Extracellular cysteine in connexins: Role as redox sensors

Indexación: Scopus.Connexin-based channels comprise hemichannels and gap junction channels. The opening of hemichannels allow for the flux of ions and molecules from the extracellular space into the cell and vice versa. Similarly, the opening of gap junction channels permits the diffusional exchange of ions and molecules between the cytoplasm and contacting cells. The controlled opening of hemichannels has been associated with several physiological cellular processes; thereby unregulated hemichannel activity may induce loss of cellular homeostasis and cell death. Hemichannel activity can be regulated through several mechanisms, such as phosphorylation, divalent cations and changes in membrane potential. Additionally, it was recently postulated that redox molecules could modify hemichannels properties in vitro. However, the molecular mechanism by which redox molecules interact with hemichannels is poorly understood. In this work, we discuss the current knowledge on connexin redox regulation and we propose the hypothesis that extracellular cysteines could be important for sensing changes in redox potential. Future studies on this topic will offer new insight into hemichannel function, thereby expanding the understanding of the contribution of hemichannels to disease progression.http://journal.frontiersin.org/article/10.3389/fphys.2016.00001/ful

La libertà d’impresa degli operatori stranieri nell’ordinamento societario cinese

Nel 2020 è entrata in vigore in Cina la cosiddetta Foreign Investment Law (FIL), ossia la nuova disciplina degli investimenti esteri, la quale modifica radicalmente il rapporto tra la Cina e le imprese occidentali operanti nel suo territorio. Tale riforma consegue a un evidente mutamento nelle esigenze dell’economia cinese, essendo da qualche tempo venute meno le ragioni che avevano indotto a dettare una disciplina differenziata delle società di capitali straniere rispetto a quella applicabile alle società cinesi. Le tipologie societarie a disposizione degli investitori esteri sono dunque oggi quelle stesse utilizzabili dall’imprenditoria cinese, ovverosia quelle tipizzate dalla Partnership Law introdotta nel 1997 e dalla Company Law entrata in vigore nel 1993. Il presente studio è volto a indagare da un lato quanto siano effettivamente funzionali i modelli tipizzati nella Company Law e dall’altro se la novella legislativa del 2020 abbia o meno comportato per gli operatori occidentali un incremento della libertà d’impresa. Da ultimo vengono proposte alcune considerazioni relativamente alla libertà di accesso che la Repubblica Popolare Cinese concede oggi all’imprenditoria straniera.In 2020, the so-called Foreign Investment Law (FIL), which radically changes relationship between China and Western companies operating in its territory, entered into force. The reform follows clear change in Chinese economy, which no longer needs a law concerning foreign companies different from that concerning Chinese companies: now corporate models that can be used by foreign investors are therefore the same ones that Chinese entrepreneurs can use that is, those governed by the 1997 Partnership Law and by the 1993 Company Law. This study is also aimed at investigating on the one hand how functional the models governed by the Company Law are and on the other whether the FIL has led to an increase in freedom of enterprise for Western operators. At the end, I propose some considerations regarding the freedom of access that People’s Republic of China now grants to foreign entrepreneurs

Obtaining and Structural Characterization of M-type Hexaferrites Doped with Two Cations in the Fe3+ Sites

A study of the microstructural and structural properties of M-type barium hexaferrites (BaM) samples doped with two dopants in the Fe3+ sites: (Co3+, Al3+), (Co2+, Ti4+) and (Co2+, Sn4+) is reported. The samples were obtained using the conventional ceramic method. The structure was investigated by using of X-ray diffraction (XRD) to determine the dopant distribution in the Fe3+ sites

Effects of successive judo matches on interlimb asymmetry and bilateral deficit

Objective: To verify the effects of successive judo matches on interlimb asymmetry and bilateral deficit in judo athletes. Design: Repeated measures Setting: University Judo center Participants: Fourteen male judo athletes Outcome measures: Four simulated matches consisting of 4-min. Before the first match and after each match athletes were submitted to single leg tests – Countermovement Jump (SLCMJ) and Standing Long Jump (SLSLJ), and handgrip strength (HGS) in the dominant and non-dominant limbs. Interlimb asymmetry was calculated in both jumps and handgrip strength tests. Results: Most jump-derived variables did not change the magnitude of asymmetry throughout the matches (p>0.05), with the exception of jump height asymmetry in SLCMJ, that increased after the second match (p=0.001). The HGS decreased in both hands from the first match (p<0.001), without asymmetry. The highest bilateral strength deficit was observed in post-match 1 and post-match 2 (close to 10%). Conclusion: Four-successive judo matches did not change the magnitude of interlimb asymmetry, with exception of SLCMJ height, which increased after the second match. The handgrip strength decreased throughout the matches, but similarly in both hands. Finally, the direction of asymmetry showed consistency throughout the matches only for SLCMJ height

From MFN to SFN: Performance Prediction Through Machine Learning

In the last decade, the transition of digital terrestrial television (DTT) systems from multi-frequency networks (MFNs) to single-frequency networks (SFNs) has become a reality. SFN offers multiple advantages concerning MFN, such as more efficient management of the radioelectric spectrum, homogenizing the network parameters, and a potential SFN gain. However, the transition process can be cumbersome for operators due to the multiple measurement campaigns and required finetuning of the final SFN system to ensure the desired quality of service. To avoid time-consuming field measurements and reduce the costs associated with the SFN implementation, this paper aims to predict the performance of an SFN system from the legacy MFN and position data through machine learning (ML) algorithms. It is proposed a ML concatenated structure based on classification and regression to predict SFN electric-field strength, modulation error ratio, and gain. The model's training and test process are performed with a dataset from an SFN/MFN trial in Ghent, Belgium. Multiple algorithms have been tuned and compared to extract the data patterns and select the most accurate algorithms. The best performance to predict the SFN electric-field strength is obtained with a coefficient of determination (R2) of 0.93, modulation error ratio of 0.98, and SFN gain of 0.89 starting from MFN parameters and position data. The proposed method allows classifying the data points according to positive or negative SFN gain with an accuracy of 0.97

Study of a Brazilian family presenting non-syndromic hearing loss with mitochondrial inheritance

O presente estudo teve como objetivo descrever os achados audiológicos e genéticos de nove membros de uma família brasileira que apresenta a mutação no DNA mitocondrial. Todos os nove membros realizaram estudo genético, avaliação foniátrica e audiológica (audiometria tonal e logoaudiometria). O estudo genético revelou a presença de mutação mitocondrial A1555G no gene 12S rRNA (MT-RNR-1) do DNA mitocondrial em todos os sujeitos. Oito sujeitos apresentaram deficiência auditiva e somente um apresentou limiares auditivos normais até o término da realização do estudo. Os resultados audiológicos apontaram para perdas auditivas bilaterais, com prevalência das simétricas, de configurações e graus variados (de moderado a profundo) e pós-linguais. Progressão da perda auditiva foi observada em dois irmãos afetados. Não foi possível afirmar a época do início da perda auditiva por falta de informação dos sujeitos, no entanto, observou-se manifestação da perda em crianças e adultos. As mutações no DNA mitocondrial representam uma causa importante de perda auditiva, sendo imprescindível a realização do diagnóstico etiopatológico, a fim de retardar o início ou evitar a progressão da surdez.We hereby report on the audiological and genetic findings in individuals from a Brazilian family, with the following mitochondrial mutation A1555G in the 12SrRNA gene (MT-RNR-1). Nine individuals underwent speech, audiologic (tonal audiometry and logoaudiometry) and genetic evaluations. Eight individuals among the A1555G carriers were affected by hearing impairment and one person had normal hearing thresholds till the end of the present study. The audiologic evaluation results indicated normal hearing thresholds all the way to bilateral profound hearing loss with post-lingual onset and variable configuration. Two affected siblings presented progressive hearing loss. It was impossible to precise the time of hearing loss onset; however, the impairment was present in both children and adults. The genetic study revealed the A1555G mitochondrial mutation in the 12SrRNA gene. Given the prevalence of mitochondrial mutations as a cause of hearing loss, it is fundamental to perform the etiopathologic diagnosis in order to postpone the onset or avoid hearing impairment progression. This kind of hearing impairment represents a challenge to the professionals since there are no physical traits that indicate genetic transmission

Head movement and its relation to hearing

Head position at any point in time plays a fundamental role in shaping the auditory information that reaches a listener, information that continuously changes as the head moves and reorients to different listening situations. The connection between hearing science and the kinesthetics of head movement has gained interest due to technological advances that have increased the feasibility of providing behavioral and biological feedback to assistive listening devices that can interpret movement patterns that reflect listening intent. Increasing evidence also shows that the negative impact of hearing deficits on mobility, gait, and balance may be mitigated by prosthetic hearing device intervention. Better understanding of the relationships between head movement, full body kinetics, and hearing health, should lead to improved signal processing strategies across a range of assistive and augmented hearing devices. The purpose of this review is to introduce the wider hearing community to the kinesiology of head movement and to place it in the context of hearing and communication with the goal of expanding the field of ecologically-specific listener behavior

Molecular mechanics of coiled coils loaded in the shear geometry

Coiled coils are important nanomechanical building blocks in biological and biomimetic materials. A mechanistic molecular understanding of their structural response to mechanical load is essential for elucidating their role in tissues and for utilizing and tuning these building blocks in materials applications. Using a combination of single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations, we have investigated the mechanics of synthetic heterodimeric coiled coils of different length (3-4 heptads) when loaded in shear geometry. Upon shearing, we observe an initial rise in the force, which is followed by a constant force plateau and ultimately strand separation. The force required for strand separation depends on the coiled coil length and the applied loading rate, suggesting that coiled coil shearing occurs out of equilibrium. This out-of-equilibrium behaviour is determined by a complex structural response which involves helix uncoiling, uncoiling-assisted sliding of the helices relative to each other in the direction of the applied force as well as uncoiling-assisted dissociation perpendicular to the force axis. These processes follow a hierarchy of timescales with helix uncoiling being faster than sliding and sliding being faster than dissociation. In SMFS experiments, strand separation is dominated by uncoiling-assisted dissociation and occurs at forces between 25-45 pN for the shortest 3-heptad coiled coil and between 35-50 pN for the longest 4-heptad coiled coil. These values are highly similar to the forces required for shearing apart short double-stranded DNA oligonucleotides, reinforcing the potential role of coiled coils as nanomechanical building blocks in applications where protein-based structures are desired

Leg Ulcer. Conservative Treatment

Durante um período de 16 anos foram estudados, de forma prospectiva, 202 doentes portadores de insuficiência venosa crónica complicada de úlcera de perna, totalizando 257 úlceras. Este conjunto constitui uma série homogénea, em que foi sempre mantida a mesma orientação diagnóstica e terapêutica, quer médica, quer cirúrgica. Foi definido como objectivo a cura da úlcera em ambulatório, com tratamento conservador. O tratamento cirúrgico definitivo, quando indicado, é preferencialmente executado em diferido, após a cura da úlcera. Dos 202 doentes incluídos inicialmente no estudo, 166 mantiveram-se até à cura ou durante um período de tratamento prolongado. Nos doentes que se mantiveram no estudo foi obtida uma taxa de curas de 91%, o que está acima dos resultados habitualmente reportados na literatura internacional. Salienta-se a importância do controlo directo de todo o tratamento pelo médico responsável

Shortening the lipid A acyl chains of Bordetella pertussis enables depletion of lipopolysaccharide endotoxic activity

Whooping cough, or pertussis, is an acute respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis. Whole-cell vaccines, which were introduced in the fifties of the previous century and proved to be effective, showed considerable reactogenicity and were replaced by subunit vaccines around the turn of the century. However, there is a considerable increase in the number of cases in industrialized countries. A possible strategy to improve vaccine-induced protection is the development of new, non-toxic, whole-cell pertussis vaccines. The reactogenicity of whole-cell pertussis vaccines is, to a large extent, derived from the lipid A moiety of the lipopolysaccharides (LPS) of the bacteria. Here, we engineered B. pertussis strains with altered lipid A structures by expressing genes for the acyltransferases LpxA, LpxD, and LpxL from other bacteria resulting in altered acyl-chain length at various positions. Whole cells and extracted LPS from the strains with shorter acyl chains showed reduced or no activation of the human Toll-like receptor 4 in HEK-Blue reporter cells, whilst a longer acyl chain increased activation. Pyrogenicity studies in rabbits confirmed the in vitro assays. These findings pave the way for the development of a new generation of whole-cell pertussis vaccines with acceptable side effects