bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Rubber Band Ligation and Hemorrhoidectomy in Patients With Symptomatic Hemorrhoids Grade III: A Multicenter, Open-Label, Randomized Controlled, Non-Inferiority Trial
Authors: van Oostendorp Justin Y. , Dekker Lisette , van Dieren Susan , Veldkamp Ruben , Bemelman Willem A. , Han-Geurts Ingrid J.M. ,   The HollAND study group
Published: February 2025

BACKGROUND:

The optimal management strategy for grade III hemorrhoids remains a subject of ongoing debate. Hemorrhoidectomy is the gold standard, but rubber band ligation offers a less invasive outpatient alternative. Treatment variability persists due to a lack of consensus on the preferred strategy.

OBJECTIVE:

To directly compare the effectiveness of rubber band ligation and hemorrhoidectomy in the treatment of grade III hemorrhoids.

DESIGN:

Open-label, parallel-group, randomized controlled non-inferiority trial.

SETTINGS:

Multicenter study across 10 Dutch hospitals from October 2019 to September 2022.

PATIENTS:

Patients (≥18 years) with symptomatic grade III (Goligher) hemorrhoids. Exclusions: prior rectal/anal surgery, >1 rubber band ligation/injection within the preceding three years, rectal radiation, preexisting sphincter injury, inflammatory bowel disease, medical unfitness for surgery (ASA >3), pregnancy, or hypercoagulability disorders.

INTERVENTIONS:

Randomized 1:1 to rubber band ligation or hemorrhoidectomy, with up to two banding sessions allowed.

MAIN OUTCOME MEASURES:

Primary: 12-month health-related quality of life and recurrence rate. Secondary: complications, pain, work resumption, and patient-reported outcome measures.

RESULTS:

Eighty-seven patients were randomized (47 rubber band ligation vs 40 hemorrhoidectomy). Rubber band ligation was not non-inferior to hemorrhoidectomy in quality adjusted life years (-0.045, 95% confidence interval -0.087 to -0.004). Recurrence rate was worse in the rubber band ligation group (47.5% vs 6.1%), with an absolute risk difference of 41% (95% confidence interval 24%–59%). Complication rates were comparable. Post-hemorrhoidectomy pain scores were higher during the first week (visual analogue scale 4 vs 1; p = 0.002). Rubber band ligation group returned to work sooner (1 vs 9 days; p = 0.021). Patient-reported hemorrhoidal symptom scores favored hemorrhoidectomy.

LIMITATIONS:

The study’s primary limitation was its early termination due to funding constraints, resulting in a relatively small sample size and limited statistical power. Patient recruitment was hindered by significant treatment preferences and the COVID-19 pandemic.

CONCLUSIONS:

Hemorrhoidectomy may benefit patients with grade III hemorrhoids in terms of quality of life, recurrence risk, and symptom burden, while Rubber Band Ligation allows faster recovery with less pain. These findings can guide clinical decision-making. See Video Abstract.

Clinical trial registration number:

NCT04621695.
A Machine-Learning Approach to Finding Gene Target Treatment Options for Long COVID
Authors: Lopez-Rincon Alejandro
Published: February 2025

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), encompasses a range of symptoms persisting for weeks or months after the acute phase of COVID-19. These symptoms, affecting multiple organ systems, significantly impact the quality of life. This study employs a machine-learning approach to identify gene targets for treating Long COVID. Using datasets GSE275334, GSE270045, and GSE157103, Recursive Ensemble Feature Selection (REFS) was applied to identify key genes associated with Long COVID. The study highlights the therapeutic potential of targeting genes such as PPP2CB, SOCS3, ARG1, IL6R, and ECHS1. Clinical trials and pharmacological interventions, including dual antiplatelet therapy and anticoagulants, are explored for their efficacy in managing COVID-19-related complications. The findings suggest that machine learning can effectively identify biomarkers and potential therapeutic targets, offering a promising avenue for personalized treatment strategies in Long COVID patients.
Amyloid-β precursor protein promotes tumor growth by establishing an immune-exclusive tumor microenvironment
Authors: Yin Tao , Wang Guoping , Ma Zhehao , Wang Liuyang , Chen Rui , Xiang Kun , Tan Lianmei , Wang Yan , Chong Mengyang , Liang Yaosi , Pan Christopher C. , Alexander Peter B. , Lim Bryan Jian Wei , Wang Ergang , Liu Bushangqing , Yan Chengsong , Li Qi-Jing , Wang Xiao-Fan
Published: February 2025

During initiation and progression, cancerous tissue hijacks a series of elaborate tissue homeostatic mechanisms to avoid immune surveillance, including neuro-immune interactions. Here, we show that amyloid-β precursor protein (APP) and its β-cleavage product amyloid-β1-42 (Aβ1-42), well-known in the pathogenesis of Alzheimer’s disease (AD), are expressed in multiple cancer tissues. However, the oncogenic activity of APP is due to its E1 domain, instead of Aβ1-42. Mechanistically, APP restricts immune cells influx into tumor microenvironment (TME) and impairs CD8+ T cell and NK cell-based immunity, by dampening type I interferon (IFN) response in TME. We also provide proof-of-concept that vaccination targeting APP is effective for cancer prevention. Our current study reveals a previously unrecognized role of APP in cancer immune surveillance, and provides a new strategy for cancer prevention and treatment by targeting APP.
Accurate Somatic SV detection via sequence graph model-based local pan-genome optimization
Authors: Tu Kailing , Zhang Qilin , Li Yang , Li Yucong , Yuan Lanfang , Tang Jie , Xia Lin , Wang Jing , Huang Wei , Xie Dan
Published: February 2025

Somatic structural variations (Somatic SVs) are critical genomic alterations with significant implications in cancer genomics. Although long-read sequencing (LRS) theoretically provides optimal resolution for detecting these variants due to its ability to span large genomic segments, current LRS - based methods, which are derived from short - read - based somatic SV detection algorithms, mainly rely on split - read information. The high error rate of long - read sequencing and the errors introduced by the seed-and-chaining strategy of mainstream alignment algorithms affect the accuracy of these split-reads, making precise detection of somatic SVs still a challenge. To address this issue, we propose the TDScope algorithm, which uses the complete sequence information of local genomic regions provided by long-read sequencing to construct a local graph genome and combines random forest technology to achieve precise detection of somatic structural variations. TDScope outperforms state-of-the-art somatic SV detection methods on paired long-read whole-genome sequencing (WGS) benchmark cell lines, with an average F1-score improvement of 20%. It also demonstrates superior performance in detecting somatic SVs and resolving heterogeneous genomes in tandem repeat-like simulated somatic SV datasets. We also provide the ScopeVIZ tool to offer users visualization evidence of local graph genomes and somatic SV sequences. All code implementations are publicly available on GitHub (https://github.com/Goatofmountain/TDScope).
Leveraging Comparative Phylogenetics for Evolutionary Medicine: Applications to Comparative Oncology
Authors: Mellon Walker J. , Sterner Beckett , Ågren J. Arvid , Vincze Orsolya , Marx Matthew T. , Kapsetaki Stefania E. , Huang Ping-Han , Yavari Bryan , McCollum Hunter W. , Natterson-Horowitz Barbara , Human Hannah , Baciu Cristina , Richker Harley , Mallo Diego , Maley Carlo , Harmon Luke J. , Compton Zachary T.
Published: February 2025

Comparative phylogenetics provides a wealth of computational tools to understand evolutionary processes and their outcomes. Advances in these methodologies have occurred in parallel with a surge in cross-species genomic and phenotypic data. To date, however, the majority of published studies have focused on classical questions in evolutionary biology, such as speciation and the ecological drivers of trait evolution. Here, we argue that evolutionary medicine in general, and our understanding of the origin and diversification of disease traits in particular, would be greatly expanded by a wider integration of phylogenetic comparative methods (PCMs). We use comparative oncology – the study of cancer across the tree of life – as a case study to demonstrate the power of the approach and show that implementing PCMs can highlight the mode and tempo of the evolutionary changes in intrinsic, species-level disease vulnerabilities.
Highly efficient genome editing inBacillus subtilisvia miniature DNA nucleases IscB
Authors: Gao Jie , Tang Hongjie , Yang Yuhan , Wang Hengyi , Li Qi
Published: February 2025

Existing CRISPR-based genome editing tools are limited inBacillus subtilisdue to the largecasgene. The recently reported DNA nuclease IscB has the potential to be developed into a novel genome editing tool due to its size being one-third of Cas9, while its application inB. subtilisremains unexplored. In this study, genome editing tools pBsuIscB/pBsuenIscB based on IscB and enIscB (enhanced IscB) were established inB. subtilisSCK6, and successfully deleted 0.6 kb to 4.3 kb genes with efficiencies up to 100%. Subsequently, the pBsuenIscB with higher deletion efficiency was used, whereby the large genomic fragment of 37.7 kb or 169.9 kb was deleted with only one ωRNA. Additionally, single-copy or multi-copymCherrygenes was integrated by using pBsuenIscB. Finally, the editing plasmid was eliminated and the second round of genome editing was completed. Overall, this study has successfully applied IscB toB.subtilis, expanded the genome editing toolbox ofB. subtilis, and will help to constructB. subtilischassis for production of a variety of biomolecules.
Alternative approaches to single-cell trajectory inference using a commute time matrix
Authors: Houston Douglas W.
Published: February 2025

Single-cell technology has enhanced the high-resolution analysis of dynamic developmental cell fate decisions. A number of elegant mathematical and computational approaches have been developed for using single-cell genomics data to identify gene regulatory events and cell state changes during embryonic development and related processes. These approaches are typically used in combination to model dynamic cell differentiation trajectories but have different underlying mathematical foundations. The extent to which commonly used algorithms for trajectory modeling, such as data imputation, pseudotemporal ordering, and cell fate probability modeling, might be derived from the same underlying approach has not been widely explored. This work describes the use of a matrix based on the commute time of a graph as a single consistent kernel for cell fate trajectory modeling. The commute time kernel is derived from significant eigenvectors of the pseudo-inverse of the graph Laplacian in a manner that preserves commute time. This kernel matrix is used directly in trajectory inference methods and recapitulates the results obtained using different algorithms using three benchmark datasets. Additionally, a comparison of commute time kernels between spliced and unspliced counts was effective for identifying populations of circadian-cycling progenitor cells in differentiating pancreatic endocrine cells. Overall, this work identifies the commute time kernel as a potential parsimonious measure for multiple aspects of trajectory inference.
EEG Microstates reveal distinct network dynamics in lucid and non-lucid REM sleep
Authors: Wang Xinlin , Peters Emma , Strelen Johannes , Lockhart Nathan , Franklin Michael , LaBerge Stephen , Koenig Thomas , Dresler Martin , Erlacher Daniel
Published: February 2025

During lucid dreaming, the dreamer is aware that they are dreaming. In past years, numerous studies have explored the characteristics of lucid dreams, which link lucid dreams to vivid visual perception, positive emotions, and wake-like metacognition and executive functions. To determine brain network activity associated with the conscious experience during lucid dreaming, we analyzed 39 sleep recordings (non-lucid REM vs. lucid REM) with 32-channel polysomnography from 8 lucid dreamers, using EEG microstate analysis. We found that microstates A and G dominated during lucid REM sleep compared to non-lucid REM sleep, and microstates B, C, and D dominated during non-lucid REM sleep compared to lucid REM sleep. We explored the correlation of our microstate maps with previous findings based on topographical similarities of the microstate maps in our study. This suggests that in our study, microstate A might be associated with emotional processing, microstate B with visual processing, microstate C with salience network activity, microstate D with executive functions, and microstate G with the default mode network. Our results suggest that lucidity during REM sleep is associated with increased self-visualization, metacognition, and executive processing, along with decreased emotional processing and reduced default mode network activity. Additionally, we found the inverse relationship between the presence of microstates/networks associated with regions that serve specific functions and evidence for the function being used. This might indicate the inhibitory function of the EEG microstates during sleep. Our study provides novel insight into the distinct network dynamics in lucid and non-Lucid REM sleep.
Genetic targeting of astrocytes associated with specific neuronal circuit in adultDrosophila
Authors: Dopp Joana , Hobin Frederik , Mastroianni Sofia , Yan Jiekun , van Ninhuys Lisa , Liu Sha
Published: February 2025

Astrocytes are the major glial population of the brain and have been associated with a vast number of functions. To probe this diversity and to reach a similar level of understanding about astrocyte physiology that we have about neurons, we need genetic tools to target specific astrocytic subpopulations. InDrosophila, we are restricted to using driver lines that drive expression in astrocytes throughout the brain. To target specific astrocytes, we have optimized the genetic tool TRACT (and refer to it as astro-TRACT), allowing effector expression specifically in local astrocytes of a given neuronal circuit. We analyzed specificity, sensitivity and reproducibility of the tool across various MB split-Gal4 drivers. We found that the number of pre-synapses correlates positively with the success of the tool. Applying the tool to characterize morphology of individual astrocytes revealed that local astrocytes around MB medial compartments project into the ellipsoid body. Astro-TRACT will be a valuable resource to investigate both mechanistic astrocyte-neuron signaling and functional and structural astrocytic diversity across the adultDrosophilabrain.
A Generalized Platform for Artificial Intelligence-powered Autonomous Protein Engineering
Authors: Singh Nilmani , Lane Stephan , Yu Tianhao , Lu Jingxia , Ramos Adrianna , Cui Haiyang , Zhao Huimin
Published: February 2025

Proteins are the molecular machines of life with numerous applications in energy, health, and sustainability. However, engineering proteins with desired functions for practical applications remains slow, expensive, and specialist-dependent1–3. Here we report a generally applicable platform for autonomous protein engineering that integrates machine learning and large language models with biofoundry automation to eliminate the need for human intervention, judgement, and domain expertise. Requiring only an input protein sequence and a quantifiable way to measure fitness, this autonomous platform can be applied to engineer virtually any protein. As a proof of concept, we engineeredArabidopsis thalianahalide methyltransferase (AtHMT)4for a 90-fold improvement in substrate preference and 16-fold improvement in ethyltransferase activity, along with developing aYersinia mollaretiiphytase (YmPhytase)5,6variant with 26-fold improvement in activity at neutral pH. This was accomplished in four rounds over four weeks, while requiring construction and characterization of fewer than a total of 500 variants for each enzyme. This platform for autonomous experimentation paves the way for rapid advancements across diverse industries, from medicine and biotechnology to renewable energy and sustainable chemistry.
TGIF2 is a major regulator of neural stem cell fate and neurogenic priming
Authors: Li Yiling , Krontira Anthi C. , Vierl Franziska , Richter Maria L. , Wang Weixu , Merl-Pham Juliane , Theis Fabian J. , Hauck Stefanie M. , Götz Magdalena
Published: February 2025

During brain development, neural stem cells (NSCs) must balance self-renewal with differentiation and ensure lineage progression. To identify novel regulators of NSCs during neurogenesis, we isolated NSCs by FACS from the mouse cerebral cortex and ganglionic eminence at mid-neurogenesis, and at birth, when gliogenesis starts in both, but neurogenesis only continues in the latter region. RNA-seq and ATAC-seq revealed major transcriptional and chromatin changes between these stages and identified TGFB-Induced Homeobox Factor 2 (TGIF2) as a key candidate factor in neurogenic NSCs.In vitroandin vivoexperiments demonstrated a potent role of TGIF2 controlling NSC fate maintenance mediated by its interaction with the SIN3A/HDAC repressor complex suppressing neuronal differentiation genes. Multiomic comparison of NSC and neuron gene expression allowed the comprehensive analysis of neurogenic priming in cortical NSCs, identifying TGIF2 as its major regulator by restraining neuronal differentiation gene activation in NSCs.
Dissection and internal observation of the giant tropical bont tickAmblyomma variegatum
Authors: Pature Naomie , Pagès Nonito , Rodrigues Valérie , Meyer Damien F.
Published: February 2025

Ticks are ectoparasites that feed on the blood of animals and humans and are among the arthropods responsible for numerous human and animal diseases worldwide. The tropical bont tick,Amblyomma variegatum, is a significant natural vector ofEhrlichia ruminantium, the causative agent of heartwater. This disease is endemic in many countries, including those in sub-Saharan Africa and certain Caribbean islands. Due to the potential of heartwater and its vector to pose an economic and health threats to non-endemic regions, they have been designated as high-consequence foreign animal diseases and pests by the United States Department of Agriculture’s Animal and Plant Health Inspection Service. Understanding the ecology and biology ofA. variegatumis critical for developing effective control methods to limit its spread to other geographic regions. A key step in this process is the isolation of tick organs and further elucidation of their functions (i.e. vector competence). However, the literature contains limited documentation of the complete internal structure ofAmblyommatick species. In this study, we describe the internal structure of unfed nymphs, partially engorged males, and unfed and partially engorged females of the tick speciesA. variegatum. The objective is to facilitate the identification and the localization organs of interest while highlighting the morphological differences between the tropical bont tick and other tick species. This foundational work will support the development of various applications following the isolation of tick organs. These findings not only deepen our understanding ofAmblyomma variegatumanatomy but also provide a critical foundation for tackling the broader challenges of tick-borne diseases and advancing vector control strategies in both endemic and non-endemic regions.
Toxoplasma gondiias a Causal Factor in Schizophrenia: Evidence from Two Large Cohorts
Authors: Israel Ariel , Weizman Avi , Israel Sarah , Stokar Joshua , Ashkenazi Shai , Vinker Shlomo , Magen Eli , Merzon Eugene
Published: February 2025

Background

Schizophrenia (SCZ) is a debilitating psychiatric disorder with a complex and poorly understood etiology. Numerous studies have reported a high prevalence ofToxoplasma gondii-specific immunoglobulins in SCZ patients, indicating past infection, yet the clinical significance of this association remains unclear.

Methods

We investigated the impact of medication purchases and past medical conditions on SCZ risk in two large cohorts. In a national cohort, we compared 3,273 individuals diagnosed with SCZ to 32,730 matched controls, adjusting for gender, age, ethnicity, socioeconomic status, and year of enrollment. Key findings were validated prospectively on the U.S. TriNetX collaborative network, which includes over 117 million individuals.

Results

In both cohorts, individuals who used atovaquone had a significantly lower risk of developing SCZ over the next decade (adjusted odds ratio = 0.26 in the national cohort; hazard ratio = 0.29 in the TriNetX cohort, bothP< 0.001). A similar reduction in SCZ risk was observed with clindamycin use, consistent with the known efficacy of both atovaquone and clindamycin againstT. gondii.

Discussion

Based on new epidemiological associations identified by this study, we propose a novel hypothesis for SCZ pathogenesis, in which persistentT. gondiicolonization in the microbiome, combined with prolonged dissemination into the central nervous system due to an impaired immune response, liver function, and/or alterations in the skin microbiome, may contribute to SCZ development in genetically susceptible individuals.

Conclusion

Individuals who received medications known to targetT. gondiihad significantly lower SCZ risk, suggesting a causative role for this pathogen and highlighting potential preventive or therapeutic roles for these medications in SCZ. The observed associations provide new insights into the mechanisms linkingT. gondiito SCZ, opening novel avenues for research and intervention strategies.
Large-scale global molecular epidemiology of antibiotic resistance determinants inStreptococcus pneumoniae
Authors: Shawrob Kazi Shefaul Mulk , Dhariwal Achal , Salvadori Gabriela , Gladstone Rebecca Ashley , Junges Roger
Published: February 2025

Background

Streptococcus pneumoniaeis a leading pathogen in terms of deaths attributable to or associated with antimicrobial resistance globally. Thus, monitoring antibiotic resistance determinants constitutes a key aspect of surveillance efforts.

Aim

Leveraging on publicly available whole-genome sequencing data, we aimed to investigate the presence and distribution patterns of antibiotic resistance inS. pneumoniaewith a focus on multi-drug resistance and serotype distribution.

Methods

Metadata and genomes were obtained from the National Center for Biotechnology Information Pathogen Detection database. Curation and harmonization were performed in R and SPSS. Data on resistance patterns was defined according to AMRFinderPlus and a combination of prediction tools were employed forin silicoserotyping.

Results

Analyses involved 75,161 genomes totaling 122,673 gene/allele counts from 14 antibiotic classes. Multi-drug resistance was observed in 16.7% of isolates with the highest increasing rates in Asia and South America. Within antibiotic classes, increase in macrolide resistance genes was highlighted, particularly in the proportion of genomes presentingmefA/msrD. Over a third of isolates with serotypes 19F, 23F, 15A, 6B, and 19A showed multi-drug resistance. We further observed the highest significant increases in the presence of resistance in 33F, 22F, 10A, and 23A. Serotype 13, not included in any vaccine formulation, presented high multi-drug resistance rates with a strong increasing trend.

Conclusions

The findings of this study highlight variations in resistance determinants globally and across serotypes over time. Collectively these data underscore the added value of utilizing public whole-genome sequencing data to investigate the effectiveness and repercussions of treatment and vaccination strategies on managing antibiotic resistance.
Gene Editing forATXN3Inactivation in Machado-Joseph disease: CRISPR-Cas9 as a Therapeutic Alternative to TALEN-Induced Toxicity
Authors: Lopes Sara Monteiro , Lopes Miguel Monteiro , Oliveira Daniela , Santana Magda Matos , Fernandes Ana Rita , Vasconcelos-Ferreira Ana , Pereira Dina , Casquinha Maria , Nóbrega Clévio , Matos Carlos A. , Sanjana Neville E. , Hsu Patrick D. , Ran Fei Ann , Swiech Lukasz , Cong Le , Zhang Feng , Nobre Rui Jorge , de Almeida Luís Pereira
Published: February 2025

Machado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder, caused by an over-repetition of the polyglutamine-codifying region in theATXN3gene. Strategies based on the suppression of the deleterious gene products have demonstrated promising results in pre-clinical studies. Nonetheless, these strategies do not target the root cause of the disease. In order to prevent the downstream toxic pathways, our goal was to develop gene editing-based strategies to permanently inactivate the humanATXN3gene. TALENs and CRISPR-Cas9 systems were designed to target exon 2 of this gene and functional characterization was performed in a human cell line. After the demonstration of TALEN’s and CRISPR-Cas9 efficiency on gene disruption, a sequence of each system was selected for furtherin vivoexperiments. Although both TALENs and CRISPR-Cas9 systems led to a drastic reduction of ATXN3 aggregates in the striatum of a lentiviral-based mouse model of MJD/SCA3, only CRISPR-Cas9 system allowed the improvement of key neuropathological markers of the disease. Importantly, the administration of the engineered system in YAC-MJD84.2/84.2 mice mediated a delay in disease progression, when compared with non-treated littermates. These data provide the firstin vivoevidence of the efficacy of a CRISPR-Cas9-based approach to permanently inactivate theATXN3gene in the brain of two mouse models of the disease, supporting its potential as a new therapeutic avenue in the context of MJD/SCA3.
Neurons in auditory cortex integrate information within constrained temporal windows that are invariant to the stimulus context and information rate
Authors: Sabat Magdalena , Gouyette Hortense , Gaucher Quentin , Lopez Espejo Mateo , David Stephen V , Norman-Haignere Sam , Boubenec Yves
Published: February 2025

Much remains unknown about the computations that allow animals to flexibly integrate across multiple timescales in natural sounds. One key question is whether multiscale integration is accomplished by diverse populations of neurons, each of which integrates information within a constrained temporal window, or whether individual units effectively integrate across many different temporal scales depending on the information rate. Here, we show that responses from neurons throughout the ferret auditory cortex are nearly completely unaffected by sounds falling beyond a time-limited "integration window". This window varies substantially across cells within the auditory cortex (~15 to ~150 ms), increasing substantially from primary to non-primary auditory cortex across all cortical layers, but is unaffected by the information rate of sound. These results indicate that multiscale computation is predominantly accomplished by diverse and hierarchically organized neural populations, each of which integrates information within a highly constrained temporal window.
Decoding auditory working memory load from EEG alpha oscillations
Authors: Yuan Yichen , Gayet Surya , Wisman Derk Christiaan , van der Stigchel Stefan , van der Stoep Nathan
Published: February 2025

Working memory (WM) enables temporary retention of task-relevant information for imminent use. Increases in visual WM load are accompanied by elevated contralateral delay activity (CDA), and EEG alpha-band power. While most WM research focuses on the visual domain, it remains unknown whether similar EEG responses also reflect WM load in the auditory domain. Using EEG, we set out to establish such neuro-markers of auditory WM load. Participants memorized the pitches of 1 to 4 pure tones presented to one ear, with 1 to 4 consistent distractor tones presented to the other ear. Behaviorally, auditory WM capacity plateaued between set-sizes two and three. Unlike for visual WM, auditory WM load was not reflected in lateralized EEG responses. This shows that the CDA is a vision-specific rather than domain-general neuro-marker of WM load. Applying multivariate pattern analyses on the delay activity revealed that auditory WM load is reflected in (mostly temporal) patterns of alpha-band oscillations. Surprisingly, a temporal generalization analysis revealed that the alpha patterns reflecting specific load conditions changed throughout the maintenance period (despite load being inherently constant), revealing dynamic coding of auditory WM load.
Sex-related gut microbiota in three geographically separated Norway lobster (Nephrops norvegicus) populations
Authors: Rusanova Polina , Nikouli Eleni , Casini Michele , Bono Gioacchino , Mente Elena , Meziti Alexandra , Kormas Konstantinos
Published: February 2025

Despite the ecological and economic interest of the Norway lobster (Nephrops norvegicus), its gut microbiota remains largely understudied. The current study aimed at investigating the gut bacterial microbiota in three geographically separatedN. norvegicuspopulations from the Mediterranean and the North Sea and detect any potential sex-related microbiota differences, by high-throughput sequencing of the V3-V4 16S rRNA gene diversity of the gut tissue. From the Greek population, egg-bearing females were also caught. A total of 2,385 operational taxonomic units (OTUs) were identified and between 417 and 1290 occurred in each population/sex group. The dominant OTUs belonged to the Fusobacteriia and Bacteroidia (Sweden), Bacilli and Gammaproteobacteria (Italy) and Spirochaetia and Bacilli (Greece) classes. In the eggs, the Actinobacteria, Alphaproteobacteria and Gammproteobacteria prevailed. Four OTUs related to theOceanispirochaeta,Kordiimonas, Desulfovibrio, Carboxylicivirgagenera and one unafilliated OTU were positively correlated (p values between 0.001 and 0.04) to body size indicating their potential role in the animal’s nutrition and growth. No statistically significant differences were found between males-females in any of the populations. However, statistically significant differences between populations for each sex, were found for all females (p values between 0.008 and 0.032) and for the males between the most distant populations, i.e. Italy and Sweden (p=0.021) and, Greece and Sweden (p=0.015). The eggs microbiota was statistically different from both the adult females (p=0.027) and males (p=0.046) gut microbiota. Overall, this study showed thatN. norvegicusgut microbiota vary for each sex between geographically distant populations.
Zebra finches produce intralaryngeal laminar flow whistles during panting
Authors: Anttonen Tommi , Loning Hugo , Felbo Freja M. , Christensen-Dalsgaard Jakob , Griffith Simon C. , Naguib Marc , Elemans Coen P.H.
Published: February 2025

Birds and mammals converged upon the same physical mechanism of vocal fold vibration to produce their broad range of voiced sounds critical to communication1. The frequency range of vocal fold vibration is limited per species by biophysical constraints to 3-4 octaves2. However, recent work reported vocalizations in zebra finches with apparent fundamental frequencies of 7-11 kHz3that far exceed the range of regular calls and song (0.5-1.5 kHz)4,5. These “heat” or “incubation” calls are suggested to have close-range communicative relevance in the global temperature rise context3,6, but their acoustics are poorly described and by what biophysical mechanism they are produced remains unknown. We recorded heat calls in adult zebra finchesin vivoand show they are extremely soft, frequency-modulated calls with source levels of 13.9 ± 3.3 dB SPL at one meter with dominant frequencies of 6.8 ± 0.6 kHz. Through a series ofin vitroexperiments, we establish that these calls are aerodynamic whistles produced inside the avian larynx, not syrinx, during inspiration. Respiratory air flow during whistle production is an order of magnitude higher than song and consistent with thermal panting for evaporative cooling6,7. Laryngeal geometry and dimensional flow analysis suggest that these whistles are laminar flow whistles that occur when a flow boundary layer is in a transition phase from laminar to turbulent flows8,9. Birds, like some rodents10-12, are thus able to produce both voiced sounds and aerodynamical whistles in their vocal tract.
LCLNCRdb: A Comprehensive Resource for Investigating long non-coding RNAs in Lung Cancer
Authors: Dwivedi Ayushi , Zulfia S Afrin , Thippana Mallikarjuna , Cholleti Sai Nikhith , Vindal Vaibhav
Published: February 2025

Lung cancer is a primary cause of death worldwide, accounting for a substantial number of mortalities. It involves several molecular mechanisms that are influenced by long non-coding RNAs (lncRNAs), a specific types of RNA molecules that do not code for proteins. Several research have revealed the importance of long non-coding RNAs (lncRNAs) in the initiation, progression, and development of resistance to lung cancer therapy. However, there are no centralized web resources or databases that collect and integrate information regarding lung cancer associated lncRNAs. This led to the development of the LCLNCRdb, a manually curated database that includes data from various sources, such as published research articles, and The Cancer Genome Atlas (TCGA) data portal. This database contains detailed information on 1102 lncRNAs that have differential expression patterns in lung cancer patients, such as lncRNA name, entrez ID, Ensemble ID, HGNC ID, NONCODE ID, lung cancer type, source, lncRNA expression pattern, experimental techniques, network analysis, and survival analysis details. The database offers a user-friendly platform for browsing, retrieving, and downloading data, and it features a dedicated submission page for researchers to share newly identified lncRNAs related to lung cancer. LCLNCRdb aims to enhance our knowledge of lncRNA deregulation in lung cancer and provides a valuable and timely resource for lncRNA research. The database is freely accessible at (https://dbtcmi.in/tools/lclncrdb/main.html).
Retention of PDGFR-β function in mice in the absence of phosphatidylinositol 3′-kinase and phospholipase Cγ signaling pathways
Authors: Tallquist Michelle D. , Klinghoffer Richard A. , Heuchel Rainer , Mueting-Nelsen Peter F. , Corrin Philip D. , Heldin Carl-Henrik , Johnson Richard J. , Soriano Philippe
Published: July 2002

Signal transduction by the platelet-derived growth-factor receptor β (PDGFR-β) tyrosine kinase is required for proper formation of vascular smooth muscle cells (VSMC). However, the importance of individual PDGFR-β signal transduction pathways in vivo is not known. To investigate the role of two of the pathways believed to be critical for PDGF signal transduction, we have generated mice that bear a PDGFR-β that can no longer activate PI3kinase or PLCγ. Although these mutant mice have normal vasculature, we provide multiple lines of evidence in vivo and from cells derived from the mutant mice that suggest that the mutant PDGFR-β operates at suboptimal levels. Our observations indicate that although loss of these pathways can lead to attenuated PDGF-dependent cellular function, certain PDGFR-β-induced signal cascades are not essential for survival in mice.
Release of Flavonoids by the Soybean Cultivars McCall and Peking and Their Perception as Signals by the Nitrogen-Fixing SymbiontSinorhizobium fredii1
Authors: Pueppke Steven G. , Bolaños-Vásquez Maria Cristina , Werner Dietrich , Bec-Ferté Marie-Pierre , Promé Jean-Claude , Krishnan Hari B.
Published: July 2002

Sinorhizobium frediistrain USDA191 forms N-fixing nodules on the soybean (Glycine max L. Merr.) cultivars (cvs) McCall and Peking, but S. fredii strain USDA257 nodulates only cv Peking. We wondered whether specificity in this system is conditioned by the release of unique flavonoid signals from one of the cultivars or by differential perception of signals by the strains. We isolated flavonoids and usednodC and nolX, which arenod-box-dependent and -independent nodgenes, respectively, to determine how signals activate genes in the microsymbionts. Seeds of cv McCall and cv Peking contain the isoflavones daidzein, genistein, and glycitein, as well as their glucosyl and malonylglucosyl glycosides. Roots exude picomolar concentrations of daidzein, genistein, glycitein, and coumestrol. Amounts are generally higher in cv Peking than in cv McCall, and the presence of rhizobia markedly influences the level of specific signals. Nanomolar concentrations of daidzein, genistein, and coumestrol induce expression of nodC and nolX in strain USDA257, but the relative nolX-inducing activities of these signals differ in strain USDA191. Glycitein and the conjugates are inactive. Strain USDA257 deglycosylates daidzin and genistin into daidzein and genistein, respectively, thereby converting inactive precursors into active inducers. Although neither soybean cultivar contains unique nod-gene-inducing flavonoids, strain- and cultivar-specific interactions are characterized by distinct patterns of signal release and response.
Characterization of Spermidine Binding to Solubilized Plasma Membrane Proteins from Zucchini Hypocotyls1
Authors: Tassoni Annalisa , Antognoni Fabiana , Luisa Battistini Maria , Sanvido Olivier , Bagni Nello
Published: July 2002

In this work [14C]spermidine binding to total proteins solubilized from plasma membrane purified from zucchini (Cucurbita pepo L.) hypocotyls was investigated. Proteins were solubilized using octyl glucoside as a detergent. Specific polyamine binding was thermolabile, reversible, pH dependent with an optimum at pH 8.0, and had a Kd value of 5 μm, as determined by glass-fiber-filter assays. Sephadex G-25 M gel-filtration assays confirmed the presence of a spermidine-protein(s) complex with a specific binding activity. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and native polyacrylamide gel electrophoresis of collected fractions having the highest specific spermidine-binding activity, several protein bands (113, 75, 66, and 44 kD) were identified. The specificity of spermidine binding was examined by gel-filtration competition experiments performed using other polyamines and compounds structurally related to spermidine. Partial purification on Sephadex G-200 led to the identification of 66- and 44-kD protein bands, which may represent the putative spermidine-binding protein(s) on the plasmalemma.
Developmental and Light Regulation of Desacetoxyvindoline 4-Hydroxylase in Catharanthus roseus (L.) G. Don.1
Authors: Vazquez-Flota Felipe A. , De Luca Vincenzo
Published: July 2002

The expression of desacetoxyvindoline 4-hydroxylase (D4H), which catalyzes the second to the last reaction in vindoline biosynthesis inCatharanthus roseus, appears to be under complex, multilevel developmental and light regulation. Developmental studies with etiolated and light-treated seedlings suggested that although light had variable effects on the levels of d4htranscripts, those of D4H protein and enzyme activity could be increased, depending on seedling development, up to 9- and 8-fold, respectively, compared with etiolated seedlings. However, light treatment of etiolated seedlings could stop and reverse the decline ofd4h transcripts at later stages of seedling development. Repeated exposure of seedlings to light was also required to maintain the full spectrum of enzyme activity observed during seedling development. Further studies showed that a photoreversible phytochrome appeared to be involved in the activation of D4H, since red-light treatment of etiolated seedlings increased the detectable levels ofd4h transcripts, D4H protein, and D4H enzyme activity, whereas far-red-light treatment completely reversed this process. Additional studies also confirmed that different major isoforms of D4H protein exist in etiolated (isoelectric point, 4.7) and light-grown (isoelectric point, 4.6) seedlings, suggesting that a component of the light-mediated activation of D4H may involve an undetermined posttranslational modification. The biological reasons for this complex control of vindoline biosynthesis may be related to the need to produce structures that could sequester away from cellular activities the cytotoxic vinblastine and vincristine dimers that are derived partially from vindoline.
Distinct Calcium Signaling Pathways Regulate Calmodulin Gene Expression in Tobacco
Authors: van der Luit Arnold H. , Olivari Claudio , Haley Ann , Knight Marc R. , Trewavas Anthony J.
Published: July 2002

Cold shock and wind stimuli initiate Ca2+ transients in transgenic tobacco (Nicotiana plumbaginifolia) seedlings (named MAQ 2.4) containing cytoplasmic aequorin. To investigate whether these stimuli initiate Ca2+ pathways that are spatially distinct, stress-induced nuclear and cytoplasmic Ca2+ transients and the expression of a stress-induced calmodulin gene were compared. Tobacco seedlings were transformed with a construct that encodes a fusion protein between nucleoplasmin (a major oocyte nuclear protein) and aequorin. Immunocytochemical evidence indicated targeting of the fusion protein to the nucleus in these plants, which were named MAQ 7.11. Comparison between MAQ 7.11 and MAQ 2.4 seedlings confirmed that wind stimuli and cold shock invoke separate Ca2+ signaling pathways. Partial cDNAs encoding two tobacco calmodulin genes, NpCaM-1 andNpCaM-2, were identified and shown to have distinct nucleotide sequences that encode identical polypeptides. Expression ofNpCaM-1, but not NpCaM-2, responded to wind and cold shock stimulation. Comparison of the Ca2+dynamics with NpCaM-1 expression after stimulation suggested that wind-induced NpCaM-1 expression is regulated by a Ca2+ signaling pathway operational predominantly in the nucleus. In contrast, expression ofNpCaM-1 in response to cold shock is regulated by a pathway operational predominantly in the cytoplasm.
Identification by Large-Scale Screening of Phytochrome-Regulated Genes in Etiolated Seedlings of Arabidopsis Using a Fluorescent Differential Display Technique
Authors: Kuno Norihito , Muramatsu Takamichi , Hamazato Fumiaki , Furuya Masaki
Published: July 2002

Phytochrome A (PhyA)-regulated genes in 6-d-old etiolated seedlings of Arabidopsis Landsbergerecta were identified by fluorescent differential display. To screen for PhyA-regulated genes, mRNA fingerprints of the wild type and the phyA-201 mutant were compared from samples prepared 4 h after far-red light irradiation. Approximately 30,000 bands of cDNA were displayed by fluorescent differential display, and 24 differentially expressed bands were observed. Sequence analysis revealed that they represent 20 distinct genes. Among them, 15 genes were confirmed as PhyA regulated by northern-blot (or reverse transcription-polymerase chain reaction) analysis. Thirteen up-regulated genes included 12 known genes that encode nine photosynthetic proteins, two enzymes involved in the biosynthesis of chlorophyll, one DNA damage repair/toleration-related protein, and one unknown gene. Two down-regulated genes were identified as encoding a xyloglucan endotransglycosylase-related protein and a novel member of the ASK protein kinase family. In thephyA-201 mutant and the phyA-201phyB-1double mutant, expression of all of these genes was photoreversibly up- or down-regulated by type II phytochromes. The results indicate that modes of photoperception differ between PhyA and PhyB, but that both types of phytochromes have overlapping effects on the photoregulation of gene expression.
Whither HR? Don’t people matter anymore?
Authors: Rabey Gordon
Published: July 2002

The boundaries of living in the last millennium have disappeared. Time, distance and space have new meanings and make new demands. Structures which gave purpose and stability to the world of work are losing their relevance. We need to build wind turbines, not shelter walls, if we are to harness the new forces. Against that backdrop, four questions are asked: amidst the changing pressures who are the key people who maintain the outputs and achieve targets, and how are they valued? Despite the teaching of many theorists has money now become the primary motivator? What is the shape of the new organisation? Are you increasing your human capital? This paper seeks to open a door for wide discussion.
Action learning revisited
Authors: Cusins Peter
Published: July 2002

Action learning is defined as a dynamic syndrome (flowing together)
of four primary activities, each of which enhances the others. In
practice, experiential learning is given focus by being
problem‐oriented. This combination of experiential learning and problem‐solving is supplemented and enhanced by the acquisition
of additional relevant knowledge and the support of a co‐learner
group. Describes in detail the processes and how they interact, and
provides practical checklists for faculty to assess their facilitation
performance.
Proximate composition of ten standardized Nigerian dishes
Authors: Oguntona Clara R.B. , Odunmbaku Justina A. , Ottun Bolanle O.
Published: July 2002

The objectives of the study are the standardization of ten Nigerian dishes and the determination of their proximate composition. Recipes for the ten dishes were obtained through the use of questionnaires. There were 200 respondents to the questionnaires consisting of housewives living in the major towns of south‐western Nigeria. One recipe for each meal was extracted from a known cookery book. The means for each ingredient of all the dishes were calculated from ten randomly selected recipes and then used in the preparation of the standardized dishes. The standardized dishes are: Burabisko, Jollof rice, Agbono soup, Stewed beans and fried plantain, Bean pudding, Melon seed and vegetable soup, Ikokore, Eba imoyo, Yam and eggs and Yam pottage. Consumer acceptability tests were conducted as well as proximate analyses according to AOAC. All dishes were considered acceptable since they scored more than 3, the benchmark for acceptability. Energy content of the dishes ranged from 281Kcal/100g (Jollof rice) to 510Kcal/100g (Agbono soup). The crude protein content ranged from 7.5g/100g for Burabisko to 27.4g/100g for Jollof rice. The results suggest that these dishes are good sources of energy and protein.
IT and Personnel Management Education
Authors: Kinnie N.J. , Arthurs A.J.
Published: July 2002

Discusses the problems faced when designing and delivering IT programmes
for Personnel practitioners and students. Argues that the future
provision of IT teaching of personnel programmes depends on the
provision of teaching materials, staff training programmes and the
diversity of student experience.
TEM: therapeutic exercise machine for recovering walking functions of stroke patients
Authors: Sakaki Taisuke
Published: July 2002

Cooperative work with Keio University has resulted in the development of a machine for exercising the hip and knee joints of stroke patients to recover their walking function. The Therapeutic Exercise Machine (TEM) has two mechanical arms to move the lower extremity of a stroke patient. The arms of the exercise machine are driven by electric motors and are controlled by a computer by means of load sensor information. The sensing and feedback control of force information is a problem for conventional machines and ultimately the therapist using the machine. TEM has the ability to be used as a training machine with embedded therapist techniques as well as the ability to monitor the patient’s condition during an exercise session. The machine has the following new features: wide range of motion, compliant motion, direct teaching, and measurement functions. The effects of TEM have been evaluated on its compliant motion against impulsive load and the short‐term effects of a continuous passive range of motion exercise in spastic patients.