Frequency preference in two-dimensional neural models: a linear analysis of the interaction between resonant and amplifying currents

Many neuron types exhibit preferred frequency responses in their voltage amplitude (resonance) or phase shift to subthreshold oscillatory currents, but the effect of biophysical parameters on these properties is not well understood. We propose a general framework to analyze the role of different ionic currents and their interactions in shaping the properties of impedance amplitude and phase in linearized biophysical models and demonstrate this approach in a two-dimensional linear model with two effective conductances g _L and g ₁. We compute the key attributes of impedance and phase (resonance frequency and amplitude, zero-phase frequency, selectivity, etc.) in the g _L ???g ₁ parameter space. Using these attribute diagrams we identify two basic mechanisms for the generation of resonance: an increase in the resonance amplitude as g ₁ increases while the overall impedance is decreased, and an increase in the maximal impedance, without any change in the input resistance, as the ionic current time constant increases. We use the attribute diagrams to analyze resonance and phase of the linearization of two biophysical models that include resonant (I _h or slow potassium) and amplifying currents (persistent sodium). In the absence of amplifying currents, the two models behave similarly as the conductances of the resonant currents is increased whereas, with the amplifying current present, the two models have qualitatively opposite responses. This work provides a general method for decoding the effect of biophysical parameters on linear membrane resonance and phase by tracking trajectories, parametrized by the relevant biophysical parameter, in pre-constructed attribute diagrams.     

Short-term variations of mycosporine-like amino acids in the carrageenan-producing red macroalga Mazzaella laminarioides (Gigartinales,Rhodophyta) are related to nitrate availability

Journal of Applied Phycology - The effect of solar UV radiation exposure and NO3– supply on mycosporine-like amino acids (MAAs) accumulation in the carrageenan-producing red macroalga...     

Deciphering the Genetic Programme Triggering Timely and Spatially-Regulated Chitin Deposition

Organ and tissue formation requires a finely tuned temporal and spatial regulation of differentiation programmes. This is necessary to balance sufficient plasticity to undergo morphogenesis with the acquisition of the mature traits needed for physiological activity. Here we addressed this issue by analysing the deposition of the chitinous extracellular matrix of Drosophila, an essential element of the cuticle (skin) and respiratory system (tracheae) in this insect. Chitin deposition requires the activity of the chitin synthase Krotzkopf verkehrt (Kkv). Our data demonstrate that this process equally requires the activity of two other genes, namely expansion (exp) and rebuf (reb). We found that Exp and Reb have interchangeable functions, and in their absence no chitin is produced, in spite of the presence of Kkv. Conversely, when Kkv and Exp/Reb are co-expressed in the ectoderm, they promote chitin deposition, even in tissues normally devoid of this polysaccharide. Therefore, our results indicate that both functions are not only required but also sufficient to trigger chitin accumulation. We show that this mechanism is highly regulated in time and space, ensuring chitin accumulation in the correct tissues and developmental stages. Accordingly, we observed that unregulated chitin deposition disturbs morphogenesis, thus highlighting the need for tight regulation of this process. In summary, here we identify the genetic programme that triggers the timely and spatially regulated deposition of chitin and thus provide new insights into the extracellular matrix maturation required for physiological activity.     

Evaluation of a 4-aminopiperidine replacement in several series of CCR5 antagonists

The bicyclic 5-amino-3-azabicyclo[3.3.0]octanes were shown to be effective replacements for the conformationally restricted 4-aminopiperidine ring found in several series of CCR5 antagonists.     

Lacaziosis and lacaziosis-like prevalence among wild, common bottlenose dolphins Tursiops truncatus from the west coast of Florida, USA

Lacaziosis (lobomycosis; Lacazia loboi) is a fungal skin disease that naturally occurs only in humans and dolphins. The first reported case of lacaziosis in a bottlenose dolphin Tursiops truncatus occurred in 1970 in Sarasota Bay, Florida, USA, and subsequent photo-ID monitoring of the Sarasota Bay dolphin population has revealed persistence of the disease. The objectives of this study were to estimate lacaziosis prevalence (P) in 2 bottlenose dolphin populations on the west coast of Florida (Sarasota Bay and Charlotte Harbor) and compare disease occurrence to other published estimates of lacaziosis in dolphin populations across the globe. Historic photographic records of dolphins captured and released for health assessment purposes (Sarasota Bay) and photo-ID studies (Charlotte Harbor) were screened for evidence of lesions consistent with lacaziosis. Health assessment data revealed a prevalence of lacaziosis in the Sarasota Bay bottlenose dolphin population between 2 and 3%, and analyses of photo-ID data provided a lacaziosis-like prevalence estimate of 2% for Charlotte Harbor dolphins. With the exception of lacaziosis prevalence estimates for dolphins inhabiting the Indian River Lagoon (P = 0.068; P = 0.12), no statistically significant differences were seen among Sarasota Bay, Charlotte Harbor, and other published estimates. Although lacaziosis is a rare disease among these dolphin populations, studies that assess disease burden among different populations can assist with the surveillance of this zoonotic pathogen.     

Skin lesions on common bottlenose dolphins (Tursiops truncatus) from three sites in the Northwest Atlantic, USA

Skin disease occurs frequently in many cetacean species across the globe; methods to categorize lesions have relied on photo-identification (photo-id), stranding, and by-catch data. The current study used photo-id data from four sampling months during 2009 to estimate skin lesion prevalence and type occurring on bottlenose dolphins (Tursiops truncatus) from three sites along the southeast United States coast [Sarasota Bay, FL (SSB); near Brunswick and Sapelo Island, GA (BSG); and near Charleston, SC (CHS)]. The prevalence of lesions was highest among BSG dolphins (P = 0.587) and lowest in SSB (P = 0.380), and the overall prevalence was significantly different among all sites (p<0.0167). Logistic regression modeling revealed a significant reduction in the odds of lesion occurrence for increasing water temperatures (OR = 0.92; 95%CI:0.906-0.938) and a significantly increased odds of lesion occurrence for BSG dolphins (OR = 1.39; 95%CI:1.203-1.614). Approximately one-third of the lesioned dolphins from each site presented with multiple types, and population differences in lesion type occurrence were observed (p<0.05). Lesions on stranded dolphins were sampled to determine the etiology of different lesion types, which included three visually distinct samples positive for herpesvirus. Although generally considered non-fatal, skin disease may be indicative of animal health or exposure to anthropogenic or environmental threats, and photo-id data provide an efficient and cost-effective approach to document the occurrence of skin lesions in free-ranging populations.     

Leukemia inhibitory factor coordinates the down-regulation of the visual cycle in the retina and retinal-pigmented epithelium

Leukemia inhibitory factor (LIF), an interleukin-6 family neurocytokine, is up-regulated in response to different types of retinal stress and has neuroprotective activity through activation of the gp130 receptor/STAT3 pathway. We observed that LIF induces rapid, robust, and sustained activation of STAT3 in both the retina and retinal pigmented epithelium (RPE). Here, we tested whether LIF-induced STAT3 activation within the RPE can down-regulate RPE65, the central enzyme in the visual cycle that provides the 11-cis-retinal chromophore to photoreceptors in vivo. We generated conditional knock-out mice to specifically delete STAT3 or gp130 in RPE, retina, or both RPE and retina. After intravitreal injection of LIF, we analyzed the expression levels of visual cycle genes and proteins, isomerase activity of RPE65, levels of rhodopsin protein, and the rates of dark adaptation and rhodopsin regeneration. We found that RPE65 protein levels and isomerase activity were reduced and recovery of bleachable rhodopsin was delayed in LIF-injected eyes. In mice with functional gp130/STAT3 signaling in the retina, rhodopsin protein was also reduced by LIF. However, the LIF-induced down-regulation of RPE65 required a functional gp130/STAT3 cascade intrinsic to RPE. Our data demonstrate that a single cytokine, LIF, can simultaneously and independently affect both RPE and photoreceptors through the same signaling cascade to reduce the generation and utilization of 11-cis-retinal.     

Domoic acid exposure in pygmy and dwarf sperm whales (Kogia spp.) from southeastern and mid-Atlantic U.S. waters

The neurotoxin domoic acid (DA) was detected in urine and fecal samples recovered from pygmy sperm whales (Kogia breviceps) and dwarf sperm whales (Kogia sima) stranding along the U.S. Atlantic coast from 1997 to 2008. Of the 41 animals analyzed from Virginia, North Carolina, South Carolina and Florida, 24 (59%) tested positive for DA at concentrations of 0.4–1.8 ng/mL in urine and 12–13,566 ng/g in feces as determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Feces appeared to be the best indicator of DA exposure in Kogia spp., with 87% of all fecal samples analyzed testing positive for this toxin. Additional stranded animals (n = 40) representing 11 other cetacean species were recovered from the same region between 2006 and 2008 and analyzed by LC–MS/MS, however DA was not detected in any of these individuals. DA is produced naturally by diatoms in the genus Pseudo-nitzschia. Although blooms of DA-producing Pseudo-nitzschia have been associated with repeated large-scale marine mammal mortalities on the west coast of the U.S., there is no documented history of similar blooms on the southeast U.S. coast, and there were no observed Pseudo-nitzschia blooms in the region associated with any of these strandings. The feeding habits of Kogia spp. are poorly documented; thus, the vector(s) for DA exposure to these deep-diving species remains to be identified. Toxin accumulation in these pelagic whale species may be an indication of cryptic harmful algal bloom activity in offshore areas not currently being monitored. This study highlights the need for a better understanding of the role of toxigenic algae in marine mammal morbidity and mortality globally.     

Soluble fibrinogen-like protein 2/fibroleukin exhibits immunosuppressive properties: suppressing T cell proliferation and inhibiting maturation of bone marrow-derived dendritic cells

Fibrinogen-like protein 2 (fgl2)/fibroleukin is a member of the fibrinogen-related protein superfamily. In addition to its established role in triggering thrombosis, it is known to be secreted by T cells. The soluble fgl2 ((s)fgl2) protein generated in a baculovirus expression system bound to both T cells and bone marrow-derived dendritic cells (DC) in a specific manner. (s)fgl2 exhibited immunomodulatory properties capable of inhibiting T cell proliferation stimulated by alloantigens, anti-CD3/anti-CD28 mAbs, and Con A in a dose-dependent manner; however, it had no inhibitory effects on CTL activity. The time- and dose-dependent inhibitory effect of (s)fgl2 on alloreactive T cell proliferation could be neutralized by a mAb against mouse fgl2. Polarization toward a Th2 cytokine profile with decreased production of IL-2 and IFN-gamma and increased production of IL-4 and IL-10 was observed in (s)fgl2-treated allogeneic cultures. Exposure of immature DC to (s)fgl2 abrogated the expression of CD80(high) and MHC class II(high) molecules and markedly inhibited NF-kappaB nuclear translocation, thus inhibiting their maturation. (s)Fgl2-treated DC had an impaired ability to stimulate allogeneic T cell proliferation. Maximal inhibition of proliferation was observed when allogeneic T cells were cultured with (s)fgl2-treated DC and (s)fgl2 protein was added in the culture. These data provide the first evidence to demonstrate that (s)fgl2 exerts immunosuppressive effects on T cell proliferation and DC maturation.