A taste of the deep-sea: The roles of gustatory and tactile searching behaviour in the grenadier fish <i>Coryphaenoides armatus</i>

The deep-sea grenadier fishes (Coryphaenoides spp.) are among the dominant predators and scavengers in the ocean basins that cover much of Earth's surface. Baited camera experiments were used to study the behaviour of these fishes. Despite the apparent advantages of rapidly consuming food, grenadiers attracted to bait spend a large proportion of their time in prolonged periods of non-feeding activity. Video analysis revealed that fish often adopted a head-down swimming attitude (mean of 21.3 degrees between the fish and seafloor), with swimming velocity negatively related to attitude. The fish also swam around and along vertical and horizontal structures of the lander with their head immediately adjacent to the structure. We initially hypothesised that this behaviour was associated with the use of the short chin barbel in foraging. Barbel histology showed numerous taste buds in the skin, and a barbel nerve with about 20,000 axons in adult fish. A tracing experiment in one undamaged animal revealed the termination fields of the barbel neurons in the trigeminal and rhombencephalic regions, indicating both a mechanoreceptory and a gustatory role for the barbel. Our conclusion was that olfactory foraging becomes ineffective at close ranges and is followed by a search phase using tactile and gustatory sensing by the barbel. The development of this sensory method probably co-evolved alongside behavioural changes in swimming mechanics to allow postural stability at low swimming speeds

Social cues in the expression of sequential alternative reproductive tactics in young males of the peacock blenny, Solaria pavo

Phenotypic change in response to variation in environmental cues has been widely documented in fish. Transitions in social dominance, in particular, have been shown to induce a rapid switch in reproductive phenotypes in many species. However, this effect has been mainly studied in adults and focused on behavioural transitions. The way social cues constraint the phenotypic development of juveniles remains poorly studied in fish. We tested the importance of social dominance and density in the phenotypic development of juveniles of the peacock blenny Solaria pavo. This species shows sequential male alternative reproductive tactics. In the first breeding season males can reproduce as nest-holders or as parasitic males (female-mimicking), or postpone reproduction; from the following season afterwards all males reproduce as nest-holders. Parasitic males have relatively larger testes that lack a testicular gland, present in the testes of nest-holders. The testicular gland is the main source of androgens in the testes and accordingly nest-holders have higher circulating androgen levels. In addition, exogenous androgen administration to parasitic males promotes the development of secondary sexual characters (SSC) only present in nest-holders such as a head crest and an anal gland. We raised juveniles under a high or low-density treatment and monitored social interactions for 1 month. No significant effect of density on the development of juvenile males was detected. However, within each replicate, the relative body size of juvenile males at the beginning of the experiment determined their dominance status, with dominant males developing towards the nest-holder morphotype. Dominant males engaged in more nest defence behaviour, showed larger testicular glands, had higher levels of 11-ketotestosterone (11-KT) and testosterone (T) and developed more SSC, as compared to subordinate males. However, these effects of social dominance were moderated by body condition as only dominant males in good body condition developed SSC. The effect of social dominance and of the area of the testicular gland on the development of SSC was mediated by 11-KT and on the expression of nest defence behaviour by T. Interestingly, in spite of the higher androgen levels and more pronounced morphologic development of SSC in dominant individuals, gonadal development was independent of social dominance and most fish still had underdeveloped testis at the end of the experiment. In conclusion, social dominance promoted the development of the testicular gland, an increase in circulating androgen levels and the development of SSC, but did not promote testicular development. This suggests a dissociation of mechanisms underlying sexual maturation and the expression of male reproductive traits. This dissociation seems to be the key for the occurrence of female-mimicking males in this species, which are sexually mature despite lacking the SSC typical of nest-holdets. (C) 2012 Elsevier Inc. All rights reserved.R&D Units Plurianual Program (R&D unit) from the Portuguese Foundation for Science and Technology (FCT) [331/2001]; FCT [SFRH/BD/6502/2001]; [POCTI/BSE/38395/2001]; [PTDC/MAR/71351/2006]info:eu-repo/semantics/publishedVersio

Antibody-drug conjugate targeting CD46 eliminates multiple myeloma cells

Multiple myeloma is incurable by standard approaches because of inevitable relapse and development of treatment resistance in all patients. In our prior work, we identified a panel of macropinocytosing human monoclonal antibodies against CD46, a negative regulator of the innate immune system, and constructed antibody-drug conjugates (ADCs). In this report, we show that an anti-CD46 ADC (CD46-ADC) potently inhibited proliferation in myeloma cell lines with little effect on normal cells. CD46-ADC also potently eliminated myeloma growth in orthometastatic xenograft models. In primary myeloma cells derived from bone marrow aspirates, CD46-ADC induced apoptosis and cell death, but did not affect the viability of nontumor mononuclear cells. It is of clinical interest that the CD46 gene resides on chromosome 1q, which undergoes genomic amplification in the majority of relapsed myeloma patients. We found that the cell surface expression level of CD46 was markedly higher in patient myeloma cells with 1q gain than in those with normal 1q copy number. Thus, genomic amplification of CD46 may serve as a surrogate for target amplification that could allow patient stratification for tailored CD46-targeted therapy. Overall, these findings indicate that CD46 is a promising target for antibody-based treatment of multiple myeloma, especially in patients with gain of chromosome 1q

Rapid haplotype inference for nuclear families

Hapi is a new dynamic programming algorithm that ignores uninformative states and state transitions in order to efficiently compute minimum-recombinant and maximum likelihood haplotypes. When applied to a dataset containing 103 families, Hapi performs 3.8 and 320 times faster than state-of-the-art algorithms. Because Hapi infers both minimum-recombinant and maximum likelihood haplotypes and applies to related individuals, the haplotypes it infers are highly accurate over extended genomic distances.National Institutes of Health (U.S.) (NIH grant 5-T90-DK070069)National Institutes of Health (U.S.) (Grant 5-P01-NS055923)National Science Foundation (U.S.) (Graduate Research Fellowship

The Cluster Variation Method for Efficient Linkage Analysis on Extended Pedigrees

BACKGROUND: Computing exact multipoint LOD scores for extended pedigrees rapidly becomes infeasible as the number of markers and untyped individuals increase. When markers are excluded from the computation, significant power may be lost. Therefore accurate approximate methods which take into account all markers are desirable. METHODS: We present a novel method for efficient estimation of LOD scores on extended pedigrees. Our approach is based on the Cluster Variation Method, which deterministically estimates likelihoods by performing exact computations on tractable subsets of variables (clusters) of a Bayesian network. First a distribution over inheritances on the marker loci is approximated with the Cluster Variation Method. Then this distribution is used to estimate the LOD score for each location of the trait locus. RESULTS: First we demonstrate that significant power may be lost if markers are ignored in the multi-point analysis. On a set of pedigrees where exact computation is possible we compare the estimates of the LOD scores obtained with our method to the exact LOD scores. Secondly, we compare our method to a state of the art MCMC sampler. When both methods are given equal computation time, our method is more efficient. Finally, we show that CVM scales to large problem instances. CONCLUSION: We conclude that the Cluster Variation Method is as accurate as MCMC and generally is more efficient. Our method is a promising alternative to approaches based on MCMC sampling

Combining SPR with atomic-force microscopy enables single-molecule insights into activation and suppression of the complement cascade

This work was supported by Leverhulme Trust Grant RPG-2015-109.Activation and suppression of the complement system compete on every serum-exposed surface, host or foreign. Potentially harmful outcomes of this competition depend on surface molecules through mechanisms that remain incompletely understood. Combining surface plasmon resonance (SPR) with atomic force microscopy (AFM), here we studied two complement system proteins at the single-molecule level: C3b, the proteolytically activated form of C3, and factor H (FH), the surface-sensing C3b-binding complement regulator. We used SPR to monitor complement initiation occurring through a positive-feedback loop wherein surface-deposited C3b participates in convertases that cleave C3, thereby depositing more C3b. Over multiple cycles of flowing factor B, factor D, and C3 over the SPR chip, we amplified C3b from ∼20 to ∼220 molecules·μm−2. AFM revealed C3b clusters of up to 20 molecules and solitary C3b molecules deposited up to 200 nm away from the clusters. A force of 0.17 ± 0.02 nanonewtons was needed to pull a single FH molecule, anchored to the AFM probe, from its complex with surface-attached C3b. The extent to which FH molecules stretched before detachment varied widely among complexes. Performing force-distance measurements with FH(D1119G), a variant lacking one of the C3b-binding sites and causing atypical hemolytic uremic syndrome, we found that it detached more uniformly and easily. In further SPR experiments, KD values between FH and C3b on a custom-made chip surface were 5-fold tighter than on commercial chips and similar to those on erythrocytes. These results suggest that the chemistry at the surface on which FH acts drives conformational adjustments that are functionally critical.Publisher PDFPeer reviewe

Pathways to ischemic neuronal cell death: are sex differences relevant?

We have known for some time that the epidemiology of human stroke is sexually dimorphic until late in life, well beyond the years of reproductive senescence and menopause. Now, a new concept is emerging: the mechanisms and outcome of cerebral ischemic injury are influenced strongly by biological sex as well as the availability of sex steroids to the brain. The principal mammalian estrogen (17 β estradiol or E2) is neuroprotective in many types of brain injury and has been the major focus of investigation over the past several decades. However, it is becoming increasingly clear that although hormones are a major contributor to sex-specific outcomes, they do not fully account for sex-specific responses to cerebral ischemia. The purpose of this review is to highlight recent studies in cell culture and animal models that suggest that genetic sex determines experimental stroke outcome and that divergent cell death pathways are activated after an ischemic insult. These sex differences need to be identified if we are to develop efficacious neuroprotective agents for use in stroke patients

The breeding season of Coryphoblennius galerita in Portuguese waters

Coryphoblennius galerita at three sites on the Portuguese coast breeds from February/March to September/October