Breaking cover: neural responses to slow and fast camouflage-breaking motion

Primates need to detect and recognize camouflaged animals in natural environments. Camouflage-breaking movements are often the only visual cue available to accomplish this. Specifically, sudden movements are often detected before full recognition of the camouflaged animal is made, suggesting that initial processing of motion precedes the recognition of motion-defined contours or shapes. What are the neuronal mechanisms underlying this initial processing of camouflaged motion in the primate visual brain? We investigated this question using intrinsic-signal optical imaging of macaque V1, V2 and V4, along with computer simulations of the neural population responses. We found that camouflaged motion at low speed was processed as a direction signal by both direction- and orientation-selective neurons, whereas at high-speed camouflaged motion was encoded as a motion-streak signal primarily by orientation-selective neurons. No population responses were found to be invariant to the camouflage contours. These results suggest that the initial processing of camouflaged motion at low and high speeds is encoded as direction and motion-streak signals in primate early visual cortices. These processes are consistent with a spatio-temporal filter mechanism that provides for fast processing of motion signals, prior to full recognition of camouflage-breaking animals.     

Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria

Background

Effective mating between laboratory-reared males and wild females is paramount to the success of vector control strategies aiming to decrease disease transmission via the release of sterile or genetically modified male mosquitoes. However mosquito colonization and laboratory maintenance have the potential to negatively affect male genotypic and phenotypic quality through inbreeding and selection, which in turn can decrease male mating competitiveness in the field. To date, very little is known about the impact of those evolutionary forces on the reproductive biology of mosquito colonies and how they ultimately affect male reproductive fitness.

Methods

Here several male reproductive physiological traits likely to be affected by inbreeding and selection following colonization and laboratory rearing were examined. Sperm length, and accessory gland and testes size were compared in male progeny from field-collected females and laboratory strains of Anopheles gambiae sensu stricto colonized from one to over 25 years ago. These traits were also compared in the parental and sequentially derived, genetically modified strains produced using a two-phase genetic transformation system. Finally, genetic crosses were performed between strains in order to distinguish the effects of inbreeding and selection on reproductive traits.

Results

Sperm length was found to steadily decrease with the age of mosquito colonies but was recovered in refreshed strains and crosses between inbred strains therefore incriminating inbreeding costs. In contrast, testes size progressively increased with colony age, whilst accessory gland size quickly decreased in males from colonies of all ages. The lack of heterosis in response to crossing and strain refreshing in the latter two reproductive traits suggests selection for insectary conditions.

Conclusions

These results show that inbreeding and selection differentially affect reproductive traits in laboratory strains overtime and that heterotic ‘supermales’ could be used to rescue some male reproductive characteristics. Further experiments are needed to establish the exact relationship between sperm length, accessory gland and testes size, and male reproductive success in the laboratory and field settings.     

Behavioral and Neurochemical Characterization of New Mouse Model of Hyperphenylalaninemia

Hyperphenylalaninemia (HPA) refers to all clinical conditions characterized by increased amounts of phenylalanine (PHE) in blood and other tissues. According to their blood PHE concentrations under a free diet, hyperphenylalaninemic patients are commonly classified into phenotypic subtypes: classical phenylketonuria (PKU) (PHE > 1200 µM/L), mild PKU (PHE 600-1200 µM/L) and persistent HPA (PHE 120-600 µM/L) (normal blood PHE < 120 µM/L). The current treatment for hyperphenylalaninemic patients is aimed to keep blood PHE levels within the safe range of 120-360 µM/L through a PHE-restricted diet, difficult to achieve. If untreated, classical PKU presents variable neurological and mental impairment. However, even mildly elevated blood PHE levels, due to a bad compliance to dietary treatment, produce cognitive deficits involving the prefrontal cortical areas, extremely sensible to PHE-induced disturbances. The development of animal models of different degrees of HPA is a useful tool for identifying the metabolic mechanisms underlying cognitive deficits induced by PHE. In this paper we analyzed the behavioral and biochemical phenotypes of different forms of HPA (control, mild-HPA, mild-PKU and classic-PKU), developed on the base of plasma PHE concentrations. Our results demonstrated that mice with different forms of HPA present different phenotypes, characterized by increasing severity of behavioral symptoms and brain aminergic deficits moving from mild HPA to classical PKU forms. In addition, our data identify preFrontal cortex and amygdala as the most affected brain areas and confirm the highest susceptibility of brain serotonin metabolism to mildly elevated blood PHE.     

The immunosuppressive effect of Wharton's jelly stromal cells depends on the timing of their licensing and on lymphocyte activation

BackgroundMesenchymal stromal cells (MSC) have been proven to have potent immunosuppressive action and hence have been proposed for the treatment of severe Graft Versus Host Disease. However, in most models, MSC were added at the same time of lymphocyte stimulation, which is quite different from what occurs in vivo.AimsTo investigate how the timing of lymphocyte activation and the exposure to activation-related cytokines (licensing) can influence the immunosuppressive action of Wharton's jelly stromal cells (WJSC).MethodsWJSC, licensed or not with activation-related cytokines, were added lymphocytes the same time or 24 hours after their stimulation with phytohaemoagglutinin. Proliferation of lymphocytes and cytokines production was measured after three days co-culture.ResultsLymphocytes stimulated in the presence of WJSC displayed a dramatic decrease in proliferation and production of cytokines, in spite of normal expression of activation markers. The suppression was weakened when targeted lymphocytes were seperated by a membrane and partially rescued by the addition of exogenous l-tryptophan, suggesting a major role for indoleamine 2,3-dioxigenase with a probable paracrine effect. Licensing of WJSC increased the immunosuppressive effect, in both contact and non-contact settings. The timing of WJSC licensing was crucial for the immunosuppressive action. Lymphocytes pre-stimulated alone for 24 h, and added afterwards to non-licensed WJSC, showed normal or even increased proliferation. On the other hand, their proliferation was strongly inhibited by licensed WJSC.ConclusionsWJSC have a potent immunosuppressive function best realized with direct contact, and increased by licensing signals before and during lymphocyte stimulation. Our results could contribute to the set up of new WJSC-based therapies for severe autoimmuno disorders.     

Structure and protein composition of sites of papillary muscle attachment to chordae tendineae in avian hearts

Summary Most cardiac myocytes transmit force across fasciae adherentes, specialized sites of cell-cell adhesion. However, some cardiac myocytes in papillary muscle terminate on collagenous connective tissue in the chordae tendineae. These papillary myotendinous junctions (MTJs) are specialized for force transmission from myocytes to extracellular matrix. In the present study, we compared structural molecules at papillary MTJs to those at fasciae adherentes and skeletal MTJs. By using indirect immunofluorescence, we found that papillary MTJs more closely resemble skeletal MTJs in their molecular composition in that they are enriched in talin, vinculin, integrin, and fibronectin. Zeugmatin and -actinin, both components of fasciae adherentes, are absent from papillary MTJs. Although papillary MTJs and skeletal MTJs display strong similarities in structural protein composition, ultrastructural organization of the two junctions is different. Papillary MTJs display little folding of the junctional membrane and, according to morphological criteria, more closely resemble sites of thin filament-membrane association in smooth muscle than skeletal MTJs. Thus, papillary MTJs display a combination of structural characteristics described previously in skeletal and smooth muscles but exhibit few structural features observed previously in cardiac fasciae adherentes.     

Invasive Pulmonary Aspergillosis Complicated by Carbapenem-Resistant Pseudomonas aeruginosa Infection During Pembrolizumab Immunotherapy for Metastatic Lung Adenocarcinoma: Case Report and Review of the Literature

Mycopathologia - The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised...     

When Chocolate Seeking Becomes Compulsion: Gene-Environment Interplay

Background

Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders.

Materials and Methods

We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R) availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot.

Results

Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a “constitutive” genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating.