Mammalian tooth development is a precise and complicated procedure. Several signaling pathways, such as nuclear factor (NF)–κB and WNT, are key regulators of tooth development. Any disturbance of ...these signaling pathways can potentially affect or block normal tooth development, and presently, there are more than 150 syndromes and 80 genes known to be related to tooth agenesis. Clarifying the interaction and crosstalk among these genes will provide important information regarding the mechanisms underlying missing teeth. In the current review, we summarize recently published findings on genes related to isolated and syndromic tooth agenesis; most of these genes function as positive regulators of cell proliferation or negative regulators of cell differentiation and apoptosis. Furthermore, we explore the corresponding networks involving these genes in addition to their implications for the clinical management of tooth agenesis. We conclude that this requires further study to improve patients’ quality of life in the future.
Abstract
The electronic instabilities in CsV
3
Sb
5
are believed to originate from the V 3
d
-electrons on the kagome plane, however the role of Sb 5
p
-electrons for 3-dimensional orders is largely ...unexplored. Here, using resonant tender X-ray scattering and high-pressure X-ray scattering, we report a rare realization of conjoined charge density waves (CDWs) in CsV
3
Sb
5
, where a 2 × 2 × 1 CDW in the kagome sublattice and a Sb 5
p
-electron assisted 2 × 2 × 2 CDW coexist. At ambient pressure, we discover a resonant enhancement on Sb
L
1
-edge (2
s
→5
p
) at the 2 × 2 × 2 CDW wavevectors. The resonance, however, is absent at the 2 × 2 × 1 CDW wavevectors. Applying hydrostatic pressure, CDW transition temperatures are separated, where the 2 × 2 × 2 CDW emerges 4 K above the 2 × 2 × 1 CDW at 1 GPa. These observations demonstrate that symmetry-breaking phases in CsV
3
Sb
5
go beyond the minimal framework of kagome electronic bands near van Hove filling.
Hepatocellular carcinoma (HCC) is linked to inflammation and immunosuppression. Chemerin is highly expressed in the liver and implicated in the regulation of inflammation. However, the role of ...chemerin in HCC remains unclear. In this study, we aimed to investigate whether chemerin is able to influence HCC progression by regulating tumor-associated inflammation. Here we demonstrated that chemerin significantly decreased in blood and tumor tissues of HCC patients, and tumor chemerin levels were inversely associated with the prognosis. In an orthotopic mouse model of HCC, Rarres2
mice exhibited aggressive tumor growth and lung metastasis, whereas chemerin overexpression greatly inhibited tumor growth. The tumor-inhibitory effect of chemerin was accompanied by a shift in tumor-infiltrating immune cells from myeloid-derived suppressive cells (MDSCs) to interferon-γ
T cells and decreased tumor angiogenesis. Furthermore, we demonstrated that the tumor-inhibitory effect of chemerin was partly dependent on T cells, as chemerin overexpression could inhibit tumor growth, albeit to a lesser extent, in Rag1
mice when compared with wild-type controls. Mechanistically, chemerin inhibited nuclear factor-κB activation and the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-6) by tumor cells and tumor-associated endothelial cell, respectively, via its receptors, and consequently, MDSC induction was impaired, leading to restoration of antitumor T-cell response and decreased tumor angiogenesis. Clinically, systemic and tumor levels of chemerin were found to inversely correlate with circulating concentrations of GM-CSF or IL-6 and tumor-infiltrating myeloid cells, respectively, in HCC patients. Moreover, neutralization of GM-CSF and IL-6 abrogated HCC progression and MDSC accumulation in Rarres2
mice. In conclusion, our study reveals the tumor-inhibitory effect of chemerin by suppressing inflammatory tumor microenvironment with therapeutic implications for inflammation-associated cancer-like HCC.
Sialic acid‐binding immunoglobulin‐like lectin‐7 (Siglec‐7) is an inhibitory receptor expressed on natural killer (NK) cells. In this study, we investigated the relationship between Siglec‐7 ...expression and NK cell functions. Siglec‐7 was highly expressed on NK cells and was preferentially expressed by mature NK cells from peripheral blood of healthy adults. Siglec‐7+ NK cells displayed higher levels of activating receptors CD38, CD16, DNAM1, NKp30 and NKp46, but lower levels of inhibitory receptors such as NKG2A and CD158b, compared with Siglec‐7– NK cells. Functional tests showed that Siglec‐7+ NK cells displayed more CD107a degranulation and IFN‐γ production than Siglec‐7– NK cells. Siglec‐7 inhibited NK cell functions when interacting with specific antibodies. These data suggest that Siglec‐7 defines a highly functional NK cell subset and suppresses NK cell‐mediated functions when cross‐linked with specific antibodies.
We designed a commitment savings product for a Philippine bank and implemented it using a randomized control methodology. The savings product was intended for individuals who want to commit now to ...restrict access to their savings, and who were sophisticated enough to engage in such a mechanism. We conducted a baseline survey on 1777 existing or former clients of a bank. One month later, we offered the commitment product to a randomly chosen subset of 710 clients; 202 (28.4 percent) accepted the offer and opened the account. In the baseline survey, we asked hypothetical time discounting questions. Women who exhibited a lower discount rate for future relative to current trade-offs, and hence potentially have a preference for commitment, were indeed significantly more likely to open the commitment savings account. Mter twelve months, average savings balances increased by 81 percentage points for those clients assigned to the treatment group relative to those assigned to the control group. We conclude that the savings response represents a lasting change in savings, and not merely a short-term response to a new product.
The influence of fine particles on the flotation separation of minerals is becoming increasingly important as new, fine grained deposits are exploited. Fine particles float poorly and less ...selectively under normal flotation conditions, having detrimental effects on recovery of other minerals. The reasons of this interacting effect are complex, which may be entrainment, pH variation, dissolved ions from mineral surfaces, aggregation/dispersion and coating behavior of particles or even the competitive adsorption effect. In this study, the influence of fine magnesite and dolomite on the flotation of quartz was investigated. It was found that at pH=9.2–9.5 and with DDA dosage of 8.6×10−4, the recovery of coarse (−100+65μm) quartz was reduced dramatically from 96.66% to 37.15% when the content of quartz was 5% in the flotation with fine (−5μm) magnesite, and when the content of fine dolomite was increased from 2.5% to 20%, the recovery of coarse quartz was reduced from 91.20% to 75.08%. To examine the reasons, zeta potential, zero point of charge and contact angles of magnesite, dolomite and quartz were measured in the absence and presence of dodecylamine (DDA). The interaction energies between particles were then calculated. Results showed that the aggregation behavior of mineral particles was likely to be the reason. Interaction energy calculated based on Extended-DLVO (Derjaguin–Landau–Verwey–Overbeek) theory predicted that in DDA surfactant solution, the interaction forces between magnesite and quartz, dolomite and quartz were attractive, between dolomite and magnesite was repulsive. The experimental results are in excellent agreement with the theoretically predicted results. The aggregation caused by interacting behavior explains the depressing effect of fine hydrophilic particles on magnesite reverse flotation.
The float products of quartz-magnesite mixture (a), quartz-dolomite mixture(b) exhibits serious coating of fine magnesite and dolomite particles on quartz by SEM analysis. Display omitted
•A novel phenomenon in magnesite flotation was discovered that fine hydrophilic particles had depressing effect.•The recovery of quartz was decreased by 59% by adding fine magnesite and by 16% by adding fine dolomite.•Zeta-potential, contact angle and surface tension of magnesite, dolomite and quartz were measured.•The interfacial interaction energy determining aggregation agrees with experimental results.
Nanostructured Cu–Ta alloys have shown promise as high-strength nanocrystalline materials in part due to their limited grain growth at high temperatures. In the present study, Cu–Ta alloy powders, ...synthesized via high-energy cryogenic mechanical alloying, were consolidated into bulk nanostructured specimens using equal channel angular extrusion (ECAE) at high temperatures. Subsequent microstructure characterization indicated full consolidation, which resulted in an equiaxed grain structure for the Cu matrix along with the formation of fine Ta precipitates, the size distributions of which varied both with composition and processing temperature. Microhardness, compression and shear punch testing indicated, in some cases, an almost threefold increase in mechanical properties above that predicted by Hall–Petch estimates for pure nanocrystalline Cu. Stress relaxation tests substantiated the strain-hardening behavior and grain-size-dependent dislocation activity observed in the nanocrystalline Cu–Ta samples.
Prenylated indole derivatives are hybrid natural products containing both aromatic and isoprenoid moieties and are widely spread in plants, fungi and bacteria. Some of these complex natural products, ...e.g. the ergot alkaloids ergotamine and fumigaclavine C as well as the diketopiperazine derivative fumitremorgin C and its biosynthetic precursors tryprostatin A and B, show a wide range of biological and pharmacological activities. Prenyl transfer reactions catalysed by prenyltransferases represent key steps in the biosynthesis of these compounds and often result in formation of products which possess biological activities distinct from their non-prenylated precursors. Recently, a series of putative indole prenyltransferase genes could be identified in the genome sequences of different fungal strains including Aspergillus fumigatus. The gene products show significant sequence similarities to dimethylallyltryptophan synthases from fungi. We have cloned and overexpressed six of these genes, fgaPT1, fgaPT2, ftmPT1, ftmPT2, 7-dmats and cdpNPT from A. fumigatus in E. coli and S. cerevisiae. The overproduced enzymes were characterised biochemically. Three additional prenyltransferases, DmaW-Cs, TdiB and MaPT were identified and characterised in a Clavicipitalean fungus, Aspergillus nidulans and Malbranchea aurantiaca, respectively. Sequence analysis and alignments with known aromatic prenyltransferases as well as phylogenetic analysis revealed that these enzymes belong to a new group of "aromatic prenyltransferases". They differ clearly from membrane-bound aromatic prenyltransferases from different sources and soluble prenyltransferases from bacteria. The characterised enzymes are soluble proteins, catalyse different prenyl transfer reactions on indole moieties of various substrates and do not require divalent metal ions for their enzymatic reactions. All of the enzymes accepted only dimethylallyl diphosphate as prenyl donor. On the other hand, they showed broad substrate specificity towards their aromatic substrates. Diverse tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted by these enzymes, providing a new strategy for convenient production of biologically active substances, e.g. by chemoenzymatic synthesis.
The local structure of NaTiSi_{2}O_{6} is examined across its Ti-dimerization orbital-assisted Peierls transition at 210 K. An atomic pair distribution function approach evidences local symmetry ...breaking preexisting far above the transition. The analysis unravels that, on warming, the dimers evolve into a short range orbital degeneracy lifted (ODL) state of dual orbital character, persisting up to at least 490 K. The ODL state is correlated over the length scale spanning ∼6 sites of the Ti zigzag chains. Results imply that the ODL phenomenology extends to strongly correlated electron systems.
Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, ...BrS was linked to mutations in the
, which encodes for the cardiac Na
channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na
, K
, Ca
, and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, pre-clinical, and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening VT/VF. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers.
PDF
