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'.

Leaders of war: modelling the evolution of conflict among heterogeneous groups.

War, in human and animal societies, can be extremely costly but can also offer significant benefits to the victorious group. We might expect groups to go into battle when the potential benefits of victory (V) outweigh the costs of escalated conflict (C); however, V and C are unlikely to be distributed evenly in heterogeneous groups. For example, some leaders who make the decision to go to war may monopolize the benefits at little cost to themselves ('exploitative' leaders). By contrast, other leaders may willingly pay increased costs, above and beyond their share of V ('heroic' leaders). We investigated conflict initiation and conflict participation in an ecological model where single-leader-multiple-follower groups came into conflict over natural resources. We found that small group size, low migration rate and frequent interaction between groups increased intergroup competition and the evolution of 'exploitative' leadership, while converse patterns favoured increased intragroup competition and the emergence of 'heroic' leaders. We also found evidence of an alternative leader/follower 'shared effort' outcome. Parameters that favoured high contributing 'heroic' leaders, and low contributing followers, facilitated transitions to more peaceful outcomes. We outline and discuss the key testable predictions of our model for empiricists studying intergroup conflict in humans and animals. This article is part of the theme issue 'Intergroup conflict across taxa'.

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.

Spontaneous abortion as a response to reproductive conflict in the banded mongoose.

When breeding females compete for limited resources, the intensity of this reproductive conflict can determine whether the fitness benefits of current reproductive effort exceed the potential costs to survival and future fertility. In group-living species, reproductive competition can occur through post-natal competition among the offspring of co-breeding females. Spontaneous abortion could be a response to such competition, allowing females to curtail reproductive expenditure on offspring that are unlikely to survive and to conserve resources for future breeding opportunities. We tested this hypothesis using long-term data on banded mongooses, Mungos mungo, in which multiple females within a group give birth synchronously to a communal litter that is cared for by other group members. As predicted, abortions were more likely during dry periods when food is scarce, and in breeding attempts with more intense reproductive competition. Within breeding events, younger, lighter females carrying smaller fetuses were more likely to abort, particularly those that were also of lower rank. Our results suggest that abortion may be a means by which disadvantaged females conserve resources for future breeding attempts in more benign conditions, and highlight that female reproductive competition may be resolved long before the production of offspring.

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.

Bone loss in a new rodent model combining spinal cord injury and cast immobilization.

OBJECTIVES: Characterize bone loss in our newly developed severe contusion spinal cord injury (SCI) plus hindlimb immobilization (IMM) model and determine the influence of muscle contractility on skeletal integrity after SCI. METHODS: Female Sprague-Dawley rats were randomized to: (a) intact controls, (b) severe contusion SCI euthanized at Day 7 (SCI-7) or (c) Day 21 (SCI-21), (d) 14 days IMM-alone, (e) SCI+IMM, or (f) SCI+IMM plus 14 days body weight supported treadmill exercise (SCI+IMM+TM). RESULTS: SCI-7 and SCI-21 exhibited a >20% reduction in cancellous volumetric bone mineral density (vBMD) in the hindlimbs (p⋜0.01), characterized by reductions in cancellous bone volume (cBV/TV%), trabecular number (Tb.N), and trabecular thickness. IMM-alone induced no observable bone loss. SCI+IMM exacerbated cancellous vBMD deficits with values being >45% below Controls (p⋜0.01) resulting from reduced cBV/TV% and Tb.N. SCI+IMM also produced the greatest cortical bone loss with distal femoral cortical area and cortical thickness being 14-28% below Controls (p⋜0.01) and bone strength being 37% below Controls (p⋜0.01). SCI+IMM+TM partially alleviated bone deficits, but values remained below Controls. CONCLUSIONS: Residual and/or facilitated muscle contractility ameliorate bone decrements after severe SCI. Our novel SCI+IMM model represents a clinically-relevant means of assessing strategies to prevent SCI-induced skeletal deficits.

Characterization of genes with a putative key role in the parasitic lifestyle of the nematode Strongyloides ratti.

Parasitic nematodes are significant pathogens of humans and other animals. The molecular and genetic basis of animal parasitism is not yet fully understood. Strongyloides spp. are a genus of gastrointestinal nematodes of which species infect approximately 100­200 million people worldwide. S. ratti is a natural parasite of the rat, and a useful and amenable laboratory model. Previous EST and microarray analyses of the S. ratti life cycle have identified genes whose expression was specific, or biased, to the parasitic adult stage, suggesting that they may play a key role in parasitism in this species. Here we have further investigated the expression of these genes (by RT-PCR) throughout the S. ratti life-cycle. We produced recombinant proteins in vitro for a subset of these genes, which were used in Western blot analyses to investigate the distribution of the gene products among different stages of the S. ratti life cycle. We tested the efficacy of these recombinant proteins as anti-S. ratti vaccines. One of the proteins was detected in the excretory/secretory products of the parasitic stages.

A longitudinal study of skeletal muscle following spinal cord injury and locomotor training.

STUDY DESIGN: Experimental rat model of spinal cord contusion injury (contusion SCI). OBJECTIVE: The objectives of this study were (1) to characterize the longitudinal changes in rat lower hindlimb muscle morphology following contusion SCI by using magnetic resonance imaging and (2) to determine the therapeutic potential of two types of locomotor training, treadmill and cycling. SETTING: University research setting. METHODS: After moderate midthoracic contusion SCI, Sprague-Dawley rats were assigned to either treadmill training, cycle training or an untrained group. Lower hindlimb muscle size was examined prior to SCI and at 1-, 2-, 4-, 8-, and 12-week post injury. RESULTS: Following contusion SCI, we observed significant atrophy in all rat hindlimb muscles with the posterior muscles (triceps surae and flexor digitorum) showing greater atrophy than the anterior muscles (tibialis anterior and extensor digitorum). The greatest amount of atrophy was measured at 2-week post injury (range from 11 to 26%), and spontaneous recovery in muscle size was observed by 4 weeks post-SCI. Both cycling and treadmill training halted the atrophic process and accelerated the rate of recovery. The therapeutic influence of both training interventions was observed within 1 week of training and no significant difference was noted between the two interventions, except in the tibialis anterior muscle. Finally, a positive correlation was found between locomotor functional scores and hindlimb muscle size following SCI. CONCLUSIONS: Both treadmill and cycle training diminish the extent of atrophy and facilitate muscle plasticity after contusion SCI.

Two hypotheses to explain why RNA interference does not work in animal parasitic nematodes.

RNA interference (RNAi) has been used extensively in model organisms such as Caenorhabditis elegans. Methods developed for RNAi in C. elegans have also been used in parasitic nematodes. However, RNAi in parasitic nematodes has been unsuccessful or has had limited success. Studies of genes essential for RNAi in C. elegans and of RNAi in Caenorhabditis spp. other than C. elegans suggest two complementary, and testable, hypotheses for the limited success of RNAi in animal parasitic nematodes. These are: (i) that the external supply of double stranded RNA (dsRNA) to parasitic nematodes is inappropriate to achieve RNAi and (ii) that parasitic nematodes are functionally defective in genes required to initiate RNAi from externally supplied dsRNA.

TGF-beta and the evolution of nematode parasitism.

The many similarities between arrested dauer larvae of free-living nematodes and infective L3 of parasitic nematodes has led to suggestions that they are analogous lifecycle stages. The control of the formation of dauer larvae in Caenorhabditis elegans is well understood, with a TGF-beta-superfamily growth factor playing a central role. Recent analyses of the expression of homologous TGF-beta genes in parasitic nematodes has allowed this analogy to be tested; but the results so far do not support it. Rather, the results imply that in the evolution of animal parasitism, parasitic nematodes have taken signalling pathways and molecules from their free-living ancestors and used them in different ways in the evolution of their parasitic lifestyles.

The effect of the host immune response on the parasitic nematode Strongyloides ratti.

The host immune response has profound effects on parasitic nematode infections. Here we have investigated how a range of infection parameters are affected by host immune responses and by their suppression and enhancement. The infection parameters considered were the number of parasitic females, their size, per capita fecundity and intestinal position. We found that in immunosuppressive treatments worms persist in the gut, sometimes with a greater per capita fecundity, maintain their size and have a more anterior gut position, compared with worms from control animals. In immunization treatments there are fewer worms in the gut, sometimes with a lower per capita fecundity and they are shorter and have a more posterior gut position, compared with worms from control animals. Worms from animals immunosuppressed by corticosteroid treatment reverse their changes in size and gut position. This description of these phenomena pave the way for a molecular biological analysis of how these changes in infection parameters are brought about by the host immune response.

Heat shock and developmental expression of hsp83 in the filarial nematode Brugia pahangi.

hsp83 was cloned from the filarial nematode Brugia pahangi. The mRNA was constitutively expressed at 37 degrees C in life cycle stages that live in the mammalian host (microfilariae and adult worms). Heat shock resulted in only a minimal increase in levels of transcription. A genomic copy of hsp83 was isolated and was shown to contain 11 introns while sequencing of the 5' upstream region revealed several heat shock elements. Using a chloramphenicol acetyltransferase (CAT) reporter gene construct the expression of hsp83 from B. pahangi (Bp-hsp83) was studied by transfection of COS-7 cells. Similar to the expression pattern in the parasite, CAT activity was detected at 37 degrees C and was not influenced by heat shock. When the free-living nematode Caenorhabditis elegans was transfected with the same construct, CAT activity was not observed at normal growth temperatures (21 degrees C) or under moderate heat shock conditions (28 degrees C). However exposure to more severe heat shock (35 degrees C) resulted in an increase in CAT activity. These results suggest that Bp-hsp83 has a temperature threshold > or = 35 degrees C for expression.

Acute effects of locomotor training on overground walking speed and H-reflex modulation in individuals with incomplete spinal cord injury.

OBJECTIVE: The purpose of this study was to assess the effect of a single bout of a locomotor-training paradigm on overground walking speed and H-reflex modulation of individuals with incomplete spinal cord injury (SCI). METHODS: Self-selected and maximum walking speeds and soleus H-reflexes (H/M ratios) during standing and stance and swing phases of walking (self-selected velocity) were obtained from 4 individuals with American Spinal Injury Association impairment classification D. Data were collected immediately before and after a single bout of locomotor training with body weight support on a treadmill. The pretraining H/M ratios of the SCI subjects were also compared with values from 4 able-bodied subjects who did not receive the intervention. Maximum H/M ratios while standing and during midstance and midswing phases of overground walking were considerably greater in the SCI subjects than in the control subjects. RESULTS: After the single bout of training, self-selected and maximum overground walking speeds of the subjects with SCI increased by 26% and 25%, respectively. Furthermore, H-reflexes were significantly more depressed in the SCI subjects during overground walking (28% less during stance, 34% less during swing). CONCLUSIONS: Although preliminary, these findings indicate that a single bout of locomotor training produced immediate increases in walking velocity and acute neurophysiologic changes in individuals with incomplete SCI.

Feasibility and safety of neural tissue transplantation in patients with syringomyelia.

Transplantation of fetal spinal cord (FSC) tissue has demonstrated significant potential in animal models for achieving partial anatomical and functional restoration following spinal cord injury (SCI). To determine whether this strategy can eventually be translated to humans with SCI, a pilot safety and feasibility study was initiated in patients with progressive posttraumatic syringomyelia (PPTS). A total of eight patients with PPTS have been enrolled to date, and this report presents findings for the first two patients through 18 months postoperative. The study design included detailed assessments of each subject at multiple pre- and postoperative time points. Outcome data were then compared with each subject's own baseline. The surgical protocol included detethering, cyst drainage, and implantation of 6-9-week postconception human FSC tissue. Immunosuppression with cyclosporine was initiated a few days prior to surgery and continued for 6 months postoperatively. Key outcome measures included: serial magnetic resonance imaging (MRI) exams, standardized measures of neurological impairment and functional disability, detailed pain assessment, and extensive neurophysiological testing. Through 18 months, the first two patients have been stable neurologically and the MRIs have shown evidence of solid tissue at the graft sites, without evidence of donor tissue overgrowth. Although it is still too soon to draw any firm conclusions, the findings from the initial two patients in this study suggest that intraspinal grafting of human FSC tissue is both feasible and safe.

Neurophysiological assessment of the feasibility and safety of neural tissue transplantation in patients with syringomyelia.

The feasibility and safety of a procedure involving fetal spinal cord tissue transplantation in patients with syringomyelia was assessed using a neurophysiological protocol designed to quantitate peripheral nerve function, spinal cord reflex excitability, and spinal cord conduction pathways essential for somatosensory evoked potentials. We report here data obtained before and for 18 months following the transplantation procedure performed on the first two patients in this study. The neurophysiological assessment protocols included measures of cortical and spinal cord evoked potentials, H-reflex excitability, and peripheral nerve conduction. Prior to the procedure, both patients had significant deficits on some of the neurophysiological measures, for example, lower extremity cortical evoked potentials. However, robust measures of intact pathways, such as upper extremity cortical evoked potentials, were also observed preoperatively in both patients. Thus, it was anticipated that conduction in these intact pathways could be at risk either from complications from the transplantation procedure and/or from continued expansion of the syrinx. Following the transplantation procedure, no negative changes were observed in any of the neurophysiological measures in either patient. In addition, patient 1 showed a decrease in the rate potentiation of tibial H-reflexes on the right side and an increase in the response probability of left tibial H-reflexes. The results of this postoperative longitudinal assessment provide a first-level demonstration of the safety of the intraspinal neural tissue transplantation procedure. However, the consideration of safety is currently limited to the grafting procedure itself, since the long-term fates of the donor tissue in these two patients remain to be shown more definitively.

Scientific basis of spasticity: insights from a laboratory model.

A variety of central nervous system injuries, diseases, and developmental deficits can lead to motor disorders that present complex mixtures of symptoms. Those that have a fundamental similarity characterized by the appearance of exaggerated velocity-dependent resistance to the lengthening of skeletal muscles are called spasticity. Reports based on clinical observations of motor disorders have and continue to provide the essential database of information regarding the range and distribution of unifying and discordant features of spasticity. Laboratory investigations employing animal models of motor disorders following experimental lesions of the central nervous system have reproduced some of the neurophysiologic changes that accompany injury of the central nervous system in humans. Those experimental lesions produced by spinal cord contusion/compression reproduce many of the histopathologic features displayed in traumatic injury of the human spinal cord as well. Studies using this model have revealed not only changes in reflex threshold and amplitude but also alterations in fundamental rate-modulation processes that regulate reflex excitability during repetitive stimulation. This report characterizes insights obtained from a laboratory investigation in search of fundamental mechanisms that contribute to the development of spasticity and provides a vantage point for understanding therapeutic strategies for treatment of spasticity.

Temperature is a cue for gene expression in the post-infective L3 of the parasitic nematode Brugia pahangi.

The temporal expression pattern of two genes, Bp-cdd and Bp-S3, was studied at defined points throughout the life cycle of Brugia pahangi. Both mRNAs were up-regulated to coincide with the transition of the L3 from the vector to the mammalian host. Bp-cdd was expressed almost exclusively in the post-infective (p.i.) L3 and L4 stages of the life cycle while Bp-S3 was also expressed in adult worms, but at a much lower level than in the larval stages. Immunogold labelling with an antiserum raised to the recombinant Bp-CDD localised the native antigen to the hypodermis in the p.i. L3 and L4. Specific labelling was not detected in the adult worm. The expression of both mRNAs could be triggered by exposure of the vector-derived L3 to a simple mammalian culture system. Analysis of the factors, which induced expression suggested that the temperature shift which accompanies the transition from mosquito to mammal was the most important cue for expression of both genes.

Modulation of triceps surae H-reflexes as a function of the reflex activation history during standing and stepping.

The facilitatory effectiveness of spindle afferent feedback is controlled by modulation of segmental reflex excitability such that the level of muscle activation is appropriate for the task. Phase-dependent modes of reflex modulation have been well-characterized. We hypothesized that segmental reflex excitability of the triceps surae was also modulated in a manner associated with the activation history of the spindle afferents and the segmental reflex pathway during isometric contractions, standing and stepping. In the first experiment. pairs of soleus (S) H-reflexes were evoked 80 ms apart with equal strength stimuli at rest and while subjects isometrically contracted their S against loads of 10%. 20%. and 50% of their maximum voluntary efforts. The percent depression of the second H-reflex relative to the first was used as a measure of the effect of reflex activation history. At rest, the second H-reflexes were depressed an average of 73% relative to the first. The degree of depression was progressively reduced as the plantarflexion torque increased. In the second experiment, paired H-reflexes were obtained from the S and medial (MG) and lateral gastrocnemii (LG) muscles while subjects were standing and during the stance phase of step initiation. The degree of depression of the second H-reflex during standing ( > 78%) was similar in magnitude to that produced at rest in Experiment I. At the end of the stance phase of stepping. depression of the second H-reflex of all three muscles was reduced to less than 25%. We conclude that the segmental reflex excitability is modulated as a function of the reflex activation history during these tasks.

The isolation of differentially expressed cDNA clones from the filarial nematode Brugia pahangi.

A cDNA library constructed from 3 day post-infective L3 of the filarial nematode Brugia pahangi was screened by differential hybridization with cDNA probes prepared from different life-cycle stages. Five cDNA clones hybridizing selectively to the mosquito-derived L3 probe were isolated and characterized. Northern blot analysis of 4 of the clones confirmed that each was most highly expressed in the mosquito-derived L3. The expression of each mRNA during parasite development in the mosquito vector was investigated using RT-PCR, and all were shown to be abundant in the immature L3. Four of the 5 cDNAs cloned coded for structural proteins: 2 cuticular collagens, and the muscle proteins tropomyosin and troponin. Further studies on troponin using an antiserum raised to the recombinant protein demonstrated that the protein, unlike the mRNA, was present in all life-cycle stages examined, while immunogold labelling demonstrated that it was localized to the muscle blocks.