Vortex Solid-Liquid Transition in Bi2_{2}Sr2_{2}CaCu2_{2}O8+δ_{8+\delta} with a High Density of Strong Pins

The introduction of a large density of columnar defects in %underdoped Bi$_{2}$Sr$_{2}$CaCu$_{2}$O$_{8+\delta}$ crystals does not, at sufficiently low vortex densities, increase the irreversibility line beyond the first order transition (FOT) field of pristine crystals. At such low fields, the flux line wandering length $r_{w}$ behaves as in pristine %Bi$_{2}$Sr$_{2}$CaCu$_{2}$O$_{8+\delta}$ crystals. Next, vortex positional correlations along the $c$--axis in the vortex Bose glass at fields above the FOT are smaller than in the low--field vortex solid. Third, the Bose-glass-to-vortex liquid transition is signaled by a rapid decrease in c-axis phase correlations. These observations are understood in terms of the ``discrete superconductor'' model.Comment: 4 pages, 4 figures Submitted to Phys. Rev. B Rapid Comm. 16-1-2004 Revised version 18-3-200

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Pharmacological intervention at CCR1 and CCR5 as an approach for cancer: help or hindrance

While a number of agents directed at chemokine receptors have entered clinic trials, the vast majority of these have failed, and the enthusiasm for this class of drugs has been attenuated. To date, there are two drugs that inhibit chemokine receptors approved by the FDA. The first to be approved in 2007 was maraviroc (brand name Selzentry, or Celsentri outside the US) which targets CCR5 and is used for the treatment of HIV infection. The second is plerixafor (Mozobil) which was approved in 2008, targets CXCR4, and is used for the mobilization of hematopoietic stem cells. This review will focus on the CC chemokine receptors CCR1 and CCR5. These G protein coupled receptors are both activated by a relatively large number of chemokines, most of which overlap. While most of the drugs for CCR1 have been assessed in the context of autoimmune diseases like multiple sclerosis and rheumatoid arthritis, and those for CCR5 were examined for HIV-infection, we review the role of these receptors in relation to cancer. Recently introduced pharmacophores that serve as agonists or antagonists for the receptors are presented. Efforts to exploit polypharmacology approaches using promiscuous compounds that target more than one receptor are also considered

Shorebird incubation behviour and its influence on the risk of nest predation

Both nest survival and incubation behaviour are highly variable among shorebirds (Charadrii), and we tested whether more conspicuous incubation behaviour increased the risk of nest predation. During 2000-2006, we monitored nest fate at 901 shorebird nests at three study sites across the circumpolar Arctic. Using miniature video recorders and nest temperature sensors, we obtained 782 days of behavioural data for 161 nests of 11 species. We related nest fate to the rate and duration of adults' nest absences or restless movements on the nest, as well as the total proportion of each day that adult birds engaged in these activities. Nest predation was positively related to the proportion of time that each species left the nest unattended. After controlling for species effects, the likelihood of a successful nesting attempt was lower for individuals that spent more time off the nest, but among failed nests, the number of days that a nest survived prior to depredation was not significantly predicted by measures of incubation behaviour. To control for weather or seasonal effects, we paired observations from nests that were ultimately depredated with observations from successful nests of the same species on the same day. In this paired sample (dominated by two species: red phalaropes, Phalaropus fulicarius, and little stints, Calidris minuta), both incubation recesses and restless movements were more numerous among failed versus successful nests. Our results suggest that more conspicuous incubation behaviour is indeed related to a higher risk of nest predation, and that this relationship may underlie patterns of nest survival within and among shorebird species. (C) 2012 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved