Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope

The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the target of three of the five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have determined crystal structures of the antigen-binding fragment for one of these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41 membrane-proximal region, at 2.0-, 2.1-, and 2.2-A resolutions, respectively. The structures reveal an extended gp41 conformation, which stretches over 30 A in length. Contacts are made with five complementarity-determining regions of the antibody as well as with nonpolymorphic regions. Only one exclusive charged face of the gp41 epitope is bound by 2F5, while the nonbound face, which is hydrophobic, may be hidden due to occlusion by other portions of the ectodomain. The structures reveal that the 2F5 antibody is uniquely built to bind to an epitope that is proximal to a membrane surface and in a manner mostly unaffected by large-scale steric hindrance. Biochemical studies with proteoliposomes confirm the importance of lipid membrane and hydrophobic context in the binding of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody that recognizes the membrane-proximal region of gp41. Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed.     

Priority effects of the early breeding fire salamander on the late breeding banded newt

Early breeding intraguild predators may have advantages over late breeding predators via priority effects; early breeding predators may reduce shared prey resources before late breeders appear and may also prey upon the late breeders. Here we show that predatory larvae of the late-breeding predatory banded newt, Triturus vittatus vittatus, occupy the same temporary pond toward the end of the developmental period of the early-breeding predatory fire salamander, Salamandra salamandra, resulting in a large size disparity between larvae of these two species while they co-occur. We conducted outdoor artificial pool experiments to assess priority effects of large larval Salamandra at the end of their larval development period, on recently hatched larval Triturus. We also assessed how artificial vegetation may influence larval Triturus performance in the presence or absence of Salamandra Salamandra, introduced into the experimental pools two weeks prior to the newt larvae, strongly reduced invertebrate prey abundance shared by these two predatory urodeles and with only a one week period of overlap, strongly reduced abundance of Triturus larvae. The artificial vegetation had only a small ameliorating effect on Triturus survival when Salamandra was present. Triturus size at metamorphosis (snout-tail length) was significantly larger in the Salamandra pools, presumably due to a combination of a strong “thinning effect” and greater vulnerability of smaller Triturus individuals to predation by Salamandra. Time to metamorphosis was not significantly affected by Salamandra. These results have conservation implications as T. v. vittatus is listed as highly endangered and may also explain the largely negative spatial association of the two species. Handling editor: K. Martens     

Adaptation to Changes in Higher-Order Stimulus Statistics in the Salamander Retina

Adaptation in the retina is thought to optimize the encoding of natural light signals into sequences of spikes sent to the brain. While adaptive changes in retinal processing to the variations of the mean luminance level and second-order stimulus statistics have been documented before, no such measurements have been performed when higher-order moments of the light distribution change. We therefore measured the ganglion cell responses in the tiger salamander retina to controlled changes in the second (contrast), third (skew) and fourth (kurtosis) moments of the light intensity distribution of spatially uniform temporally independent stimuli. The skew and kurtosis of the stimuli were chosen to cover the range observed in natural scenes. We quantified adaptation in ganglion cells by studying linear-nonlinear models that capture well the retinal encoding properties across all stimuli. We found that the encoding properties of retinal ganglion cells change only marginally when higher-order statistics change, compared to the changes observed in response to the variation in contrast. By analyzing optimal coding in LN-type models, we showed that neurons can maintain a high information rate without large dynamic adaptation to changes in skew or kurtosis. This is because, for uncorrelated stimuli, spatio-temporal summation within the receptive field averages away non-gaussian aspects of the light intensity distribution.     

Spike propagation in dendrites with stochastic ion channels

We investigate the effects of the stochastic nature of ion channels on the faithfulness, precision and reproducibility of electrical signal transmission in weakly active, dendritic membrane under in vitro conditions. The properties of forward and backpropagating action potentials (BPAPs) in the dendritic tree of pyramidal cells are the subject of intense empirical work and theoretical speculation (Larkum et al., 1999; Zhu, 2000; Larkum et al., 2001; Larkum and Zhu, 2002; Schaefer et al., 2003; Williams, 2004; Waters et al., 2005). We numerically simulate the effects of stochastic ion channels on the forward and backward propagation of dendritic spikes in Monte-Carlo simulations on a reconstructed layer 5 pyramidal neuron. We report that in most instances there is little variation in timing or amplitude for a single BPAP, while variable backpropagation can occur for trains of action potentials. Additionally, we find that the generation and forward propagation of dendritic Ca²⁺ spikes are susceptible to channel variability. This indicates limitations on computations that depend on the precise timing of Ca²⁺ spikes. Action Editor : Alain Destexhe     

Recovery of Streptococcus iniae from Diseased Fish Previously Vaccinated with a Streptococcus Vaccine

Streptococcus iniae was recovered from diseased rainbow trout (Oncorhynchus mykiss, Walbaum) previously vaccinated against streptococcosis. PCR and serological methods indicate the presence of a new serotype in the diseased fish.     

Morphological Heterogeneity and Attachment of Phaeobacter inhibens

The Roseobacter clade is a key group of bacteria in the ocean exhibiting diverse metabolic repertoires and a wide range of symbiotic life-styles. Many Roseobacters possess remarkable capabilities of attachment to both biotic and abiotic surfaces. When attached to each other, these bacteria form multi-cellular structures called rosettes. Phaeobacter inhibens, a well-studied Roseobacter, exhibits various cell sizes and morphologies that are either associated with rosettes or occur as single cells. Here we describe the distribution of P. inhibens morphologies and rosettes within a population. We detect an N-acetylglucosamine-containing polysaccharide on the poles of some cells and at the center of all rosettes. We demonstrate that rosettes are formed by the attachment of individual cells at the polysaccharide-containing pole rather than by cell division. Finally, we show that P. inhibens attachment to abiotic surfaces is hindered by the presence of DNA from itself, but not from other bacteria. Taken together, our findings demonstrate that cell adhesiveness is likely to play a significant role in the life cycle of P. inhibens as well as other Roseobacters.     

Collinear Stimuli Induce Local and Cross-Areal Coherence in the Visual Cortex of Behaving Monkeys

Background

Collinear patterns of local visual stimuli are used to study contextual effects in the visual system. Previous studies have shown that proximal collinear flankers, unlike orthogonal, can enhance the detection of a low contrast central element. However, the direct neural interactions between cortical populations processing the individual flanker elements and the central element are largely unknown.

Methodology/Principal Findings

Using voltage-sensitive dye imaging (VSDI) we imaged neural population responses in V1 and V2 areas in fixating monkeys while they were presented with collinear or orthogonal arrays of Gabor patches. We then studied the spatio-temporal interactions between neuronal populations processing individual Gabor patches in the two conditions. Time-frequency analysis of the stimulus-evoked VSDI signal showed power increase mainly in low frequencies, i.e., the alpha band (α; 7–14 Hz). Power in the α-band was more discriminative at a single trial level than other neuronal population measures. Importantly, the collinear condition showed an increased intra-areal (V1-V1 and V2-V2) and inter-areal (V1-V2) α-coherence with shorter latencies than the orthogonal condition, both before and after the removal of the stimulus contribution. α-coherence appeared between discrete neural populations processing the individual Gabor patches: the central element and the flankers.

Conclusions/Significance

Our findings suggest that collinear effects are mediated by synchronization in a distributed network of proximal and distant neuronal populations within and across V1 and V2.