Miracle-dz/UniFAR-FTUs huggingface dataset:
Methylation of the N‐terminal histidine protects a lytic polysaccharide monooxygenase from auto‐oxidative inactivation

The catalytically crucial N‐terminal histidine (His1) of fungal lytic polysaccharide monooxygenases (LPMOs) is post‐translationally modified to carry a methylation. The functional role of this methylation remains unknown. We have carried out an in‐depth functional comparison of two variants of a family AA9 LPMO from Thermoascus aurantiacus (TaLPMO9A), one with, and one without the methylation on His1. Various activity assays showed that the two enzyme variants are identical in terms of substrate preferences, cleavage specificities and the ability to activate molecular oxygen. During the course of this work, new functional features of TaLPMO9A were discovered, in particular the ability to cleave xyloglucan, and these features were identical for both variants. Using a variety of techniques, we further found that methylation has minimal effects on the pKa of His1, the affinity for copper and the redox potential of bound copper. The two LPMOs did, however, show clear differences in their resistance against oxidative damage. Studies with added hydrogen peroxide confirmed recent claims that low concentrations of H2O2 boost LPMO activity, whereas excess H2O2 leads to LPMO inactivation. The methylated variant of TaLPMO9A, produced in Aspergillus oryzae, was more resistant to excess H2O2 and showed better process performance when using conditions that promote generation of reactive‐oxygen species. LPMOs need to protect themselves from reactive oxygen species generated in their active sites and this study shows that methylation of the fully conserved N‐terminal histidine provides such protection.
An analysis of the characteristics of road traffic injuries and a prediction of fatalities in China from 1996 to 2015

Abstract Objectives: This study analyzed the characteristics and burdens of road traffic injuries (RTIs) from the 3 perspectives of time, space, and population in China and predicted traffic fatalities using 2 models. Methods: By extracting data from the China Statistical Yearbooks and GBD 2015 (Global Health Data Exchange), we described the change in the time trend of traffic crashes and economic losses associated with the rate of motorization in China from 1996 to 2015; analyzed the geographical distribution of these events by geographic information system; and evaluated the age-, sex-, and cause-specific death rate, disability-adjusted life year (DALY) rate, years of life lost (YLL) rate, and years lost due to disability (YLD) rate lost from RTIs from 1990 to 2015. In addition, we predicted the traffic fatality (per population or vehicles) trend using the log-linear model derived from Smeed’s and Borsos’ models. Results: From 1996 to 2015, the motorization rate showed rapid growth, increasing from 0.023 to 0.188. With the growth in the motorization rate, the time trends of traffic crashes and economic losses in China changed, showing a tendency to first increase and then later decrease. The crashes and losses were closely correlated and mainly distributed in some of the economically developed provinces, including Zhejiang, Jiangsu, Anhui, Sichuan, and Guangdong provinces. The health burden of RTIs presented a time trend similar to that of the economic burden, and it was higher among males than females. The death rate among older pedestrians was higher. The DALY rate and YLL rate among young and middle-aged pedestrians were higher. The YLD rate among older motor vehicle drivers was higher. In addition, the fatalities per 10,000 vehicles continued to decline, and Borsos’s model was better fitted to the reported traffic fatalities than Smeed’s model. Conclusions: Although the burden of RTIs in China has declined, the burden of RTIs is still heavy. Hence, RTIs remain a universal problem of great public health concern in China, and we need to work hard to reduce them.
Heuristics as Mental Shortcuts in Evaluating Interactive Systems

Heuristics refer to the specific “rules-of-thumb” discovered from knowledge or experience which can simplify the complexity of making judgments. Heuristics are mental shortcuts to draw conclusions when evaluating interactive systems. In this study, a set of heuristics had been discovered by end-users while developing a series of prototypes of a test blueprint system. This study suggests that the design process of an interactive system should cater to the following two (2) components, namely: technical heuristics and specialized domain heuristics. Heuristics from these components should be the emphasis during the evaluation of the interactive system that has been designed using a user-centered paradigm of development called the Interaction Design Model (IDM).
Further evidence for the involvement of EFL1 in a Shwachman–Diamond-like syndrome and expansion of the phenotypic features

Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman–Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent.
An Action Plan to Face the Challenge of Dementia: INTERNATIONAL STATEMENT ON DEMENTIA from IAP for Health

An international committee set up through the IAP for Health met to develop an action plan for dementia. Comprehensive international and national initiatives should move forward with calls for action that include increased public awareness regarding brain health and dementia, support for a broad range of dementia research objectives, and investment in national health care systems to ensure timely competent person-centred care for individuals with dementia. The elements of such action plans should include: 1) Development of national plans including assessment of relevant lifecourse risk and protective factors; 2) Increased investments in national research programs on dementia with approximately 1% of the national annual cost of the disease invested; 3) Allocating funds to support a broad range of biomedical, clinical, and health service and systems research; 4) Institution of risk reduction strategies; 5) Building the required trained workforce (health care workers, teachers, and others) to deal with the dementia crisis; 6) Ensuring that it is possible to live well with dementia; and 7) Ensuring that all have access to prevention programs, care, and supportive living environments.
Effects of a Six-Month Multi-Ingredient Nutrition Supplement Intervention of Omega-3 Polyunsaturated Fatty Acids, vitamin D, Resveratrol, and Whey Protein on Cognitive Function in Older Adults: A Randomised, Double-Blind, Controlled Trial

ObjectivesTo investigate the impact of a six-month multi-ingredient nutrition supplement intervention (Smartfish®), containing omega-3 polyunsaturated fatty acids (PUFAs), vitamin D, resveratrol, and whey protein, on cognitive function in Irish older adults.DesignDouble-blind, randomised controlled trial (ClinicalTrials.gov: NCT02001831). A quantitative, mixedmodel design was employed in which the dependent variable (cognitive function) was analysed with a between-subjects factor of group (placebo, intervention) and within-subjects factor of testing occasion (baseline, three-months, six-months). SettingCommunity-based intervention including assessments conducted at University College Dublin, Ireland.ParticipantsThirty-seven community-dwelling older adults (68-83 years; mean (x̅)= 75.14 years; standard deviation (SD)= 3.64; 18 males) with normal cognitive function (>24 on the Mini Mental State Examination) were assigned to the placebo (n= 17) or intervention (n= 20) via a block randomisation procedure.InterventionDaily consumption for six-months of a 200mL liquid juice intervention comprising 3000mg omega-3 PUFAs [1500mg docosahexaenoic acid (DHA) and 1500mg eicosapentaenoic acid (EPA)], 10μg vitamin D3, 150mg resveratrol and 8g whey protein isolate. The placebo contained 200mL juice only.MeasurementsA standardised cognitive assessment battery was conducted at baseline and follow-ups. Individual test scores were z-transformed to generate composite scores grouped into cognitive domains: executive function, memory, attention and sensorimotor speed. Motor imagery accuracy and subjective awareness of cognitive failures variables were computed from raw scores.ResultsA hierarchical statistical approach was used to analyse the data; first, by examining overall cognitive function, then by domain, and then by individual test scores. Using mixed between-within subjects, analyses of variance (ANOVAs), no significant differences in overall cognitive function or composite cognitive domains were observed between groups over time. The only significant interaction was for Stroop Color-Word Time (p< 0.05). The intervention group demonstrated reduced task completion time at three- and six-month follow-ups, indicating enhanced performance.ConclusionThe present nutrition intervention encompassed a multi-ingredient approach targeted towards improving cognitive function, but overall had only a limited beneficial impact in the older adult sample investigated. Future investigations should seek to establish any potential clinical applications of such targeted interventions with longer durations of supplementation, or in populations with defined cognitive deficits.
Cone Vision Changes in the Enhanced S-Cone Syndrome Caused by NR2E3 Gene Mutations.

Purpose To determine the progression of cone vision loss in patients with recessive disease from NR2E3 gene mutations. Methods Patients with NR2E3 mutations (n = 37) were studied as a retrospective observational case series clinically and with chromatic static perimetry. Patients were investigated cross-sectionally, and a subset was followed longitudinally. Results Patients showed a range of visual acuities; there was no clear relationship to age. With kinetic perimetry (V4e target), a full field could be retained over many years. Other patients showed progression from a full field, with or without pericentral scotomas, to a small central island. Three patterns of S-cone function were defined, based on percentage of hypersensitive S-cone loci in the field. From occupying most of the visual field, hyperfunctioning S-cone loci could diminish in percent, remaining largely in the periphery. Normal S-cone functioning then dominates, followed by the appearance of an annular region of abnormal S-cone loci approximately 10° to 40° from the fovea. Overall, S-cone sensitivity declined 2.6 times faster than L/M-cone sensitivity. Conclusions Murine proof-of-concept studies suggest that clinical trials of patients with NR2E3 mutations may be forthcoming. Patterns of S-cone hyperfunction across the field would serve as a means to categorize patients as entry criteria or cohort selection in clinical trials. S-cone perimetry can be measured in the clinic and would be the logical efficacy monitor for therapeutic strategies. Given further understanding of the natural history of the disease, targeting the annular region of S-cone dysfunction for a focal therapy or for monitoring in a retina-wide intervention warrants consideration.
High-performance liquid chromatography/electrospray ionisation mass spectrometric characterisation of metabolites produced by Pseudovibrio sp. W64, a marine sponge derived bacterium isolated from Irish waters.

RATIONALE In recent years, metabolites produced by Pseudovibrio species have gained scientific attention due to their potent antimicrobial activity. Recently, we also have assessed the antibacterial activities of Pseudovibrio sp. W64 isolates against Staphylococcus aureus, where only the dominant tropodithietic acid (TDA) was identified. However, characterisation of other metabolites is necessary as these metabolites may also serve as potent antimicrobial agents. METHODS Liquid chromatography/tandem mass spectrometry (LC/MS/MS), aided by accurate mass measurements, was employed to screen and characterise a range of metabolites produced by Pseudovibrio sp. W64 via assessment of ethyl acetate fractions generated from bacterial cultures. RESULTS Thirteen metabolites unique to the bacterial culture were detected and their chemical structures were assigned by MS/MS and accurate mass measurements. Among the thirteen metabolites, a methyl ester of TDA, a number of cholic acid derivatives, and amino diols and triols were characterised. CONCLUSIONS Pseudovibrio sp. W64 produces methylated TDA in addition to TDA, and metabolises lipids and amino acids in the cell-culture medium. To the best of our knowledge, this is the first report of methylated TDA, cholic acid and its various analogs, and sphinganine being detected in this Pseudovibrio strain. The data generated may help to better understand the biochemical processes and metabolism of bacterial strains towards discovery of antimicrobial agents from marine sources.
Validating the targets for neurostimulation in essential tremor

Deep brain stimulation (DBS) is considered for the treatment of essential tremor (ET) that is resistant to pharmacologic treatment.1 To date, the neuroanatomic target of choice for ET is the nucleus ventralis intermedius (VIM) of the thalamus. Although VIM-DBS has shown good efficacy, side effects such as stimulation-induced ataxia or deterioration of speech may hamper therapeutic success in at least a subgroup of patients undergoing DBS. Furthermore, the effects of VIM stimulation may attenuate over time. Some studies have reported such “tolerance” in as little as 10 weeks,2 while other studies have reported more sustained benefit.3
An oxanthroquinone derivative that disrupts RAS plasma membrane localization inhibits cancer cell growth

Oncogenic RAS proteins are commonly expressed in human cancer. To be functional, RAS proteins must undergo post-translational modification and localize to the plasma membrane (PM). Therefore, compounds that prevent RAS PM targeting have potential as putative RAS inhibitors. Here we examine the mechanism of action of oxanthroquinone G01 (G01), a recently described inhibitor of KRAS PM localization. We show that G01 mislocalizes HRAS and KRAS from the PM with similar potency and disrupts the spatial organization of RAS proteins remaining on the PM. G01 also inhibited recycling of epidermal growth factor receptor and transferrin receptor, but did not impair internalization of cholera toxin, indicating suppression of recycling endosome function. In searching for the mechanism of impaired endosomal recycling we observed that G01 also enhanced cellular sphingomyelin (SM) and ceramide levels and disrupted the localization of several lipid and cholesterol reporters, suggesting that the G01 molecular target may involve SM metabolism. Indeed, G01 exhibited potent synergy with other compounds that target SM metabolism in KRAS localization assays. Furthermore, G01 significantly abrogated RAS-RAF-MAPK signaling in Madin-Darby canine kidney (MDCK) cells expressing constitutively activated, oncogenic mutant RASG12V. G01 also inhibited the proliferation of RAS-less mouse embryo fibroblasts expressing oncogenic mutant KRASG12V or KRASG12D but not RAS-less mouse embryo fibroblasts expressing oncogenic mutant BRAFV600E. Consistent with these effects, G01 selectively inhibited the proliferation of KRAS-transformed pancreatic, colon, and endometrial cancer cells. Taken together, these results suggest that G01 should undergo further evaluation as a potential anti-RAS therapeutic.
Characterization and Dynamic Shift of Microbial Communities during Start-Up, Overloading and Steady-State in an Anaerobic Membrane Bioreactor

A lab-scale anaerobic membrane bioreactor (AnMBR) with a side stream tubular membrane was developed to treat synthetic domestic sewage to evaluate its performance and the dynamic shift of bacterial and archaeal communities during the start-up, steady-state, overloading and recovery periods of operation at mesophilic temperatures. During the start-up period, the bacterial and archaeal communities changed drastically, and Proteobacteria and Bacteroidetes predominated. During the steady-state period, the AnMBR exhibited excellent COD removal above 91%, and COD of the effluent was below 50 mg/L. High-throughput sequencing analysis results revealed that bacterial and archaeal communities shifted significantly from the start-up to the steady-state period, and that the Proteobacteria phylum predominated on days 140, 162 and 190, and the archaea community hydrogenotrophic methanogen genus Methanolinea (1.5–6.64%) predominated over the aceticlastic methanogen genus Methanothrix (1.35–3.07%). During the overloading period, significant changes occurred in microbial community on day 210, e.g., the phyla Bacteroidetes (30%), Proteobacteria (23%) and Firmicutes (18%) predominated and the archaeal community was completely suppressed, and Methanobrevibacter (0.7%) was the only methanogen genus that emerged in the overloading period. After a shock loading period, the microbial communities exhibited significant changes within the ranks of methanogens and shifted to dominance of the aceticlastic methanogen pathway. In addition, the TVFAs to alkalinity ratio in this study was suitable as an indicator of monitoring performance in the AnMBR operation.
A quantized approach for occupancy grids for autonomous vehicles: Q-Trees

ABSTRACT Map Representation of the Real World is an essential step in robotics for using the mathematical methods in an abstract way. In addition to grid-based and topological studies on this area, this paper uses both approaches representing the environment with independent graph trees for all axes. We are proposing a methodology that allows us to substitute point clouds on grids in an efficient way and can be easily adapted to multi-system approaches even in real time with low-level computational systems. GRAPHICAL ABSTRACT
Behavioral remodeling of normal and cancerous epithelial cell lines with differing invasion potential induced by substrate elastic modulus

ABSTRACT The micro-environment of cancer cells in the body is mechanically stiffer than that of normal cells. We cultured three breast cell lines of MCF10A-normal, MCF7-noninvasive, and MDA-MB-231-invasive on PDMS substrates with different elastic moduli and different cellular features were examined.Effects of substrate stiffness on cell behavior were evident among all cell lines. Cancerous cells were more sensitive to substrate stiffness for cell behaviors related to cell motility and migration which are necessary for invasion. The invasive cancerous cells were the most motile on substrates with moderate stiffness followed by non-invasive cancerous cells. Gene markers alterations were generally according to the analyzed cell movement parameters. Results suggest that alterations in matrix stiffness may be related to cancer disease and progression.
Protective Effects of a Lipid Extract from Hard-Shelled Mussel (Mytilus coruscus) on Intestinal Integrity after Lipopolysaccharide Challenge in Mice

This study investigated the protective effects of a lipid extract from hard-shelled mussel (HMLE) on intestinal integrity and the underlying mechanisms after a lipopolysaccharide (LPS) challenge in mice by using a 3 × 2 factorial design. Mice received olive oil, fish oil, and HMLE (n = 12 per group) by using gastric gavage for six weeks, respectively. Then half the mice in each group was injected intraperitoneally with LPS and the other half with phosphate buffered saline. Four hours after injection, mice were sacrificed and samples were collected. n-3 PUFAs were significantly enriched in erythrocytes following fish oil and HMLE supplementation. Both fish oil and HMLE improved intestinal morphology by restoring the ileac villus height and barrier function, which is indicated by decreased colonic myeloperoxidase activity and increased diamine oxidase activity as well as enhanced mRNA expression of intestinal tight junction proteins known as occludin and claudin-1 when compared with olive oil. In addition, both fish oil and HMLE increased colon production and the expression of anti-inflammatory cytokine, IL-10, while they inhibited the abnormal production and expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 relative to the olive oil. Lastly, in comparison with olive oil, both fish oil and HMLE downregulated the TLR-4 signaling pathway by reducing the expression of two key molecules in this pathway, which are called TLR-4 and MyD88. These results suggest that HMLE had a protective effect on intestinal integrity after the LPS challenge, which was equivalent to that of fish oil. This effect might be associated with the regulation of inflammatory mediators and the inhibition of the TLR-4 signaling pathway.
Computerized nursing process: development of a mobile technology for use with neonates.

OBJECTIVE to build a mobile technology to assist nurses during data collection, diagnostic reasoning, and identification of interventions in neonates. METHOD methodological study with a qualitative approach. The development was carried out in three phases, namely: bibliographical survey, construction of a database of diagnosis/interventions, and development of the software. We used the development tools Ruby on Rails, IONIC 2, PostgresSQL, and Amazon EC2. RESULTS The developed technology received the name Natus, able to contribute to the development of the nursing process applied to patients of neonatal units. Its requirements are: to define human needs, select nursing diagnoses, select interventions, define time periods, and issue printed files. FINAL CONSIDERATIONS the technology built is a computerized tool that allows for the development of the nursing process, facilitating data collection, diagnostic reasoning, and identification and grouping of the clinical signs presented by the newborn in neonatal units.