Alterations in the cerebrospinal fluid relating to apolipoprotein E after traumatic brain injury and subarachnoid haemorrhage.

Background: The human gene coding for apolipoprotein E is polymorphic, and the APOE4 allele has been associated with less favourable outcome after acute brain injury including traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Experimental studies identify key roles for apoE in the central nervous system such as the scavenging and recycling of lipids for cellular maintenance and repair and formation of cerebral amyloid aggregate. Human in-vivo evidence supporting the concept that apoE is involved in the response of the brain to acute injury is sparse. Objectives: This study tests the hypothesis that apoE is involved in the response of the human brain to injury, and this role is reflected by changes in cerebrospinal fluid (CSF) apoE concentration after brain injury which correlate with injury severity and outcome. In addition it was hypothesised that changes in apoE concentration would be paralleled by changes in the composition of CSF lipoprotein particles (Lps) of which apoE is a major component. Lastly, apoE is reported to chaperone amyloid-beta peptide (Abeta), therefore we hypothesised that alteration in CSF apoE after brain injury would parallel alterations in Abeta. Methods: Enzyme linked immunosorbant assay (ELISA) was used to determine the concentration of apoE, Abeta, S100B and Tau (as surrogate markers of brain injury) in CSF from TBI and SAH patients and a non-brain injured control group. Lipoprotein particles were isolated from CSF using size exclusion chromatography and characterised in relation to cholesterol, phospholipid, apolipoprotein E, and apohpoprotein AI composition. Injury severity was determined using the Glasgow Coma Score, and clinical outcome using the Glasgow Outcome Score. Results: Compared to controls there was a sustained decrease in the concentration of apoE in the CSF after TBI and SAH which was paralleled by a depletion of apoE containing lipoprotein particles. Furthermore, CSF Abeta also decreased, and the decrease correlated with injury severity and clinical outcome. In contrast the levels of S100B and Tau in brain injury CSF was substantially elevated. Conclusion: Despite the likely leakage of plasma apolipoprotein E into the subarachnoid space at the time of brain injury, apoE in the form of LpE is cleared from the CSF within days of injury. In addition, indirect evidence suggesting apoE-Abeta interactions in-vivo support the concept that apoE may form insoluble aggregates with Abeta soon after brain injury. The finding that these alterations in the CSF correlate with injury severity and outcome provides novel indirect in-vivo evidence that apoE is important to the response of the human brain to injury

Theory of Phase Ordering Kinetics

The theory of phase ordering dynamics -- the growth of order through domain coarsening when a system is quenched from the homogeneous phase into a broken-symmetry phase -- is reviewed, with the emphasis on recent developments. Interest will focus on the scaling regime that develops at long times after the quench. How can one determine the growth laws that describe the time-dependence of characteristic length scales, and what can be said about the form of the associated scaling functions? Particular attention will be paid to systems described by more complicated order parameters than the simple scalars usually considered, e.g. vector and tensor fields. The latter are needed, for example, to describe phase ordering in nematic liquid crystals, on which there have been a number of recent experiments. The study of topological defects (domain walls, vortices, strings, monopoles) provides a unifying framework for discussing coarsening in these different systems.Comment: To appear in Advances in Physics. 85 pages, latex, no figures. For a hard copy with figures, email [email protected]

Novel codon-optimized mini-intronic plasmid for efficient, inexpensive, and xeno-free induction of pluripotency

The development of human induced pluripotent stem cell (iPSC) technology has revolutionized the regenerative medicine field. This technology provides a powerful tool for disease modeling and drug screening approaches. To circumvent the risk of random integration into the host genome caused by retroviruses, non-integrating reprogramming methods have been developed. However, these techniques are relatively inefficient or expensive. The mini-intronic plasmid (MIP) is an alternative, robust transgene expression vector for reprogramming. Here we developed a single plasmid reprogramming system which carries codon-optimized (Co) sequences of the canonical reprogramming factors (Oct4, Klf4, Sox2, and c-Myc) and short hairpin RNA against p53 ("4-in-1 CoMiP"). We have derived human and mouse iPSC lines from fibroblasts by performing a single transfection. Either independently or together with an additional vector encoding for LIN28, NANOG, and GFP, we were also able to reprogram blood-derived peripheral blood mononuclear cells (PBMCs) into iPSCs. Taken together, the CoMiP system offers a new highly efficient, integration-free, easy to use, and inexpensive methodology for reprogramming. Furthermore, the CoMIP construct is color-labeled, free of any antibiotic selection cassettes, and independent of the requirement for expression of the Epstein-Barr Virus nuclear antigen (EBNA), making it particularly beneficial for future applications in regenerative medicine

The spiritual revolution and suicidal ideation: an empirical enquiry among 13- to 15-year-old adolescents in England and Wales

The association between conventional religiosity and suicide inhibition has been well explored and documented since the pioneering work of Durkheim. Commentators like Heelas and Woodhead point to ways in which conventional religiosity is giving way in England and Wales to a range of alternative spiritualities, including renewed interest in paranormal phenomena. Taking a sample of 3095 13- to 15-year-old adolescents, the present study examines the association between suicidal ideation and both conventional religiosity and paranormal beliefs, after controlling for individual differences in sex, age and personality (extraversion, neuroticism and psychoticism). The data demonstrate that, while conventional religiosity is slightly associated with lower levels of suicidal ideation, paranormal beliefs are strongly associated with higher levels of suicidal ideation

Cerebello-cerebral connectivity in the developing brain

Disrupted cerebellar development and injury is associated with impairments in both motor and non-motor domains. Methods to non-invasively characterize cerebellar afferent and efferent connections during early development are lacking. The aim of this study was to assess the feasibility of delineating cortico-ponto-cerebellar (CPC) and cerebello-thalamo-cortical (CTC) white matter tracts during brain development using high angular resolution diffusion imaging (HARDI). HARDI data were obtained in 24 infants born between 24+6 and 39 weeks gestational age (median 33+4 weeks) and scanned between 29+1 and 44 weeks postmenstrual age (PMA) (median 37+1 weeks). Probabilistic tractography of CPC and CTC fibers was performed using constrained spherical deconvolution. Connections between cerebellum and contralateral cerebral hemisphere were identified in all infants studied. Fractional anisotropy (FA) values of CTC and CPC pathways increased with increasing PMA at scan (p < 0.001). The supratentorial regions connecting to contralateral cerebellum in most subjects, irrespective of PMA at scan, included the precentral cortex, superior frontal cortex, supplementary motor area, insula, postcentral cortex, precuneus, and paracentral lobule. This study demonstrates the feasibility of assessing CTC and CPC white matter connectivity in vivo during the early stages of development. The ability to assess cerebellar connectivity during this critical developmental period may help improve our understanding of the role of the cerebellum in a wide range of neuromotor and neurocognitive disorders

Effects of external loads on postural sway during quiet stance in adults aged 20–80 years

The purpose of this study was to investigate the effects of holding external loads on postural sway during upright stance across age decades. Sixty-five healthy adults (females, n = 35), aged 18–80 years were assessed in four conditions; (1) standing without holding a load, holding a load corresponding to 5% body mass in the (2) left hand, (3) right hand and (4) both hands. The centre of pressure (COP) path length and anteroposterior and mediolateral COP displacement were used to indirectly assess postural sway. External loading elicited reductions in COP measures of postural sway in older age groups only (P 0.05). Holding external loads during standing is relevant to many activities of daily living (i.e. holding groceries). The reduction in postural sway may suggest this type of loading has a stabilising effect during quiet standing among older adults

Experimental study of the astrophysically important Na 23 (α,p) Mg 26 and Na 23 (α,n) Al 26 reactions

The Na23(α,p)Mg26 and Na23(α,n)Al26 reactions are important for our understanding of the Al26 abundance in massive stars. The aim of this work is to report on a direct and simultaneous measurement of these astrophysically important reactions using an active target system. The reactions were investigated in inverse kinematics using He4 as the active target gas in the detector. We measured the excitation functions in the energy range of about 2 to 6 MeV in the center of mass. We have found that the cross sections of the Na23(α,p)Mg26 and the Na23(α,n)Al26 reactions are in good agreement with previous experiments and with statistical-model calculations. The astrophysical reaction rate of the Na23(α,n)Al26 reaction has been reevaluated and it was found to be larger than the recommended rate

Search for the 1/2+ intruder state in P 35

The excitation energy of deformed intruder states (specifically the 2p2h bandhead) as a function of proton number Z along N=20 is of interest both in terms of better understanding the evolution of nuclear structure between spherical Ca40 and the Island of Inversion nuclei, and for benchmarking theoretical descriptions in this region. At the center of the N=20 Island of Inversion, the npnh (where n=2,4,6) neutron excitations across a diminished N=20 gap result in deformed and collective ground states, as observed in Mg32. In heavier isotones, npnh excitations do not dominate in the ground states but are present in the relatively low-lying level schemes. With the aim of identifying the expected 2p2h - s1/2+ state in P35, the only N=20 isotone for which the neutron 2p2h excitation bandhead has not yet been identified, the S36(d,He3)P35 reaction has been revisited in inverse kinematics with the HELical Orbit Spectrometer (HELIOS) at the Argonne Tandem Linac Accelerator System (ATLAS). While a candidate state has not been located, an upper limit for the transfer reaction cross section to populate such a configuration within a 2.5 to 3.6 MeV energy range provides a stringent constraint on the wave function compositions in both S36 and P35

Reaction rate for carbon burning in massive stars

Carbon burning is a critical phase for nucleosynthesis in massive stars. The conditions for igniting this burning stage, and the subsequent isotope composition of the resulting ashes, depend strongly on the reaction rate for C12+C12 fusion at very low energies. Results for the cross sections for this reaction are influenced by various backgrounds encountered in measurements at such energies. In this paper, we report on a new measurement of C12+C12 fusion cross sections where these backgrounds have been minimized. It is found that the astrophysical S factor exhibits a maximum around Ecm=3.5-4.0 MeV, which leads to a reduction of the previously predicted astrophysical reaction rate

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter