Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum.

The malaria parasite Plasmodium falciparum has a great capacity for evolutionary adaptation to evade host immunity and develop drug resistance. Current understanding of parasite evolution is impeded by the fact that a large fraction of the genome is either highly repetitive or highly variable and thus difficult to analyze using short-read sequencing technologies. Here, we describe a resource of deep sequencing data on parents and progeny from genetic crosses, which has enabled us to perform the first genome-wide, integrated analysis of SNP, indel and complex polymorphisms, using Mendelian error rates as an indicator of genotypic accuracy. These data reveal that indels are exceptionally abundant, being more common than SNPs and thus the dominant mode of polymorphism within the core genome. We use the high density of SNP and indel markers to analyze patterns of meiotic recombination, confirming a high rate of crossover events and providing the first estimates for the rate of non-crossover events and the length of conversion tracts. We observe several instances of meiotic recombination within copy number variants associated with drug resistance, demonstrating a mechanism whereby fitness costs associated with resistance mutations could be compensated and greater phenotypic plasticity could be acquired

Salvage of failed distal radioulnar joint reconstruction

In the patient in whom primary distal radioulnar joint surgery has failed, consideration must be given to the anatomy and biomechanics of the native joint; how this has been disrupted by injury, disease, and previous trauma; and what is required to reconstruct the joint. The forearm relies on a congruent condylar cam of the distal ulna, with intact soft tissue restraints for normal biomechanics. Surgical reconstruction using tendon graft, autologous bone graft, allograft interposition, and prosthetic reconstruction are discussed in this article. If these procedures fail, then salvage procedures including wide excision of the ulna or one-bone forearm can be performed.</p

The limit of macroscopic homogeneous ice nucleation at the nanoscale

Nucleation in small volumes of water has garnered renewed interest due to the relevance of pore condensation and freezing under conditions of low partial pressures of water, such as in...J.A.H. acknowledges studentship funding from the Engineering and Physical Sciences Research Council (EP/T517847/1). T.F.W. thanks the Leverhulme Trust and the University of Warwick for supporting an Early Career Fellowship (ECF-2018-127). S.J.C. is a Royal Society University Research Fellow (Grant No. URF\R1\211144)at the University of Cambridge

Research data supporting "The limit of macroscopic homogeneous ice nucleation at the nanoscale"

Research data the supports the finding of the study "The limit of macroscopic homogeneous ice nucleation at the nanoscale". Includes all relevant results, input files for the simulations, and all data used in the figures.J.A.H. acknowledges studentship funding from the Engineering and Physical Sciences Research Council. T.F.W. thanks the Leverhulme Trust and the University of Warwick for supporting an Early Career Fellowship (ECF-2018-127). S.J.C. is a Royal Society University Research Fellow (Grant No. URF\R1\211144) at the University of Cambridge

The limit of macroscopic homogeneous ice nucleation at the nanoscale

Nucleation in small volumes of water has garnered renewed interest due to the relevance of pore condensation and freezing under conditions of low partial pressures of water, such as in the upper troposphere. Molecular simulations can in principle provide insight on this process at the molecular scale that is challenging to achieve experimentally. However, there are discrepancies in the literature as to whether the rate in confined systems is enhanced or suppressed relative to bulk water at the same temperature and pressure. In this study, we investigate the extent to which the size of the critical nucleus and the rate at which it grows in thin films of water are affected by the thickness of the film. Our results suggest that nucleation remains bulk-like in films that are barely large enough accommodate a critical nucleus. This conclusion seems robust to the presence of physical confining boundaries. We also discuss the difficulties in unambiguously determining homogeneous nucleation rates in nanoscale systems, owing to the challenges in defining the volume. Our results suggest any impact on a film's thickness on the rate is largely inconsequential for present day experiments.Comment: 26 pages, 6 figures in main script, 6 in ESI, submitted to Faraday Discussions for the "Water at interfaces Faraday Discussion" in September 202

The limit of macroscopic homogeneous ice nucleation at the nanoscale †

Acknowledgements: J. A. H. acknowledges studentship funding from the Engineering and Physical Sciences Research Council (EP/T517847/1). T. F. W. thanks the Leverhulme Trust and the University of Warwick for supporting an Early Career Fellowship (ECF-2018-127). S. J. C. is a Royal Society University Research Fellow (Grant No. URF\R1\211144) at the University of Cambridge.Nucleation in small volumes of water has garnered renewed interest due to the relevance of pore condensation and freezing under conditions of low partial pressures of water, such as in the upper troposphere. Molecular simulations can in principle provide insight on this process at the molecular scale that is challenging to achieve experimentally. However, there are discrepancies in the literature as to whether the rate in confined systems is enhanced or suppressed relative to bulk water at the same temperature and pressure. In this study, we investigate the extent to which the size of the critical nucleus and the rate at which it grows in thin films of water are affected by the thickness of the film. Our results suggest that nucleation remains bulk-like in films that are barely large enough accommodate a critical nucleus. This conclusion seems robust to the presence of physical confining boundaries. We also discuss the difficulties in unambiguously determining homogeneous nucleation rates in nanoscale systems, owing to the challenges in defining the volume. Our results suggest any impact on a film’s thickness on the rate is largely inconsequential for present day experiments

The limit of macroscopic homogeneous ice nucleation at the nanoscale †

Acknowledgements: J. A. H. acknowledges studentship funding from the Engineering and Physical Sciences Research Council (EP/T517847/1). T. F. W. thanks the Leverhulme Trust and the University of Warwick for supporting an Early Career Fellowship (ECF-2018-127). S. J. C. is a Royal Society University Research Fellow (Grant No. URF\R1\211144) at the University of Cambridge.Nucleation in small volumes of water has garnered renewed interest due to the relevance of pore condensation and freezing under conditions of low partial pressures of water, such as in the upper troposphere. Molecular simulations can in principle provide insight on this process at the molecular scale that is challenging to achieve experimentally. However, there are discrepancies in the literature as to whether the rate in confined systems is enhanced or suppressed relative to bulk water at the same temperature and pressure. In this study, we investigate the extent to which the size of the critical nucleus and the rate at which it grows in thin films of water are affected by the thickness of the film. Our results suggest that nucleation remains bulk-like in films that are barely large enough accommodate a critical nucleus. This conclusion seems robust to the presence of physical confining boundaries. We also discuss the difficulties in unambiguously determining homogeneous nucleation rates in nanoscale systems, owing to the challenges in defining the volume. Our results suggest any impact on a film’s thickness on the rate is largely inconsequential for present day experiments

Presence of fibrocytes in dupuytren’s disease (DD) and control carpal tunnel (CT) blood and tissue confirmed through FACS and immunohistology.

<p>(<b>A–D</b>) The gating strategy used in identifying triple positive cells in CT and DD samples. The cells were labelled with antibodies against CD45RO, 25F9 and MRP8/14 cell surface markers. In a CD45RO vs. side scatter plot, CD45RO⁺ were selected and these cells were gated in a 25F9 vs. MRP8/14 plot. In the second plot, cells positive for both 25F9 and MRP8/14 were selected (along with total population as the gating was shown to be unnecessary as all 25F9⁺/MRP8/14⁺ cells were always CD45RO⁺) that are now considered to be triple positive (CD45RO⁺/25F9⁺/MRP8/14⁺). Cell viability was assessed separately through propidium iodide labelling. Cells were analyzed on Accuri C6 flow cytometer as explained in the materials and methods. (<b>E</b>) The fresh cells were obtained from the DD blood and tissue biopsies as explained in the methods. The cells were washed and passed through 70 µm nylon mesh filter before being labelled with antibodies as described above. Fibrocytes were highly expressed in freshly isolated MNCs from blood (1.8%) and in DD nodule (2.4%) compared to other tissue types. An unpaired two-tailed t-test was performed to check the statistical significance of the results. Error bars represent standard deviation. (<b>F</b>) H&E and immunofluorescence images of carpal tunnel (CT) fat and palmar fascia (n = 4 patients). CT fat and fascia are shown to be almost completely devoid of doubly positive collagen 1/CD34 cells. Red = Collagen I, Green = CD34, Blue = DAPI. CB = Collagen bundles. (<b>G</b>) H&E and immunofluorescence images of DD skin, cord and nodule (n = 4 patients). Cord typically shows linear arrangement of collagen bundles (LCB), while nodule here show circular arrangement of collagen fibers (CCB). DD cord and nodule showed the presence of clusters of doubly positive collagen 1/CD34 cells. Arrows points to the doubly positive cells that appeared as orange. Red = Collagen I, Green = CD34, Blue = DAPI, Orange = doubly positive cells. LCB = Linear collagen bundles; CCB = Circular collagen bundles. All scale bars: 100 µm.</p

Immunofluorescent labelling of cultured fibrocytes (n = 6 patients).

<p>Fibrocytes have been found to be double positive for Col1/LSP-1 and Col1/CD34. Our labelling here shows that mononuclear cells (MNCs) from dupuytren’s disease (DD) blood and DD fascia with or without serum amyloid P treatment were positive for both set of markers. We therefore confirmed that the cells in our experiments were fibrocytes and not resident fibroblasts. Magnification bar = 20 µm.</p

A flow chart depicting the study design.

<p>The flow chart here describes how the obtained tissue samples that were utilized for confirmation of the presence of fibrocytes in Dupuytren’s Disease.</p