Donor Characteristics of Pancreas Transplantation in Australia and New Zealand: A Cohort Study 1984-2014

Background The aim of this study was to audit the characteristics of pancreas donors over time in Australia and New Zealand. Pancreas transplantation was introduced in Australian and New Zealand in 1984. Methods We analyzed data from the Australia and New Zealand Islet and Pancreas Transplant Registry, 1984 to 2014. We investigated the variation of donor characteristics of sex, age, body mass index, smoking status, blood group, multiple organ donation, cytomegalovirus status, terminal creatinine, hypertension, and cause of death for pancreas transplantation over time. We used χ2 test (Fisher test when necessary) or analysis of variance to test difference for categorical or continuous characteristics, respectively. Results There were 628 pancreas donors from 1984 to 2014. Donor body mass index (from 21.9 to 24.0, P < 0.001) and age (from 23.9 to 28.5, P = 0.02) have both increased while terminal creatinine has decreased (86.3 to 73.3, P = 0.01) from 1995 to 2014. In the meantime, the proportions of donors with hypertension (from 19% to 1%, P < 0.001) and who were smokers (from 54% to 15%, P < 0.001) have decreased. Profile of cause of donor death has also changed over time (P = 0.06) with increase in cerebral hypoxia/ischemia (from 3% to 17%) and reductions in intracranial hemorrhage (27% to 13%). Conclusions Many donor characteristics have changed over time. The most significant changes appear to reflect changes in the general population, rather than changes in donor selection

Australia and New Zealand Islets and Pancreas Transplant Registry Annual Report 2018—Pancreas Waiting List, Recipients, and Donors

Background This is a synopsis of the registry report from the Australia and New Zealand islet and pancreas transplant registry. The full report is available at http://anziptr.org/reports/. Methods We report data for all solid organ pancreas transplant activity from inception in 1984 to end 2017. Islet-cell transplantation activity is reported elsewhere. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX). Results From 1984 to 2017 a total of 809 solid organ pancreas transplants have been performed in Australia and New Zealand, in 790 individuals. In 2017, 52 people received a pancreas transplant. By center, this was; Auckland (4), Monash (17), and Westmead (31). In 2017, 51 transplants were simultaneous pancreas kidney, whereas 1 was pancreas after kidney, and none were pancreas transplant alone. Conclusions The number of pancreas transplants performed in Australia and New Zealand was slightly lower in 2017 but continues to increase over time

When one phenotype is not enough: divergent evolutionary trajectories govern venom variation in a widespread rattlesnake species

Artículo 10 páginas, 3 figuras 1 tablaUnderstanding the origin and maintenance of phenotypic variation, particularly across a continuous spatial distribution, represents a key challenge in evolutionary biology. For this, animal venoms represent ideal study systems: they are complex, variable, yet easily quantifiable molecular phenotypes with a clear function. Rattlesnakes display tremendous variation in their venom composition, mostly through strongly dichotomous venom strategies, which may even coexist within a single species. Here, through dense, widespread population-level sampling of the Mojave rattlesnake, Crotalus scutulatus, we show that genomic structural variation at multiple loci underlies extreme geographical variation in venom composition, which is maintained despite extensive gene flow. Unexpectedly, neither diet composition nor neutral population structure explain venom variation. Instead, venom divergence is strongly correlated with environmental conditions. Individual toxin genes correlate with distinct environmental factors, suggesting that different selective pressures can act on individual loci independently of their co-expression patterns or genomic proximity. Our results challenge common assumptions about diet composition as the key selective driver of snake venom evolution and emphasize how the interplay between genomic architecture and local-scale spatial heterogeneity in selective pressures may facilitate the retention of adaptive functional polymorphisms across a continuous space.Funding: Leverhulme Trust Grant RPG 2013-315 to WW, Santander Early Career Research Scholarship to GZ, Ministerio de Economía y Competitividad Grant BFU2013-42833-P to JJC.Peer reviewe

Reproductive biology of the pampas deer (Ozotoceros bezoarticus): a review

The pampas deer (Ozotoceros bezoarticus) is a South American grazing deer which is in extreme danger of extinction. Very little is known about the biology of the pampas deer. Moreover, most information has not been published in peer-reviewed scientific journals, and is only available in local publications, theses, etc. Therefore, our aim was to update and summarize the available information regarding the reproductive biology of the pampas deer. Moreover, in most sections, we have also included new, unpublished information. Detailed descriptions are provided of the anatomy of both the female and the male reproductive tract, puberty onset, the oestrous cycle and gestational length. Birthing and the early postpartum period are described, as are maternal behaviour and early fawn development, seasonal distribution of births, seasonal changes in male reproduction and antler cycle, reproductive behaviour, semen collection, and cryopreservation. Finally, an overview is given and future directions of research are proposed

Local expression of IDO, either alone or in combination with CD40Ig, IL10 or CTLA4Ig,inhibits indirect xenorejection responses

Background: To overcome cell-mediated xenorejection by transgenic expression of immunomodulatory molecules by a graft, it is likely that expression of multiple molecules will be required. Previous studies support the use of the immunomodulatory agents indoleamine 2,3-dioxygenase (IDO), CD40Ig, interleukin 10 (IL10), and CTLA4Ig for suppression of rejection responses. We examined the effects of local expression of these molecules by a porcine cell line (PIEC) on indirect murine xenorejection responses in vitro and in vivo. Methods: The PIEC stable lines expressing IDO, CD40Ig, and IL10 as single molecules were generated. In addition, PIEC lines expressing IDO with either CD40Ig, IL10 or CTLA4Ig were generated to produce cell lines expressing two molecules. BALB/c mice were primed with wild type PIEC, followed by harvesting splenocytes used as responder cells and PIEC expressing immunomodulatory molecules as stimulators, in proliferation and cytokine assays. In vivo effects of modified PIEC were examined by transplantation of PIEC lines expressing the immunomodulatory molecules under the renal capsule of naïve mice. PIEC grafts were harvested for histological evaluation at days 7 and 14. Results: Proliferation of primed BALB/c splenocytes was inhibited most significantly by IDO compared with control cells (49%, P = 0.02). In addition both Th1 (interferon-gamma) and Th2 (IL4 and IL10) cytokines were markedly inhibited in vitro by IDO expression. IL10 expressing cells did not inhibit proliferation as potently (37%, P = 0.03) whilst CD40Ig lead to an increase in proliferative responses (59%, P = 0.02). Co-expression of CD40Ig, IL10, and CTLA4Ig with IDO resulted in further modest reductions in proliferation compared with IDO expression alone. When transplanted under the renal capsule of BALB/c mice, those grafts expressing IDO demonstrated significantly lower levels of lymphocyte infiltration at days 7 and 14 than control grafts and those expressing CD40Ig, CTLA4Ig or IL10 alone. Grafts co-expressing IDO and a second molecule were no better protected than those expressing IDO alone. Graft cell viability (PIECs) was reduced in some IDO expressing grafts suggesting high levels of IDO expression may inhibit PIEC viability, however, grafts co-expressing IDO-CTLA4Ig and IDO-IL10 were not affected in this way. Conclusion: Indoleamine 2,3-dioxygenase appears to be a potent molecule for protecting xenografts from cell-mediated rejection responses activated via the indirect pathway. Co-expression of IDO with both CTLA4Ig and IL10 warrants further investigation. Overall these findings support pursuing further studies, in larger animal models, to determine whether increased IDO activity within the graft itself can attenuate xenorejection responses

JUN Amino-Terminal Kinase 1 Signaling in the Proximal Tubule Causes Cell Death and Acute Renal Failure in Rat and Mouse Models of Renal Ischemia/Reperfusion Injury

Activation of the JUN amino-terminal kinase (JNK) pathway is prominent in most forms of acute and progressive tubulointerstitial damage, including acute renal ischemia/reperfusion injury (IRI). There are two forms of JNK expressed in the kidney, JNK1 and JNK2. Systemic administration of pan-JNK inhibitors suppresses renal IRI; however, the contribution of JNK1 versus JNK2, and the specific role of JNK activation in the proximal tubule in IRI, remains unknown. These questions were addressed in rat and mouse models of acute bilateral renal IRI. Administration of the JNK inhibitor, CC-930, substantially reduced the severity of renal failure, tubular damage, and inflammation at 24 hours in a rat IRI model. Next, Jnk1(-/-) mice, but not Jnk2(-/-) mice, were shown to be significantly protected against acute renal failure, tubular damage, and inflammation in the IRI model. Furthermore, mice with conditional Jnk1 deletion in the proximal tubule also showed considerable protection from IRI-induced renal failure, tubular damage, and inflammation. Finally, primary cultures of Jnk1(-/-), but not Jnk2(-/-), tubular epithelial cells were protected from oxidant-induced cell death, in association with preventing phosphorylation of proteins (receptor interacting serine/threonine kinase 3 and mixed lineage kinase domain-like pseudokinase) in the necroptosis pathway. In conclusion, JNK1, but not JNK2, plays a specific role in IRI-induced cell death in the proximal tubule, leading to acute renal failure