Conformity in mate choice, the overlooked social component of animal and human culture.

Although conformity as a major driver for human cultural evolution is a well-accepted and intensely studied phenomenon, its importance for non-human animal culture has been largely overlooked until recently. This limited for decades the possibility of studying the roots of human culture. Here, we provide a historical review of the study of conformity in both humans and non-human animals. We identify gaps in knowledge and propose an evolutionary route towards the sophisticated cultural processes that characterize humanity. A landmark in the study of conformity is Solomon Asch's famous experiment on humans in 1955. By contrast, interest in conformity among evolutionary biologists has only become salient since the turn of the new millennium. A striking result of our review is that, although studies of conformity have examined many biological contexts, only one looked at mate choice. This is surprising because mate choice is probably the only context in which conformity has self-reinforcing advantages across generations. Within a metapopulation, i.e. a group of subpopulations connected by dispersing individuals, dispersers able to conform to the local preference for a given type of mate have a strong and multigenerational fitness advantage. This is because once females within one subpopulation locally show a bias for one type of males, immigrant females who do not conform to the local trend have sons, grandsons, etc. of the non-preferred phenotype, which negatively and cumulatively affects fitness over generations in a process reminiscent of the Fisher runaway process. This led us to suggest a sex-driven origin of conformity, indicating a possible evolutionary route towards animal and human culture that is rooted in the basic, and thus ancient, social constraints acting on mating preferences within a metapopulation. In a generic model, we show that dispersal among subpopulations within a metapopulation can effectively maintain independent Fisher runaway processes within subpopulations, while favouring the evolution of social learning and conformity at the metapopulation scale; both being essential for the evolution of long-lasting local traditions. The proposed evolutionary route to social learning and conformity casts surprising light on one of the major processes that much later participated in making us human. We further highlight several research avenues to define the spectrum of conformity better, and to account for its complexity. Future studies of conformity should incorporate experimental manipulation of group majority. We also encourage the study of potential links between conformity and mate copying, animal aggregations, and collective actions. Moreover, validation of the sex-driven origin of conformity will rest on the capacity of human and evolutionary sciences to investigate jointly the origin of social learning and conformity. This constitutes a stimulating common agenda and militates for a rapprochement between these two currently largely independent research areas.

Sensing a binding event through charge transport variations using an aromatic oligoamide capsule.

The selective binding properties of a 13-mer oligoamide foldamer capsule composed of 4 different aromatic subunits are reported. The capsule was designed to recognize dicarboxylic acids through multiple-point interactions owing to a combination of protonation/deprotonation events, H-bonding, and geometrical constraints imparted by the rigidity of the foldamer backbone. Compared to tartaric acid, binding of 2,2-difluorosuccinic acid or 2,2,3,3-tetrafluorosuccinic acid resulted in symmetry breaking due to deprotonation of only one of the two carboxylic acid groups of the encapsulated species as shown by NMR studies in solution and by single-crystal X-ray diffraction in the solid state. An analogous 14-mer foldamer capsule terminated with a thiol anchoring group was used to probe the complexation event in self-assembled monolayers on Au substrates. Ellipsometry and polarization-modulation infrared absorption-reflection spectroscopy studies were consistent with the formation of a single molecule layer of the foldamer capsule oriented vertically with respect to the surface. The latter underwent smooth complexation of 2,2-difluorosuccinic acid with deprotonation of one of the two carboxylic acid groups. A significant (80-fold) difference in the charge transport properties of the monolayer upon encapsulation of the dicarboxylic acid was evidenced from conducting-AFM measurements (S = 1.1 × 10-9 vs. 1.4 × 10-11 ohm-1 for the empty and complexed capsule, respectively). The modulation in conductivity was assigned to protonation of the aromatic foldamer backbone.

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers.

Four-component coupling reactions between xanthogenates, alkenes, CO, and sulfonyl oxime ethers were studied. In the presence of hexabutylditin, working as a propagating radical reagent, the chain reaction proceeds, as expected, taking into account reagents polarities, affording the corresponding functionalized α-keto oximes. Although yields are modest, this rare one-pot four-component process is easy to carry out and the resulting compounds, bearing multiple functionalities, have the potential for further elaboration.

Maturity onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience.

The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients.

[History of medical progress in renal transplantation: a review of 3,000 consecutive kidney grafts at Bicetre-Kremlin, Bicetre University Hospital - France]. / Histoire du progrès médical en transplantation rénale. A propos d'une série de 3 000 transplantations consécutives réalisées dans le CHU de Bicêtre.

Major medical progress has been made in the field of renal transplantation over the last 40 years, thanks to advances in areas such as metabolism, immunology, therapeutics, and pathology. This progress has been accompanied by important changes in French legislation that governs organ harvest and transplantation, as well as the institutions that regulate organ allocation. Patient and graft survival have both increased markedly, although long-term improvements have been somewhat offset by complications, including adverse effects of immunosuppression. On average recipients are older than in the past and some recipients are now dying from age-related comorbidities despite having functional grafts.

Efficacy and safety of the H1N1 monovalent vaccine in renal-transplant recipients and dialysis patients.

BACKGROUND: The (H1N)1v influenza virus infection emerged in 2009 as a serious disease in targeted populations. Herein, we report on the tolerability and efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients. METHODS: 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12 patients treated with peritoneal dialysis (PDP), 7 patients treated with haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted-vaccine injection, and RTRs received two unadjuvanted vaccine injections within a 21-day period. Serologic response was defined as a haemagglutination inhibition titre of > 40 (seroprotection) and/or at least a four-fold increase in antibody titre from baseline (seroconversion). RESULTS: Seroprotection rate after vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p = 0.001). Serologic response was similar in PDPs and HDPs. CONCLUSIONS: Serologic response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was low in RTRs as compared to DPs.

Outcomes of renal transplantation in patients with autosomal dominant polycystic kidney disease: a nationwide longitudinal study.

Renal transplantation in patients with autosomal dominant polycystic kidney disease (ADPKD) is a medical and surgical challenge. Detailed longitudinal epidemiological studies on large populations are lacking and it is mandatory to care better for these patients. The success of such a project requires the development of a validated epidemiological database. Herein, we present the results of the largest longitudinal study to date on renal transplant in patients with ADPKD. The 15-year outcomes following renal transplantation of 534 ADPKD patients were compared with 4779 non-ADPKD patients. This comprehensive, longitudinal, multicenter French study was performed using the validated database, DIVAT (Données Informatisées et VAlidées en Transplantaion). We demonstrate that renal transplantation in ADPKD is associated with better graft survival, more thromboembolic complications, more metabolic complications, and increased incidence of hypertension, whereas the prevalence of infections is not increased. This study provides important new insights that could lead to a better care for renal transplant patients with ADPKD.

Emerging strategies to preserve renal function.

Although there has been tremendous improvement in managing chronic kidney disease (CKD) with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in the last 15 years, CKD still progresses. Therefore, new emerging strategies are needed. The gold standard still lies with optimum renin-angiotensin-aldosterone system blockade, although many questions remain about how this is best achieved, such as regarding the efficacy of combinations of ACE inhibitor and ARBs, supramaximal doses of ARBs alone and combinations of either ACE inhibitor or ARBs with direct renin inhibitors, antialdosterone agents. Other promising molecules currently being tested are endothelin receptor antagonists and glitazones. Also, the role of other current therapies being used during CKD, including statins, vitamin D and erythropoiesis-stimulating agents, will be discussed, as these may also exert nephroprotective effects.

[Use of new non-nephrotoxic immunosuppressive drugs in kidney transplantation, especially after ischemia-reperfusion injury]. / Utilisation de nouvelles molécules immunosuppres- sives non néphrotoxiques en transplantation rénale, en particulier après lésions d'ischémie-reperfusion.

Medium- and long-term renal graft survival depends on 4 main factors: the quality of the harvested graft, ischemia-reperfusion injury during harvesting and re-implantation, rejection, and the nephrotoxicity of certain drugs (especially immunosuppressants) used in this setting. The most nephrotoxic immunosuppressive drugs are the anticalcineurins (cyclosporine A and tacrolimus), a class discovered in the late 1970s and currently representing a basic component of all immunosuppressive protocols for solid organ graft recipients. The renal tubular and vascular toxicity of anticalcineurins is due to their immunosuppressive mechanism: they block the calcineurin pathway and thereby prevent transmission of the first signal from the T cell receptor to the nucleus, which normally triggers cytokine synthesis, New non-nephrotoxic immunosuppressants are therefore needed, especially for grafts of poor quality or subject to severe ischemia-reperfusion injury. Attention is turning to "old " molecules such as anti-thymocyte globulins, but exciting new immunosuppressants are now appearing. Alefacept is a fusion protein that binds to the immunological synapse-associated molecule CD2, which normally interacts with LFA-3. Belatacept, another fusion protein, blocks the T cell second signal CD 28-B7.1/B7.2. Finally, new chemical agents are being developed, such as sautrasporine, a tyrosine kinase inhibitor, and tofacitinib, a Jak inhibitor.

Co-signals in organ transplantation.

PURPOSE OF REVIEW: The nonimmune effects of currently used immunosuppressive drugs result in a high incidence of late graft loss due to nephrotoxicity and death. As an immune-specific alternative to conventional immunosuppressants, new biotechnology tools can be used to block the costimulation signal of T-cell activation. RECENT FINDINGS: Many experimental studies, particularly preclinical studies in nonhuman primates, have focused on blocking 'classical' B7/CD28 and CD40/CD40L pathways, which are critical in primary T-cell activation, but also on new B7/CD28 and TNF/TNF-R pathways families of costimulatory molecules that can deliver positive or negative costimulation signals to regulate the alloimmune response. SUMMARY: Belatacept is a new fusion protein derived from CTLA4-Ig that can be used to prevent acute rejection in renal transplantation instead of calcineurin inhibitors. Belatacept can also prevent acute rejection efficiently in humans and, more interestingly, can improve renal function and cardiovascular risk factors in this population.

Advances in immunosuppression for renal transplantation.

The development of immunosuppressants with minimal adverse and nephrotoxic effects is important to improve outcomes, such as acute and chronic antibody-mediated rejection, after organ transplantation. In addition, the application of expanded criteria for donors and transplantation in immunized patients necessitates the development of new therapies. Drug development over the past 10 years has generally been disappointing, but several new promising compounds have been or are being developed to prevent acute and chronic transplant rejection. In this Review, we report on several compounds that have been developed to remove allogenic T cells and/or to inhibit T-cell activation. We also discuss compounds that interfere with antibody-mediated rejection.

Expanding the criteria of renal kidneys for transplantation: use of donors with acute renal failure.

BACKGROUND: Increased numbers of patients waiting for renal transplantation have led to widening selection criteria for grafts. Thus, we have evaluated the outcome of transplanted kidneys procured in the presence of acute renal failure (ARF). METHODS: Transplant patients (n = 52) with a kidney procured with ARF were studied. Clinical data from donors and recipients, serum creatinine (SCr), creatinine clearance [estimated glomerular filtration rate (eGFR)], cold ischaemia duration, time to urine flow recovery or renal function recovery, and the number of haemodialysis sessions, were collected retrospectively. RESULTS: Mean donor age was 45.7 +/- 12.7 years, and the mean SCr at the time of harvesting was 276.3 +/- 104.2 micromol/l. Recipients' mean age was 51.1 +/- 12.1 years. After transplantation, recovery of renal function was observed after 7.6 +/- 7.1 days, and required 1.9 +/- 3.0 haemodialysis sessions. SCr was 124.6 +/- 49.5 micromol/l, and eGFR was 56.2 +/- 19.8 ml/min at last follow-up. eGFR was significantly lower if the donor's death was due to stroke or cerebral haemorrhage (CH), or if the donors had previous cardiovascular disease (CVD) (P < 0.02). Patients with eGFR of <50 ml/min (n = 23) had donors who were older, and whose cause of death was more frequently related to CVD factors or to CH/stroke (P < 0.03). There were no significant differences between the two groups regarding age of recipient, gender of the donor or recipient, cold ischaemia time, occurrence of cardiac arrest, collapse or acute rejection. Linear regression analysis indicated that donor age and occurrence of acute rejection were independent factors associated with eGFR. CONCLUSIONS: ARF before organ procurement does not have a negative effect on subsequent renal function. However, old age, CVD risk factors or CH, and late renal function recovery after transplantation are correlated with subsequent lower renal function. Thus, renal grafts with ARF can be used for renal transplantations.

IgA nephropathy associated with ankylosing spondylitis is not controlled by infliximab therapy.

The association between seronegative spondyloarthro- pathies and IgA nephropathy is well documented, mainly in cases of ankylosing spondylitis (AS). However, although these diseases have been associated, the physiopathological links between each other appear unclear. Anti-TNFalpha agents have transformed the outcome of axial forms of AS resistant to conventional anti-inflammatory therapies. Infliximab, a monoclonal anti-TNFalpha antibody, has greatly improved the evolution of AS although several adverse events have been described. On the other hand, infliximab has been demonstrated to reduce renal symptoms associated with chronic inflammatory rheumatological diseases, such as amyloid A (AA) amyloidosis, but few data are available on its efficacy in controlling IgA nephropathy associated with AS [1,2]. We report here a case of IgA nephropathy associated with AS that became symptomatic, whereas infliximab therapy efficiently controlled the rheumatological disease. This suggests that even though infliximab therapy effectively controls rheumatological manifestations, it may not be able to prevent IgA nephropathy associated with AS. Thus, this case report illustrates the complexity of the physiopathology of both diseases.

Alagille syndrome in adult patients: it is never too late.

Alagille syndrome (AGS; Online Mendelian Inheritance in Man no. 118450) is a multisystem autosomal dominant disorder with highly variable expression characterized by chronic cholestasis caused by a paucity of interlobular bile ducts, skeletal abnormalities, peculiar facies, ocular abnormalities, and cardiovascular disorders. AGS is diagnosed almost exclusively in children in the setting of predominant liver manifestations or, more rarely, in their adult relatives. We report 2 patients in whom AGS was diagnosed in adulthood during the workup of renal disease in the absence of a well-defined familial history. Renal disease caused by AGS probably is underdiagnosed in adult patients.