bluuebunny/crossref_metadata_2025_split huggingface dataset:
MULTIPLE DISTINCT TIMESCALES OF RAPID SENSORY ADAPATION IN THE THALAMOCORTICAL CIRCUIT
Authors: Liew Yi Juin , Dimwamwa Elaida D , Wright Nathaniel C , Zhang Yong , Stanley Garrett B 
Published: February 2025

Numerous studies have shown that neuronal representations in sensory pathways are far from static but are instead strongly shaped by the complex properties of the sensory inputs they receive. Adaptation dynamically shapes the neural signaling that underlies our perception of the world yet remains poorly understood. We investigated rapid adaptation across timescales from hundreds of milliseconds to seconds through simultaneous multi-electrode recordings from the ventro-posteromedial nucleus of the thalamus (VPm) and layer 4 of the primary somatosensory cortex (S1) in male and female anesthetized mice in response to controlled, persistent whisker stimulation. Observations in VPm and S1 reveal a degree of adaptation that progresses through the pathway. Under these experimental conditions, signatures of two distinct timescales of rapid adaptation in the firing rates of both thalamic and cortical neuronal populations were revealed, also reflected in the synchrony of the thalamic population and in the thalamocortical synaptic efficacy that was measured in putatively monosynaptically connected thalamocortical pairs. Controlled optogenetic activation of VPm further demonstrated that the longer timescale adaptation observed in S1 is likely inherited from slow decreases in thalamic firing rate and synchrony. Despite the degraded sensory responses, adaptation induced by the controlled repetitive stimulation presented here resulted in a shift in coding strategy that favors theoretical discrimination over detection across the observed timescales of adaptation. Overall, although multiple mechanisms contribute to rapid adaptation at distinct timescales, they support a unifying framework on the role of adaptation in sensory processing.Significance StatementAlthough the perceptual effects of persistent sensory stimulation have been known for centuries, the rapid sensory adaptation of the underlying neural signaling to these persistent inputs are not well understood. Here, we present evidence for two distinct timescales of adaptation over several seconds across the thalamocortical circuit in mice. We identify both the overall level of neural activity and the corresponding population synchrony of the thalamic inputs to primary somatosensory cortex as key role players shaping the cortical adaptation.
The effect of microsaccades in the primary visual cortex: increased synchronization in the fovea during a two-phase response modulation
Authors: Nativ Yarden , Bouhnik Tomer , Slovin Hamutal 
Published: February 2025

Our eyes are never still. Even when we attempt to fixate, the visual gaze is never motionless, as we continuously perform miniature oculomotor movements termed as fixational eye movements. The fastest eye movements during the fixation epochs are termed microsaccades (MSs), that are leading to continual motion of the visual input, affecting mainly neurons in the fovea. Yet our vision appears to be stable. To explain this gap, previous studies suggested the existence of an extra-retinal input (ERI) into the visual cortex that can account for the motion and produce visual stability. Here, we investigated the existence of an ERI to V1 fovea in macaque monkeys (male) while they performed spontaneous MSs, during fixation. We used voltage-sensitive dye imaging (VSDI) to measure and characterize at high spatio-temporal resolution the influence of MSs on neural population activity, in the foveal region of the primary visual cortex (V1). Microsaccades performed over a blank screen, induced a two-phase response modulation: an early suppression followed by an enhancement. A correlation analysis revealed a widespread foveal increase in neural synchronization, peaking around ∼100 ms after MS onset. Next, we investigated the MS effects in the presence of a small visual stimulus, and found that this modulation was different from the blank condition yet both modulations co-existed in the fovea. Finally, the VSD response to an external motion of the fixation point could not explain the MS modulation. These results support an ERI that may be involved in visual stabilization already at the level of V1.Significance statementMicrosaccades are tiny fixational saccades, leading to the continual motion of the visual input on the fovea, during visual fixation. Yet our vision appears to be stable. To explain this gap, we investigated the existence of an extra-retinal input into the fovea of the primary visual cortex (V1) in behaving monkeys while they performed microsaccades over a blank screen with a tiny fixation point. The population response aligned on microsacades showed a widespread, transient increased neural synchronization along with a two-phase response modulation. Microsaccades in the presence of a visual stimulus induced distinct spatio-temporal response from that in the blank condition. Our results support the existence of an extra-retinal input that may be involved in visual stabilization at V1 area.
The electrically silent Kv5.1 subunit forms heteromeric Kv2 channels in cortical neurons and confers distinct functional properties
Authors: Ferns Michael , van der List Deborah , Vierra Nicholas C. , Lacey Taylor , Murray Karl , Kirmiz Michael , Stewart Robert G. , Sack Jon T. , Trimmer James S. 
Published: February 2025

Voltage-gated K+channels of the Kv2 family are highly expressed in brain and play dual roles in regulating neuronal excitability and in organizing endoplasmic reticulum - plasma membrane (ER-PM) junctions. Studies in heterologous cells suggest that Kv2.1 and Kv2.2 co-assemble with “electrically silent” KvS subunits to form heterotetrameric channels with distinct biophysical properties, but the prevalence and localization of these channels in native neurons is unknown. Here, using mass spectrometry-based proteomics, we identified five KvS subunits as components of native Kv2.1 channels immunopurified from mouse brain of both sexes, the most abundant being Kv5.1. We found that Kv5.1 co-immunoprecipitates with Kv2.1 and to a lesser extent with Kv2.2 from brain lysates, and that Kv5.1 protein levels are decreased by 70% in Kv2.1 knockout mice and 95% in Kv2.1/Kv2.2 double knockout mice. RNAscope and immunolabelling revealed that Kv5.1 is prominently expressed in neocortex, where it is detected in a substantial fraction of Kv2.1/Kv2.2 positive neurons in layers 2/3, 5, and 6. At the subcellular level, Kv5.1 protein is co-clustered with Kv2.1 and Kv2.2 at presumptive ER-PM junctions on the soma and proximal dendrites of cortical neurons. Moreover, in addition to modifying channel conductance, we found that Kv2/Kv5.1 channels are less phosphorylated and insensitive to RY785, a potent and selective Kv2 channel inhibitor. Together, these findings demonstrate that KvS subunits create multiple Kv2 channel subtypes in brain. Most notably, Kv2/Kv5.1 channels are highly expressed in cortical neurons, where their unique properties likely modulate the critical conducting and non-conducting roles of Kv2 channels.Significance StatementVoltage-gated Kv2 potassium channels play important roles in regulating neuronal excitability and organizing endoplasmic reticulum - plasma membrane (ER-PM) junctions in brain neurons. Here, we use mass spectrometry to identify five KvS channel subunits as components of native Kv2 channels in brain. The most abundant of these subunits, Kv5.1, is prominently expressed in cortex, where it clusters at ER-PM junctions with Kv2 subunits in a subpopulation of cortical neurons. Kv5.1 expression depends on Kv2 subunits, and Kv2/Kv5.1 heteromeric channels differ in their biophysical and pharmacological properties. We propose that differential expression of Kv5.1 in subclasses of cortical neurons diversifies Kv2 channel function.
Representasi Akidah dalam Seni Syiir Tradisional “Blug-Geblug” Chanel Youtube Abi Channel
Authors: Hakim Lukman , Zuhriyah Luluk Fikri 
Published: February 2025

Penelitian ini bertujuan untuk mengetahui representasi” akidah dalam Seni Syiir Tradisional Blug-geblug Chanel Youtube Abi Channel dan bagaimana proses analisis semiotik Roland Barthes pada Seni Syiir Tradisional Blug-geblug Chanel Youtube Abi Channel. Jenis penelitian ini merupakan penelitian analisis teks media dengan pendekatan semiotik Roland Barthes. Akidah dalam Seni Syiir Tradisional Blug-geblug mempresentasikan akidah keimanan kepada Allah SWT, Hari akhir, dan qada qadar. Analisis semiotik Roland Barthes pada penelitian ini menghasilkan Tanda berupa Syiir Blug-geblug, Petanda yang terdiri dari salam pembuka, lirik Syiir Blug-geblug dan salam penutup. Denotasi yang berupa Melantunkan Syiir Blug-geblug. Konotasi yang berupa Bersenandung dan Mitos berupa Syiiran Blug-geblug. Peneliti merekomendasikan agar pada penelitian selanjutnya dapat meneliti dan mengkaji lebih dalam dengan menggunakan metode penelitian yang berbeda dengan harapan dapat memiliki nilai kebaruan dalam penelitian tersebut.
Long-Term Physical Exercise for Preventing CKD in Older Adults
Authors: Hallan Stein I. , Øvrehus Marius A. , Shlipak Michael G. , Potok O. Alison , Romundstad Solfrid , Aspvik Nils P. , Wisløff Ulrik , Ix Joachim H. , Stensvold Dorthe , Langlo Knut A. 
Published: February 2025

Background:
Chronic kidney disease (CKD) is a growing global public health issue. Physical exercise mitigates several kidney-related pathophysiological pathways, yet its impact on kidney function remains underexplored. We investigated the dose-response effect of physical exercise on kidney function preservation in older adults.

Methods:
Post-hoc analysis of the Generation 100 Study, a 5-year open-label, randomized, parallel-arm clinical trial conducted from 2012 to 2018 in Trondheim, Norway. All inhabitants aged 70-77 years were invited (n=6,966). Main exclusion criteria were dementia; severe, uncontrolled cardiovascular disease or hypertension; or conditions precluding exercise. The control group (n=385) received information on national physical activity recommendations. Intervention groups underwent supervised moderate-intensity continuous training (70% of peak heart rate) for 50 minutes (n=380) twice weekly for five years or high-intensity interval training (90% of peak heart rate) for 4 minutes x4 (n=391) twice weekly for five years. The primary outcome was cystatin C-based rapid eGFR decline (>5mL/min/1.73m2 per year).

Results:
A total of 1,156 participants were randomized with median (interquartile range) age 72 (3) years and eGFR 95 (20) mL/min/1.73 m2. Oxygen uptake increased by 1.8, 2.3, and 3.3 mL/kg/min in the control, moderate-intensity, and high-intensity groups. Rapid eGFR decline occurred in 117 (30%), 108 (28%), and 92 (23%) participants, respectively. Compared to controls, relative risk (RR) was 0.93 (0.75-1.16) for moderate-intensity and 0.75 (95% CI 0.59-0.95) for high-intensity, demonstrating a significant dose-response relationship (P for trend 0.02). In observational analyses, participants with decreasing moderate-vigorous activity (> -20 minute/week) had RR 1.30 (95% CI 0.93-1.83) for rapid eGFR decline, while those with increasing activity (> +20 minutes/week) had RR 0.73 (0.53-0.99) compared to stable activity after adjusting for baseline age, sex, VO2peak and eGFR.

Conclusions:
High-intensity interval training significantly reduced the risk of rapid eGFR decline in older adults.
RE-SHAPING THE PROPHET: Baḥr al-Mādhī, Vernacular Fracture and Characteristics of Hadith Commentary in Nusantara
Authors: Firdausy Hilmy 
Published: February 2025

<p class="06IsiAbstrak"><em></em>Baḥr al-Mādhī Syarah Bagi Mukhtasar Sahih al-Tirmidhi by Muhammad Idris al-Marbawi is one of the hadith works of Nusantara scholars, which contains wealthy textual data. It provides 22 chapters divided into 11 volume bundles. However well, not much research has touched on Baḥr al-Mādhī. This paper will specifically reveal the “locality” and distinctive aspects of the hadith commentary scheme in Baḥr al-Mādhī. For this purpose, this paper will use and apply the theory of vernacularization. The theory will record the meeting of “the local” and “ the universal”, which is expected to capture aroma of the Nusantara in the Baḥr al-Mādhī Syarah Bagi Sahih al-Tirmidhi written in Malay language with Pegon script. As a result, at least five methodical characteristics are applied by al-Marbawi in hadith commentary, methods that are never applied by other hadith scholars when observing and explaining the same hadith. The vernacularization or momentum of locality displayed in Baḥr al-Mādhī occurs at once at all its semiotic levels. In the context of the hadith commentary method, there are at least specific characteristics that distinguish Baḥr al-Mādhī from the typical hadith commentary books; 1) visualization of interpretation in the form of drawings and illustrations, 2) utilization of storytelling techniques, 3) the emergence of two-way dialogue and translation spaces, 4) clustering of quotations and 5) the use of pointers.<br />[Baḥr al-Mādhī Syarah Bagi Sahih al-Tirmidhi karya Muhammad Idris al-Marbawi adalah salah satu karya hadis ulama Nusantara yang memuat data tekstual yang sangat kaya. Ia menyediakan 22 juz bahasan yang dibagi ke dalam 11 bundel jilid. Namun sayangnya, tidak banyak penelitian yang menyentuh Baḥr al-Mādhī. Paper ini secara spesifik akan menguak aspek “lokalitas” dan yang khas dalam skema pensyarahan hadis dalam Baḥr al-Mādhī. Untuk kepentingan itu, teori vernakularisasi akan digunakan. Teori tersebut akan merekam pertemuan “yang lokal” dan “yang universal” ini diharapkan mampu memotret aroma kenusantaraan atau “roso jawi” dalam kitab syarah hadis yang ditulis dalam Bahasa Melayu beraksara pegon tersebut. Hasilnya, ada setidaknya lima karakteristik metodis yang diterapkan oleh al-Marbawi dalam mensyarah hadis; metode-metode yang tidak pernah diterapkan oleh para ulama hadis lainnya ketika mensyarah hadis yang sama. Vernakularisasi atau momentum lokalitas yang ditampilkan dalam Baḥr al-Mādhī terjadi sekaligus pada semua tataran semiotiknya. Dalam konteks metode tafsir hadis, setidaknya ada ciri-ciri khusus yang membedakan Bahr al-Mādhī dengan kitab tafsir hadis pada umumnya; 1) visualisasi interpretasi berupa gambar dan ilustrasi, 2) pemanfaatan teknik bercerita, 3) munculnya dialog dua arah dan ruang penerjemahan, 4) pengelompokan kutipan dan 5) penggunaan pointer.]<br /><br /></p>
Structure of the 30S translation initiation complex coupled to paused RNA polymerase and its potential for riboregulation
Authors: Luisi Ben , Roske Johann , Paris Giulia , Goyal Akanksha , Rodnina Marina , Zenkin Nikolay , Bandyra Katarzyna 
Published: February 2025

Abstract

In many bacterial species, transcription and translation can be coupled physically, with potential impact on the rates and efficiency of gene expression. Here, we present structural evidence from cryo-EM demonstrating that a bacterial RNA polymerase that is paused proximally to the promoter can associate with the pioneering 30S translation initiation complex (30S IC) through mutual binding of the transcription factor NusG. These findings suggest that the physical link between transcription and translation can be established prior to commitment to protein synthesis. Although the mRNA is embedded in this ‘early expressome’ complex, it can nonetheless interact with small regulatory RNA (sRNA) and be targeted for cleavage in the protein-coding region by the RNA degradosome assembly in vitro. The potential tagging of transcripts with sRNA during pioneering and subsequent stages of translation initiation, when the 30S IC is at the 5′ end of a polyribosome, may support surveillance processes that ensure efficient and rapid termination of gene expression in response to regulatory signals.
Comparative Study of Host DNA Depletion Methods for Microbial Metagenomics
Authors: Farraj Suha A. , El-Kafrawy Sherif A. , Kumosani Taha A. , Yousef Jehad M. , Alsubhi Tagreed L. , Alandijany Thamir A. , Bajrai Leena H. , Badreddine Samar A. , Atrouni Ahmed Al , Azhar Esam I. 
Published: February 2025

Abstract

One of the biggest obstacles in applying metagenomics in the clinical field is the increase of human genome reads in the resulting sequences. In this study, three depletion methods were compared that utilize the methylation of cytosine in human DNA as a mechanism of action. Two commercial kits NEBNext Microbiome DNA Enrichment Kit and MethylMiner™ Methylated DNA Enrichment Kit bind methylated cytosines to specific antibodies, along with MspJI restriction enzyme that digests methylated cytosines. The depletion methods were applied to a HeLa cell suspension (as a source for the human genome) spiked with well-characterized bacterial isolates of Staphylococcus aureus, ‎‎Klebsiella pneumoniae and Cryptococcus neoformans. The products of the depletion methods were run in parallel with undepleted samples as controls on Miseq. The outcome of the NEBNext Microbiome DNA Enrichment Kit showed the most significant decrease in human genome (p = 0.005) compared to undepleted samples and a significant increase in both K. pneumoniae (p = 0.005) and S. aureus reads (p = 0.014). While MethylMiner™ Methylated DNA Enrichment kit showed a significant increase for C. neoformans (p = 0.007) besides a significant increase in the percent coverage of the references for C. neoformans and K. pneumoniae (p = 0.046 and p = 0.004, respectively). Results showed that both kits could help in depleting human DNA and enriching spiked pathogens in the study sample. The findings of this study are recommended to be validated on a large number of clinical samples.
Gene Expression Variations Induced by Sevoflurane in Glia and Glioma Cells and the Role of EPHA3 in Sevoflurane’s Anti-Glioma Effect
Authors: Liu Hui , Yu Hao , Cao Yu , Gao Yang , Wei Shaoting , Shi Jinghui , Liu Desheng 
Published: February 2025

Introductions:
Sevoflurane, a commonly used anesthetic in surgery, can produce
anesthetic effects such as sedation and muscle relaxation upon inhalation, which
may lead to postoperative cognitive dysfunction. However, the molecular mechanism by
which sevoflurane affects nervous system diseases like glioma remains unclear.

Method:
In this study, we analyzed high-throughput single-cell transcriptome data of
sevoflurane treatment and identified immune cells that play crucial roles in biological
processes such as the immunoinflammatory response and the maintenance of the blood-
-brain barrier. A total of 11,244 genes and their variations were obtained by analyzing
the cell development trajectory. Additionally, 10 key genes affected by sevoflurane were
manually retrieved, and their protein-protein interaction network was constructed. The
Chinese Glioma Genome Atlas (CGGA) dataset was utilized for survival analysis.

Results:
This article reveals that sevoflurane can generate anesthetic effects through signaling
pathways such as the immunoinflammatory response, neuronal differentiation,
and the maintenance of the blood-brain barrier, all of which have implications for organ
injury and protection. Meanwhile, genes that play a key role in these immune pathways,
such as the DAAM2 and EPHA3 genes, are significantly associated with the survival of
glioma patients. This association implies that sevoflurane's influence on these genes
might potentially affect postoperative cognitive dysfunction and the overall outcome of
organ-organ interactions during and after surgery. Moreover, the experimental results demonstrated
that sevoflurane inhibits the invasion and migration of glioma cells by suppressing
the expression of EPHA3.

Conclusion:
The discovery of this new target may pave the way for identifying causative
gene regulation events and emphasize personalized treatments for nervous system
diseases.
Exploring the Dynamics of Asparagus racemosus Phytochemicals as Dual Target Inhibitors of Monkeypox Virus
Authors: Mishra Saurav Kumar , Chandra Anshuman , Mitra Namrata , Krishna Nikita , Singh Nagendra , Akash Shopnil , Jardan Yousef A. Bin , Bourhia Mohammed , Georrge John J. 
Published: February 2025

Aim:
This study aimed to screen the potential phytochemicals derived from
Asparagus racemosus (Shatavari) against Thymidylate Kinase (TMPK) and D9 decapping
enzyme, which is the vital target of the monkeypox virus and helps in the host--
pathogen interaction mechanism, using integrated docking, QSAR analysis, and a molecular
dynamics approach.

Background:
The Monkeypox Virus (MPXV) is a recently emerging outbreak with ongoing
infection cases. Drugs and vaccines for smallpox are being used to contain it.
However, no specific drugs or vaccines are available to combat this infection.

Methods:
The TMPK and D9 decapping enzymes were retrieved from the MPXV virus
UK strain in FASTA format. Due to the unavailability of an experimentally determined
structure, the 3D structure was modelled via SWISS-MODEL and further enhanced and
validated. The structure was subjected to docking analysis with the derived phytochemicals
from Asparagus racemosus using a maestro module. The potential inhibitors were
examined via QSAR analysis. Additionally, through MD simulation 250ns, the stability
was analyzed, and the MM-GBSA was employed to calculate the binding affinities.

Results:
The molecular investigation revealed asparoside-C (PubChem ID: 158598) and
asparoside-D (PubChem ID: 158597) to be potential hits among others for both targets
(TMPK and D9 decapping enzyme) compared to the reference drugs, i.e., tecovirimat,
brincidofovir, and cidofovir, possessing antiviral and required bioactivity analyzed via
the ADME and QSAR analyses. Moreover, the simulation study of over 250ns revealed
strong stability, followed by RMSD, RMSF, etc. The free energy calculation via MMGBSA
exhibited strong affinities of asparoside-C and asparoside-D towards the TMPK
and the D9 decapping enzyme according to their respective scores.

result:
The molecular investigation revealed Asparoside-C; (PubChem ID: 158598) and Asparoside-D (PubChem ID: 158597) as potential hits among others for both targets (TMPK and D9 decapping enzyme) compared to the reference drugs, i.e., Tecovirimat, Brincidofovir, and Cidofovir and also possess antiviral and required bioactivity analysed via the ADME and QSAR analysis. Moreover, the simulation study of over 250ns revealed strong stability, followed by their RMSD, RMSF, etc. The free energy calculation via MM-GBSA exhibited strong affinities of Asparoside-C and Asparoside-D towards the TMPK and the D9 decapping enzyme by their respective scores.

Conclusion:
The docking, QSAR, and simulation investigation revealed dual-target inhibitors
activity of phytochemicals from Asparagus racemosus towards the MPXV via
targeting TMPK and D9 decapping enzyme. It has been observed that asparoside-D and
asparoside-C can potentially combat MPXV.