Biology subjects

Zhao, X.

Publications and source records attributed to Zhao, X..

At least 19 recordsLinked to original sources

bioRxiv2018

HiAlc Klebsiella pneumonia, one of potential chief culprits of non-alcoholic fatty liver disease: through generation of endogenous ethanol

Non-alcoholic fatty liver disease (NAFLD), a prelude of cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. NAFLD has been considerated to be associated with the composition of gut microbiota. However, causal relationship between change of gut microbiome and NAFLD remains unclear. Here we show that Klebsiella pneumoniae was significantly associated with NAFLD through inducing generation of endogenous ethanol. A strain of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) was initially isolated from fecal samples of patient with non-alcoholic steatohepatitis (NASH) accompanied with auto-brewery syndrome (ABS). Gavage of HiAlc Kpn was capable of inducing murine model of fatty liver disease (FLD) in which had typical pathological changes of hepatic steatosis and similar liver gene expression profiles to those of alcohol intake in mice. Data derived from germ-free mice by gnotobiotic gavage further demonstrated that the HiAlc Kpn is the major cause of the changes in FLD mice. Furthermore, using proteomic and metabolitic analysis, we found that HiAlc Kpn induced generation of endogenous alcohol through the 2,3-butanediol fermentation pathway. More interestingly, the blood alcohol concentration was elevated in FLD mice induced by HiAlc Kpn after glucose intake. Clinical analysis showed that HiAlc Kpn were observed in up to 60% of patients with NAFLD. Our results suggested that HiAlc Kpn make important contribution to NAFLD, possibly through generation of the endogenous alcohol. Thus, targeting these bacteria might provide a novel therapeutic for clinical treatment of NAFLD.\n\nIn BriefFatty liver disease induced by high alcohol-producing Klebsiella pneumoniae\n\nCompeting Financial Interest StatementThe authors declare no conflicts of interest.

microbiology↗

bioRxiv2018

High stretchability, strength and toughness of living cells enabled by hyperelastic vimentin network

In many normal and abnormal physiological processes, including cellular migration during normal development and invasion in cancer metastasis, cells are required to withstand severe deformations. The structural integrity of eukaryotic cells under small deformations has been known to depend on the cytoskeleton including actin filaments (F-actin), microtubules and intermediate filaments (IFs). However, it remains unclear how cells resist severe deformations since both F-actin and microtubules fluidize or disassemble under moderate strains. Here, we demonstrate that vimentin intermediate filaments (VIFs), a marker of mesenchymal cells, dominate cytoplasmic mechanics at large deformations. Our results show that cytoskeletal VIFs form a stretchable, hyperelastic network. This network works synergistically with other dissipative cytoplasmic components, substantially enhancing the strength, stretchability, resilience and toughness of the living cytoplasm.

biophysics↗

bioRxiv2018

Determination of sex of sacrum in adult Macaca mulatta

[Abstract]O_ST_ABSBackgroundC_ST_ABSSacrum being a part of pelvis is an important bone for identification of sex in both living primates and fossil ones.\n\nAimAim of this work was to examine the sex differences of sacral parameters in rhesus macaques and to compare with those of the other primates.\n\nMaterials and MethodsFifty-six adult scara of macaques (17 males and 39 females) have been investigated. Measurement of various parameters was done using sliding vernier calliper; and statistical analysis was done using SPSS 23.0 package.\n\nResultsThe present study showed that the cranial breadth of the sacrum, the sacral length, transverse diameter and sagittal diameter of the cranial articular surface, and two indices of relative sacral breadth were highly significant for sex determination in Macaca mulatta. Comparison of the present data with other studies suggest that sex determination of sacrum can be very different in various types of primates.\n\nConclusionThe results suggest that these measures may be functionally integrated in response to locomotion, obstetric adequacy and cephalopelvic proportions in primates. Sacral index is more reliable and should be applied for sex determination of sacrum in various anatomical and anthropological investigations.

animal behavior and cognition↗

bioRxiv2018

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

Diabetic retinopathy (DR) caused visual performance degradation seriously endangers human beings health, uncovering the underlying mechanism might shed light on the discovery of DR therapeutic treatments. In this study, we found that the effects of glucose on retinal pigment epithelium (RPE) varies in a dose dependent manner, high-glucose promotes ROS generation and cell apoptosis, inhibits mitophagy as well as proliferative abilities, while low-glucose induces ROS production and cell mitophagy, but has little impacts on cell apoptosis and proliferation. Of note, the toxic effects of high-glucose on RPE are alleviated by ROS scavengers and aggravated by autophagy inhibitor 3-methyladenine (3-MA) or mitophagy inhibitor cyclosporin A (CsA). High-glucose induced ROS generation is merely eliminated by ROS scavengers instead of mitophagy or autophagy inhibitor. We also proved that high-glucose inhibits cell proliferation and promotes cell apoptosis by regulating ROS mediated inhibition of mitophagy. In addition, mitophagy associated proteins PINK1 and Parkin are downregulated by high-glucose or hydrogen peroxide treatments, which are reversed by ROS scavengers. Of note, Knock-down of PINK1 decreases phospharylated Parkin instead of total Parkin levels in RPE. Intriguingly, high-glucoses inhibiting effects on cell mitophagy as well as proliferation and its promoting effects on cell apoptosis are reversed by either PINK1 or Parkin overexpression. Therefore, we concluded that high-glucose promotes RPE apoptosis and inhibits cell proliferation as well as mitophagy by regulating oxidative stress mediated inactivation of ROS/PINKl/Parkin signal pathway.

cell biology↗

bioRxiv2018

The role of BMP6 in the proliferation and differentiation of chicken cartilage cells

Previous studies have indicated that bone morphogenetic protein (BMP) 6 plays an important role in skeletal system development and progression. However, the mechanism underlying the effects of BMP6 in cartilage cell proliferation and differentiation remains unknown. In this study, cartilage cells were isolated from shanks of chicken embryos and treated with different concentrations of GH. Cell proliferation and differentiation potential was assessed using real-time polymerase chain reaction (RT-PCR) and CCK-8 assays in vitro. The results showed that at 48 h, the Collagen II and BMP6 expression levels in 50 ng/l GH-treated cartilage cells were significantly higher than in groups treated with 100 ng/l or 200 ng/l GH. We further observed that knockdown of BMP6 in cartilage cells led to significantly decreased expression levels of Collagen II and Collagen X. Moreover, the suppression of BMP6 expression by a specific siRNA vector led to significantly decreased expression levels of IGF1R, JAK, PKC, PTH, IHH and PTHrP. Taken together, our data suggest that BMP6 may play a critical role in chicken cartilage cell proliferation and differentiation through the regulation of IGF1, JAK2, PKC, PTH, and Ihh-PTHrP signaling pathways.

cell biology↗

bioRxiv2018

Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq

The tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. We profiled the breast cancer tumor microenvironment by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. This study explores the diversity of the cell types in the tumor microenvironment and provides information on the mechanisms of escape from clearance by immune cells in breast cancer.\n\nOne Sentence SummaryLandscape of tumor cells and immune cells in breast cancer by single cell RNA-seq

cancer biology↗

bioRxiv2018

3’ Branch Ligation: A Novel Method to Ligate Non-Complementary DNA to Recessed or Internal 3’OH Ends in DNA or RNA

Nucleic acid ligases are crucial enzymes that repair breaks in DNA or RNA during synthesis, repair and recombination. Various molecular tools have been developed using the diverse activities of DNA/RNA ligases. Herein, we demonstrate a non-conventional ability of T4 DNA ligase to join 5 phosphorylated blunt-end double-stranded DNA to DNA breaks at 3 recessive ends, gaps, or nicks to form a 3 branch structure. Therefore, this base pairing-independent ligation is termed 3 branch ligation (3BL). In an extensive study of optimal ligation conditions, similar to blunt-end ligation, the presence of 10% PEG-8000 in the ligation buffer significantly increased ligation efficiency. A low level of nucleotide preference was observed at the junction sites using different synthetic DNAs. Furthermore, we discovered that T4 DNA ligase efficiently ligated DNA to the 3 recessed end of RNA, not to that of DNA, in a DNA/RNA hybrid, whereas RNA ligases are less efficient in this reaction. These novel properties of T4 DNA ligase can be utilized as a broad molecular technique in many important applications. We performed a proof-of-concept study of a new directional tagmentation protocol for next generation sequencing (NGS) library construction that eliminates inverted adapters and allows sample barcode insertion adjacent to genomic DNA. 3BL after single transposon tagmentation can theoretically achieve 100% usable template, and our empirical data demonstrate that the new approach produced higher yield compared with traditional double transposon or Y transposon tagmentation. We further explore the potential use of 3BL for preparing targeted RNA NGS libraries with mitigated structure-based bias and adapter dimer problems.

molecular biology↗

bioRxiv2018

Bats adjust temporal features of echolocation calls but not those of communication calls in response to traffic noise

Summary statementThis study reveals the impact of anthropogenic noise on spectrally distinct vocalizations and the limitations of the acoustic masking hypothesis to explain the vocal response of bats to chronic noise.\n\nAbstractThe acoustic masking hypothesis states that auditory masking may occur if the target sound and interfering sounds overlap spectrally, and it suggests that animals exposed to noise will modify their acoustic signals to increase signal detectability. However, it is unclear if animals will put more effort into changing their signals that spectrally overlap more with the interfering sounds than when the signals overlap less. We examined the dynamic changes in the temporal features of echolocation and communication vocalizations of the Asian particolored bat (Vespertilio sinensis) when exposed to traffic noise. We hypothesized that traffic noise has a greater impact on communication vocalizations than on echolocation vocalizations and predicted that communication vocalization change would be greater than echolocation. The bats started to adjust echolocation vocalizations on the fourth day of noise exposure, including an increased number of call sequences, decreased number of calls, and vocal rate within a call sequence. However, there was little change in the duration of the call sequence. In contrast, these communication vocalization features were not significantly adjusted under noise conditions. These findings suggest that the degree of spectral overlap between noise and animal acoustic signals does not predict the level of temporal vocal response to the noise.

animal behavior and cognition↗

bioRxiv2018

Reliable Multiplex Sequencing with Rare Index Mis-Assignment on DNB-Based NGS Platform

BackgroundMassively-parallel-sequencing, coupled with sample multiplexing, has made genetic tests broadly affordable. However, intractable index mis-assignments (commonly exceeds 1%) were repeatedly reported on some widely used sequencing platforms.\n\nResultsHere, we investigated this quality issue on BGI sequencers using three library preparation methods: whole genome sequencing (WGS) with PCR, PCR-free WGS, and two-step targeted PCR. BGIs sequencers utilize a unique DNB technology which uses rolling circle replication for DNA-nanoball preparation; this linear amplification is PCR free and can avoid error accumulation. We demonstrated that single index mis-assignment from free indexed oligos occurs at a rate of one in 36 million reads, suggesting virtually no index hopping during DNB creation and arraying. Furthermore, the DNB-based NGS libraries have achieved an unprecedentedly low sample-to-sample mis-assignment rate of 0.0001% to 0.0004% under recommended procedures.\n\nConclusionsSingle indexing with DNB technology provides a simple but effective method for sensitive genetic assays with large sample numbers.

genomics↗

bioRxiv2018

Trio deep-sequencing does not reveal unexpected mutations in Cas9-edited monkeys

CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect remains a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, no comprehensive in vivo off-target assessment has been conducted in NHPs. Here we performed whole genome trio sequencing of Cas9-treated monkeys. We found they only carried a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected mutations were detected.

bioengineering↗

bioRxiv2018

Hepatitis C virus NS5A inhibitor daclatasvir allosterically impairs NS4B-involved protein-protein interactions within the viral replicase and disrupts the replicase quaternary structure in a replicase assembly surrogate system

Daclatasvir (DCV) is a highly potent direct-acting antiviral that targets the non-structural protein 5A (NS5A) of hepatitis C virus (HCV) and has achieved great clinical successes. Previous studies demonstrate its impact on the viral replication complex assembly. However the precise mechanism by which DCV impairs the replication complex assembly remains elusive. In this study, by using HCV subgenomic replicons and a viral replicase assembly surrogate system that expresses the HCV NS3-5B polyprotein to mimic the viral replicase assembly, we dissected the impacts of DCV on aggregation and tertiary structure of NS5A, the protein-protein interactions within the viral replicase and the quaternary structure of the viral replicase. We found that DCV didnt affect aggregation and tertiary structure of NS5A. DCV induced a quaternary structural change of the viral replicase, evidenced by selectively increasing of the NS4Bs sensitivity to proteinase K digestion. Mechanically, DCV impaired the NS4B-involved protein-protein interactions within the viral replicase. The DCV-resistant mutant Y93H was refractory to the DCV-induced reduction of the NS4B-invoved protein interactions and the quaternary structural change of the viral replicase. In addition, Y93H reduced NS4B-involed protein-protein interactions within the viral replicase and attenuated viral replication. We propose that DCV may induce a position change of NS5A, which allosterically affects the protein interactions within the replicase components and disrupts the replicase assembly.\n\nImportanceThe development of the direct-acting antivirals (DAA) has resulted in great clinical achievements for Hepatitis C Virus (HCV) treatment. Daclatasvir (DCV) is an inhibitor targeting the non-enzymatic NS5A, with the 50% effective concentration values in the picomolar range. Accumulated data suggest that DCV blocks the biogenesis of the HCV replication complex. However the mechanistic actions of DCV are still largely unknown. Insights into the action mechanism of DCV on the viral replication complex assembly of HCV may enlighten the development of next generation of DAAs and new anti-viral strategies for other positive-strand RNA viruses for which there are a scarcity of DAAs. Herein, using HCV subgenomic replicons and a viral replicase assembly surrogate system, we dissected the mechanistic actions of DCV on the viral replicase assembly. We found that DCV allosterically impairs NS4B-involved protein-protein interactions within the viral replicase and disrupts the quaternary structure of the viral replicase.

microbiology↗

bioRxiv2018

Rate fluctuations not steps dominate LIP activity during decision-making

The idea that lateral intraparietal cortex (LIP) integrates information for and against a decision, is one of the most popular models in neuroscience. However, a recent statistical analysis has suggested that LIP does not integrate information but that individual neurons activities jump. The result was based on a model comparison, which is often hard to interpret. There are two worries that can render comparisons problematic. (1) Important aspects of variance are contained in neither model. (2) The analysis is complicated, making it hard to verify. We thus followed up with a simple approach for model comparison: crossvalidation. We find evidence that baseline fluctuations describe much of the variance, which are properly modeled by neither the original papers drift-diffusion model, nor simple ramp or step models. Moreover, we find that our straightforward analysis strategy prefers ramping models, both with and without trial-by-trial baseline fluctuations. Our analysis, implementable in a few lines of code, suggests the importance of simple analyses.

neuroscience↗

bioRxiv2018

A CRISPR/Cas9 based strategy to manipulate the Alzheimer’s amyloid pathway

The gradual accumulation of amyloid-{beta} (A{beta}) is a neuropathologic hallmark of Alzheimers disease (AD); playing a key role in disease progression. A{beta} is generated by the sequential cleavage of amyloid precursor protein (APP) by {beta}- and {gamma}-secretases, with BACE-1 ({beta}-site APP cleaving enzyme-1) cleavage as the rate limiting step 1-3. CRISPR/Cas9 guided gene-editing is emerging as a promising tool to edit pathogenic mutations and hinder disease progression 4,5,6 However, few studies have applied this technology to neurologic diseases 7-9. Besides technical caveats such as low editing efficiency in brains and limited in vivo validation 7, the canonical approach of mutation-correction would only be applicable to the small fraction of neurodegenerative cases that are inherited (i.e. < 10% of AD, Parkinsons, ALS); with a new strategy needed for every gene. Moreover, feasibility of CRISPR/Cas9 as a therapeutic possibility in sporadic AD has not been explored. Here we introduce a strategy to edit endogenous APP at the extreme C-terminus and reciprocally manipulate the amyloid pathway - attenuating {beta}-cleavage and A{beta}, while up-regulating neuroprotective a-cleavage. APP N-terminus, as well as compensatory APP homologues remain intact, and key physiologic parameters remain unaffected. Robust APP-editing is seen in cell lines, cultured neurons, human embryonic stem cells/iPSC-neurons, and mouse brains. Our strategy works by limiting the physical association of APP and BACE-1, and we also delineate the mechanism that abrogates APP/BACE-1 interaction in this setting. Our work offers an innovative cut and silence gene-editing strategy that could be a new therapeutic paradigm for AD.

neuroscience↗

bioRxiv2018

Interhomolog polymorphism shapes meiotic crossover within RAC1 and RPP13 disease resistance genes

During meiosis chromosomes undergo DNA double-strand breaks (DSBs), which can produce crossovers via interhomolog repair. Meiotic recombination frequency is variable along chromosomes and concentrates in narrow hotspots. We mapped crossovers within Arabidopsis thaliana hotspots located within the RAC1 and RPP13 disease resistance genes, using varying haplotypic combinations. We observed a negative non-linear relationship between interhomolog divergence and crossover frequency, consistent with polymorphism suppressing crossover repair of DSBs. Anti-recombinase mutants fancm, recq4a recq4b, figl1 and msh2, or lines with increased HEI10 dosage, are known to show increased crossovers. Surprisingly, RAC1 crossovers were either unchanged or decreased in these genetic backgrounds. We employed deep-sequencing of crossovers to examine recombination topology within RAC1, in wild type, fancm and recq4a recq4b mutant backgrounds. The RAC1 recombination landscape was broadly conserved in anti-recombinase mutants and showed a negative relationship with interhomolog divergence. However, crossovers at the RAC1 5-end were relatively suppressed in recq4a recq4b backgrounds, indicating that local context influences recombination outcomes. Our results demonstrate the importance of interhomolog divergence in shaping recombination within plant disease resistance genes and crossover hotspots.

genetics↗

bioRxiv2018

Deficiency of the E3 Ubiquitin Ligase RBCK1 Causes Diffuse Brain Polyglucosan Accumulation and Neurodegeneration

Glycogen synthesis is vital, malstructure resulting in precipitation and accumulation into neurotoxic polyglucosan bodies (PBs). One well-understood mechanism of PB generation is glycogen branching enzyme deficiency (GBED). Less understood is Lafora disease (LD), resulting from absence of the glycogen phosphatase laforin or the E3 ubiquitin ligase malin, and accumulation of hyperphosphorylated PBs. LD afforded first insight that glycogen sphericity depends on more than adequate branching activity. Unexpectedly, deficiencies of the Linear Ubiquitin Chain Assembly Complex (LUBAC) components RBCK1 and HOIP result in PBs in muscle tissues. Here we analyzed nervous system phenotypes of mice lacking RBCK1 and find profuse PB accumulations in brain and spinal cord with extensive neurodegeneration and neurobehavioral deficits. Brain glycogen in these mice is characterized by long chains and hyperphosphorylation, similar to LD. Like in LD, glycogen synthase and branching enzyme are unaltered. Regional PB distribution mirrors LD and not GBED. Perisynaptic PB localization is unlike LD or GBED. The results indicate that RBCK1 is part of a system supplementing laforin-malin in regulating glycogen architecture including in unique neuronal locales.

molecular biology↗

bioRxiv2018

Rapid interpretation of clinical exomes using Phenoxome: a computational phenotype-driven approach

Clinical exome sequencing (CES) has become the preferred diagnostic platform for complex pediatric disorders with suspected monogenic etiologies, solving up to 20%-50% of cases depending on indication. Despite rapid advancements in CES analysis, the major challenge still resides in identifying the casual variants among the thousands of variants detected during CES testing, and thus establishing a molecular diagnosis. To improve the clinical exome diagnostic efficiency, we developed Phenoxome, a robust phenotype-driven model that adopts a network-based approach to facilitate automated variant prioritization and subsequent classification. Phenoxome dissects the phenotypic manifestation of a patient in conjunction with their genomic profile to filter and then prioritize putative pathogenic variants. To validate our method, we have compiled a clinical cohort of 105 positive patient samples (i.e. at least one reported pathogenic variant) that represent a wide range of genetic heterogeneity from The Childrens Hospital of Philadelphia. Our approach identifies the causative variants within the top 5, 10, or 25 candidates in more than 50%, 71%, or 88% of these patient samples respectively. Furthermore, we show that our method is optimized for clinical testing by yielding superior ranking of the pathogenic variants compared to current state-of-art methods. The web application of Phenoxome is available to the public at http://phenoxome.chop.edu/.

bioinformatics↗

bioRxiv2018

Plasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis

Neutrophil extracellular traps (NETs) entrap circulating tumor cells (CTCs) and promote metastasis within distant organs in preclinical models1,2. In these models, NETosis is triggered by exogenous massive inflammatory stimuli, and thus it remains unknown whether cancer hosts under physiologic inflammation-free conditions experience NETosis and consequent cancer metastasis. Here we show that plasma redox imbalance caused by albumin oxidation promotes inflammation-independent NETosis and cancer metastasis specifically in the lungs. Albumin is the major source of free thiol that maintains redox balance in vitro and in vivo. Oxidation of albumin-derived free thiol is sufficient to trigger NETosis via accumulation of reactive oxygen species within neutrophils. The resultant NETs are found predominantly within lungs where they contribute to the colonization of CTCs leading to pulmonary metastases in mouse models. These effects are abrogated by pharmacologic inhibition of NET formation. Moreover, albumin oxidation and the resultant decline of plasma free thiol are associated with pulmonary metastasis in a cohort of head and neck cancer patients. These results implicate plasma redox balance as an endogenous and physiologic regulator of NETosis and pulmonary cancer metastasis, providing new therapeutic and diagnostic opportunities for combatting cancer progression.

cancer biology↗

bioRxiv2018

Swedish Nerve Growth Factor Mutation (NGFR100W) Defines a Role for TrkA and p75NTR in Nociception

Nerve growth factor (NGF) exerts multiple functions on target neurons throughout development. The recent discovery of a point mutation leading to a change from arginine to tryptophan at residue 100 in the mature NGF{beta} sequence (NGFR100W) in patients with hereditary sensory and autonomic neuropathy, type V (HSAN V), made it possible to distinguish the signaling mechanisms that lead to two functionally different outcomes of NGF: trophic versus nociceptive. We performed extensive biochemical, cellular and live imaging experiments to examine the binding and signaling properties of NGFR100W. Our results show that, similar to the wildtype NGF (wtNGF), the naturally occurring NGFR100W mutant was capable of binding to and activating the TrkA receptor and its downstream signaling pathways to support neuronal survival and differentiation. However, NGFR100W failed to bind and stimulate the 75kD neurotrophic factor receptor (p75NTR)-mediated signaling cascades (i.e. the RhoA-Cofilin pathway). Intraplantar injection of NGFR100W into adult rats induced neither TrkA-mediated thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia based on agonism for TrkA signaling. Taken together, our studies provide evidence that NGFR100W retains trophic support capability through TrkA and one aspect of its nociceptive signaling, but fails to engage p75NTR signaling pathways. Our findings suggest that wtNGF acts through TrkA to regulate the delayed priming of nociceptive responses. The integration of both TrkA and p75NTR signaling thus appears to regulate neuroplastic effects of NGF in peripheral nociception.\n\nSignificance StatementIn the present study, we characterized the naturally occurring NGFR100W mutant that is associated with hereditary sensory and autonomic neuropathy, type V. We have demonstrated for the first time that NGFR100W retains trophic support capability through TrkA but fails to engage p75NTR signaling pathways. Furthermore, following Intraplantar injection into adult rats, NGFR100W induced neither thermal nor mechanical acute hyperalgesia, but retained the ability to induce chronic hyperalgesia. We have also provided evidence that the integration of both TrkA-and p75NTR-mediated signaling thus appears to regulate neuroplastic effects of NGF in peripheral nociception. Our study with NGFR100W suggests that it is possible to uncouple trophic effect from nociceptive function, both induced by wildtype NGF.\n\nAbbreviations

neuroscience↗