Cybernetic combatants support the importance of duels in the evolution of extreme weapons.

A current evolutionary hypothesis predicts that the most extreme forms of animal weaponry arise in systems where combatants fight each other one-to-one, in duels. It has also been suggested that arms races in human interstate conflicts are more likely to escalate in cases where there are only two opponents. However, directly testing whether duels matter for weapon investment is difficult in animals and impossible in interstate conflicts. Here, we test whether superior combatants experience a disproportionate advantage in duels, as compared with multi-combatant skirmishes, in a system analogous to both animal and military contests: the battles fought by artificial intelligence agents in a computer war game. We found that combatants with experimentally improved fighting power had a large advantage in duels, but that this advantage deteriorated as the complexity of the battlefield was increased by the addition of further combatants. This pattern remained under the two different forms of the advantage granted to our focal artificial intelligence (AI) combatants, and became reversed when we switched the roles to feature a weak focal AI among strong opponents. Our results suggest that one-on-one combat may trigger arms races in diverse systems. These results corroborate the outcomes of studies of both animal and interstate contests, and suggest that elements of animal contest theory may be widely applicable to arms races generally.

Muscle mass drives cost in sexually selected arthropod weapons.

Sexually selected weapons often function as honest signals of fighting ability. If poor-quality individuals produce high-quality weapons, then receivers should focus on other, more reliable signals. Cost is one way to maintain signal integrity. The costs of weapons tend to increase with relative weapon size, and thereby restrict large weapons to high-quality individuals who can produce and maintain them. Weapon cost, however, appears to be unpredictably variable both within and across taxa, and the mechanisms underlying this variation remain unclear. We suggest variation in weapon cost may result from variation in weapon composition-specifically, differences in the amount of muscle mass directly associated with the weapon. We test this idea by measuring the metabolic cost of sexually selected weapons in seven arthropod species and relating these measures to weapon muscle mass. We show that individuals with relatively large weapon muscles have disproportionately high resting metabolic rates and provide evidence that this trend is driven by weapon muscle mass. Overall, our results suggest that variation in weapon cost can be partially explained by variation in weapon morphology and that the integrity of weapon signals may be maintained by increased metabolic cost in species with relatively high weapon muscle mass.

The metabolic costs of fighting and host exploitation in a seed-drilling parasitic wasp.

Oviposition sites may be challenging and energetically costly to access for females in the presence of competitors contesting that resource. Additionally, oviposition sites may be difficult to reach, and penetrating a hard substrate can raise energy costs. In the seed-drilling parasitic wasp Eupelmus vuilleti, females actively fight with conspecific competitors over access to hosts. They are often observed laying eggs on already parasitized hosts (superparasitism) living inside cowpea seeds despite the resulting larval competition. Using flow-through respirometry, we quantified the metabolic costs of fighting and of drilling through the seed to access the host, to understand the wasp's fighting strategies and the occurrence of superparasitism. Agonistic interactions such as kicks or pushes generated very small instantaneous costs, but the females that won their contests had higher pre-contest metabolic rates, suggesting a potential long-term cost associated with dominance. We also found that drilling holes through the seed accounted for approximately 15% of a wasp's estimated daily energy budget, and that females can reduce these drilling costs by reusing existing holes. Because exploiting new seeds incurs both drilling costs and the risk of fights, it appears cost effective in some situations for females to avoid confrontations and lay eggs in existing holes, on already parasitized hosts. Our study helps explain the evolution of superparasitism in this system.

Habituation in non-neural organisms: evidence from slime moulds.

Learning, defined as a change in behaviour evoked by experience, has hitherto been investigated almost exclusively in multicellular neural organisms. Evidence for learning in non-neural multicellular organisms is scant, and only a few unequivocal reports of learning have been described in single-celled organisms. Here we demonstrate habituation, an unmistakable form of learning, in the non-neural organism Physarum polycephalum In our experiment, using chemotaxis as the behavioural output and quinine or caffeine as the stimulus, we showed that P. polycephalum learnt to ignore quinine or caffeine when the stimuli were repeated, but responded again when the stimulus was withheld for a certain time. Our results meet the principle criteria that have been used to demonstrate habituation: responsiveness decline and spontaneous recovery. To distinguish habituation from sensory adaptation or motor fatigue, we also show stimulus specificity. Our results point to the diversity of organisms lacking neurons, which likely display a hitherto unrecognized capacity for learning, and suggest that slime moulds may be an ideal model system in which to investigate fundamental mechanisms underlying learning processes. Besides, documenting learning in non-neural organisms such as slime moulds is centrally important to a comprehensive, phylogenetic understanding of when and where in the tree of life the earliest manifestations of learning evolved.

Resource allocation strategies and mechanical constraints drive the diversification of stick and leaf insect eggs.

The diversity of insect eggs is astounding but still largely unexplained. Here, we apply phylogenetic analyses to 208 species of stick and leaf insects, coupled with physiological measurements of metabolic rate and water loss on five species, to evaluate classes of factors that may drive egg morphological diversification: life history constraints, material costs, mechanical constraints, and ecological circumstances. We show support for all three classes, but egg size is primarily influenced by female body size and strongly trades off with egg number. Females that lay relatively fewer but larger eggs, which develop more slowly because of disproportionately low metabolic rates, also tend to bury or glue them in specific locations instead of simply dropping them from the foliage (ancestral state). This form of parental care then directly favors relatively elongated eggs, which may facilitate their placement and allow easier passage through the oviducts in slender species. In addition, flightless females display a higher reproductive output and consequently lay relatively more and larger eggs compared with flight-capable females. Surprisingly, local climatic conditions had only weak effects on egg traits. Overall, our results suggest that morphological diversification of stick insect eggs is driven by a complex web of causal relationships among traits, with dominant effects of resource allocation and oviposition strategies, and of mechanical constraints.

Genomic Characterization of a Tetracycline-Resistant Strain of Brochothrix thermosphacta Highlights Plasmids Partially Shared between Various Strains.

The Gram-positive bacterium Brochothrix thermosphacta is a spoilage agent commonly found on meat products. While the tet(L) gene, which confers resistance to tetracycline, has been identified in certain strains of B. thermosphacta, only a limited number of studies have investigated this gene and its potential presence on mobile DNA elements. This study aims to analyze the tetracycline-resistant strain B. thermosphacta BT469 at the genomic level to gain insight into the molecular determinants responsible for this resistance. Three plasmids have been identified in the strain: pBT469-1, which contains a tetR gene; pBT469-2, which harbours the tet(L) gene responsible for tetracycline resistance; and pBT469-3, which carries genes encoding for a thioredoxin and a phospholipase A2. Homology searches among sequences in public databases have revealed that the plasmid pBT469-2 is currently unique to the BT469 strain. However, the pBT469-1 plasmid is also found in three other strains of B. thermosphacta. Notably, sequences similar to pBT469-1 and pBT469-2 were also found in other bacterial genera, suggesting that these plasmids may be part of a diverse family present in several bacterial genera. Interestingly, sequences of various strains of B. thermosphacta show a high level of similarity with pBT469-3, suggesting that variants of this plasmid could be frequently found in this bacterium.

Clinical and MRI Evolution After Local Injection of Bone Marrow-Derived Mesenchymal Stem Cells in Perianal Fistulae in Crohn's Disease: Results From a Prospective Monocentric Study.

BACKGROUND: Local injection of adipose tissue-derived mesenchymal stem cells [MSCs] is effective in fistulizing perianal Crohn's disease [CD]. Less is known about bone marrow-derived MSCs and little is known about predictive factors of response and magnetic resonance imaging [MRI] evolution of the fistulae after MSC injection. Our aims were to evaluate the safety and clinical outcome of bone marrow-derived MSC injection for perianal fistulizing CD, to evaluate the MRI evolution of the fistulae and to identify factors associated with fistula closure. PATIENTS AND METHODS: All CD patients with perianal fistula and appropriate drainage with a seton without abscess at MRI were eligible. Clinical examination, biomarkers and pelvic MRI were performed at weeks 0, 12 and 48. The clinical outcome was assessed by closure of the treated external openings at clinical examination and MRI exploration. RESULTS: Sixteen patients with a median age of 49 years and a median duration of perianal CD of 8 months were included. No unexpected safety event occurred. At weeks 12 and 48, 9/16 and 8/16 patients had complete fistula[e] closure, respectively, whereas 11/16 patients had at least partial closure. At MRI, the degree of fibrosis increased significantly after MSC injection. In total, 86% of patients with >80% of fibrosis of the fistula tract at week 48 had fistula closure. Fistula closure at week 12 was predictive of fistula closure at week 48. The MAGNIFI-CD did not change significantly over time. CONCLUSION: Open-label injection of bone marrow-derived MSCs was safe and was effective in half of the patients in fistulizing perianal CD and induced significant MRI changes associated with favourable clinical outcome.

Evolution of horn length and lifting strength in the Japanese rhinoceros beetle Trypoxylus dichotomus.

What limits the size of nature's most extreme structures? For weapons like beetle horns, one possibility is a tradeoff associated with mechanical levers: as the output arm of the lever system-the beetle horn-gets longer, it also gets weaker. This "paradox of the weakening combatant" could offset reproductive advantages of additional increases in weapon size. However, in contemporary populations of most heavily weaponed species, males with the longest weapons also tend to be the strongest, presumably because selection drove the evolution of compensatory changes to these lever systems that ameliorated the force reductions of increased weapon size. Therefore, we test for biomechanical limits by reconstructing the stages of weapon evolution, exploring whether initial increases in weapon length first led to reductions in weapon force generation that were later ameliorated through the evolution of mechanisms of mechanical compensation. We describe phylogeographic relationships among populations of a rhinoceros beetle and show that the "pitchfork" shaped head horn likely increased in length independently in the northern and southern radiations of beetles. Both increases in horn length were associated with dramatic reductions to horn lifting strength-compelling evidence for the paradox of the weakening combatant-and these initial reductions to horn strength were later ameliorated in some populations through reductions to horn length or through increases in head height (the input arm for the horn lever system). Our results reveal an exciting geographic mosaic of weapon size, weapon force, and mechanical compensation, shedding light on larger questions pertaining to the evolution of extreme structures.

Multi-modal locomotor costs favor smaller males in a sexually dimorphic leaf-mimicking insect.

BACKGROUND: In most arthropods, adult females are larger than males, and male competition is a race to quickly locate and mate with scattered females (scramble competition polygyny). Variation in body size among males may confer advantages that depend on context. Smaller males may be favored due to more efficient locomotion leading to higher mobility during mate searching. Alternatively, larger males may benefit from increased speed and higher survivorship. While the relationship between male body size and mobility has been investigated in several systems, how different aspects of male body morphology specifically affect their locomotor performance in different contexts is often unclear. RESULTS: Using a combination of empirical measures of flight performance and modelling of body aerodynamics, we show that large body size impairs flight performance in male leaf insects (Phyllium philippinicum), a species where relatively small and skinny males fly through the canopy in search of large sedentary females. Smaller males were more agile in the air and ascended more rapidly during flight. Our models further predicted that variation in body shape would affect body lift and drag but suggested that flight costs may not explain the evolution of strong sexual dimorphism in body shape in this species. Finally, empirical measurements of substrate adhesion and subsequent modelling of landing impact forces suggested that smaller males had a lower risk of detaching from the substrates on which they walk and land. CONCLUSIONS: By showing that male body size impairs their flight and substrate adhesion performance, we provide support to the hypothesis that smaller scrambling males benefit from an increased locomotor performance and shed light on the evolution of sexual dimorphism in scramble competition mating systems.

Population differences in the strength of sexual selection match relative weapon size in the Japanese rhinoceros beetle, Trypoxylus dichotomus (Coleoptera: Scarabaeidae)†.

Exaggerated weapons of sexual selection often diverge more rapidly and dramatically than other body parts, suggesting that relevant agents of selection may be discernible in contemporary populations. We examined the ecology, reproductive behavior, and strength of sexual selection on horn length in five recently diverged rhinoceros beetle (Trypoxylus dichotomus) populations that differ in relative horn size. Males with longer horns were better at winning fights in all locations, but the link between winning fights and mating success differed such that selection favored large males with long horns at the two long-horned populations, but was relaxed or nonexistent at the populations with relatively shorter horns. Observations of local habitat conditions and breeding ecology point to shifts in the relative abundance of feeding territories as the most likely cause of population differences in selection on male weapon size in this species. Comparisons of ecological conditions and selection strength across populations offer critical first steps toward meaningfully linking mating system dynamics, selection patterns, and diversity in sexually selected traits.

Sexual dimorphism divergence between sister species is associated with a switch in habitat use and mating system in thorny devil stick insects.

The habitat and resource use of females critically affects their pattern of distribution and consequently their monoposibility by males and the mating system of a species. Shifts in habitat use are therefore likely to be associated with changes in mating system and sexual selection acting on males' phenotypes, consequently affecting patterns of sexual dimorphism. Although sexual dimorphism is often correlated with shifts in habitat use at the macroevolutionary scale, the underlying microevolutionary processes involved are typically unclear. Here, we used the New Guinean stick insect genus Eurycantha to investigate how changes in habitat use and mating system were associated with a change in sexual dimorphism seen specifically in the thorny devil stick insects (Eurycantha calcarata and Eurycantha horrida). Male thorny devils display sexually dimorphic and enlarged hindlegs endowed with a sharp spine. Sexual size dimorphism is also very reduced in these species relative to other phasmids. Using field observations, morphological measurements and radiotelemetry, we investigated changes in mating system associated with the reduction of sexual dimorphism and tested predictions from the hypothesis that sexual selection drove the evolution of this unusual male morphology. We found that thorny devils switched from solitary roosting in the canopy during the day to communal roosting inside cavities of a few host trees, shifting the distribution of females from scattered to clumped. Male thorny devils used their large hindlegs to fight with rivals for positions on the tree close to cavities containing females, and larger males were associated with cavities containing relatively more females. In contrast, the sister species, Eurycantha insularis, displays relatively small and unarmoured males (ancestral state). Adult female E. insularis were always scattered in the canopy, and this species displayed a scramble competition mating system typical of other phasmids, where mobility, rather than fighting ability, is probably critical to males' reproductive success. Overall, our study illustrates how a drastic change in sexual dimorphism can be associated with a switch from solitary to communal roosting and from a scramble competition to a defense-based polygyny mating system.

Overcoming mechanical adversity in extreme hindleg weapons.

The size of sexually selected weapons and their performance in battle are both critical to reproductive success, yet these traits are often in opposition. Bigger weapons make better signals. However, due to the mechanical properties of weapons as lever systems, increases in size may inhibit other metrics of performance as different components of the weapon grow out of proportion with one another. Here, using direct force measurements, we investigated the relationship between weapon size and weapon force production in two hindleg weapon systems, frog-legged beetles (Sagra femorata) and leaf-footed cactus bugs (Narnia femorata), to test for performance tradeoffs associated with increased weapon size. In male frog-legged beetles, relative force production decreased as weapon size increased. Yet, absolute force production was maintained across weapon sizes. Surprisingly, mechanical advantage was constant across weapon sizes and large weaponed males had disproportionately large leg muscles. In male leaf-footed cactus bugs, on the other hand, there was no relationship between weapon size and force production, likely reflecting the importance of their hindlegs as signals rather than force-producing structures of male-male competition. Overall, our results suggest that when weapon force production is important for reproductive success, large weaponed animals may overcome mechanical challenges by maintaining proportional lever components and investing in (potentially costly) compensatory mechanisms.

Structural characterization of CD6: properties of two distinct epitopes involved in T cell activation.

Studies from our laboratory have shown that anti-T12, a mAb which recognizes CD6, is a macrophage-dependent mitogen for human T cells and can augment T cell autoreactivity in vitro. To obtain additional information regarding the potential biological role of CD6 we sought to further characterize its biochemical properties. The CD6 molecule on 125I-surface-labeled T cells and by Western blot analysis was a monomer of mol. wt 130,000 under reducing conditions and mol. wt 117,000 under non-reducing conditions, suggesting the presence of intrachain disulfide bonds. The polypeptide contains a protease sensitive site. In activated T cells, the protein was serine phosphorylated. Analysis of biosynthetically labeled CD6 in the presence of tunicamycin revealed a reduction in mol. wt from 130,000 to 100,000, indicating that the polypeptide is extensively N-glycosylated. The mAb, anti-2H1, had been shown to activate T cells in combination with PMA or the anti-T11(3) mAb but, unlike anti-T12, not in the presence of macrophages alone. The present studies demonstrate by sequential immunoprecipitation that these two mAbs recognize the same polypeptide. However, Western blot analysis and indirect immunofluorescence cross-blocking studies demonstrate that the two mAbs recognize different determinants on CD6. Anti-T12 recognizes an epitope that is present only under non-reducing/non-denaturing conditions, while anti-2H1 recognizes an epitope that is also preserved under reducing/denaturing conditions. A direct comparison of activation properties of the mAbs confirmed that anti-T12 was optimally mitogenic in the presence of macrophages but not PMA, while, conversely, anti-2H1 was optimally mitogenic in combination with PMA but not macrophages, suggesting that the differences in epitope specificity may account for the distinct activation properties of each mAb. Taken together, the structural and functional data strongly suggest that the CD6 membrane glycoprotein may function as a physiologically important receptor structure on human T lymphocytes.

Mixed cryoglobulinemia in chronic hepatitis C infection. A clinicopathologic analysis of 10 cases and review of recent literature.

We present 10 cases of mixed cryoglobulinemia in patients infected with hepatitis C, including pertinent clinical, serologic, and pathological data. The findings attributable to MC appear to be similar in patients who are HCV-infected as in those with unknown HCV status. The prevalence of MC in HCV-infected patients appears to be lower in our region (13%) than in southern Europe (50-90%) although some of this difference is due to our requirement that patients included in our study have a cryocrit of at least 5%. In our patients, cryoglobulins were shown to be deposited in skin and kidney, but not in liver. The mechanisms by which HCV and MC are related remain uncertain. Although we and others have evidence for enrichment of HCV RNA in the cryoprecipitates of some patients, this was not always the case, and it is not yet clear that this finding is of fundamental pathogenic importance. Finally, it appears that some patients with HCV and MC may have a beneficial clinical response of vasculitic symptoms to therapy with alpha-interferon, as well as to glucocorticoids or other immunosuppressants. In our group, no predictors were apparent to distinguish responders from nonresponders before treatment. Similarly, the duration of response remains to be determined.

Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases.

The monoclonal antibodies anti-2H4 and anti-4B4 identify the suppressor-inducer (CD4+2H4+) and helper-inducer (CD4+4B4+) subpopulations of CD4 (T4+) lymphocytes, respectively. The cell surface phenotype of peripheral blood lymphocytes and synovial fluid lymphocytes in patients with rheumatoid arthritis and other inflammatory joint diseases was analyzed by use of these and other well-characterized anti-T-cell monoclonal antibodies. In the synovial fluid of patients with rheumatoid arthritis, there was a markedly decreased percentage of T4+2H4+ suppressor-inducer cells (3.1 +/- 1 percent) and an increased percentage of T4+4B4+ helper-inducer cells (29.1 +/- 9 percent) as compared with the proportions found in the peripheral blood of normal individuals (T4+2H4+: 19.0 +/- 6 percent, T4+4B4+: 23.0 +/- 7 percent). Moreover, patients with other chronic and acute inflammatory joint diseases exhibited highly similar synovial T-cell findings to those of the patients with rheumatoid arthritis (T4+2H4+: 4.2 +/- 3 percent, T4+4B4+: 33.1 +/- 9 percent). In contrast, there were no significant differences between the normal control subjects and patients with rheumatoid arthritis in the percentage of T4+2H4+ cells in peripheral blood lymphocytes, nor were there significant differences between normal control subjects, patients with rheumatoid arthritis, and patients with other joint diseases (osteoarthritis, gout, B27+ spondyloarthropathy, and psoriatic arthritis) in the number of T4+4B4+ cells or in the T4/T8 ratio of peripheral blood lymphocytes. However, very low numbers of T4+2H4+ (suppressor-inducer) peripheral blood lymphocytes were seen in a subgroup of patients, including five of seven with Reiter's syndrome and several patients with systemic rheumatic disease syndromes. In addition, although the percentage of T4+2H4+ cells in peripheral blood lymphocytes of patients with osteoarthritis (13.7 +/- 7 percent) and gout (14.3 +/- 7 percent) was decreased compared with that of normal controls (19.0 +/- 6 percent) (osteoarthritis versus normal controls p less than 0.025), this difference appeared to reflect alterations due to age rather than disease. Consistent with the phenotypic changes observed, synovial T cells were also functionally defective, since autologous mixed lymphocyte reaction-activated T4 cells from the synovial fluid of patients with rheumatoid arthritis failed to exhibit suppressor-inducer activity.(ABSTRACT TRUNCATED AT 400 WORDS)

A monoclonal antibody that blocks class II histocompatibility-related immune interactions.

Previous studies using conventional hetero- or isoantisera have indicated the involvement of class II (Ia) molecules in presentation of soluble antigen by monocytes to inducer T lymphocytes, stimulation of inducer T cells in MLR, and recognition of Ia-bearing target cells by cytotoxic T lymphocytes (CTL). The experience in using monoclonal anti-Ia reagents capable of blocking these phenomena in the human system is limited. Recently, however, we have characterized a lytic IgG2a monoclonal antibody, 9-49, that binds to functionally significant class II molecules. This antibody blocks (in the absence of complement): (1) specific binding of peripheral blood lymphocytes (PBL) to antigen-pulsed monocyte monolayers, (2) proliferation of PBL in response to soluble antigen (tetanus toxoid or mumps) or cell surface class II antigen stimulation in allogeneic or autologous MLR, (3) proliferation of cloned T4+ (inducer) lymphocyte cell lines to class II antigens, (4) generation of cytotoxic lymphocytes during allogeneic MLR, and (5) recognition (and killing) of class II-bearing target cells by T4+ CTL clones. Proliferation and CTL activity of a T8+ clone is unaffected by the 9-49 antibody. These results indicate the usefulness of this monoclonal reagent in studies evaluating the functional role of Ia molecules in immune recognition phenomena.

Mixed cryoglobulinemia secondary to hepatitis C virus infection.

Mixed cryoglobulinemia is a systemic vasculitis with clinical manifestations ranging from the characteristic benign-appearing syndrome of palpable purpura, arthrologies, and fatigue to severe vasculitis involving vital organs. A strong association of the disease with hepatitis C virus infection and the demonstration of the specific concentration of the virus in the cryoglobulins have implicated hepatitis C virus in the etiopathogenesis of the disease. The increase in illicit intravenous drug use in the past 30 years seems to have raised the occurrence in the United States of this once uncommon disease and changed the demographics: there seem to be more male intravenous drug users in their forties with the disease than women without risk factors for hepatitis C virus infection in their fifties and sixties. Pathogenesis, therapy, and the hypothesis on the etiologic role of hepatitis C virus are reviewed, and the implications of recent studies and new concepts for treatment of this often benign-appearing but deceptive and potentially life-threatening disease are discussed.

Cherubism. Findings in three cases in the same family.

Cherubism is a benign hereditary giant-cell lesion of the mandibular and maxillary spongiosa which appears during childhood between the age of 2 and 5 years and progresses until puberty when it spontaneously regresses. It appears as a bilateral, painless swelling. It normally requires no treatment. Three children in the same Algerian family who suffered from this disease were brought to our department. Radiographic examinations were carried out, giving good definition of the lesions. The 3 patients were finally operated on, as operative treatment was, effectively, necessary.

[Frontal sinus injuries: apropos of 67 cases]. / Traumatismes des sinus frontaux: à propos de 67 cas.

The authors report their experience in the treatment of frontal sinus fractures, between 1979 and 1987, about 67 cases. 52% of these trauma involve alone, the anterior and/or posterior wall of the frontal sinus, with or without cerebrospinal fluid rhinorrhea. The sinus surgery was composed of cranialization in 20 cases (30%) and open reduction with reconstruction, with or without tube to stent the nasofrontal duct, in 30 cases (48%). Two points appear to them, essential to guide the treatment, osteomeningeal tear and naso-frontal duct injury.