The present white paper is submitted as part of the "Snowmass" process to help inform the long-term plans of the United States Department of Energy and the National Science Foundation for high-energy ...physics. It summarizes the science questions driving the Ultra-High-Energy Cosmic-Ray (UHECR) community and provides recommendations on the strategy to answer them in the next two decades.
The processing, intracellular transport, and endocytosis of the GM2 activator protein (GM2AP), an essential cofactor of beta-hexosaminidase A for the degradation of ganglioside GM2, was investigated ...in human epidermal keratinocytes. The GM2AP precursor is synthesized as an 18-kDa peptide, which is singly glycosylated, resulting in 22-kDa high mannose and 24-27-kDa complex glycoforms. A small portion of the 22-kDa form bears phosphomannosyl residues. About 30% of the GM2AP precursor is secreted during 12 h after synthesis, consisting almost exclusively of complex glycoforms. In a post-Golgi compartment, the intracellular remainder is converted to a 20-kDa mature form within 24 h, bearing a heavily trimmed N-glycan on a 17-kDa backbone. Interestingly, even nonglycosylated GM2AP is delivered to the lysosome, as shown by tunicamycin treatment and subcellular fractionation. Also, its endocytosis is independent of carbohydrate-linked signals and is even more effective for nonglycosylated GM2AP. We conclude that a mannose-6-phosphate-independent pathway for the lysosomal delivery of GM2AP exists in cultured human keratinocytes.
The extent of the pulmonary reaction to intensive exposure to dust is influenced by a number of factors, in particular the nature of the fibre, morphometry, solubility, duration of dust exposure, ...dust concentration, and, finally, the manufacturing process of the MMMF product and its chemical composition. The biological effect of the fibres on the lung is manifest by enhanced infiltration by macrophages and an increase in the number of neutrophils. In agreement with numerous published results, our own investigations failed to reveal any signs of a fibrogenic effect of MMMF. The reason for this is presumably the lack of biostability, the tendency of the fibres to fracture crosswise, and the much lower concentration of fibres in the critical length-diameter range. In contrast, MMMF have been shown to induce an irritation of the mucosa and the upper airways. With respect to possible long-term damage produced by MMMF from our own production, we have had no such experience to date.
This is a case report on a 66-year old woman who suffered from chronic polyarthritis for 15 years and developed a sicca syndrome pattern for 2 years. 2 years later epithelioid cell granulomas were ...found from a submandibular lymph node as well as from a suspicious area at the epiglottis and the mucosa of the upper lip. Moreover, there was a chronic keratoconjunctivitis and discrete lung involvement. The sarcoidosis on the lip and at the epiglottis disappeared, and lung involvement and conjunctivitis improved under corticosteroid therapy. In spite of above therapy, the sicca syndrome pattern and the rheumatic complaints (osteoporosis) persisted.
The carbene precursor 3-azi-1-(6-3H-2-acetamido-2-deoxy-1-β-D-galactopyranosyl)thio-butane (also designated 3H-1-ATB-GalNAc) has been used as a photoaffinity label for human lysosomal ...β-hexosaminidase B (Hex B, EC 3.2.1.52) purified to apparent homogeneity from postmortal liver. 3H-1-ATB-GalNAc behaved as an active site-directed inhibitor, which bound covalently to Hex B upon photolysis at 350 nm and resulted in 15% inactivation of enzyme activity. Up to 75% of the inactivation of Hex B was prevented by including the competitive inhibitor 2-acetamido-2-deoxy-D-glucono-1,5-lactone in the photoaffinity experiment. Incubation of 3H-1-ATB-GalNAc with the enzyme followed by irradiation and subsequent separation of the three polypeptides composing the β-subunit led mainly to labeling of the βa-polypeptide. Subsequent proteolysis of βa with trypsin and separation of the resulting peptides by high pressure liquid chromatography yielded one prominently labeled peptide fraction. Edman degradation resulted in the sequence E339ISEVFPDQFIHLGGDEVEFK359. However, no modified amino acid was detected, indicating that the photoaffinity label was presumably bound to the peptide by a labile ester linkage. This was proven when the radiolabel was almost completely released from the peptide by treatment with aqueous ammonium hydroxide. Simultaneously, Glu-355 was converted into Gln-355, which is located within a region of Hex B that shows considerable homology with the α-subunit of human hexosaminidase A and other hexosaminidases from various species.
A fourth of the global seabed sediment volume is buried at depths where temperatures exceed 80 °C, a previously proposed thermal barrier for life in the subsurface. Here, we demonstrate, utilizing an ...extensive suite of radiotracer experiments, the prevalence of active methanogenic and sulfate-reducing populations in deeply buried marine sediment from the Nankai Trough subduction zone, heated to extreme temperature (up to ~120 °C). The small microbial community subsisted with high potential cell-specific rates of energy metabolism, which approach the rates of active surface sediments and laboratory cultures. Our discovery is in stark contrast to the extremely low metabolic rates otherwise observed in the deep subseafloor. As cells appear to invest most of their energy to repair thermal cell damage in the hot sediment, they are forced to balance delicately between subsistence near the upper temperature limit for life and a rich supply of substrates and energy from thermally driven reactions of the sedimentary organic matter.
PDF
