Active gaze control improves optic flow-based segmentation and steering

An observer traversing an environment actively relocates gaze to fixate objects. Evidence suggests that gaze is frequently directed toward the center of an object considered as target but more likely toward the edges of an object that appears as an obstacle. We suggest that this difference in gaze might be motivated by specific patterns of optic flow that are generated by either fixating the center or edge of an object. To support our suggestion we derive an analytical model that shows: Tangentially fixating the outer surface of an obstacle leads to strong flow discontinuities that can be used for flow-based segmentation. Fixation of the target center while gaze and heading are locked without head-, body-, or eye-rotations gives rise to a symmetric expansion flow with its center at the point being approached, which facilitates steering toward a target. We conclude that gaze control incorporates ecological constraints to improve the robustness of steering and collision avoidance by actively generating flows appropriate to solve the task.     

Molecular and functional characterization of the odorant receptor2 (OR2) in the tiger mosquito Aedes albopictus

In mosquitoes, the olfactory system plays a crucial role in many types of behavior, including nectar feeding, host preference selection and oviposition. Aedes albopictus, known also as the tiger mosquito, is an anthropophilic species, which in the last few years, due to its strong ecological plasticity, has spread throughout the world. Although long considered only a secondary vector of viruses, the potential of its vector capacity may constitute a threat to public health. Based on the idea that an improved understanding of the olfactory system of mosquitoes may assist in the development of control methods that interfere with their behavior, we have undertaken a study aimed at characterizing the A. albopictus Odorant Receptors. Here we report the identification, cloning and functional characterization of the AalOR2 ortholog, that represents the first candidate member of the odorant receptor (OR) family of proteins from A. albopictus. AalOR2 is expressed in the larval heads and antennae of adults. Our data indicate that A. albopictus OR2 (AalOR2) shares a high degree of identity with other mosquito OR2 orthologs characterized to date, confirming that OR2 is one of the most conserved mosquito ORs. Our data indicate that AalOR2 is narrowly tuned to indole, and inhibited by (-)-menthone. In agreement with this results, these two compounds elicit two opposite effects on the olfactory-based behavior of A. albopictus larvae, as determined through a larval behavioral assay. In summary, this work has led to the cloning and de-orphaning of the first Odorant Receptor in the tiger mosquito A. albopictus. In future control strategies this receptor may be used as a potential molecular target.     

First chemoenzymatic synthesis of (+)-2-carboxypyrrolidine-3-acetic acid, the nucleus of kainoid amino acids

The distinctive nucleus of kainoid amino acids, (2S,3R)-(+)-2-carboxypyrrolidine-3-acetic acid 6, was synthesized by a chemoenzymatic process, exploiting the diastereomeric cis/trans methyl pyroglutamate derivatives 10a-c/11a-c as key intermediates. These mixtures, when subjected to a kinetic resolution mediated by α-chymotrypsin, reacted diastereo-, regio-, and enantioselectively to give the trans derivatives (+)-10a-c possessing the correct (2S,3R) configuration. Subsequently, the desired product (2S,3R)-(+)-6 could be obtained after well-established transformations.     

Representation of motion onset and offset in an augmented Barlow-Levick model of motion detection

Kinetic occlusion produces discontinuities in the optic flow field, whose perception requires the detection of an unexpected onset or offset of otherwise predictably moving or stationary contrast patches. Many cells in primate visual cortex are directionally selective for moving contrasts, and recent reports suggest that this selectivity arises through the inhibition of contrast signals moving in the cells’ null direction, as in the rabbit retina. This nulling inhibition circuit (Barlow-Levick) is here extended to also detect motion onsets and offsets. The selectivity of extended circuit units, measured as a peak evidence accumulation response to motion onset/offset compared to the peak response to constant motion, is analyzed as a function of stimulus speed. Model onset cells are quiet during constant motion, but model offset cells activate during constant motion at slow speeds. Consequently, model offset cell speed tuning is biased towards higher speeds than onset cell tuning, similarly to the speed tuning of cells in the middle temporal area when exposed to speed ramps. Given a population of neurons with different preferred speeds, this asymmetry addresses a behavioral paradox—why human subjects in a simple reaction time task respond more slowly to motion offsets than onsets for low speeds, even though monkey neuron firing rates react more quickly to the offset of a preferred stimulus than to its onset.     

p300/CBP acetyl transferases interact with and acetylate the nucleotide excision repair factor XPG

Nucleotide excision repair (NER) is an important DNA repair mechanism through which cells remove bulky DNA lesions. Following DNA damage, the histone acetyltransferase (HAT) p300 (also referred to as lysine acetyltransferase or KAT) is known to associate with proliferating cell nuclear antigen (PCNA), a master regulator of DNA replication and repair processes. This interaction, which results in HAT inhibition, may be dissociated by the cell cycle inhibitor p21^CDKN1A, thereby restoring p300 activity; however, the role of this protein interplay is still unclear. Here, we report that silencing p300 or its homolog CREB-binding protein (CBP) by RNA interference (RNAi) significantly reduces DNA repair synthesis in human fibroblasts. In addition, we determined whether p300 and CBP may associate with and acetylate specific NER factors such as XPG, the 3′-endonuclease that is involved in the incision/excision step and is known to interact with PCNA. Our results show that p300 and CBP interact with XPG, which has been found to be acetylated in vivo. XPG is acetylated by p300 in vitro, and this reaction is inhibited by PCNA. Knocking down both p300/CBP by RNAi or by chemical inhibition with curcumin greatly reduced XPG acetylation, and a concomitant accumulation of the protein at DNA damage sites was observed. The ability of p21 to bind PCNA was found to regulate the interaction between p300 and XPG, and an abnormal accumulation of XPG at DNA damage sites was also found in p21^−/− fibroblasts. These results indicate an additional function of p300/CBP in NER through the acetylation of XPG protein in a PCNA–p21 dependent manner.     

Remote health monitoring for elderly through interactive television

ABSTRACT: BACKGROUND: Providing remote health monitoring to specific groups of patients represents an issue of great relevance for the national health systems, because of the costs related to moving health operators, the time spent to reach remote sites, and the high number of people needing health assistance. At the same time, some assistance activities, like those related to chronical diseases, may be satisfied through a remote interaction with the patient, without a direct medical examination. METHODS: Moving from this considerations, our paper proposes a system architecture for the provisioning of remote health assistance to older adults, based on a blind management of a network of wireless medical devices, and an interactive TV Set Top Box for accessing health related data. The selection of TV as the interface between the user and the system is specifically targeted to older adults. Due to the private nature of the information exchanged, a certified procedure is implemented for data delivery, through the use of non conditional smart cards. All these functions may be accomplished through a proper design of the system management, and a suitable interactive application. RESULTS: The interactive application acting as the interface between the user and the system on the TV monitor has been evaluated able to help readability and clear understanding of the contents and functions proposed. Thanks to the limited amount of data to transfer, even a Set Top Box equipped with a traditional PSTN modem may be used to support the proposed service at a basic level; more advanced features, like audio/video connection, may be activated if the Set Top Box enables a broadband connection (e.g. ADSL). CONCLUSIONS: The proposed layered architecture for a remote health monitoring system can be tailored to address a wide range of needs, according with each patient's conditions and capabilities. The system exploits the potentialities offered by Digital Television receivers, a friendly MHP interface, and the familiar remote control, to make the service effective and easy to use also for elderly people.     

Replication fork stalling in WRN-deficient cells is overcome by prompt activation of a MUS81-dependent pathway

Failure to stabilize and properly process stalled replication forks results in chromosome instability, which is a hallmark of cancer cells and several human genetic conditions that are characterized by cancer predisposition. Loss of WRN, a RecQ-like enzyme mutated in the cancer-prone disease Werner syndrome (WS), leads to rapid accumulation of double-strand breaks (DSBs) and proliferating cell nuclear antigen removal from chromatin upon DNA replication arrest. Knockdown of the MUS81 endonuclease in WRN-deficient cells completely prevents the accumulation of DSBs after fork stalling. Also, MUS81 knockdown in WS cells results in reduced chromatin recruitment of recombination enzymes, decreased yield of sister chromatid exchanges, and reduced survival after replication arrest. Thus, we provide novel evidence that WRN is required to avoid accumulation of DSBs and fork collapse after replication perturbation, and that prompt MUS81-dependent generation of DSBs is instrumental for recovery from hydroxyurea-mediated replication arrest under such pathological conditions.     

NAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes.

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a cytosolic two-electron reductase, and compounds of the quinone family such as mitomycin C are efficiently bioactivated by this enzyme. The observation that DT-diaphorase is highly expressed in many cancerous tissues compared to normal tissues has provided us with a potentially selective target that can be exploited in the design of novel anticancer agents. Because of the relative lack of information about the cell-specific expression of DT-diaphorase, the purpose of this study was to map the distribution of this enzyme in normal human tissues. Fifteen tissue samples from normal human kidney were analyzed for expression of DT-diaphorase by immunohistochemistry (two-step indirect method). We found a specific high expression of DT-diaphorase in glomerular visceral epithelial cells (podocytes). These results suggest that a high expression of DT-diaphorase in podocytes could play a major role in the pathogenesis of renal toxicity and mitomycin C-induced hemolytic uremic syndrome, in which injury to the glomerular filtration mechanism is the primary damage, leading to a cascade of deleterious events including microangiopathic hemolytic anemia and thrombocytopenia. This observation has potential therapeutic implications because the DT-diaphorase metabolic pathway is influenced by many agents, including drugs, diet, and environmental cell factors such as pH and oxygen tension.     

Calix[4]arene decorated with four Tn antigen glycomimetic units and P3CS immunoadjuvant: synthesis, characterization, and anticancer immunological evaluation

A novel anticancer vaccine candidate built on a nonpeptidic scaffold has been synthesized. Four S-Tn tumor-associated glycomimetic antigens have been clustered onto a calix[4]arene scaffold bearing an immunoadjuvant moiety (P3CS). The immunogenicity of the synthetic construct has been investigated by immunization of mice in vivo. ELISA assay has evidenced that the tetravalent construct stimulates a higher production of anti-Tn antigen IgG antibodies when compared to an analogous monovalent compound. This result is ascribable to an antigen cluster effect and makes the reported vaccine candidate a good mimic of the natural motifs present on the mucine surface.     

Ruthenium(III) dimethyl sulfoxide pyridinehydroxamic acid complexes as potential antimetastatic agents: synthesis,characterisation and in vitro pharmacological evaluation

Reaction of 3-pyridinehydroxamic acid and 4-pyridinehydroxamic acid (3-pyha and 4-pyha) with either [NBu₄][RuCl₄(dmso-S)₂] or [(dmso)₂H][RuCl₄(dmso-S)₂] (dmso is dimethyl sulfoxide) in acetone afforded three new ruthenium(III) dimethyl sulfoxide pyridinehydroxamic acid complexes: [NBu₄][trans-RuCl₄(dmso-S)(4-pyha)]·CH₃COCH₃ (1), [3-pyhaH][trans-RuCl₄(dmso-S)(3-pyha)] (2) and [4-pyhaH][trans-RuCl₄(dmso-S)(4-pyha)] (3). The solid-state structure of [NBu₄][trans-RuCl₄(dmso-S)(4-pyha)]·CH₃COCH₃ (1) was determined by X-ray crystallography. 2 and 3 were pharmacologically evaluated for their in vitro cytotoxicity, their ability to inhibit cell invasion and their gelatinase activity. 2 and 3 were devoid of cytotoxicity against the cell lines tested. 2 inhibited invasion of the highly invasive MDA-MB-231 cells to a much greater extent than 3. Contrary to expectations, neither 2 nor 3 had any inhibitory effect on matrix metalloproteinase (MMP) production and/or activity and in fact 3 was found to enhance the production and/or activity of both MMP-2 and MMP-9.