Post-surgical Pancreatitis Masquerading as Recurrent Neuroendocrine Cancer

Neuroendocrine tumours of the pancreas can have a spectrum of behaviour from relatively benign to aggressive. Resection can result in cure although metastatic disease is described. We present an unusual case of an apparent local recurrence of previously resected neuroendocrine tumour in a young man who had undergone distal pancreatectomy. Pathological analysis demonstrated focal post-surgical pancreatitis with radiological appearances bearing striking similarity to the original primary tumour

Purification and electron cryomicroscopy of coronavirus particles.

Intact, enveloped coronavirus particles vary widely in size and contour, and are thus refractory to study by traditional structural means such as X-ray crystallography. Electron microscopy (EM) overcomes some problems associated with particle variability and has been an important tool for investigating coronavirus ultrastructure. However, EM sample preparation requires that the specimen be dried onto a carbon support film before imaging, collapsing internal particle structure in the case of coronaviruses. Moreover, conventional EM achieves image contrast by immersing the specimen briefly in heavy-metal-containing stain, which reveals some features while obscuring others. Electron cryomicroscopy (cryo-EM) instead employs a porous support film, to which the specimen is adsorbed and flash-frozen. Specimens preserved in vitreous ice over holes in the support film can then be imaged without additional staining. Cryo-EM, coupled with single-particle image analysis techniques, makes it possible to examine the size, structure and arrangement of coronavirus structural components in fully hydrated, native virions. Two virus purification procedures are described

Toward a physiological explanation of juvenile growth curves

Juvenile growth curves are generally sigmoid in shape: Growth is initially nearly exponential, but it slows to near zero as the animal approaches maturity. The drop‐off in growth rate is puzzling because, everything else being equal, selection favors growing as fast as possible. Existing theory posits sublinear scaling of resource acquisition with juvenile body mass and linear scaling of the requirement for maintenance, so the difference, fuel for growth, decreases as the juvenile increases in size. Experimental evidence, however, suggests that maintenance metabolism increases sublinearly not linearly with size. Here, we develop a new theory consistent with the experimental evidence. Our theory is based on the plausible assumption that there is a trade‐off in the capacity of capillaries to supply growing and developed cells. As the proportion of non‐growing cells increases, they take up more macromolecules from the capillaries, leaving fewer to support growing cells. The predicted growth curves are realistic and similar to those of previous models (Bertalanffy, Gompertz, and Logistic) but have the advantage of being derived from a plausible physiological model. We hope that our focus on resource delivery in capillaries will encourage new experimental work to identify the detailed physiological basis of the trade‐off underlying juvenile growth curves

Ecological and taxonomic variation among human RNA viruses

AbstractOnly a minority of RNA viruses that can infect humans are capable of spreading in human populations independently of a zoonotic reservoir. This is especially true of vector-borne RNA viruses; the majority of these are not transmissible (via the vector) between humans at all. Understanding the biology underlying this observation will help us evaluate the public health risk associated with novel vector-borne RNA viruses

Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA

Antimicrobial activity of an iron triple helicate

The prevalence of antibiotic resistance has resulted in the need for new approaches to be developed to combat previously easily treatable infections. Here we investigated the potential of the synthetic metallomolecules [Fe2L3]4+ and [Cu2(L’)2]2+ as antibacterial agents. Both molecules have been shown to bind DNA; [Fe2L3]4+ binds in the major groove and causes DNA coiling, whilst [Cu2(L’)2]2+ can act as an artificial nuclease. The work described here shows that only [Fe2L3]4+ is bactericidal for Bacillus subtilis and Escherichia coli. We demonstrate that [Fe2L3]4+ binds bacterial DNA in vivo and, strikingly, that it kills B. subtilis cells very rapidly

Paradoxical popups: Why are they hard to catch?

Even professional baseball players occasionally find it difficult to gracefully approach seemingly routine pop-ups. This paper describes a set of towering pop-ups with trajectories that exhibit cusps and loops near the apex. For a normal fly ball, the horizontal velocity is continuously decreasing due to drag caused by air resistance. But for pop-ups, the Magnus force (the force due to the ball spinning in a moving airflow) is larger than the drag force. In these cases the horizontal velocity decreases in the beginning, like a normal fly ball, but after the apex, the Magnus force accelerates the horizontal motion. We refer to this class of pop-ups as paradoxical because they appear to misinform the typically robust optical control strategies used by fielders and lead to systematic vacillation in running paths, especially when a trajectory terminates near the fielder. In short, some of the dancing around when infielders pursue pop-ups can be well explained as a combination of bizarre trajectories and misguidance by the normally reliable optical control strategy, rather than apparent fielder error. Former major league infielders confirm that our model agrees with their experiences.Comment: 28 pages, 10 figures, sumitted to American Journal of Physic

Multiscale modelling of nanoparticle distribution in a realistic tumour geometry following local injection

Radiosensitizers have proven to be an effective method of improving radiotherapy outcomes, with the distribution of particles being a crucial element to delivering optimal treatment outcomes due to the short range of effect of these particles. Here we present a computational model for the transport of nanoparticles within the tumour, whereby the fluid velocity and particle deposition are obtained and used as input into the convection-diffusion equation to calculate the spatio-temporal concentration of the nanoparticles. The effect of particle surface charge and injection locations on the distribution of nanoparticle concentration within the interstitial fluid and deposited onto cell surfaces is assessed. The computational results demonstrate that negatively charged particles can achieve a more uniform distribution throughout the tumour as compared to uncharged or positively charged particles, with particle volume within the fluid being 100% of tumour volume and deposited particle volume 44.5%. In addition, varying the injection location from the end to the middle of the tumour caused a reduction in particle volume of almost 20% for negatively charged particles. In conclusion, radiosensitizing particles should be negatively charged to maximise their spread and penetration within the tumour. Choosing an appropriate injection location can further improve the distribution of these particles