Adaptive group coordination and role differentiation

Many real world situations (potluck dinners, academic departments, sports teams, corporate divisions, committees, seminar classes, etc.) involve actors adjusting their contributions in order to achieve a mutually satisfactory group goal, a win-win result. However, the majority of human group research has involved situations where groups perform poorly because task constraints promote either individual maximization behavior or diffusion of responsibility, and even successful tasks generally involve the propagation of one correct solution through a group. Here we introduce a group task that requires complementary actions among participants in order to reach a shared goal. Without communication, group members submit numbers in an attempt to collectively sum to a randomly selected target number. After receiving group feedback, members adjust their submitted numbers until the target number is reached. For all groups, performance improves with task experience, and group reactivity decreases over rounds. Our empirical results provide evidence for adaptive coordination in human groups, and as the coordination costs increase with group size, large groups adapt through spontaneous role differentiation and self-consistency among members. We suggest several agent-based models with different rules for agent reactions, and we show that the empirical results are best fit by a flexible, adaptive agent strategy in which agents decrease their reactions when the group feedback changes. The task offers a simple experimental platform for studying the general problem of group coordination while maximizing group returns, and we distinguish the task from several games in behavioral game theory.     

Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory

The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional UGT1A6. Out of 22 additional taxa sampled, representative of most Carnivora families, only brown hyena (Parahyaena brunnea) and northern elephant seal (Mirounga angustirostris) showed inactivating UGT1A6 mutations. A comprehensive literature review of the natural diet of the sampled taxa indicated that all species with defective UGT1A6 were hypercarnivores (>70% dietary animal matter). Furthermore those species with UGT1A6 defects showed evidence for reduced amino acid constraint (increased dN/dS ratios approaching the neutral selection value of 1.0) as compared with species with intact UGT1A6. In contrast, there was no evidence for reduced amino acid constraint for these same species within UGT1A1, the gene encoding the enzyme responsible for detoxification of endogenously generated bilirubin. Our results provide the first evidence suggesting that diet may have played a permissive role in the devolution of a mammalian drug metabolizing enzyme. Further work is needed to establish whether these preliminary findings can be generalized to all Carnivora.     

Clinical features of symptomatic patellofemoral joint osteoarthritis

Introduction

Patellofemoral joint osteoarthritis (OA) is common and leads to pain and disability. However, current classification criteria do not distinguish between patellofemoral and tibiofemoral joint OA. The objective of this study was to provide empirical evidence of the clinical features of patellofemoral joint OA (PFJOA) and to explore the potential for making a confident clinical diagnosis in the community setting.

Methods

This was a population-based cross-sectional study of 745 adults aged ≥50 years with knee pain. Information on risk factors and clinical signs and symptoms was gathered by a self-complete questionnaire, and standardised clinical interview and examination. Three radiographic views of the knee were obtained (weight-bearing semi-flexed posteroanterior, supine skyline and lateral) and individuals were classified into four subsets (no radiographic OA, isolated PFJOA, isolated tibiofemoral joint OA, combined patellofemoral/tibiofemoral joint OA) according to two different cut-offs: ''any OA'' and ''moderate to severe OA''. A series of binary logistic and multinomial regression functions were performed to compare the clinical features of each subset and their ability in combination to discriminate PFJOA from other subsets.

Results

Distinctive clinical features of moderate to severe isolated PFJOA included a history of dramatic swelling, valgus deformity, markedly reduced quadriceps strength, and pain on patellofemoral joint compression. Mild isolated PFJOA was barely distinguished from no radiographic OA (AUC 0.71, 95% CI 0.66, 0.76) with only difficulty descending stairs and coarse crepitus marginally informative over age, sex and body mass index. Other cardinal signs of knee OA - the presence of effusion, bony enlargement, reduced flexion range of movement, mediolateral instability and varus deformity - were indicators of tibiofemoral joint OA.

Conclusions

Early isolated PFJOA is clinically manifest in symptoms and self-reported functional limitation but has fewer clear clinical signs. More advanced disease is indicated by a small number of simple-to-assess signs and the relative absence of classic signs of knee OA, which are predominantly manifestations of tibiofemoral joint OA. Confident diagnosis of even more advanced PFJOA may be limited in the community setting.     

Polyamines are intracellular messengers in the beta-adrenergic regulation of Ca2+ fluxes, [Ca2+]i and membrane transport in rat heart myocytes

The beta-adrenergic agonist 1-isoproterenol (0.1 microM) evokes an acute (less than 5-10 sec) transient increase in the activity of ornithine decarboxylase (ODC), and the levels of polyamines (putrescine, spermidine, spermine) in acutely isolated rat ventricular myocytes. Isoproterenol rapidly (less than 15 sec) increases 45Ca influx and efflux, decreases [Ca2+]i, and stimulates Ca2+-dependent membrane transport (endocytosis, hexose transport, amino acid transport). The beta-adrenergic antagonist propranolol blocks isoproterenol-induced membrane transport. The ODC inhibitor alpha-difluoromethylornithine (DFMO, 5-10 mM) blocks the isoproterenol-evoked increase in ODC activity and polyamine levels and the changes in 45Ca fluxes, [Ca2+]i and membrane transport. Putrescine (0.5-1 mM) replenishes cellular polyamines and reverses the DFMO effect. These data exclude an increase in [Ca2+]i in stimulus-transport coupling, and support the hypothesis that polyamines are messengers in beta-adrenoceptor-mediated regulation of transmembrane Ca2+ fluxes, [Ca2+]i, and Ca2+-dependent membrane transport.     

Blood brain barrier breakdown in brain edema following cold injury is mediated by microvascular polyamines

A focal freeze injury to rat cerebral cortex induces an early (less than 5 min) increase in brain ornithine decarboxylase activity and an accumulation of polyamines involving cerebral microvessels. This polyamine synthesis correlates with the abnormal increase in microvascular permeability, monitored by uptake of Evans Blue and sod. fluorescein. The ornithine decarboxylase inhibitor alpha-difluoromethylornithine suppressed the injury-induced increment in spermidine and spermine and microvascular permeability. Putrescine nullified alpha-difluoromethylornithine inhibition and restored microvessel spermidine and spermine and the pathological increase in microvascular permeability. These results indicate that polyamine synthesis is obligatory for blood-brain barrier breakdown. alpha-Difluoromethylornithine may be useful in the treatment of vasogenic brain edema.     

Testosterone induces a rapid stimulation of endocytosis,amino acid and hexose transport in mouse kidney cortex

Testosterone induced a rapid (<1 min) stimulation of endocytosis, amino acid and hexose transport, measured by the temperature-sensitive uptake of HRP, ¹⁴C-AIB and ³H-DG, in mouse kidney cortex slices. The hormonal increment in uptake persisted for at least 60–120 min, showed time-, energy-, and Na⁺-dependence, and varied with substrate and testosterone concentration. Testosterone was maximally effective at 10^?8 to 10^?7 M. Peroxidase histochemistry indicated that the hormonal increase in HRP uptake is restricted to proximal tubules. Testosterone was more effective than DHT, whereas cyproterone acetate, androsterone and dexamethasone had little or no stimulating effect on this uptake. Kidney slices from androgen-insensitive $\text{tfm}\text{Y}$ mice did not respond to testosterone. The rapid increase in endocytosis, amino acid and hexose transport may represent a direct, receptor-mediated response of the surface membrane of target cells to testosterone.