mSphere of Influence: Surface Sensing in Biofilm Formation.

Kara B. De Leόn works in the field of microbial ecology, environmental biofilms, and microbial genetics. In this mSphere of Influence article, she reflects on how the paper "Multigenerational memory and adaptive adhesion in early bacterial biofilm communities" by C. K. Lee et al. (C. K. Lee, J. de Anda, A. E. Baker, R. R. Bennett, et al., Proc Natl Acad Sci U S A 115:4471-4476, 2018, https://dx.doi.org/10.1073/pnas.1720071115) made an impact on her by changing the way she thinks about initial cell attachment to a surface in an environment.

Corrigendum to "Spin structure relation to phase contrast imaging of isolated magnetic Bloch and Néel skyrmions" [Ultramicroscopy 212 (2020) 112973].

Several errors are present in the text and Fig. 3 of the article Ultramicroscopy 212 (2020) 112973. This includes minor confusions concerning the skyrmion helicities and a wrong orientation of a color wheel that represents the electron phase gradient direction. Further, the presented correction factors for finite probe sizes were based on an erratic simulation which is now corrected. This leads to different error values for the measured skyrmion size. These flaws do not affect the main message of the paper which is the relation of the skyrmion structure with the electron phase at all. They only affect the small section of the proof of principle skyrmion size measurement where aberrations were included.

COP1 destabilizes DELLA proteins in Arabidopsis.

DELLA transcriptional regulators are central components in the control of plant growth responses to the environment. This control is considered to be mediated by changes in the metabolism of the hormones gibberellins (GAs), which promote the degradation of DELLAs. However, here we show that warm temperature or shade reduced the stability of a GA-insensitive DELLA allele in Arabidopsis thaliana Furthermore, the degradation of DELLA induced by the warmth preceded changes in GA levels and depended on the E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1). COP1 enhanced the degradation of normal and GA-insensitive DELLA alleles when coexpressed in Nicotiana benthamiana. DELLA proteins physically interacted with COP1 in yeast, mammalian, and plant cells. This interaction was enhanced by the COP1 complex partner SUPRESSOR OF phyA-105 1 (SPA1). The level of ubiquitination of DELLA was enhanced by COP1 and COP1 ubiquitinated DELLA proteins in vitro. We propose that DELLAs are destabilized not only by the canonical GA-dependent pathway but also by COP1 and that this control is relevant for growth responses to shade and warm temperature.

Spin structure relation to phase contrast imaging of isolated magnetic Bloch and Néel skyrmions.

Magnetic skyrmions are promising candidates for future storage devices with a large data density. A great variety of materials have been found that host skyrmions up to the room-temperature regime. Lorentz microscopy, usually performed in a transmission electron microscope (TEM), is one of the most important tools for characterizing skyrmion samples in real space. Using numerical calculations, this work relates the phase contrast in a TEM to the actual magnetization profile of an isolated Néel or Bloch skyrmion, the two most common skyrmion types. Within the framework of the used skyrmion model, the results are independent of skyrmion size and wall width and scale with sample thickness for purely magnetic specimens. Simple rules are provided to extract the actual skyrmion configuration of pure Bloch or Néel skyrmions without the need of simulations. Furthermore, first differential phase contrast (DPC) measurements on Néel skyrmions that meet experimental expectations are presented and showcase the described principles. The work is relevant for material sciences where it enables the engineering of skyrmion profiles via convenient characterization.

Teriparatide alleviates osteoporosis by promoting osteogenic differentiation of hMSCs via miR-375/RUNX2 axis.

OBJECTIVE: To investigate whether Teriparatide (TP) contributed to the osteogenic differentiation of human marrow mesenchymal cells (hMSCs) through the regulation of miR-375, thereby alleviating osteoporosis (OP). PATIENTS AND METHODS: The expression levels of miR-375 in the serum and hMSCs of patients with OP were determined by quantitative real time-polymerase chain reaction (qRT-PCR). hMSCs were extracted from bone marrows of OP patients and underwent osteogenic differentiation for 1 day, 3 days, 7 days and 10 days, respectively. The mRNA levels of alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2) in TP-treated hMSCs transfected with miR-375 mimics or negative control were detected by qRT-PCR. Western blot was conducted to determine the protein expression of RUNX2 in TP-treated hMSCs transfected with miR-375 mimics or negative control. Besides, the osteogenic capacity and mineralization capacity of hMSCs were evaluated by the detection of ALP activity, ALP staining and Alizarin red staining, respectively. Dual-Luciferase reporter gene assay was performed to verify the binding between RUNX2 and miR-375. Subsequently, RUNX2 expression was detected in hMSCs transfected with miR-375 mimics or inhibitor. Rescue experiments were finally performed to determine whether miR-375 was involved in TP-induced osteogenic differentiation by targeting RUNX2. RESULTS: MiR-375 remained at a high level in serum of OP patients, while gradually decreased with the prolongation of osteogenic differentiation in isolated hMSCs. TP induction increased the osteogenic and mineralization capacities of hMSCs, which were inhibited after miR-375 overexpression. Through Dual-Luciferase reporter gene assay, we confirmed the binding relationship between miR-375 and RUNX2. Besides, both mRNA and protein levels of RUNX2 were negatively regulated by miR-375. Finally, we verified that co-overexpression of miR-375 and RUNX2 in TP-induced hMSCs significantly enhanced the mineralization capacity compared to overexpression of miR-375 alone. CONCLUSIONS: Teriparatide promoted the osteogenic differentiation of hMSCs through miR-375/RUNX2 axis.

Mice expressing the variant rs1143679 allele of ITGAM (CD11b) show impaired DC-mediated T cell proliferation.

Genome-wide association studies (GWAS) and functional genomic analyses have implicated several ITGAM (CD11b) single-nucleotide polymorphisms (SNPs) in the development of SLE and other disorders. ITGAM encodes the αM chain of the ß2 integrin Mac-1, a receptor that plays important roles in myeloid cell functions. The ITGAM SNP rs1143679, which results in an arginine to histidine change at amino acid position 77 of the CD11b protein, has been shown to reduce binding to several ligands and to alter Mac-1-mediated cellular response in vitro. Importantly, however, the potential contribution of this SNP variant to the initiation and/or progression of immune and inflammatory processes in vivo remains unexplored. Herein, we describe for the first time the generation and characterization of a mouse line expressing the 77His variant of CD11b. Surprisingly, we found that 77His did not significantly affect Mac-1-mediated leukocyte migration and activation as assessed using thioglycollate-induced peritonitis and LPS/TNF-α-induced dermal inflammation models. In contrast, expression of this variant did alter T cell immunity, as evidenced by significantly reduced proliferation of ovalbumin (OVA)-specific transgenic T cells in 77His mice immunized with OVA. Reduced antigen-specific T cell proliferation was also observed when either 77His splenic dendritic cells (DCs) or bone marrow-derived DCs were used as antigen-presenting cells (APCs). Although more work is necessary to determine how this alteration might influence the development of SLE or other diseases, these in vivo findings suggest that the 77His variant of CD11b can compromise the ability of DCs to induce antigen-driven T cell proliferation.

[Cancer epidemics and the cancer prevention and control strategies in the United States: a review study].

In the past two decades,the United States made an impressed progress in the prevention and control of cancer that the overall morbidity and mortality of cancer had shown a downward trend, while China had seen an opposite trend. Cancer, one of the major public health concerns in China, has imposed an enormous burden onthe society and individuals. Therefore,in order to scientifically formulate cancer prevention and control policies, it is essential to make a comprehensive understanding of the practical experience in the field of cancer prevention and control from the United States. This article reviews the relevant literature on cancer trends as well as the prevention and control strategies in the United States,depictsthe cancer epidemic situation in the United States in the past 30 years, and summarizes the influencing factors, strategies and intervention experiences that lead to the improvement of cancer epidemic. It highlights the policy support, surveillance and intervention adopted by the United States for the cancer prevention and control. This article is expected to provide some implications and reference for the cancer prevention and control in China.

The overexpression of Fra1 disorders the inflammatory cytokine secretion by mTEC of myasthenia gravis thymus.

The thymus of a myasthenia gravis (MG) patient is often accompanied by and effected with follicular hyperplasia. Inflammatory cytokines in thymus induce the formation of germinal centres (GC). MG thymic inflammatory cytokines are predominantly secreted by stromal cells. Our previous studies revealed that the expression level of the Fra1 protein, which is a Fos member of the activator protein 1 transcription factors (AP-1), was higher in the MG thymus compared with that of the normal thymus. Based on that, we demonstrated that Fra1 was mainly expressed in medulla thymic epithelial cells (mTECs) and that the rate of Fra1 positive mTECs in the MG thymus was higher than normal. In vitro, we found that the expression of CCL-5, CCL-19 and CCL-21 could be regulated by Fra1 in mTEC and that IL-1ß, IL-6, IL-8 and ICAM1 were downregulated in the Fra1 overexpression group and upregulated in the Fra1 knock-down group. Meanwhile, we detected that the expression levels of suppressor of cytokine signalling 3 (SOCS3) were significantly upregulated along with the overexpression of Fra1. Hence, we considered that the overexpression of Fra1 disrupted inflammatory cytokine secretion by mTEC in the MG thymus and that STAT3 and SOCS3 were strongly involved in this process.

T Cells in Allergic Asthma: Key Players Beyond the Th2 Pathway.

Asthma is a common chronic lung disease that affects 300 million people worldwide. It causes the airways of the lungs to swell and narrow due to inflammation (swelling and excess mucus build-up in the airways) and airway constriction (tightening of the muscles surrounding the airways). Atopic asthma is the most common form of asthma, and is triggered by inhaled allergens that ultimately promote the activation of the Th2-like T cells and the development of Th2-mediated chronic inflammation. Different subsets of T cells, including T follicular helper cells, tissue-resident T, cells and Th2 effector cells, play different functions during allergic immune response. Dendritic cells (DCs) are known to play a central role in initiating allergic Th2-type immune responses and in the development of the T cell phenotype. However, this function depends on the complex interaction with other cells of the immune system and determines whether the response to environmental allergens will be one of tolerance or allergic inflammation. This review discusses cell interactions leading to the initiation and maintenance of allergic Th2-type immune responses, particularly those associated with allergic asthma.

Depinning of domain walls in permalloy nanowires with asymmetric notches.

Effective control of the domain wall (DW) motion along the magnetic nanowires is of great importance for fundamental research and potential application in spintronic devices. In this work, a series of permalloy nanowires with an asymmetric notch in the middle were fabricated with only varying the width (d) of the right arm from 200 nm to 1000 nm. The detailed pinning and depinning processes of DWs in these nanowires have been studied by using focused magneto-optic Kerr effect (FMOKE) magnetometer, magnetic force microscopy (MFM) and micromagnetic simulation. The experimental results unambiguously exhibit the presence of a DW pinned at the notch in a typical sample with d equal to 500 nm. At a certain range of 200 nm < d < 500 nm, both the experimental and simulated results show that the DW can maintain or change its chirality randomly during passing through the notch, resulting in two DW depinning fields. Those two depinning fields have opposite d dependences, which may be originated from different potential well/barrier generated by the asymmetric notch with varying d.

Expression of somatostatin receptor subtype 2 in growth hormone-secreting pituitary adenoma and the regulation of miR-185.

INTRODUCTION: Long-acting somatostatin analogs (SSAs) are most widely used to treat growth hormone (GH)-secreting pituitary adenoma. However, approximately 30 % of treated patients show resistance to SSAs, which may be associated with the reduction of somatostatin receptor subtype 2 (SSTR2) mRNA and protein expression. MATERIALS AND METHODS: The present study used immunohistochemistry to detect the expression of SSTR2 and SSTR5 in twenty human GH-secreting adenoma samples treated with SSAs and seven normal pituitary samples. RESULTS: The staining intensities of SSTR2 and SSTR5 were stronger in most adenoma samples than in normal pituitary. The expression of SSTR2 tended to be lower in the SSA non-responder group than in responders. A search of the Bioinformatics data bank and the miRCURY™ LNA array confirmed miR-185 as the putative mircoRNA (miRNA) regulating the expression of SSTR2. An in vitro study using Dual Luciferase reporter assay demonstrated that miR-185 likely targets the 3'-UTR of SSTR2 mRNA in the rat pituitary adenoma GH3 cell line. MiR-185 also downregulated or upregulated the expression of SSTR2 mRNA and SSTR2 protein, following transfection with miR-185 mimics or inhibitors, respectively. CONCLUSION: MiR-185 enhanced the cell proliferation and inhibited the apoptosis of GH3 cells.

Impaired heterologous immunity in aged ferrets during sequential influenza A H1N1 infection.

The major burden of influenza morbidity resides within the elderly population. The challenge managing influenza-associated illness in the elderly is the decline of immune function, where mechanisms leading to immunological senescence have not been elucidated. To better represent the immune environment, we investigated clinical morbidity and immune function during sequential homologous and heterologous H1N1 influenza infection in an aged ferret model. Our findings demonstrated experimentally that aged ferrets had significant morbidity during monosubtypic heterologous 2° challenge with significant weight loss and respiratory symptoms. Furthermore, increased clinical morbidity was associated with slower and shorter hemagglutinin antibody generation and attenuated type 1 T-cell gene responses in peripheral blood. These results revealed dampened immune activation during sequential influenza infection in aged ferrets. With the presence of an aged model, dissecting clinical morbidity, viral dynamics and immune response during influenza infection will aid the development of future prophylactics such as age specific influenza vaccines.

Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection.

The role of Group X secreted phospholipase A2 (GX-sPLA2) during influenza infection has not been previously investigated. We examined the role of GX-sPLA2 during H1N1 pandemic influenza infection in a GX-sPLA2 gene targeted mouse (GX(-/-)) model and found that survival after infection was significantly greater in GX(-/-) mice than in GX(+/+) mice. Downstream products of GX-sPLA2 activity, PGD2, PGE2, LTB4, cysteinyl leukotrienes and Lipoxin A4 were significantly lower in GX(-/-) mice BAL fluid. Lung microarray analysis identified an earlier and more robust induction of T and B cell associated genes in GX(-/-) mice. Based on the central role of sPLA2 enzymes as key initiators of inflammatory processes, we propose that activation of GX-sPLA2 during H1N1pdm infection is an early step of pulmonary inflammation and its inhibition increases adaptive immunity and improves survival. Our findings suggest that GX-sPLA2 may be a potential therapeutic target during influenza.

Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion.

Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus-epithelial cell interaction.

Study on characteristics of chemokine CXCL10 gene cloned from cDNA expression library of Ujumqin sheep.

Chemokines were a major regulator of body's inflammatory and immune responses. In this study, the cDNA fragment of chemokine CXC ligand 10 (CXCL10) was cloned from the Ujumqin sheep ear marginal tissue cDNA expression library; the CXCL10 gene had 103 amino acids and a molecular weight of 11.47 kDa, and it shared a high homology among cattle, sheep, and goat, while a low homology compared with mouse. The CXCL10 protein had 4 conservative cysteine residues, located in 28, 30, 55, and 72 sites. The expression pattern and intracellular distribution of recombinant CXCL10 proteins in Ujumqin sheep fibroblast cells showed that there were green fluorescence signals both in cytoplasm and nucleolus after 24 h of transfection, the number of positive cells was increased with time, the peak level of fluorescence signal was reached after 48 h of transfection and the transfection efficiency was 33.3%; there was a significant decrease in fluorescence intensity after 72 h of transfection. Expression of recombinant CXCL10 gene in Escherichia coli had a time- and temperature-dependency on the amount of protein expression, and a small quantity of inducer was needed.

Indoleamine 2,3-dioxygenase is differentially expressed by different white blood cell populations of rhesus macaques (Macaca mulatta).

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is involved in immune processes such as transplant and fetal rejection, autoimmunity, cancer, and infection; however, its expression in rhesus macaques has not been fully addressed. METHODS: Indoleamine 2,3-dioxygenase mRNA and protein in the white blood cells (WBCs) of Chinese rhesus macaques were examined by RT-PCR, western blotting, real-time RT-PCR, and flow cytometry. RESULTS: Both IDO protein and mRNA could be readily detected in WBCs or peripheral blood mononuclear cells (PBMCs) of normal rhesus macaques. IDO+ cell frequency was the highest among CD14(+) mononuclear cells, followed by CD56(+) cells and DCs. No difference in the frequency of IDO+ cells between CD4(+) and CD8(+) T cells; however, Th17 cells have higher frequency of IDO+ cells than Th1 cells, with Th2 cells the lowest. Toll-like receptor (TLR) stimulation significantly increased IDO protein level in CD14(+) , CD56(+) , CD1c(+) , CD11c(+) , and CD123(+) myeloid cells. CONCLUSION: Rhesus macaques express IDO differentially in their leukocyte subsets and are suitable for IDO-related pathophysiological studies.

A novel marine drug, SZ-685C, induces apoptosis of MMQ pituitary tumor cells by downregulating miR-200c.

OBJECTIVE: We found a novel marine drug, SZ-685C, that was isolated from the secondary metabolites of a mangrove endophytic fungus (No. 1403) collected from the South China Sea, which has been reported to inhibit the proliferation of certain tumor cells. However, its anticancer mechanism remains unknown. The aims of this study were to observe the effectiveness of SZ-685C on pituitary adenoma cells and determine the underlying mechanisms of action. METHODS: A rat prolactinoma cell line, MMQ, was used in this study. A dose escalation of SZ-685C was performed on this cell line, and cell viability was assessed using an MTT assay. Hoechst 33342, Annexin V-FITC/PI, TUNEL staining and flow cytometry were used to evaluate the extent of apoptosis at each concentration of SZ-685C. The effect of SZ-685C on prolactin expression was also evaluated using RT-PCR and immunoblotting. Quantitative RT-PCR was used to detect the expression of miR-200c in SZ-685C-stimulated MMQ cells and pituitary adenoma tissues. This miRNA was then overexpressed in MMQ cells via transfection of a miR-200c mimic to identify the mechanism underling the anti-tumor effect of SZ-685C. RESULTS: SZ-685C inhibited MMQ cell growth in a dose-dependent manner but showed little toxicity toward rat pituitary cells (RPCs). The IC50s of SZ-685C in MMQ cells and RPCs were 13.2 ± 1.3 mM and 49.1 ± 11.5 mM, respectively, which was statistically significant. Increasing numbers of apoptotic cells were observed in response to escalating concentrations of SZ-685C, and the expression level of prolactin (PRL) was inhibited. Nevertheless, the level of PRL mRNA was unchanged. Additionally, miR-200c was upregulated in MMQ cells compared with RPCs, and downregulation of miR- 200c was observed in SZ-685C-treated MMQ cells. Furthermore, the overexpression of miR-200c weakened the effect of SZ-685C-induced apoptosis of MMQ cells. CONCLUSIONS: Our results suggest that SZ-685C induces MMQ cell apoptosis in a miR-200c-dependent manner. Therefore, SZ-685C might be a useful alternative treatment for pituitary adenoma.

Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza A infection.

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.

Induction of mouthpart deformities in chironomid larvae exposed to contaminated sediments.

The aim of the present study was to improve the cause-effect relationship between toxicant exposure and chironomid mouthpart deformities, by linking induction of mouthpart deformities to contaminated field sediments, metal mixtures and a mutagenic polycyclic aromatic compound metabolite (acridone). Mouthpart deformities in Chironomus riparius larvae were induced by both the heavy metal mixture and by acridone. A clear correlation between metal concentrations in the sediment and deformities incidence was only observed when the contaminated field sediments were left out of the analysis, probably because these natural sediments contained other toxic compounds, which could be responsible for a higher incidence of deformities than predicted by the measured metal concentrations only. The present study clearly improved the cause-effect relationship between toxicant exposure and the induction of mouthpart deformities. It is concluded that the incidence of mouthpart deformities may better reflect the potential toxicity of contaminated sediments than chemical analysis.

High-resolution extracellular stimulation of dispersed hippocampal culture with high-density CMOS multielectrode array based on non-Faradaic electrodes.

We introduce a method to electrically stimulate individual neurons at single-cell resolution in arbitrary spatiotemporal patterns with precise control over stimulation thresholds. By exploiting a custom microelectronic chip, up to 65,000 non-Faradaic electrodes can be uniquely addressed with electrode density exceeding 6500 electrodes mm(-2). We demonstrate extracellular stimulation of dispersed primary hippocampal neuronal cultures using the chip at single-cell resolution.