bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tightly-coupled inhibitory and excitatory functional networks in the early visual cortex
Authors: Mulholland Haleigh N. , Hein Bettina , Kaschube Matthias , Smith Gordon B. 
Published: August 2021

AbstractIntracortical inhibition plays a critical role in shaping activity patterns in the mature cortex. However, little is known about the structure of inhibition in early development prior to the onset of sensory experience, a time when spontaneous activity exhibits long-range correlations predictive of mature functional networks. Here, using calcium imaging of GABAergic neurons in the early ferret visual cortex, we show that spontaneous activity in inhibitory neurons is already highly organized into distributed modular networks before visual experience. Inhibitory neurons exhibit spatially modular activity with long-range correlations and precise local organization that is in quantitative agreement with excitatory networks. Furthermore, excitatory and inhibitory networks are strongly co-aligned at both millimeter and cellular scales. These results demonstrate a remarkable degree of organization in inhibitory networks early in the developing cortex, providing support for computational models of self-organizing networks and suggesting a mechanism for the emergence of distributed functional networks during development.
Molecular Basis for CPC-Sgo1 Interaction: Implications for Centromere Localisation and Function of the CPC
Authors: Abad Maria Alba , Gupta Tanmay , Hadders Michael A , Meppelink Amanda , Wopken J Pepijn , Blackburn Elizabeth , Zou Juan , Buzuk Lana , Kelly David A , McHugh Toni , Rappsilber Juri , Lens Susanne M A , Jeyaprakash A Arockia 
Published: August 2021

AbstractThe Chromosomal Passenger Complex (CPC; consisting of Borealin, Survivin, INCENP and Aurora B kinase) and Shugoshin 1 (Sgo1) are key regulators of chromosome bi-orientation, a process essential for error-free chromosome segregation. Their functions rely on their ability to associate with centromeres. Two histone phosphorylations, histone H3 Thr3 (H3T3ph; directly recognised by Survivin) and histone H2A Thr120 (H2AT120ph; indirectly recognised via Sgo1), together with CPC’s intrinsic ability to bind nucleosome, facilitate CPC centromere recruitment. The molecular basis for CPC-Sgo1 binding and how their direct interaction influences CPC centromere localisation and function are lacking. Here, using an integrative structure-function approach, we show that the histone H3-like Sgo1 N-terminal tail interacts with Survivin acting as a hot-spot for CPC-Sgo1 assembly, while downstream Sgo1 residues, mainly with Borealin contributes for high affinity interaction. Disruption of the Sgo1 N-terminal tail-Survivin interaction abolished CPC-Sgo1 assembly in vitro and perturbed centromere localisation and function of CPC. Our findings provide evidence that CPC binding to Sgo1 and histone H3 N-terminal tail are mutually exclusive, suggesting that these interactions will likely take place in a spatially/temporally restricted manner and provide a rationale for the Sgo1-mediated ‘kinetochore proximal centromere’ pool of CPC.
Combining genetic resources and elite material populations to improve the accuracy of genomic prediction in apple
Authors: Cazenave Xabi , Petit Bernard , Laurens François , Durel Charles-Eric , Muranty Hélène 
Published: August 2021

AbstractGenomic selection is an attractive strategy for apple breeding that could reduce the length of breeding cycles. A possible limitation to the practical implementation of this approach lies in the creation of a training set large and diverse enough to ensure accurate predictions. In this study, we investigated the potential of combining two available populations, i.e. genetic resources and elite material, in order to obtain a large training set with a high genetic diversity. We compared the predictive ability of genomic predictions within-population, across-population or when combining both populations, and tested a model accounting for population-specific marker effects in this last case. The obtained predictive abilities were moderate to high according to the studied trait and were always highest when the two populations were combined into a unique training set. We also investigated the potential of such a training set to predict hybrids resulting from crosses between the two populations, with a focus on the method to design the training set and the best proportion of each population to optimize predictions. The measured predictive abilities were very similar for all the proportions, except for the extreme cases where only one of the two populations was used in the training set, in which case predictive abilities could be lower than when using both populations. Using an optimization algorithm to choose the genotypes in the training set also led to higher predictive abilities than when the genotypes were chosen at random. Our results provide guidelines to initiate breeding programs that use genomic selection when the implementation of the training set is a limitation.
The connecting cilium inner scaffold provides a structural foundation to maintain photoreceptor integrity
Authors: Mercey Olivier , Kostic Corinne , Bertiaux Eloïse , Giroud Alexia , Sadian Yashar , Chang Ning , Arsenijevic Yvan , Guichard Paul , Hamel Virginie 
Published: August 2021

AbstractRetinal degeneration is a leading cause of human blindness due to progressive loss of ciliated photoreceptors cells. While this degradation can be associated with cohesion defects of the microtubule-based connecting cilium (CC) structure, the underlying mechanism is not understood. Here, using expansion microscopy and electron microscopy, we reveal the molecular architecture of the CC and demonstrate that microtubules are linked together by a CC-inner scaffold (CC-IS) containing POC5, CENTRIN and FAM161A. Monitoring CC-IS assembly during photoreceptor development in mouse reveals that it acts as a structural zipper, progressively bridging microtubule doublets and straightening the CC. Consistently, Fam161a mutations lead to a specific CC-IS loss and trigger microtubule doublets spreading, prior to outer segment collapse and photoreceptor degeneration, providing a molecular mechanism for retinitis pigmentosa disease.One Sentence SummaryThe connecting cilium inner scaffold acts as a structural zipper granting photoreceptor integrity.
Multiplex immunohistochemistry differences between Q fever and atherosclerotic abdominal aortic aneurysms indicate immune suppression
Authors: Cortenbach Kimberley R.G. , Staal Alexander H.J. , Schoffelen Teske , Gorris Mark A.J. , van der Woude Lieke L. , Jansen Anne F.M. , Poyck Paul , van Suylen Robert Jan , Wever Peter C. , Bleeker-Rovers Chantal P. , Srinivas Mangala , Hebeda Konnie M. , van Deuren Marcel , van der Meer Jos W.M. , De Vries I. Jolanda M. , van Kimmenade Roland R.J. 
Published: August 2021

AbstractBackgroundChronic Q fever is a zoonosis caused by the bacterium Coxiella burnetii which can manifest as infection of an abdominal aortic aneurysm (AAA). Antibiotic therapy often fails, resulting in severe morbidity and high mortality. Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue.MethodsMultiplex immunohistochemistry was used to investigate local inflammation in Q fever AAAs compared to atherosclerotic AAAs in aorta tissue specimen. Two six-plex panels were used to study both the innate and adaptive immune system.ResultsQ fever AAAs and atherosclerotic AAAs contained similar numbers of CD68+ macrophages and CD3+ T cells. However, in Q fever AAAs the number of CD68+CD206+ M2 macrophages was increased, while expression of GM-CSF was decreased compared to atherosclerotic AAAs. Furthermore, Q fever AAAs showed an increase in both the number of CD8+ cytotoxic T cells and CD3+FoxP3+ regulatory T cells. Lastly, Q fever AAAs did not contain any well-defined granulomas.ConclusionsThese findings demonstrate that despite the presence of pro-inflammatory effector cells, there is an immune suppressive micro environment in Q fever AAA resulting in persistent local infection with C. burnetii.
A functional network target for tic reduction during thalamic stimulation for Tourette Syndrome
Authors: Baldermann Juan Carlos , Hennen Christina , Schüller Thomas , Andrade Pablo , Visser-Vandewalle Veerle , Horn Andreas , Dembek Till A. , Petry-Schmelzer Jan Niklas , Strelow Joshua Niklas , Jergas Hannah , Kuhn Jens , Barbe Michael T. , Huys Daniel 
Published: August 2021

ABSTRACTBackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results.MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction.ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofrontal cortex was negatively associated. The overall connectivity pattern was robust to leave-one-out cross-validation, explaining 25 % of outcome variance (R = 0.500; p = 0.005).ConclusionsWe delineated a functional connectivity profile seeding from stimulation sites associated with TS-DBS outcome. This pattern comprised areas linked to the processing of premonitory urges and tic execution, thereby extending our current understanding of effective neuromodulation for TS.
Neurosecretory protein GL-induced fat accumulation is accompanied by repressing the immune-inflammatory response in the adipose tissue of mice
Authors: Fukumura Keisuke , Narimatsu Yuki , Iwakoshi-Ukena Eiko , Furumitsu Megumi , Bono Hidemasa , Ukena Kazuyoshi 
Published: August 2021

AbstractWe have recently identified neurosecretory protein GL (NPGL), a small secretory protein expressed in the vertebrate hypothalamus, as an orexigenic factor with remarkable fat accumulation by overexpression of the NPGL precursor gene (Npgl) for two months. In the present study, we analyzed the effects of short-term Npgl overexpression for 18 days as the early stage of obesity to address the mechanisms underlying obese-like phenotype. Similar to previous studies, short-term Npgl overexpression stimulated food intake and fat accumulation in the white adipose tissues (WAT), whereas the masses of the brown adipose tissue, testis, liver, heart, and muscle remained unchanged. In addition, we observed increased blood insulin and leptin levels due to Npgl overexpression, while little changes were induced in blood glucose, free fatty acids, triglyceride, and cholesterol levels. Furthermore, transcriptome analysis of the inguinal WAT using RNA-sequencing technique revealed that overexpression of Npgl upregulated the genes involved in cytoskeleton regulation, whereas it decreased those involved in immune-inflammatory responses. These results suggest that NPGL plays a crucial role in enlarging adipocytes and suppressing inflammation to avoid metabolic abnormalities, eventually contributing to accelerating energy storage.
Multimodal measurements of phototoxicity in nonlinear optical microscopy
Authors: Zhang Xinyi , Dorlhiac Gabriel , Landry Markita P. , Streets Aaron 
Published: August 2021

AbstractNonlinear optical imaging modalities, such as two-photon microscopy and stimulated Raman scattering (SRS) microscopy, make use of pulsed-laser excitation with high peak intensity that can perturb the native state of cells. In this study, we investigated the short and long-term effects of pulsed laser induced phototoxicity. We used bulk RNA sequencing, quantitative measurement of cell proliferation, and measurement of the generation of reactive oxygen species (ROS) to assess phototoxic effects, at different time scales, for a range of laser excitation settings relevant to SRS imaging. We define a range of laser excitation settings for which there was no significant ROS generation, differential gene expression, or change in proliferation rates of mouse Neuro2A cells. Changes in proliferation rate and ROS generation were observed under imaging conditions with an excitation intensity of over 600 mW/μm2. Repeated imaging of the same field of view at this excitation intensity of over 600 mW/μm2 resulted in visual damage to N2A cells. Laser induced perturbations in live cells may impact downstream measurements of cell state including subsequent imaging or molecular measurements. This study provides guidance for imaging parameters that minimize photo-induced perturbations in SRS microscopy to ensure accurate interpretation of experiments with time-lapse imaging or with paired measurements of imaging and sequencing on the same cells.
HPF1-dependent histone ADP-ribosylation triggers chromatin relaxation to promote the recruitment of repair factors at sites of DNA damage
Authors: Smith Rebecca , Zentout Siham , Chapuis Catherine , Timinszky Gyula , Huet Sébastien 
Published: August 2021

ABSTRACTPARP1 activity is regulated by its cofactor HPF1. The binding of HPF1 on PARP1 controls the grafting of ADP-ribose moieties on serine residues of proteins nearby the DNA lesions, mainly PARP1 and histones. However, the impact of HPF1 on DNA repair regulated by PARP1 remains unclear. Here, we show that HPF1 controls both the number and the length of the ADP-ribose chains generated by PARP1 at DNA lesions. We demonstrate that HPF1-dependent histone ADP-ribosylation, rather than auto-modification of PARP1, triggers the rapid unfolding of the chromatin structure at the DNA damage sites and promotes the recruitment of the repair factors CHD4 and CHD7. Together with the observation that HPF1 contributes to efficient repair both by homologous recombination and non-homologous end joining, our findings highlight the key roles played by this PARP1 cofactor at early stages of the DNA damage response.
Six1 Promotes Skeletal Muscle Thyroid Hormone Response through Regulation of the MCT10 Transporter
Authors: Girgis John , Yang Dabo , Chakroun Imane , Liu Yubing , Blais Alexandre 
Published: August 2021

AbstractThe Six1 transcription factor is implicated in controlling the development of several tissue types, notably skeletal muscle. Six1 also contributes to muscle metabolism and its activity is associated with the fast-twitch, glycolytic phenotype. Six1 regulates the expression of certain genes of the fast muscle program by directly stimulating their transcription or indirectly acting through a long non-coding RNA. Under the hypothesis that additional mechanisms of action might be at play, a combined analysis of gene expression profiling and genome-wide location analysis data was performed. TheSlc16a10gene, encoding the thyroid hormone transmembrane transporter MCT10, was identified as a gene with a transcriptional enhancer directly bound by Six1 and requiring Six1 activity for full expression in adult mouse tibialis anterior, a predominantly fast-twitch muscle. Of the various thyroid hormone transporters, MCT10 mRNA was found to be the most abundant in skeletal muscle, and to have a stronger expression in fast-twitch compared to slow-twitch muscle groups. Loss-of-function of MCT10 in the tibialis anterior recapitulated the effect of Six1 on the expression of fast-twitch muscle genes and led to lower activity of a thyroid hormone receptor-dependent reporter gene. These results shed light on the molecular mechanisms controlling the tissue expression profile of MCT10 and identify modulation of the thyroid hormone signaling pathway as an additional mechanism by which Six1 influences skeletal muscle metabolism.
Interorganelle lipid flux revealed by enzymatic mass tagging in vivo
Authors: John Peter Arun T. , Peter Matthias , Kornmann Benoît 
Published: August 2021

AbstractThe distinct activities of cellular organelles are dependent on the proper function of their membranes. Coordinated membrane biogenesis of the different organelles necessitates interorganelle transport of lipids from their site of synthesis to their destination membranes. Several proteins and trafficking pathways have been proposed to participate in lipid distribution, but despite the basic importance of this process, in vivo evidence linking the absence of putative transport pathways to specific transport defects remains scarce. An obvious reason for this scarcity is the near absence of in vivo lipid trafficking assays. Here we introduce a versatile method named METALIC (Mass tagging-Enabled TrAcking of Lipids In Cells) to track interorganelle lipid flux inside living cells. In this strategy, two enzymes, one directed to a “donor” and the other to an “acceptor” organelle, add two distinct mass tags to lipids. Mass spectrometry-based detection of lipids bearing the two mass tags is then used as a proxy for lipid exchange between the two organelles. By applying this approach to ER and mitochondria, we show that the ERMES and Vps13-Mcp1 complexes have lipid transport activity in vivo, and unravel their relative contributions to ER-mitochondria lipid exchange.
Renal Interstitial Cells Promote Nephron Regeneration by Secreting Prostaglandin E2
Authors: Liu Xiaoliang , Yu Ting , Tan Xiaoqin , Jin Daqing , Zhang Jiangping , Zhang Yunfeng , Liao Shuyi , Yang Wenmin , Zhao Jinghong , Zhong Tao P , Liu Chi 
Published: August 2021

AbstractIn organ regeneration, progrnitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation and differentiation. However, what kind of cells provide a native microenvironment for renal progenitor cells has not been clarified. Here, single-cell sequencing of zebrafish kidney revealed that fabp10 was a marker of renal interstitial cells (RICs), and the Tg(fabp10a:GFP) transgenic line can specifically label RICs in zebrafish kidney. The formation of RICs and nephrons are closely accompanied during nephron regeneration. RICs form a network to wrap the renal progenitor cell aggregates. RICs in close contact with cell aggregates express cyclooxygenase 2 and secrete prostaglandin 2 (PGE2). Inhibiting PGE2 production prevented nephrogenesis by reducing the proliferation and differentiation of progenitor cell aggregates. PGE2 promoted maturation of the nephron by activating the WNT signaling pathway in progenitor cell aggregates in cooperation with Wnt4a. These findings suggest that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.
A highly active phosphate-insensitive phosphatase is widely distributed in nature
Authors: Lidbury Ian D.E.A. , Scanlan David J. , Murphy Andrew R. J. , Christie-Oleza Joseph A. , Aguilo-Ferretjans Maria M. , Hitchcock Andrew , Daniell Tim 
Published: August 2021

AbstractThe regeneration of bioavailable phosphate from immobilised organophosphorus represents a key process in the global phosphorus cycle and is facilitated by enzymes known as phosphatases. Most bacteria possess at least one of three major phosphatases, known as PhoA, PhoX and PhoD, whose activity is optimal under alkaline conditions. The production and activity of these three phosphatase families is negatively regulated by phosphate availability and thus these enzymes play a major role in scavenging phosphorus only during times of phosphate scarcity. Here, we reveal a previously overlooked phosphate-insensitive phosphatase, PafA, prevalent inBacteroidetes, which is highly abundant in nature and represents a major route for the remineralisation of phosphate in the environment. UsingFlavobacterium johnsoniaeas the model, we reveal PafA is highly active towards phosphomonoesters. Unlike other major phosphatases, PafA is fully functional in the presence of its metabolic product, phosphate, and is essential for growth on phosphorylated carbohydrates as a sole carbon source. PafA, which is constitutively produced under all growth conditions tested, rapidly remineralises phosphomonoesters producing significant quantities of bioavailable phosphate that can cross feed into neighbouring cells.pafAis both abundant and highly expressed in the global ocean and abundant in plant rhizospheres, highlighting a new and important enzyme in the global phosphorus cycle with applied implications for agriculture as well as biogeochemical cycling. We speculate PafA expands the metabolic niche ofBacteroidetesby enabling utilisation of abundant organophosphorus substrates in the presence of excess phosphate, when other microbes are rendered incapable.Significance statementPhosphorus is an essential element for all life on Earth. Global primary production, and thus the ability for oceans and soils to drawdown atmospheric carbon dioxide, is in part controlled by the availability of inorganic phosphate. Likewise, global food production is also reliant on adequate supplies of phosphorus to both plants and animals. A major fraction of the total phosphorus pool exists as organic phosphorus, which requires mineralisation to phosphate prior to incorporation into cellular biomolecules. This important process is performed by enzymes known as phosphatases. Here, we reveal that the unique bacterial phosphatase, PafA, is a key player in the global phosphorus cycle and presents a major route for the regeneration of bioavailable phosphate required for both primary and secondary production.
Evolutionary analyses of visual opsin genes in anurans reveals diversity and positive selection suggestive of functional adaptation to distinct light environments
Authors: Schott Ryan K , Perez Leah , Kwiatkowski Matthew A , Imhoff Vance , Gumm Jennifer M 
Published: August 2021

AbstractAmong major vertebrate groups, anurans (frogs and toads) are understudied with regards to their visual systems and little is known about variation among species that differ in ecology. We sampled North American anurans representing diverse evolutionary and life histories that likely possess visual systems adapted to meet different ecological needs. Using standard molecular techniques, visual opsin genes, which encode the protein component of visual pigments, were obtained from anuran retinas. Additionally, we extracted the visual opsins from publicly available genome and transcriptome assemblies, further increasing the phylogenetic and ecological diversity of our dataset. We found that anurans consistently express four visual opsin genes (RH1, LWS, SWS1, and SWS2, but not RH2) even though reported photoreceptor complements vary widely among species. We found the first evidence of visual opsin duplication in an amphibian with the duplication of the LWS gene in the African bullfrog, which had distinct LWS copies on the sex chromosomes. The proteins encoded by these genes showed considerable sequence variation among species, including at sites known to shift the spectral sensitivity of visual pigments in other vertebrates and thus mediate dim-light and color vision. Using molecular evolutionary analyses of selection (dN/dS) we found significant evidence for positive selection at a subset of sites in the dim-light rod opsin gene RH1 and the long wavelength sensitive cone opsin gene LWS. The function of sites inferred to be under positive selection are largely unknown, but a few are likely to affect spectral sensitivity and other visual pigment functions based on proximity to previously identified sites in other vertebrates. The observed variation cannot fully be explained by evolutionary relationships among species alone. Taken together, our results suggest that other ecological factors, such as habitat and life history, as well as behaviour, may be driving changes to anuran visual systems.