bluuebunny/crossref_metadata_2025_split huggingface dataset:
Route Learning and Transport of Resources during Colony Relocation in Australian Desert Ants
Authors: Deeti Sudhakar , McLean Donald James , Murray Trevor , Cheng Ken 
Published: August 2024

AbstractMany ant species are able to respond to dramatic changes in local conditions by relocating the entire colony to a new location. While we know that careful learning walks enables the homing behavior of foraging ants to their original nest, we do not know whether additional learning is required to navigate to the new nest location. To answer this question, we investigated the nest relocation behavior of a colony of Australian desert antsMelophorus bagotithat relocated their nest in response to heavy rainfall in the semi-desert terrain of Alice Springs. We identified five types of behavior: exploration between nests (Old-to-New nest and New-to-Old nest), transport from Old to New nest, and re-learning walks at Old and New nests. Initially, the workers performed relearning walks at the Old nest and exploratory walks between the Old and New nests. Once they completed the exploratory walks, the workers transported resources and brood to the new nest. Finally, we observed the workers performing relearning walks at the New nest. While the relearning walks at the Old nest were slow and appear to enable exploratory walks to the New nest, the relearning walks at the new nest were faster and appeared to enable homing from foraging trips. These observations shed insight on how learning helps these ants to respond to sudden changes in their environment.Statement of significanceIn this study, we examined one nest of red honey ants,Melophorus bagoti, in Central Australia relocating their nest after a spell of heavy rainfall, which, we presumed, damaged the nest that the colony was living in. After the new nest some 20 m away was mostly dug, we examined the behaviors that orchestrated the move. Workers did a bit of learning of the route to the new nest before transporting any resources. They executed short loops around the old nest, mostly aimed in the direction of the new nest, known as relearning walks. Then they walked back and forth between the old and new nests without carrying any resources, a process we called exploration walks. Then the workers undertook the laborious process of moving house, that is, transporting workers unfamiliar with the route, larvae, and pupae to the new nest. After this stage, we observed ants doing more relearning walks at the new nest in preparation for foraging from their new home. These relearning walks covered all directions around the nest. Our study showed for the first time the importance of the process of learning in nest relocation, a key response to extreme environmental challenges, broadening the role of learning in the lives of these social insects.
A novel baseline-effect shift tracking model for more sensitive detection of differences in the effects of closely related dopamine transporter inhibitor/ sigma receptor antagonist drug combinations on psychostimulant use
Authors: Paul Reshma , Gandhi Roshni M , Job Martin O 
Published: August 2024

AbstractBackgroundFor the purpose of improving the ability to distinguish the activity of closely related drugs on psychostimulant use to enable more specific drug effect characterization, we have developed a new model termed the baseline-effect shift tracking (BEST) model. BEST compares/contrasts the baseline-drug activity relationship(s).AimTo compare the current model to our BEST model to determine which was more effective in distinguishing the effects of combinations of a dopamine transporter inhibitor (methylphenidate, MPD) and selective sigma1 (BD1063) and non-selective sigma (BD1008) receptor antagonists on cocaine consumption.MethodsMale Sprague Dawley rats were trained to self-administer cocaine (n = 9, 0.32 mg/kg/infusion) or sucrose pellets (n = 6, 20 mg pellets/delivery). We determined the effects for cocaine/sucrose of combinations of MPD (1 mg/kg i.p) and 1) BD1063 (0, 3.2, 10 mg/kg i.p), and 2) BD1008 (0, 3.2, 10 mg/kg i.p) on a) consumption at zero price (Q0), and b) essential value (eValue, demand elasticity) estimated using behavioral economic analysis of within-session demand curves, and c) the total intake under the price response curve (TIPR). We compared the models using ANOVA/ regression analysis.ResultsThe current model did not detect any differences in the effects of these drug combinations on cocaine/ sucrose taking behavior. For cocaine, but not for sucrose, the BEST model detected differences in the effects of these drug combinations on TIPR in subjects with higher baseline activity.ConclusionBEST model (with TIPR analysis) is more sensitive than the current models in differentiating drug effects on cocaine consumption.
The ERGtools2 package: A Toolset for Processing and Analysing Visual Electrophysiology Data
Authors: Lindner Moritz 
Published: August 2024

AbstractIntroductionVisual electrophysiology techniques play a key role in assessing the functional integrity of the visual pathway. Recent advancements and applications demand flexible analysis tools. Heren, ERGtools2, an open-source R package designed for processing and analysing visual electrophysiology data is introduced.MethodsA dataset comprising Electroretinogram (ERG) recordings from both eyes of C57Bl/6J mice, subjected to standard ISCEV stimuli, was used to present the functionality of ERGtools2. ERGtools2 stores and organizes all recordings, metadata, and measurement information from individual examination in a single object, maintaining raw data throughout the analysis process.ResultsA standard workflow is presented exemplifying how ERGtools2 can be used to efficiently import, pre-process and analyse ERG data. Following this workflow, basic ERG measurements likeaandB-wave amplitudes and visualisation of a single exam as well as group statistics are obtained. Moreover, special use cases are described, including for the handling of noisy data and the storage of data in the HDF5 format to ensure long-term preservation and accessibility. ERGtools2 also provides a graphical interface.DiscussionERGtools2 provides a comprehensive, flexible, and device-independent solution for visual electrophysiology data analysis. Its emphasis on maintaining raw data integrity, combined with advanced processing and analysis capabilities, makes it a useful tool for preclinical and clinical research applications. The open-source nature and the use of open data formats promote reproducibility and data sharing in visual neurosciences.
An alternative mechanism for activation of innate immune signaling by MDA5
Authors: Quack Salina , Maity Sourav , America Pim P. B. , Klein Misha , del Valle Alba Herrero , Singh Rahul , Smitskamp Quinte , Papini Flavia S. , Broedersz Chase P. , Roos Wouter H. , Modis Yorgo , Dulin David 
Published: August 2024

AbstractLong double-stranded (ds) RNA in the cytosol acts as a potent inflammatory molecule recognized by the receptor MDA5, triggering the innate immune response. Mutations in MDA5 affecting dsRNA recognition can lead to increased infection sensitivity or autoimmune disease. The current model proposes that MDA5 nucleoprotein filament assembly-disassembly dynamics regulates long dsRNA recognition and signaling. We show that MDA5 preferentially loads onto dsRNA via a 3’ recessed end and uses ATP hydrolysis to translocate towards the 5’-end until obstructed, such as by another MDA5 on the opposite strand. Multiple MDA5 monomers accumulate at the blockade, forming a partial filament that extrudes the associated RNA in single-stranded loops and thereby compacting the MDA5-RNA complex. The compacted state is further stabilized by oligomerization of the MDA5’s caspase recruitment domain (CARD) and can withstand significant forces, offering an alternative intermediate in the activation of MDA5-dependent innate immunity.
The evolution of reversible plasticity in stable environments
Authors: Walasek Nicole , Panchanathan Karthik , Frankenhuis Willem E. 
Published: August 2024

AbstractPhenotypic plasticity– the capacity of a genotype to develop into different phenotypes depending on environmental inputs – is widespread in nature. Although theconstructionof phenotypes is often the focus of research, many animals are also able todeconstructphenotypic adjustments. Organisms routinely use suchreversible plasticityto adjust to changes in their social or physical environment. For example, various invertebrates are able to deconstruct defensive morphologies previously built to defend against predators. Theory that explores the selection pressures favoring reversibility is scarce. Existing theory has almost exclusively focused on traits that develop instantaneously rather than incrementally, as is common with many morphological traits. Here, we present a model of the evolution of reversible plasticity when organisms develop incrementally. In our model, organisms repeatedly sample cues to infer the environmental state – which varies between generations but is stable across the lifetime – and incrementally adjust their phenotype to match their environment. Organisms have the possibility to deconstruct phenotypic adjustments. We assume two different modes of phenotypic deconstruction: Organisms can either deconstruct phenotypic adjustments incrementally or completely deconstruct all phenotypic adjustments in one time period. We highlight two results. First, while plasticity in construction is typically highest early in ontogeny, the highest levels of plasticity in deconstruction typically occur in mid-ontogeny. Second, contrasting previous models, we find that reversibility evolves frequently in stable environments and in species with shorter lifespans. Our model thus shows that reversibility does not require environmental change. Rather, reversibility may be favored when organisms are uncertain about the environmental state because the environment can change across generations. Our work illustrates the capacity for reversibility in species who experience environmental changes for the first time in their lives.
ANLN directly interacts with PCNA to regulate UV induced translesion synthesis
Authors: Tong Bei-Bei , Cao Yu-Fei , Wen Bing , Fu Teng , Deng Dan-Xia , Yang Qian-Hui , Wu Yu-Qiu , Zou Hua-Yan , Liao Lian-Di , Xu Li-Yan , Li En-Min 
Published: August 2024

AbstractAnillin (ANLN) is a cytoskeletal binding protein involved in mitosis. ANLN is located in the nucleus during interphase and in the cytoplasmic contractile rings during mitosis. Our previous studies found that ANLN is abnormally overexpressed in esophageal squamous cell carcinoma (ESCC), promoting cell division by regulating contractile ring localization. However, the exact function of ANLN in the nucleus remains unclear. Here, we found that the expression of ANLN in the nucleus is associated with poor prognosis in ESCC patients, rather than in the cytoplasm. Protein mass spectrometry and bioinformatics analysis revealed that ANLN is related to DNA synthesis, and proliferating cell nuclear antigen (PCNA) is found to be a potential interacting protein of ANLN. PCNA directly interacts with the PIP box domain of ANLN and co-localizes in the nucleus. ANLN promotes DNA replication and S phase progression in a PCNA dependent manner and independent with the cytoskeletal function of ANLN. Importantly, ANLN is involved in transletion synthesis (TLS), a type of DNA synthesis under stress, by promoting PCNA monoubiquitination at K164 residue. Mechanistically, ANLN binds and recruits the E3 ligase RAD18 to promote PCNA monoubiquitination and DNA polymerase eta loading under UV radiation conditions. Consistently, depletion of ANLN leads to increased genomic instability and increased sensitivity to UV radiation. The findings of the study showed that ANLN in the nucleus as a protein scaffold is involved in UV induced DNA synthesis pathway, providing new insights into the function and mechanism of ANLN in cancer cells.
The Effect of THz Electromagnetic Field on the Conductance of Potassium and Sodium Channels
Authors: Song Zigang , Xue Lingfeng , Ouyang Qi , Song Chen 
Published: August 2024

AbstractIon channels are essential to various physiological processes and their defects are associated with many diseases. Previous research has revealed that Terahertz electromagnetic field can alter the channel conductance by affecting the motion of chemical groups of ion channels, and hence regulate the electric signals of neurons. In this study, we conducted molecular dynamics simulations to systematically investigate the effects of terahertz electromagnetic fields on the conductance of voltage-gated potassium and sodium channels, particularly focusing on the bound ions in the selectivity filters that have not been studied previously. Our results identified multiple new characteristic frequencies and showed that 1.4, 2.2, or 2.9 THz field increases the conductance of Kv1.2, and 2.5 or 48.6 THz field increases the conductance of Nav1.5. The conductance-enhancing effects are specific to the frequencies and directions of the electric field, which are determined by the intrinsic oscillation motions of the permeating ions in the selectivity filter or certain chemical groups of the ion channels. The amplitude of the THz field positively correlates with the change in ion conductance. Therefore, this study demonstrates that THz fields can specifically regulate ion channel conductances, which may carry great potential in biomedical applications.
Onset of infectiousness explains differences in transmissibility acrossMycobacterium tuberculosislineages
Authors: Windels Etthel M. , Agüí Cecilia Valenzuela , de Jong Bouke C. , Meehan Conor J. , Loiseau Chloé , Goig Galo A. , Zwyer Michaela , Borrell Sonia , Brites Daniela , Gagneux Sebastien , Stadler Tanja 
Published: August 2024

AbstractMycobacterium tuberculosiscomplex (MTBC) lineages show substantial variability in virulence, but the epidemiological consequences of this variability have not been studied in detail. Here, we aimed for a lineage-specific epidemiological characterization by applying phylodynamic models to genomic data from different countries, representing the most abundant MTBC lineages. Our results show that all lineages are associated with similar durations and levels of infectiousness, resulting in similar reproductive numbers. However, L1 and L6 are associated with a delayed onset of infectiousness, leading to longer periods between subsequent transmission events. Together, our findings highlight the role of MTBC phylogenetic diversity in tuberculosis disease progression and transmission.
Glioblastoma stem cells show transcriptionally correlated spatial organization
Authors: Ayyadhury Shamini , Sachamitr Patty , Kushida Michelle M. , Park Nicole I , Coutinho Fiona J. , Whitley Owen , Prinos Panagiotis , Arrowsmith Cheryl H. , Dirks Peter B. , Pugh Trevor J. , Bader Gary D. 
Published: August 2024

AbstractGlioblastoma (GBM) is an aggressive brain cancer with a poor survival rate. Despite hundreds of clinical trials, there is no effective targeted therapy. Glioblastoma stem cells (GSCs) are an important GBM model system. In culture, these cells form spatial structures that share morphological aspects with their source tumors. We collected 17,000 phase contrast images of 15 patient-derived GSC lines growing to confluence. We find that GSCs grow in characteristic multicellular patterns depending on their transcriptional state. Interpretable computer vision algorithms identified specific image features that predict transcriptional state across multiple cell confluency levels. This relationship will be useful in developing GSC screens where image features can be used to identify how GSC biology changes in response to perturbations simply by imaging cultured cells on plates.
Heterologous Production of Cyprosin B inNicotiana benthamiana: Unveiling the Role of the Plant-Specific Insert Domain in Protein Function and Subcellular Localization
Authors: Muthusamy Saraladevi , Vetukuri Ramesh R , Lundgren Anneli , Kim Sungyong , Kalyandurg Pruthvi B. , Strid Åke , Zhu Li-Hua , Kanagarajan Selvaraju , Brodelius Peter E. 
Published: August 2024

AbstractThe aqueous extract ofCynara cardunculusflowers is traditionally used in cheese production across Mediterranean countries. To meet the growing industrial demand for plant-based milk-clotting enzymes and to explore potential biotechnological applications, we initiated a study to heterologously produce cyprosin B (CYPB), a key milk-clotting enzyme fromC. cardunculus, inNicotiana benthamiana. We also investigated the role of its plant-specific insert (PSI) domain in the CYPB’s activity and its localization. In this study, full-length CYPB and a PSI domain deleted CYPB (CYPBΔPSI) were transiently expressed inN. benthamianaleaves usingAgrobacterium-mediated infiltration. The leaves were harvested nine days post-infiltration, and proteins were purified, yielding approximately 81 mg/kg (CYPB) and 60 mg/kg (CYPBΔPSI) fresh weight. CYPBΔPSI showed significantly higher proteolytic activity (156.72 IU/mg) than CYPB (57.2 IU/mg), indicating that the PSI domain is not essential for enzymatic activity and that its removal results in enhanced enzymatic efficiency. In the milk-clotting activity assay, CYPBΔPSI demonstrated a significantly faster clotting time than full-length CYPB, indicating enhanced milk-clotting efficiency for CYPBΔPSI. Subcellular localization studies revealed that CYPB and PSI were localized in the vacuole and endocytic vesicles. In contrast, CYPBΔPSI was primarily localized in the endoplasmic reticulum (ER) and the tonoplast, suggesting that the PSI domain is critical for vacuolar targeting and membrane permeabilization that affects overall protein yield. This study demonstrates the feasibility of usingN. benthamianaas a platform for the scalable production of more efficient recombinant CYPB. It highlights the multifunctional role of the PSI domain in vacuolar sorting without impairing its functionality. These results underscore the potential of plant-based expression systems as a viable alternative for the industrial production of plant milk-clotting enzymes, with significant implications for sustainable cheese production.
Information-making processes in the speaker’s brain drive human conversations forward
Authors: Goldstein Ariel , Wang Haocheng , Sheffer Tom , Schain Mariano , Zada Zaid , Niekerken Leonard , Aubrey Bobbi , Nastase Samuel A. , Gazula Harshvardhan , Costo Colton , Doyle Werner , Friedman Daniel , Devore Sasha , Dugan Patricia , Hassidim Avinatan , Brenner Michael , Matias Yossi , Devinsky Orrin , Flinker Adeen , Hasson Uri 
Published: August 2024

AbstractA conversation following an overly predictable pattern is likely boring and uninformative; conversely, if it lacks structure, it is likely nonsensical. The delicate balance between predictability and surprise has been well studied using information theory during speech perception, focusing on how listeners predict upcoming words based on context and respond to unexpected information. However, less is known about how speakers’ brains generate structured yet surprisingly informative speech. This study uses continuous electrocorticography (ECoG) recordings during free, 24/7 conversations to investigate the neural basis of speech production and comprehension. We employed large language models (Llama-2 and GPT-2) to calculate word probabilities based on context and categorized words into probable (top 30%) and improbable (bottom 30%) groups. We then extracted word embeddings from the LLMs and used encoding models to estimate the neural activity while producing or listening to probable and improbable words. Our findings indicate that before word-onset, the human brain functions in opposing, perhaps complementary, ways while listening and speaking. Results show that listeners exhibit increased neural encoding for predictable words before word onset, while speakers show increased encoding for surprising, improbable words. Speakers also show a lower speech production rate before articulating unexpected words, suggesting additional cognitive processes are involved in producing novel information. This indicates that human speech production includes information-making processes for generating informative words that are absent in language models, which primarily rely on statistical probabilities to generate contextually appropriate speech.
Dynamic positioning of a TFIIE-related winged-helix domain in RNA polymerase elongation complex III underpins its multi-functionality
Authors: Wu Jheng-Syong , Lin Yu-Chun , Wei Yi-Yu , Lin Hsin-Hung , Liu Yang-Chih , Chang Jen-Wei , Tu I-Ping , Chen Hung-Ta , Chang Wei-Hau 
Published: August 2024

AbstractRNA polymerase III (Pol III) is a large protein complex that efficiently synthesizes structural and non-translated RNAs. The tandem-wing-helix (tWH) domain (WH1 and WH2) in the Rpc34 subunit of the TFIIE-related sub-complex plays multiple roles central to Pol III transcription, but the structural basis remains conundrum due to its cryo-EM density missing in enlongation complex (EC). Here, by site-specifically incorporating an azido unnatural amino acid (UAA) into Pol III Rpc34 WH2 and developing a simple protocol to enable selective labeling using strain-promoted azide-alkyne cycloadditio—the Bertozzi click reaction, we probed Rpc34 WH2 dynamics using single-molecule Förster resonance energy transfer (smFRET) between an acceptor in Rpc34 WH2 and a donor in DNA. Our smFRET resolved multiple FRET states with inter-state transitions exhibiting characteristic kinetics. Further nano-positioning analysis localized the docking positions of those FRET states on Pol III EC, including sites related to initiation and transcription bubble management. Our findings of Rpc34 WH2 dynamical positioning suggest the docking interactions are weak and promiscuous, providing a mechanism to rationalize multi-functionality of Pol III Rpc34 tWH. This study expands our understanding of Pol III transcription machinery and our chemical biology means are widely applicable to explore structural dynamics of large protein complexes.
The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC
Authors: Richard Jonathan , Grunst Michael W. , Niu Ling , Díaz-Salinas Marco A. , Tolbert William D. , Marchitto Lorie , Zhou Fei , Bourassa Catherine , Yang Derek , Chiu Ta Jung , Chen Hung-Ching , Benlarbi Mehdi ,   Guillaume-Beaudoin-Buissières, Gottumukkala Suneetha , Li Wenwei , Dionne Katrina , Bélanger Étienne , Chatterjee Debashree , Medjahed Halima , Hendrickson Wayne A. , Sodroski Joseph , Lang Zabrina C. , Morton Abraham J. , Huang Rick K. , Matthies Doreen , Smith Amos B. , Mothes Walther , Munro James B. , Pazgier Marzena , Finzi Andrés 
Published: August 2024

ABSTRACTHIV-1 envelope glycoproteins (Env) from primary HIV-1 isolates typically adopt a pretriggered “closed” conformation that resists to CD4-induced (CD4i) non-neutralizing antibodies (nnAbs) mediating antibody-dependent cellular cytotoxicity (ADCC). CD4-mimetic compounds (CD4mcs) “open-up” Env allowing binding of CD4i nnAbs, thereby sensitizing HIV-1-infected cells to ADCC. Two families of CD4i nnAbs, the anti-cluster A and anti-coreceptor binding site (CoRBS) Abs, are required to mediate ADCC in combination with the indane CD4mc BNM-III-170. Recently, new indoline CD4mcs with improved potency and breadth have been described. Here, we show that the lead indoline CD4mc, CJF-III-288, sensitizes HIV-1-infected cells to ADCC mediated by anti-CoRBS Abs alone, contributing to improved ADCC activity. Structural and conformational analyses reveal that CJF-III-288, in combination with anti-CoRBS Abs, potently stabilizes an asymmetric “open” State-3 Env conformation, This Env conformation orients the anti-CoRBS Ab to improve ADCC activity and therapeutic potential.