Meeting report: a hard look at the state of enamel research.

The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field

АДАПТАЦИОННЫЕ ВОЗМОЖНОСТИ, ФЕРТИЛЬНОСТЬ И ЖИЗНЕСПОСОБНОСТЬ ПОТОМСТВА САМОК КРЫС ПРИ РАЗЛИЧНОЙ ДЛИТЕЛЬНОСТИ ВОЗДЕЙСТВИЯ ЭТАНОЛА

The investigation was carried out on the white outbred female rats (n = 80) which were being under the influence of15 % solution of ethanol during pregnancy, from the first to the sixth months before its approach and on their viable posterity (n = 440). Anatomic, macro-microscopic and statistical methods of research were used. Two periods of increasing mortality in rats were revealed: the first fell on 1st month of the experiment (mortality reached 25 %) and the second - on 5th and 6th months of the experiment when this indicator rose up to 10 %. The rats' pregnancy duration was increased: the most considerable prolongation of pregnancy (for 5 days) was determined in the female rats which were under the ethanol influence within six months before its approach. The pre-implantation mortality was prevailed in structure of the general antenatal mortality. The highest rates of these indicators were noted in the rats under the ethanol only during pregnancy, and also within two and six months before its approach. The maximum post-implantation mortality was registered in the animals which were affected by alcohol throughout five months before pregnancy. The indicator of mortality of posterity in the early post-natal period reached 100 % in posterity of female rats under the ethanol within three months before pregnancy and for its duration.Работа выполнена на самках беспородных белых крыс (n = 80), находившихся под воздействием 15 %-го раствора этанола во время беременности, от одного до шести месяцев до ее наступления, и на их жизнеспособном потомстве (n = 440). Использованы анатомические, макромикроскопические и статистические методы исследования. Выявлено два периода повышения уровня смертности самок крыс: первый приходился на 1-й месяц эксперимента (смертность достигала 25 %) и второй - 5-й и 6-й месяцы эксперимента, когда этот показатель повышался до 10 %. У крыс наблюдалось увеличение длительности беременности: наиболее значительная пролонгация беременности (на 5 дней) выявилась у самок, находившихся под воздействием этанола в течение шести месяцев до ее наступления. В структуре общей внутриутробной смертности преобладала доимплантационная смертность, наиболее высокие показатели которой отмечались у крыс, получавших этанол только во время беременности, а также в течение двух и шести месяцев до ее наступления. Максимальная постимплантационная смертность регистрировалась у самок, подвергавшихся воздействию алкоголя на протяжении пяти месяцев до беременности. Показатель смертности потомства в раннем постнатальном периоде достигал 100 % у потомства самок, получавших этанол в течение трех месяцев до наступления беременности и на ее протяжении

Spectropolarimetry of R Coronae Borealis in 1998--2003: Discovery of Transient Polarization at Maximum Brightness

We present an extended optical spectropolarimetry of R CrB from 1998 January to 2003 September. The polarization was almost constant in the phase of maximum brightness, being consistent with past observations. We detected, however, temporal changes of polarization ($\sim 0.5$ %) in 2001 March and August, which were the first detection of large polarization variability in R CrB near maximum brightness. The amplitude and the position angle of the `transient polarization' were almost constant with wavelength in both two events. There was a difference by about 20 degrees in the position angle between the two events. Each event could be explained by light scattering due to short-lived dust puff occasionally ejected off the line of sight. The flatness of the polarization against the wavelength suggests that the scatterer is a mixture of dust grains having various sizes. The rapid growth and fading of the transient polarization favors the phenomenological model of dust formation near the stellar photosphere (e.g., within two stellar radii) proposed for the time evolution of brightness and chromospheric emission lines during deeply declining periods, although the fading timescale can hardly be explained by a simple dispersal of expanding dust puff with a velocity of $\sim 200-350$ km s $^{-1}$. Higher expansion velocity or some mechanism to destroy the dust grains should be needed.Comment: 22 pages, 10 figures, accepted for publication in A

In Vivo Binding and Retention of CD4-Specific DARPin 57.2 in Macaques

The recently described Designed Ankyrin Repeat Protein (DARPin) technology can produce highly selective ligands to a variety of biological targets at a low production cost.To investigate the in vivo use of DARPins for future application to novel anti-HIV strategies, we identified potent CD4-specific DARPins that recognize rhesus CD4 and followed the fate of intravenously injected CD4-specific DARPin 57.2 in rhesus macaques. The human CD4-specific DARPin 57.2 bound macaque CD4(+) cells and exhibited potent inhibitory activity against SIV infection in vitro. DARPin 57.2 or the control E3_5 DARPin was injected into rhesus macaques and the fate of cell-free and cell-bound CD4-specific DARPin was evaluated. DARPin-bound CD4(+) cells were detected in the peripheral blood as early as 30 minutes after the injection, decreasing within 6 hours and being almost undetectable within 24 hours. The amount of DARPin bound was dependent on the amount of DARPin injected. CD4-specific DARPin was also detected on CD4(+) cells in the lymph nodes within 30 minutes, which persisted with similar kinetics to blood. More extensive analysis using blood revealed that DARPin 57.2 bound to all CD4(+) cell types (T cells, monocytes, dendritic cells) in vivo and in vitro with the amount of binding directly proportional to the amount of CD4 on the cell surface. Cell-free DARPins were also detected in the plasma, but were rapidly cleared from circulation.We demonstrated that the CD4-specific DARPin can rapidly and selectively bind its target cells in vivo, warranting further studies on possible clinical use of the DARPin technology

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR

Simulation results for future measurements of electromagnetic proton form factors at \PANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel $\bar p p \to e^+ e^-$ is studied on the basis of two different but consistent procedures. The suppression of the main background channel, $\textit{i.e.}$ $\bar p p \to \pi^+ \pi^-$, is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance

Two HIV-1 Variants Resistant to Small Molecule CCR5 Inhibitors Differ in How They Use CCR5 for Entry

HIV-1 variants resistant to small molecule CCR5 inhibitors recognize the inhibitor-CCR5 complex, while also interacting with free CCR5. The most common genetic route to resistance involves sequence changes in the gp120 V3 region, a pathway followed when the primary isolate CC1/85 was cultured with the AD101 inhibitor in vitro, creating the CC101.19 resistant variant. However, the D1/86.16 escape mutant contains no V3 changes but has three substitutions in the gp41 fusion peptide. By using CCR5 point-mutants and gp120-targeting agents, we have investigated how infectious clonal viruses derived from the parental and both resistant isolates interact with CCR5. We conclude that the V3 sequence changes in CC101.19 cl.7 create a virus with an increased dependency on interactions with the CCR5 N-terminus. Elements of the CCR5 binding site associated with the V3 region and the CD4-induced (CD4i) epitope cluster in the gp120 bridging sheet are more exposed on the native Env complex of CC101.19 cl.7, which is sensitive to neutralization via these epitopes. However, D1/86.16 cl.23 does not have an increased dependency on the CCR5 N-terminus, and its CCR5 binding site has not become more exposed. How this virus interacts with the inhibitor-CCR5 complex remains to be understood

Feasibility studies of the time-like proton electromagnetic form factor measurements with PANDA at FAIR

The possibility of measuring the proton electromagnetic form factors in the time-like region at FAIR with the \PANDA detector is discussed. Detailed simulations on signal efficiency for the annihilation of $\bar p +p$ into a lepton pair as well as for the most important background channels have been performed. It is shown that precision measurements of the differential cross section of the reaction $\bar p +p \to e^++ e^-$ can be obtained in a wide angular and kinematical range. The individual determination of the moduli of the electric and magnetic proton form factors will be possible up to a value of momentum transfer squared of $q^2\simeq 14$ (GeV/c)$^2$. The total $\bar p +p\to e^++e^-$ cross section will be measured up to $q^2\simeq 28$ (GeV/c)$^2$. The results obtained from simulated events are compared to the existing data. Sensitivity to the two photons exchange mechanism is also investigated.Comment: 12 pages, 4 tables, 8 figures Revised, added details on simulations, 4 tables, 9 figure

Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation. Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.Peer reviewe

Aboriginal Australian mitochondrial genome variation - An increased understanding of population antiquity and diversity

Aboriginal Australians represent one of the oldest continuous cultures outside Africa, with evidence indicating that their ancestors arrived in the ancient landmass of Sahul (present-day New Guinea and Australia) ∼55 thousand years ago. Genetic studies, though limited, have demonstrated both the uniqueness and antiquity of Aboriginal Australian genomes. We have further resolved known Aboriginal Australian mitochondrial haplogroups and discovered novel indigenous lineages by sequencing the mitogenomes of 127 contemporary Aboriginal Australians. In particular, the more common haplogroups observed in our dataset included M42a, M42c, S, P5 and P12, followed by rarer haplogroups M15, M16, N13, O, P3, P6 and P8. We propose some major phylogenetic rearrangements, such as in haplogroup P where we delinked P4a and P4b and redefined them as P4 (New Guinean) and P11 (Australian), respectively. Haplogroup P2b was identified as a novel clade potentially restricted to Torres Strait Islanders. Nearly all Aboriginal Australian mitochondrial haplogroups detected appear to be ancient, with no evidence of later introgression during the Holocene. Our findings greatly increase knowledge about the geographic distribution and phylogenetic structure of mitochondrial lineages that have survived in contemporary descendants of Australia's first settlers. © The Author(s) 2017