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Summary: Narcolepsy type 1 is a chronic central disorder of hypersomnolence, and it is frequently accompanied by overweight, but the association between narcolepsy type 1 and eating disorders is controversial. Our study aims to compare patients with narcolepsy type 1 and controls on the symptomatology of eating disorders and to evaluate the association between clinical factors. This is a cross‐sectional study, with consecutive recruitment of patients with narcolepsy type 1 attending the Outpatient Clinic for Narcolepsy at the IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy) for routine follow‐up visits. Healthy subjects from general populations were recruited as controls. Patients underwent a questionnaire‐based assessment using the Eating Disorder Examination Questionnaire (EDE‐Q), Binge Eating Scale (BES), Italian Night Eating Questionnaire (I‐NEQ), Epworth Sleepiness Scale (ESS), and Narcolepsy Severity Scale (NSS). One hundred and thirty‐eight patients with narcolepsy type 1 and 162 controls were enrolled. This study showed that individuals with narcolepsy type 1 reported higher scores on the EDE‐Q, I‐NEQ, and a higher body mass index (BMI) than the controls. The logistic regression analysis results, with EDE‐Q positivity as a dependent variable, demonstrate a significant association with antidepressant drugs, female sex, and the use of sodium oxybate. We found an association between antidepressant drug consumption, the NSS total score, and female sex with BES positivity as the dependent variable. The logistic regression analysis for I‐NEQ positivity found an association with antidepressant drug use. This study shows that patients with narcolepsy type 1 frequently present with comorbid eating disorder symptomatology, mainly night eating syndrome. Investigating the possible presence of eating disorders symptomatology through questionnaires is fundamental during the assessment of patients with narcolepsy type 1. [ABSTRACT FROM AUTHOR]

The question of how local adaptation takes place remains a fundamental question in evolutionary biology. The variation of allele frequencies in genes under selection over environmental gradients remains mainly theoretical and its empirical assessment would help understanding how adaptation happens over environmental clines. To bring new insights to this issue we set up a broad framework which aimed to compare the adaptive trajectories over environmental clines in two domesticated mammal species co‐distributed in diversified landscapes. We sequenced the genomes of 160 sheep and 161 goats extensively managed along environmental gradients, including temperature, rainfall, seasonality and altitude, to identify genes and biological processes shaping local adaptation. Allele frequencies at putatively adaptive loci were rarely found to vary gradually along environmental gradients, but rather displayed a discontinuous shift at the extremities of environmental clines. Of the 430 candidate adaptive genes identified, only 6 were orthologous between sheep and goats and those responded differently to environmental pressures, suggesting different putative mechanisms involved in local adaptation in these two closely related species. Interestingly, the genomes of the 2 species were impacted differently by the environment, genes related to signatures of selection were most related to altitude, slope and rainfall seasonality for sheep, and summer temperature and spring rainfall for goats. The diversity of candidate adaptive pathways may result from a high number of biological functions involved in the adaptations to multiple eco‐climatic gradients, and a differential role of climatic drivers on the two species, despite their co‐distribution along the same environmental gradients. This study describes empirical examples of clinal variation in putatively adaptive alleles with different patterns in allele frequency distributions over continuous environmental gradients, thus showing the diversity of genetic responses in adaptive landscapes and opening new horizons for understanding genomics of adaptation in mammalian species and beyond. [ABSTRACT FROM AUTHOR]

Summary: Narcolepsy type 1 (NT1) is a central disorder of hypersomnolence often arising in childhood and adolescence. NT1 has a significant, but poorly defined, psychological impact. We aimed to investigate the psycho‐social functioning of children and adolescents with NT1. We performed a cross‐sectional, child and parent‐reported questionnaire survey in 37 children and adolescents (6–17 years) with NT1, compared with age‐ and sex‐matched controls. Questionnaires (SSHS, ESS‐CHAD, CDI, MASC, CBCL, CRS‐R, and SNAP‐IV) evaluated various aspects of behavioural and emotional profiles, sleep habits, and daytime sleepiness. Subsequently, NT1 intra‐group analysis was performed to investigate the effect of sex (males vs females) and pharmacological treatment (treated vs non‐treated) on psychological features. The NT1 questionnaires total scores were then correlated with the clinical characteristics (age, body mass index [BMI], ESS‐CHAD score, cerebrospinal hypocretin‐1 [Hcrt‐1] levels, and diagnostic delay). Patients with NT1 showed a higher tendency to depressive symptoms, anxiety, somatisation, inattention, hyperactivity, oppositional/defiant problems, and other maladaptive behaviours compared with controls. Among NT1 patients, females showed a higher propensity to anxiety, and non‐treated patients displayed higher depressive symptoms. Psychological symptoms increased with age, BMI, and daytime sleepiness in patients with NT1, while a younger age was associated with more frequent somatisation symptoms. Lower cerebrospinal Hcrt‐1 levels correlated with poorer social competencies, daily activities, and inattention. Diagnostic delay was associated with a higher impact of depressive symptoms and behavioural problems. NT1 in children and adolescents is associated with poorer functioning in multiple psychological domains calling for a multidisciplinary approach and monitoring to reduce disease burden and to prevent psychiatric consequences. [ABSTRACT FROM AUTHOR]

Summary Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep‐related disease symptoms of the disease (excessive daytime sleepiness with early occurrence of rapid eye movement sleep, sleep‐related hallucinations, sleep paralysis, rapid eye movement parasomnia), as possible dysregulation of rapid eye movement sleep, and cataplexy resembling an intrusion of rapid eye movement atonia during wake. The relevance of non‐sleep‐related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular morbidities, has subsequently been recognized. The diagnostic tools have been improved, but sleep‐onset rapid eye movement periods on polysomnography and Multiple Sleep Latency Test remain key criteria. The pathogenic mechanisms of narcolepsy type 1 have been partly elucidated after the discovery of strong HLA class II association and orexin/hypocretin deficiency, a neurotransmitter that is involved in altered rapid eye movement sleep regulation. Conversely, the causes of narcolepsy type 2, where cataplexy and orexin deficiency are absent, remain unknown. Symptomatic medications to treat patients with narcolepsy have been developed, and management has been codified with guidelines, until the recent promising orexin‐receptor agonists. The present review retraces the steps of the research on narcolepsy that linked the features of the disease with rapid eye movement sleep abnormality, and those that do not appear associated with rapid eye movement sleep. [ABSTRACT FROM AUTHOR]

Background and purpose: This study compared the features of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and antidepressant‐related REM sleep behaviour disorder (RBD) with the aim of highlighting markers that might distinguish the two entities. Methods: The observational cohort study included RBD patients with and without antidepressant use (antiD+ and antiD− patients, respectively), without cognitive impairment and parkinsonism. Clinical features of RBD, subtle motor and non‐motor symptoms of parkinsonism, sleep architecture, REM atonia index, dopamine transporter‐single photon emission computed tomography (DAT‐SPECT) and skin biopsies for the intraneuronal alpha‐synuclein (α‐syn), were evaluated in the baseline work‐up. Results: Thirty‐nine patients, 10 antiD+ and 29 antiD−, were included. AntiD+ patients (more frequently female) reported more psychiatric symptoms, less violent dream enactment, and less frequent hyposmia. Dermal α‐syn was detected in 93.1% of antiD− versus 30% of antiD+ patients (p = 0.00024). No differences appeared in other motor and non‐motor symptoms, Movement Disorder Society–Unified Parkinson's Disease Rating Scale part III score, DAT‐SPECT, or polysomnographic features. Conclusions: Patients with antidepressant‐related RBD have clinical and neuropathological features suggesting a lower risk of evolution than those with iRBD. [ABSTRACT FROM AUTHOR]

Ambipolar electrolyte‐gated transistors (EGTs) based on reduced graphene oxide (rGO) have been demonstrated as ultra‐sensitive and highly specific immunosensors. However, the physics and chemistry ruling the device operation are still not fully unraveled. In this work, the aim is to elucidate the nature of the observed sensitivity of the device. Toward this aim, a physical–chemical model that, coupled with the experimental characterization of the rGO‐EGT, allows one to quantitatively correlate the biorecognition events at the gate electrode and the electronic properties of rGO‐EGT is proposed. The equilibrium of biorecognition occurring at the gate electrode is shown to determine the apparent charge neutrality point (CNP) of the rGO channel. The multiparametric analysis of the experimental transfer characteristics of rGO‐EGT reveals that the recognition events modulate the CNP voltage, the excess carrier density Δn, and the quantum capacitance of rGO. This analysis also explains why hole and electron carrier mobilities, interfacial capacitance, the curvature of the transfer curve, and the transconductances are insensitive to the target concentration. The understanding of the mechanisms underlying the transistor transduction of the biorecognition events is key for the interpretation of the response of the rGO‐EGT immunosensors and to guide the design of novel and more sensitive devices. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to assess work productivity and activity impairments and to explore their association with excessive daytime sleepiness, body mass index (BMI), depression, and anxiety in patients with narcolepsy type 1. We carried out a cross‐sectional study in which patients with narcolepsy type 1 and matched controls for sex, age, and education were assessed for occupational features, EDS (Epworth Sleepiness Scale), BMI, depression (Beck Depression Inventory), anxiety (State–Trait Anxiety Inventory), and Work Productivity and Activity Impairment (WPAI). Different statistical approaches were used to investigate differences between groups and correlations between WPAI scores and clinical features. The 127 patients with narcolepsy type 1 (mean age 38.2 ± 15.5, 91.3% taking drugs for narcolepsy) and 131 controls (mean age of 37.4 ± 14.3) included did not differ in terms of occupational features, except for hours worked/week (29.9 in patients vs. 34.9 in controls) and officially recognised disability (30.7% vs. 5.3%). Impairment in all WPAI scores was approximately three times greater in patients. Narcolepsy was associated with work time missed in 27.4% of patients, while 93.2% to 95.5% of them had some impairment while working or during daily activities (vs. 37.5–46.8% of controls). Correlations with WPAI scores were found for excessive daytime sleepiness only in patients, and for both depression and anxiety in patients and controls, with a stronger correlation for activity impairment in patients. These results suggest that, despite treatment, narcolepsy type 1 was associated with extensive impairment especially regarding job effectiveness and daily activities. Future studies should investigate risk factors and effects of interventions on these outcomes. [ABSTRACT FROM AUTHOR]

The next generation of brain–machine interfaces are envisioned to couple signal transduction, filtering, and sorting on board with minimum power consumption and maximum bio‐integrability. These functional needs shall be mandatorily met in order to design efficient closed‐loop brain–machine interfaces aimed at treating and monitoring various disorders of the central and peripheral nervous system. Here, the pivotal role is highlighted that organic bioelectronics may have in the contextual development of all these three desiderata, by demonstrating a modular organic‐electronics circuit toward real‐time signal filtering. The inherent filtering capabilities of electrolyte‐gated organic transistor are tuned via adjustment of operational conditions and benchmarked in an electromyography experiment. Additionally, a whole‐organic signal processing circuitry is presented, coupling such transistors with ad hoc designed organic passive components. This provides the possibility to sort complex signals into their constitutive frequency components in real time, thereby delineating innovative strategies to devise organic‐based functional building‐blocks for brain–machine interfaces. [ABSTRACT FROM AUTHOR]

A growth mode of pentacene thin films deposited by high vacuum sublimation where the morphology versus thickness h "rings" back and forth between rough 3D films with pyramid islands and smooth 2D films with ziqqurat islands is discovered. The roughness σ versus h exhibits seamless coherent oscillations whose amplitude and wavelength increase as integer multiples of 1.5 ML thickness. The quantized oscillations are reconducted to dynamic wetting/dewetting transitions involving the upper layers of pentacene film. Importantly, the transconductance of organic field effect transistors, either in solid state or electrolyte‐gated, exhibits antiphase oscillations with one‐decade swing. Charge mobilities in the wetting regime reach 0.1 cm2 V−1 s−1, in line with high‐end values reported for thin‐film pentacene transistors. Controlling this growth mode enables the limitations of charge transport imposed by the roughening transition to be overcome, a universal feature of high vacuum growth to date. [ABSTRACT FROM AUTHOR]

Semiconducting single walled carbon nanotubes (SWCNTs) are promising materials for biosensing applications with electrolyte‐gated transistors (EGT). However, to be employed in EGT devices, SWCNTs often require lengthy solution‐processing fabrication techniques. Here, we introduce a simple solution‐based method that allows fabricating EGT devices from stable dispersions of SWCNTs/bovine serum albumin (BSA) hybrids in water. The dispersion is then deposited on a substrate allowing the formation of a SWCNTs random network as the semiconducting channel. We demonstrate that this methodology allows the fabrication of EGT devices with electric performances that allow their use in biosensing applications. We demonstrate their application for the detection of cortisol in solution, upon gate electrode functionalization with anti‐cortisol antibodies. This is a robust and cost‐effective methodology that sets the ground for a SWCNT/BSA‐based biosensing platform that allows overcoming many limitations of standard SWCNTs biosensor fabrications. [ABSTRACT FROM AUTHOR]

Multi‐electrode arrays with 3D micropillars allow the recording of electrophysiological signals in vitro with higher precision and signal‐to‐noise ratio than planar arrays. This is the result of the tight interaction between the 3D electrode and the cell membrane. Most 3D electrodes are manufactured on rigid substrates and their integration on flexible substrates is largely unexplored. Here, a straightforward approach is presented for fabricating soft interfaces featuring 3D poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) micropillars on a soft flexible substrate made of polydimethylsiloxane (PDMS). Large‐area isotropic arrays of PEDOT:PSS micropillars with tailored geometric area, surface properties, and electrochemical characteristics are fabricated via a combination of soft‐lithography and electrodeposition. A 60% increase in capacitance is achieved for high density micropillars compared to planar electrodes and this is found to be correlated with the increased electroactive surface area. Furthermore, 3D PEDOT:PSS micropillars support adhesion, growth and differentiation of SH‐SY5Y cells, and influence the direction of neurite outgrowth. Finally, by virtue of their elasticity, soft micropillars act as excellent anchoring loci for elongating neurites, facilitating their bending and twisting around the micropillar, increasing the number of contact points between the cells and the electrode, a key requirement to obtain high performance neural interfaces. [ABSTRACT FROM AUTHOR]

Cerebellar‐dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids—mainly referred to as estrogens—may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo‐vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular‐motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular‐motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites. [ABSTRACT FROM AUTHOR]

The transition from dividing progenitors to postmitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. Here, we identify a post‐transcriptional role of a MN‐specific transcriptional unit (MN2) harboring a lncRNA (lncMN2‐203) and two miRNAs (miR‐325‐3p and miR‐384‐5p) in this transition. Through the use of in vitro mESC differentiation and single‐cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2‐203 affects MN differentiation by sponging miR‐466i‐5p and upregulating its targets, including several factors involved in neuronal differentiation and function. In parallel, miR‐325‐3p and miR‐384‐5p, co‐transcribed with lncMN2‐203, act by repressing proliferation‐related factors. These findings indicate the functional relevance of the MN2 locus and exemplify additional layers of specificity regulation in MN differentiation. Synopsis: The transition from dividing progenitors to post‐mitotic motor neurons is known to be controlled by the activity of specific transcription factors. Here, the noncoding MN2 locus is identified as a bifunctional modulator of motor neuron differentiation by controlling multiple post‐transcriptional circuitries. The MN2 locus controls the transition of dividing progenitors to post‐mitotic motor neurons (MNs).MN2 function is mediated by expression of both short (miRNA) and long (lncRNA) non‐coding RNAs.The long noncoding RNA lncMN2‐203 promotes MN maturation as a sponge for miR‐466i‐5p and upregulating targets involved in MN differentiation and function.Co‐transcribed miRNAs miR‐325‐3p and miR‐384‐5p repress proliferation gene pathways through the control of cell cycle‐related factors. [ABSTRACT FROM AUTHOR]

Organic electrochemical transistors (OECTs) are finding widespread application in biosensing, thanks to their high sensitivity, broad dynamic range, and low limit of detection. An OECT biosensor requires the immobilization of a biorecognition probe on the gate, or else on the channel, through several, often lengthy, chemical steps. In this work, a fast and straightforward way to functionalize the carbon gate of a fully screen‐printed OECT by means of a polydopamine (PDA) film is presented. By chemical immobilization of an amine‐terminated single‐stranded oligonucleotide, containing the HSP70 promoter CCAAT sequence, on the PDA film, the detection of the complementary DNA strand is demonstrated. Furthermore, the specificity of the developed genosensor is assessed by comparing its response to the fully complementary strand with the one to partially complementary and noncomplementary oligonucleotides. The developed sensor shows a theoretical limit of detection (LOD) of 100 × 10−15m and a dynamic range over four orders of magnitude. [ABSTRACT FROM AUTHOR]

Next‐generation neural interfaces for bidirectional communication with the central nervous system aim to achieve the intimate integration with the neural tissue with minimal neuroinflammatory response, high spatio‐temporal resolution, very high sensitivity, and readout stability. The design and manufacturing of devices for low power/low noise neural recording and safe and energy‐efficient stimulation that are, at the same time, conformable to the brain, with matched mechanical properties and biocompatibility, is a convergence area of research where neuroscientists, materials scientists, and nanotechnologists operate synergically. The biotic–abiotic neural interface, however, remains a formidable challenge that prompts for new materials platforms and innovation in device layouts. Conductive polymers (CP) are attractive materials to be interfaced with the neural tissue and to be used as sensing/stimulating electrodes because of their mixed ionic‐electronic conductivity, their low contact impedance, high charge storage capacitance, chemical versatility, and biocompatibility. This manuscript reviews the state‐of‐the‐art of poly(3,4‐ethylenedioxythiophene)‐based neural interfaces for extracellular recording and stimulation, focusing on those technological approaches that are successfully demonstrated in vivo. The aim is to highlight the most reliable and ready‐for‐clinical‐use solutions, in terms of materials technology and recording performance, other than spot major limitations and identify future trends in this field. [ABSTRACT FROM AUTHOR]

Neurofilaments are structural scaffolding proteins of the neuronal cytoskeleton. Upon axonal injury, the neurofilament light chain (NF‐L) is released into the interstitial fluid and eventually reaches the cerebrospinal fluid and blood. Therefore, NF‐L is emerging as a biomarker of neurological disorders, including neurodegenerative dementia, Parkinson's disease, and multiple sclerosis. It is challenging to quantify NF‐L in bodily fluids due to its low levels. This work reports the detection of NF‐L in aqueous solutions with an organic electronic device. The biosensor is based on the electrolyte‐gated organic field‐effect transistor (EGOFET) architecture and can quantify NF‐L down to sub‐pM levels; thanks to modification of the device gate with anti‐NF‐L antibodies imparted with potentially controlled orientation. The response is fitted to the Guggenheim–Anderson–De Boer adsorption model to describe NF‐L adsorption at the gate/electrolyte interface, to consider the formation of a strongly adsorbed protein layer bound to the antibody and the formation of weakly bound NF‐L multilayers, an interpretation which is also backed up by morphological characterization via atomic force microscopy. The label‐free, selective, and rapid response makes this EGOFET biosensor a promising tool for the diagnosis and monitoring of neuronal damages through the detection of NF‐L in physio‐pathological ranges. [ABSTRACT FROM AUTHOR]

Successful translation of organic transistors as sensors and transducers to clinical settings is hampered by safety and stability issues. The operation of such devices demands driving voltages across the biotic/abiotic interface, which may result in undesired electrochemical reactions that may harm both the patient and the device. In this study, a novel operational mode is presented for electrolyte‐gated organic transistors that avoid these drawbacks: the common‐drain/grounded‐source configuration. This approach reverts the standard common‐source/common‐ground configuration and achieves maximum signal amplification while applying null net bias across the electrolyte, with no parasitic currents. The viability of the proposed configuration is demonstrated by recording in vivo the somatosensory evoked activity from the barrel cortex of rats. The main inherent advantage of transistors with respect to passive electrodes is preserved in the proposed scheme: a superior signal‐to‐noise ratio is achieved which enables the detection of evoked activity at the single‐trial level. Then, common‐drain/grounded‐source organic transistors are proposed as ideal candidate devices for a harmless translational recording platform. [ABSTRACT FROM AUTHOR]

Background: Melanopsin retinal ganglion cell (mRGC)‐mediated pupillary light reflex (PLR) abnormalities have been documented in several neurodegenerative disorders including Parkinson's disease. Overall, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents the strongest prodromal risk factor for impending α‐synucleinopathies. Objectives: To quantitatively compare PLR and mRGC‐mediated contribution to PLR in 16 iRBD patients and 16 healthy controls. Methods: iRBD and controls underwent extensive neuro‐ophthalmological evaluation and chromatic pupillometry. In iRBD, PLR metrics were correlated with clinical variables and with additional biomarkers including REM atonia index (RAI), DaTscan, and presence of phosphorylated‐α‐synuclein (p‐α‐syn) deposition in skin biopsy. Results: We documented higher baseline pupil diameter and decreased rod‐transient PLR amplitude in iRBD patients compared to controls. PLR rod‐contribution correlated with RAI. Moreover, only iRBD patients with evidence of p‐α‐syn deposition at skin biopsy showed reduced PLR amplitude compared to controls. Conclusion: The observed PLR abnormalities in iRBD might be considered as potential biomarkers for the risk stratification of phenoconversion of the disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Organic neuromorphic devices mimic signal processing features of biological synapses, with short‐term plasticity, STP, modulated by the frequency of the input voltage pulses. Here, an artificial synapse, made of intracortical microelectrodes, is demonstrated that exhibits either depressive or facilitative STP. The crossover between the two STP regimes is controlled by the frequency of the input voltage. STP features are described with an equivalent circuit where an inductance component is introduced in parallel with the RC circuit associated with poly(3,4‐ethylenedioxythiophene)/polystyrene sulfonate (PEDOT/PSS)||electrolyte interface. The proposed RLC circuit explains the physical origin of the observed STP and its two timescales in terms of charge build up in PEDOT/PSS. [ABSTRACT FROM AUTHOR]

A general single‐step approach is introduced for the green fabrication of hybrid biosensors from water dispersion. The resulting device integrates the semiconducting properties of a carbon nanotube (CNT) and the functionality of a protein. In the initial aqueous phase, the protein (viz., lysozyme [LZ]) disperses the (6,5)CNT. Drop‐casting of the dispersion on a test pattern (a silicon wafer with interdigitated Au source and drain electrodes) yields a fully operating, robust, electrolyte‐gated transistor (EGT) in one step. The EGT response to biorecognition is then assessed using the LZ inhibitor N‐acetyl glucosamine trisaccharide. Analysis of the output signal allows one to extract a protein‐substrate binding constant in line with values reported for the free (without CNT) system. The methodology is robust, easy to optimize, redirectable toward different targets and sets the grounds for a new class of CNT‐protein biosensors that overcome many limitations of the technology of fabrication of CNT biosensors. [ABSTRACT FROM AUTHOR]

Low‐cost, minimally invasive sensors able to provide real‐time monitoring of wound infection can enable the optimization of healthcare resources in chronic wounds management. Here, a novel printed organic electrochemical transistors (OECT) biosensor for monitoring uric acid (UA), a bacterial infection biomarker in wounds, is demonstrated in artificial wound exudate. The sensor exploits the enzymatic conversion of UA to 5‐hydroxyisourate, catalyzed by Uricase entrapped in a dual‐ionic‐layer hydrogel membrane casted onto the gate. The sensor response is based on the catalytic oxidation of the hydrogen peroxide, generated as part of the Uricase regeneration process, at the Pt modified gate. The proposed dual membrane avoids the occurrence of nonspecific faradic reactions as, for example, the direct oxidation of UA or other electroactive molecules that would introduce a potentially false negative response. The biosensor is robust and its response is reproducible both in phosphate buffer saline and in complex solutions mimicking the wound exudate. The sensor has a high sensitivity in the range encompassing the pathological levels of UA in wounds (<200 μm) exhibiting a limit of detection of 4.5 μm in artificial wound exudate. All these characteristics make this OECT‐based biosensor attractive for wound monitoring interfaced to the patient. [ABSTRACT FROM AUTHOR]

Summary: Phase‐mode electrostatic force microscopy (EFM‐Phase) is a viable technique to image surface electrostatic potential of silicon oxide stripes fabricated by oxidation scanning probe lithography, exhibiting an inhomogeneous distribution of localized charges trapped within the stripes during the electrochemical reaction. We show here that these nanopatterns are useful benchmark samples for assessing the spatial/voltage resolution of EFM‐phase. To quantitatively extract the relevant observables, we developed and applied an analytical model of the electrostatic interactions in which the tip and the surface are modelled in a prolate spheroidal coordinates system, fitting accurately experimental data. A lateral resolution of ∼60 nm, which is comparable to the lateral resolution of EFM experiments reported in the literature, and a charge resolution of ∼20 electrons are achieved. This electrostatic analysis evidences the presence of a bimodal population of trapped charges in the nanopatterned stripes. [ABSTRACT FROM AUTHOR]

Specific detection of dopamine (DA) is achieved with organic neuromorphic devices with no specific recognition function in an electrolyte solution. The response to voltage pulses consists of amplitude‐depressed current spiking mimicking the short‐term plasticity (STP) of synapses. An equivalent circuit hints that the STP timescale of the device arises from the capacitance and resistance of the poly(3,4‐ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) in series with the electrolyte resistance. Both the capacitance and resistance of PEDOT:PSS change with solution compositions. Dose curves are constructed from the STP timescale for each DA metabolite from pM to mM range of concentrations. The STP response of DA is distinctive from the other metabolites even when differences are by one functional group. Both STP and sensitivity to DA are larger across the patho‐physiological range with respect to those to DA metabolites. Density functional theory calculations hint to a stronger hydrogen bond pattern of DA ammonium compared to cationic metabolites. The exponential correlation between STP and the binding energy of DA metabolites interacting with PEDOT:PSS indicates that the slow dynamics of ionic species in and out PEDOT:PSS is the origin of the neuromorphic STP. The sensing framework discriminates differences of nonspecific interactions of few kcal mol−1, corresponding to one functional group in the molecule. [ABSTRACT FROM AUTHOR]

Summary: The ’omics revolution has made a large amount of sequence data available to researchers and the industry. This has had a profound impact in the field of bioinformatics, stimulating unprecedented advancements in this discipline. Mostly, this is usually looked at from the perspective of human ’omics, in particular human genomics. Plant and animal genomics, however, have also been deeply influenced by next‐generation sequencing technologies, with several genomics applications now popular among researchers and the breeding industry. Genomics tends to generate huge amounts of data, and genomic sequence data account for an increasing proportion of big data in biological sciences, due largely to decreasing sequencing and genotyping costs and to large‐scale sequencing and resequencing projects. The analysis of big data poses a challenge to scientists, as data gathering currently takes place at a faster pace than does data processing and analysis, and the associated computational burden is increasingly taxing, making even simple manipulation, visualization and transferring of data a cumbersome operation. The time consumed by the processing and analysing of huge data sets may be at the expense of data quality assessment and critical interpretation. Additionally, when analysing lots of data, something is likely to go awry—the software may crash or stop—and it can be very frustrating to track the error. We herein review the most relevant issues related to tackling these challenges and problems, from the perspective of animal genomics, and provide researchers that lack extensive computing experience with guidelines that will help when processing large genomic data sets. [ABSTRACT FROM AUTHOR]

The small ungauged basins of the highly urbanized area of the city of Rome are often the subject of critical flood conditions for the significant human-made transformations. In this work the EBA4SUB framework, implementing the hydrogeomorphic width function instantaneous unit hydrograph rainfall runoff model, and using digital elevation model, land use and synthetic precipitation as main input information, is applied for evaluating extreme hydrologic forcing conditions at the basic scale. The goal is to understand the rationale behind the observed increasing frequency of local urban inundations that are also observed in the uplands. Results present the impact of urbanization expressed by both the run-off coefficient, the artificial drainage, impacted by paved surfaces and a dramatic number of river-road intersections (i.e. culverts), and the upstream to downstream non-natural scaling behaviour of hydrologic parameters and in particular the peak discharge per unit drainage area. [ABSTRACT FROM AUTHOR]

Isolated infraspinatus atrophy (IIA) is a common condition among overhead‐activity athletes, which affects the hitting shoulder and is caused by suprascapular nerve injury. As the suprascapular nerve is a mixed nerve, such damage could lead to reduced afferent proprioceptive information and impaired shoulder sensorimotor control. This study aimed to evaluate the proprioception of the shoulder with IIA, through the assessment of shoulder position sense. The shoulder position sense was assessed in 24 professional volleyball players (12 players with IIA and 12 healthy players) with a blind dynamic shoulder repositioning test (all participants were blindfolded during the test). Three functional glenohumeral movements were tested as follows: abduction, forward flexion, and a combination of abduction and external rotation. In all three tested movements, the affected shoulder of players with isolated infraspinatus atrophy showed significantly higher hand position error than the healthy contralateral (P<10−3, for all movements) and the healthy control group hitting shoulder (P<10−3, for abduction and flexion; P=.02, for combined movement of abduction and external rotation). The study highlights a reduced sense of position of the hitting shoulder in professional volleyball players with IIA secondary to suprascapular nerve palsy. The higher hand position error of the pathologic shoulder suggests an impairment of the shoulder sensorimotor control system, which likely results from reduced afferent proprioceptive information. Deficient afferent proprioceptive information may result in poor accuracy in descending motor commands and impairment of the shoulder neuromuscular function, leading to reduced shoulder functional stability and increased risk of injury. [ABSTRACT FROM AUTHOR]

High-mobility organic semiconductors such as [1]benzothieno[3,2-b]benzothiophene (BTBT) derivatives are potential candidates for ultrasensitive biosensors. Here 2,7-dioctyl BTBT (C8-BTBT-C8)-based liquid-gated organic electronic devices are demonstrated with two device architectures, viz. electrolyte-gated organic field-effect transistor (EGOFET) and electrolyte-gated organic synapstor (EGOS), and different electrode materials, viz. gold and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS). EGOFETs exhibit a mean transconductance of about 45 µS, on a par with literature, and a max value up to 256 µS at the state-of-the-art in aqueous electrolyte, with a mean product of charge mobility and effective capacitance of about 0.112 and 0.044 µS V−1 for gold and PEDOT:PSS electrodes, respectively. EGOSs exhibit a dynamic response with 15 ms characteristic timescale with Au electrodes and about twice with PEDOT:PSS electrodes. These results demonstrate a promising route for sensing applications in physiological environment based on fully solution-processed whole-organic electronic devices featuring ultrahigh sensitivity and fast response. [ABSTRACT FROM AUTHOR]

Lakes or reservoirs are complex environmental systems, and the sustainable management of their water resources requires advanced hydrological modelling techniques of the main state parameters (water levels and volumes, temperature, pollution level, etc.) to forecast the impacts of human activities on their natural context. Bolsena Lake in northern Lazio is a typical Italian lake environment, being a source of both environmental and economic wealth for the neighbouring area, drawing tourists and providing drinking and irrigation water. The complexity of this hydrogeological and anthropogenic system, and the current technical/scientific relevance of the several water emergencies that have occurred at the lake over the past decade, highlighted the need for a solid plan to manage the possible extreme scenarios that can affect the lake basin, including mitigation of decreases in the lake levels and for controlling lake water quality and water flow rates. The objective of this study was to assess the water budget of Lake Bolsena, accounting for the various jointly involved components, in order to model the lake levels, and to examine possible future scenarios that consider both natural and anthropogenic basin factors. Hydrometeorological data are analysed for setting such scenarios. An open-source computational model ( CEQUEAU) was calibrated with the available data and then used to evaluate possible outcomes. The model simulation results demonstrated the developed hydrological model is capable of predicting water-level fluctuations with a good accuracy for both drought and flood events, identifying it as a valuable tool for basin/lake and lake/river management and simulations. [ABSTRACT FROM AUTHOR]

Local breeds of livestock are of conservation significance as components of global biodiversity and as reservoirs of genetic variation relevant to the future sustainability of agriculture. One such rare historic breed, the Chillingham cattle of northern England, has a 350-year history of isolation and inbreeding yet shows no diminution of viability or fertility. The Chillingham cattle have not been subjected to selective breeding. It has been suggested previously that the herd has minimal genetic variation. In this study, high-density SNP genotyping with the 777K SNP chip showed that 9.1% of loci on the chip are polymorphic in the herd, compared with 62-90% seen in commercial cattle breeds. Instead of being homogeneously distributed along the genome, these loci are clustered at specific chromosomal locations. A high proportion of the Chillingham individuals examined were heterozygous at many of these polymorphic loci, suggesting that some loci are under balancing selection. Some of these frequently heterozygous loci have been implicated as sites of recessive lethal mutations in cattle. Linkage disequilibrium equal or close to 100% was found to span up to 1350 kb, and LD was above r2 = 0.25 up to more than 5000 kb. This strong LD is consistent with the lack of polymorphic loci in the herd. The heterozygous regions in the Chillingham cattle may be the locations of genes relevant to fitness or survival, which may help elucidate the biology of local adaptation in traditional breeds and facilitate selection for such traits in commercial cattle. [ABSTRACT FROM AUTHOR]

Charge transfer at organic‐organic heterojunctions is fundamental to several organic electronics devices, including light‐emitting diodes, photovoltaic cells, light‐emitting transistors, and ambipolar field‐effect transistors. Here, probe charge transfer (CT) processes during the formation of an organic‐organic heterojunction are probed by performing in situ real‐time electrical characterization during the growth of pentacene/C60 ambipolar transistors. N‐type C60 channel formation follows two different percolation pathways, one being associated to linear C60 structures growing along pentacene grain boundaries and the other to C60 island percolation. Upon n‐channel formation a shift of pentacene p‐type transfer characteristics is observed, which is attributed to CT across the heterojunction interface as a result of Fermi level alignment. The findings allow estimation of the energy of thermally accessible CT‐states and their mobility along the interface. Finally, a model is proposed that relates the amount of transferred charge to details in the bilayer morphology and layer thicknesses. The model relies on the capacitive coupling between C60 and pentacene in the accumulation layer, which is consistent with a single hole transport channel. [ABSTRACT FROM AUTHOR]

Since the beginning of the genomic era, the number of available single nucleotide polymorphism ( SNP) arrays has grown considerably. In the bovine species alone, 11 SNP chips not completely covered by intellectual property are currently available, and the number is growing. Genomic/genotype data are not standardized, and this hampers its exchange and integration. In addition, software used for the analyses of these data usually requires not standard (i.e. case specific) input files which, considering the large amount of data to be handled, require at least some programming skills in their production. In this work, we describe a software toolkit for SNP array data management, imputation, genome-wide association studies, population genetics and genomic selection. However, this toolkit does not solve the critical need for standardization of the genotypic data and software input files. It only highlights the chaotic situation each researcher has to face on a daily basis and gives some helpful advice on the currently available tools in order to navigate the SNP array data complexity. [ABSTRACT FROM AUTHOR]

Here, we investigate the in vitro biocompatibility of polyvinylidenefluoride (PVDF)-polytrifluoroethylene (PTrFE) copolymer thin films using neuronal cells. The aim is to obtain an optimal capping layer material for hybrid bio-organic electronic transducers based on organic electronic devices, which can be applied for bidirectional communication with the central nervous system. PVDF:PTrFE thin films were grown by spin coating and characterized by AFM. Human neuroblastoma SHSY5Y cells were used as neuronal model and their interaction with PVDF:PTrFE films was investigated in term of cell adhesion, proliferation, differentiation, and cytoskeleton organization. We show that PVDF:PTrFE thin films allowed standard SHSY5Y proliferation and neuronal differentiation, even if with reduced short-term cell adhesion and spreading. [ABSTRACT FROM AUTHOR]

Genotype imputation is routinely applied in a large number of cattle breeds. Imputation has become a need due to the large number of SNP arrays with variable density (currently, from 2900 to 777 962 SNPs). Although many authors have studied the effect of different statistical methods on imputation accuracy, the impact of a (likely) change in the reference genome assembly on imputation from lower to higher density has not been determined so far. In this work, 1021 Italian Simmental SNP genotypes were remapped on the three most recent reference genome assemblies. Four imputation methods were used to assess the impact of an update in the reference genome. As expected, the four methods behaved differently, with large differences in terms of accuracy. Updating SNP coordinates on the three tested cattle reference genome assemblies determined only a slight variation on imputation results within method. [ABSTRACT FROM AUTHOR]

The introduction of side chains in π-conjugated molecules is a design strategy widely exploited to increase molecular solubility thus improving the processability, while directly influencing the self-assembly and consequently the electrical properties of thin films. Here, a multiscale structural analysis performed by X-ray diffraction, X-ray reflectivity, and atomic force microscopy on thin films of dicyanoperylene molecules decorated with either linear or branched side chains is reported. The substitution with asymmetric branched alkyl chains allows obtaining, upon thermal annealing, field-effect transistors with enhanced transport properties with respect to linear alkyl chains. Branched chains induce molecular disorder during the film growth from solution, effectively favouring 2D morphology. Post-deposition thermal annealing leads to a structural transition towards the bulk-phase for molecules with branched chains, still preserving the 2D morphology and allowing efficient charge transport between crystalline domains. Conversely, molecules with linear chains self-assemble into 3D islands exhibiting the bulk-phase structure. Upon thermal annealing, these 3D islands keep their size constant and no major changes are observed in the organic field effect transistor characteristics. These findings demonstrate that the disorder generated by the asymmetric branched chains when the molecule is physisorbed in thin film can be instrumental for enhancing charge transport via thermal annealing. [ABSTRACT FROM AUTHOR]

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In an earlier study, serum levels of natural antibody isotypes Ig M- and Ig G-binding keyhole limpet hemocyanin were found to be indicative for survival through the laying period of hens and therefore considered as promising traits for future implementation in breeding programs for higher survival of layers. In the present study, we first estimated the genetic parameters for the two isotypes at 20, 40 and 65 weeks of age ( Ig M20, Ig M40 and Ig M65; Ig G20, Ig G40 and Ig G65). Pooled genetic parameters were estimated from the total population of 2504 hens from nine purebred layer lines, with line included in the model to account for admixture. Moderate heritabilities (0.14-0.44) indicated that selection for isotype titers is feasible, especially for IgM. Secondly, associations between 1022 SNP markers and the above-mentioned six immunological traits were estimated in 650 genotyped hens from the nine lines. The association study was performed across lines to detect markers that are closer to the QTL and have the same phase of association in the entire population. Forty-three significant associations between SNPs and isotype titers were detected. The SNPs of interleukins IL10 and IL19 were associated with both isotypes; SNPs of tripartite motif containing 33 ( TRIM33) and IL6 showed significant association with Ig G20 and Ig M20 respectively; SNPs of heat shock protein 90kDa alpha (cytosolic), class B member 1 ( HSP90AB1) were associated with IgG titers at older ages. Some detected SNPs were also reported associated with other immune and behavioral traits. [ABSTRACT FROM AUTHOR]

The aim of the present study was to detect quantitative trait loci (QTL) for innate and adaptive immunity in laying hens. For this purpose, the associations between 1022 single nucleotide polymorphism (SNP) markers and immune traits were studied in 583 hens from nine different layer lines. Immune traits were natural antibodies for keyhole limpet haemocyanin (KLH) and lipopolysaccharide (LPS) at 20, 40 and 65 weeks, acquired antibodies to the vaccinal virus of Newcastle disease at 20 weeks, and complement activity measured on sheep and bovine red blood cells at 20, 40 and 65 weeks. We adopted a novel approach based on across-line analysis and testing of the SNP-by-line interaction. Among lines, linkage disequilibrium is conserved at shorter distances than in individual lines; therefore, SNPs significantly associated with immune traits across lines are expected to be near the functional mutations. In the analysis, the SNPs that had a significant across-line effect but did not show significant SNP-by-line interaction were identified to test whether the association was consistent in the individual lines. Ultimately, 59 significant associations between SNPs and immune traits were detected. Our results confirmed some previously identified QTL and identified new QTL potentially involved in the immune function. We found evidence for a role of IL17A (chromosome 3) in natural and acquired antibody titres and in the classical and alternative pathways of complement activation. The major histocompatibility genes on chromosome 16 showed significant association with natural and acquired antibody titres and classical complement activity. The IL12B gene on chromosome 13 was associated with natural antibody titres. [ABSTRACT FROM AUTHOR]