T1b Glottic Tumor and Anterior Commissure Involvement: Is the Transoral CO2 Laser Microsurgery a Safe Option?

[Abstract] Objectives: Transoral CO2 laser therapy represents the treatment of choice for early-stage laryngeal tumors. The anterior commissure involvement (ACI) is related to a worse local control and a lower rates of organ preservation. The objective of this study is to analyze the differences in survival, local control, and organ preservation in T1b glottic patients according to the presence of ACI. Methods: Observational prospective study in pT1b treated with transoral CO2 laser between 2009 and 2014. Results: Forty patients (37 male and 3 female) with a mean age of 66.43 ± 8.16 years were recruited. Anterior commissure involvement was present in 70% of the patients. The 5-year specific cause survival was 91.66%, with 32.50% of local recurrences. Laryngeal preservation was 80%, being lower in the group with local recurrence (P < .000). The involvement of the anterior commissure does not influence the organ preservation (P = .548), the appearance of local recurrences (P = .391), or the survival (P = .33). Conclusions: Transoral CO2 laser therapy is an effective and reproducible treatment for early-stage laryngeal tumors. The results obtained are similar to previous studies, although they present discrepancies in relation to the role of the ACI. Prospective randomized trials are required focusing also on the patients’ quality of life and functional outcome in order to clarify the role of the ACI and the need to implement changes in its evaluation, staging, and evolution

Molecular genetics of naringenin biosynthesis, a typical plant secondary metabolite produced by Streptomyces clavuligerus

Background: Some types of flavonoid intermediates seemed to be restricted to plants. Naringenin is a typical plant metabolite, that has never been reported to be produced in prokariotes. Naringenin is formed by the action of a chal cone synthase using as starter 4-coumaroyl-CoA, which in dicotyledonous plants derives from phenylalanine by the action of a phenylalanine ammonia lyase. Results: A compound produced by Streptomyces clavuligerus has been identified by LC–MS and NMR as naringenin and coelutes in HPLC with a naringenin standard. Genome mining of S. clavuligerus revealed the presence of a gene for a chalcone synthase (ncs), side by side to a gene encoding a P450 cytochrome (ncyP) and separated from a gene encoding a Pal/Tal ammonia lyase (tal). Deletion of any of these genes results in naringenin non producer mutants. Complementation with the deleted gene restores naringenin production in the transformants. Furthermore, narin genin production increases in cultures supplemented with phenylalanine or tyrosine. Conclusion: This is the first time that naringenin is reported to be produced naturally in a prokariote. Interestingly three non-clustered genes are involved in naringenin production, which is unusual for secondary metabolites. A ten tative pathway for naringenin biosynthesis has been proposed

Robotics and augmented reality for elderly assistance

This article presents a tele-assistance system based on augmented reality for elderly people that is integrated in a mobile platform. We propose the use of augmented reality for simplifying interaction with its users. The first prototype has been designed to help in medication control for ederly people. In this paper, both hardware and software architectures are described.The robotic platform is a slightly modified version of the Turtlebot platform. The software is based on ROS for the platform control, and in ArUco for the augmented reality interface. It also integrates other related systems in teleassistance such as VoIP, friendly user interface, etc

The Drosophila FMRP and LARK RNA-binding proteins function together to regulate eye development and circadian behavior

Fragile X syndrome (FXS) is the most common form of hereditary mental retardation. FXS patients have a deficit for the fragile X mental retardation protein (FMRP) that results in abnormal neuronal dendritic spine morphology and behavioral phenotypes, including sleep abnormalities. In a Drosophila model of FXS, flies lacking the dfmr1 protein (dFMRP) have abnormal circadian rhythms apparently as a result of altered clock output. In this study, we present biochemical and genetic evidence that dFMRP interacts with a known clock output component, the LARK RNA-binding protein. Our studies demonstrate physical interactions between dFMRP and LARK, that the two proteins are present in a complex in vivo, and that LARK promotes the stability of dFMRP. Furthermore, we show genetic interactions between the corresponding genes indicating that dFMRP and LARK function together to regulate eye development and circadian behavior

dAtaxin-2 Mediates Expanded Ataxin-1-Induced Neurodegeneration in a Drosophila Model of SCA1

Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of neurodegenerative disorders sharing atrophy of the cerebellum as a common feature. SCA1 and SCA2 are two ataxias caused by expansion of polyglutamine tracts in Ataxin-1 (ATXN1) and Ataxin-2 (ATXN2), respectively, two proteins that are otherwise unrelated. Here, we use a Drosophila model of SCA1 to unveil molecular mechanisms linking Ataxin-1 with Ataxin-2 during SCA1 pathogenesis. We show that wild-type Drosophila Ataxin-2 (dAtx2) is a major genetic modifier of human expanded Ataxin-1 (Ataxin-1[82Q]) toxicity. Increased dAtx2 levels enhance, and more importantly, decreased dAtx2 levels suppress Ataxin-1[82Q]-induced neurodegeneration, thereby ruling out a pathogenic mechanism by depletion of dAtx2. Although Ataxin-2 is normally cytoplasmic and Ataxin-1 nuclear, we show that both dAtx2 and hAtaxin-2 physically interact with Ataxin-1. Furthermore, we show that expanded Ataxin-1 induces intranuclear accumulation of dAtx2/hAtaxin-2 in both Drosophila and SCA1 postmortem neurons. These observations suggest that nuclear accumulation of Ataxin-2 contributes to expanded Ataxin-1-induced toxicity. We tested this hypothesis engineering dAtx2 transgenes with nuclear localization signal (NLS) and nuclear export signal (NES). We find that NLS-dAtx2, but not NES-dAtx2, mimics the neurodegenerative phenotypes caused by Ataxin-1[82Q], including repression of the proneural factor Senseless. Altogether, these findings reveal a previously unknown functional link between neurodegenerative disorders with common clinical features but different etiology

The AXH Domain of Ataxin-1 Mediates Neurodegeneration through Its Interaction with Gfi-1/Senseless Proteins

SummarySpinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by an expanded glutamine tract in human Ataxin-1 (hAtx-1). The expansion stabilizes hAtx-1, leading to its accumulation. To understand how stabilized hAtx-1 induces selective neuronal degeneration, we studied Drosophila Atx-1 (dAtx-1), which has a conserved AXH domain but lacks a polyglutamine tract. Overexpression of hAtx-1 in fruit flies produces phenotypes similar to those of dAtx-1 but different from the polyglutamine peptide alone. We show that the Drosophila and mammalian transcription factors Senseless/Gfi-1 interact with Atx-1’s AXH domain. In flies, overexpression of Atx-1 inhibits sensory-organ development by decreasing Senseless protein. Similarly, overexpression of wild-type and glutamine-expanded hAtx-1 reduces Gfi-1 levels in Purkinje cells. Deletion of the AXH domain abolishes the effects of glutamine-expanded hAtx-1 on Senseless/Gfi-1. Interestingly, loss of Gfi-1 mimics SCA1 phenotypes in Purkinje cells. These results indicate that the Atx-1/Gfi-1 interaction contributes to the selective Purkinje cell degeneration in SCA1

Interaction of Akt-Phosphorylated Ataxin-1 with 14-3-3 Mediates Neurodegeneration in Spinocerebellar Ataxia Type 1

AbstractSpinocerebellar ataxia type 1 (SCA1) is one of several neurological disorders caused by a CAG repeat expansion. In SCA1, this expansion produces an abnormally long polyglutamine tract in the protein ataxin-1. Mutant polyglutamine proteins accumulate in neurons, inducing neurodegeneration, but the mechanism underlying this accumulation has been unclear. We have discovered that the 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation. The association of ataxin-1 with 14-3-3 is regulated by Akt phosphorylation, and in a Drosophila model of SCA1, both 14-3-3 and Akt modulate neurodegeneration. Our finding that phosphatidylinositol 3-kinase/Akt signaling and 14-3-3 cooperate to modulate the neurotoxicity of ataxin-1 provides insight into SCA1 pathogenesis and identifies potential targets for therapeutic intervention

Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation

Cleavage of mutant huntingtin (HTT) is an essential process in Huntington's disease (HD), an inherited neurodegenerative disorder. Cleavage generates N-ter fragments that contain the polyQ stretch and whose nuclear toxicity is well established. However, the functional defects induced by cleavage of full-length HTT remain elusive. Moreover, the contribution of non-polyQ C-terminal fragments is unknown. Using time- and site-specific control of full-length HTT proteolysis, we show that specific cleavages are required to disrupt intramolecular interactions within HTT and to cause toxicity in cells and flies. Surprisingly, in addition to the canonical pathogenic N-ter fragments, the C-ter fragments generated, that do not contain the polyQ stretch, induced toxicity via dilation of the endoplasmic reticulum (ER) and increased ER stress. C-ter HTT bound to dynamin 1 and subsequently impaired its activity at ER membranes. Our findings support a role for HTT on dynamin 1 function and ER homoeostasis. Proteolysis-induced alteration of this function may be relevant to disease. Synopsis The development of a time and site-specifically controlled cleavage of the mutant huntingtin protein reveals a pathogenic mechanism induced by the non-polyQ-containing fragments that are generated upon proteolysis during disease progression. Huntingtin proteolysis generates N-ter fragments that contain the toxic polyQ stretch but also the corresponding C-ter fragments. N-ter to C-ter intramolecular interactions present in full-length huntingtin are abrogated by sequential cleavages. Whereas the N-ter polyQ fragments translocate into the nucleus, the non-polyQ C-ter huntingtin fragments remain in the cytoplasm and cause ER dilation, stress and cell death. C-ter huntingtin fragments bind and inactivate dynamin 1 at the ER thus causing ER dilation and toxicity. Site-specifically controlled cleavage of the mutant huntingtin protein reveals a pathogenic mechanism induced by non-polyQ-containing fragments that are generated upon proteolysis during disease progression.</p

Tunable Energy-Transfer Process in Heterometallic MOF Materials Based on 2,6-Naphthalenedicarboxylate: Solid-State Lighting and Near-Infrared Luminescence Thermometry

Trivalent lanthanide ions (Ln3+) are used to prepare a plethora of coordination compounds, with metal-organic frameworks (MOFs) being among the most sought-after in recent years. The porosity of Ln-MOFs is often complemented by the luminescence imparted by the metal centers, making them attractive multifunctional materials. Here, we report a class of three-dimensional (3D) MOFs obtained from a solvothermal reaction between 2,6-naphthalenedicarboxylic acid (H2NDC) and lanthanide chlorides, yielding three types of compounds depending on the chosen lanthanide: [LnCl(NDC)(DMF)] for Ln3+ = La3+, Ce3+, Pr3+, Nd3+, Sm3+ (type 1), [Eu(NDC)1.5(DMF)]·0.5DMF (type 2), and [Ln2(NDC)3(DMF)2] for Ln3+ = Tb3+, Dy3+, Y3+, Er3+, Yb3+ (type 3). Photoluminescent properties of selected phases were explored at room temperature. The luminescence thermometry capability of Yb3+-doped Nd-MOF was fully investigated in the 15-300 K temperature range under 365 and 808 nm excitation. To describe the optical behavior of the isolated MOFs, we introduce the total energy-transfer balance model. Therein, the sum of energy-transfer rates is considered along with its dependence on the temperature - the sign, magnitude, and variation of this parameter - permitting to afford a thorough interpretation of the observed behavior of the luminescent species of all materials presented here. The combination of novel theoretical and experimental studies presented herein to describe energy-transfer processes in luminescent materials can pave the way toward the design of MOF-based chemical and physical sensors working in an optical range of interest for biomedical applications.Fil: Gomez, Germán Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Marin, Riccardo. University of Ottawa; CanadáFil: Carneiro Neto, Albano N.. Universidade de Aveiro; PortugalFil: Botas, Alexandre M. P.. Universidade de Aveiro; PortugalFil: Ovens, Jeffrey. University of Ottawa; CanadáFil: Kitos, Alexandros A.. University of Ottawa; CanadáFil: Bernini, Maria Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Carlos, Luís D.. Universidade de Aveiro; PortugalFil: Soler Illia, Galo Juan de Avila Arturo. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Murugesu, Muralee. University of Ottawa; Canad

La ciudad de Las Palmas en Gran Canaria contestando a varios impresos publicados en la Villa de Santa Cruz de Tenerife, demuestra su superioridad respecto de esta ultima : setiembre de 1842

Mención de responsabilidad tomada del final del textoTít. tomado de Vizcaya Cárpente