On some descriptive generalizations in Romance

In this work we intend to present a number of cross-linguistic descriptive generalizations concerning Romance languages and point out their theoretical relevance for syntactic theory. We will make extensive use of dialectal variation, viewing it as a way to shed light on diachronic processes on the one side and on the complexity of syntactic structure on the other. We will restrict the empirical domain considering in general only some areas of Romance languages and Italian dialects. The linguistic domain that we take into consideration includes three distinct areas of syntactic processes: wh-items and questions in general, personal pronouns and negation. The choice of the grammatical topics is due to both practical and theoretical reasons, as these three domains have been - and still are - central to the development of syntactic theory, and have been systematically explored during fieldwork in the last ten years. The geographical area we have chosen is the one whose micro-variation has been more extensively investigated, both with respect to modern and preceding stages (going back to the 13th century). The aim of this article is not to provide new analyses for a single phenomenon, but to show how cross-linguistic variation can direct our research towards a precise path and narrow down the number of possible analyses of a given phenomenon. As will appear in what follows, descriptive generalizations will be formulated in their strongest form: this does not mean that we are particularly sure that they cannot be falsified if the domain of languages studied is widened. We think that a generalization has an empirical side, which has the function of a challenge: it provokes further, more detailed, observations and possibly more accurate description. Even if a generalization ends up being falsified, we will have increased our empirical basis and, more generally, our knowledge of how languages work. In section 2 we examine the pattern of clitic wh-elements and illustrate some empirical generalizations that are valid both diachronically and cross-linguistically; in section 3 we do the same with respect to the emergence of pronominal clitics . A comparison between the two evolutionary patterns is presented in section 4, where we isolate some properties common to both wh-items and pronouns. In section 5, we present and discuss some empirical generalizations that lead us to analyze wh- in situ and wh-doubling in Romance as closely related phenomena. Section 6 illustrates the factors that influence the cliticization process of a preverbal negation marker, namely modality and verb movement. Section 7 deals with the common properties of cliticization phenomena. Although the factors favoring cliticization are different for the various classes of elements (wh-items, pronouns and negative markers) that undergo the process, it appears that the pattern of cliticization is essentially the same wherever it is manifested. The clitic elements appear in positions where the strong counterpart used to move to; this can either be hypothesized or attested for past stages of a language or directly observed in the present, in closely related dialects or inside the same one as an option with slightly different interpretations

Expanding the molecular and phenotypic spectrum of truncating MT-ATP6 mutations

Objective To describe the clinical and functional consequences of 1 novel and 1 previously reported truncating MT-ATP6 mutation. Methods Three unrelated probands with mitochondrial encephalomyopathy harboring truncating MT-ATP6 mutations are reported. Transmitochondrial cybrid cell studies were used to confirm pathogenicity of 1 novel variant, and the effects of all 3 mutations on ATPase 6 and complex V structure and function were investigated. Results Patient 1 presented with adult-onset cerebellar ataxia, chronic kidney disease, and diabetes, whereas patient 2 had myoclonic epilepsy and cerebellar ataxia; both harbored the novel m.8782G>A; p.(Gly86*) mutation. Patient 3 exhibited cognitive decline, with posterior white matter abnormalities on brain MRI, and severely impaired renal function requiring transplantation. The m.8618dup; p.(Thr33Hisfs*32) mutation, previously associated with neurogenic muscle weakness, ataxia, and retinitis pigmentosa, was identified. All 3 probands demonstrated a broad range of heteroplasmy across different tissue types. Blue-native gel electrophoresis of cultured fibroblasts and skeletal muscle tissue confirmed multiple bands, suggestive of impaired complex V assembly. Microscale oxygraphy showed reduced basal respiration and adenosine triphosphate synthesis, while reactive oxygen species generation was increased. Transmitochondrial cybrid cell lines studies confirmed the deleterious effects of the novel m.8782 G>A; p.(Gly86*) mutation. Conclusions We expand the clinical and molecular spectrum of MT-ATP6-related mitochondrial disorders to include leukodystrophy, renal disease, and myoclonic epilepsy with cerebellar ataxia. Truncating MT-ATP6 mutations may exhibit highly variable mutant levels across different tissue types, an important consideration during genetic counseling

Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features

Background: Mitochondria provide ATP through the process of oxidative phosphorylation, physically located in the inner mitochondrial membrane (IMM). The mitochondrial contact site and organising system (MICOS) complex is known as the € mitoskeleton' due to its role in maintaining IMM architecture. APOO encodes MIC26, a component of MICOS, whose exact function in its maintenance or assembly has still not been completely elucidated. Methods: We have studied a family in which the most affected subject presented progressive developmental delay, lactic acidosis, muscle weakness, hypotonia, weight loss, gastrointestinal and body temperature dysautonomia, repetitive infections, cognitive impairment and autistic behaviour. Other family members showed variable phenotype presentation. Whole exome sequencing was used to screen for pathological variants. Patient-derived skin fibroblasts were used to confirm the pathogenicity of the variant found in APOO. Knockout models in Drosophila melanogaster and Saccharomyces cerevisiae were employed to validate MIC26 involvement in MICOS assembly and mitochondrial function. Results: A likely pathogenic c.350T>C transition was found in APOO predicting an I117T substitution in MIC26. The mutation caused impaired processing of the protein during import and faulty insertion into the IMM. This was associated with altered MICOS assembly and cristae junction disruption. The corresponding mutation in MIC26 or complete loss was associated with mitochondrial structural and functional deficiencies in yeast and D. melanogaster models. Conclusion: This is the first case of pathogenic mutation in APOO, causing altered MICOS assembly and neuromuscular impairment. MIC26 is involved in the assembly or stability of MICOS in humans, yeast and flies

Selective Disruption of Mitochondrial Thiol Redox State in Cells and In Vivo.

Mitochondrial glutathione (GSH) and thioredoxin (Trx) systems function independently of the rest of the cell. While maintenance of mitochondrial thiol redox state is thought vital for cell survival, this was not testable due to the difficulty of manipulating the organelle's thiol systems independently of those in other cell compartments. To overcome this constraint we modified the glutathione S-transferase substrate and Trx reductase (TrxR) inhibitor, 1-chloro-2,4-dinitrobenzene (CDNB) by conjugation to the mitochondria-targeting triphenylphosphonium cation. The result, MitoCDNB, is taken up by mitochondria where it selectively depletes the mitochondrial GSH pool, catalyzed by glutathione S-transferases, and directly inhibits mitochondrial TrxR2 and peroxiredoxin 3, a peroxidase. Importantly, MitoCDNB inactivates mitochondrial thiol redox homeostasis in isolated cells and in vivo, without affecting that of the cytosol. Consequently, MitoCDNB enables assessment of the biomedical importance of mitochondrial thiol homeostasis in reactive oxygen species production, organelle dynamics, redox signaling, and cell death in cells and in vivo.We acknowledge the Biotechnology and Biological Sciences Research Council (BB/I012826/1), the Wellcome Trust (WT110158/Z/15/Z, 110159/Z/15/Z and RG88195), the University of Glasgow (JMG Studentship), and the Medical Research Council (MC_U105663142 and MC_ UU_00015/7)

Doñana. Acta vertebrata. vol 22 (1/2)

Relación entre el uso del espacio del mito (Aeghitalos caudatus) y la disponibilidad de artrópodos durante el periodo primavera-veranoHábitos frugívoros de la corzuela parda (Mazama gouazoubira, Ficher, 1814) (Mammalia: Cervidae), en un ambiente secundario de yungasComparación entre varias técnicas de estimación de la edad en zorros, Vulpes vulpes, de Doñana (sur de la Península Ibérica)Características morfológicas de los corzos (Capreolus capreolus) de las sierras de Cádiz-Málaga.Etograma y relación de la conducta con el hábitat y con la edad en el ñandú (Rhea americana)Variación estacional del área de campeo de Oxymycterus rufus (Rodentia: Cricetidae), en el delta del rio Paraná, ArgentinaTracking of a female american mink (Mustela vison, Schreber, 1777) in NE Spain.Nidificación de láridos en la provincia de Almeria (SE Ibérico)Expansión del área de distribución de Microtus arvalis asturianus Miller, 1908 (Rodentia, Arvicolidae) en la meseta norte (España)Diet of the thekla lark, Galerida theklae, in a shrubsteppe of southeastern SpainAlimentación de la lechuza campestre (Asio flammeus) en la submeseta norte (España), durante el periodo reproductorUso de cajas anidaderas por lirones grises (Glis glis) y ratones leonados (Apodemus flavicollis) en el norte de la Península Ibérica.Theoretical flight ranges of waders resting in the Ebro Delta during autumn migrationPeer reviewe

Topic, Focus and V2: defining the CP sublayers

none2noneBENINCA' PAOLA; POLETTO C.Beninca', Paola; Poletto, Cecili