Control of the lac operon with isopropyl β-D-1-thiogalactopyranoside (IPTG) has been used to regulate gene expression in Escherichia coli for countless applications, including metabolic engineering ...and recombinant protein production. However, optogenetics offers unique capabilities, such as easy tunability, reversibility, dynamic induction strength and spatial control, that are difficult to obtain with chemical inducers. We have developed a series of circuits for optogenetic regulation of the lac operon, which we call OptoLAC, to control gene expression from various IPTG-inducible promoters using only blue light. Applying them to metabolic engineering improves mevalonate and isobutanol production by 24% and 27% respectively, compared to IPTG induction, in light-controlled fermentations scalable to at least two-litre bioreactors. Furthermore, OptoLAC circuits enable control of recombinant protein production, reaching yields comparable to IPTG induction but with easier tunability of expression. OptoLAC circuits are potentially useful to confer light control over other cell functions originally designed to be IPTG-inducible.
Full text
Available for:
GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Summary
Activated acid-sensing ion channel 1a (ASIC1a) is involved in acid-induced osteoclastogenesis by regulating activation of the transcription factor NFATc1. These results indicated that ASIC1a ...activation by extracellular acid may cause osteoclast migration and adhesion through Ca
2+
-dependent integrin/Pyk2/Src signaling pathway.
Introduction
Osteoclast adhesion and migration are responsible for osteoporotic bone loss. Acidic conditions promote osteoclastogenesis. ASIC1a in osteoclasts is associated with acid-induced osteoclastogenesis through modulating transcription factor NFATc1 activation. However, the influence and the detailed mechanism of ASIC1a in regulating osteoclast adhesion and migration, in response to extracellular acid, are not well characterized.
Methods
In this study, knockdown of ASIC1a was achieved in bone marrow macrophage cells using small interfering RNA (siRNA). The adhesion and migration abilities of osteoclast precursors and osteoclasts were determined by adhesion and migration assays, in vitro. Bone resorption was performed to measure osteoclast function. Cytoskeletal changes were assessed by F-actin ring formation. αvβ3 integrin expression in osteoclasts was measured by flow cytometry. Western blotting and co-immunoprecipitation were performed to measure alterations in integrin/Pyk2/Src signaling pathway.
Results
Our results showed that blockade of ASIC1a using ASIC1a-siRNA inhibited acid-induced osteoclast precursor migration and adhesion, as well as osteoclast adhesion and bone resorption; we also demonstrated that inhibition of ASIC1a decreased the cell surface αvβ3 integrin and β3 protein expression. Moreover, blocking of ASIC1a inhibited acidosis-induced actin ring formation and reduced Pyk2 and Src phosphorylation in osteoclasts and also inhibited the acid-induced association of the αvβ3 integrin/Src/Pyk2.
Conclusion
Together, these results highlight a key functional role of ASIC1a/αvβ3 integrin/Pyk2/Src signaling pathway in migration and adhesion of osteoclasts.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
As the potential role of the complement system in diabetic nephropathy (DN) is increasingly reported, this study aimed to investigate C1q and C3c deposition as seen on renal histopathology, as well ...as its association with clinical and pathological parameters, in DN patients.
Renal biopsy specimens from 161 DN patients were investigated using direct immunofluorescence, light, and electron microscopy. For direct immunofluorescence, staining for C1q and C3c on fresh-frozen renal tissue was performed immediately after biopsy. Complement deposition was defined as the presence of C1q or C3c of at least 1 + on a 0–4 + Scale. The association between complement deposition and clinicopathological data was also analyzed.
On direct immunofluorescence microscopy, C1q and C3c were detected in specimens from 44/161 (27.3%) and 89/161 (55.3%) patients, respectively. Regarding clinical data, patients with C1q deposition had a significantly higher level of urinary protein (7.25 ± 4.20 g/24 h vs. 4.97 ± 3.76 g/24 h; P < 0.01) and significantly lower estimated glomerular filtration rate (eGFR; 34.16 ± 25.21 mL/min/1.73 m2 vs. 51.17 ± 31.56 mL/min/1.73 m2, respectively; P < 0.01), whereas patients with vs. without C3c deposition had a significantly lower eGFR (40.09 ± 27.97 mL/min/1.73 m2 vs. 54.48 ± 32.49 mL/min/1.73 m2, respectively; P < 0.01). On renal histopathology, patients with C1q deposition had significantly higher Scores for interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and vascular lesions (P < 0.01, P < 0.05 and P < 0.05, respectively), whereas patients with C3c deposition had significantly higher IFTA Scores and proportions of global sclerosis (P < 0.01 and P < 0.01, respectively).
Complement deposition of C1q and C3c on renal histopathology is associated with more severe kidney damage in patients with DN.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Four different atomic component metallic glasses were studied under nanoindentation tests to determine their strain rate sensitivities of hardness.•Strain rate sensitivity of four different BMGs ...were calculated, the mechanism and influencing factors of negative SRS are studied.•The variation trends along with different factors were observed and discussed, creep behavior was observed and we note that the study of the creep behavior can be useful of exploring the deformation mechanism of metallic glasses.
Nanoindentation tests were conducted on Pd40Cu30Ni10P20, (Fe0.6Co0.4)0.75B0.2Si0.0596Nb4, Zr48Cu34Pd2Al8Ag8 and Zr48Cu32Ni4Al8Ag8 bulk metallic glasses to determine their strain rate sensitivities of hardness. Strain rate sensitivities for different experimental conditions were calculated, it was found that all specimens exhibit negative strain rate sensitivity. Different variation trend of strain rate sensitivity values along with different factors were observed, these observations were utilized to discuss the reasons for negative strain rate sensitivity, and its dependence on the composition and other factors of metallic glasses.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Soil organic matter (SOM) is a key property determining soil functions and a major form of carbon stored in soil. Understanding the spatial and temporal variability of SOM and the driving forces ...responsible for spatial and temporal changes is important to assess regional soil quality and carbon sequestration potential and, particularly, to establish better practices for land use and management. We evaluated the spatio‐temporal change in SOM content from 1979–1982 to 2006 and its driving forces in Jiangsu Province, East China, using geostatistics. The results showed that mean SOM content increased from 16.60 ± 8.50 to 18.31 ± 8.32 g/kg over a 26‐yr period. The maps of SOM generated by ordinary kriging represented the increasing trend from north to south across the province in the two periods. The level of SOM in 1979–1982 affected the pattern of change: the SOM increasing in areas initially with a small content while decreasing in areas having a large content. The map of SOM change showed that the rate of increase decreased from north to south within the province. Increased fertilizer application promoted crop production with more residual biomass being retained in the soil, which resulted in increased SOM content. Land use changes to paddy, upland or forest improved SOM content, whereas abandoning land reduced SOM content.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A long‐standing problem concerning dipolarization front (DF) is why energetic electrons only appear in half the DF events? By analyzing MMS measurements, here we answer this question. We find a DF ...structure, behind which energetic‐electron fluxes are modulated by magnetosonic waves: At wave troughs (B‐minimum) electron fluxes are high; at wave crests (B‐maximum) electron fluxes are low. This phenomenon challenges the classical theory of betatron mechanism, so we need to propose a new theory to explain it. In our theory, there exists a magnetic bottle with time‐varying belly but steady neck behind the DF. When the belly expands, a magnetic bottle is formed, and electrons are trapped; when the belly contracts, the magnetic bottle disappears, and electrons are expelled. Quantitatively, we validate the existence of this bottle and estimate its size as 2–3 RE. Our theory can explain both the presence and absence of energetic electrons behind DFs.
Key Points
Energetic‐electron fluxes increase at B‐minimum but decrease at B‐maximum
This phenomenon challenges the classical theory and thus requires new explanation
Our new theory includes a magnetic bottle with time‐varying belly but steady neck
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Background Exosomes are nanometer-sized vesicles that are released by normal and neoplastic cells. Previous studies have focused on the interaction between tumour-derived exosomes and the ...immune system, as a consequence of immune suppression or enhancement. However, the effects of tumour-derived exosomes on tumour cells themselves have not been well studied. Aims To investigate the effects of gastric cancer exosomes on tumour cell proliferation and the possible mechanisms. Methods By serial centrifugation and sucrose gradient ultracentrifugation, we isolated and purified the exosomes from gastric cancer SGC7901 cells, then viewed them by electron microscopy. Cell proliferation was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay. Protein expression was assayed by Western blotting. Results SGC7901-cell-derived exosomes promoted the proliferation of SGC7901 and BGC823 cells. The increase in proliferation induced by exosomes was accompanied by activation of Akt and extracellular-regulated protein kinase, and phosphoinositide 3-kinase or extracellular-regulated protein kinase inhibitor partially reversed the proliferative effect of exosomes. Moreover, the exosome-induced increase in activity of Akt and extracellular-regulated protein kinase coincided with decreased expression of the Casitas B-lineage lymphoma family of ubiquitin ligases. Conclusion Gastric cancer exosomes promoted tumour cell proliferation, at least in part, by activation of PI3K/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinase pathways. The decreased expression of Casitas B-lineage lymphoma proteins might have contributed to the activation of Akt and extracellular-regulated protein kinase.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Highlights • There is a TLR4-mediated PTEN/PI3K/AKT/NF-κB signaling pathway in rat hippocampal neurons. • This signaling pathway is associated with the activation of neuroinflammatory response. • The ...activation of this pathway results in TNF-α and IL-1β production.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Development and comparison of two classifiers, random forest and linear discriminant, for distinguishing between radiation pneumonitis (RP) and immune-related pneumonitis (CIP) in lung cancer ...patients receiving radiotherapy(RT) and immune checkpoint inhibitors (ICIs).•Identification of four most discriminating features, including Long Run Low Gray Level Emphasis, Median, Joint Average, and Busyness, that contribute to the classification of CIP and RP.•Demonstration of the potential of CT radiomics signatures in accurately diagnosing and distinguishing between different types of pneumonitis in lung cancer patients undergoing RT and ICIs.•Highlighting the need for further characterization of the relationship between radiomics features and pathologic features to enhance the understanding of disease pathology in patients receiving RT and ICIs.
To develop a CT-based model to classify pneumonitis etiology in patients with non-small cell lung cancer(NSCLC) after radiotherapy(RT) and Immune checkpoint inhibitors(ICIs).
We retrospectively identified 130 NSCLC patients who developed pneumonitis after receipt of ICIs only (n = 50), thoracic RT only (n = 50) (ICIs only + thoracic RT only, the training cohort, n = 100), and RT + ICIs (the test cohort, n = 30). Clinical and CT radiomics features were described and compared between different groups. We constructed a random forest (RF) classifier and a linear discriminant analysis (LDA) classifier by CT radiomics to discern pneumonitis etiology.
The patients in RT + ICIs group have more high grade (grade 3–4) pneumonitis compared to patients in ICIs only or RT only group (p < 0.05). Pneumonitis after the combined therapy was not a simple superposition mode of RT-related pneumonitis(RP) and ICI-related pneumonitis(CIP), resulting in the distinct characteristics of both RT and ICIs-related pneumonitis. The RF classifier showed favorable discrimination between RP and CIP with an area under the receiver operating curve (AUC) of 0.859 (95 %CI: 0.788-0.929) in the training cohort and 0.851 (95 % CI: 0.700–1) in the test cohort. The LDA classifier achieved an AUC of 0.881 (95 %CI: 0.815–0.947) in the training cohort and 0.842 (95 %CI: 0.686–0.997) in the test cohort. Our analysis revealed four principal CT-based features shared across both models:original_glrlm_LongRunLowGrayLevelEmphasis, wavelet-HLL_firstorder_Median, wavelet-LLL_ngtdm_Busyness， and wavelet-LLL_glcm_JointAverage.
CT radiomics-based classifiers could provide a noninvasive method to identify the predominant etiology in NSCLC patients who developed pneumonitis after RT alone, ICIs alone or RT + ICIs.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In low-dimensional electron systems, charge density waves (CDW) and superconductivity are two of the most fundamental collective quantum phenomena. For all known quasi-two-dimensional ...superconductors, the origin and exact boundary of the electronic orderings and superconductivity are still attractive problems. Through transport and thermodynamic measurements, we report on the field-temperature phase diagram in 2H-TaS2 single crystals. We show that the superconducting transition temperature (Tc) increases by one order of magnitude from temperatures at 0.98 K up to 9.15 K at 8.7 GPa when the Tc becomes very sharp. Additionally, the effects of 8.7 GPa illustrate a suppression of the CDW ground state, with critically small Fermi surfaces. Below the Tc the lattice of magnetic flux lines melts from a solid-like state to a broad vortex liquid phase region. Our measurements indicate an unconventional s-wave-like picture with two energy gaps evidencing its multi-band nature.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF