Response to Yang et al

Non peer reviewe

Avian blood parasites in an endangered columbid: Leucocytozoon marchouxi in the Mauritian Pink Pigeon Columba mayeri

There is increasing evidence that pathogens can play a significant role in species decline. This study of a complete free-living species reveals a cost of blood parasitism to an endangered host, the Pink Pigeon Columba mayeri, endemic to Mauritius. We investigated the prevalence and effect of infection of the blood parasite, Leucocytozoon marchouxi, in the free-living Pink Pigeon population. Overall, L. marchouxi infection prevalence detected was 18·3%. Juveniles were more likely to be infected than older birds and there was geographical variation in infection prevalence. Survival of birds infected with L. marchouxi was lower than that of uninfected birds to 90 days post-sampling. This study suggests that while common haematozoa are well tolerated in healthy adults, these parasites may have greater pathogenic potential in susceptible juveniles. The study is unusual given its completeness of species sampling (96%) within a short time-period, the accurate host age data, and its focus on blood parasites in a threatened bird species. Species for which long-term life-history data are available for every individual serve as valuable models for dissecting the contribution of particular pathogens to species decline

Molecular Motor Constructed from a Double-Walled Carbon Nanotube Driven by Axially Varying Voltage

A new molecular motor is conceptually constructed from a double-walled carbon nanotube (DWNT) consisting of a long inner single-walled carbon nanotube (SWNT) and a short outer SWNT with different chirality. The interaction between inner and outer tubes is the sum of the Lennard-Jones potentials between carbon atoms in inner tube and those in outer one. Within the framework of Smoluchowski-Feynman ratchet, it is theoretically shown that this system in an isothermal bath will exhibit a unidirectional rotation in the presence of a varying axial electrical voltage.Comment: 11 pages + 3 figure

Multiscale Modeling of a Nanoelectromechanical Shuttle

In this article, we report a theoretical analysis of a nanoelectromechanical shuttle based on a multiscale model that combines microscopic electronic structure data with macroscopic dynamics. The microscopic part utilizes a (static) density functional description to obtain the energy levels and orbitals of the shuttling particle together with the forces acting on the particle. The macroscopic part combines stochastic charge dynamics that incorporates the microscopically evaluated tunneling rates with a Newtonian dynamics. We have applied the multiscale model to describe the shuttling of a single copper atom between two gold-like jellium electrodes. We find that energy spectrum and particle surface interaction greatly influence shuttling dynamics; in the specific example that we studied the shuttling is found to involve only charge states Q=0 and Q=+e. The system is found to exhibit two quasi-stable shuttling modes, a fundamental one and an excited one with a larger amplitude of mechanical motion, with random transitions between them.Comment: 9 pages, 9 figure

THE RESULTS OF PANCREATIC RESECTIONS AND LONG- TERM SURVIVAL FOR PANCREATIC DUCTAL ADENOCARCINOMA : A SINGLE-INSTITUTION EXPERIENCE

Objectives: Since the early 1990s, low long-term survival rates following pancreatic surgery for pancreatic ductal adenocarcinoma have challenged us to improve treatment. In this series, we aim to show improved survival from pancreatic ductal adenocarcinoma during the era of centralized pancreatic surgery. Methods: Analysis of all pancreatic resections performed at Helsinki University Hospital and survival of pancreatic ductal adenocarcinoma patients during 2000-2013 were included. Post-operative complications such as fistulas, reoperations, and mortality rates were recorded. Patient and tumor characteristics were compared with survival data. Results: Of the 853 patients undergoing pancreatic surgery, 581 (68%) were pancreaticoduodenectomies, 195 (21%) distal resections, 28 (3%) total pancreatectomies, and 49 (6%) other procedures. Mortality after pancreaticoduodenectomy was 2.1%. The clinically relevant B/C fistula rate was 7% after pancreaticoduodenectomy and 13% after distal resection, and the re-operation rate was 5%. The 5- and 10-year survival rates for pancreatic ductal adenocarcinoma were 22% and 14%; for T1-2, N0 and R0 tumors, the corresponding survival rates were 49% and 31%. Carbohydrate antigen 19-9 >75 kU/L, carcinoembryonic antigen >5 mu g/L, N1, lymph-node ratio >20%, R1, and lack of adjuvant therapy were independent risk factors for decreased survival. Conclusion: After centralization of pancreatic surgery in southern Finland, we have managed to enable pancreatic ductal adenocarcinoma patients to survive markedly longer than in the early 1990s. Based on a 1.7-million population in our clinic, mortality rates are equal to those of other high-volume centers and long-term survival rates for pancreatic ductal adenocarcinoma have now risen to some of the highest reported.Peer reviewe

Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues

<p>Abstract</p> <p>Background</p> <p>We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R) and its ligand the tuberoinfundibular peptide of 39 residues (TIP39) by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP) are compared with the complex to examine their interactions.</p> <p>Findings</p> <p>In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation.</p> <p>Conclusions</p> <p>A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.</p

Technical note: Emulation of a large-eddy simulator for stratocumulus clouds in a general circulation model

Here we present for the first time a proof of concept for an emulation-based method that uses a large-eddy simulations (LESs) to present sub-grid cloud processes in a general circulation model (GCM). We focus on two key variables affecting the properties of shallow marine clouds: updraft velocity and precipitation formation. The LES is able to describe these processes with high resolution accounting for the realistic variability in cloud properties. We show that the selected emulation method is able to represent the LES outcome with relatively good accuracy and that the updraft velocity and precipitation emulators can be coupled with the GCM practically without increasing the computational costs. We also show that the emulators influence the climate simulated by the GCM but do not consistently improve or worsen the agreement with observations on cloud-related properties, although especially the updraft velocity at cloud base is better captured. A more quantitative evaluation of the emulator impacts against observations would, however, have required model re-tuning, which is a significant task and thus could not be included in this proof-of-concept study. All in all, the approach introduced here is a promising candidate for representing detailed cloud- and aerosol-related sub-grid processes in GCMs. Further development work together with increasing computing capacity can be expected to improve the accuracy and the applicability of the approach in climate simulations.</p

Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation

Hepatocytes are dynamic cells that, upon injury, can alternate between nondividing differentiated and dedifferentiated proliferating states in vivo . However, in two‐dimensional cultures, primary human hepatocytes (PHHs) rapidly dedifferentiate, resulting in loss of hepatic functions that significantly limits their usefulness as an in vitro model of liver biology, liver diseases, as well as drug metabolism and toxicity. Thus, understanding the underlying mechanisms and stalling of the dedifferentiation process would be highly beneficial to establish more‐accurate and relevant long‐term in vitro hepatocyte models. Here, we present comprehensive analyses of whole proteome and transcriptome dynamics during the initiation of dedifferentiation during the first 24 hours of culture. We report that early major rearrangements of the noncoding transcriptome, hallmarked by increased expression of small nucleolar RNAs, long noncoding RNAs, microRNAs (miRNAs), and ribosomal genes, precede most changes in coding genes during dedifferentiation of PHHs, and we speculated that these modulations could drive the hepatic dedifferentiation process. To functionally test this hypothesis, we globally inhibited the miRNA machinery using two established chemically distinct compounds, acriflavine and poly‐l ‐lysine. These inhibition experiments resulted in a significantly impaired miRNA response and, most important, in a pronounced reduction in the down‐regulation of hepatic genes with importance for liver function. Thus, we provide strong evidence for the importance of noncoding RNAs, in particular, miRNAs, in hepatic dedifferentiation, which can aid the development of more‐efficient differentiation protocols for stem‐cell‐derived hepatocytes and broaden our understanding of the dynamic properties of hepatocytes with respect to liver regeneration. Conclusion: miRNAs are important drivers of hepatic dedifferentiation, and our results provide valuable information regarding the mechanisms behind liver regeneration and possibilities to inhibit dedifferentiation in vitro

Computational Cancer Biology: An Evolutionary Perspective

ISSN:1553-734XISSN:1553-735