Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis, Regulation and Degradation of Carotenoids Under Low Level UV-B Radiation in the Filamentous Cyanobacterium Chlorogloeopsis fritschii PCC 6912

Carotenoids in cyanobacteria play an important role in protecting against and in repairing damage against low level UV-B radiation. Here we use transcriptomics and metabolomic HPLC pigment analysis to compare carotenoid pathway regulation in the filamentous cyanobacterium Chlorogloeopsis fritschii PCC 6912 exposed to white light and to white light supplemented with low level UV-B. Under UV-B changes in carotenoid transcription regulation were found associated with carotenogenesis (carotenoid synthesis), photoprotection and carotenoid cleavage. Transcriptional regulation was reflected in corresponding pigment signatures. All carotenogenesis pathway genes from geranylgeranyl-diphosphate to lycopene were upregulated. There were significant increases in expression of gene homologs (crtW, crtR, cruF, and cruG) associated with routes to ketolation to produce significant increases in echinenone and canthaxanthin concentrations. There were gene homologs for four β-carotene-ketolases (crtO and crtW) present but only one crtW was upregulated. Putative genes encoding enzymes (CruF, CrtR, and CruG) for the conversion of γ-carotene to myxol 2′-methylpentoside were upregulated. The hydroxylation pathway to nostaxanthin via zeaxanthin and caloxanthin (gene homologs for CrtR and CrtG) were not upregulated, reflected in the unchanged corresponding pigment concentrations in zeaxanthin, caloxanthin and nostaxanthin, Transcripts for the non-photochemical quenching related Orange-Carotenoid-Protein (OCP) and associated Fluoresence-Recovery-Protein (FRP) associated with photoprotection were upregulated, and one carotenoid binding Helical-Carotenoid-Protein (HCP) gene homolog was downregulated. Multiple copies of genes encoding putative apocarotenoid related carotenoid oxygenases responsible for carotenoid cleavage were identified, including an upregulated apo-β-carotenal-oxygenase gene homologous to a retinal producing enzyme. Our study provides holistic insight into the photoregulatory processes that modulate the synthesis, photoprotection and cleavage of carotenoids in cyanobacterial cells exposed to low level UV-B. This is important to understanding how regulation of metabolism responds to a changing environment and how metabolism can be modulated for biotechnological purposes.
Effect of Underwater Treadmill Gait Training With Water-Jet Resistance on Balance and Gait Ability in Patients With Chronic Stroke: A Randomized Controlled Pilot Trial

Objective: The purpose of this study was to determine the effects of underwater treadmill gait training with water-jet resistance and underwater treadmill gait training with ankle weights on balance and gait abilities in chronic stroke patients. Methods: Twenty-two inpatients and outpatients with stroke-induced impairments were randomly assigned into two groups: an underwater treadmill gait training with water-jet resistance group (n = 11) and an underwater treadmill gait training with ankle weights group (n = 11). Participants received conventional physical therapy for 30 min and underwater treadmill gait training with water-jet resistance or ankle weights for 30 min. Intervention was performed 5 days a week for 4 weeks. The Balance System SD was used to assess static and dynamic balance. The GAITRite system was used to assess gait velocity, cadence, step length, stride length, and swing phase. All measurements were performed at the beginning of the study and 4 weeks after the intervention. Results: The water-jet resistance group and ankle weights group showed significant improvement in static balance (P < 0.00 vs. P = 0.01), dynamic balance (P < 0.00 vs. P = 0.57), gait velocity (P < 0.00 vs. P = 0.037), cadence (P < 0.00 vs. P = 0.001), step length (P < 0.00 vs. P = 0.003), stride length (P < 0.00 vs. P = 0.023), and swing phase (P < 0.00 vs. P < 0.00). However, the static and dynamic balance ability score (P < 0.00), gait velocity (P < 0.00), cadence (P < 0.00), step length (P < 0.00), stride length (P < 0.00), and swing phase (P = 0.023) in the group that received underwater treadmill gait training with water-jet resistance improved more than in the group that received underwater treadmill gait training with ankle weights. Conclusions: Our results demonstrated that underwater treadmill gait training with water-jet resistance is effective in improving static and dynamic balance as well as gait abilities in chronic stroke patients. Thus, training using underwater treadmill gait training with water-jet resistance may be useful in facilitating active rehabilitation in chronic stroke patients.
Solution of Levinthal’s Paradox and a Physical Theory of Protein Folding Times

“How do proteins fold? ” Researchers have been studying different aspects of this question for more than 50 years. The most conceptual aspect of the problem is how protein can find the global free energy minimum in a biologically reasonable time, without exhaustive enumeration of all possible conformations, the so-called “Levinthal’s paradox. ” Less conceptual but still critical are aspects about factors defining folding times of particular proteins and about perspectives of machine learning for their prediction. We will discuss in this review the key ideas and discoveries leading to the current understanding of folding kinetics, including the solution of Levinthal’s paradox, as well as the current state of the art in the prediction of protein folding times.
The status of tobacco control in the Eastern Mediterranean Region: progress in the implementation of the MPOWER measures.

Background The World Health Organization (WHO) MPOWER measures are a set of highly effective tobacco control measures drawn from the WHO Framework Convention on Tobacco Control (FCTC), designed to help countries reduce the prevalence of tobacco use. The WHO Report on the Global Tobacco Epidemic is published biennially to monitor global implementation of these measures. Aims This review aimed to critically assess the status of MPOWER implementation in the Eastern Mediterranean Region. Methods Data were collected for WHO Reports on the Global Tobacco Epidemic, focusing on the most recent 2019 edition. Regional population coverage figures were calculated using this data and population figures for the countries of the Region. Results Between 2007 and 2018, for any MPOWER measure, there were 29 cases of countries progressing to the highest level of achievement; 23 cases of countries progressing to the intermediate levels from the lowest level; 12 cases of countries falling from the highest level; and 18 cases of countries falling to the lowest level. 57.7% of people are covered at the highest level for the monitoring measure; 63.7% for the smoke-free policies measure; 6.7% for the cessation measure; 60.7% for the health warnings measure; 37.4% for the mass media measure; 29.4% for the advertising bans measure; and 16.1% for the taxation measure. Conclusions Countries must work comprehensively to improve tobacco control. Regional priorities should include lifting more people out of lowest level coverage for the health warnings and mass media measures, increasing taxation on tobacco products and improving access to cessation services.
Primary resistance to osimertinib despite acquired T790M

Current National Comprehensive Cancer Network (NCCN) guidelines suggest plasma‐based testing (liquid biopsy) for T790M in epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung carcinoma (NSCLC) with acquired resistance to first‐/second‐generation EGFR tyrosine kinase inhibitors (TKIs). Positivity for resistant mutation on liquid biopsy may obviate the need for invasive tissue biopsy. We report a rare case of primary resistance to osimertinib, although liquid biopsy revealed EGFR T790M positivity. A 63‐year‐old male, never smoker, was diagnosed with stage IV lung adenocarcinoma with EGFR exon 19 deletion. Treatment started with erlotinib and was continued for 15 months until disease progression. Osimertinib was initiated when liquid biopsy showed EGFR T790M positivity. However, primary resistance to osimertinib was noted on follow‐up imaging. Re‐biopsy revealed small cell lung cancer. Detection of T790M via liquid biopsy among NSCLC patients with acquired resistance to EGFR‐TKI might miss other possible resistant mechanisms. Tissue biopsy should be considered to exclude small cell lung carcinoma (SCLC) transformation.
Simultaneous extraction and purification of fucoxanthin from Tisochrysis lutea microalgae using compressed fluids.

The marine microalga Tisochrysis lutea, a Haptophyta with a thin cell wall and currently used mainly in aquaculture is a potential source of several bioactive compounds of interest such as carotenoids. In the present study, the simultaneous extraction and purification of fucoxanthin, the main carotenoid from T. lutea, was optimized using pressurized fluid extraction followed by in-cell purification. An experimental design was employed to maximize carotenoids' extraction; the experimental factors chosen were: (i) percentage of ethanol/ethyl acetate (0 - 100 %), (ii) temperature (40 - 150 °C) and (iii) number of static extraction cycles (1 - 3). The maximum carotenoids' recovery, mainly fucoxanthin, was obtained with pure ethyl acetate at 40 °C using one extraction cycle, achieving values of 132.8 mg of carotenoids per g of extract. Once the optimum extraction conditions were confirmed, in-cell purification strategies using different adsorbents were developed to obtain fucoxanthin-enriched extracts. Activated charcoal showed potential retention of chlorophylls allowing an effective purification of fucoxanthin in the obtained extracts. Chemical characterization of extracts was carried out by reversed-phase high-performance liquid chromatography with diode array detection. Therefore, a selective fractionation of high value compounds was achieved using the proposed green downstream platform based on the use of compressed fluids. This article is protected by copyright. All rights reserved.
Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte

Zusammenfassung Das primäre Offenwinkelglaukom (POWG) wird derzeit als eine neurodegenerative Systemerkrankung angesehen. Die alleinige individualisierte Augeninnendrucksenkung wird dabei dem komplexen Geschehen im chronischen Verlauf der Erkrankung nicht gerecht werden, sodass begleitende medikamentöse Therapiekonzepte sinnvoll sind. Anhand von 4 Therapiestrategien, wie die Verbesserung der mitochondrialen Atmungskette mit Coenzym Q10, die Stabilisierung der mitochondrialen und zellulären Plasmamembranen mit Citicolin, die Verminderung des oxidativen Stresses am Auge und im Körper mit Curcumin und die Verbesserung des Fettstoffwechsels, speziell des LDL-Cholesterins, mit der Anwendung der Statine, soll ein Einblick in mögliche additive Therapieansätze gegeben werden. Da neuroprotektive Therapien als Monotherapien wenig erfolgversprechend sein dürften, werden sie eher in der Kombination aus verschiedenen Therapieansätzen bestehen.
Phylogenetic and pathotype analysis of Escherichia coli stool isolates from Egyptian patients with inflammatory bowel disease.

Introduction The role of Escherichia coli in the pathogenesis of inflammatory bowel disease (IBD) is still controversial. The study aimed to investigate the pathotypes and the phylogenetic groups of E. coli in Egyptian patients with IBD in an attempt to find an association between any type or group with the severity of the disease. Methods Thirty ulcerative colitis (UC), 30 Crohn's disease (CD), and 20 control subjects with normal colonoscopy were included in a cross-sectional study. E. coli were isolated from stool samples by culture. Eight intestinal virulence genes coding for diarrheagenic E. coli were investigated using multiplex PCR. Phylogenetic grouping was performed by a triplex PCR. Antimicrobial susceptibility of all isolates was done using disc diffusion method. Results Enteroaggregative E. coli (EAEC) were identified in 25% (15/60) of IBD cases and in none of the controls (p=0.013). Out the 60 IBD cases, 30 (50%) were from phylogenetic group B2. No statistically significant differences in the distribution of E. coli phylogenetic groups were found between study groups. However, 80% of EAEC were assigned to group B2 and D. No statistically significant differences in calprotectin level or in disease severity scores were reported between the four phylogenetic groups. E. coli from both UC and CD patients showed a high rate of resistance to most antimicrobials when compared to the control group. Conclusions The identification of EAEC belonging mainly to group B2 and D in IBD cases may indicate the importance of this pathotype in the pathogenesis of IBD in Egyptian patients.
Influence of Cryptotanshinone on Memory and Antioxidation Ability in APP/PS1 Double Transgenic Mice

OBJECTIVE To study the effect of cryptotanshinone on memory and antioxidation ability in APP/PS1 double transgenic mice.METHODS Three-month-old APP/PS1 double transgenic mice were randomly divided into 5 gorups.Besides,negative control mice were served as control group.There were 10 mice in each group and all of them were intragastrically administered for 4 months.Then the learning and memory ability of mice were detected by Morris water maze test.The activities of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in serum and brain tissue were measured with spectrophotometer.RESULTS Compared with control group,APP/PS1 double transgenic mice significantly prolonged the latency of searching the hidden platform in directional swimming test,decreased the time spent in swimming in the target quadrant in probe test.Compared with APP/PS1 double transgenic mice,cryptotanshinone could dose-dependently shorten the latency of searching the hidden platform in directional swimming test,increased the time spent in swimming in the target quadrant in probe test.The activities of GSH-Px and SOD decreased and the MDA content increased in APP/PS1 double transgenic mice,while in cryptotanshinone treatment groups,the activities of GSH-Px and SOD heightened and MDA content decreased,and there was significant difference compared with Alzheimer's disease model group.CONCLUSION Seven-month-old APP/PS1 double transgenic mice became imitated learning and memory dysfunction and the antioxidation ability reduction;cryptotanshinone could dose-dependently ameliorate the impaired learning and memory function of Alzheimer's disease mice and improve antioxidation ability.
Unilateral phacoemulsification in a captive African elephant (Loxodonta africana)

Background: The following case reports describe the clinical presentation, surgical protocol, post-operative care, and long-term follow-up of an African elephant (Loxodonta Africana) presenting with a unilateral cataract. Case description: A 42-year-old female African elephant presented for the assessment of ocular discomfort and visual deterioration in the left eye. Pre-surgical treatment included topical anti-inflammatory medication for 20 days prior to surgery. On the day of surgery, following anesthetic induction, a two-handed phacoemulsification technique was performed in the left eye. She was left aphakic post-operatively. Nine days post-operatively, the patient had an intact menace response, dazzle reflex, and direct pupillary light reflex. Fundoscopy at that stage was unremarkable. Follow-up information was available for 5 years, from the time of surgery to the present day. Conclusion: Despite remaining aphakic, this case presents a successful visual outcome. To the best of the authors’ knowledge, there is no other published report of phacoemulsification in a captive elephant.
The evolution of protein domain repertoires: Shedding light on the origins of the Herpesviridae family

Abstract Herpesviruses (HVs, Family: Herpesviridae) have large genomes that encode hundreds of proteins. Apart from amino acid mutations, protein domain acquisitions, duplications and losses are also common modes of evolution. HV domain repertoires differ across species, and only a core set is shared among all species, aspect that raises a question: How have HV domain repertoires diverged while keeping some similarities? To answer such question, we used profile Hidden Markov Models (HMMs) to search for domains in all possible translated open reading frames (ORFs) of fully sequenced HV genomes. With at least 274 domains being identified, we built a matrix of domain counts per species, and applied a parsimony method to reconstruct the ancestral states of these domains along the HV phylogeny. It revealed events of domain gain, duplication, and loss over more than 400 millions of years, where Alpha-, Beta-, and GammaHVs expanded and condensed their domain repertoires at distinct rates. Most of the acquired domains perform ‘Modulation and Control’, ‘Envelope’, or ‘Auxiliary’ functions, categories that showed high flexibility (number of domains) and redundancy (number of copies). Conversely, few gains and duplications were observed for domains involved in ‘Capsid assembly and structure’, and ‘DNA Replication, recombination and metabolism’. Among the forty-one primordial domains encoded by Herpesviridae ancestors, twenty-eight are still found in all present-day HVs. Because of their distinct evolutionary strategies, HV domain repertoires are very specific at the subfamily, genus and species levels. Differences in domain composition may not only explain HV host range and tissue tropism, but also provide hints to the origins of HVs.
How different rearing temperatures affect growth and stress status of Siberian sturgeon Acipenser baerii larvae.

Environmental temperature is one of the critical factors affecting fish development. The aim of this study was to examine the impact of three different rearing temperatures (16°C, 19°C and 22°C) throughout the endogenous feeding phase of the Siberian sturgeon Acipenser baerii. This was performed by assessing i) larval survival and growth, ii) immunofluorescence localization and expression of genes involved in muscle development and growth - myog and Igf1, and iii) stress status through the expression of thermal stress genes - Hsp70, Hsp90α and Hsp90β - and whole body cortisol. Overall survival rate and larval weight did not differ significantly across temperatures. Larvae subjected to 22°C showed faster absorption of the yolk-sac than larvae subjected to 19°C or 16°C. Both at schooling and at the end of the trial, larvae reared at 16°C showed significantly lower levels of cortisol than those reared at 19°C or 22°C. IGF-1 immunopositivity was particularly evident in red muscle at schooling stage in all temperatures. The expression of all Hsps as well as the myog and Igf1 genes was statistically higher in larvae reared at 16°C but limited to the schooling stage. Cortisol levels were higher in larvae at 22°C, probably because of the higher metabolism demand rather than a stress response. The observed apparent incongruity between Hsps gene expression and cortisol levels could be due to the lack of a mature system. Further studies are necessary, especially regarding the exogenous feeding phase, in order to better understand if this species is actually sensitive to thermal stress. This article is protected by copyright. All rights reserved.
Neuropsychological and neurophysiological aspects of brain‐computer‐interface (BCI) control in paralysis

Brain‐computer interfaces (BCIs) aim to help paralysed patients to interact with their environment by controlling external devices using brain activity, thereby bypassing the dysfunctional motor system. Some neuronal disorders, such as amyotrophic lateral sclerosis (ALS), severely impair the communication capacity of patients. Several invasive and non‐invasive brain‐computer interfaces (BCIs), most notably using electroencephalography (EEG), have been developed to provide a means of communication to paralysed patients. However, except for a few reports, all available BCI literature for the paralysed (mostly ALS patients) describes patients with intact eye movement control, i.e. patients in a locked‐in state (LIS) but not a completely locked‐in state (CLIS). In this article we will discuss: (1) the fundamental neuropsychological learning factors and neurophysiological factors determining BCI performance in clinical applications; (2) the difference between LIS and CLIS; (3) recent development in BCIs for communication with patients in the completely locked‐in state; (4) the effect of BCI‐based communication on emotional well‐being and quality of life; and (5) the outlook and the methodology needed to provide a means of communication for patients who have none. Thus, we present an overview of available studies and recent results and try to anticipate future developments which may open new doors for BCI communication with the completely paralysed.
Parotid sparing in RapidPlan Oropharynx models: To split or not to split

Differences in knowledge and experience, patient anatomy and tumour location and manipulation of inverse planning objectives and priorities will lead to a variability in the quality of radiation planning. The aim of this study was to investigate whether parotid glands should be treated as separate or combined structures when using knowledge‐based planning (KBP) to create oropharyngeal plans, based on the dose they receive.
Postural control of arm and fingers through integration of movement commands

Every movement ends in a period of stillness. Current models assume that commands that hold the limb at a target location do not depend on the commands that moved the limb to that location. Here, we report a surprising relationship between movement and posture in primates: on a within-trial basis, the commands that hold the arm and finger at a target location depend on the mathematical integration of the commands that moved the limb to that location. Following damage to the corticospinal tract, both the move and hold period commands become more variable. However, the hold period commands retain their dependence on the integral of the move period commands. Thus, our data suggest that the postural controller possesses a feedforward module that uses move commands to calculate a component of hold commands. This computation may arise within an unknown subcortical system that integrates cortical commands to stabilize limb posture.
Downregulated long non-coding RNA LINC01093 in liver fibrosis promotes hepatocyte apoptosis via increasing ubiquitination of SIRT1.

The apoptosis of hepatocytes contributes to the activation of hepatic stellate cells (HSCs), thus promoting the accumulation of extracellular matrix proteins and aggravating liver fibrosis. SIRT1 is an anti-fibrotic protein whose downregulation induces hepatocyte apoptosis. This study aims to identify whether SIRT1 is regulated by long non-coding RNA LINC01093 and explore its underlying mechanisms. Liver fibrosis was induced in mice using CCl4, and the differential expressions of several fibrosis-related lncRNAs were detected in liver tissues. The effect of LINC01093 on cell apoptosis and viability of hepatocytes was investigated after LINC01093 overexpression or knockdown using flow cytometry and MTT assay. The anti-fibrotic effect of LINC01093 overexpression was observed in vivo. LncRNA LINC01093 is downregulated in CCl4-induced liver tissues and TGF-β1-stimulated hepatocytes. Downregulated LINC01093 promoted cell apoptosis and inhibited cell viability of hepatocytes. The co-culture between LINC01093-knockdown hepatocytes and HSCs increased the expressions of pro-fibrotic proteins. Downregulated LINC01093 promoted hepatocyte apoptosis via promoting degradation and ubiquitination of SIRT1 under TGF-β1 stimulation. The injection of LINC01093-overexpressing vectors alleviated liver fibrosis in vivo. In liver fibrosis, the downregulated LINC01093 promoted hepatocyte apoptosis, which is mediated by increasing the degradation and ubiquitination of SIRT1.