Novel insights into the transport mechanism of the human amino acid transporter LAT1 (SLC7A5) : probing critical residues for substrate translocation

BACKGROUND: LAT1 (SLC7A5) is the transport competent unit of the heterodimer formed with the glycoprotein CD98 (SLC3A2). It catalyzes antiport of His and some neutral amino acids such as Ile, Leu, Val, Cys, Met, Gln and Phe thus being involved in amino acid metabolism. Interestingly, LAT1 is over-expressed in many human cancers that are characterized by increased demand of amino acids. Therefore LAT1 was recently acknowledged as a novel target for cancer therapy. However, knowledge on molecular mechanism of LAT1 transport is still scarce. METHODS: Combined approaches of bioinformatics, site-directed mutagenesis, chemical modification, and transport assay in proteoliposomes, have been adopted to unravel dark sides of human LAT1 structure/function relationships. RESULTS: It has been demonstrated that residues F252, S342, C335 are crucial for substrate recognition and C407 plays a minor role. C335 and C407 cannot be targeted by SH reagents. The transporter has a preferential dimeric structure and catalyzes an antiport reaction which follows a simultaneous random mechanism. CONCLUSIONS: Critical residues of the substrate binding site of LAT1 have been probed. This site is not freely accessible by molecules other than substrate. Similarly to LeuT, K+ has some regulatory properties on LAT1. GENERAL SIGNIFICANCE: The collected data represent a solid basis for deciphering molecular mechanism underlying LAT1 function

The association between water kilomasers and compact radio sources in the starburst galaxy NGC2146

We report the detection of 22 GHz water vapor emission toward the starburst galaxy NGC2146, made using the Effelsberg 100-m telescope. Interferometric observations with the Very Large Array (VLA) show that a part of the emission originates from two prominent sites of star formation that are associated with compact radio continuum sources, likely ultra-compact HII regions. It is concluded that the emission arises from the most luminous and distant water `kilomasers' detected so far. Our data increase the number of water maser detections in northern galaxies (Dec > -30 deg) with 100 micron IRAS point source fluxes > 50 Jy to 18%.Comment: 4 pages including 3 figures, accepted for publication in A&A Lette

Summary of the Very Large Hadron Collider Physics and Detector Workshop

One of the options for an accelerator beyond the LHC is a hadron collider with higher energy. Work is going on to explore accelerator technologies that would make such a machine feasible. This workshop concentrated on the physics and detector issues associated with a hadron collider with an energy in the center of mass of the order of 100 to 200 TeV

SLC1A5 (solute carrier family 1 (neutral amino acid transporter), member 5)

Review on human SLC1A5, with data on DNA/RNA, on the protein encoded and pathological and physiological implications

The Agile Alert System For Gamma-Ray Transients

In recent years, a new generation of space missions offered great opportunities of discovery in high-energy astrophysics. In this article we focus on the scientific operations of the Gamma-Ray Imaging Detector (GRID) onboard the AGILE space mission. The AGILE-GRID, sensitive in the energy range of 30 MeV-30 GeV, has detected many gamma-ray transients of galactic and extragalactic origins. This work presents the AGILE innovative approach to fast gamma-ray transient detection, which is a challenging task and a crucial part of the AGILE scientific program. The goals are to describe: (1) the AGILE Gamma-Ray Alert System, (2) a new algorithm for blind search identification of transients within a short processing time, (3) the AGILE procedure for gamma-ray transient alert management, and (4) the likelihood of ratio tests that are necessary to evaluate the post-trial statistical significance of the results. Special algorithms and an optimized sequence of tasks are necessary to reach our goal. Data are automatically analyzed at every orbital downlink by an alert pipeline operating on different timescales. As proper flux thresholds are exceeded, alerts are automatically generated and sent as SMS messages to cellular telephones, e-mails, and push notifications of an application for smartphones and tablets. These alerts are crosschecked with the results of two pipelines, and a manual analysis is performed. Being a small scientific-class mission, AGILE is characterized by optimization of both scientific analysis and ground-segment resources. The system is capable of generating alerts within two to three hours of a data downlink, an unprecedented reaction time in gamma-ray astrophysics.Comment: 34 pages, 9 figures, 5 table

Heavy Quark Parton Distributions: Mass-Dependent or Mass-Independent Evolution?

In a consistently formulated pQCD framework incorporating non-zero mass heavy quark partons, there is still the freedom to define parton distributions obeying either mass-independent or mass-dependent evolution equations, contrary to statements made in a recent paper by MRRS. With properly matched hard cross-sections, different choices merely correspond to different factorization schemes, and they yield the same physical cross-sections. We demonstrate this principle in a concrete order \alpha_s calculation of the DIS charm structure function. We also examine the proper matching between parton definitions and subtractions in the hard cross-section near threshold where the calculation is particularly sensitive to mass effects of the heavy quark. The results obtained from the general-mass formalism are quite stable against different choices of scale and exhibit a smooth transition in the threshold region (using either mass-independent or mass-dependent evolution), in contrast to results of another recently proposed scheme.Comment: 6 pages, LaTeX, 4 PostScript figures, uses epsf.sty and aipproc.sty; Contribution to DIS97 Workshop, 14-18 April, Chicago, IL, US

Species at Risk (SPEAR) index indicates effects of insecticides on stream invertebrate communities in soy production regions of the Argentine Pampas

We investigated relationships among insecticides and aquatic invertebrate communities in 22 streams of two soy production regions of the Argentine Pampas over three growing seasons. Chlorpyrifos, endosulfan, cypermethrin, and lambda-cyhalothrin were the insecticides most frequently detected in stream sediments. The Species at Risk (SPEAR) pesticide bioassessment index (SPEARpesticides) was adapted and applied to evaluate relationships between sediment insecticide toxic units (TUs) and invertebrate communities associated with both benthic habitats and emergent vegetation habitats. SPEARpesticides was the only response metric that was significantly correlated with total insecticide TU values for all three averaged data sets, consistently showing a trend of decreasing values with increasing TU values (r2 = 0.35 to 0.42, p-value = 0.001 to 0.03). Although pyrethroids were the insecticides that contributed the highest TU values, toxicity calculated based on all insecticides was better at predicting changes in invertebrate communities than toxicity of pyrethroids alone. Crustaceans, particularly the amphipod Hyalella spp., which are relatively sensitive to pesticides, played a large role in the performance of SPEARpesticides, and the relative abundance of all crustaceans also showed a significant decreasing trend with increasing insecticide TUs for two of three data sets (r2 = 0.30 to 0.57, p-value = 0.003 to 0.04) examined. For all data sets, total insecticide TU was the most important variable in explaining variance in the SPEARpesticides index. The present study was the first application of the SPEAR index in South America, and the first one to use it to evaluate effects of pesticides on invertebrate communities associated with aquatic vegetation. Although the SPEAR index was developed in Europe, it performed well in the Argentine Pampas with only minor modifications, and would likely improve in performance as more data are obtained on traits of South American taxa, such as pesticide sensitivity and generation time.Instituto de Limnología "Dr. Raúl A. Ringuelet