Dynamic Sounds Capture the Boundaries of Peripersonal Space Representation in Humans

Background

We physically interact with external stimuli when they occur within a limited space immediately surrounding the body, i.e., Peripersonal Space (PPS). In the primate brain, specific fronto-parietal areas are responsible for the multisensory representation of PPS, by integrating tactile, visual and auditory information occurring on and near the body. Dynamic stimuli are particularly relevant for PPS representation, as they might refer to potential harms approaching the body. However, behavioural tasks for studying PPS representation with moving stimuli are lacking. Here we propose a new dynamic audio-tactile interaction task in order to assess the extension of PPS in a more functionally and ecologically valid condition.

Methodology/Principal Findings

Participants vocally responded to a tactile stimulus administered at the hand at different delays from the onset of task-irrelevant dynamic sounds which gave the impression of a sound source either approaching or receding from the subject’s hand. Results showed that a moving auditory stimulus speeded up the processing of a tactile stimulus at the hand as long as it was perceived at a limited distance from the hand, that is within the boundaries of PPS representation. The audio-tactile interaction effect was stronger when sounds were approaching compared to when sounds were receding.

Conclusion/Significance

This study provides a new method to dynamically assess PPS representation: The function describing the relationship between tactile processing and the position of sounds in space can be used to estimate the location of PPS boundaries, along a spatial continuum between far and near space, in a valuable and ecologically significant way.     

Canine cutaneous leishmaniasis caused by neotropical Leishmania infantum despite of systemic disease: A case report

Visceral leishmaniasis is an anthropozoonosis caused by a protozoan Leishmania infantum (syn. Leishmania chagasi). Here, we report a typical case of canine cutaneous leishmaniasis due to L. infantum infection without any other systemic symptom in one dog in the city of Rio de Janeiro, Brazil. A mongrel female dog was admitted in a veterinary clinic with reports of chronic wounds in the body. Physical examination revealed erosive lesions in the limbs, nasal ulcers, presence of ectoparasites and seborrheic dermatitis. Blood samples and fragments of healthy and injured skin were collected. The complete hemogram revealed aregenerative normocytic normochromic anemia and erythrocyte rouleaux, and biochemical analysis revealed normal renal and hepatic functions. Cytology of the muzzle and skin lesions suggested pyogranulomatous inflammatory process. The histopathology of a skin fragment was performed and revealed suspicion of protozoa accompanied by necrotizing dermatitis. The diagnosis of leishmaniasis was accomplished by positive serology, isolation of Leishmania from the skin lesion, and also by molecular test (PCR targeting the conserved region of Leishmania kDNA). Culture was positive for damaged skin samples. PCR targeting a fragment of Leishmania hsp70 gene was performed employing DNA extracted from damaged skin. RFLP of the amplified hsp70 fragment identified the parasite as L. infantum, instead of Leishmania braziliensis, the main agent of cutaneous leishmaniasis in Rio de Janeiro. Characterization of isolated promastigotes by five different enzymatic systems confirmed the species identification of the etiological agent. Serology was positive by ELISA and rapid test. This case warns to the suspicion of viscerotropic Leishmania in cases of chronic skin lesions and brings the discussion of the mechanisms involved in the parasite tissue tropism.     

Analysis of predisposing factors for contamination of bone and tendon allografts

Bone and tissue allografts are widely used in transplantation. The increasing demand for safe allografts must be met, while minimizing disease transmission. We analysed the incidence and potential risk factors of allograft contamination and the effectiveness of disinfection, by reviewing 22 years of tissue bank activity and 474 donor procurements. We also compared different disinfection procedures used over the 22 years. The overall contamination rate was 10.1%. Risk factors were related to the donor or procurement method. Immediate culture at the tissue recovery site diminished the rate of false positives by reducing later sample manipulation. High-virulence allograft contamination was mainly related to donor factors, while low-virulence contamination was related to procurement methods. Analysis of donor-related risk factors showed no statistical differences for age, sex, or cause of death. An intensive care unit stay was associated with less contamination with high-virulence microbes. Procurement in a setting other than an operating theatre was associated with higher contamination rate. Team experience reduced contamination. Pelvic and tendon allografts were most frequently contaminated. Proper disinfection considerably reduced the contamination rate to 3.6%. We conclude that procurement must be performed under aseptic conditions, with short delays, and by trained personnel. Grafts should be disinfected and packed as soon as possible.     

Gastric pythiosis in a dog

BackgroundPythiosis is caused by the agent Pythium insidiosum, an aquatic oomycete of the kingdom Stramenopila.AimsTo describe the symptoms, pathological changes and diagnosis methods of gastric pythiosis in dogs.MethodsA three-year-old female German shepherd, with access to wetlands, was attended due to vomiting and recurrent diarrhea of 30 days of duration. A palpable mass in the abdomen filling the left epigastric region was identified in the clinical examination. Simple and contrasted radiological examination and ultrasound of abdominal cavity were performed. The animal was referred for exploratory laparotomy for the removal of the mass. The extent of the mass prevented from the excision and the animal was euthanized. Samples of the tumor mass were collected and sent for morphological study and immunohistochemistry.ResultsThe changes observed in imaging studies were consistent with gastric pythiosis. In cytology and histopathology, non-septate hyphae were identified, and in immunohistochemistry a strong positivity of anti-Pythium antibodies was observed, confirming the diagnosis of pythiosis.ConclusionsPythiosis in dogs is diagnosed late and tends to evolve in the animal's death. The definitive diagnosis is by cytology, histology and immunohistochemistry.     

A small ribozyme with dual-site kinase activity

Phosphoryl transfer onto backbone hydroxyls is a recognized catalytic activity of nucleic acids. We find that kinase ribozyme K28 possesses an unusually complex active site that promotes (thio)phosphorylation of two residues widely separated in primary sequence. After allowing the ribozyme to radiolabel itself by phosphoryl transfer from [γ-³²P]GTP, DNAzyme-mediated cleavage yielded two radiolabeled cleavage fragments, indicating phosphorylation sites within each of the two cleavage fragments. These sites were mapped by alkaline digestion and primer extension pausing. Enzymatic digestion and mutational analysis identified nucleotides important for activity and established the active structure as being a constrained pseudoknot with unusual connectivity that may juxtapose the two reactive sites. Nuclease sensitivities for nucleotides near the pseudoknot core were altered in the presence of GTPγS, indicating donor-induced folding. The 5′ target site was more strongly favored in full-length ribozyme K28 (128 nt) than in truncated RNAs (58 nt). Electrophoretic mobilities of self-thiophosphorylated products on organomercurial gels are distinct from the 5′ mono-thiophosphorylated product produced by reaction with polynucleotide kinase, potentially indicating simultaneous labeling of both sites within individual RNA strands. Our evidence supports a single, compact structure with local dynamics, rather than global rearrangement, as being responsible for dual-site phosphorylation.     

The role of membrane stiffness and actin turnover on the force exerted by DRG lamellipodia

We used optical tweezers to analyze the effect of jasplakinolide and cyclodextrin on the force exerted by lamellipodia from developing growth cones (GCs) of isolated dorsal root ganglia (DRG) neurons. We found that 25 nM of jasplakinolide, which is known to inhibit actin filament turnover, reduced both the maximal exerted force and maximal velocity during lamellipodia leading-edge protrusion. By using atomic force microscopy, we verified that cyclodextrin, which is known to remove cholesterol from membranes, decreased the membrane stiffness of DRG neurons. Lamellipodia treated with 2.5 mM of cyclodextrin exerted a larger force, and their leading edge could advance with a higher velocity. Neither jasplakinolide nor cyclodextrin affected force or velocity during lamellipodia retraction. The amplitude and frequency of elementary jumps underlying force generation were reduced by jasplakinolide but not by cyclodextrin. The action of both drugs at the used concentration was fully reversible. These results support the notion that membrane stiffness provides a selective pressure that shapes force generation, and confirm the pivotal role of actin turnover during protrusion.     

The mitochondrial permeability transition pore (PTP) - an example of multiple molecular exaptation?

The mitochondrial permeability transition (PT) is a well-recognized phenomenon that allows mitochondria to undergo a sudden increase of permeability to solutes with molecular mass ≤ 1500Da, leading to organelle swelling and structural modifications. The relevance of PT relies on its master role in the manifestation of programmed cell death (PCD). This function is performed by a mega-channel (in some cases inhibited by cyclosporin A) named permeability transition pore (PTP), whose function could derive from the assembly of different mitochondrial proteins. In this paper we examine the distribution and characteristics of PTP in mitochondria of eukaryotic organisms so far investigated in order to draw a hypothesis on the mechanism of its evolution. As a result, we suggest that PTP may have arisen as a new function linked to a multiple molecular exaptation of different mitochondrial proteins, even though they could nevertheless still play their original role. Furthermore, we suggest that the early appearance of PTP could have had a crucial role in the establishment of endosymbiosis in eukaryotic cells, by the coordinated balancing of ATP production by glycolysis (performed by the primary phagocyte) and oxidative phosphorylation (accomplished by the endosymbiont). Indeed, we argue on the possibility that this new energetic equilibrium could have opened the way to the subsequent evolution toward metazoans.     

Genomic analysis of ICEVchBan8: An atypical genetic element in Vibrio cholerae

Genomic islands (GIs) and integrative conjugative elements (ICEs) are major players in bacterial evolution since they encode genes involved in adaptive functions of medical or environmental importance. Here we performed the genomic analysis of ICEVchBan8, an unusual ICE found in the genome of a clinical non-toxigenic Vibrio cholerae O37 isolate. ICEVchBan8 shares most of its genetic structure with SXT/R391 ICEs. However, this ICE codes for a different integration/excision module is located at a different insertion site, and part of its genetic cargo shows homology to other pathogenicity islands of V. cholerae.     

CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons

Mutations of the cyclin-dependent kinase-like 5 (CDKL5) and netrin-G1 (NTNG1) genes cause a severe neurodevelopmental disorder with clinical features that are closely related to Rett syndrome, including intellectual disability, early-onset intractable epilepsy and autism. We report here that CDKL5 is localized at excitatory synapses and contributes to correct dendritic spine structure and synapse activity. To exert this role, CDKL5 binds and phosphorylates the cell adhesion molecule NGL-1. This phosphorylation event ensures a stable association between NGL-1 and PSD95. Accordingly, phospho-mutant NGL-1 is unable to induce synaptic contacts whereas its phospho-mimetic form binds PSD95 more efficiently and partially rescues the CDKL5-specific spine defects. Interestingly, similarly to rodent neurons, iPSC-derived neurons from patients with CDKL5 mutations exhibit aberrant dendritic spines, thus suggesting a common function of CDKL5 in mice and humans.