bioRxiv最新文献

{"title":"Comparison of Cd concentration in rice grain between OsNramp5 knock-out mutants and OsHAM3-overexpressing line","authors":"Yuejing Gui, J. Teo, D. Tian, Raji Mohan, Zhongchao Yin","doi":"10.1101/2024.07.11.603016","DOIUrl":"https://doi.org/10.1101/2024.07.11.603016","url":null,"abstract":"Cadmium (Cd) is a highly toxic element that causes cancer and serious diseases in human beings. Rice is prone to accumulate Cd in its grain, which causes health concerns for rice consumers. OsNramp5 is a major Cd and Mn transporter in rice, whereas OsHMA3 is a tonoplast-localized transporter that is involved in Cd sequestration in vacuoles. We generated an OsNramp5 knock-out mutant in T5105 genetic background by gene editing approach. Cd and Mn concentrations in the grain of OsNramp5 knock-out mutants were measured and compared with those in the grain of an OsHMA3-overexpressing line developed in a previous study. We found that the OsHMA3 overexpression approach worked more efficiently than the OsNramp5 knock-out method in generating low-Cd rice grain without affecting Mn uptake and transport in rice.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A SMARTR workflow for multi-ensemble atlas mapping and brain-wide network analysis","authors":"Michelle Jin, Simon O. Ogundare, Marcos Lanio, Sophia Sorid, Alicia R. Whye, Sofia Leal Santos, Alessandra Franceschini, Christine A. Denny","doi":"10.1101/2024.07.12.603299","DOIUrl":"https://doi.org/10.1101/2024.07.12.603299","url":null,"abstract":"In the last decade, activity-dependent strategies for labelling multiple immediate early gene (IEG) ensembles in mice have generated unprecedented insight into the mechanisms of memory encoding, storage, and retrieval. However, few strategies exist for brain-wide mapping of multiple ensembles, including their overlapping population, and none incorporate capabilities for downstream network analysis. Here, we introduce a scalable workflow to analyze traditionally coronally-sectioned datasets produced by activity-dependent tagging systems. Intrinsic to this pipeline is simple multi-ensemble atlas registration and statistical testing in R (SMARTR), an R package which wraps mapping capabilities with functions for statistical analysis and network visualization. We demonstrate the versatility of SMARTR by mapping the ensembles underlying the acquisition and expression of learned helplessness (LH), a robust stress model. Applying network analysis, we find that exposure to inescapable shock (IS), compared to context training (CT), results in decreased centrality of regions engaged in spatial and contextual processing and higher influence of regions involved in somatosensory and affective processing. During LH expression, the substantia nigra emerges as a highly influential region which shows a functional reversal following IS, indicating a possible regulatory function of motor activity during helplessness. We also report that IS results in a robust decrease in reactivation activity across a number of cortical, hippocampal, and amygdalar regions, indicating suppression of ensemble reactivation may be a neurobiological signature of LH. These results highlight the emergent insights uniquely garnered by applying our analysis approach to multiple ensemble datasets and demonstrate the strength of our workflow as a hypothesis-generating toolkit.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring the Immune Memory Response of In Vitro Polarized Th1, Th2, and Th17 Cells in the Face of OVA Transgenic Leishmania major in Mouse Model","authors":"Mebrahtu G. Tedla, Musammat F. Nahar, Alison L. Every, Jean-Pierre Y. Scheerlinck","doi":"10.1101/2024.07.10.601391","DOIUrl":"https://doi.org/10.1101/2024.07.10.601391","url":null,"abstract":"Th1 and Th2 cytokines determine the outcome of Leishmania major infection and immune protection depends mainly on memory T cells induced during vaccination. This largely hinges on the nature and type of memory T cells produced. In this study, transgenic Leishmania major expressing membrane associated ovalbumin (mOVA) and soluble ovalbumin (sOVA) are used as a model to study whether fully differentiated Th1/ Th2 &Th17 cells can recall immune memory and tolerate pathogen manipulation. Naïve OT-II T cells were in vitro polarised into Th1/Th2, and these cells were transferred adoptively into recipient mice. Following transferring the memory cells, recipient mice were challenged with OVA transgenic Leishmania major and wild type parasite was used a control. The in vitro polarised T helper cells continued to produce the same cytokine signatures after challenged by both forms of OVA-expressing Leishmania major parasites in vivo. This suggests antigen-experienced cells cells remain the same or unaltered in the face of OVA transgenic Leishmania major. Such ability of the antigen-experienced cells to remain resilient to manipulation by the parasite signifies that vaccines might be able to produce immune memory responses and withstand against the parasite immune manipulation and protect the host from infection.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct piriform-to-auditory cortical projections shape auditory-olfactory integration","authors":"Nathan W. Vogler, Ruoyi Chen, Alister Virkler, Violet Y. Tu, Jay A. Gottfried, M. Geffen","doi":"10.1101/2024.07.11.602976","DOIUrl":"https://doi.org/10.1101/2024.07.11.602976","url":null,"abstract":"In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory-olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake mice, we found that odor stimuli modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel cortical circuit shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory-olfactory integration. Significance Statement All living organisms exist within multisensory environments, yet there is a lack in our understanding of how the brain integrates multisensory information. This work elucidates novel circuits governing auditory-olfactory integration in the auditory cortex. Our results shed new light on a relatively understudied area of multisensory research, promising a more robust understanding of how animals and humans perceive and interact within complex environments.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A distant TANGO1 family member promotes vitellogenin export from the ER in C. elegans","authors":"Jimmy H. Mo, Chao Zhai, Kwangsek Jung, Yan Li, Yonghong Yan, Mengqiu Dong, H. Y. Mak","doi":"10.1101/2024.07.15.603539","DOIUrl":"https://doi.org/10.1101/2024.07.15.603539","url":null,"abstract":"Vitellogenin belongs to the Large Lipid Transfer Protein superfamily and is thought to share a common ancestor with human Apolipoprotein B (ApoB) for systemic lipid transport1–5. Vitellogenin forms part of yolk granules (also known as yolk organelles), as maternal contribution of nutrients that support the embryonic development of oviparous animals6,7. In Caenorhabditis elegans, vitellogenin proteins (VIT-1 to VIT-6) are synthesized in the hermaphrodite intestine, secreted into the pseudocoelom and internalized by oocytes8–13. Although a general route for inter-tissue vitellogenin transport has been described, the full mechanism that underlies its intracellular trafficking within the intestine remains obscure9,12,13. In humans, transport and Golgi organization protein 1 (TANGO1) and TANGO1-like (TALI) proteins generate super-sized membrane carriers to accommodate bulky ApoB-containing lipoprotein particles for their export from ER exit sites14–17. Transport facilitated by TANGO1 family of proteins is considered as an alternative, COPII-independent ER exit pathway18–24. Thus far, TANGO1 orthologs have been discovered in most metazoans, except nematodes24,25. Here, we report the C. elegans protein R148.3 (now Transport and Golgi organization 1-like or TNGL-1) as a mediator of vitellogenin export from the ER. TNGL-1 depletion triggers VIT-2 accumulation in the intestinal ER lumen. TNGL-1 requires its C-terminal unstructured domain for its localization to ER exit sites. Like TANGO1, it utilizes a luminal globular domain for cargo engagement. Our findings support TNGL-1 as a distant TANGO1 family member.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Southeast Asian Anopheles mosquito species with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a cross-correlation approach","authors":"Victor Chaumeau, Sunisa Sawasdichai, Thu Zar Ma Ma Moe Min, Thithiwarada Kularbkeeree, Naw Jaruwan, Naw Gloria, Naw Yu Lee, Muesuwa Trackoolchengkaew, Monticha Phanaphadungtham, Patcharamai Rongthong, Aritsara Inta, Wanitda Watthanaworawit, F. Nosten","doi":"10.1101/2024.07.10.602996","DOIUrl":"https://doi.org/10.1101/2024.07.10.602996","url":null,"abstract":"Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is proposed for mosquito species identification. The absence of public repositories for sharing mass spectra and of open-source data analysis pipelines for fingerprint matching to mosquito species limits widespread use of this technology. The objective of this study was to develop an open-source data analysis pipeline for Anopheles species identification with MALDI-TOF MS. Malaria mosquitos were captured in 33 villages in Karen (Kayin) state in Myanmar. 359 specimens were identified with DNA barcodes and assigned to 21 sensu stricto species and 5 sibling species pairs or complexes. 3584 mass spectra of the head of these specimens identified with DNA barcoding were acquired and the similarity between mass spectra was quantified using a cross-correlation approach adapted from the published literature. A simulation experiment was carried out to evaluate the performance of species identification with MALDI-TOF MS at varying thresholds of cross-correlation index for the algorithm to output an identification result and with varying numbers of technical replicates for the tested specimens, considering PCR identification results as the reference. With one spot and a threshold value of −14 for the cross-correlation index on the log scale, the sensitivity was 0.99 (95%CrI: 0.98 to 1.00), the predictive positive value was 0.99 (95%CrI: 0.98 to 0.99) and the accuracy was 0.98 (95%CrI: 0.97 to 0.99). It was not possible to directly estimate the sensitivity and negative predictive value because there was no true negative in the assessment. In conclusion, the modified cross-correlation approach can be used for matching mass spectral fingerprints to predefined taxa and MALDI-TOF MS is a valuable tool for rapid, accurate and affordable identification of malaria mosquitos.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How the window of visibility varies around polar angle","authors":"Y. Kwak, Zhong-Lin Lu, Marisa Carrasco","doi":"10.1101/2024.07.12.603257","DOIUrl":"https://doi.org/10.1101/2024.07.12.603257","url":null,"abstract":"Contrast sensitivity, the amount of contrast required to detect or discriminate an object, depends on spatial frequency (SF): The Contrast Sensitivity Function (CSF) peaks at intermediate SFs and drops at lower and higher SFs and is the basis of computational models of visual object recognition. The CSF varies from foveal to peripheral vision, but only a couple studies have assessed changes around polar angle of the visual field. Sensitivity is generally better along the horizontal than the vertical meridian, and better at the lower vertical than the upper vertical meridian, yielding polar angle asymmetries. Here, we investigate CSF attributes at polar angle locations at both group and individual levels, using Hierarchical Bayesian Modeling. This method enables precise estimation of CSF parameters by decomposing the variability of the dataset into multiple levels and analyzing covariance across observers. At the group level, peak contrast sensitivity and corresponding spatial frequency with the highest sensitivity are higher at the horizontal than vertical meridian, and at the lower than upper vertical meridian. At an individual level, CSF attributes (e.g., maximum sensitivity, the most preferred SF) across locations are highly correlated, indicating that although the CSFs differ across locations, the CSF at one location is predictive of the CSF at another location. Within each location, the CSF attributes co-vary, indicating that CSFs across individuals vary in a consistent manner (e.g., as maximum sensitivity increases, wso does the SF at which sensitivity peaks), but more so at the horizontal than the vertical meridian locations. These results show similarities and uncover some critical polar angle differences across locations and individuals, suggesting that the CSF should not be generalized across iso-eccentric locations around the visual field. Our window of visibility varies with polar angle: It is enhanced and more consistent at the horizontal meridian. Author summary The contrast sensitivity function (CSF), depicting how our ability to perceive contrast depends on spatial frequency, characterizes our “window of visibility”: We can only see objects with contrast and spatial frequency properties encompassed by this function. The CSF is mostly assessed only along the horizontal meridian of the visual field and sometimes averaged across locations, but visual performance varies with polar angle (e.g., we are more sensitive to objects along the horizontal than the vertical meridian). Here, we systematically assess the key attributes of the CSF and show critical differences in the window of visibility across polar angles and individuals. We found that at the horizontal meridian, our overall contrast sensitivity and preferred SF are higher, and CSFs of individual observers co-vary more than at the vertical meridian. This research highlights that this fundamental perceptual measure is not the same and should be assessed around the visual field. P","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Card9 and MyD88 differentially regulate Th17 immunity to the commensal yeast Malassezia in the murine skin","authors":"Meret Tuor, Mark H. T. Stappers, Fiorella Ruchti, Alice Desgardin, Florian Sparber, Selinda J. Orr, NA Gow, S. Leibundgut-Landmann","doi":"10.1101/2024.07.12.603211","DOIUrl":"https://doi.org/10.1101/2024.07.12.603211","url":null,"abstract":"The fungal community of the skin microbiome is dominated by a single genus, Malassezia. Besides its symbiotic lifestyle at the host interface, this commensal yeast has also been associated with diverse inflammatory skin diseases in humans and pet animals. Stable colonization is maintained by antifungal type 17 immunity. The mechanisms driving Th17 responses to Malassezia remain, however, unclear. Here, we show that the C-type lectin receptors Mincle, Dectin-1, and Dectin-2 recognize conserved patterns in the cell wall of Malassezia and induce dendritic cell activation in vitro, while only Dectin-2 is required for Th17 activation during experimental skin colonization in vivo. In contrast, Toll-like receptor recognition was redundant in this context. Instead, inflammatory IL-1 family cytokines signaling via MyD88 were also implicated in Th17 activation in a T cell-intrinsic manner. Taken together, we characterized the pathways contributing to protective immunity against the most abundant member of the skin mycobiome. This knowledge contributes to the understanding of barrier immunity and its regulation by commensals and is relevant considering how aberrant immune responses are associated with severe skin pathologies.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of truthful and misleading instructions on statistical learning across the autism spectrum","authors":"Nikitas Angeletos Chrysaitis, Peggy Seriès","doi":"10.1101/2024.07.12.603256","DOIUrl":"https://doi.org/10.1101/2024.07.12.603256","url":null,"abstract":"Bayesian studies of perception have documented how the brain learns the statistics of a new environment and uses them to interpret sensory information. Impairments in this process have been hypothesised to be central to autism spectrum disorders. However, very few such studies have differentiated between implicit and explicit learning. We manipulated the instructions given before a cue-stimulus association task to investigate their effects on statistical learning. The task was conducted online, in 335 participants with varying autistic traits. In the implicit condition, where no information was provided, participants acquired weak prior beliefs about the task regularities. Conversely, explicit information about the presence of regularities resulted in strong priors, correctly reflecting the task’s statistics, regardless of the information’s veracity. Autistic traits correlated with greater uncertainty and faster updating in the implicit condition, but no significant differences were found in the influence of priors. Our findings illuminate how instructions affect statistical learning and how these effects differ across the autism spectrum. Author Summary Perception is greatly influenced by the brain’s prior knowledge of the environment, through a process called Bayesian inference. Recent theories of psychiatric disorders and particularly autism view them as impairments in this process. A crucial aspect of this process is how individuals form their knowledge of the environment. However, previous studies have not differentiated between learning that occurs when participants are aware of what they are learning and learning that happens implicitly. In the present study, we conducted an experiment with four conditions, each varying in terms of what participants were trying to learn and whether they were aware of the general form of the regularities. Our findings revealed that participants form much stronger beliefs about the regularities when they are informed about their presence. Additionally, we discovered that participants with strong autistic traits tend to be slightly more uncertain in their beliefs and quicker to update them, but only when they are unaware of the presence of regularities.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation","authors":"Bhaskar K. Chatterjee, Maroof Alam, Arghya Chakravorty, Shannon M. Lacy, Jason Rech, Charles L. Brooks, Peter D. Arvan, Matthias C. Truttmann","doi":"10.1101/2024.07.13.603377","DOIUrl":"https://doi.org/10.1101/2024.07.13.603377","url":null,"abstract":"The AMP transferase, FICD, is an emerging drug target finetuning stress signaling in the endoplasmic reticulum (ER). FICD is a bi-functional enzyme, catalyzing both AMP addition (AMPylation) and removal (deAMPylation) from the ER resident chaperone BiP/GRP78. Despite increasing evidence linking excessive BiP/GRP78 AMPylation to human diseases, small molecules to inhibit pathogenic FICD variants are lacking. Using an in-vitro high-throughput screen, we identify two small-molecule FICD inhibitors, C22 and C73. Both molecules significantly inhibit FICD-mediated BiP/GRP78 AMPylation in intact cells while only weakly inhibiting BiP/GRP78 deAMPylation. C22 and C73 also efficiently inhibit pathogenic FICD variants and improve proinsulin processing in β cells. Our study identifies and validates FICD inhibitors, highlighting a novel therapeutic avenue against pathologic protein AMPylation.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}