Detailed α-decay study of 180Tl

International audienceA detailed $\alpha$-decay spectroscopy study of $^{180}\mathrm{Tl}$ has been performed at ISOLDE (CERN). $Z$-selective ionization by the Resonance Ionization Laser Ion Source (RILIS) coupled to mass separation provided a high-purity beam of $^{180}\mathrm{Tl}$. Fine-structure $\alpha$ decays to excited levels in the daughter $^{176}\mathrm{Au}$ were identified and an $\alpha$-decay scheme of $^{180}\mathrm{Tl}$ was constructed based on an analysis of $\alpha$-$\gamma$ and $\alpha$-$\gamma$-$\gamma$ coincidences. Multipolarities of several $\gamma$-ray transitions deexciting levels in $^{176}\mathrm{Au}$ were determined. Based on the analysis of reduced $\alpha$-decay widths, it was found that all $\alpha$ decays are hindered, which signifies a change of configuration between the parent and all daughter states

Combining Path Integration and Remembered Landmarks When Navigating without Vision

This study investigated the interaction between remembered landmark and path integration strategies for estimating current location when walking in an environment without vision. We asked whether observers navigating without vision only rely on path integration information to judge their location, or whether remembered landmarks also influence judgments. Participants estimated their location in a hallway after viewing a target (remembered landmark cue) and then walking blindfolded to the same or a conflicting location (path integration cue). We found that participants averaged remembered landmark and path integration information when they judged that both sources provided congruent information about location, which resulted in more precise estimates compared to estimates made with only path integration. In conclusion, humans integrate remembered landmarks and path integration in a gated fashion, dependent on the congruency of the information. Humans can flexibly combine information about remembered landmarks with path integration cues while navigating without visual information.National Institutes of Health (U.S.) (Grant T32 HD007151)National Institutes of Health (U.S.) (Grant T32 EY07133)National Institutes of Health (U.S.) (Grant F32EY019622)National Institutes of Health (U.S.) (Grant EY02857)National Institutes of Health (U.S.) (Grant EY017835-01)National Institutes of Health (U.S.) (Grant EY015616-03)United States. Department of Education (H133A011903

A Novel Animal Model of Borrelia recurrentis Louse-Borne Relapsing Fever Borreliosis Using Immunodeficient Mice

Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primates (i.e., not in other laboratory or domestic animals). Here, we present the first non-primate animal model of LBRF, using SCID (-B, -T cells) and SCID BEIGE (-B, -T, -NK cells) immunocompromised mice. These animals were infected with B. recurrentis A11 or A17, or with B. duttonii 1120K3 as controls. B. recurrentis caused a relatively mild but persistent infection in SCID and SCID BEIGE mice, but did not proliferate in NUDE (-T) and BALB/c (wild-type) mice. B. duttonii was infectious but not lethal in all animals. These findings demonstrate that the immune response can limit relapsing fever even in the absence of humoral defense mechanisms. To study the significance of phagocytic cells in this context, we induced systemic depletion of such cells in the experimental mice by injecting them with clodronate liposomes, which resulted in uncontrolled B. duttonii growth and a one-hundred-fold increase in B. recurrentis titers in blood. This observation highlights the role of macrophages and other phagocytes in controlling relapsing fever infection. B. recurrentis evolved from B. duttonii to become a primate-specific pathogen that has lost the ability to infect immunocompetent rodents, probably through genetic degeneration. Here, we describe a novel animal model of B. recurrentis based on B- and T-cell-deficient mice, which we believe will be very valuable in future research on LBRF. Our study also reveals the importance of B-cells and phagocytes in controlling relapsing fever infection

Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G>A and c.707T>C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dop

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

Decay studies of the long-lived states in Tl-186

Decay spectroscopy of the long-lived states in Tl-186 has been performed at the ISOLDE Decay Station at ISOLDE, CERN. The a decay from the low-spin (2(-)) state in Tl-186 was observed for the first time and a half-life of 3.4(-0.)(4)(+0.5) s was determined. Based on the alpha-decay energy, the relative positions of the long-lived states were fixed, with the (2(-)) state as the ground state, the 7((+)) state at 77(56) keV, and the 10((-)) state at 451(56) keV. The level scheme of the internal decay of the Tl-186(10((-))) state [T-1/2 = 3.40(9) s], which was known to decay solely through emission of 374-keV gamma-ray transition, was extended and a lower limit for the beta-decay branching b(beta) > 5.9(3)% was determined. The extracted retardation factors for the gamma decay of the 10((-) )state were compared to the available data in neighboring odd-odd thallium isotopes indicating the importance of the pi d(3/2) shell in the isomeric decay and significant structure differences between Tl-184 and Tl-186.Peer reviewe

South Atlantic paleobathymetry since early Cretaceous

We present early Cretaceous to present paleobathymetric reconstructions and quantitative uncertainty estimates for the South Atlantic, offering a strong basis for studies of paleocirculation, paleoclimate and paleobiogeography. Circulation in an initially salty and anoxic ocean, restricted by the topography of the Falkland Plateau, Rio Grande Ridge and Walvis Rise, favoured deposition of thick evaporites in shallow water of the Brazilian-Angolan margins. This ceased as sea oor spreading propagated northwards, opening an equatorial gateway to shallow and intermediate circulation. This gateway, together with subsiding volcano-tectonic barriers would have played a key role in Late Cretaceous climate changes. Later deepening and widening of the South Atlantic, together with gateway opening at Drake Passage would lead, by mid-Miocene (∼15 Ma) to the establishment of modern-style thermohaline circulation

Transcriptional Silencing of the Wnt-Antagonist DKK1 by Promoter Methylation Is Associated with Enhanced Wnt Signaling in Advanced Multiple Myeloma

The Wnt/β-catenin pathway plays a crucial role in the pathogenesis of various human cancers. In multiple myeloma (MM), aberrant auto-and/or paracrine activation of canonical Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation. Since DKK1 itself is a target of TCF/β-catenin mediated transcription, these findings suggest that DKK1 is part of a negative feedback loop in MM and may act as a tumor suppressor. In line with this hypothesis, we show here that DKK1 expression is low or undetectable in a subset of patients with advanced MM as well as in MM cell lines. This absence of DKK1 is correlated with enhanced Wnt pathway activation, evidenced by nuclear accumulation of β-catenin, which in turn can be antagonized by restoring DKK1 expression. Analysis of the DKK1 promoter revealed CpG island methylation in several MM cell lines as well as in MM cells from patients with advanced MM. Moreover, demethylation of the DKK1 promoter restores DKK1 expression, which results in inhibition of β-catenin/TCF-mediated gene transcription in MM lines. Taken together, our data identify aberrant methylation of the DKK1 promoter as a cause of DKK1 silencing in advanced stage MM, which may play an important role in the progression of MM by unleashing Wnt signaling