Emerging biosensing technologies for neuroinflammatory and neurodegenerative disease diagnostics

Neuroinflammation plays a critical role in the onset and progression of many neurological disorders, including Multiple Sclerosis, Alzheimer’s and Parkinson’s diseases. In these clinical conditions the underlying neuroinflammatory processes are significantly heterogeneous. Nevertheless, a common link is the chronic activation of innate immune responses and imbalanced secretion of pro and anti-inflammatory mediators. In light of this, the discovery of robust biomarkers is crucial for screening, early diagnosis, and monitoring of neurological diseases. However, the difficulty to investigate biochemical processes directly in the central nervous system (CNS) is challenging. In recent years, biomarkers of CNS inflammatory responses have been identified in different body fluids, such as blood, cerebrospinal fluid, and tears. In addition, progress in micro and nanotechnology has enabled the development of biosensing platforms capable of detecting in real-time, multiple biomarkers in clinically relevant samples. Biosensing technologies are approaching maturity where they will become deployed in community settings, at which point screening programs and personalized medicine will become a reality. In this multidisciplinary review, our goal is to highlight both clinical and recent technological advances toward the development of multiplex-based solutions for effective neuroinflammatory and neurodegenerative disease diagnostics and monitoring.IM and AC acknowledge the financial support from the Marie Curie COFUND Programme Nano TRAIN for Growth from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 600375. This article is a result of the project Nanotechnology based functional solutions (FEDERNORTE-01-0145-FEDER-000019), co-financed by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). PM acknowledges the Ph.D. fellowship from Fundação para a Ci?ncia e Tecnologia, Portugal (PD/BD/105751/2014)

Tratamiento de la ingestión de cuerpos extranos ˜ en una unidad de urgencias de otorrinolaringología: estudio prospectivo de 204 casos

AIMS: To determine how often ingested foreign bodies are found and what parameters may predict their retrieval. METHODS: During 1 year, we prospectively studied all patients referred to our Ear Nose and Throat Emergency Unit because of foreign body ingestion. RESULTS: During the study, 204 (median age-42 years [10 months-84 years]) patients were admitted because of ingested foreign body. The most common was fish bone (88%). Most patients were admitted <24-hour after ingestion (72%) and complained of symptoms above the cricoid cartilage (79%). A foreign body was removed by Ear Nose and Throat team in 108 (53%) patients. Twenty-three (11%) patients were referred to Gastroenterology. In 9 (39%) of these patients, a foreign body was identified by esophagogastroscopy, always from the esophagus. Predictive variables for retrieval of foreign body by Ear Nose and Throat team were ingested fish bone (P=.000; odds ratio [OR]=17.3), short duration (<6hours) of symptoms (P=.001; OR=2.3) and symptoms above or at the level of cricoid cartilage (P=.000; OR=8.9). In patients with symptoms below the cricoid cartilage the rate of retrieval of foreign body by Ear Nose and Throat team (11%) was significantly increased by Gastroenterology (41%; P=.03). CONCLUSIONS: Patients with ingestion of foreign body who ingest fish bone, present within the first 6hours or complain of symptoms at or above cricoid cartilage deserve greater investment in terms of time and resources for retrieval of ingested foreign body by Ear Nose and Throat team

Electronic Spin Transport in Dual-Gated Bilayer Graphene

The elimination of extrinsic sources of spin relaxation is key in realizing the exceptional intrinsic spin transport performance of graphene. Towards this, we study charge and spin transport in bilayer graphene-based spin valve devices fabricated in a new device architecture which allows us to make a comparative study by separately investigating the roles of substrate and polymer residues on spin relaxation. First, the comparison between spin valves fabricated on SiO2 and BN substrates suggests that substrate-related charged impurities, phonons and roughness do not limit the spin transport in current devices. Next, the observation of a 5-fold enhancement in spin relaxation time in the encapsulated device highlights the significance of polymer residues on spin relaxation. We observe a spin relaxation length of ~ 10 um in the encapsulated bilayer with a charge mobility of 24000 cm2/Vs. The carrier density dependence of spin relaxation time has two distinct regimes; n<4 x 1012 cm-2, where spin relaxation time decreases monotonically as carrier concentration increases, and n>4 x 1012 cm-2, where spin relaxation time exhibits a sudden increase. The sudden increase in the spin relaxation time with no corresponding signature in the charge transport suggests the presence of a magnetic resonance close to the charge neutrality point. We also demonstrate, for the first time, spin transport across bipolar p-n junctions in our dual-gated device architecture that fully integrates a sequence of encapsulated regions in its design. At low temperatures, strong suppression of the spin signal was observed while a transport gap was induced, which is interpreted as a novel manifestation of impedance mismatch within the spin channel

The CAG repeat at the Huntington disease gene in the Portuguese population : insights into its dynamics and to the origin of the mutation

Huntington disease (HD) is caused by an expansion of a CAG repeat. This repeat is a dynamic mutation that tends to undergo intergenerational instability. We report the analysis of the CAG repeat in a large population sample (2,000 chromosomes) covering all regions of Portugal, and a haplotype study of (CAG)n and (CCG)n repeats in 140 HD Portuguese families. Intermediate class 2 alleles represented 3.0% of the population; and two expanded alleles (36 and 40 repeats, 0.11%) were found. There was no evidence for geographical clustering of the intermediate or expanded alleles. The Portuguese families showed three different HD founder haplotypes associated with 7-, 9- or 10-CCG repeats, suggesting the possibility of different origins for theHDmutation among this population. The haplotype carrying the 7-CCG repeat was the most frequent, both in normal and in expanded alleles. In general, we propose that three mechanisms, occurring at different times,may lead to the evolution from normal CAGs to full expansion: first, a mutation bias towards larger alleles; then, a stepwise process that could explain the CAGdistributions observed in themore recent haplotypes; and, finally, a pool of intermediate (class 2) alleles more prone to give rise to expanded HD alleles.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/9759/ 2003.Instituto de Genética Médica Jacinto Magalhães

Yeast diversity in relation to the production of fuels and chemicals

In addition to ethanol, yeasts have the potential to produce many other industrially-relevant chemicals from numerous different carbon sources. However there remains a paucity of information about overall capability across the yeast family tree. Here, 11 diverse species of yeasts with genetic backgrounds representative of different branches of the family tree were investigated. They were compared for their abilities to grow on a range of sugar carbon sources, to produce potential platform chemicals from such substrates and to ferment hydrothermally pretreated rice straw under simultaneous saccharification and fermentation conditions. The yeasts differed considerably in their metabolic capabilities and production of ethanol. A number could produce significant amounts of ethyl acetate, arabinitol, glycerol and acetate in addition to ethanol, including from hitherto unreported carbon sources. They also demonstrated widely differing efficiencies in the fermentation of sugars derived from pre-treated rice straw biomass and differential sensitivities to fermentation inhibitors. A new catabolic property of Rhodotorula mucilaginosa (NCYC 65) was discovered in which sugar substrate is cleaved but the products are not metabolised. We propose that engineering this and some of the other properties discovered in this study and transferring such properties to conventional industrial yeast strains could greatly expand their biotechnological utility

Degradation of metalaxyl and folpet by filamentous fungi isolated from Portuguese (Alentejo) vineyard soils

Degradation of xenobiotics by microbial populations is a potential method to enhance the effectiveness of ex situ or in situ bioremediation. The purpose of this study was to evaluate the impact of repeated metalaxyl and folpet treatments on soil microbial communities and to select soil fungal strains able to degrade these fungicides. Results showed enhanced degradation of metalaxyl and folpet in vineyards soils submitted to repeated treatments with these fungicides. Indeed, the greatest degradation ability was observed in vineyard soil samples submitted to greater numbers of treatments. Respiration activities, as determined in the presence of selective antibiotics in soil suspensions amended with metalaxyl and folpet, showed that the fungal population was the microbiota community most active in the degradation process. Batch cultures performed with a progressive increase of fungicide concentrations allowed the selection of five tolerant fungal strains: Penicillium sp. 1 and Penicillium sp. 2, mycelia sterila 1 and 3, and Rhizopus stolonifer. Among these strains, mycelium sterila 3 and R. stolonifer presented only in vineyard soils treated with repeated application of these fungicides and showed tolerance >1,000 mg l−1 against commercial formulations of metalaxyl (10 %) plus folpet (40 %). Using specific methods for inducing sporulation, mycelium sterila 3 was identified as Gongronella sp. Because this fungus is rare, it was compared using csM13-polymerase chain reaction (PCR) with the two known species, Gongronella butleri and G. lacrispora. The high tolerance to metalaxyl and folpet shown by Gongronella sp. and R. stolonifer might be correlated with their degradation ability. Our results point out that selected strains have potential for the bioremediation of metalaxyl and folpet in polluted soil sites