The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946

Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.     

Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand

In a variety of cells, the Ca2+ signalling process is mediated by the endoplasmic-reticulum-membrane-associated Ca2+ release channel, inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R). Being ubiquitous and present in organisms ranging from humans to Caenorhabditis elegans, InsP3R has a vital role in the control of cellular and physiological processes as diverse as cell division, cell proliferation, apoptosis, fertilization, development, behaviour, memory and learning. Mouse type I InsP3R (InsP3R1), found in high abundance in cerebellar Purkinje cells, is a polypeptide with three major functionally distinct regions: the amino-terminal InsP3-binding region, the central modulatory region and the carboxy-terminal channel region. Here we present a 2.2-A crystal structure of the InsP3-binding core of mouse InsP3R1 in complex with InsP3. The asymmetric, boomerang-like structure consists of an N-terminal beta-trefoil domain and a C-terminal alpha-helical domain containing an 'armadillo repeat'-like fold. The cleft formed by the two domains exposes a cluster of arginine and lysine residues that coordinate the three phosphoryl groups of InsP3. Putative Ca2+-binding sites are identified in two separate locations within the InsP3-binding core.     

Partial sequence of the tyrosine region of neocarzinostatin

Zusammenfassung Das antitumoraktive Protein-Antibiotikum Neocarzinostatin wurde mit Dithiothreit in flüssigem Ammoniak reduziert und mit Chloressigsäure alkyliert. Tryptische Spaltung des tetra-S-carboxymethylierten Proteins ergab 5 Fragmente. Die Sequenz von 25 Aminosäureresten im tyrosinhaltigen Fragment H₃ wurde durchEdman-Abbau im automatisierten Sequenator ermittelt.

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This work was supported in part by Public Health Service Research Grants No. C-6516 from the National Cancer Institute and No. FR-05526 from the Division of Research Facilities and Resource, National Institutes of Health, to the Children's Cancer Research Foundation and by grants No. AM 04501 and No. AM 11794 from the National Institute of Arthritis and Metabolic Diseases to the Endocrine Unit, Massachusetts General Hospital.     

Restoration of the poor oxygen transport function of ACD-stored blood by pyridoxal 5'-phosphate.

Pyridoxal 5'-phosphate is easily incorporated into ACD-stored erythrocytes without decrease of ATP, and restores the poor oxygen transport function with a similar effect to 2,3'-diphosphoglycerate.     

A negative association of HLA-BW52 with Graves' disease and insulin-dependent diabetes mellitus with juvenile onset among Japanese population

Summary The present study demonstrated that a decreased frequency of HLA-BW52 was a common characteristic shared by the patients with Graves' disease and insulin-dependent diabetes mellitus with juvenile onset among Japanese.     

预蠕变损伤对高温疲劳宏观裂纹扩展的影响

针对ＳＵＳ３０４不锈钢光滑试棒预先导入１０７３ Ｋ·ｃｐ－ｔｙｐｅ条件下的预蠕变疲劳损伤，然后开小切口进行时间依存性 ９２３ Ｋ·ｃｐ－ｔｙｐｅ，１０７３ Ｋ·ｃｐ－ｔｙｐｅ及循环数依存性９２３ Ｋ·ｐｐ－ｔｙｐｅ的宏观裂纹扩展试验，考察了试棒内部因预蠕变疲劳而产生的大量的粒界微小裂纹对高温疲劳宏观裂纹扩展的影响．结果如下： １．预损伤加速了９２３ Ｋ·ｃｐ－ｔｙｐｅ下的蠕变裂纹扩展，对于同一蠕变Ｊ积分范围△Ｊｃ，损伤值越大，裂纹扩展速度ｄｌ／ｄＮ也越大．这种加速起因于主裂纹与微小裂纹的合体． ２．１０７３ Ｋ·ｃｐ－ｔｙｐｅ下的预损伤材料和处女材料的ｄｌ／ｄＮ在同一△Ｊｃ。下相等．即，损伤材料的裂纹扩展速度的上限值由１０７３ Ｋ·ｃｐ－ｔｙｐｅ下的处女材料的ｄｌ／ｄＮ－△Ｊｃ关系给出． ３．在９２３ Ｋ·ｐｐ－ｔｙｐｅ条件下，对于同一疲劳Ｊ积分范围△Ｊｆ，预损伤材料的ｄｌ／ｄＮ要比处女材料快１０倍左右．一般ｐｐ－ｔｙｐｅ的破坏形式为粒内破坏．预损伤材料的场合，因为试棒内部分布有大量的微小粒界裂纹，主裂纹便沿这些破坏阻抗最小的微小裂纹边合体边扩展，主要在粒界上扩展．即微小粒界裂纹是裂纹扩展阻抗减小的主因．     

The effects of microinjection of carbachol or hemicholinium into the amygdala on the levels of plasma and adrenal corticosterone in rats

Summary Microinjection of 0.4 g of carbachol into the amygdala caused a rise of corticosterone (CS) in the morning, when the prestimulating level of CS was lower. But the same procedure with a larger dose had no effect in the afternoon, when the prestimulating level of CS was higher.     

Rab44, a novel large Rab GTPase,negatively regulates osteoclast differentiation by modulating intracellular calcium levels followed by NFATc1 activation

Rab44 is an atypical Rab GTPase that contains some additional domains such as the EF-hand and coiled-coil domains as well as Rab-GTPase domain. Although Rab44 genes have been found in mammalian genomes, no studies concerning Rab44 have been reported yet. Here, we identified Rab44 as an upregulated protein during osteoclast differentiation. Knockdown of Rab44 by small interfering RNA promotes RANKL-induced osteoclast differentiation of the murine monocytic cell line, RAW-D or of bone marrow-derived macrophages (BMMs). In contrast, overexpression of Rab44 prevents osteoclast differentiation. Rab44 was localized in the Golgi complex and lysosomes, and Rab44 overexpression caused an enlargement of early endosomes. A series of deletion mutant studies of Rab44 showed that the coiled-coil domain and lipidation sites of Rab44 is important for regulation of osteoclast differentiation. Mechanistically, Rab44 affects nuclear factor of activated T-cells c1 (NFATc1) signaling in RANKL-stimulated macrophages. Moreover, Rab44 depletion caused an elevation in intracellular Ca²⁺ transients upon RANKL stimulation, and particularly regulated lysosomal Ca²⁺ influx. Taken together, these results suggest that Rab44 negatively regulates osteoclast differentiation by modulating intracellular Ca²⁺ levels followed by NFATc1 activation.     

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.