C9ORF72 Gene GGGGCC Hexanucleotide Expansion: A High Clinical Variability from Amyotrophic Lateral Sclerosis to Frontotemporal Dementia.

The expanded GGGGCC hexanucleotide repeat (HRE) in the non-coding region of the C9ORF72 gene (C9ORF72-HRE) is the most common genetic cause of familial forms of amyotrophic lateral sclerosis (ALS), FTD, and concurrent ALS and FTD (ALS-FTD), in addition to contributing to the sporadic forms of these diseases. Both syndromes overlap not only genetically, but also sharing similar clinical and neuropathological findings, being considered as a spectrum. In this paper we describe the clinical-genetic findings in a Basque family with different manifestations within the spectrum, our difficulties in reaching the diagnosis, and a narrative review, carried out as a consequence, of the main features associated with C9ORF72-HRE. Family members underwent a detailed clinical assessment, neurological examination, and genetic analysis by repeat-primed PCR. We studied 10 relatives of a symptomatic carrier of the C9ORF72-HRE expansion. Two of them presented the expansion in the pathological range, one of them was symptomatic whereas the other one remained asymptomatic at 72 years. Given the great intrafamilial clinical variability of C9ORF72-HRE, the characterization of patients and family members with particular clinical and genetic subgroups within ALS and FTD becomes a bottleneck for medication development, in particular for genetically focused medicines for ALS and FTD.

Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.

Introduction: Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants. Methods: This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates. Results: The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death. Conclusion: NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.

Impact of CO2 overpressure on yeast mitochondrial associated proteome during the "prise de mousse" of sparkling wine production.

The "prise de mousse" stage during sparkling wine elaboration by the traditional method (Champenoise) involves a second fermentation in a sealed bottle followed by a prolonged aging period, known to contribute significantly to the unique organoleptic properties of these wines. During this stage, CO2 overpressure, nutrient starvation and high ethanol concentrations are stress factors that affect yeast cells viability and metabolism. Since mitochondria are responsible for energy generation and are required for cell aging and response to numerous stresses, we hypothesized that these organelles may play an essential role during the prise de mousse. The objective of this study is to characterize the mitochondrial response of a Saccharomyces cerevisiae strain traditionally used in sparkling wine production along the "prise de mousse" and study the effect of CO2 overpressure through a proteomic analysis. We observed that pressure negatively affects the content of mitochondrion-related proteome, especially to those proteins involved in tricarboxylic acid cycle. However, proteins required for the branched-amino acid synthesis, implied in wine aromas, and respiratory chain, also previously reported by transcriptomic analyses, were found over-represented in the sealed bottles. Multivariate analysis of proteins required for tricarboxylic cycle, respiratory chain and amino acid metabolism revealed differences in concentrations, allowing the wine samples to group depending on the time and CO2 overpressure parameters. Ethanol content along the second fermentation could be the main reason for this changing behavior observed at proteomic level. Further research including genetic studies, determination of ROS, characterization of mitochondrial activity and targeted metabolomics analyses is required. The list of mitochondrial proteins provided in this work will lead to a better understanding of the yeast behavior under these conditions of special interest in the wine industry.

A Differential Proteomic Approach to Characterize the Cell Wall Adaptive Response to CO2 Overpressure during Sparkling Wine-Making Process.

In this study, a first proteomic approach was carried out to characterize the adaptive response of cell wall-related proteins to endogenous CO2 overpressure, which is typical of second fermentation conditions, in two wine Saccharomyces cerevisiae strains (P29, a conventional second fermentation strain, and G1, a flor yeast strain implicated in sherry wine making). The results showed a high number of cell wall proteins in flor yeast G1 under pressure, highlighting content at the first month of aging. The cell wall proteomic response to pressure in flor yeast G1 was characterized by an increase in both the number and content of cell wall proteins involved in glucan remodeling and mannoproteins. On the other hand, cell wall proteins responsible for glucan assembly, cell adhesion, and lipid metabolism stood out in P29. Over-represented proteins under pressure were involved in cell wall integrity (Ecm33p and Pst1p), protein folding (Ssa1p and Ssa2p), and glucan remodeling (Exg2p and Scw4p). Flocculation-related proteins were not identified under pressure conditions. The use of flor yeasts for sparkling wine elaboration and improvement is proposed. Further research based on the genetic engineering of wine yeast using those genes from protein biomarkers under pressure alongside the second fermentation in bottle is required to achieve improvements.

Autophagic Proteome in Two Saccharomyces cerevisiae Strains During Second Fermentation for Sparkling Wine Elaboration.

A correlation between autophagy and autolysis has been proposed in order to acceleratethe acquisition of wine organoleptic properties during sparkling wine elaboration. In this context, aproteomic analysis was carried out in two industrial Saccharomyces cerevisiae strains (P29,conventional sparkling wine strain and G1, implicated in sherry wine elaboration) with the aim ofstudying the autophagy-related proteome and comparing the effect of CO2 overpressure duringsparkling wine elaboration. In general, a detrimental effect of pressure and second fermentationdevelopment on autophagy-related proteome was observed in both strains, although it was morepronounced in flor yeast strain G1. Proteins mainly involved in autophagy regulation andautophagosome formation in flor yeast G1, and those required for vesicle nucleation and expansionin P29 strain, highlighted in sealed bottle. Proteins Sec2 and Sec18 were detected 3-fold underpressure conditions in P29 and G1 strains, respectively. Moreover, 'fingerprinting' obtained frommultivariate data analysis established differences in autophagy-related proteome between strainsand conditions. Further research is needed to achieve more solid conclusions and design strategiesto promote autophagy for an accelerated autolysis, thus reducing cost and time production, as wellas acquisition of good organoleptic properties.

Effect of endogenous CO2 overpressure on the yeast "stressome" during the "prise de mousse" of sparkling wine.

Sparkling wines elaboration by the "Champenoise" method involves a second fermentation of a base wine in hermetically sealed bottles and a subsequent aging period. The whole process is known as "prise de mousse". The endogenous CO2 pressure produced during the second fermentation by the yeast Saccharomyces cerevisiae could modify the sub-proteome involved in the response to different stresses, or "stressome", and cell viability thus affecting the wine organoleptic properties. This study focuses on the stressome evolution along the prise de mousse under CO2 overpressure conditions in an industrial S. cerevisiae strain. The results reveal an important effect of endogenous CO2 overpressure on the stress sub-proteome, cell viability and metabolites such as glycerol, reducing sugars and ethanol. Whereas the content of glycerol biosynthesis-related proteins increased in sealed bottle, those involved in the response to toxic metabolites like ROS, ethanol, acetaldehyde and acetic acid, decreased in content. Proteomic profile obtained in this study may be used to select suitable wine yeast strains for sparkling wine elaboration and improve their stress tolerance.

First Proteomic Approach to Identify Cell Death Biomarkers in Wine Yeasts during Sparkling Wine Production.

Apoptosis and later autolysis are biological processes which take place in Saccharomyces cerevisiae during industrial fermentation processes, which involve costly and time-consuming aging periods. Therefore, the identification of potential cell death biomarkers can contribute to the creation of a long-term strategy in order to improve and accelerate the winemaking process. Here, we performed a proteomic analysis based on the detection of possible apoptosis and autolysis protein biomarkers in two industrial yeast strains commonly used in post-fermentative processes (sparkling wine secondary fermentation and biological aging) under typical sparkling wine elaboration conditions. Pressure had a negatively effect on viability for flor yeast, whereas the sparkling wine strain seems to be more adapted to these conditions. Flor yeast strain experienced an increase in content of apoptosis-related proteins, glucanases and vacuolar proteases at the first month of aging. Significant correlations between viability and apoptosis proteins were established in both yeast strains. Multivariate analysis based on the proteome of each process allowed to distinguish among samples and strains. The proteomic profile obtained in this study could provide useful information on the selection of wine strains and yeast behavior during sparkling wine elaboration. Additionally, the use of flor yeasts for sparkling wine improvement and elaboration is proposed.

An approach to precise nitrogen management using hand-held crop sensor measurements and winter wheat yield mapping in a Mediterranean environment.

Regardless of the crop production system, nutrients inputs must be controlled at or below a certain economic threshold to achieve an acceptable level of profitability. The use of management zones and variable-rate fertilizer applications is gaining popularity in precision agriculture. Many researchers have evaluated the application of final yield maps and geo-referenced geophysical measurements (e.g., apparent soil electrical conductivity-ECa) as a method of establishing relatively homogeneous management zones within the same plot. Yield estimation models based on crop conditions at certain growth stages, soil nutrient statuses, agronomic factors, moisture statuses, and weed/pest pressures are a primary goal in precision agriculture. This study attempted to achieve the following objectives: (1) to investigate the potential for predicting winter wheat yields using vegetation measurements (the Normalized Difference Vegetation Index-NDVI) at the beginning of the season, thereby allowing for a yield response to nitrogen (N) fertilizer; and (2) evaluate the feasibility of using inexpensive optical sensor measurements in a Mediterranean environment. A field experiment was conducted in two commercial wheat fields near Seville, in southwestern Spain. Yield data were collected at harvest using a yield monitoring system (RDS Ceres II-volumetric meter) installed on a combine. Wheat yield and NDVI values of 3498 ± 481 kg ha(-1) and 0.67 ± 0.04 nm nm(-1) (field 1) and 3221 ± 531 kg ha(-1) and 0.68 ± 0.05 nm nm(-1) (field 2) were obtained. In both fields, the yield and NDVI exhibited a strong Pearson correlation, with r(xy) = 0.64 and p < 10(-4) in field 1 and r(xy) = 0.78 and p < 10(-4) in field 2. The preliminary results indicate that hand-held crop sensor-based N management can be applied to wheat production in Spain and has the potential to increase agronomic N-use efficiency on a long-term basis.

Development of a telemetry and yield-mapping system of olive harvester.

Sensors, communication systems and geo-reference units are required to achieve an optimized management of agricultural inputs with respect to the economic and environmental aspects of olive groves. In this study, three commercial olive harvesters were tracked during two harvesting seasons in Spain and Chile using remote and autonomous equipment that was developed to determine their time efficiency and effective based on canopy shaking for fruit detachment. These harvesters work in intensive/high-density (HD) and super-high-density (SHD) olive orchards. A GNSS (Global Navigation Satellite System) and GSM (Global System for Mobile Communications) device was installed to track these harvesters. The GNSS receiver did not affect the driver's work schedule. Time elements methodology was adapted to the remote data acquisition system. The effective field capacity and field efficiency were investigated. In addition, the field shape, row length, angle between headland alley and row, and row alley width were measured to determinate the optimum orchard design parameters value. The SHD olive harvester showed significant lower effective field capacity values when alley width was less than 4 m. In addition, a yield monitor was developed and installed on a traditional olive harvester to obtain a yield map from the harvested area. The hedge straddle harvester stood out for its highly effective field capacity; nevertheless, a higher field efficiency was provided by a non-integral lateral canopy shaker. All of the measured orchard parameters have influenced machinery yields, whether effective field capacity or field efficiency. A saving of 40% in effective field capacity was achieved with a reduction from 4 m or higher to 3.5 m in alley width for SHD olive harvester. A yield map was plotted using data that were acquired by a yield monitor, reflecting the yield gradient in spite of the larger differences between tree yields.

Wi-Fi and satellite-based location techniques for intelligent agricultural machinery controlled by a human operator.

In the new agricultural scenarios, the interaction between autonomous tractors and a human operator is important when they jointly perform a task. Obtaining and exchanging accurate localization information between autonomous tractors and the human operator, working as a team, is a critical to maintaining safety, synchronization, and efficiency during the execution of a mission. An advanced localization system for both entities involved in the joint work, i.e., the autonomous tractors and the human operator, provides a basis for meeting the task requirements. In this paper, different localization techniques for a human operator and an autonomous tractor in a field environment were tested. First, we compared the localization performances of two global navigation satellite systems' (GNSS) receivers carried by the human operator: (1) an internal GNSS receiver built into a handheld device; and (2) an external DGNSS receiver with centimeter-level accuracy. To investigate autonomous tractor localization, a real-time kinematic (RTK)-based localization system installed on autonomous tractor developed for agricultural applications was evaluated. Finally, a hybrid localization approach, which combines distance estimates obtained using a wireless scheme with the position of an autonomous tractor obtained using an RTK-GNSS system, is proposed. The hybrid solution is intended for user localization in unstructured environments in which the GNSS signal is obstructed. The hybrid localization approach has two components: (1) a localization algorithm based on the received signal strength indication (RSSI) from the wireless environment; and (2) the acquisition of the tractor RTK coordinates when the human operator is near the tractor. In five RSSI tests, the best result achieved was an average localization error of 4 m. In tests of real-time position correction between rows, RMS error of 2.4 cm demonstrated that the passes were straight, as was desired for the autonomous tractor. From these preliminary results, future work will address the use of autonomous tractor localization in the hybrid localization approach.

Design of a soil cutting resistance sensor for application in site-specific tillage.

One objective of precision agriculture is to provide accurate information about soil and crop properties to optimize the management of agricultural inputs to meet site-specific needs. This paper describes the development of a sensor equipped with RTK-GPS technology that continuously and efficiently measures soil cutting resistance at various depths while traversing the field. Laboratory and preliminary field tests verified the accuracy of this prototype soil strength sensor. The data obtained using a hand-operated soil cone penetrometer was used to evaluate this field soil compaction depth profile sensor. To date, this sensor has only been tested in one field under one gravimetric water content condition. This field test revealed that the relationships between the soil strength profile sensor (SSPS) cutting force and soil cone index values are assumed to be quadratic for the various depths considered: 0-10, 10-20 and 20-30 cm (r2 = 0.58, 0.45 and 0.54, respectively). Soil resistance contour maps illustrated its practical value. The developed sensor provides accurate, timely and affordable information on soil properties to optimize resources and improve agricultural economy.

Development and evaluation of a combined cultivator and band sprayer with a row-centering RTK-GPS guidance system.

Typically, low-pressure sprayers are used to uniformly apply pre- and post-emergent herbicides to control weeds in crop rows. An innovative machine for weed control in inter-row and intra-row areas, with a unique combination of inter-row cultivation tooling and intra-row band spraying for six rows and an electro-hydraulic side-shift frame controlled by a GPS system, was developed and evaluated. Two weed management strategies were tested in the field trials: broadcast spraying (the conventional method) and band spraying with mechanical weed control using RTK-GPS (the experimental method). This approach enabled the comparison between treatments from the perspective of cost savings and efficacy in weed control for a sugar beet crop. During the 2010-2011 season, the herbicide application rate (112 L ha(-1)) of the experimental method was approximately 50% of the conventional method, and thus a significant reduction in the operating costs of weed management was achieved. A comparison of the 0.2-trimmed means of weed population post-treatment showed that the treatments achieved similar weed control rates at each weed survey date. Sugar beet yields were similar with both methods (p = 0.92). The use of the experimental equipment is cost-effective on ≥20 ha of crops. These initial results show good potential for reducing herbicide application in the Spanish beet industry.

Design of a new sensor for determination of the effects of tractor field usage in southern Spain: soil sinkage and alterations in the cone index and dry bulk density.

Variations in sinkage and cone index are of crucial importance when planning fieldwork, and for determining the trafficability of farm machinery. Many studies have highlighted the link between higher values of these parameters and dramatic decreases in crop yield. Variations in the dry bulk density and cone index of clayey soil in Southern Spain were measured following each of five successive passes over the same land with the three types of tractor most widely used in the area (tracked, two-wheel drive and four-wheel drive). In addition, sinkage (rut depth) of the running gear was measured using a laser microrelief profile meter. This device, which integrates three sensors, was specifically designed for these experiments, as was an electrical penetrometer to determine the cone index, and both instruments proved reliable and accurate in the field. The main goal of this study was to design, manufacture and test these new devices. The first pass caused most soil alteration when compared to successive passes for all types of tractor tested and soil conditions prevailing during the tests. (Heavier) four-wheel drive tractors were found to cause greater soil damage (sinkage, cone index and dry bulk density) than two-wheel drive and track tractors. There was no statistically significant difference between the two latter types. The greatest alterations were recorded in the top 10 cm of the soil. The results show that soil compaction should be avoided as much as possible. This can be achieved by ensuring that tractors always travel along the same tracks, especially in the wet season. At present these aspects are not considered by farmers in this area.