AKAP150-anchored PKA regulation of synaptic transmission and plasticity, neuronal excitability and CRF neuromodulation in the lateral habenula.

Numerous studies of hippocampal synaptic function in learning and memory have established the functional significance of the scaffolding A-kinase anchoring protein 150 (AKAP150) in kinase and phosphatase regulation of synaptic receptor and ion channel trafficking/function and hence synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a critical role in brain's processing of rewarding/aversive experiences. Here we focused on an unexplored role of AKAP150 in the lateral habenula (LHb), a diencephalic brain region that integrates and relays negative reward signals from forebrain striatal and limbic structures to midbrain monoaminergic centers. LHb aberrant activity (specifically hyperactivity) is also linked to depression. Using whole cell patch clamp recordings in LHb of male wildtype (WT) and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), we found that the genetic disruption of PKA anchoring to AKAP150 significantly reduced AMPA receptor (AMPAR)-mediated glutamatergic transmission and prevented the induction of presynaptic endocannabinoid (eCB)-mediated long-term depression (LTD) in LHb neurons. Moreover, ΔPKA mutation potentiated GABAA receptor (GABAAR)-mediated inhibitory transmission postsynaptically while increasing LHb intrinsic neuronal excitability through suppression of medium afterhyperpolarizations (mAHPs). Given that LHb is a highly stress-responsive brain region, we further tested the effects of corticotropin releasing factor (CRF) stress neuromodulator on synaptic transmission and intrinsic excitability of LHb neurons in WT and ΔPKA mice. As in our earlier study in rat LHb, CRF significantly suppressed GABAergic transmission onto LHb neurons and increased intrinsic excitability by diminishing small-conductance potassium (SK) channel-mediated mAHPs. ΔPKA mutation-induced suppression of mAHPs also blunted the synaptic and neuroexcitatory actions of CRF in mouse LHb. Altogether, our data suggest that AKAP150 complex signaling plays a critical role in regulation of AMPAR and GABAAR synaptic strength, glutamatergic plasticity and CRF neuromodulation possibly through AMPAR and potassium channel trafficking and eCB signaling within the LHb.

Caregiver's cognitive traits are associated with pup fitness in a cooperatively breeding mammal.

Studies across diverse taxa have revealed the importance of early life environment and parenting on characteristics later in life. While some have shown how early life experiences can impact cognitive abilities, very few have turned this around and looked at how the cognitive skills of parents or other carers during early life affect the fitness of young. In this study, we investigate how the characteristics of carers may affect proxies of fitness of pups in the cooperatively breeding banded mongoose (Mungos mungo). We gave adult mongooses a spatial memory test and compared the results to the success of the pups those individuals cared for. Our results show a tradeoff between speed and accuracy in the spatial memory task, with those individuals which were faster to move between cups in the test arena making more erroneous re-visits to cups that they had already checked for food. Furthermore, the accuracy of their carer predicted future survival, but not weight gain of the pups and the effect was contrary to expected, with pups that were cared for by less accurate individuals being more likely to survive to adulthood. Our research also provides evidence that while younger carers were less accurate during the test, the age of the carer did not have an impact on the chance of raising young that live to sexual maturity. Our findings suggest that banded mongoose carers' cognitive traits have fitness consequences for the young they care for, affecting the chance that these young live to maturity.

The social formation of fitness: lifetime consequences of prenatal nutrition and postnatal care in a wild mammal population.

Research in medicine and evolutionary biology suggests that the sequencing of parental investment has a crucial impact on offspring life history and health. Here, we take advantage of the synchronous birth system of wild banded mongooses to test experimentally the lifetime consequences to offspring of receiving extra investment prenatally versus postnatally. We provided extra food to half of the breeding females in each group during pregnancy, leaving the other half as matched controls. This manipulation resulted in two categories of experimental offspring in synchronously born litters: (i) 'prenatal boost' offspring whose mothers had been fed during pregnancy, and (ii) 'postnatal boost' offspring whose mothers were not fed during pregnancy but who received extra alloparental care in the postnatal period. Prenatal boost offspring lived substantially longer as adults, but postnatal boost offspring had higher lifetime reproductive success (LRS) and higher glucocorticoid levels across the lifespan. Both types of experimental offspring had higher LRS than offspring from unmanipulated litters. We found no difference between the two experimental categories of offspring in adult weight, age at first reproduction, oxidative stress or telomere lengths. These findings are rare experimental evidence that prenatal and postnatal investments have distinct effects in moulding individual life history and fitness in wild mammals. This article is part of the theme issue 'Evolutionary ecology of inequality'.

A veil of ignorance can promote fairness in a mammal society.

Rawls argued that fairness in human societies can be achieved if decisions about the distribution of societal rewards are made from behind a veil of ignorance, which obscures the personal gains that result. Whether ignorance promotes fairness in animal societies, that is, the distribution of resources to reduce inequality, is unknown. Here we show experimentally that cooperatively breeding banded mongooses, acting from behind a veil of ignorance over kinship, allocate postnatal care in a way that reduces inequality among offspring, in the manner predicted by a Rawlsian model of cooperation. In this society synchronized reproduction leaves adults in a group ignorant of the individual parentage of their communal young. We provisioned half of the mothers in each mongoose group during pregnancy, leaving the other half as matched controls, thus increasing inequality among mothers and increasing the amount of variation in offspring birth weight in communal litters. After birth, fed mothers provided extra care to the offspring of unfed mothers, not their own young, which levelled up initial size inequalities among the offspring and equalized their survival to adulthood. Our findings suggest that a classic idea of moral philosophy also applies to the evolution of cooperation in biological systems.

Elevated glucocorticoid concentrations during gestation predict reduced reproductive success in subordinate female banded mongooses.

Dominant females in social species have been hypothesized to reduce the reproductive success of their subordinates by inducing elevated circulating glucocorticoid (GC) concentrations. However, this 'stress-related suppression' hypothesis has received little support in cooperatively breeding species, despite evident reproductive skews among females. We tested this hypothesis in the banded mongoose (Mungos mungo), a cooperative mammal in which multiple females conceive and carry to term in each communal breeding attempt. As predicted, lower ranked females had lower reproductive success, even among females that carried to term. While there were no rank-related differences in faecal glucocorticoid (fGC) concentrations prior to gestation or in the first trimester, lower ranked females had significantly higher fGC concentrations than higher ranked females in the second and third trimesters. Finally, females with higher fGC concentrations during the third trimester lost a greater proportion of their gestated young prior to their emergence from the burrow. Together, our results are consistent with a role for rank-related maternal stress in generating reproductive skew among females in this cooperative breeder. While studies of reproductive skew frequently consider the possibility that rank-related stress reduces the conception rates of subordinates, our findings highlight the possibility of detrimental effects on reproductive outcomes even after pregnancies have become established.

Evidence for frequent incest in a cooperatively breeding mammal.

As breeding between relatives often results in inbreeding depression, inbreeding avoidance is widespread in the animal kingdom. However, inbreeding avoidance may entail fitness costs. For example, dispersal away from relatives may reduce survival. How these conflicting selection pressures are resolved is challenging to investigate, but theoretical models predict that inbreeding should occur frequently in some systems. Despite this, few studies have found evidence of regular incest in mammals, even in social species where relatives are spatio-temporally clustered and opportunities for inbreeding frequently arise. We used genetic parentage assignments together with relatedness data to quantify inbreeding rates in a wild population of banded mongooses, a cooperatively breeding carnivore. We show that females regularly conceive to close relatives, including fathers and brothers. We suggest that the costs of inbreeding avoidance may sometimes outweigh the benefits, even in cooperatively breeding species where strong within-group incest avoidance is considered to be the norm.

Methods used by Dental Practice-based Research Network (DPBRN) dentists to diagnose dental caries.

OBJECTIVES: To (1) identify the methods that dentists in The Dental Practice-Based Research Network (DPBRN) use to diagnose dental caries; (2) quantify their frequency of use and (3) test the hypothesis that certain dentist and dental practice characteristics are significantly associated with their use. METHODS: A questionnaire about methods used for caries diagnosis was sent to DPBRN dentists who reported doing some restorative dentistry; 522 dentists participated. Questions included the use of dental radiographs, the dental explorer, laser fluorescence, air-drying and fiber-optic devices and magnification as used when diagnosing primary, secondary/recurrent or non-specific caries lesions. Variations on the frequency of their use were tested using multivariate analysis and Bonferroni tests. RESULTS: Overall, the dental explorer was the instrument most commonly used to detect primary occlusal caries and caries at the margins of existing restorations. In contrast, laser fluorescence was rarely used to help diagnose occlusal primary caries. For proximal caries, radiographs were used to help diagnose 75%­100% of lesions by 96% of the DPBRN dentists. Dentists who use radiographs most often to assess proximal surfaces of posterior teeth were significantly more likely to also report providing a higher percentage of patients with individualized caries prevention (p=.040) and seeing a higher percentage of pediatric patients (p=.001). CONCLUSION: The use of specific diagnostic methods varied substantially. The dental explorer and radiographs are still the most commonly used diagnostic methods..

Comparison of a solution of super-oxidized water (Sterilox) with glutaraldehyde for the disinfection of bronchoscopes, contaminated.

The efficacy of Sterilox, a super-oxidized water holding a reduction/oxidation potential of greater than 950 mV was compared with the efficacy of glutaraldehyde against clinical isolates of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare. An in use method using an automated bronchoscope washing machine demonstrated that over five cycles, Sterilox with a contact time of 5 min gave log10 reduction factors for M. tuberculosis and M. avium-intracellulare of >6 and >5, respectively. Glutaraldehyde with a contact time of 10 min gave log10 reduction factors for both M. tuberculosis and M. avium-intracellulare of >4, and at a contact time of 20 min >5 each. The non-toxic nature of Sterilox, together with the reduction in viable counts demonstrated in this study, suggest that the solution is an effective alternative mycobactericidal agent to the established disinfectants for the disinfection of bronchoscopes and, therefore, justifies further investigation.

The Agrobacterium tumefaciens motor gene, motA, is in a linked cluster with the flagellar switch protein genes, fliG, fliM and fliN.

We report the sequence of 3978 bp of the Agrobacterium tumefaciens chromosome which contains a putative operon encoding the homologues of the transmembrane proton channel protein MotA, and the flagellar switch proteins FliM, FliN and FliG. Two transposon insertions in fliG result in a non-flagellate phenotype, indicating that this gene at least is required for flagellar assembly.