The structural basis for autonomous dimerization of the pre-T-cell antigen receptor

The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR β-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent αβ T-cell lineage differentiation. Whereas αβTCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant α-chain (pre-Tα) that pairs with any TCR β-chain (TCRβ) following successful TCR β-gene rearrangement. Here we provide the basis of pre-Tα-TCRβ assembly and pre-TCR dimerization. The pre-Tα chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR α-chain; nevertheless, the mode of association between pre-Tα and TCRβ mirrored that mediated by the Cα-Cβ domains of the αβTCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-Tα domain to interact with the variable (V) β domain through residues that are highly conserved across the Vβ and joining (J) β gene families, thus mimicking the interactions at the core of the αβTCR's Vα-Vβ interface. Disruption of this pre-Tα-Vβ dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-Tα chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR β-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-Tα represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex.     

Hydrometallurgical application for treating a Nigerian chalcopyrite ore in chloride medium: Part I. Dissolution kinetics assessment

The dissolution kinetics of a Nigerian chalcopyrite ore in hydrochloric acid was studied in this article. Acid concentration, reaction temperature, and ore particle size were chosen as experimental parameters. The chemical and morphological studies of the ore before and after leaching at optimal conditions were carried out by X-ray diffraction (XRD) and scanning electron microscopy (SEM). It is revealed that increasing the acid concentration and system temperature and decreasing the ore particle size greatly enhances the dissolution rate. The dissolution kinetics was found to follow the shrinking core model for the diffusion control mechanism where the activation energy (E_a) of 32.92 kJ·mol?1 was obtained for the process and supported by morphological changes at a higher dissolution of 91.33%.     

Short Report： Cyclic patterns of incidence rate for skin malignant melanoma： association with heliogeophysical activity

Background： Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma （SMM; ICD9, Dx： 172） in the Czech Republic （period T=7.50～7.63 years）, UK （T= 11.00 years） and Bulgaria （T= 12.20 years）. Incidences com- pared with the sunspot index Rz （lag-period dT=＋2, ＋4, ＋6, ＋ 10 or ＋ 12 years） have indicated that maximal rates are most likely to appear on descending slopes of the ;ll-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity （HGA） components exhibiting similar cyclicity. Methods： Annual incidences of SMM from 5 countries （Czech Republic, UK, Bulgaria, USA and Canada） over various time spans during the years 1964-1992 were analyzed and their correlations with cyclic Rz （sunspot number） and aa （planetary geomagnetic activity） indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. Results： Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA （T=8.63 years, P〈0.05） and Canada （Ontario, T=9.91 years, P〈0.10）. Also, various ＇hypercycles＇ were established （T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively） describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz （dT=＋6 and ＋7 years, respectively） and aa （dT=-10 and ＋9 years, respectively） was described. Possible interactions of cyclic non-photic influences （UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations） with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. Conclusion： The above findings on cyclicity and temporal assoc     

Lateral presynaptic inhibition mediates gain control in an olfactory circuit

Olfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Crosstalk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odour responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively removed most interglomerular input to genetically identified second-order olfactory neurons. Here we show that this broadens the odour tuning of these neurons, implying that interglomerular inhibition dominates over interglomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this interglomerular inhibition acts at a presynaptic locus, and our results imply that this is mediated by both ionotropic and metabotropic receptors on the same nerve terminal.     

A role for VEGF as a negative regulator of pericyte function and vessel maturation

Angiogenesis does not only depend on endothelial cell invasion and proliferation: it also requires pericyte coverage of vascular sprouts for vessel stabilization. These processes are coordinated by vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) through their cognate receptors on endothelial cells and vascular smooth muscle cells (VSMCs), respectively. PDGF induces neovascularization by priming VSMCs/pericytes to release pro-angiogenic mediators. Although VEGF directly stimulates endothelial cell proliferation and migration, its role in pericyte biology is less clear. Here we define a role for VEGF as an inhibitor of neovascularization on the basis of its capacity to disrupt VSMC function. Specifically, under conditions of PDGF-mediated angiogenesis, VEGF ablates pericyte coverage of nascent vascular sprouts, leading to vessel destabilization. At the molecular level, VEGF-mediated activation of VEGF-R2 suppresses PDGF-Rbeta signalling in VSMCs through the assembly of a previously undescribed receptor complex consisting of PDGF-Rbeta and VEGF-R2. Inhibition of VEGF-R2 not only prevents assembly of this receptor complex but also restores angiogenesis in tissues exposed to both VEGF and PDGF. Finally, genetic deletion of tumour cell VEGF disrupts PDGF-Rbeta/VEGF-R2 complex formation and increases tumour vessel maturation. These findings underscore the importance of VSMCs/pericytes in neovascularization and reveal a dichotomous role for VEGF and VEGF-R2 signalling as both a promoter of endothelial cell function and a negative regulator of VSMCs and vessel maturation.     

A GaAs polariton light-emitting diode operating near room temperature

The increasing ability to control light-matter interactions at the nanometre scale has improved the performance of semiconductor lasers in the past decade. The ultimate optimization is realized in semiconductor microcavities, in which strong coupling between quantum-well excitons and cavity photons gives rise to hybrid half-light/half-matter polariton quasiparticles. The unique properties of polaritons-such as stimulated scattering, parametric amplification, lasing, condensation and superfluidity-are believed to provide the basis for a new generation of polariton emitters and semiconductor lasers. Until now, polariton lasing and nonlinearities have only been demonstrated in optical experiments, which have shown the potential to reduce lasing thresholds by two orders of magnitude compared to conventional semiconductor lasers. Here we report an experimental realization of an electrically pumped semiconductor polariton light-emitting device, which emits directly from polariton states at a temperature of 235 K. Polariton electroluminescence data reveal characteristic anticrossing between exciton and cavity modes, a clear signature of the strong coupling regime. These findings represent a substantial step towards the realization of ultra-efficient polaritonic devices with unprecedented characteristics.     

Isolation of cDNA clones encoding T cell-specific membrane-associated proteins

Of 10 distinct cloned DNA copies of mRNAs expressed in T lymphocytes but not in B lymphocytes and associated with membrane-bound polysomes, one hybridizes to a region of the genome that has rearranged in a T-cell lymphoma and several T-cell hybridomas. These characteristics suggest that it encodes one chain of the elusive antigen receptor on the surface of T lymphocytes.     

无机膜应用于废润滑油再生

废润滑油污染对环境的潜在危害正日益显现,传统的废润滑油再生方法产生大量的酸性淤泥,造成二次污染,故提出膜分离应用于废润滑油再生的新思路,根据废油的特点来选取合适的膜来处理废润滑油,并利用降低油液黏度和压力膜过程来提高膜的渗透通量,使膜的渗透通量明显增加.