bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of parallelβ-sheet nanofibrils using Monte-Carlo search, coarse-grained simulations, and experimental testing
Authors: Sarma Sudeep , Sudarshan Tarunya Rao , Nguyen Van , Robang Alicia S. , Xiao Xingqing , Le Justin V. , Helmicki Michael E. , Paravastu Anant K. , Hall Carol K. 
Published: November 2023

AbstractPeptide self-assembly into amyloid fibrils provides numerous applications in drug delivery and biomedical engineering applications. We augment our previously-established computational screening technique along with experimental biophysical characterization to discover 7-mer peptides that self-assemble into “parallel β-sheets”, i.e., β-sheets with N-terminus-to-C-terminusβ-strand vectors oriented in parallel. To accomplish the desired β-strand organization, we applied thePepADamino acid sequence design software to the Class-1 cross-β spine defined by Sawaya et al. This molecular configuration includes two layers of parallel β-sheets stacked such that N-terminus-to-C-terminus vectors are oriented antiparallel for molecules on adjacent β-sheets. The first cohort ofPepADidentified peptides were examined for their fibrillation behavior in DMD/PRIME20 simulations, and the top performing sequence was selected as a prototype for a subsequent round of sequence refinement. The two rounds of design resulted in a library of eight 7-mer peptides. In DMD/PRIME20 simulations, five of these peptides spontaneously formed fibril-like structures with a predominantly parallelβ-sheet arrangement, two formed fibril-like structure with <50% in parallelβ-sheet arrangement and one remained a random coil. Among the eight candidate peptides produced by PepAD and DMD/PRIME20, five were synthesized and purified. All five assembled into amyloid fibrils composed of parallel β-sheets based on Fourier Transform Infrared Spectroscopy, Circular Dichroism, Electron Microscopy, and Thioflavin-T fluorescence spectroscopy measurements.
Characterising the contribution of auditory and somatosensory inputs to TMS-evoked potentials following stimulation of prefrontal, premotor and parietal cortex
Authors: Biabani Mana , Fornito Alex , Goldsworthy Mitchell , Thompson Sarah , Graetz Lynton , Semmler John G. , Opie George M. , Bellgrove Mark A. , Rogasch Nigel C. 
Published: November 2023

AbstractTranscranial magnetic stimulation (TMS) results in a series of evoked potentials (TEPs) in electroencephalography (EEG) recordings. However, it remains unclear whether these responses reflect neural activity resulting from transcranial stimulation of the cortex, or from the sensory experiences of TMS. Across three experiments (total n = 135), we recorded EEG activity following TMS to the dorsolateral prefrontal cortex, premotor cortex, and parietal cortex as well as a sensory control condition (stimulation of the shoulder or electrical stimulation of the scalp with a click sound). We found that TEPs showed a stereotypical frontocentral N100/P200 complex following TMS of all cortical sites and control conditions, regardless of TMS intensity or the type of sensory control. In contrast, earlier TEPs (<60 ms) showed site-specific characteristics which were largest at the site of stimulation. Self-reported sensory experiences differed across sites, with prefrontal stimulation resulting in stronger auditory (click sound perception) and somatosensory input (scalp muscle twitch, discomfort) than premotor or parietal stimulation, a pattern that was reflected in the amplitude of later (N100/P200), but not earlier (<60 ms) TEP peak amplitudes. Later TEPs were also larger in individuals who experienced stronger click sound perception and, to a lesser extent, TMS-evoked scalp muscle twitches. Increasing click sound perception by removing auditory masking increased N100/P200 amplitudes without altering earlier peaks, an effect which was more prominent at sites with more successful masking. Together, these findings suggest that the frontocentral N100/P200 complex represents a generalised sensory response resulting from TMS-related auditory and somatosensory input. In contrast, early TEP peaks likely reflect activity resulting from transcranial stimulation of the cortex. The results have important implications for designing and interpreting TEP studies, especially when comparing TEPs between stimulation sites and participant groups showing differences in sensory experiences following TMS.
Sensory-memory interactions via modular structure explain errors in visual working memory
Authors: Yang Jun , Zhang Hanqi , Lim Sukbin 
Published: November 2023

AbstractErrors in stimulus estimation reveal how stimulus representation changes during cognitive processes. Repulsive bias and minimum variance observed near cardinal axes are well-known error patterns typically associated with visual orientation perception. Recent experiments suggest that these errors continuously evolve during working memory, posing a challenge that neither static sensory models nor traditional memory models can address. Here, we demonstrate that these evolving errors, maintaining characteristic shapes, require network interaction between two distinct modules. Each module fulfills efficient sensory encoding and memory maintenance, which cannot be achieved simultaneously in a single-module network. The sensory module exhibits heterogeneous tuning with strong inhibitory modulation reflecting natural orientation statistics. While the memory module, operating alone, supports homogeneous representation via continuous attractor dynamics, the fully connected network forms discrete attractors with moderate drift speed and nonuniform diffusion processes. Together, our work underscores the significance of sensory-memory interaction in continuously shaping stimulus representation during working memory.
Quantifyingin vivocollagen reorganization during immunotherapy in murine melanoma with second harmonic generation imaging
Authors: Heaton Alexa R. , Burkard Nathaniel J. , Sondel Paul M. , Skala Melissa C. 
Published: November 2023

AbstractSignificanceIncreased collagen linearization and deposition during tumorigenesis can impede immune cell infiltration and lead to tumor metastasis. Although melanoma is well studied in immunotherapy research, studies that quantify collagen changes during melanoma progression and treatment are lacking.AimImagein vivocollagen in preclinical melanoma models during immunotherapy and quantify the collagen phenotype in treated and control mice.ApproachSecond harmonic generation imaging of collagen was performed in mouse melanoma tumorsin vivoover a treatment time-course. Animals were treated with a curative radiation and immunotherapy combination. Collagen morphology was quantified over time at an image and single fiber level using CurveAlign and CT-FIRE software.ResultsIn immunotherapy-treated mice, collagen reorganized toward a healthy phenotype, including shorter, wider, curlier collagen fibers, with modestly higher collagen density. Temporally, collagen fiber straightness and length changed late in treatment (Day 9 and 12) while width and density changed early (Day 6) compared to control mice. Single fiber level collagen analysis was most sensitive to the changes between treatment groups compared to image level analysis.ConclusionsQuantitative second harmonic generation imaging can provide insight into collagen dynamicsin vivoduring immunotherapy, with key implications in improving immunotherapy response in melanoma and other cancers.
The greening-causing agent alters the behavioral and electrophysiological responses of the Asian citrus psyllid to a putative sex pheromone
Authors: Volpe Haroldo X. L. , Carmo-Sousa Michele , Luvizotto Rejane A. G. , de Freitas Renato , Esperança Victoria , Darolt Josiane C. , Pegoraro Abner A. L. , Magalhães Diego M. , Favaris Arodi P. , Wulff Nelson A. , Miranda Marcelo P. , Bento José Maurício S. , Leal Walter S. 
Published: November 2023

AbstractThe Asian Citrus Psyllid (ACP),Diaphorina citri,is a vector of the pathological bacteriumCandidatusLiberibacter asiaticus (CLas), which causes the most devastating disease to the citrus industry worldwide, known as greening or huanglongbing (HLB). Earlier field tests with an acetic acid-based lure in greening-free, ‘Valencia’ citrus orange groves in California showed promising results. The same type of lures tested in São Paulo, Brazil, showed unsettling results. During the unsuccessful trials, we noticed a relatively large proportion of females in the field, ultimately leading us to test field-collected males and females forWolbachiaand CLas. The results showed high rates ofWolbachiaand CLas infection in field populations. We then compared the olfactory responses of laboratory-raised, CLas-free, and CLas-infected males to acetic acid. As previously reported, CLas-uninfected males responded to acetic acid at 1 µg. Surprisingly, CLas-infected males required 50x higher doses of the putative sex pheromone, thus explaining the failure to capture CLas-infected males in the field. CLas infection was also manifested in electrophysiological responses. Electroantennogram responses from CLas-infected ACP males were significantly higher than those obtained with uninfected males. To the best of our knowledge, this is the first report of a pathogen infection affecting a vector’s response to a sex attractant.
Single-cell transcriptomic analysis of immune cell dynamics in the healthy human endometrium
Authors: Chen Kaixing , Yu Qiaoni , Sha Qing , Wang Junyu , Fang Jingwen , Li Xin , Shen Xiaokun , Fu Binqing , Guo Chuang 
Published: November 2023

AbstractThe microenvironment of the endometrial immune system is crucial to the success of placental implantation and healthy pregnancy. However, the functionalities of immune cells across various stages of the reproductive cycle have yet to be fully comprehended. To address this, we conducted advanced bioinformatic analyses on 230,049 high-quality single-cell transcriptomes from healthy endometrial samples obtained during the proliferative, secretory, early pregnancy, and late pregnancy stages. Our investigation revealed that proliferative natural killer (NK) cells, a potential source of endometrial NK cells, exhibit the most robust proliferative and differentiation potential during non-pregnant stages. During early pregnancy, NK cells display high oxidative phosphorylation metabolism activity, and together with macrophages and T cells, exhibit a strong type II interferon response. Based on our cell-cell interaction analyses, we identify a large majority of interaction pairs to occur in late pregnancy. Finally, we explored the correlation between stage-specific alterations in transcriptomics and the risk genes of common reproductive diseases, unveiling that MHC class I/II molecules, along withTGFBR1, exhibited the potential to serve as biomarkers. Our study provides insights into the dynamics of the endometrial immune microenvironment during different reproductive cycle stages, thus serving as a reference for detecting pathological changes during pregnancy.
Mind the gap: exploring the usefulness of historical data to assess the impacts of land-use change on bird diversity in a farmland mosaic of Northeastern Portugal (1980-2000)
Authors: Múrias Tiago , Ribeiro Sérgio B. , Lomba Angela , Ferrand De Almeida Nuno 
Published: November 2023

SummaryAgriculture intensification and land abandonment are the main threats to bird communities in farmlands. Although they represent the opposite endpoints of a gradient of land-use change, they are usually examined separately. In this study, we assessed the effects of the occurrence of both drivers in space and in time, on bird assemblages. The study was performed in a Mediterranean vineyard-dominated farmland mosaic located in North-Eastern Portugal, where land abandonment and (mechanized) intensification coexisted for twenty years. The aims of this study were (1) to describe the temporal patterns of land-use change; (2) to investigate whether these changes affected the local bird species composition and ecological guild structure; and (3) to assess which species/ecological traits were more responsive to land-use changes. We compared the occurrence of birds before (1979-84) and after (2002-03) the triggering of the land-use change proccess. Results showed the prevalence of three interacting gradients of land-use change: land intensification, and direct and indirect effects of land abandonment. While the composition and ecological structure of the bird communities remained stable during the period analyzed, trait and species-specific analysis showed significant correlations with the gradients of change. This suggest that the local bird communities were able to cope with the synergic dynamics of the land-use change, possibly due to a combination of a resilient pre-change bird assemblage and the buffering effect of the competing drivers. The pros and cons of the approach adopted and the utility of past datasets as baselines to assess and monitor the impacts of environmental change on farmland bird diversity are discussed.
State-dependent alteration of respiration in a rat model of Parkinson disease
Authors: Walker Jean Jacques , Meunier Estelle , Garcia Samuel , Messaoudi Belkacem , Mouly Anne-Marie , Veyrac Alexandra , Buonviso Nathalie , Courtiol Emmanuelle 
Published: November 2023

AbstractParkinson disease (PD) is the second most frequent neurodegenerative disorder. Besides major deficits in motor coordination, patients may also display sensory and cognitive impairments, which are often overlooked despite being inherently part of the PD symptomatology. Amongst those symptoms, respiration, a key mechanism involved in the regulation of multiple physiological and neuronal processes, appears to be altered. Importantly, breathing patterns are highly correlated with the animal’s behavioral states, and although respiration has been investigated in different models of PD, no study has yet taken into consideration the potential impact of behavioral state on respiration deficits in these models. To explore this variable, we first characterized the respiratory parameters in a neurotoxin-induced rat model of PD (6-OHDA) across different vigilance states: sleep, quiet waking and exploration. We noted a significantly higher respiratory frequency in 6-OHDA rats during quiet waking compared to Sham rats. A higher respiratory amplitude was also observed in 6-OHDA rats during both quiet waking and exploration. No effect of the treatment was noted during sleep. Given the relation between respiration and olfaction and the presence of olfactory deficits in PD patients, we then investigated the odor-evoked sniffing response in PD rats, using an odor habituation/cross-habituation paradigm. No substantial differences were observed in olfactory abilities between the two groups, as assessed through sniffing frequency. These results corroborate the hypothesis that respiratory impairments in 6-OHDA rats are vigilance-dependent. Our results also shed light on the importance of considering the behavioral state as an impacting factor when analyzing respiration.HighlightsSpecific respiratory patterns associated to different vigilance statesSpecific alteration of respiration during quiet waking in a rodent model of PDPreserved olfactory abilities as assessed through sniffing in a rodent model of PD
Trinucleotide mRNA cap analog N6-benzylated at the site of posttranscriptionalm6Am mark facilitates mRNA purification and confers superior translational properties in vitro and in vivo
Authors: Warminski Marcin , Trepkowska Edyta , Smietanski Miroslaw , Sikorski Pawel J. , Baranowski Marek R. , Bednarczyk Marcelina , Kedzierska Hanna , Majewski Bartosz , Mamot Adam , Papiernik Diana , Popielec Agnieszka , Serwa Remigiusz A. , Shimanski Brittany A. , Sklepkiewicz Piotr , Sklucka Marta , Sokolowska Olga , Spiewla Tomasz , Toczydlowska-Socha Diana , Warminska Zofia , Wolosewicz Karol , Zuberek Joanna , Mugridge Jeffrey S. , Nowis Dominika , Golab Jakub , Jemielity Jacek , Kowalska Joanna 
Published: November 2023

AbstractEukaryotic mRNAs undergo co-transcriptional 5’-end modification with a 7-methylguanosine cap. In higher eukaryotes, the cap carries additional methylations, such asm6Am– a common epitranscriptomic mark unique to the mRNA 5’-end. This modification is regulated by the Pcif1 methyltransferase and the FTO demethylase, but its biological function is still unknown. Here, we designed and synthesized a trinucleotide FTO-resistantN6-benzyl analog of them6Am-cap – m7GpppBn6AmpG (termedAvantCap) and incorporated it into mRNA using T7 polymerase. mRNAs carryingBn6Amshowed several advantages over typical capped transcripts. TheBn6Ammoiety was shown to act as an RP-HPLC purification handle, allowing separation of capped and uncapped RNA species, and to produce transcripts with lower dsRNA content than reference caps. In some cultured cells,Bn6AmmRNAs provided higher protein yields than mRNAs carrying Amorm6Am, although the effect was cell line-dependent. m7GpppBn6AmpG-capped mRNAs encoding reporter proteins administered intravenously to mice provided up to 6-fold higher protein outputs than reference mRNAs, while mRNAs encoding tumor antigens showed superior activity in therapeutic setting as anti-cancer vaccines. The biochemical characterization suggests several phenomena underlying the biological properties ofAvantCap: (i) increased competitiveness of the mRNA 5’-end for eIF4E protein by reducing its propensity for unspecific interactions, (ii) direct involvement of eIF3 in alternative translation initiation, (iii) subtle differences in mRNA impurity profiles, or a combination of these effects.AvantCapped-mRNAs bearing theBn6Ammay pave the way for more potent mRNA-based vaccines and therapeutics and serve as molecular tools to unravel the role of them6Amin mRNA.
Dynamics of odor-source localization: Insights from real-time odor plume recordings and head-motion tracking in freely moving mice
Authors: Tariq Mohammad F. , Sterrett Scott C. , Moore Sidney , Lane  , Perkel David J. , Gire David H. 
Published: November 2023

AbstractAnimals navigating turbulent odor plumes exhibit a rich variety of behaviors, and employ efficient strategies to locate odor sources. A growing body of literature has started to probe this complex task of localizing airborne odor sources in walking mammals to further our understanding of neural encoding and decoding of naturalistic sensory stimuli. However, correlating the intermittent olfactory information with behavior has remained a long-standing challenge due to the stochastic nature of the odor stimulus. We recently reported a method to record real-time olfactory information available to freely moving mice during odor-guided navigation, hence overcoming that challenge. Here we combine our odor-recording method with head-motion tracking to establish correlations between plume encounters and head movements. We show that mice exhibit robust head-pitch motions in the 5-14Hz range during an odor-guided navigation task, and that these head motions are modulated by plume encounters. Furthermore, mice reduce their angles with respect to the source upon plume contact. Head motions may thus be an important part of the sensorimotor behavioral repertoire during naturalistic odor-source localization.
Continuity of Mitochondrial Budding: Insights from BS-C-1 Cells byin-situCryo-Electron Tomography
Authors: Hu Judy Z , Qiao Lijun , Zhao Xianhai , Liu Chang-Jun , Hu Guo-Bin 
Published: November 2023

AbstractMitochondrial division is a fundamental biological process that is crucial to cellular functionality and vitality. The prevailing hypothesis of Drp1 regulation with the involvement of ER and cytoskeleton does not account for all the observations. Following up our previous study in HeLa cells which led to the new hypothesis of mitochondrial division by budding, we employedin-situCryo-Electron Tomography (Cryo-ET) to visualize mitochondrial budding in intact healthy monkey kidney cells (BS-C-1 cells). Our findings reaffirm single and multiple mitochondrial budding, supporting the new hypothesis. Notably, the budding regions vary significantly in diameter and length, which may represent different stages of budding. More interestingly, no rings, or ring-like structures, or ER wrapping is presented in the budding regions suggesting mitochondrial budding is independent from Drp1 and ER. Meanwhile, we uncovered direct interactions between mitochondria and large vesicles, distinct from small mitochondrial-derived vesicles and extracellular mitovesicles. We propose these interacting vesicles may have mitochondrial origins.
Activation of glucocorticoid receptor signaling inhibits KSHV-induced inflammation and tumorigenesis
Authors: Chen Luping , Ding Ling , Wang Xian , Huang Yufei , Gao Shou-Jiang 
Published: November 2023

AbstractHyperinflammation is the hallmark of Kaposi’s sarcoma (KS), the most common cancer in AIDS patients caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection. However, the role and mechanism of induction of inflammation in KS remain unclear. In a screening for inhibitors of KSHV-induced oncogenesis, over half of the identified candidates were anti-inflammatory agents including dexamethasone functions by activating glucocorticoid receptor (GR) signaling. Here, we examined the mechanism mediating KSHV-induced inflammation. We found that numerous inflammatory pathways were activated in KSHV-transformed cells. Particularly, interleukin-1 alpha (IL-1α) and IL-1 receptor antagonist (IL-1Ra) from the IL-1 family were the most induced and suppressed cytokines, respectively. We found that KSHV miRNAs mediated IL-1α induction while both miRNAs and vFLIP mediated IL-1Ra suppression. Furthermore, GR signaling was inhibited in KSHV-transformed cells, which was mediated by vFLIP and vCyclin. Dexamethasone treatment activated GR signaling, and inhibited cell proliferation and colony formation in soft agar of KSHV-transformed cells but had a minimal effect on matched primary cells. Consequently, dexamethasone suppressed the initiation and growth of KSHV-induced tumors in mice. Mechanistically, dexamethasone suppressed IL-1α but induced IL-1Ra expression. Treatment with recombinant IL-1α protein rescued the inhibitory effect of dexamethasone while overexpression of IL-1Ra caused a weak growth inhibition of KSHV-transformed cells. Furthermore, dexamethasone induced IκBα expression resulting in inhibition of NF-κB pathway and IL-1α expression. These results reveal an important role of IL-1 pathway in KSHV-induced inflammation and oncogenesis, which can be inhibited by dexamethasone-activated GR signaling, and identify IL-1-mediated inflammation as a potential therapeutic target for KSHV-induced malignancies.ImportanceKaposi’s sarcoma (KS) is the most common cancer in HIV-infected patients caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection. Hyperinflammation is the hallmark of KS. In this study, we have shown that KSHV mediates hyperinflammation by inducing IL-1α and suppressing IL-1Ra. Mechanistically, KSHV miRNAs and vFLIP induce hyperinflammation by activating the NF-κB pathway. A common anti-inflammatory agent dexamethasone blocks KSHV-induced hyperinflammation and tumorigenesis by activating glucocorticoid receptor signaling to suppress IL-1α and induce IL-1Ra. This work has identified IL-1-mediated inflammation as a potential therapeutic target and dexamethasone as a potential therapeutic agent for KSHV-induced malignancies.