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In this paper, we study a diffusive predator–prey model with hyperbolic mortality and prey-taxis under homogeneous Neumann boundary condition. We first analyze the influence of prey-taxis on the local stability of constant equilibria. It turns out that prey-taxis has influence on the stability of the unique positive constant equilibrium, but has no influence on the stability of the trivial equilibrium and the semi-trivial equilibrium. We then derive Hopf bifurcation and steady state bifurcation related to prey-taxis, which imply that the prey-taxis plays an important role in the dynamics. [ABSTRACT FROM AUTHOR]

mDia formin proteins regulate the dynamics and organization of the cytoskeleton through their linear actin nucleation and polymerization activities. We previously showed that mDia1 deficiency leads to aberrant innate immune activation and induces myelodysplasia in a mouse model, and mDia2 regulates enucleation and cytokinesis of erythroblasts and the engraftment of hematopoietic stem and progenitor cells (HSPCs). However, whether and how mDia formins interplay and regulate hematopoiesis under physiological and stress conditions remains unknown. Here, we found that both mDia1 and mDia2 are required for HSPC regeneration under stress, such as serial plating, aging, and reconstitution after myeloid ablation. We showed that mDia1 and mDia2 form hetero-oligomers through the interactions between mDia1 GBD-DID and mDia2 DAD domains. Double knockout of mDia1 and mDia2 in hematopoietic cells synergistically impaired the filamentous actin network and serum response factor-involved transcriptional signaling, which led to declined HSPCs, severe anemia, and significant mortality in neonates and newborn mice. Our data demonstrate the potential roles of mDia hetero-oligomerization and their non-rodent functions in the regulation of HSPCs activity and orchestration of hematopoiesis. Author summary: Blood production and generation entirely depend on the hematopoietic stem progenitor cells (HSPCs) that have to be tightly controlled. mDia formin proteins are critical regulators for linear-actin synthesis that are involved in actin filament formation and cytoskeleton organization. Previous studies have revealed the important roles of mDia1 or mDia2 in regulating the functions of T cells, neutrophils, or red blood cells, but there is a lack of evidence for the non-redundant roles of these two factors in vivo. Here we combined genetic manipulation of the mDia1 and mDia2 double deficient mouse with biochemical analysis. We find that mDia1 interacts directly with mDia2 to form hetero-oligomers in vitro and in vivo, and both mDia1 and mDia2 are required to maintain HSPCs hemostasis during stress in mice. Dual deficiency of mDia1 and mDia2 in mice leads to compromised serum response factor (SRF) signaling, with declined HSPC, severe anemia, and increased animal mortality. Our work not only provides a previously unrecognized working model for the mDia1-mDia2 complex but also highlights their cooperative roles in hematopoiesis. [ABSTRACT FROM AUTHOR]

This paper is concerned with a diffusive predator–prey model with prey‐taxis and prey‐stage structure under the homogeneous Neumann boundary condition. The stability of the unique positive constant equilibrium of the predator–prey model is derived. Hopf bifurcation and steady‐state bifurcation are also concluded. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the potentially predictive role and dynamic changes of immune checkpoints on T cell subsets in patients with breast cancer receiving neoadjuvant chemotherapies. Methods: Fluorescent multiplex immunohistochemistry (mIHC) was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in paired breast cancer samples before and after neoadjuvant therapies (NAT) in a prospective cohort (n = 50). Singleplex IHC was conducted to stain for CD3 in 100 cases with inclusion of extra retrospective 50 cases. Cell levels were correlated with clinicopathological parameters and pathological complete response (pCR). Results: In pretreatment tumors, the percentages of infiltrating CD8+, PD1+, PD1+CD8+, and the ratio of PD1+CD8+/CD8+ cells, were higher in pCR than non‐pCR patients in either the stromal or intratumoral area, but PD1+CD4+, TIM3+CD4+, TIM3+CD8+ cells and CD4+/CD8+ ratio was not. Multivariate analyses showed that the percentage of intratumoral CD8+ cells (OR, 1.712; 95% CI: 1.052–2.786; P = 0.030) and stromal PD1+CD8+/CD8+ ratio (OR, 1.109; 95% CI: 1.009–1.218; P = 0.032) were significantly associated with pCR. Dynamically, reduction in the percentages of PD1+, CD8+ and PD1+CD8+ cells after therapy strongly correlated with pCR. Notably, incremental percentages of PD1+CD8+ cells, rather than TIM3+CD8+, were shown in tumors from non‐pCR patients after NAT. CD3 staining confirmed the percentage of T cells were associated with pCR. Conclusions: PD1+CD8+ rather than TIM3+CD8+ cells are main predictive components within tumor‐infiltrating T cells in NAT breast cancer patients. Dynamically incremental levels of PD1+CD8+ cells occurred in non‐pCR cases after NAT, suggesting the combination of chemotherapy with PD1 inhibition might benefit these patients. Key points: Significant findings of the study: PD1+CD8+, rather than TIM3+CD8+, T cells are the main component to predict the response of neoadjuvant therapies in breast cancer. What this study adds: Incremental levels of PD1+CD8+ T cells in non‐pCR post‐NAT tumors suggest PD1 inhibition might benefit in the neoadjuvant setting. [ABSTRACT FROM AUTHOR]

Next generation sequencing (NGS) technology is an increasingly important clinical tool for therapeutic decision-making. However, interpretation of NGS data presents challenges at the point of care, due to limitations in understanding the clinical importance of gene variants and efficiently translating results into actionable information for the clinician. The present study compared two approaches for annotating and reporting actionable genes and gene mutations from tumor samples: The traditional approach of manual curation, annotation and reporting using an experienced molecular tumor bioinformationist; and a cloud-based cognitive technology, with the goal to detect gene mutations of potential significance in Chinese patients with lung cancer. Data from 285 gene-targeted exon sequencing previously conducted on 115 patient tissue samples between 2014 and 2016 and subsequently manually annotated and evaluated by the Guangdong Lung Cancer Institute (GLCI) research team were analyzed by the Watson for Genomics (WfG) cognitive genomics technology. A comparative analysis of the annotation results of the two methods was conducted to identify quantitative and qualitative differences in the mutations generated. The complete congruence rate of annotation results between WfG analysis and the GLCI bioinformatician was 43.48%. In 65 (56.52%) samples, WfG analysis identified and interpreted, on average, 1.54 more mutation sites in each sample than the manual GLCI review. These mutation sites were located on 27 genes, including EP300, ARID1A, STK11 and DNMT3A. Mutations in the EP300 gene were most prevalent, and present in 30.77% samples. The Tumor Mutation Burden (TMB) interpreted by WfG analysis (1.82) was significantly higher than the TMB (0.73) interpreted by GLCI review. Compared with manual curation by a bioinformatician, WfG analysis provided comprehensive insights and additional genetic alterations to inform clinical therapeutic strategies for patients with lung cancer. These findings suggest the valuable role of cognitive computing to increase efficiency in the comprehensive detection and interpretation of genetic alterations which may inform opportunities for targeted cancer therapies. [ABSTRACT FROM AUTHOR]

Background: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex., Methods: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases., Results: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group., Conclusions: This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.

Background: This study aimed to explore the potentially predictive role and dynamic changes of immune checkpoints on T cell subsets in patients with breast cancer receiving neoadjuvant chemotherapies., Methods: Fluorescent multiplex immunohistochemistry (mIHC) was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in paired breast cancer samples before and after neoadjuvant therapies (NAT) in a prospective cohort (n = 50). Singleplex IHC was conducted to stain for CD3 in 100 cases with inclusion of extra retrospective 50 cases. Cell levels were correlated with clinicopathological parameters and pathological complete response (pCR)., Results: In pretreatment tumors, the percentages of infiltrating CD8 + , PD1 + , PD1 + CD8 + , and the ratio of PD1 + CD8 + /CD8 + cells, were higher in pCR than non-pCR patients in either the stromal or intratumoral area, but PD1 + CD4 + , TIM3 + CD4 + , TIM3 + CD8 + cells and CD4 + /CD8 + ratio was not. Multivariate analyses showed that the percentage of intratumoral CD8 + cells (OR, 1.712; 95% CI: 1.052-2.786; P = 0.030) and stromal PD1 + CD8 + /CD8 + ratio (OR, 1.109; 95% CI: 1.009-1.218; P = 0.032) were significantly associated with pCR. Dynamically, reduction in the percentages of PD1 + , CD8 + and PD1 + CD8 + cells after therapy strongly correlated with pCR. Notably, incremental percentages of PD1 + CD8 + cells, rather than TIM3 + CD8 + , were shown in tumors from non-pCR patients after NAT. CD3 staining confirmed the percentage of T cells were associated with pCR., Conclusions: PD1 + CD8 + rather than TIM3 + CD8 + cells are main predictive components within tumor-infiltrating T cells in NAT breast cancer patients. Dynamically incremental levels of PD1 + CD8 + cells occurred in non-pCR cases after NAT, suggesting the combination of chemotherapy with PD1 inhibition might benefit these patients., Key Points: SIGNIFICANT FINDINGS OF THE STUDY: PD1 + CD8 + , rather than TIM3 + CD8 + , T cells are the main component to predict the response of neoadjuvant therapies in breast cancer., What This Study Adds: Incremental levels of PD1 + CD8 + T cells in non-pCR post-NAT tumors suggest PD1 inhibition might benefit in the neoadjuvant setting., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Fluorescent nanomaterials such as single-walled carbon nanotubes (SWCNTs) have many advantages in terms of their photophysics, but it is difficult to target them to specific locations in living systems. In contrast, the green fluorescent protein (GFP) has been genetically fused to proteins in many cells and organisms. Therefore, GFP can be seen not only as a fluorophore but as a universal target/handle. Here, we report the conjugation of GFP-binding nanobodies to DNA-wrapped SWCNTs. This approach combines the targeting capabilities of GFP-binding nanobodies and the nonbleaching near-infrared fluorescence (850-1700 nm) of SWCNTs. These conjugates allow us to track single Kinesin-5-GFP motor proteins in developing embryos of Drosophila melanogaster. Additionally, they are sensitive to the neurotransmitter dopamine and can be used for targeted sensing of dopamine in the nm regime., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Motor proteins are important for transport and force generation in a variety of cellular processes and in morphogenesis. Here, we describe a general strategy for conditional motor mutants by inserting a protease cleavage site into the 'neck' between the head domain and the stalk of the motor protein, making the protein susceptible to proteolytic cleavage at the neck by the corresponding protease. To demonstrate the feasibility of this approach, we inserted the cleavage site of the tobacco etch virus (TEV) protease into the neck of the tetrameric motor Kinesin-5. Application of TEV protease led to a specific depletion and functional loss of Kinesin-5 in Drosophila embryos. With our approach, we revealed that Kinesin-5 stabilizes the microtubule network during interphase in syncytial embryos. The 'molecular guillotine' can potentially be applied to many motor proteins because Kinesins and myosins have conserved structures with accessible neck regions.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Canoe/Afadin and the GTPase Rap1 specify the subapical domain during cellularization in Drosophila embryos. The timing of domain formation is unclear. The subapical domain might gradually mature or emerge synchronously with the basal and lateral domains. The potential mechanism for activation of Rap1 by guanyl nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs) is unknown. Here, we retraced the emergence of the subapical domain at the onset of cellularization by in vivo imaging with CanoeYFP in comparison to the lateral and basal markers ScribbledGFP and CherrySlam. CanoeYFP accumulates at a subapical position at about the same time as the lateral marker ScribbledGFP but a few minutes prior to basal CherrySlam. Furthermore, we show that the unconventional GEF complex ELMO-Sponge is subapically enriched and is required for subapical restriction of Canoe. The localization dynamics of ELMO-Sponge suggests a patterning mechanism for positioning the subapical region adjacent to the apical region. While marking the disc-like apical regions before cellularization, ELMO-Sponge redistributes to a ring-like pattern surrounding the apical region at the onset of cellularization., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Background: Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1), UGT1A1*28 polymorphism can reduce UGT1A1 enzymatic activity, which may lead to severe toxicities in patients who receive irinotecan. This study tries to build a fragment analysis method to detect UGT1A1*28 polymorphism., Methods: A total of 286 blood specimens from the lung cancer patients who were hospitalized in Guangdong General Hospital between April 2014 to May 2015 were detected UGT1A1*28 polymorphism by fragment analysis method., Results: Comparing with Sanger sequencing, precision and accuracy of the fragment analysis method were 100%. Of the 286 patients, 236 (82.5% harbored TA6/6 genotype, 48 (16.8%) TA 6/7 genotype and 2 (0.7%) TA7/7 genotype., Conclusions: Our data suggest hat the fragment analysis method is robust for detecting UGT1A1*28 polymorphism in clinical practice. It's simple, time-saving, and easy-to-carry.