Juvenile hormone as a key regulator for asymmetric caste differentiation in ants.

Caste differentiation involves many functional traits that diverge during larval growth and metamorphosis to produce adults irreversibly adapted to reproductive division of labor. Investigating developmental differentiation is important for general biological understanding and has increasingly been explored for social phenotypes that diverge in parallel from similar genotypes. Here, we use ants to investigate the extent to which canalized worker development can be shifted toward gyne (virgin-queen) phenotypes by juvenile hormone (JH) treatment.

miR-3940-5p reduces amyloid β production via selectively targeting .

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid beta (Aβ) in brain. Mounting evidence has revealed critical roles of microRNAs (miRNAs) in AD pathogenesis; however, the miRNAs directly targeting (), which encodes the catalytic core subunit of γ-secretase that limits the production of Aβ from amyloid precursor protein (APP), are extremely understudied. The present study aimed to identify miRNAs targeting and its effect on Aβ production.

Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner.

Although studies have demonstrated that genome instability is accumulated in patients with Alzheimer's disease (AD), the specific types of genome instability linked to AD pathogenesis remain poorly understood. Here, we report the first characterization of the age- and sex-related trajectories of telomere length (TL) and micronuclei in APP/PS1 mice model and wild-type (WT) controls (C57BL/6). TL was measured in brain (prefrontal cortex, cerebellum, pituitary gland, and hippocampus), colon and skin, and MN was measured in bone marrow in 6- to 14-month-old mice.

Contribution of µ Opioid Receptor-expressing Dorsal Horn Interneurons to Neuropathic Pain-like Behavior in Mice.

Background: Intersectional genetics have yielded tremendous advances in our understanding of molecularly identified subpopulations and circuits within the dorsal horn in neuropathic pain. The authors tested the hypothesis that spinal µ opioid receptor-expressing neurons (Oprm1-expressing neurons) contribute to behavioral hypersensitivity and neuronal sensitization in the spared nerve injury model in mice.

Methods: The authors coupled the use of Oprm1Cre transgenic reporter mice with whole cell patch clamp electrophysiology in lumbar spinal cord slices to evaluate the neuronal activity of Oprm1-expressing neurons in the spared nerve injury model of neuropathic pain.

Activation of Wnt/β-Catenin signaling in EpCAMhigh/CD44+ cells endow colorectal cancer with tumor proliferation and oxaliplatin chemoresistance.

Aims: The present study investigated the exact proportion, the extent of in vitro proliferation potential, and oxaliplatin chemoresistance of EpCAMhigh/CD44+ cancer stem cells in colorectal cancer. Its underlying mechanism was also explored.

Background: Colorectal cancer stem cells (CSC) play crucial roles in tumorigenicity and chemoresistance.

Postsurgical Latent Pain Sensitization Is Driven by Descending Serotonergic Facilitation and Masked by µ-Opioid Receptor Constitutive Activity in the Rostral Ventromedial Medulla.

Following tissue injury, latent sensitization (LS) of nociceptive signaling can persist indefinitely, kept in remission by compensatory µ-opioid receptor constitutive activity (MOR) in the dorsal horn of the spinal cord. To demonstrate LS, we conducted plantar incision in mice and then waited 3-4 weeks for hypersensitivity to resolve. At this time (remission), systemic administration of the opioid receptor antagonist/inverse agonist naltrexone reinstated mechanical and heat hypersensitivity.

A comprehensive study of the genotoxic and anti-genotoxic effects of homocysteine in HUVECs and mouse bone marrow cells.

Elevated Homocysteine (Hcy) is associated with increased risk of vascular disease, but whether it induces genotoxicity to vascular endothelial cells remains unknown. Here, we conducted a comprehensive study of the genotoxicity, and unexpected anti-genotoxicity, of Hcy by cytokinesis-blocked micronucleus assay in HUVECs and erythrocyte micronucleus test in mouse bone marrow cells. Our experiments led to several important findings.

Genetic and functional evidence for gp130/IL6ST-induced transient receptor potential ankyrin 1 upregulation in uninjured but not injured neurons in a mouse model of neuropathic pain.

Peripheral nerve injuries result in pronounced alterations in dorsal root ganglia, which can lead to the development of neuropathic pain. Although the polymodal mechanosensitive transient receptor potential ankyrin 1 (TRPA1) ion channel is emerging as a relevant target for potential analgesic therapies, preclinical studies do not provide unequivocal mechanistic insight into its relevance for neuropathic pain pathogenesis. By using a transgenic mouse model with a conditional depletion of the interleukin-6 (IL-6) signal transducer gp130 in Nav1.

CREG1 promotes lysosomal biogenesis and function.

CREG1 is a small glycoprotein which has been proposed as a transcription repressor, a secretory ligand, a lysosomal, or a mitochondrial protein. This is largely because of lack of antibodies for immunolocalization validated through gain- and loss-of-function studies. In the present study, we demonstrate, using antibodies validated for immunofluorescence microscopy, that CREG1 is mainly localized to the endosomal-lysosomal compartment.

Short-term in vitro glutamine restriction differentially impacts the chromosomal stability of transformed and non-transformed cells.

Glutamine (Gln) is a non-essential amino acid central for generating building blocks and cellular energy in tumours and rapidly proliferating non-transformed cells. However, the influence of Gln on regulating chromosomal stability of transformed and non-transformed cells remain poorly understand. We hypothesised that Gln is required for maintaining a homeostatic level of chromosomal stability.

PTEN suppresses epithelial-mesenchymal transition and cancer stem cell activity by downregulating Abi1.

The epithelial-mesenchymal transition (EMT) is an embryonic program frequently reactivated during cancer progression and is implicated in cancer invasion and metastasis. Cancer cells can also acquire stem cell properties to self-renew and give rise to new tumors through the EMT. Inactivation of the tumor suppressor PTEN has been shown to induce the EMT, but the underlying molecular mechanisms are less understood.

PTEN dephosphorylates Abi1 to promote epithelial morphogenesis.

The tumor suppressor PTEN is essential for early development. Its lipid phosphatase activity converts PIP3 to PIP2 and antagonizes the PI3K-Akt pathway. In this study, we demonstrate that PTEN's protein phosphatase activity is required for epiblast epithelial differentiation and polarization.

Impaired mechanical, heat, and cold nociception in a murine model of genetic TACE/ADAM17 knockdown.

TNF-α-converting enzyme, a member of the ADAM (A disintegrin and metalloproteinase) protease family and also known as ADAM17, regulates inflammation and regeneration in health and disease. ADAM17 targets are involved in pain development and hypersensitivity in animal models of inflammatory and neuropathic pain. However, the role of ADAM17 in the pain pathway is largely unknown.

SOD1 Phosphorylation by mTORC1 Couples Nutrient Sensing and Redox Regulation.

Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrated with redox regulation is an interesting, but not fully understood, question.

Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive.

Microgravity simulation activates Cdc42 via Rap1GDS1 to promote vascular branch morphogenesis during vasculogenesis.

Gravity plays an important role in normal tissue maintenance. The ability of stem cells to repair tissue loss in space through regeneration and differentiation remains largely unknown. To investigate the impact of microgravity on blood vessel formation from pluripotent stem cells, we employed the embryoid body (EB) model for vasculogenesis and simulated microgravity by clinorotation.

Randomized controlled trial: Standard versus supplemental bowel preparation in patients with Bristol stool form 1 and 2.

Background: Bristol stool form 1 and 2 is an important predictor of inadequate bowel preparation.

Aim: To evaluate the efficacy of supplemental preparation in bowel cleansing quality among patients with Bristol stool form 1 and 2, as well as the feasibility of tailored bowel preparation guided by Bristol stool form scale.

Methods: Patients with Bristol stool form 1 and 2 from 3 Chinese tertiary hospitals randomly received either 2 L PEG-ELP (group A) or 10 mg bisacodyl plus 2 L PEG-ELP (group B); patients with Bristol stool form 3 to 7 received 2 L PEG-ELP (group C) for bowel preparation.

Acetylated tubulin is essential for touch sensation in mice.

At its most fundamental level, touch sensation requires the translation of mechanical energy into mechanosensitive ion channel opening, thereby generating electro-chemical signals. Our understanding of this process, especially how the cytoskeleton influences it, remains unknown. Here we demonstrate that mice lacking the α-tubulin acetyltransferase Atat1 in sensory neurons display profound deficits in their ability to detect mechanical stimuli.

Integrin and dystroglycan compensate each other to mediate laminin-dependent basement membrane assembly and epiblast polarization.

During early embryogenesis, endodermal γ1-laminin expression is required for basement membrane (BM) assembly, promoting conversion of non-polar pluripotent cells into polarized epiblast. The influence of laminin-111 (Lm111) and its integrin and dystroglycan (DG) receptors on epiblast in embryoid bodies (EBs), a model for differentiation of the embryonic plate, was further investigated. Lm111 added to the medium of EBs initiated conversion of inner nonpolar cell to the polarized epiblast epithelium with an exterior-to-central basal-to-apical orientation.

CREG1 Interacts with Sec8 to Promote Cardiomyogenic Differentiation and Cell-Cell Adhesion.

Understanding the regulation of cell-cell interactions during the formation of compact myocardial structures is important for achieving true cardiac regeneration through enhancing the integration of stem cell-derived cardiomyocytes into the recipient myocardium. In this study, we found that cellular repressor of E1A-stimulated genes 1 (CREG1) is highly expressed in both embryonic and adult hearts. Gain- and loss-of-function analyses demonstrated that CREG1 is required for differentiation of mouse embryonic stem (ES) cell into cardiomyocytes and the formation of cohesive myocardium-like structures in a cell-autonomous fashion.

Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons.

Sensing force is crucial to maintain the viability of all living cells. Despite its fundamental importance, how force is sensed at the molecular level remains largely unknown. Here we show that stomatin-like protein-3 (STOML3) controls membrane mechanics by binding cholesterol and thus facilitates force transfer and tunes the sensitivity of mechano-gated channels, including Piezo channels.

Construction of interference vector targeting Ep-CAM gene and its effects on colorectal cancer cell proliferation.

Background: Prior study indicates that abnormal protein expression and functional changes in the development and progression of colorectal cancer is related to gene expression. The aim of this study was to construct an interference plasmid targeting the Ep-CAM gene and to investigate its effects on the proliferation of colorectal cancer cells.

Methods: In this study, HT-29 and HCT-116 colorectal cancer cell lines were selected as cell models.

A chimeric embryoid body model to study vascular morphogenesis.

Embryonic stem cell (ESC)-derived embryoid body (EB) is a unique model for studying vascular development, in that it provides a three-dimensional microenvironment that mimics an in vivo milieu. When using gene-targeting EBs to study certain defects in vascular morphogenesis, it is necessary to determine whether the defect is due to the intrinsic loss of the gene in endothelial cells (EC) or rather due to the lack of surrounding factors that would typically promote vascular development. Here we describe a chimeric EB vessel development model, in which the utilization of the PECAM-GFP reporter gene in wild-type ESCs allows for the introduction of "normal" extracellular factors formed by its parallel differentiation to the gene-deletion EC that might otherwise be devoid of these factors.

Regulation of migratory activity of human keratinocytes by topography of multiscale collagen-containing nanofibrous matrices.

Nanofibrous matrices hold great promise in skin wound repair partially due to their capability of recapturing the essential attributes of native extracellular matrix (ECM). With regard to limited studies on the effect of nanofibrous matrices on keratinocytes, the present study was aimed to understand how the topographical feature of nanofibrous matrices regulates keratinocyte motility by culturing keratinocytes on polycaprolactone (PCL)/collagen nanofibrous matrices (rough surface with fiber diameters of 331 ± 112 nm) or the matrices coated with a thin layer of collagen gel to form a secondary ultrafine fibrous network (smooth surface with ultrafine fiber diameters of 55 ± 26 nm). It was found that the PCL/collagen nanofibrous matrices alone did not stimulate cell migration, while collagen gel coating could significantly increase cell motility.

GATA-6 promotes cell survival by up-regulating BMP-2 expression during embryonic stem cell differentiation.

GATA-6 is a zinc-finger transcription factor essential for early embryogenesis. Ablation of GATA-6 in mice impairs endoderm differentiation and causes apoptosis of epiblast cells. The endoderm defects have been attributed to the loss of HNF4, disabled-2, and GATA-4.