Humans best judge how much to cooperate when facing hard problems in large groups

We report the results of a game-theoretic experiment with human players who solve the problems of increasing complexity by cooperating in groups of increasing size. Our experimental environment is set up to make it complicated for players to use rational calculation for making the cooperative decisions. This environment is directly translated into a computer simulation, from which we extract the collaboration strategy that leads to the maximal attainable score. Based on this, we measure the error that players make when estimating the benefits of collaboration, and find that humans massively underestimate these benefits when facing easy problems or working alone or in small groups. In contrast, when confronting hard problems or collaborating in large groups, humans accurately judge the best level of collaboration and easily achieve the maximal score. Our findings are independent on groups' composition and players' personal traits. We interpret them as varying degrees of usefulness of social heuristics, which seems to depend on the size of the involved group and the complexity of the situation.Comment: 18 pages, 1 figure. In press for Scientific Report

Supramolecular Organization of the Repetitive Backbone Unit of the Streptococcus pneumoniae Pilus

Streptococcus pneumoniae, like many other Gram-positive bacteria, assembles long filamentous pili on their surface through which they adhere to host cells. Pneumococcal pili are formed by a backbone, consisting of the repetition of the major component RrgB, and two accessory proteins (RrgA and RrgC). Here we reconstruct by transmission electron microscopy and single particle image reconstruction method the three dimensional arrangement of two neighbouring RrgB molecules, which represent the minimal repetitive structural domain of the native pilus. The crystal structure of the D2-D4 domains of RrgB was solved at 1.6 Å resolution. Rigid-body fitting of the X-ray coordinates into the electron density map enabled us to define the arrangement of the backbone subunits into the S. pneumoniae native pilus. The quantitative fitting provide evidence that the pneumococcal pilus consists uniquely of RrgB monomers assembled in a head-to-tail organization. The presence of short intra-subunit linker regions connecting neighbouring domains provides the molecular basis for the intrinsic pilus flexibility

Prodromal Parkinson’s disease, DOPAL and the olfactory bulb: from an organotypic model to clinical relevance

Parkinson’s disease (PD) is an untreatable neurodegenerative disorder affecting more than six million people worldwide, a figure expected to more than double within a generation. The causes of PD are still largely unknown and, at present, no cure is able to halt the progression of the disease, with the available treatments offering merely symptomatic relief. A main limitation in the development of new therapies is the lack of relevant models, especially those mimicking the prodromal stage of the disease. Particularly affected in this phase is the olfactory bulb (OB), the brain region responsible for the initial processing of olfactory sensory information. OB pathology is observed in patients both at a functional and molecular level, with olfactory dysfunction being a prominent feature of prodromal PD and accompanied by the aggregation of α-synuclein, another hallmark of the disease, in olfactory regions. In order to provide a testing platform for the development of disease-modifying therapies, a novel prodromal model of olfactory pathology was successfully developed using both organotypic and primary OB cultures. The use of ex vivo organotypic slices combines the advantages of an in vitro system, such as easy experimental access, simplicity and reduced costs and time, without the loss of the complex milieu and three dimensional architecture of the in vivo tissue. To induce parkinsonian features, cultures were exposed to 3,4- dihydroxyphenylacetylaldehyde (DOPAL), a metabolite of dopamine, that, according to the “catecholaldehyde hypothesis” is thought to play a central role in PD pathogenesis. As DOPAL accumulation has been detected in post-mortem parkinsonian brains and is present in the OB, the use of this metabolite makes our models more physiologically relevant than those based on other toxins, such as hydroxydopamine. Exposure of cultured olfactory bulb slices to DOPAL is able to recapitulate many aspects of PD pathology. In particular, increased oxidative stress, mitochondrial dysfunction, neurodegeneration and protein aggregation are measurable impacts. Moreover, the toxic metabolite induces transcriptomic changes consistent with those reported in clinical studies of familial cases of PD. Lastly, a pilot study was conducted to explore the utility of biochemical detection of α- synuclein in nasal secretions, in combination with a smell test, as potential early- biomarkers of PD. The protein, found in great abundance in olfactory regions, was successfully detected at higher levels in nasal secretions compared to salivary samples. The University of Pennsylvania smell identification test (UPSIT) was used to detect olfactory impairment in a cohort of patients and controls, and its applicability within Ireland has been discussed in detail. Collectively, the results presented here highlight the involvement of DOPAL as a contributing cause of Parkinson’s progression and open the possibility of early detection of PD, by monitoring OB pathology using molecular and functional assays. This novel experimental platform shows great promise as an innovative, easy and accessible technology for the development of new restorative and regenerative treatments for PD, raising the enticing possibility of early-stage intervention.2023-11-0

La formazione di Uqua nella Sezione Valbertad (The Uqua Fm in the Valbertad Section)

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