A novel device for islet transplantation providing immune protection and oxygen supply

Islet transplantation as a biological β-cell replacement therapy has emerged as a promising option for achieving restoration of metabolic control in type 1 diabetes patients. However, partial or complete loss of islet graft function occurs in relatively short time (months to few years) after implantation. The high rate of early transplant dysfunction has been attributed to poorly viable and/or functional islets and is mediated by innate inflammatory response at the intravascular (hepatic) transplant site and critical lack of initial nutrient/oxygen supply prior to islet engraftment. In addition, the diabetogenic effect of mandatory immunosuppressive agents, limited control of alloimmunity, and the recurrence of autoimmunity limit the long-term success of islet transplantation. In order to abrogate instant blood-mediated inflammatory reaction and to provide oxygen supply for the islet graft, we have developed an extravascular (subcutaneous) transplant macrochamber (the 'βAir' device). This device contains islets immobilized in alginate, protected from the immune system by a thin hydrophilized teflon membrane impregnated with alginate and supplied with oxygen by daily refueling with oxygen-CO (2) mixture. We have demonstrated successful utilization of the oxygen-refueling macrochamber for sustained islet viability and function as well as immunoprotection after allogeneic subcutaneous transplantation in healthy minipigs. Considering the current limitations of intraportal islet engraftment and the restricted indication for islet transplantation mainly due to necessary immunosuppressive therapy, this work could very likely lead to remarkable improvements in the procedure and moreover opens up further strategies for porcine islet cell xenotransplantation.     

The impact of dengue illness on social distancing and caregiving behavior

BackgroundHuman mobility among residential locations can drive dengue virus (DENV) transmission dynamics. Recently, it was shown that individuals with symptomatic DENV infection exhibit significant changes in their mobility patterns, spending more time at home during illness. This change in mobility is predicted to increase the risk of acquiring infection for those living with or visiting the ill individual. It has yet to be considered, however, whether social contacts are also changing their mobility, either by socially distancing themselves from the infectious individual or increasing contact to help care for them. Social, or physical, distancing and caregiving could have diverse yet important impacts on DENV transmission dynamics; therefore, it is necessary to better understand the nature and frequency of these behaviors including their effect on mobility.Methodology and principal findingsThrough community-based febrile illness surveillance and RT-PCR infection confirmation, 67 DENV positive (DENV+) residents were identified in the city of Iquitos, Peru. Using retrospective interviews, data were collected on visitors and home-based care received during the illness. While 15% of participants lost visitors during their illness, 22% gained visitors; overall, 32% of all individuals (particularly females) received visitors while symptomatic. Caregiving was common (90%), particularly caring by housemates (91%) and caring for children (98%). Twenty-eight percent of caregivers changed their behavior enough to have their work (and, likely, mobility patterns) affected. This was significantly more likely when caring for individuals with low “health-related quality of well-being” during illness (Fisher’s Exact, p = 0.01).Conclusions/SignificanceOur study demonstrates that social contacts of individuals with dengue modify their patterns of visitation and caregiving. The observed mobility changes could impact a susceptible individual’s exposure to virus or a presymptomatic/clinically inapparent individual’s contribution to onward transmission. Accounting for changes in social contact mobility is imperative in order to get a more accurate understanding of DENV transmission.     

Blood feeding patterns of mosquitoes: random or structured?

Background

During the non-breeding period, many birds migrate to milder areas, found closer to the equator than their breeding sites. Opposite movements are very rare. In the Southern Ocean, the abundance of ¹³C declines markedly with more southern latitude, providing a characteristic ¹³C isoscape. This can be used as a tracer for the movement of seabirds between breeding and inter-breeding areas, by comparing stable isotope ratios of feathers grown at different times of the year.

Results

We studied seasonal movements of Thin-billed prions (Aves, Procellariiformes), breeding at the Subantarctic Falkland/Malvinas Islands, compared with those of Wilson's storm-petrels breeding in the Antarctic South Shetland Islands. The two species showed opposite migratory movements. While Wilson's storm-petrels moved to warmer waters north of the Drake Passage in winter, Thin-billed prions showed a reversed movement towards more polar waters. Carbon stable isotope ratios in recent and historical feathers indicated that poleward winter movements of Thin-billed prions were less common historically (45% in 1913-1915), and have only recently become dominant (92% in 2003-2005), apparently in response to warming sea temperatures.

Conclusions

This study shows that pelagic seabirds can rapidly change migration strategies within populations, including migration towards more poleward waters in winter.     

Reproduction and sexual dimorphism in the viviparous lizard Sceloporus palaciosi (Squamata: Phrynosomatidae) from the Trans‐Mexican Volcanic Belt,Mexico

In this study, sexual dimorphism, reproductive cycles, litter size and offspring size of a population of the little‐known species Sceloporus palaciosi in central Mexico were analysed. Significant male‐biased sexual size dimorphism was recorded in snout–vent length (SVL), head length, head width, forearm length and tibia length. Both sexes showed asynchronous reproductive cycles, and males reached sexual maturity at a smaller SVL (33 mm) than females (37 mm). Testes volumes were small from January to February, testicular recrudescence began from March to June, and decreased in July, but increased again in August and September, followed by a second decrease from October to December. In females, vitellogenesis began from May until ovulation in December. Embryonic development extended from November to March, and a small number of females carried embryos through July. Mean litter size was 4.0 and was positively correlated with female SVL. The length of the reproductive period in S. palaciosi recorded in this study is longer than that recorded for other populations in other parts of this species range. Further studies are needed to clarify reproductive cycles in the other isolated populations of S. palaciosi, and then extended to other species and chromosome races in the Sceloporus grammicus complex.     

The Efficacy of an Immunoisolating Membrane System for Islet Xenotransplantation in Minipigs

Developing a device that protects xenogeneic islets to allow treatment and potentially cure of diabetes in large mammals has been a major challenge in the past decade. Using xenogeneic islets for transplantation is required in light of donor shortage and the large number of diabetic patients that qualify for islet transplantation. Until now, however, host immunoreactivity against the xenogeneic graft has been a major drawback for the use of porcine islets. Our study demonstrates the applicability of a novel immunoprotective membrane that allows successful xenotransplantation of rat islets in diabetic minipigs without immunosuppressive therapy. Rat pancreatic islets were encapsulated in highly purified alginate and integrated into a plastic macrochamber covered by a poly-membrane for subcutaneous transplantation. Diabetic Sinclair pigs were transplanted and followed for up to 90 days. We demonstrated a persistent graft function and restoration of normoglycemia without the need for immunosuppressive therapy. This concept could potentially offer an attractive strategy for a more widespread islet replacement therapy that would restore endogenous insulin secretion in diabetic patients without the need for immunosuppressive drugs and may even open up an avenue for safe utilization of xenogeneic islet donors.     

Quaternary structure effects on the hexacoordination equilibrium in rice hemoglobin rHb1: Insights from molecular dynamics simulations

Nonsymbiotic hemoglobins (nsHbs) form a widely distributed class of plant proteins, which function remains unknown. Despite the fact that class 1 plant nonsymbiotic hemoglobins are hexacoordinate (6c) heme proteins (hxHbs), their hexacoordination equilibrium constants are much lower than in hxHbs from animals or bacteria. In addition, they are characterized by having very high oxygen affinities and low oxygen dissociation rate constants. Rice hemoglobin 1 (rHb1) is a class 1 nonsymbiotic hemoglobin. It crystallizes as a fully associated homodimer with both subunits in 6c state, but showing slightly different conformations, thus leading to an asymmetric crystallographic homodimer. The residues that constitute the dimeric interface are conserved among all nsHbs, suggesting that the quaternary structure could be relevant to explain the chemical behavior and biological function of this family of proteins. In this work, we analyze the molecular basis that determine the hexacoordination equilibrium in rHb1. Our results indicate that dynamical features of the quaternary structure significantly affect the hexacoordination process. Specifically, we observe that the pentacoordinate state is stabilized in the dimer with respect to the isolated monomers. Moreover, the dimer behaves asymmetrically, in a negative cooperative scheme. The results presented in this work are fully consistent with our previous hypothesis about the key role played by the nature of the CD region in determining the coordination state of globins. Proteins 2013. © 2012 Wiley Periodicals, Inc.     

Hearth-side socioeconomics, hunting and paleoecology during the late Lower Paleolithic at Qesem Cave, Israel

The late Lower Paleolithic archaeofaunas of Qesem Cave in the southern Levant span 400-200 ka and associate with Acheulo-Yabrudian (mainly Amudian) industries. The large mammals are exclusively Eurasian in origin and formed under relatively cool, moist conditions. The zooarchaeological findings testify to large game hunting, hearth-centered carcass processing and meat sharing during the late Lower Paleolithic, not unlike the patterns known from Middle and Upper Paleolithic caves in the region. Well-defined hearth features are rarely preserved in Qesem Cave, but the heterogeneous distributions of burned bones indicate areas of frequent hearth rebuilding throughout the occupation sequence. The hominins delayed consumption of high quality body parts until they could be moved to the cave, where hearths were hubs of processing activities and social interaction. Paradoxically, the cut marks on the Qesem bones are both more abundant and more randomly oriented than those observed in Middle and Upper Paleolithic cases in the Levant. These results suggest that several individuals were directly involved in cutting meat from the bones and that the social mechanics of meat sharing during the late Lower Paleolithic at Qesem Cave differed from those typical of both the Middle and Upper Paleolithic in the region.