Biology subjects

Zhang, C.

Publications and source records attributed to Zhang, C..

At least 865 records · Page 48Linked to original sources

bioRxiv2020

Developmentally regulated activation of defense allows for rapid inhibition of infectionin age-related resistance to Phytophthora capsici in cucumber fruit

BackgroundAge-related resistance (ARR) is a developmentally regulated phenomenon conferring resistance to pathogens or pests. Although ARR has been observed in several host-pathogen systems, the underlying mechanisms are largely uncharacterized. In cucumber, rapidly growing fruit are highly susceptible to Phytophthora capsici but become resistant as they complete exponential growth. We previously demonstrated that ARR is associated with the fruit peel and identified gene expression and metabolomic changes potentially functioning as preformed defenses. ResultsHere, we compare the response to infection in fruit at resistant and susceptible ages using microscopy, quantitative bioassays, and weighted gene co-expression analyses. We observed strong transcriptional changes unique to resistant aged fruit 2-4 hours post inoculation (hpi). Microscopy and bioassays confirmed this early response, with evidence of pathogen death and infection failure as early as 4 hpi and cessation of pathogen growth by 8-10 hpi. Expression analyses identified candidate genes involved in conferring the rapid response including those encoding transcription factors, hormone signaling pathways, and defenses such as reactive oxygen species metabolism and phenylpropanoid biosynthesis. ConclusionThe early pathogen death and rapid defense response in resistant-aged fruit provide insight into potential mechanisms for ARR, implicating both pre-formed biochemical defenses and developmentally regulated capacity for pathogen recognition as key factors shaping age-related resistance.

plant biology↗

bioRxiv2020

ATF3 drives senescence by reconstructing accessible chromatin profiles

Chromatin architecture and gene expression profile undergo tremendous reestablishment during senescence. However, the regulatory mechanism between chromatin reconstruction and gene expression in senescence remain elusive. The chromatin accessibility is an excellent perspective to reveal the latent regulatory elements. Thus, we depicted the landscapes of chromatin accessibility and gene expression during HUVECs senescence. We found that chromatin accessibilities are re-distributed during senescence. The senescence related increased accessible regions (IARs) and the decreased accessible regions (DARs) are mainly distributed in distal intergenic regions. The DARs are correlated with the function declines caused by senescence, whereas the IARs are involved in the regulation for senescence program. Moreover, the heterochromatin contributes most of IARs in senescent cells. We identified that the AP-1 transcription factors, especially ATF3 is responsible for driving chromatin accessibility reconstruction in IARs. In particular, DNA methylation is negatively correlated with chromatin accessibility during senescence. AP-1 motifs with low DNA methylation may improve their binding affinity in IARs and further opens the chromatin nearby. Our results described a dynamic landscape of chromatin accessibility whose remodeling contributes to the senescence program. And we identified a cellular senescence regulator, AP-1, which promotes senescence through organizing the accessibility profile in IARs.

cell biology↗

bioRxiv2020

Characterization of a novel gene, srpA, conferring resistance to streptogramin A, pleuromutilins, and lincosamides in Streptococcus suis

Antimicrobial resistance is undoubtedly one of the greatest global health threats. The emergence of multidrug-resistant (MDR) gram-positive pathogens, like methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and {beta}-lactamase-resistant Streptococcus pneumonia, has severely limited our antibiotic arsenal. Numerous ribosome-targeting antibiotics, especially pleuromutilins, oxazolidinones, and streptogramins, are viewed as promising alternatives against aggressive MDR pathogens. In this study, we identified a new ABC-F family determinant, srpA, in Streptococcus suis by a comparative analysis of whole genome sequences of tiamulin-resistant and -sensitive bacteria. Functional cloning confirmed that the deduced gene can mediate cross-resistance to pleuromutilins, lincosamides, and streptogramin A in S. suis and S. aureus. A sequence alignment revealed that srpA shares the highest amino acid identity with Vga(E) (36%) and shows canonical characteristics of ABC-F family members. In SrpA-ribosome docked compounds, the extended loop region of SrpA approaches the valnemulin binding pocket in the ribosome peptidyl-transferase center and competes with bound valnemulin. A detailed mutational analysis of the loop residues confirmed that this domain is crucial for SrpA activity, as substitutions or truncations of this region affect the efficiency and specificity of antibiotic resistance. A ribosome binding assay supported the protective effects of SrpA on the ribosome by preventing antibiotic binding as well as displacing bound drugs. These findings clarify the mechanisms underlying resistance to ribosomal antibiotics.

microbiology↗

bioRxiv2020

RobMixReg: an R package for robust, flexible and high dimensional mixture regression

MotivationMixture regression has been widely used as a statistical model to untangle the latent subgroups of the sample population. Traditional mixture regression faces challenges when dealing with: 1) outliers and versatile regression forms; and 2) the high dimensionality of the predictors. Here, we develop an R package called RobMixReg, which provides comprehensive solutions for robust, flexible as well as high dimensional mixture modeling. Availability and ImplementationRobMixReg R package and associated documentation is available at CRAN: https://CRAN.R-project.org/package=RobMixReg.

bioinformatics↗

bioRxiv2020

Effects of Starter Feeds of Different Physical Forms on Rumen Fermentation and Microbial Composition for Pre-weaning and Post-weaning Lambs

This study aimed to evaluate the effects of starter feeds of different physical forms on rumen fermentation and microbial composition for lambs. Twenty-four eight-day-old male Hu lambs (5.04 {+/-} 0.75 kg body weight) were fed either milk replacer (MR) and pelleted starter feed (PS), or MR and textured starter feed (TS) in pre-weaning (day 8 to 35) and post-weaning (day 36 to 42) lambs. And the MR was fed by bottles to lambs at 2% of body weight at day 8 divided as three equal amounts at 08:00, 14:00 and 20:00 in pre-weaning. And the lambs were readily availed starter feeds and clean fresh water in the whole experiment. Six lambs for each treatment were euthanized at day 21 or 42 for sampling. The results showed the total volatile fatty acids, propionate and butyrate of rumen liquid in TS groups were all higher than them in PS groups respectively for pre-weaning and post-weaning lambs (P < 0.05), and the pH of rumen liquid in TS group was lower than it in PS group for post-weaning lambs (P < 0.05). Moreover, the pH of rumen and OTUs in TS group had trends to lower than them in PS group for pre-weaned lambs (P = 0.061, P = 0.066). TS established the predominant Phylum, Bacteroidetes, earlier than PS, and increased significantly the relative abundances of Sharpea compared to PS at level of genus (P < 0.05) for pre-weaning and post-weaning lambs. TS were more benefits to trigger rumen development for lambs. IMPORTANCEEarly use of starter feed could trigger rumen fermentation and establishment of dominant flora, which were in favour of growth and development of rumen for ruminants. The physical form of starter feed is one of the important factors to promote rumen fermentation and establishment of dominant flora for ruminants of transition. However, limited study on effects of physical forms of starter feeds, especially the texturized starters containing steam-flaked grains, to rumen fermentative pattern and microbial composition for pre-weaning and post-weaning lambs to date. It was necessary to investigate the effects of physical form of starter feed on rumen fermentation and microbial composition for lambs. The significance of our research showed TS were better benefits to promote the rumen fermentation and establishment of dominant flora for lambs, which will greatly enhance our understanding of physical forms of starter feeds, leading to broader studies on rumen development for lambs.

developmental biology↗

bioRxiv2020

NEURAL ENCODING OF FELT AND IMAGINED TOUCH WITHIN HUMAN POSTERIOR PARIETAL CORTEX

In the human posterior parietal cortex (PPC), single units encode high-dimensional information with partially mixed representations that enable small populations of neurons to encode many variables relevant to movement planning, execution, cognition, and perception. Here we test whether a PPC neuronal population previously demonstrated to encode visual and motor information is similarly selective in the somatosensory domain. We recorded from 1423 neurons within the PPC of a human clinical trial participant during objective touch presentation and during tactile imagery. Neurons encoded experienced touch with bilateral receptive fields, organized by body part, and covered all tested regions. Tactile imagery evoked body part specific responses that shared a neural substrate with experienced touch. Our results are the first neuron level evidence of touch encoding in human PPC and its cognitive engagement during tactile imagery which may reflect semantic processing, sensory anticipation, and imagined touch.

neuroscience↗

bioRxiv2020

Dynamic signatures of lipid droplets as new markers to quantify cellular metabolic changes

The metabolic properties of live cells are very susceptible to intra- or extra-cellular perturbations, making their measurements challenging tasks. We show that the dynamics of lipid droplets (LDs) carry information to measure the lipid metabolism of live cells. Coherent anti-Stokes Raman scattering microscopy was used to statistically quantify LD dynamics in living cells in a label-free manner. We introduce dynamic signatures of cells derived from the LD displacement, speed, travel length, and directionality, which allows for the detection of cellular changes induced by stimuli such as fluorescent labeling, temperature change, starvation, and chemical treatment. Histogram fittings of the dynamic signatures using lognormal distribution functions provide quantification of changes in cellular metabolic states. The LD dynamics also enable separation of subpopulations of LDs correlated with different functions. We demonstrate that LD dynamics are new markers to quantify the metabolic changes in live cells.

biophysics↗

bioRxiv2020

Single-cell landscape of immunological responses in COVID-19 patients

In COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ Effector-GNLY (Granulysin), CD8+ Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.

immunology↗

bioRxiv2020

Peramivir, an anti-influenza virus drug, exhibits potential anti-cytokine storm effects

Coronavirus Disease 2019 (COVID-19) infected by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has been declared a public health emergency of international concerns. Cytokine storm syndrome (CSS) is a critical clinical symptom of severe COVID-19 patients, and the macrophage is recognized as the direct host cell of SARS-CoV-2 and potential drivers of CSS. In the present study, peramivir was identified to reduce TNF- by partly intervention of NF-{kappa}B activity in LPS-induced macrophage model. In vivo, peramivir reduced the multi-cytokines in serum and bronchoalveolar lavage fluid (BALF), alleviated the acute lung injury and prolonged the survival time in mice. In human peripheral blood mononuclear cells (hPBMCs), peramivir could also inhibit the release of TNF-. Collectively, we proposed that peramivir might be a candidate for the treatment of COVID-19 and other infections related CSS. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/201806v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@667e34org.highwire.dtl.DTLVardef@e7bf85org.highwire.dtl.DTLVardef@ced400org.highwire.dtl.DTLVardef@c055a5_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Nuclear GSK-3β and Oncogenic KRas Promote Expansion of Terminal Duct Cells and the Development of Intraductal Papillary Mucinous Neoplasm

Intraductal papillary mucinous neoplasm (IPMN) represents one type of pancreatic ductal adenocarcinoma (PDA) precursor lesion, however its cell-of-origin remains unclear. Here we describe a new mouse model in which pancreas-specific Cre activation of a nuclear glycogen synthase kinase-3{beta} transgene is combined with oncogenic KRas (referred to as KNGC). KNGC mice show accumulation of neoplastic ductal cells at 4-weeks that progressively develop into IPMN with low-grade dysplasia in advanced age. RNA-sequencing identified expression of several terminal duct cell lineage genes including Agr2 and Aqp5. Interestingly, Aqp5, a water channel, was found to be required for the development of IPMN lesions in KNGC mice. Staining of human IPMN samples indicates that these preneoplastic lesions also arise from expansion of the terminal duct population. Altogether, these data highlight the utility of the KNGC model for understanding the biology of IPMN and potential utility in defining predictive biomarkers of IPMN - PDA development. Statement of significanceUnderstanding the cell-of-origin of IPMN is crucial to developing early detection methods that specifically target aggressive precursors of PDA. This work, using a novel mouse model, identifies Aqp5-modulated development of Agr2+ terminal ducts that could potentially serve as a clinical biomarker for IPMN.

cancer biology↗

bioRxiv2020

Multi-scale predictions distinctively modulate tone perception in schizophrenia patients with auditory verbal hallucinations

AbstractsAuditory verbal hallucinations (AVHs) are one of the most pronounced symptoms that manifest the underlying mechanisms of deficits in schizophrenia. Cognitive models postulate that malfunctioned source monitoring incorrectly weights the top-down prediction and bottom-up sensory processing and causes hallucinations. Here, we investigate the featural-temporal characteristics of source monitoring in AVHs. Schizophrenia patients with and without AVHs, and healthy controls identified target tones in noise at the end of tone sequences. Predictions of different timescales were manipulated by either an alternating pattern in the preceding tone sequences, or a repetition between the target tone and the tone immediately before. The sensitivity index, d, was obtained to assess the modulation of predictions on tone identification. We found that patients with AVHs showed higher d when the target tones conformed to the long-term regularity of alternating pattern in the preceding tone sequence than that when the targets were inconsistent with the pattern. Whereas, the short-term regularity of repetitions modulated the tone identification in patients without AVHs. Predictions did not influence tone identification in healthy controls. These findings suggest that malfunctioned source monitoring in AVHs heavily weights predictions to form incorrect perception. The weighting function in source monitoring can extend to the process of basic tonal features, and predictions at multiple timescales differentially modulate perception in different clinical populations. These collaboratively reveal the featural and temporal characteristics of weighting function in source monitoring of AVHs and suggest that the malfunctioned interaction between top-down and bottom-up processes might underlie the development of auditory hallucinations. HighlightsMalfunctioned source monitoring incorrectly weights the top-down prediction and bottom-up sensory processing underlie pathogenesis of auditory verbal hallucinations in schizophrenia. The weighting function in top-down predictions and bottom-up sensory processing can extend to tonal features. Predictions at multiple timescales differentially modulate perception in different clinical schizophrenia populations.

neuroscience↗

bioRxiv2020

Intraneuronal chloride accumulation via NKCC1 is not essential for hippocampal network development in vivo

NKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development of in vivo network dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreases in-vitro excitatory GABA actions and impairs neuronal synchrony in neonatal hippocampal brain slices. In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics and behavioral performance are subtle. Our data reveal a neural network function of depolarizing GABA in the hippocampus in vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development.

neuroscience↗

bioRxiv2020

Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM

The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗

bioRxiv2020

Mass-spectrometry-based near complete draft of the Saccharomyces cerevisiae proteome

Proteomics approaches designed to catalogue all open reading frames (ORFs) under a defined set of growth conditions of an organism have flourished in recent years. However, no proteome has been sequenced completely so far. Here we generate the largest yeast proteome dataset, including 5610 identified proteins using a strategy based on optimized sample preparation and high-resolution mass spectrometry. Among the 5610 identified proteins, 94.1% are core proteins, which achieves near complete coverage of the yeast ORFs. Comprehensive analysis of missing proteins in our dataset indicate that the MS-based proteome coverage has reached the ceiling. A review of protein abundance shows that our proteome encompasses a uniquely broad dynamic range. Additionally, these values highly correlate with mRNA abundance, implying a high level of accuracy, sensitivity and precision. We present examples of how the data could be used, including re-annotating gene localization, providing expression evidence of pseudogenes. Our near complete yeast proteome dataset will be a useful and important resource for further systematic studies.

biochemistry↗

bioRxiv2020

Efficient precise in vivo base editing in adult dystrophic mice

ABSTRACTBackground Recent advances in the base editing technology have created an exciting opportunity to precisely correct disease-causing mutations. However, the large size of base editors and their inherited off-target activities pose challenges for in vivo base editing. Moreover, the requirement of a protospacer adjacent motif (PAM) sequence within a suitable window near the mutation site further limits the targeting feasibility. In this work, we rationally improved the adenine base editor (ABE) to overcome these challenges and demonstrated the exceptionally high efficiency to precisely edit the Duchenne muscular dystrophy (DMD) mutation in adult mice.Methods We employed a fluorescence reporter assay to assess the feasibility of ABE to correct the dystrophin mutation in mdx4cv mice. The intein protein trans-splicing (PTS) was used to split the oversized ABE into two halves for efficient packaging into adeno-associated virus 9 (AAV9). The ABE with broadened PAM recognition (ABE-NG) was rationally re-designed for improved off-target RNA editing activity and on-target DNA editing efficiency. The mdx4cv mice at the 5 weeks of age receiving intramuscular or intravenous injections of AAV9 carrying the improved ABE-NG were analyzed at 10 weeks or 10 months of age. The editing outcomes were analyzed by Sanger and deep sequencing of the amplicons, immunofluorescence staining, Western blot and contractile function measurements. The off-target activities, host immune response and long-term toxicity were analyzed by deep sequencing, ELISA and serological assays, respectively.Results We showed efficient in vitro base correction of the dystrophin mutation carried in mdx4cv mice using ABE-NG. The super-fast intein-splits of ABE-NG enabled the expression of full-length ABE-NG and efficient AAV9 packaging. We rationally improved ABE-NG with eliminated off-target RNA editing activity and minimal PAM requirement, and packaged into AAV9 (AAV9-iNG). Intramuscular and intravenous administration of AAV9-iNG resulted in dystrophin restoration and functional improvement. At 10 months after AAV9-iNG treatment, a near complete rescue of dystrophin was measured in mdx4cv mouse hearts. The off-target activities remained low and no obvious toxicity was detected.Conclusions This study highlights the promise of permanent base editing using iABE-NG for the treatment of monogenic diseases, in particular, the genetic cardiomyopathies.Competing Interest StatementThe authors have submitted a patent application based on the results reported in this paper.View Full Text

bioengineering↗

bioRxiv2020

Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

microbiology↗

bioRxiv2020

Individual cell-based modeling of tumor cell plasticity-induced immune escape after CAR-T therapy

Chimeric antigen receptor (CAR) therapy targeting CD19 is an effective treatment for refractory B cell malignancies, especially B cell acute lymphoblastic leukemia (B-ALL). The majority of patients achieve a complete response following a single infusion of CD19-targeted CAR-modified T cells (CAR-19 T cells); however, many patients suffer relapse after therapy, and the underlying mechanism remains unclear. To better understand the mechanism of tumor relapse, we developed an individual cell based computational model for tumor cell plasticity and the heterogeneous responses to the CAR-T treatment. Model simulations reproduced the process of tumor relapse, and predicted that CAR-T stress-induced cell plasticity can lead to tumor relapse in B-ALL. Model predictions were verified by applying the second-generation CAR-T cells to mice injected with NALM-6-GL leukemic cells, in which 60% of the mice relapse within 3 months, and relapsed tumors retained CD19 expression but exhibited a subpopulation of cells with CD34 transcription. These findings lead to a mechanism of tumor replace by which CAR-T treatment induced tumor cells to transition to hematopoietic stem-like cells (HSLCs) and myeloid-like cells and hence escape of CAR-T targeting. The computational model framework was successfully developed to recapitulate the individual evolutionary dynamics, which could predict clinical survival outcomes in B-ALL patients after CAR-T therapy.

cancer biology↗

bioRxiv2020

A Novel Therapeutic Approach to Corneal Alkaline Burn Model by Targeting Fidgetin-like 2, a Microtubule Regulator

Purpose To determine the efficacy of nanoparticle-encapsulated FL2 siRNA (FL2-NPsi), a novel therapeutic agent targeting the Fidgetin-like 2 (FL2) gene, for the treatment of corneal alkaline chemical injury.Methods Eighty 12-week-old, male Sprague-Dawley rats were divided evenly into 8 treatment groups: prednisolone, empty nanoparticles, control-NPsi (1 μM, 10 μM, 20 μM) and FL2-NPsi (1 μM, 10 μM, 20 μM). An alkaline burn was induced onto the cornea of each rat, which was then treated for 14 days according to group assignment. Clinical (N=10 per group), histopathologic (N=6 per group), and immunohistochemical (N=4 per group) analyses were conducted to assess for wound healing. FL2-NPsi-mediated knockdown of FL2 was confirmed by in vitro qPCR. Toxicity assays were performed to assess for apoptosis (TUNEL assay, N=3 per group) and nerve damage (whole mount immunochemical staining, N=2 per group). Statistical analyses were performed using student’s t-test and ANOVA.Results Compared to controls, FL2-NPsi-treated groups demonstrated enhanced corneal wound healing, with the 10 and 20 μM FL2-NPsi-treated groups demonstrating maximum rates of corneal re-epithelialization (p=0.0003 at Day 4 and p<0.0001 at Day 8) as assessed by ImageJ software, enhanced corneal transparency, and improved stromal organization on histology. Immunohistochemical analysis of vascular endothelial cells, macrophages, and neutrophils did not show significant differences between treatment groups. FL2-NPsi was not found to be toxic to nerves or induce apoptosis (p=0.917).Conclusion Dose-response studies found both 10 and 20 μM FL2-NPsi to be efficacious in this rat model. FL2-NPsi may offer a novel treatment for corneal alkaline chemical injuries.Competing Interest StatementDr. Wang, Dr. Kramer, Dr. Baker, and Dr. Dey are employees of MicroCures, Inc. Dr. Sharp is co-founder and Chief Scientific Officer for MicroCures, Inc and is the inventor of U.S. Patent #20130022667 entitled "Fidgetin-like 2 as a target to enhance wound healing,” which has been licensed by MicroCures. Dr. Chuck is a scientific advisor for MicroCures, Inc. Dr. Friedman holds stock in MicroCures. No other author has a conflict of interest.View Full Text

physiology↗