Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation

Rab GTPases control membrane identity, fusion, and transport by interaction with effector proteins. Effectors that influence the activation/inactivation cycle of their own or other Rabs contribute to the timely conversion of Rab identities. Rab5 and its effector Rabaptin5 are generally considered the prime example for a positive feedback loop in which Rab5·GTP recruits Rabaptin5 complexed to Rabex5, the GDP/GTP exchange factor of Rab5, to early endosomes, thus maintaining the membrane's Rab5 identity. By deletion analysis, we found membrane recruitment of Rabaptin5 to require binding to Rab4 and Rabex5, but not Rab5. Deletion of either one of two Rab5 binding domains or silencing of Rab5 expression did not affect Rabaptin5 recruitment, but produced giant endosomes with early and late endosomal characteristics. The results contradict feedback activation of Rab5 and instead indicate that Rabaptin5 is recruited by Rabex5 recognizing ubiquitinated cargo and by Rab4 to activate Rab5 in a feed-forward manner

Multiphoton Transitions in a Spin System Driven by Strong Bichromatic Field

EPR transient nutation spectroscopy is used to measure the effective field (Rabi frequency) for multiphoton transitions in a two-level spin system bichromatically driven by a transverse microwave (MW) field and a longitudinal radio-frequency (RF) field. The behavior of the effective field amplitude is examined in the case of a relatively strong MW field, when the derivation of the effective Hamiltonian cannot be reduced to first-order perturbation theory in w_{1} / w_{rf} (w_{1} is the microwave Rabi frequency, w_{rf} is the RF frequency). Experimental results are consistently interpreted by taking into account the contributions of second and third order in w_{1} / w_{rf} evaluated by Krylov-Bogolyubov-Mitropolsky averaging. In the case of inhomogeneously broadened EPR line, the third-order correction modifies the nutation frequency, while the second-order correction gives rise to a change in the nutation amplitude due to a Bloch-Siegert shift.Comment: 7 pages, 6 figure

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD

Regulating Assisted Reproduction in Canada, Switzerland, and the USA: Comparing the Judicialization of Policy-making

This article analyses the extent to which courts shape policies for assisted reproduction. While the USA is considered to be the most litigious country, Canada has observed a growing involvement of the courts from the 1980’s onward, and Switzerland is characterized by a modest degree of judicialization. Based on national patterns, we would expect litigation and court impact to vary across these three countries. As this paper demonstrates, policy-process specific variables such as the structure of policy conflicts, the novelty of regulation, self-regulation by key stakeholders, and the policies in place better explain the variation in the judicialization of policy-making

hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33

The completion of the Human Genome Project resulted in discovery of many unknown novel genes. This feat paved the way for the future development of novel therapeutics for the treatment of human disease based on novel biological functions and pathways. Towards this aim, we undertook a bioinformatics analysis of in-house microarray data derived from purified hematopoietic stem cell populations. This effort led to the discovery of HSS1 (Hematopoietic Signal peptide-containing Secreted 1) and its splice variant HSM1 (Hematopoietic Signal peptide-containing Membrane domain-containing 1). HSS1 gene is evolutionarily conserved across species, phyla and even kingdoms, including mammals, invertebrates and plants. Structural analysis showed no homology between HSS1 and known proteins or known protein domains, indicating that it was a truly novel protein. Interestingly, the human HSS1 (hHSS1) gene is located at chromosome 19q13.33, a genomic region implicated in various cancers, including malignant glioma. Stable expression of hHSS1 in glioma-derived A172 and U87 cell lines greatly reduced their proliferation rates compared to mock-transfected cells. hHSS1 expression significantly affected the malignant phenotype of U87 cells both in vitro and in vivo. Further, preliminary immunohistochemical analysis revealed an increase in hHSS1/HSM1 immunoreactivity in two out of four high-grade astrocytomas (glioblastoma multiforme, WHO IV) as compared to low expression in all four low-grade diffuse astrocytomas (WHO grade II). High-expression of hHSS1 in high-grade gliomas was further supported by microarray data, which indicated that mesenchymal subclass gliomas exclusively up-regulated hHSS1. Our data reveal that HSS1 is a truly novel protein defining a new class of secreted factors, and that it may have an important role in cancer, particularly glioma

Common Avian Infection Plagued the Tyrant Dinosaurs

Background: Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name 'Sue') has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids

A New Horned Crocodile from the Plio-Pleistocene Hominid Sites at Olduvai Gorge, Tanzania

BACKGROUND: The fossil record reveals surprising crocodile diversity in the Neogene of Africa, but relationships with their living relatives and the biogeographic origins of the modern African crocodylian fauna are poorly understood. A Plio-Pleistocene crocodile from Olduvai Gorge, Tanzania, represents a new extinct species and shows that high crocodylian diversity in Africa persisted after the Miocene. It had prominent triangular "horns" over the ears and a relatively deep snout, these resemble those of the recently extinct Malagasy crocodile Voay robustus, but the new species lacks features found among osteolaemines and shares derived similarities with living species of Crocodylus. METHODOLOGY/PRINCIPAL FINDINGS: The holotype consists of a partial skull and skeleton and was collected on the surface between two tuffs dated to approximately 1.84 million years (Ma), in the same interval near the type localities for the hominids Homo habilis and Australopithecus boisei. It was compared with previously-collected material from Olduvai Gorge referable to the same species. Phylogenetic analysis places the new form within or adjacent to crown Crocodylus. CONCLUSIONS/SIGNIFICANCE: The new crocodile species was the largest predator encountered by our ancestors at Olduvai Gorge, as indicated by hominid specimens preserving crocodile bite marks from these sites. The new species also reinforces the emerging view of high crocodylian diversity throughout the Neogene, and it represents one of the few extinct species referable to crown genus Crocodylus

The Weyl double copy from twistor space

The Weyl double copy is a procedure for relating exact solutions in biadjoint scalar, gauge and gravity theories, and relates fields in spacetime directly. Where this procedure comes from, and how general it is, have until recently remained mysterious. In this paper, we show how the current form and scope of the Weyl double copy can be derived from a certain procedure in twistor space. The new formalism shows that the Weyl double copy is more general than previously thought, applying in particular to gravity solutions with arbitrary Petrov types. We comment on how to obtain anti-self-dual as well as self-dual fields, and clarify some conceptual issues in the twistor approach

A new species of Argyromys (Rodentia, Mammalia) from the oligocene of the valley of lakes (Mongolia): its importance for palaeobiogeographical homogeneity across Mongolia, China and Kazakhstan

We describe a new species of Rodentia (Mammalia), Argyromys cicigei sp. nov. from Toglorhoi (fossil bed TGW-A/2a) in Mongolia and Ulantatal (fossil beds UTL 1 and UTL 7) in China. Its tooth morphology differs from the type species Argyromys aralensis from Akespe in Kazakhstan by smaller size and simpler structures. Argyromys has been assigned in different families of Muroidea, such as Tachyoryctoididae and Spalacidae. However, the presence of common characters indicates a closer relationship of Argyromys with the genera of Cricetidae s.l. (subfamilies Eucricetodontinae; Cricetopinae; Cricetodontinae and Gobicricetodontinae among others) from Asia than with the earliest representatives of Spalacidae or the endemic Tachyoryctoididae. Argyromys cicigei sp. nov. possesses a simple anterocone and anteroconid in the upper and lower first molars, respectively, which is characteristic for Cricetidae s.l. It has a flat occlusal surface in worn specimens; weakly-developed posterolophs; an oblique protolophule and metaloph on the upper molars and it lacks a labial anterolophid on the m1. These traits are also typical of the Oligocene genera Aralocricetodon and Plesiodipus, included in the subfamilies Cricetodontinae and Gobicricetodontinae respectively. The cladistic analysis performed here supports this hypothesis. The clade formed by Argyromys species is grouped with other cricetid taxa (s.l). Spalacids, however, form a different clade, as do the tachyoryctoids. Previous authors state that the Aral Formation (Kazakhstan) should be dated to the Oligocene instead of the Miocene, based on the presence of several taxa. The finds of Argyromys in both regions supports the statement that they are closer in age than previously thought. The occurrence of Argyromys in Kazakhstan, Mongolia and China evidences the biogeographic unity of the Central Asian bioprovince during the Oligocene