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Abstract Plant biostimulants are widely applied in agriculture for their ability to improve plant fitness. In the present work, the impact of Graminaceae-derived protein hydrolysate (P) and its lighter molecular fraction F3 (

In recent years, the search for novel natural-based ingredients by food and related industries has sparked extensive research aimed at discovering new sources of functional molecules. Camellia japonica, traditionally known as an ornamental plant, has gained attention due to its diverse array of bioactive compounds with potential industrial applications. Although C. japonica flowers are edible, their phytochemical profile has not been thoroughly investigated. In this study, a phenolic profile screening through an HPLC–ESI-QQQ-MS/MS approach was applied to C. japonica flower extracts, revealing a total of 36 compounds, including anthocyanins, curcuminoids, dihydrochalcones, dihydroflavonols, flavonols, flavones, hydroxybenzoic acids, hydroxycinnamic acids, isoflavonoids, stilbenes, and tyrosols. Following extract profiling, their bioactivity was assessed by means of in vitro antioxidant, antimicrobial, cytotoxic, and neuroprotective activities. The results showed a multifaceted high correlation of phenolic compounds with all the tested bioactivities according to Pearson’s correlation analysis, unraveling the potential of C. japonica flowers as promising sources of nutraceuticals. Overall, these findings provide insight into the valorization of C. japonica flowers from different unexplored cultivars thus diversifying their industrial outcome.

Introduction The night eating syndrome (NES, DSM-V: 307.59) was described in 1955 as a disorder defined by morning anorexia, nocturnal hyperphagia (25% of the daily intake of food during sleep) and insomnia. Attributed to a delay in the circadian rhythm of feeding is characterized by suppression of the daytime appetite and increased in the early morning. It is more prevalent in obese people. Treatment focuses on selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Objectives Description of a NES clinical case demonstrated satisfactory response to pharmacological treatment with trazodone. Methods Brief case presentation and review of the NES literature. Results A 40-year-old woman diagnosed with binge eating disorder followed by Endocrinology. She had morbid obesity grade III. After the failure of various treatments addressed to impulse control and early morning intakes (topiramate, zonisamide, liraglutide, gastric balloon, hydrochloride Naltrexone/Bupropion and SSRI) she was referred to a mental health center. She was started on Trazodone therapy. Interestingly, Insomnia/binge decreased from 7 to 2 episodes/ week leading to a significant weight reduction with a 500 mg/week rate, loosing 4 kg. The case was oriented as a NES but successfully treated as maintenance insomnia. Conclusions NES leads to frequent awakenings and early morning intakes. Awareness of the episode and ability to remember differentiates NES from the sleep-related eating disorder, where the nighttime ingestions cannot be remembered. Unlike binge eating disorder, where the goal is satiety and not falling asleep, so the hypnotic function of nocturnal intake is key in the differential diagnosis with NES . Trazodone, indicated in insomnia of maintenance, has not been reported as a treatment of choice in the NES, enabling a significant decrease on awakenings and consequently the intake. Disclosure of Interest None Declared

Arnica montana L. (Asteraceae family) is a plant commonly used in traditional medicine, and several reports have characterized this plant’s bioactivities, especially its phenolic compounds. These compounds are well known for their numerous beneficial biological properties. Consequently, industry stakeholders from the feed, food, cosmetic, and pharmaceutical sectors are seeking extracts rich in phenolic compounds, which could be interesting for the development of bio-based applications. The objective of the present study was to characterize the phenolic profile of this species to lay the groundwork for further optimization studies to obtain the highest amount of phenolic compounds. Therefore, A. montana was extracted with an ethanol/water ratio of 80:20 (v/v) at room temperature for 1 h, and phenolic compounds were identified and quantified through UPLC (HPLC Dionex Ultimate 3000) with a mass detector (TSQ Quantis). In the extract, phenolics belonging to different groups were identified, namely eriodictyol-O-glucuronide (flavanone), hispidulin and luteolin (flavones), kaempferol and 6-methoxykaempferol, (flavonols), p-coumaric, feruloylquinic, caffeoylquinic, and dicaffeoylquinic isomers (hydroxycinnamic acids). However, only four of them could be quantified: kaempferol and the three hydroxycinnamic acids. The total phenolic content (mg/g of dry sample) was estimated to be 27.34 mg/g, with the most prevalent compounds being the dicaffeoylquinic acids (accounting for 79.5% of the total phenolics). It has been demonstrated that dicaffeoylquinic acids present anti-inflammatory and antioxidant activities, which have been linked to several beneficial effects. Thus, obtaining phenolic-rich extracts of A. montana may allow us to exploit this plant’s significant biological properties, and it could be a new ingredient for developing new applications in the nutraceutical, cosmetic, and/or pharmaceutical industries.

Taxus cell cultures are a reliable biotechnological source of the anticancer drug paclitaxel. However, the interplay between taxane production and other metabolic pathways during elicitation remains poorly understood. In this study, we combined untargeted metabolomics and elicited Taxus baccata cell cultures to investigate variations in taxane-associated metabolism under the influence of 1 µM coronatine (COR) and 150 µM salicylic acid (SA). Our results demonstrated pleiotropic effects induced by both COR and SA elicitors, leading to differential changes in cell growth, taxane content, and secondary metabolism. Metabolite annotation revealed significant effects on N-containing compounds, phenylpropanoids, and terpenoids. Multivariate analysis showed that the metabolomic profiles of control and COR-treated samples are closer to each other than to SA-elicited samples at different time points (8, 16, and 24 days). The highest level of paclitaxel content was detected on day 8 under SA elicitation, exhibiting a negative correlation with the biomarkers kauralexin A2 and taxusin. Our study provides valuable insights into the intricate metabolic changes associated with paclitaxel production, aiding its potential optimization through untargeted metabolomics and an evaluation of COR/SA elicitor effects.

Elicited cell cultures of Taxus spp. are successfully used as sustainable biotechnological production systems of the anticancer drug paclitaxel, but the effect of the induced metabolomic changes on the synthesis of other bioactive compounds by elicitation has been scarcely studied. In this work, a powerful combinatorial approach based on elicitation and untargeted metabolomics was applied to unravel and characterize the effects of the elicitors 1 µM of coronatine (COR) or 150 µM of salicylic acid (SA) on phenolic biosynthesis in Taxus baccata cell suspensions. Differential effects on cell growth and the phenylpropanoid biosynthetic pathway were observed. Untargeted metabolomics analysis revealed a total of 83 phenolic compounds, mainly flavonoids, phenolic acids, lignans, and stilbenes. The application of multivariate statistics identified the metabolite markers attributed to elicitation over time: up to 34 compounds at 8 days, 41 for 16 days, and 36 after 24 days of culture. The most notable metabolic changes in phenolic metabolism occurred after 8 days of COR and 16 days of SA elicitation. Besides demonstrating the significant and differential impact of elicitation treatments on the metabolic fingerprint of T. baccata cell suspensions, the results indicate that Taxus ssp. biofactories may potentially supply not only taxanes but also valuable phenolic antioxidants, in an efficient optimization of resources.

Summary: Dosage compensation in Drosophila melanogaster involves a 2-fold transcriptional upregulation of the male X chromosome, which relies on the X-chromosome-binding males-specific lethal (MSL) complex. However, how such 2-fold precision is accomplished remains unclear. Here, we show that a nuclear pore component, Mtor, is involved in setting the correct levels of transcription from the male X chromosome. Using larval tissues, we demonstrate that the depletion of Mtor results in selective upregulation at MSL targets of the male X, beyond the required 2-fold. Mtor and MSL components interact genetically, and depletion of Mtor can rescue the male lethality phenotype of MSL components. Using RNA fluorescence in situ hybridization (FISH) analysis and nascent transcript sequencing, we find that the effect of Mtor is not due to defects in mRNA export but occurs at the level of nascent transcription. These findings demonstrate a physiological role for Mtor in the process of dosage compensation, as a transcriptional attenuator of X chromosome gene expression.

Evaluation of cooperative automated driving applications requires the capability of simulating the vehicle and traffic dynamics as well as the communications with a level of accuracy that most of the current tools still lack. In this paper, we explore the use of game engines in hybrid traffic-network simulators. We describe and validate a novel framework based on this approach: Veneris. Our framework is made of a traffic simulator, implemented on the top of the Unity game engine, which includes a realistic vehicle model and a set of driving and lane change behaviors adapted to a 3D environment that reproduces real-world traffic dynamics; a ray-launching propagation simulator on graphics-processing-unit (GPU), called Opal, and a set of modules, which enable bidirectional coupling with the OMNET++ network simulator. The more relevant and novel mechanisms of Veneris are introduced, but further implementation details can be checked on the source code provided in our repository. We discuss the validation tests we have performed and show how it provides accurate results in three key areas: 1) the fidelity of the vehicle dynamics; 2) the recreation of realistic traffic flows, and; 3) the accuracy of the propagation simulation. In addition, the general results of the expected performance are provided.

Algae are underexplored resources in Western countries and novel approaches are needed to boost their industrial exploitation. In this work, eight edible seaweeds were subjected to their valorization in terms of nutritional characterization, thermochemical properties, and bioactive profile. Our results suggest that seaweeds present a rich nutritional profile, in which carbohydrates are present in high proportions, followed by a moderate protein composition and a valuable content of ω-3 polyunsaturated fatty acids. The thermochemical characterization of seaweeds showed that some macroalgae present a low ash content and high volatile matter and carbon fixation rates, being promising sources for alternative biofuel production. The bioactive profile of seaweeds was obtained from their phenolic and carotenoid content, together with the evaluation of their associated bioactivities. Among all the species analyzed, Porphyra purpurea presented a balanced composition in terms of carbohydrates and proteins and the best thermochemical profile. This species also showed moderate anti-inflammatory activity. Additionally, Himanthalia elongata extracts showed the highest contents of total phenolics and a moderate carotenoid content, which led to the highest rates of antioxidant activity. Overall, these results suggest that seaweeds can be used as food or functional ingredient to increase the nutritional quality of food formulations.

The search for waste minimization and the valorization of by-products are key practices for good management and improved sustainability in the food industry. The production of almonds generates a large amount of waste, most of which is not used. Until now, almonds have been used for their high nutritional value as food, especially almond meat. The other remaining parts (skin, shell, hulls, etc.) are still little explored, even though they have been used as fuel by burning or as livestock feed. However, interest in these by-products has been increasing as they possess beneficial properties (caused mainly by polyphenols and unsaturated fatty acids) and can be used as new ingredients for the food, cosmetic, and pharmaceutical industries. Therefore, it is important to explore almond’s valorization of by-products for the development of new added-value products that would contribute to the reduction of environmental impact and an improvement in the sustainability and competitiveness of the almond industry.

The search for waste minimization and the valorization of by-products are key to good management and improved sustainability in the food industry. The great production of almonds, based on their high nutritional value as food, especially almond kernels, generates tons of waste yearly. The remaining parts (skin, shell, hulls, etc.) are still little explored, even though they have been used as fuel by burning or as livestock feed. The interest in these by-products has been increasing, as they possess beneficial properties, caused by the presence of different bioactive compounds, and can be used as promising sources of new ingredients for the food, cosmetic and pharmaceutical industry. Additionally, the use of almond by-products is being increasingly applied for the fortification of already-existing food products, but there are some limitations, including the presence of allergens and mycotoxins that harden their applicability. This review focuses on the extraction technologies applied to the valorization of almond by-products for the development of new value-added products that would contribute to the reduction of environmental impact and an improvement in the sustainability and competitiveness of the almond industry.

Algae are an underexploited source of natural bioactive compounds in Western countries, so an increasing interest in the valorization of these marine organisms has emerged in recent years. In this work, the effect of extracting solvent on the extraction yield, phenolic content, antioxidant capacity, and antimicrobial activity of nine brown macroalgae species (Ascophyllum nodosum, Himanthalia elongata, Undaria pinnatifida, Pelvetia canaliculata, Saccharina latissima, Bifurcaria bifurcata, Laminaria ochroleuca, Sargassum muticum, and Fucus spiralis) was assessed. Total phenolic content (TPC) and the antioxidant properties of extracts by different assays: radical scavenging activity (DPPH-RSA) and ferric reducing antioxidant power (FRAP) were performed. The antimicrobial activity of extracts was studied against six different foodborne microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Escherichia coli, Salmonella enteritidis, and Pseudomonas aeruginosa. The highest extraction yield was achieved in ethanolic extracts. However, the highest TPC and FRAP values were obtained on the ethyl acetate extracts, especially from A. nodosum. Concerning algal species, the highest TPC and FRAP values were found in A. nodosum, while the highest DPPH-RSA values were achieved in the hexane extracts of B. bifurcata. The antimicrobial activity of algal extracts varied according to the solvent and alga selected, suggesting the species- and solvent-dependent behavior of this property, with B. bifurcata extracts showing the highest results for a wide range of bacteria. Our results provide insight on the characterization of widespread brown algae in the coasts of the North-Western region of the Iberian Peninsula, reflecting multiple health-enhancing properties which may lead to their exploitation in food, pharmacological, and cosmetic industries.

Millimeter wave (mm-wave) frequencies have been proposed to achieve high capacity in 5G communications. Although meaningful research on the channel characteristics has been performed in the 28-, 38-, and 60-GHz bands in both indoor and short-range scenarios, only a small number of trials (experiments) have been carried out in other mm-wave bands. The objective of this paper is to study the viability and evaluate the performance of the 94-GHz frequency band for MIMO-OFDM transmission in an indoor environment. Starting from a measurement campaign, the performance of MIMO algorithms is studied in terms of throughput for four different antenna configurations.

In this paper, the impact of considering diffuse multipath components at mm-wave frequencies as well as the significance of selecting appropriate diffuse scattering model parameters is shown. Two different diffuse models, namely, the Lambertian model and the directive model, have been parameterized for several materials typically present in indoor environments. These models are formulated to embed the diffuse scattering phenomenon easily into ray tracing tools. The estimation of the parameters has been performed by comparing measurements and simulations using the models. Once the best fitting parameters have been estimated, they are included in the diffuse components simulation section of a general ray tracing tool. This tool has been used to simulate the power delay profile at 60 GHz in an indoor scenario, including single and double bounce diffuse components. Thanks to the estimated model parameters, the wireless channel at the 60-GHz band can be analyzed, including the diffuse scattering phenomenon, without the need for any previous measurement or simulation. Thus, the channel analysis with ray tracing tools, including dense components, becomes easier, faster, and more reliable.

Introdução: A pneumonia adquirida na Unidade de Terapia Intensiva (UTI) ocasiona o prolongamento da hospitalização e impacta na mortalidade. Intervenções educativas com profissionais de saúde são estratégias de prevenção relevantes nas infecções relacionadas à assistência à saúde. Objetivo: Avaliar o resultado de uma ação educativa na adesão à manutenção do decúbito elevado, acima de 30 graus, como medida para prevenção de pneumonia associada à ventilação mecânica. Métodos: Estudo quase experimental do tipo antes e depois desenvolvido na UTI do Hospital Universitário de Londrina, no período de março e junho de 2010, dividido em três fases (pré-intervenção, intervenção e pós-intervenção). Durante o período de estudo, foram treinados 49 profissionais. Foram realizadas observações diretas da altura do decúbito antes e após o treinamento e coletados dados clínicos dos pacientes admitidos na UTI. A adesão à recomendação de manter o decúbito elevado foi definida como a manutenção de decúbito acima de 30 graus para cada observação. Resultados: A média de angulação do decúbito apresentou aumento significativo do período pré-intervenção (27,85 ± 6,76 graus) para o primeiro mês pós-intervenção (30,70 ± 8,18 graus; p

OBJETIVO: Avaliar o impacto da implantação de um guia terapêutico para o tratamento empírico de pneumonia hospitalar. MÉTODOS: Foi realizado um ensaio clínico com controle histórico, no período de junho de 2002 a junho de 2003, em pacientes internados na unidade de terapia intensiva (UTI) que adquiriram pneumonia hospitalar. Todos foram tratados de acordo com um guia terapêutico desenvolvido pela Comissão de Controle de Infecção Hospitalar da instituição (grupo com intervenção). Para o controle, foram analisados os prontuários dos pacientes que adquiriram pneumonia hospitalar no período de junho de 2000 a junho de 2001 (grupo sem intervenção). Foram determinados taxa de mortalidade, tempo médio de tratamento e tempo de internação na UTI e no hospital dos pacientes que adquiriram pneumonia hospitalar. RESULTADOS: A mortalidade relacionada à pneumonia foi menor no grupo tratado de acordo com o guia terapêutico (26 x 53,6%; p = 0,00). Quanto à mortalidade geral, não houve diferença estatisticamente significativa entre os dois períodos (51 x 57,9%; p = 0,37). Também não foi encontrada diferença quanto aos tipos de microorganismos isolados, tempo de tratamento e tempo de internação na UTI e no hospital. CONCLUSÃO: A implantação do guia terapêutico para tratamento de pneumonia hospitalar adquirida em UTI pode ser eficaz na diminuição das taxas de mortalidade.OBJECTIVE: To evaluate the impact that the implementation of therapeutic guidelines has on the empirical treatment of nosocomial pneumonia. METHODS: A clinical trial, using historical controls and involving current ICU patients who had acquired nosocomial pneumonia, was carried out from June of 2002 to June of 2003. All were treated according to therapeutic guidelines developed by the Commission for Nosocomial Infection Control of the institution (group with intervention). As controls, the medical charts of the patients who acquired nosocomial pneumonia between June of 2000 and June of 2001 (group without intervention) were analyzed. Mortality and mean treatment period, as well as the length of hospital and ICU stays, were determined for the patients who acquired nosocomial pneumonia. RESULTS: Mortality associated with pneumonia was lower in the group treated according to the therapeutic guidelines (26 vs. 53.6%; p = 0.00). As for overall mortality, there was no statistically significant difference between the two periods (51 vs. 57.9%; p = 0.37). There was also no difference in the type of microorganisms isolated, treatment period, length of hospital stay or length of ICU stay. CONCLUSION: The implementation of therapeutic guidelines for the treatment of nosocomial pneumonia acquired in the ICU can be efficacious in decreasing mortality rates.

Abstract Background Gene expression is achieved by the coordinated action of multiple factors to ensure a perfect synchrony from chromatin epigenetic regulation through to mRNA export. Sus1 is a conserved mRNA export/transcription factor and is a key player in coupling transcription initiation, elongation and mRNA export. In the nucleus, Sus1 is associated to the transcriptional co-activator SAGA and to the NPC associated complex termed TREX2/THSC. Through these associations, Sus1 mediates the nuclear dynamics of different gene loci and facilitate the export of the new transcripts. Results In this study, we have investigated whether the yeast Sus1 protein is linked to factors involved in mRNA degradation pathways. We provide evidence for genetic interactions between SUS1 and genes coding for components of P-bodies such as PAT1, LSM1, LSM6 and DHH1. We demonstrate that SUS1 deletion is synthetic lethal with 5'→3' decay machinery components LSM1 and PAT1 and has a strong genetic interaction with LSM6 and DHH1. Interestingly, Sus1 overexpression led to an accumulation of Sus1 in cytoplasmic granules, which can co-localise with components of P-bodies and stress granules. In addition, we have identified novel physical interactions between Sus1 and factors associated to P-bodies/stress granules. Finally, absence of LSM1 and PAT1 slightly promotes the Sus1-TREX2 association. Conclusions In this study, we found genetic and biochemical association between Sus1 and components responsible for cytoplasmic mRNA metabolism. Moreover, Sus1 accumulates in discrete cytoplasmic granules, which partially co-localise with P-bodies and stress granules under specific conditions. These interactions suggest a role for Sus1 in gene expression during cytoplasmic mRNA metabolism in addition to its nuclear function.

In response to the increased popularity of medicinal plants, a number of conservation groups are recommending the investigation on poorly characterized and widely distributed species, as it is the case of camellias. In particular, Camellia japonica L. is a widespread species found in Galicia (NW Spain), where it has been largely exploited with ornamental purposes. Recent findings on its phytochemical characterization showed thousands of bioactive ingredients, mostly represented by phenolic compounds, together with terpenoids, and fatty acids. These molecules present associated biological activities, acting as antioxidant, antimicrobial, anti-inflammatory, and anticancer agents. This review is aimed at describing the main bioactive compounds of C. japonica, as well as the health-enhancing properties attributed to this medicinal plant. Novel strategies are needed to implement an efficient industrialization process for C. japonica, ranging from small-scale approaches to the establishment of large plantations, thus involving important sectors, such as the food, pharmaceutical and cosmetic industries.

Cellular ability to mount an enhanced transcriptional response upon repeated exposure to external cues is termed transcriptional memory, which can be maintained epigenetically through cell divisions and can depend on a nuclear pore component Nup98. The majority of mechanistic knowledge on transcriptional memory has been derived from bulk molecular assays. To gain additional perspective on the mechanism and contribution of Nup98 to memory, we used single-molecule RNA FISH (smFISH) to examine the dynamics of transcription in Drosophila cells upon repeated exposure to the steroid hormone ecdysone. We combined smFISH with mathematical modeling and found that upon hormone exposure, cells rapidly activate a low-level transcriptional response, but simultaneously begin a slow transition into a specialized memory state characterized by a high rate of expression. Strikingly, our modeling predicted that this transition between non-memory and memory states is independent of the transcription stemming from initial activation. We confirmed this prediction experimentally by showing that inhibiting transcription during initial ecdysone exposure did not interfere with memory establishment. Together, our findings reveal that Nup98’s role in transcriptional memory is to stabilize the forward rate of conversion from low to high expressing state, and that induced genes engage in two separate behaviors – transcription itself and the establishment of epigenetically propagated transcriptional memory.

Parvalbumin-positive (PV+) γ-aminobutyric acid (GABA) interneurons are critically involved in producing rapid network oscillations and cortical microcircuit computations, but the significance of PV+ axon myelination to the temporal features of inhibition remains elusive. Here, using toxic and genetic mouse models of demyelination and dysmyelination, respectively, we find that loss of compact myelin reduces PV+ interneuron presynaptic terminals and increases failures, and the weak phasic inhibition of pyramidal neurons abolishes optogenetically driven gamma oscillations in vivo. Strikingly, during behaviors of quiet wakefulness selectively theta rhythms are amplified and accompanied by highly synchronized interictal epileptic discharges. In support of a causal role of impaired PV-mediated inhibition, optogenetic activation of myelin-deficient PV+ interneurons attenuated the power of slow theta rhythms and limited interictal spike occurrence. Thus, myelination of PV axons is required to consolidate fast inhibition of pyramidal neurons and enable behavioral state-dependent modulation of local circuit synchronization.

Brown algae are ubiquitously distributed in the NW coastline of the Iberian Peninsula, where they stand as an underexploited resource. In this study, five solvents were applied to the extraction of pigments from nine brown algae, followed by their determination and quantification by HPLC-DAD. A total of 13 compounds were detected: Six were identified as chlorophylls, six were classified as xanthophylls, and one compound was reported as a carotene. Fucoxanthin was reported in all extracts, which is the most prominent pigment of these algae. Among them, L. saccharina and U. pinnatifida present the highest concentration of fucoxanthin (4.5–4.7 mg∙g−1 dry weight). Ethanol and acetone were revealed as the most efficient solvents for the extraction of pigments, showing a maximal value of 11.9 mg of total pigments per gram of dry alga obtained from the ethanolic extracts of H. elongata, followed by the acetonic extracts of L. ochroleuca. Indeed, ethanol was also revealed as the most efficient solvent according to its high extraction yield along all species evaluated. Our results supply insights into the pigment composition of brown algae, opening new perspectives on their commercial exploitation by food, pharmaceutical, and cosmeceutical industries.

GABAergic fast-spiking parvalbumin-positive (PV) interneurons are frequently myelinated in the cerebral cortex. However, the factors governing the topography of cortical interneuron myelination remain incompletely understood. Here, we report that segmental myelination along neocortical interneuron axons is strongly predicted by the joint combination of interbranch distance and local axon caliber. Enlargement of PV+ interneurons increased axonal myelination, while reduced cell size led to decreased myelination. Next, we considered regular-spiking SOM+ cells, which normally have relatively shorter interbranch distances and thinner axon diameters than PV+ cells, and are rarely myelinated. Consistent with the importance of axonal morphology for guiding interneuron myelination, enlargement of SOM+ cell size dramatically increased the frequency of myelinated axonal segments. Lastly, we confirm that these findings also extend to human neocortex by quantifying interneuron axonal myelination from ex vivo surgical tissue. Together, these findings establish a predictive model of neocortical GABAergic interneuron myelination determined by local axonal morphology.

Seaweeds are industrially exploited for obtaining pigments, polysaccharides, or phenolic compounds with application in diverse fields. Nevertheless, their rich composition in fiber, minerals, and proteins, has pointed them as a useful source of these components. Seaweed proteins are nutritionally valuable and include several specific enzymes, glycoproteins, cell wall-attached proteins, phycobiliproteins, lectins, or peptides. Extraction of seaweed proteins requires the application of disruptive methods due to the heterogeneous cell wall composition of each macroalgae group. Hence, non-protein molecules like phenolics or polysaccharides may also be co-extracted, affecting the extraction yield. Therefore, depending on the macroalgae and target protein characteristics, the sample pretreatment, extraction and purification techniques must be carefully chosen. Traditional methods like solid–liquid or enzyme-assisted extraction (SLE or EAE) have proven successful. However, alternative techniques as ultrasound- or microwave-assisted extraction (UAE or MAE) can be more efficient. To obtain protein hydrolysates, these proteins are subjected to hydrolyzation reactions, whether with proteases or physical or chemical treatments that disrupt the proteins native folding. These hydrolysates and derived peptides are accounted for bioactive properties, like antioxidant, anti-inflammatory, antimicrobial, or antihypertensive activities, which can be applied to different sectors. In this work, current methods and challenges for protein extraction and purification from seaweeds are addressed, focusing on their potential industrial applications in the food, cosmetic, and pharmaceutical industries.

The nuclear pore complex is a transport channel embedded in the nuclear envelope and made up of 30 different components termed nucleoporins (Nups). In addition to their classical role in transport, a subset of Nups has a conserved role in the regulation of transcription via direct binding to chromatin. The molecular details of this function remain obscure, and it is unknown how metazoan Nups are recruited to their chromatin locations or what transcription steps they regulate. Here, we demonstrate genome-wide and physical association between Nup98 and histone-modifying complexes MBR-R2/NSL and Trx/MLL. Importantly, we identify a requirement for MBD-R2 in recruitment of Nup98 to many of its genomic target sites. Consistent with its interaction with the Trx/MLL complex, Nup98 is shown to be necessary for Hox gene expression in developing fly tissues. These findings introduce roles of Nup98 in epigenetic regulation that may underlie the basis of oncogenicity of Nup98 fusions in leukemia.

Objetivo: Descrever a experiência de um único centro com o uso de colistina para tratar infecções hospitalares causadas por bactérias Gram-negativas resistentes a múltiplos fármacos e identificar fatores associados com lesão renal aguda e mortalidade. Métodos: Estudo longitudinal retrospectivo que avaliou pacientes gravemente enfermos, com infecções causadas por bactérias Gram-negativas resistentes a múltiplos fármacos. Foram considerados elegíveis para este estudo, durante o período compreendido entre janeiro e dezembro de 2008, todos os pacientes adultos com necessidade de tratamento com colistina endovenosa (colistimetato de sódio). As informações coletadas incluem dados demográficos, diagnóstico, duração do tratamento, presença de lesão renal aguda e mortalidade em 30 dias. Resultados: A colistina foi utilizada para tratar uma infecção em 109 de 789 pacientes (13,8%) admitidos à unidade de terapia intensiva. A mortalidade em 30 dias observada nestes pacientes foi de 71,6%. Vinte e nove pacientes (26,6%) tinham lesão renal prévia ao tratamento com colistina, sendo que seis deles conseguiram recuperar a função renal, mesmo durante o tratamento com colistina. Vinte e um pacientes (19,2%) desenvolveram lesão renal aguda durante o tratamento com colistina, sendo que 11 destes pacientes necessitaram ser submetidos à diálise. A variável independentemente associada com a presença de lesão renal aguda foi a pontuação segundo o sistema Sequential Organ Failure Assessment no início do tratamento com colistina (OR=1,46; IC95%=1,20-1,79; p

INTRODUCTION:This epidemiological survey estimates the hospitalization burden related to Parkinson´s Disease in Spain. METHODS:This observational retrospective survey was performed by reviewing data from the National Surveillance System for Hospital Data, which includes more than 98% of Spanish hospitals. All hospitalizations of patients with Parkinson´s disease that were reported from 1997-2012 were analyzed. Codes were selected using the 9th International Classification of Diseases: ICD-9-CM: 332.0. RESULTS:A total of 438,513 hospital discharges of patients with Parkinson´s Disease were reported during the study period. The annual hospitalization rate was 64.2 cases per 100,000. The average length of hospital stay was 10 days. The trend for the annual hospitalization rate differed significantly depending on whether Parkinson´s disease was the main cause of hospitalization (n = 23,086, 1.14% annual increase) or was not the main cause of hospitalization (n = 415,427, 15.37% annual increase). The overall case-fatality rate among hospitalized patients was 10%. The case fatality rate among patient´s hospitalized with Parkinson´s disease as the main cause of hospitalization was 2.5%. The hospitalization rate and case-fatality rate significantly increased with age. The primary causes of hospitalization when Parkinson´s disease was not coded as the main cause of hospitalization were as follows: respiratory system diseases (24%), circulatory system diseases (19%), injuries and poisoning, including fractures (12%), diseases of the digestive system (10%) and neoplasms (5%). The annual average cost for National Health Care System was € 120 M, with a mean hospitalization cost of €4,378. CONCLUSIONS:Parkinson´s disease poses a significant health threat in Spain, particularly in the elderly. While hospitalizations due to Parkinson´s Disease are relatively stable over time, the number of patients presenting with Parkinson´s disease as an important comorbidity has increased dramatically. Medical staff must be specifically trained to treat the particular needs of hospitalized patients suffering from Parkinson´s disease as an important comorbidity.

Cellular ability to mount an enhanced transcriptional response upon repeated exposure to external cues is termed transcriptional memory, which can be maintained epigenetically through cell divisions and can depend on a nuclear pore component Nup98. The majority of mechanistic knowledge on transcriptional memory has been derived from bulk molecular assays. To gain additional perspective on the mechanism and contribution of Nup98 to memory, we used single-molecule RNA FISH (smFISH) to examine the dynamics of transcription in Drosophila cells upon repeated exposure to the steroid hormone ecdysone. We combined smFISH with mathematical modeling and found that upon hormone exposure, cells rapidly activate a low-level transcriptional response, but simultaneously begin a slow transition into a specialized memory state characterized by a high rate of expression. Strikingly, our modeling predicted that this transition between non-memory and memory states is independent of the transcription stemming from initial activation. We confirmed this prediction experimentally by showing that inhibiting transcription during initial ecdysone exposure did not interfere with memory establishment. Together, our findings reveal that Nup98's role in transcriptional memory is to stabilize the forward rate of conversion from low to high expressing state, and that induced genes engage in two separate behaviors - transcription itself and the establishment of epigenetically propagated transcriptional memory., Competing Interests: PP, SL, MC No competing interests declared, (© 2022, Pascual-Garcia et al.)

The nuclear pore complex (NPC) is a massive nuclear envelope-embedded protein complex, the canonical function of which is to mediate selective nucleocytoplasmic transport. In addition to its transport function, the NPC has been shown to interact with the underlying chromatin and to influence both activating and repressive gene regulatory processes, contributing to the establishment and the epigenetic maintenance of cell identity. In this review, we discuss diverse gene regulatory functions of NPC components and emerging mechanisms underlying these functions, including roles in genome architecture, transcription complex assembly, chromatin remodeling, and coordination of transcription and mRNA export. These functional roles highlight the importance of the NPC as a nuclear scaffold directing genome organization and function., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Interactions between the genome and the nuclear pore complex (NPC) have been implicated in multiple gene regulatory processes, but the underlying logic of these interactions remains poorly defined. Here, we report high-resolution chromatin binding maps of two core components of the NPC, Nup107 and Nup93, in Drosophila cells. Our investigation uncovered differential binding of these NPC subunits, where Nup107 preferentially targets active genes while Nup93 associates primarily with Polycomb-silenced regions. Comparison to Lamin-associated domains (LADs) revealed that NPC binding sites can be found within LADs, demonstrating a linear binding of the genome along the nuclear envelope. Importantly, we identified a functional role of Nup93 in silencing of Polycomb target genes and in spatial folding of Polycomb domains. Our findings lend to a model where different nuclear pores bind different types of chromatin via interactions with specific NPC sub-complexes, and a subset of Polycomb domains is stabilized by interactions with Nup93., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nuclear pore complexes have emerged in recent years as chromatin-binding nuclear scaffolds, able to influence target gene expression. However, how nucleoporins (Nups) exert this control remains poorly understood. Here we show that ectopically tethering Drosophila Nups, especially Sec13, to chromatin is sufficient to induce chromatin decondensation. This decondensation is mediated through chromatin-remodeling complex PBAP, as PBAP is both robustly recruited by Sec13 and required for Sec13-induced decondensation. This phenomenon is not correlated with localization of the target locus to the nuclear periphery, but is correlated with robust recruitment of Nup Elys. Furthermore, we identified a biochemical interaction between endogenous Sec13 and Elys with PBAP, and a role for endogenous Elys in global as well as gene-specific chromatin decompaction. Together, these findings reveal a functional role and mechanism for specific nuclear pore components in promoting an open chromatin state., (© 2019 Kuhn et al.)

Nuclear genome architecture relies on interactions between the genome and various nuclear scaffolds. One such a nuclear scaffold is the nuclear pore complex (NPC), which in addition to its nuclear transport function, can interact with underlying chromatin. In particular, NPCs have been recently reported to associate with a number of enhancers and superenhancers in metazoan genomes, and select NPC components have been shown to promote the formation of specific genomic loops. Here, we provide a brief overview of current models of enhancer function, and discuss recent evidence that NPCs bind enhancers and contribute to topological genome organization. We also examine possible models of how gene and enhancer targeting to NPCs may contribute to tissue-specific genome architecture and expression programs, including the possibility that NPCs may promote phase separation of transcriptional compartments., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Nuclear pore complex components (Nups) have been implicated in transcriptional regulation, yet what regulatory steps are controlled by metazoan Nups remains unclear. We identified the presence of multiple Nups at promoters, enhancers, and insulators in the Drosophila genome. In line with this binding, we uncovered a functional role for Nup98 in mediating enhancer-promoter looping at ecdysone-inducible genes. These genes were found to be stably associated with nuclear pores before and after activation. Although changing levels of Nup98 disrupted enhancer-promoter contacts, it did not affect ongoing transcription but instead compromised subsequent transcriptional activation or transcriptional memory. In support of the enhancer-looping role, we found Nup98 to gain and retain physical interactions with architectural proteins upon stimulation with ecdysone. Together, our data identify Nups as a class of architectural proteins for enhancers and supports a model in which animal genomes use the nuclear pore as an organizing scaffold for inducible poised genes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In response to infection, the innate immune system rapidly activates an elaborate and tightly orchestrated gene expression program to induce critical antimicrobial genes. While many key players in this program have been identified in disparate biological systems, it is clear that there are additional uncharacterized mechanisms at play. Our previous studies revealed that a rapidly-induced antiviral gene expression program is active against disparate human arthropod-borne viruses in Drosophila. Moreover, one-half of this program is regulated at the level of transcriptional pausing. Here we found that Nup98, a virus-induced gene, was antiviral against a panel of viruses both in cells and adult flies since its depletion significantly enhanced viral infection. Mechanistically, we found that Nup98 promotes antiviral gene expression in Drosophila at the level of transcription. Expression profiling revealed that the virus-induced activation of 36 genes was abrogated upon loss of Nup98; and we found that a subset of these Nup98-dependent genes were antiviral. These Nup98-dependent virus-induced genes are Cdk9-dependent and translation-independent suggesting that these are rapidly induced primary response genes. Biochemically, we demonstrate that Nup98 is directly bound to the promoters of virus-induced genes, and that it promotes occupancy of the initiating form of RNA polymerase II at these promoters, which are rapidly induced on viral infection to restrict human arboviruses in insects.

Functional compartmentalization of the genome relies on interactions between genomic regions and various nuclear scaffolds and macro-complexes. The Nuclear Pore Complex (NPC) is a large nuclear envelope-embedded protein complex, which creates a highly regulated transport channel between the nucleus and the cytoplasm. In addition to its central role in transport, the NPC has been linked to genome compartmentalization via binding to specific regions of the genome and association with gene regulatory machinery. Although originally proposed to preferentially associate with active genes, the NPC has now been implicated in both gene activating and gene silencing processes. Here, we review recent findings that highlight the roles of various components of the NPC in transcriptional activation, transcriptional memory, heterochromatin formation, post-transcriptional gene silencing and RNA processing. Together, these findings suggest that the nuclear pore is utilized as a regulatory platform for a number of distinct gene expression processes and further point to its central role in setting up particular expression environments on the genomic template., (Copyright © 2014 Elsevier Ltd. All rights reserved.)