter) season sampling carried out with the support and participation of Pelólxw Tribe. Briefly, the Healthy Waters – CFN team determined basic water properties (temperature, conductivity, pH, dissolved oxygen and turbidity) in situ at sampling sites on December 20, 2023. Water samples were collected from four water categories, including source water (3 samples), stream and river water (3 samples), road runoff (3 samples), and Fraser River water (3 samples). Samples were then pooled by water category and analysed for coliform, metals, nutrients and physical parameters, pesticides, polycyclic aromatic hydrocarbons (PAHs), pharmaceuticals and personal care products (PPCPs), polychlorinated biphenyls (PCBs), alkylphenol ethoxylates (APEs), bisphenols, per- and poly-fluoroalkyl substances (PFAS), sucralose and 6-PPD Quinone. Overall, the Sqwa:la (Hope Slough) watershed had relatively good water quality in the wet season, but additional sampling and analysis will provide additional insight into contamination impacts from forest fires, domestic wastewater, industrial chemicals and runoff (roads, agriculture) on the health of this valued watershed.
KOBALT-NIKEL KEKINI TANLAB ERITISHNING MAQBUL PARAMETRLARINI TADQIQ QILISH
Authors:   Milliy texnologik tadqiqotlar universiteti “MISiS”  Olmaliq filiali, Qarshiyev Humoyun Komilovich , Xasanov Abdurashid Saliyevich ,   Olmaliq “KMK” AJ, Murashkeyevich Svetlana Mixaylovna ,   Pirogidrometallurgiya bo‘limi boshlig‘i. Innovatsion texnologiyalarni ishlab chiqish va joriy qilish texnologik markazi, Olmaliq, O‘zbekiston, Abdiyeva Manzura Matkarimovna ,   Loyiha ishlari boshqarmasi muhandis-konstruktori, Olmaliq “KMK” AJ,  Olmaliq, O‘zbekiston
Published: November 2024

Ushbu maqolada kobalt metallurgiyasining zamonaviy ahvoli, zahiralari, kobalt saqlagan minerallar haqida qolaversa kobalt saqlagan ikkilamchi va oraliq mahsulotlar ularning kimyoviy tarkibi, ulardan kobaltni ajratib olishning keng tarqalgan zamonaviy usullari keltirilgan. Kekni kimyoviy, granulometrik va birikma holidagi tahlillari jadval va rasm ko‘rinishida ko‘rsatilgan. Shuningdek mahalliy reagentlar hisobiga kadmiy ishlab chiqarishda ajralib chiqadigan oraliq mahsulot kobalt-nikelli keklarni tanlab eritish tajriba sinovlari va jarayon so‘nggida olingan natijalari keltirilgan. Tanlab eritishga ta‘sir etuvchi asosiy omillar harorat, pH muhit va tanlab eritish davomiyligi haqida ham xulosalar keltirilib, tanlab eritishning optimal sharoiti aniqlandi. Hozirda ushbu metalli eritmadan metallarni ajratib olish bo‘yicha sementatsiya hamda oksidlab cho‘ktirish tajriba sinovlari davom ettirilmoqda.
Undergraduate Students’ Readiness Toward English Medium Instruction In Higher Studies In Bangladesh: A Comparison Of Possibilities Of Public And Private Universities’ Internationalization
Authors: ALIA RAWSHAN BANU  , MD. HASIB ULLAH  , RAWSHAN TABASSUM
Published: November 2024

Assessing students’ readiness for English Medium Instruction (EMI) is crucial for understanding the efficacy of EMI as a pathway to internationalization in non-native English-speaking higher education contexts. This study investigates undergraduate students’ readiness for EMI in higher education in Bangladesh, compares the preparedness of students of public and private universities. The objective is to assess how readiness—defined by perceived ability, engagement, attitudes toward EMI, and perceived challenges—varies across different academic years and institutional types. Using a cross-sectional correlational design, data were collected from 267 undergraduate students from public and private universities through a structured survey questionnaire. Key variables included perceived ability to succeed in EMI (PASE), attitude towards EMI and internationalization (ATEI), learning engagement of students in EMI (LESE), and perceived challenges of facing EMI (PCFE). Independent samples t-tests, one-way ANOVA, and multiple regression analyses were employed. Results showed no significant differences in EMI readiness across the four academic years, meaning that progression in readiness is limited despite increased exposure to EMI. The t-test revealed significant differences only in perceived challenges (PCFE) between public and private universities, with private university students reporting higher challenges. Regression analysis indicated that PASE, ATEI, and PCFE significantly predicted LESE, with ATEI having the strongest impact on learning engagement. These findings suggest that sustained exposure to EMI alone may be insufficient to enhance readiness, especially without institutional language support and resources. Therefore, universities must take care of the strategic goals of internationalization in higher education.
Camille Laurin et la politique comme psychothérapie1
Authors: Klein Alexandre
Published: November 2024

Camille Laurin a toujours envisagé sa carrière politique comme une continuation de sa carrière psychiatrique. Les relations entre ces deux activités professionnelles restent pourtant floues parce que peu étudiées. En retraçant la généalogie de sa pensée psychiatrico-politique, depuis sa conception du Canada français comme une personnalité traumatique jusqu’à l’application de la loi 101 comme thérapeutique en passant par sa représentation du souverainisme comme soin, cet article entend clarifier les enjeux psychiatriques de l’engagement politique de Laurin et mettre en lumière sa conception de la politique comme une psychothérapie collective, mais peut-être aussi individuelle.
« Les Français du Canada » : appartenance nationale et crises impériales (1870-1904)1
Authors: Baraton Édouard
Published: November 2024

La réouverture des relations officielles entre la France et le Canada à partir de 1859 laissa place à un réinvestissement politique de l’ancienne métropole par le nationalisme canadien-français, à l’initiative des nationalistes rouges canadiens. Dès lors, à travers les crises internationales (de la guerre de 1870 à la guerre des Boers en passant par Fachoda) et les crises nationales canadiennes (du Nord-Ouest à la pendaison de Riel puis à la solidarité impériale), la question des « Français du Canada » va mettre à rude épreuve la paix du Dominion jusqu’au retournement consécutif à l’Entente cordiale de 1904.
«Strategic business company» in the understanding of the Law on Foreign Investments
Authors: Milchakova Olesya Vladimirovna
Published: November 2024

The object of the study is the implementation of foreign investments in strategic sectors of the economy, the subject of the study is a «strategic business entity» as an object of investment activity. The author examines aspects of the normative and legal definition of «a business entity of strategic importance for ensuring the defense of the country and the security of the state», the features of the use of this concept in law enforcement. Particular attention is paid to the role of strategic business entities in ensuring the implementation of the National Security Strategy of the Russian Federation. The methodological basis of the study was made up of general logical methods of theoretical analysis, as well as a special formal-legal method and a method of technical-legal analysis. The conclusion is substantiated about the law enforcement agency going beyond the literal interpretation of the regulatory definition of a «strategic business entity» and a new concept of such a company is formulated and understood as «a legal entity created in the Russian Federation, implementing and (or) having the ability to implement, on the basis of a license, other permit document or agreement, any of the types of activities that are of strategic importance for ensuring the defense of the country and the security of the state and the implementation of national priorities provided for by the National Security Strategy of the Russian Federation (including performing work, providing services, delivering products necessary for another legal entity to implement the specified type of activity)». This definition must be provided for in the law in order to ensure legal certainty and create a positive investment climate.
Communicative consciousness and principles of environmental design in the experimental project "Stone. Inversion. Vessel"
Authors: Chang Xiaogeng , Potekhina Alena Evgenevna
Published: November 2024

The article is based on the analysis and summary of the design process of the work of the Chinese author "Stone. Inversion. Vessel". It examines three key aspects of the development of environmental design. Firstly, it is a combination of modern technologies with aesthetic representations of traditional Chinese culture. Through the study of the project, it is demonstrated how traditional Chinese art can be combined with modern technologies when creating a design object. Secondly, the project highlights the features of the development of design in the modern era. It is characterized by problems of volatility, uncertainty, complexity and ambiguity, which can be mitigated through interdisciplinary integration with the use of the latest technologies. Environmental design, thanks to the multifaceted concept of "environment", meets the conditions of development of the modern era. Thirdly, the article focuses on the fact that the communication of the subjects of the creative process is based on the images embodied in a specific project. Environmental design as an interdisciplinary field is based on the methods of different scientific fields, since the environment that changes under the influence of human activity is not the same. In the proposed article, the author uses the art criticism method when describing blue-and-green landscape painting, and also assigns a large role to the communicative method of sociology developed by the American scientist Harold Dwight Lasswell. The novelty of the research lies in the fact that the author was able to show the possibility of a harmonious combination of modern 3D modeling technologies with the traditional Chinese art of blue-and-green landscape painting (青绿山水 qīng lǜ shān shuǐ). In other words, a planar image turns into a design object, with the help of which can be realized various spatial combinations. Through artistic thinking, one can enjoy not only the functional, but also the aesthetic possibilities of the design object. So, in the described project, the author focuses on the imagination of the observer, forcing him to climb a mountain peak, but inside the building. This is how communication takes place between the author, the "viewer" and the project itself. The image is the basis of communication between various objects of the environment involved in the design process. The creative process combines the material (functional) and spiritual (image-induced) needs of a person. Environmental design, through the synthesis of spiritual and material, establishing communication between design objects and integrating disciplines through the prism of an image, explores how design affects human activity.
Risking your Tail: Modeling Individual Differences in Risk-sensitive Exploration using Bayes Adaptive Markov Decision Processes
Authors: Shen Tingke , Dayan Peter
Published: November 2024

Novelty is a double-edged sword for agents and animals alike: they might benefit from untapped resources or face unexpected costs or dangers such as predation. The conventional exploration/exploitation tradeoff is thus coloured by risk-sensitivity. A wealth of experiments has shown how animals solve this dilemma, for example using intermittent approach. However, there are large individual differences in the nature of approach, and modeling has yet to elucidate how this might be based on animals’ differing prior expectations about reward and threat, and differing degrees of risk aversion. To capture these factors, we built a Bayes adaptive Markov decision process model with three key components: an adaptive hazard function capturing potential predation, an intrinsic reward function providing the urge to explore, and a conditional value at risk (CVaR) objective, which is a contemporary measure of trait risk-sensitivity. We fit this model to a coarse-grain abstraction of the behaviour of 26 animals who freely explored a novel object in an open-field arena (Akiti et al.
Neuron
110, 2022). We show that the model captures both quantitative (frequency, duration of exploratory bouts) and qualitative (stereotyped tail-behind) features of behavior, including the substantial idiosyncrasies that were observed. We find that “brave” animals, though varied in their behavior, are generally more risk neutral, and enjoy a flexible hazard prior. They begin with cautious exploration, and quickly transition to confident approach to maximize exploration for reward. On the other hand, “timid” animals, characterized by risk aversion and high and inflexible hazard priors, display self-censoring that leads to the sort of asymptotic maladaptive behavior that is often associated with psychiatric illnesses such as anxiety and depression. Explaining risk-sensitive exploration using factorized parameters of reinforcement learning models could aid in the understanding, diagnosis, and treatment of psychiatric abnormalities in humans and other animals.
Targeting IRE1α improves insulin sensitivity and thermogenesis and suppresses metabolically active adipose tissue macrophages in obesity
Authors: Wu Dan , Eeda Venkateswararao , Maria Zahra , Rawal Komal , Wang Audrey , Herlea-Pana Oana , Undi Ram Babu , Lim Hui-Ying , Wang Weidong
Published: November 2024

Overnutrition engenders the expansion of adipose tissue and the accumulation of immune cells, in particular, macrophages, in the adipose tissue, leading to chronic low-grade inflammation and insulin resistance. In obesity, several proinflammatory subpopulations of adipose tissue macrophages (ATMs) identified hitherto include the conventional “M1-like” CD11C-expressing ATM and the newly discovered metabolically activated CD9-expressing ATM; however, the relationship among ATM subpopulations is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) is activated in the adipocytes and immune cells under obesity. It is unknown whether targeting IRE1α is capable of reversing insulin resistance and obesity and modulating the metabolically activated ATMs. We report that pharmacological inhibition of IRE1α RNase significantly ameliorates insulin resistance and glucose intolerance in male mice with diet-induced obesity. IRE1α inhibition also increases thermogenesis and energy expenditure, and hence protects against high fat diet-induced obesity. Our study shows that the “M1-like” CD11c
+
ATMs are largely overlapping with but yet non-identical to CD9
+
ATMs in obese white adipose tissue. Notably, IRE1α inhibition diminishes the accumulation of obesity-induced metabolically activated ATMs and “M1-like” ATMs, resulting in the curtailment of adipose inflammation and ensuing reactivation of thermogenesis, without augmentation of the alternatively activated M2 macrophage population. Our findings suggest the potential of targeting IRE1α for the therapeutic treatment of insulin resistance and obesity.
Repeated activation of preoptic area-recipient neurons in posterior paraventricular nucleus mediates chronic heat-induced negative emotional and hyperarousal states
Authors: Cao Zhiping , Yung Wing-Ho , Ke Ya
Published: November 2024

Mental and behavioral disorders are associated with extended period of hot weather as found in heatwaves, but the underlying neural circuit mechanism is poorly known. The posterior paraventricular thalamus (pPVT) is a hub for emotional processing and receives inputs from the hypothalamic preoptic area (POA), the well-recognized thermoregulation center. The present study was designed to explore whether chronic heat exposure leads to aberrant activities in POA recipient pPVT neurons and subsequent changes in emotional states. By devising an air heating paradigm mimicking the condition of heatwaves and utilizing emotion-related behavioral tests, viral track tracing,
in vivo
calcium recordings, optogenetic manipulations and electrophysiological recordings, we found that chronic heat exposure for 3 weeks led to negative emotional and hyperarousal states in mice. The pPVT neurons receive monosynaptic excitatory and inhibitory innervations from the POA. These neurons exhibited a persistent increase in neural activity following chronic heat exposure, which was essential for chronic heat-induced emotional changes. Notably, these neurons were also prone to display stronger neuronal activities associated with anxiety responses to stressful situations. Furthermore, we observed saturated neuroplasticity in the POA-pPVT excitatory pathway after chronic heat exposure that occluded further potentiation. Taken together, long-term aberration in the POA to pPVT pathway offers a neurobiological mechanism of emotional and behavioral changes seen in extended period of hot weather like heatwaves.
Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX
Authors: Vaškevičius Aivaras , Baronas Denis , Leitans Janis , Kvietkauskaitė Agnė , Rukšėnaitė Audronė , Manakova Elena , Toleikis Zigmantas , Kaupinis Algirdas , Kazaks Andris , Gedgaudas Marius , Mickevičiūtė Aurelija , Juozapaitienė Vaida , Schiöth Helgi B , Jaudzems Kristaps , Valius Mindaugas , Tars Kaspars , Gražulis Saulius , Meyer-Almes Franz-Josef , Matulienė Jurgita , Zubrienė Asta , Dudutienė Virginija , Matulis Daumantas
Published: November 2024

We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: 1) primary sulfonamide group recognizing carbonic anhydrases (CA), 2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and 3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification. Our designed prodrug candidates bearing moderately active pre-vinyl sulfone esters or weakly active carbamates optimized for mild covalent modification activity to avoid toxic non-specific modifications and selectively target CAIX. The lead inhibitors reached 2 pM affinity, highest among known CAIX inhibitors. The strategy could be used for any disease drug target protein bearing a His residue in the vicinity of the active site.
Context-Dependent Modulations of Subthalamo-Cortical Synchronization during Rapid Reversals of Movement Direction in Parkinson’s Disease
Authors: Winkler Lucie , Butz Markus , Sharma Abhinav , Vesper Jan , Schnitzler Alfons , Fischer Petra , Hirschmann Jan
Published: November 2024

The role of beta band activity in cortico-basal ganglia interactions during motor control has been studied extensively in resting-state and for simple movements, such as button pressing. However, little is known about how beta oscillations change and interact in more complex situations involving rapid changes of movement in various contexts.To close this knowledge gap, we combined magnetoencephalography (MEG) and local field potential recordings from the subthalamic nucleus (STN) in Parkinson’s disease patients to study beta dynamics during initiation, stopping, and rapid reversal of rotational movements. The action prompts were manipulated to be predictable vs. unpredictable.We observed movement-related beta suppression at motor sequence start, and a beta rebound after motor sequence stop in STN power, motor cortical power, and STN-cortex coherence. Despite involving a brief stop of movement, no clear rebound was observed during reversals of turning direction. On the cortical level, beta power decreased bilaterally following reversals, but more so in the hemisphere ipsilateral to movement, due to a floor effect on the contralateral side. In the STN, power modulations varied across patients, with patients revealing brief increases or decreases of high-beta power. Importantly, cue predictability affected these modulations. Event-related increases of STN-cortex beta coherence were generally stronger in the unpredictable than in the predictable condition.In summary, this study reveals the influence of movement context on beta oscillations in basal ganglia-cortex loops when humans change ongoing movements according to external cues. We find that movement scenarios requiring higher levels of caution involve enhanced modulations of subthalamo-cortical beta synchronization. Further, our results confirm that beta oscillations reflect the start and end of motor sequences better than movement changes within a sequence.
A macroevolution-inspired approach to reveal novel antibiotic resistance mechanisms
Authors: de Carvalho Luiz Pedro , Subtil Fernanda , Machado Teresa , Douglas Holly , Kirkpatrick Joanna , Skehel Mark , Garza-Garcia Acely
Published: November 2024

With the continuous rise in antibiotic resistance, novel methods that can reveal currently unknown antibiotic resistance mechanisms are essential to prepare and inform health responses. Here we built a library of species representative of the genus
Mycobacterium
and determined their antibiotic resistance profiles, allowing systematic multispecies comparisons. Analyzing antibiotic resistance in the context of other closely related organisms revealed species with truly exceptional traits, thus providing a solid starting point for the exploration of novel determinants of antibiotic resistance. We illustrate the utility of this genus-level approach to discovery of novel traits by characterizing a previously unrecognized rifamycin-inactivating enzyme that is present in a wide range of bacterial genera.
MED26-enriched condensates drive erythropoiesis through modulating transcription pausing
Authors: Zhu Shicong , Zhang Xiaoting , Li Na , Zhao Xinying , Li Man , Xie Si , Yue Qiuyu , Li Yunfeng , Li Dong , Wu Fan , Zhang Zile , Feng Ziqi , Zhang Yiyang , Choi Wonhyung , Jia Xinyi , Deng Yuelin , Hu Qi , Yao Xingyun , Gao Xiaofei , Lee Hsiang-Ying
Published: November 2024

The Mediator complex regulates various aspects of hematopoietic development, but whether composition of the Mediator complex undergoes dynamic changes for diversifying transcription and functional outputs is unknown. Here, we found that MED26, a subunit in the core Mediator complex, played a distinctive role in facilitating transcription pausing essential for erythroid development. While most Mediator subunits drastically decreased during this process, MED26 remained relatively abundant. Intriguingly, in the early stages, more than half of MED26 occupancy sites did not co-localize with MED1, a representative Mediator subunit, suggesting these subunits exert context-dependent gene regulation. We revealed that MED26-enriched loci were associated with RNA polymerase Ⅱ pausing. MED26 manifested a markedly preferential recruitment of pausing-related factors, leading to an increase in Pol Ⅱ pausing critical for genome-wide transcription repression during erythropoiesis. Moreover, MED26 exhibited pronounced condensate-forming capability, which was necessary for its function in promoting erythropoiesis and recruiting pausing-related factors. Collectively, this study provides mechanistic insights into the functional coordination of distinct Mediator subunits during development and highlights the switch of transcription condensates towards a MED26 enriched form, which modulates transcription pausing to facilitate transcription repression and erythroid development.
PointTree: Automatic and accurate reconstruction of long-range axonal projections of single-neuron
Authors: Cai Lin , Fan Taiyu , Qu Xuzhong , Zhang Ying , Gou Xianyu , Ding Quanwei , Feng Weihua , Cao Tingting , Lv Xiaohua , Liu Xiuli , Huang Qing , Quan Tingwei , Zeng Shaoqun
Published: November 2024

Single-neuron axonal projections reveal the route map of neuron output and provide a key cue for understanding how information flows across the brain. Reconstruction of single-neuron axonal projections requires intensive manual operations in tens of terabytes of brain imaging data, and is highly time-consuming and labor-intensive. The main issue lies in the need for precise reconstruction algorithms to avoid reconstruction errors, yet current methods struggle with densely distributed axons, focusing mainly on skeleton extraction. To overcome this, we introduce a point assignment-based method that uses cylindrical point sets to accurately represent axons and a minimal information flow tree model to suppress the snowball effect of reconstruction errors. Our method successfully reconstructs single-neuron axonal projections across hundreds of GBs images with an average of 80% F1-score, while current methods only provide less than 40% F1-score reconstructions from a few hundred MBs images. This huge improvement is helpful for high-throughput mapping of neuron projections.
DendroTweaks: An interactive approach for unraveling dendritic dynamics
Authors: Makarov Roman , Chavlis Spyridon , Poirazi Panayiota
Published: November 2024

Neurons rely on the interplay between dendritic morphology and ion channels to transform synaptic inputs into a sequence of somatic spikes. Detailed biophysical models with active dendrites have been instrumental in exploring this interaction. However, such models can be challenging to understand and validate due to the large number of parameters involved. In this work, we introduce
DendroTweaks
— a toolbox designed to illuminate how morpho-electric properties map to dendritic events and how these dendritic events shape neuronal output.
DendroTweaks
features a web-based graphical interface, where users can explore single-cell neuronal models and adjust their morphological and biophysical parameters with real-time visual feedback. In particular,
DendroTweaks
is tailored to interactive fine-tuning of subcellular properties, such as kinetics and distributions of ion channels, as well as the dynamics and allocation of synaptic inputs. It offers an automated approach for standardization and refinement of voltage-gated ion channel models to make them more comprehensible and reusable. The toolbox allows users to run various experimental protocols and record data from multiple dendritic and somatic locations, thereby enhancing model validation. Finally, it aims to deepen our understanding of which dendritic properties are essential for neuronal input-output transformation. Using this knowledge, one can simplify models through a built-in morphology reduction algorithm and export them for further use in faster, more interpretable networks. With
DendroTweaks
, users can gain better control and understanding of their models, advancing research on dendritic input-output transformations and their role in network computations.
Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis in Mycobacterium ulcerans infection
Authors: Hsieh Louise Tzung-Harn , Hall Belinda S , Newcombe Jane , Mendum Tom A , Santana-Varela Sonia , Umrania Yagnesh , Deery Michael J , Shi Wei Q , Diaz-Delgado Josué , Salguero Francisco J , Simmonds Rachel E
Published: November 2024

The drivers of tissue necrosis in
Mycobacterium ulcerans
infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action of the diffusible exotoxin, mycolactone. However, its role in the clinically-evident vascular component of disease aetiology remains poorly explained. We have now dissected mycolactone’s effects on primary vascular endothelial cells
in vitro
and
in vivo
. We show that mycolactone-induced changes in endothelial morphology, adhesion, migration, and permeability are dependent on its action at the Sec61 translocon. Unbiased quantitative proteomics identified a profound effect on proteoglycans, driven by rapid loss of type II transmembrane proteins of the Golgi, including enzymes required for glycosaminoglycan (GAG) synthesis, combined with a reduction in the core proteins themselves. Loss of the glycocalyx is likely to be of particular mechanistic importance, since knockdown of galactosyltransferase II (beta-1,3-galactotransferase 6; B3GALT6), the GAG linker-building enzyme, phenocopied the permeability and phenotypic changes induced by mycolactone. Additionally, mycolactone depleted many secreted basement membrane components and microvascular basement membranes were disrupted
in vivo
. Remarkably, exogenous addition of laminin-511 reduced endothelial cell rounding, restored cell attachment and reversed the defective migration caused by mycolactone. Hence supplementing mycolactone-depleted extracellular matrix may be a future therapeutic avenue, to improve wound healing rates.
Hypothalamic corticotropin-releasing hormone neurons modulate sevoflurane anesthesia and the post-anesthesia stress responses
Authors: Jiang Shan , Chen Lu , Qu Wei-Min , Huang Zhi-Li , Chen Chang-Rui
Published: November 2024

General anesthesia (GA) is an indispensable procedure necessary for safely and compassionately administering a significant number of surgical procedures and invasive diagnostic tests. However, the undesired stress response associated with GA causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVHCRH neurons), is discovered to play a role in regulating sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition of PVHCRH neurons accelerates induction and delays awakening. Moreover, optogenetic stimulation of PVHCRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These ﬁndings identify PVHCRH neurons modulate states of anesthesia in sevoflurane GA, being a part of anesthesia regulatory network of sevoflurane.
Shortcutting from self-motion signals reveals a cognitive map in mice
Authors: Xu Jiayun , Girardi-Schappo Mauricio , Beique Jean-Claude , Longtin André , Maler Leonard
Published: November 2024

Animals navigate by learning the spatial layout of their environment. We investigated spatial learning of mice in an open maze where food was hidden in one of a hundred holes. Mice leaving from a stable entrance learned to efficiently navigate to the food without the need for landmarks. We developed a quantitative framework to reveal how the mice estimate the food location based on analyses of trajectories and active hole checks. After learning, the computed ‘target estimation vector’ (TEV) closely approximated the mice’s route and its hole check distribution. The TEV required learning both the direction and distance of the start to food vector, and our data suggests that different learning dynamics underlie these estimates. We propose that the TEV can be precisely connected to the properties of hippocampal place cells. Finally, we provide the first demonstration that, after learning the location of two food sites, the mice took a shortcut between the sites, demonstrating that they had generated a cognitive map.
Human immunodeficiency virus-1 induces host genomic R-loop and preferentially integrates its genome near the R-loop regions
Authors: Park Kiwon , Lee Dohoon , Jeong Jiseok , Lee Sungwon , Kim Sun , Ahn Kwangseog
Published: November 2024

Although HIV-1 integration sites favor active transcription units in the human genome, high-resolution analysis of individual HIV-1 integration sites has shown that the virus can integrate into a variety of host genomic locations, including non-genic regions. The invisible infection by HIV-1 integrating into non-genic regions, challenging the traditional understanding of HIV-1 integration site selection, is more problematic because they are selected for preservation in the host genome during prolonged antiretroviral therapies. Here, we showed that HIV-1 integrates its viral genome into the vicinity of R-loops, a genomic structure composed of DNA– RNA hybrids. VSV-G-pseudotyped HIV-1 infection initiates the formation of R-loops in both genic and non-genic regions of the host genome and preferentially integrates into R-loop-rich regions. Using a HeLa cell model that can independently control transcriptional activity and R-loop formation, we demonstrated that the exogenous formation of R-loops directs HIV-1 integration-targeting sites. We also found that HIV-1 integrase proteins physically bind to the host genomic R-loops. These findings provide novel insights into the mechanisms underlying retroviral integration and the new strategies for antiretroviral therapy against HIV-1 latent infection.
Leveraging machine learning for the detection of structured interference in Global Navigation Satellite Systems
Authors: Nabi Imtiaz , Farooq Salma Zainab , Saeed Sunnyaha , Irtaza Syed Ali , Shehzad Khurram , Arif Mohammad , Khan Inayat , Ahmad Shafiq
Published: November 2024

Radio frequency interference disrupts services offered by Global Navigation Satellite Systems (GNSS). Spoofing is the transmission of structured interference signals intended to deceive GNSS location and timing services. The identification of spoofing is vital, especially for safety-of-life aviation services, since the receiver is unaware of counterfeit signals. Although numerous spoofing detection and mitigation techniques have been developed, spoofing attacks are becoming more sophisticated, limiting most of these methods. This study explores the application of machine learning techniques for discerning authentic signals from counterfeit ones. The investigation particularly focuses on the secure code estimation and replay (SCER) spoofing attack, one of the most challenging type of spoofing attacks, ds8 scenario of the Texas Spoofing Test Battery (TEXBAT) dataset. The proposed framework uses tracking data from delay lock loop correlators as intrinsic features to train four distinct machine learning (ML) models: logistic regression, support vector machines (SVM) classifier, K-nearest neighbors (KNN), and decision tree. The models are trained employing a random six-fold cross-validation methodology. It can be observed that both logistic regression and SVM can detect spoofing with a mean F1-score of 94%. However, logistic regression provides 165dB gain in terms of time efficiency as compared to SVM and 3 better than decision tree-based classifier. These performance metrics as well as receiver operating characteristic curve analysis make logistic regression the desirable approach for identifying SCER structured interference.
A comparative analysis of variants of machine learning and time series models in predicting women’s participation in the labor force
Authors: Elstohy Rasha , Aneis Nevein , Mounir Ali Eman
Published: November 2024

Labor force participation of Egyptian women has been a chronic economic problem in Egypt. Despite the improvement in the human capital front, whether on the education or health indicators, female labor force participation remains persistently low. This study proposes a hybrid machine-learning model that integrates principal component analysis (PCA) for feature extraction with various machine learning and time-series models to predict women’s employment in times of crisis. Various machine learning (ML) algorithms, such as support vector machine (SVM), neural network, K-nearest neighbor (KNN), linear regression, random forest, and AdaBoost, in addition to popular time series algorithms, including autoregressive integrated moving average (ARIMA) and vector autoregressive (VAR) models, have been applied to an actual dataset from the public sector. The manpower dataset considered gender from different regions, ages, and educational levels. The dataset was then trained, tested, and evaluated. For performance validation, forecasting accuracy metrics were constructed using mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE), mean absolute percent error (MAPE), R-squared (R2), and cross-validated root mean squared error (CVRMSE). Another Dickey-Fuller test was performed to evaluate and compare the accuracy of the applied models, and the results showed that AdaBoost outperforms the other methods by an accuracy of 100%. Compared to alternative works, our findings demonstrate a comprehensive comparative analysis for predicting women’s participation in different regions during an economic crisis.
Cryophysiology of coral microfragments: effects of chilling and cryoprotectant toxicity
Authors: Lager Claire V. A. , Perry Riley , Daly Jonathan , Page Christopher , Mizobe Mindy , Bouwmeester Jessica , Consiglio Anthony N. , Carter Jake , Powell-Palm Matthew J. , Hagedorn Mary
Published: November 2024

Coral reefs are being degraded at alarming rates and decisive intervention actions are urgently needed. One such intervention is coral cryopreservation. Although the cryopreservation of coral sperm and larvae has been achieved, preservation of coral fragments including both its tissue and skeleton, has not. The overarching aim of this study was to understand and assess the physiological stressors that might underlie coral fragment cryopreservation, understand the long-term consequences of these exposures to continued growth, and develop a health metrics scale for future research. Therefore, we assessed small fragments (~1 cm2) from the Hawaiian coral, Porites compressa, examining: (1) chill sensitivity; (2) chemical sensitivity to complex cryoprotectants; (3) methods to safely remove algal symbionts of coral for cryopreservation; (4) continued growth over time of coral fragments exposed to chilling and cryoprotectants; and (5) assessment of health and viability of coral fragments post the applied treatments. Corals were able to withstand chilling to 0 °C for 1 min and after 2 weeks were not significantly different from the live controls, whereas, corals exposed to complex cryoprotectants needed 3 weeks of recovery. Most importantly, it appears that once the coral fragments had surpassed this initial recovery, there was no difference in subsequent growth. Technological advances in cryo-technology promise to support successful coral fragment cryopreservation soon, and its success could help secure much of the genetic and biodiversity of reefs in the next decade.