bluuebunny/crossref_metadata_2025_split huggingface dataset:
The basolateral amygdala to lateral septum circuit is critical for regulating sociability in mice
Authors: Rodriguez Lionel A. , Kim Sun-Hong , Page Stephanie C. , Nguyen Claudia V. , Pattie Elizabeth A. , Hallock Henry L. , Valerino Jessica , Maynard Kristen R. , Jaffe Andrew E. , Martinowich Keri 
Published: October 2021

ABSTRACTThe lateral septum (LS) is a GABAergic region in the basal forebrain that is implicated in sociability. However, the neural circuits and cell signaling pathways that converge on the LS to mediate social behaviors aren’t well understood. Multiple lines of evidence suggest that brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays important roles in social behavior. While BDNF is not locally produced in LS, we demonstrate that nearly all GABAergic neurons in LS express TrkB. Local knock-down of TrkB expression from LS neurons decreased sociability and reduced recruitment of social novelty-induced neural activity. Since BDNF is not synthesized in LS, we evaluated which inputs to the LS could serve as potential BDNF sources for controlling sociability. By selectively ablating inputs to LS, we demonstrated that inputs from the basolateral amygdala (BLA), but not ventral CA1 (vCA1), regulate sociability. Moreover, depleting BDNF selectively in BLA-LS projection neurons phenocopied the decreased sociability observed following either local LS TrkB knockdown or ablation of BLA-LS inputs. These data support the hypothesis that BLA-LS projection neurons could serve as a critical source of BDNF for activating TrkB signaling in LS neurons to control sociability.
Commensal bacteria promote type I interferon signaling to maintain immune tolerance
Authors: Ayala Adriana Vasquez , Hsu Chia-Yun , Matsuo Kazuhiko , Buzun Ekaterina , Terrazas Marvic Carrillo , Loomis Luke R. , Lu Hsueh-Han , Park Jong Hwee , Rivaud Paul , Thomson Matt , Chu Hiutung 
Published: October 2021

ABSTRACTType I interferons (IFN) exert a broad range of biological effects important in coordinating immune responses. Host and microbial factors regulate IFN production, triggering a signaling cascade that has classically been studied in the context of pathogen clearance. In particular, commensal bacteria have been shown to induce IFN to protect against viral infections. Yet, whether immunomodulatory bacteria operate through IFN pathways to support immune tolerance remains elusive. Here, we demonstrate microbiota-dependent IFN signaling is required for priming tolerogenic T regulatory cells (Tregs) by intestinal dendritic cells (DCs). DCs deficient in IFN signaling through deletion of IFNAR-1 display dysregulated cytokine production in response to the commensal bacteria Bacteroides fragilis, resulting in blunted downstream Treg responses. Single cell RNA sequencing of gut tissues demonstrated that colonization with B. fragilis promotes a distinct type I IFN gene signature in Tregs during homeostasis and intestinal inflammation. Moreover, B. fragilis-mediated protection during experimental colitis was abrogated in IFNAR1-deficient mice. Altogether, our findings demonstrate an important role of microbiota-mediated immune tolerance via tonic type I IFN signaling.
Proteomic analysis of mouse kidney tissue associates peroxisomal dysfunction with early diabetic kidney disease
Authors: Tserga Aggeliki , Pouloudi Despoina , Saulnier-Blache Jean Sébastien , Stroggilos Rafael , Theochari Irene , Gakiopoulou Harikleia , Mischak Harald , Zoidakis Jerome , Schanstra Joost Peter , Vlahou Antonia , Makridakis Manousos 
Published: October 2021

ABSTRACTBackgroundThe absence of efficient inhibitors for DKD progression reflects the gaps in our understanding of DKD molecular pathogenesis. A comprehensive proteomic analysis was performed on glomeruli and kidney cortex of diabetic mice with subsequent validation of findings in human biopsies and - omics datasets aiming to better understand the underlying molecular biology of early DKD development and progression.MethodsLC–MS/MS was employed to analyze the kidney proteome of DKD mouse models: Glomeruli of Ins2Akita mice 2 month and 4 month old, and cortex of db/db mice 6 month old. Following label-free quantification, the abundance of detected proteins were correlated with existing kidney datasets and functionally annotated. Tissue sections from 16 DKD patients were analyzed by IHC.ResultsPathway analysis of differentially expressed proteins in the early and late DKD versus controls predicted dysregulation in DKD hallmarks (such as peroxisomal lipid metabolism, β-oxidation and TCA cycle) supporting the functional relevance of the findings. Comparing the observed protein changes in early and late DKD, consistent upregulation of 21 and downregulation of 18 proteins was detected. Among these were downregulated peroxisomal proteins such as NUDT19, ACOX1, and AMACR and upregulated mitochondrial proteins related to aminoacid metabolism including GLS, GLDC, and GCAT. Several of these changes were also observed in the kidney cortex proteome of db/db mice. IHC of human kidney further confirmed the differential expression of NUDT19, AGPS, AMACR and CAT proteins in DKD.ConclusionsOur study shows an extensive differential expression of peroxisomal proteins in the early stages of DKD that persists regardless of the disease severity. These proteins therefore represent potential markers of early DKD pathogenesis. Collectively, essential pathways associated with peroxisomes such as lipid β-oxidation, plasmalogen synthesis, aminoacid metabolism and response to oxidative stress are downregulated in early DKD, providing new perspectives and potential markers of diabetic kidney dysfunction.
Colour Vision in Stomatopod Crustaceans: more questions than answers
Authors: Streets Amy , England Hayley , Marshall Justin 
Published: October 2021

AbstractStomatopod crustaceans, or mantis shrimps, are known for their extensive range of spectral sensitivities but relatively poor spectral discrimination. Instead of the colour-opponent mechanism of other colour vision systems, the 12 narrow-band colour channels they possess may underlie a different method of colour processing. We investigated one hypothesis, in which the photoreceptors are proposed to act as individual wave-band detectors, interpreting colour as a parallel pattern of photoreceptor activation, rather than a ratiometric comparison of individual signals. This different form of colour detection has been used to explain previous behavioural tests in which low saturation blue was not discriminated from grey potentially because of similar activation patterns. Results here, however, indicate that the stomatopod, Haptosquilla trispinosa was able to easily distinguish several colours, including blue of both high and low saturation, from greys. The animals did show a decrease in performance over time in an artificially lit environment, indicating plasticity in colour discrimination ability. This rapid plasticity, most likely the result of a change in opsin (visual pigment) expression, has now been noted in several animal lineages (both invertebrate and vertebrate) and is a factor we suggest needing care and potential re-examination in any colour-based behavioural tests. As for stomatopods, it remains unclear why they achieve poor colour discrimination using the most comprehensive set of spectral sensitivities in the animal kingdom and also what form of colour processing they may utilise.
The HIV-1 Integrase C-Terminal domain induces TAR RNA structural changes promoting Tat binding
Authors: Rocchi Cecilia , Louvat Camille , Miele Adriana , Batisse Julien , Guillon Christophe , Ballut Lionel , Lener Daniela , Negroni Matteo , Ruff Marc , Gouet Patrice , Fiorini Francesca 
Published: October 2021

ABSTRACTRecent evidence indicated that HIV-1 Integrase (IN) binds genomic viral RNA (gRNA) playing a critical role in viral particle morphogenesis and gRNA stability in host cells. Combining biophysical and biochemical approaches we show that the C-terminal flexible 18-residues tail of IN acts as a sensor of the peculiar apical structure of trans-activation response element RNA (TAR), directly interacting with its hexaloop. We highlighted how the whole IN C-terminal domain, once bound to TAR, can change its structure assisting the binding of Tat, the HIV trans-activator protein, which finally displaces IN from TAR. Our results are consistent with the emerging role of IN in early stage of proviral transcription and suggest new steps of HIV-1 life cycle that can be considered as therapeutic targets.
Learning the statistics of pain: computational and neural mechanisms
Authors: Mancini Flavia , Zhang Suyi , Seymour Ben 
Published: October 2021

ABSTRACTPain invariably changes over time, and these temporal fluctuations are riddled with uncertainty about body safety. In theory, statistical regularities of pain through time contain useful information that can be learned, allowing the brain to generate expectations and inform behaviour. To investigate this, we exposed healthy participants to probabilistic sequences of low and high-intensity electrical stimuli to the left hand, containing sudden changes in stimulus frequencies. We demonstrate that humans can learn to extract these regularities, and explicitly predict the likelihood of forthcoming pain intensities in a manner consistent with optimal Bayesian models with dynamic update of beliefs. We studied brain activity using functional MRI whilst subjects performed the task, which allowed us to dissect the underlying neural correlates of these statistical inferences from their uncertainty and update. We found that the inferred frequency (posterior probability) of high intensity pain correlated with activity in bilateral sensorimotor cortex, secondary somatosensory cortex and right caudate. The uncertainty of statistical inferences of pain was encoded in the right superior parietal cortex. An intrinsic part of this hierarchical Bayesian model is the way that unexpected changes in frequency lead to shift beliefs and update the internal model. This is reflected by the KL divergence between consecutive posterior distributions and associated with brain responses in the premotor cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. In conclusion, this study extends what is conventionally considered a sensory pain pathway dedicated to process pain intensity, to include the generation of Bayesian internal models of temporal statistics of pain intensity levels in sensorimotor regions, which are updated dynamically through the engagement of premotor, prefrontal and parietal regions.
A holistic insight of mycobacteriophage induced changes in mycobacterial cells
Authors: Calcuttawala Fatema , Shaw Rahul , Sarbajna Arpita , Dutta Moumita , Sinha Saptarshi , Das Gupta Sujoy K. 
Published: October 2021

AbstractMycobacteriophages are phages that interact with mycobacteria resulting in their killing. Although lysis is the major mechanism by which mycobacteriophages cause cell death, other mechanisms may also be involved. The present study was initiated with the objective of investigating the changes that take place at the cellular level following the infection of mycobacterial cells by phage D29. To investigate this issue, we took recourse to performing immunofluorescence and electron microscopic studies. Transmission electron microscopic examination revealed the adsorption of phages on to the surface of mycobacteria, following which penetration of the tail through the thick mycoloic acid layer was seen. At later time points discrete populations of cells at different stages of lysis were observed, which comprised of completely lysed cells, in which the cells were fragmented and those at the early onset stage exhibited formation of membrane pores through which the phages and intracellular contents were released. SEM results also indicated that phages may come out through the entire surface of the cell, or alternatively through gaps in the surface. In some of the images we observed structures that apparently resembled membrane blebs which are normally encountered when cells undergo programmed cell death (PCD). In addition, we observed significant increase in DNA fragmentation as well as membrane depolarization, which are also indicative of occurrence of PCD. As several bacterial PCD pathways are mediated by the toxin-antitoxin (TA) modules, the expression profile of all the TA systems was examined before and after phage infection. Apart from specifically addressing the issue of PCD in mycobacteriophage infected cells, this investigation has led to the development of facile tools necessary for investigating mycobacteriophage-mycobacteria interactions by means of microscopic methods.
Neuropeptide Neuromedin B does not alter body weight and glucose homeostasis nor does it act as an insulin-releasing peptide
Authors: Cikes Domagoj , Atanes Patricio , Huang Guo-Cai , Persaud Shanta J. , Penninger Josef M. 
Published: October 2021

AbstractNeuromedin B (NMB) is a member of the neuromedin family of neuropeptides with a high level of region-specific expression in the brain. Several GWAS studies on non-obese and obese patients suggested that polymorphisms in NMB predispose to obesity by affecting appetite control and feeding preference. Furthermore, several studies proposed that NMB can act as an insulin releasing peptide. Since the functional study has never been done, the in vivo role of NMB as modulator of weight gain or glucose metabolism remains unclear. Here, we generated Nmb conditional mice and nervous system deficient NmB mice. We then performed olfactory and food preference analysis, as well as metabolic analysis under standard and high fat diet. Additionally, in direct islet studies we evaluated the role of NMB on basal and glucose-stimulated insulin secretion in mouse and humans.
Cooperative Effects of RIG-I-like Receptor Signaling and IRF1 on DNA Damage-Induced Cell Death
Authors: Zander David Y. , Burkart Sandy S. , Wüst Sandra , Magalhães Vladimir G. , Binder Marco 
Published: October 2021

AbstractProperly responding to DNA damage is vital for eukaryotic cells, including the induction of DNA repair, growth arrest and, as a last resort to prevent neoplastic transformation, cell death. Besides being crucial for ensuring homeostasis, the same pathways and mechanisms are at the basis of chemoradiotherapy in cancer treatment, which involves therapeutic induction of DNA damage by chemical or physical (radiological) measures. Apart from typical DNA damage response mediators, the relevance of cell-intrinsic antiviral signaling pathways in response to DNA breaks has recently emerged. Originally known for combatting viruses via expression of antiviral factors including IFNs and establishing of an antiviral state, RIG-I-like receptors (RLRs) were found to be critical for adequate induction of cell death upon the introduction of DNA double-strand breaks. We here show that presence of IRF3 is crucial in this process, most likely through direct activation of pro-apoptotic factors rather than transcriptional induction of canonical downstream components, such as IFNs. Investigating genes reported to be involved in both DNA damage response and antiviral signaling, we demonstrate that IRF1 is an obligatory factor for DNA damage-induced cell death. Interestingly, its regulation doesnotrequire activation of RLR signaling, but rather sensing of DNA double strand breaks by ATM and ATR. Hence, even though independently regulated, both RLR signaling and IRF1 are essential for proper induction/execution of intrinsic apoptosis. Our results not only support more broadly developing IRF1 as a biomarker predictive for the effectiveness of chemoradiotherapy, but also suggest investigating a combined pharmacological stimulation of RLR and IRF1 signaling as a potential adjuvant regimen in tumor therapy.
Contribution of cytoplasm viscoelastic properties to mitotic spindle positioning
Authors: Xie Jing , Najafi Javad , Borgne Rémi Le , Verbavatz Jean-Marc , Durieu Catherine , Sallé Jeremy , Minc Nicolas 
Published: October 2021

ABSTRACTCells are filled with macromolecules and polymer networks that set scale-dependent viscous and elastic properties to the cytoplasm. Although the role of these parameters in molecular diffusion, reaction kinetics and cellular biochemistry is being increasingly recognized, their contributions to the motion and positioning of larger organelles, such as mitotic spindles for cell division remain unknown. Here, using magnetic tweezers to displace and rotate mitotic spindles in living embryos, we uncovered that the cytoplasm can impart viscoelastic reactive forces that move spindles, or passive objects with similar size, back to their original position. These forces are independent of cytoskeletal force generators, yet reach hundreds of piconewtons and scale with cytoplasm crowding. Spindle motion shears and fluidizes the cytoplasm, dissipating elastic energy and limiting spindle recoils with functional implications for asymmetric and oriented divisions. These findings suggest that bulk cytoplasm material properties may constitute important control elements for the regulation of division positioning and cellular organization.Significance StatementThe regulation of mitotic spindle positioning is a key process for tissue architecture, embryo development and stem cells. To date, most models have assumed that spindles are positioned by forces exerted by polar cytoskeleton networks, like microtubule asters or acto-myosin bundles. Here, usingin situmagnetic tweezers to apply calibrated forces and torques to mitotic spindles in live dividing sea urchin cells, we found that the viscoelastic properties of the cytoplasm medium in which spindles are embedded can hold spindles in place, and move them back if their original position is perturbed. These viscoelastic forces are large and may significantly participate in the force balance that position and orient mitotic spindles in many cell types.
Actin filaments act as a size-dependent diffusion barrier around centrosomes
Authors: Cheng Hsuan , Kao Yu-Lin , Sharma Lohitaksh , Yang Wen-Ting , Huang Shih-Han , Lin Hong-Rui , Huang Yao-Shen , Kao Chi-Ling , Yang Lee-Wei , Bearon Rachel , Lin Yu-Chun 
Published: October 2021

AbstractThe centrosome, a non-membranous organelle, constrains various soluble molecules locally to execute its functions. As the centrosome is surrounded by various dense components, we hypothesized that the centrosome may be bordered by a putative diffusion barrier. After quantitatively measuring the trapping kinetics of soluble proteins of varying size at centrosomes by a chemically inducible diffusion trapping assay, we found that centrosomes were highly accessible to soluble molecules with a Stokes radius of ≤ 5.1 nm, whereas larger molecules rarely reach centrosomes, indicating the existence of a size-dependent diffusion barrier at centrosomes. The permeability of barriers was tightly regulated by branched actin filaments outside of centrosomes. Such barrier gated the microtubule nucleation. We propose that actin filaments spatiotemporally constrain the distribution of molecules at centrosomes in a size-dependent manner.Significance StatementCentrosome maintains its microenvironment without membrane. Whether the dense protein complexes outside centrosomes including pericentriolar matrix, microtubules, and branched actin filaments provide physical obstruction is unclear yet. We here established a series of new tools for quantitative evaluation of the diffusion rates of varisized soluble proteins in different sub-compartments of centrosomes. Our results demonstrated that branched actin filaments, but not pericentriolar matrix or microtubules, around centrosome have acted as a size-dependent diffusion barrier and physically constrain centrosome microtubule nucleation.
Hyperphosphatemia increases inflammation to exacerbate anemia and skeletal muscle wasting independently of FGF23-FGFR4 signaling
Authors: Czaya Brian , Heitman Kylie , Campos Isaac , Yanucil Christopher , Kentrup Dominik , Westbrook David , Gutierrez Orlando , Babitt Jodie L. , Jung Grace , Salusky Isidro B. , Hanudel Mark R. , Faul Christian 
Published: October 2021

AbstractElevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a phosphate-rich diet. Whether hyperphosphatemia and/or associated changes in metabolic regulators, including elevations of fibroblast growth factor 23 (FGF23) directly contribute to specific complications of CKD is uncertain. Here we report that similar to patients with CKD, mice with adenine-induced CKD develop inflammation, anemia and skeletal muscle wasting. These complications are also observed in mice fed high phosphate diet even without CKD. Ablation of pathologic FGF23- FGFR4 signaling did not protect mice on an increased phosphate diet or mice with adenine- induced CKD from these sequelae. However, low phosphate diet ameliorated anemia and skeletal muscle wasting in a genetic mouse model of CKD. Our mechanistic in vitro studies indicate that phosphate elevations induce inflammatory signaling and increase hepcidin expression in hepatocytes, a potential causative link between hyperphosphatemia, anemia and skeletal muscle dysfunction. Our study suggests that high phosphate intake, as caused by the consumption of processed food, may have harmful effects irrespective of pre-existing kidney injury, supporting not only the clinical utility of treating hyperphosphatemia in CKD patients but also arguing for limiting phosphate intake in healthy individuals.
Active disturbance rejection attitude control of unmanned quadrotor via paired coevolution pigeon-inspired optimization
Authors: Yuan Yang , Duan Haibin 
Published: October 2021

Purpose
The purpose of this paper is to develop a novel active disturbance rejection attitude controller for quadrotors and propose a controller parameters identification approach to obtain better control results.

Design/methodology/approach
Aiming at the problem that quadrotor is susceptible to disturbance in outdoor flight, the improved active disturbance rejection control (IADRC) is applied to design attitude controller. To overcome the difficulty that adjusting the parameters of IADRC controller manually is complex, paired coevolution pigeon-inspired optimization (PCPIO) algorithm is used to optimize the control parameters.

Findings
The IADRC, where nonlinear state error feedback control law is replaced by non-singular fast terminal sliding mode control law and a third-order tracking differentiator is designed for second derivative of the state, has higher control accuracy and better robustness than ADRC. The improved PIO algorithm based on evolutionary mechanism, named PCPIO, is proposed. The optimal parameters of ADRC controller are found by PCPIO with the optimization criterion of integral of time-weighted absolute value of the error. The effectiveness of the proposed method is verified by a series of simulation experiments.

Practical implications
IADRC can improve the accuracy of attitude control of quadrotor and resist external interference more effectively. The proposed PCPIO algorithm can be easily applied to practice and can help the design of the quadrotor control system.

Originality/value
An improved active disturbance rejection controller is designed for quadrotor attitude control, and a hybrid model of PIO and evolution mechanism is proposed for parameters identification of the controller.