Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional and Evolutionary Relationship between Arginine Biosynthesis and Prokaryotic Lysine Biosynthesis through α-Aminoadipate

ABSTRACT Our previous studies revealed that lysine is synthesized through α-aminoadipate in an extremely thermophilic bacterium, Thermus thermophilus HB27. Sequence analysis of a gene cluster involved in the lysine biosynthesis of this microorganism suggested that the conversion from α-aminoadipate to lysine proceeds in a way similar to that of arginine biosynthesis. In the present study, we cloned anargD homolog of T. thermophilus HB27 which was not included in the previously cloned lysine biosynthetic gene cluster and determined the nucleotide sequence. A knockout of theargD-like gene, now termed lysJ, inT. thermophilus HB27 showed that this gene is essential for lysine biosynthesis in this bacterium. The lysJ gene was cloned into a plasmid and overexpressed in Escherichia coli, and the LysJ protein was purified to homogeneity. When the catalytic activity of LysJ was analyzed in a reverse reaction in the putative pathway, LysJ was found to transfer the ɛ-amino group ofN2-acetyllysine, a putative intermediate in lysine biosynthesis, to 2-oxoglutarate. WhenN2-acetylornithine, a substrate for arginine biosynthesis, was used as the substrate for the reaction, LysJ transferred the δ-amino group ofN2-acetylornithine to 2-oxoglutarate 16 times more efficiently than whenN2-acetyllysine was the amino donor. All these results suggest that lysine biosynthesis in T. thermophilus HB27 is functionally and evolutionarily related to arginine biosynthesis.
Impact of Post-Surgical Therapies on Endoscopic and External Dacryocystorhinostomy: Systematic Review and Meta-Analysis

Background Epiphora is a common ophthalmologic sign that is most commonly caused by distal acquired lacrimal obstruction. Recent data have demonstrated that external dacryocystorhinostomy (EXT-DCR) and endoscopic endonasal dacryocystorhinostomy (END-DCR) can be considered the treatments of choice. However, different post-surgical medical therapies are available and are currently used to improve surgical outcomes, although no direct comparison has been performed. Objective To analyse the influence of post-surgical medical treatments on END-DCR and EXT-DCR outcomes. Methods A structured search was conducted using the U.S. National Library of Medicine (PubMed), EMBASE, SCOPUS, and Cochrane databases with a final search performed in May 2020. The research identified papers published later than 2000 with at least 50 single clinician procedures performed in EXT-DCR and END-DCR. Articles that studied acute infections, revision cases, mixed cohort studies of acquired and congenital obstruction, and tumour were excluded. The influence of systemic antibiotic/steroids, local application of mitomycin C, nasal/ocular antibiotic, nasal/ocular steroids and nasal decongestants was analysed. Results In total, 11,445 papers were selected, 2,741 of which were reviewed after screening, and 18 included after full text review (0.6% of the initial articles reviewed) which involved 3,590 procedures. Considering the low number of publications on EXT-DCR, statistical analysis of post-surgical therapy was not feasible. In END-DCR, the analyses were performed only for nasal steroids (p = 0.58), oral antibiotics (p = 0.45) and nasal decongestant (p = 0.27), which demonstrated no meaningful influence. Given the variable association between adjunctive medical therapies, pharmacologic molecular heterogeneity and modality/concentration of application, these results should be considered critically. Additionally, no differences were seen for application of silicone stenting, whereas, no statistical analysis was performed for mitomycin C. Conclusions Given the high success rate of EXT-DCR and END-DCR and the heterogeneity of literature data, the effective influence of post-surgical medical therapy is difficult to identify. Future large prospective randomized studies could help in detecting the optimal adjunctive therapy for these surgeries.
Diagnostic value of rapid on-site evaluation in interventional pulmonology

Abstract Background: Rapid on-site evaluation (ROSE) is a kind of rapid evaluation of specimen satisfaction, preliminary diagnosis and priority strategy, the diagnostic accuracy of ROSE in the field of pulmonary intervention shows wide variation. The aim of the study was to further clarify the accuracy and diagnostic efficacy of ROSE in interventional pulmonology. Methods: This review summarizes and meta-analyzes studies of ROSE in interventional pulmonology, the ROSE diagnoses would be compared with the final pathologic diagnoses. The following electronic databases have been searched: PubMed, Cochrane Library, Embase, Web of science, CNKI, and WANFANG DATA. The methodologic quality of studies has been assessed using the Quality of Diagnostic Studies (QUADAS-2) instrument. This review is conducted using standard methods for systematic reviews of diagnostic accuracy studies. STATA SE 12.0 is used for data synthesis and analysis. Results: This review evaluates the accuracy and diagnostic efficacy of ROSE in interventional pulmonology, and the process factors that may influence the ROSE diagnosis are analyzed, such as Smear method, profession of smear technician, staining method, Profession of stain technician, Profession of reading slides, invasive procedure, Anesthesia method and etc. Conclusion: This review will stimulate proper evaluation of ROSE and provide assistance for clinical practice.
Seasonal Variation in Assimilated Diets of American Beavers

Abstract American beavers (Castor canadensis) forage on various aquatic and terrestrial plant species. We used stable isotope analysis of carbon (C) and nitrogen (N) to estimate source contributions of seasonal assimilated beaver diets in Voyageurs National Park, Minnesota, from Apr. 2007 to Nov. 2008. Mean (±95% confidence interval) annual beaver diets were estimated as 45.5 ± 11.4% terrestrial and 55.5% aquatic vegetation (22.0 ± 14.5 emergent and 33.5 ± 7.9 floating leaf). Percentages of floating leaf and terrestrial vegetation were similar between winter and summer assimilated diets, but emergent vegetation increased 45% in summer. Although &dgr;15N was 7% greater in summer, &dgr;15N and &dgr;13C were similar by age class and sex, as were assimilated percentages of emergent, floating leaf or terrestrial vegetation. Variation in total assimilated aquatic vegetation did not affect subadult and adult seasonal changes in body mass, tail thickness or tail area, but kit body condition was negatively related to total assimilated aquatic vegetation. Aquatic vegetation accounted for more assimilated diet during winter than previously reported.
Activation of PGK1 under hypoxic conditions promotes glycolysis and increases stem cell-like properties and the epithelial-mesenchymal transition in oral squamous cell carcinoma cells via the AKT signalling pathway

Although it has been previously documented that a hypoxic environment can promote glycolysis and the malignant progression of oral squamous cell carcinoma (OSCC) cells, the specific underlying mechanism remains unclear. Phosphoglycerate kinase 1 (PGK1) has been previously reported to serve an important role in tumor metabolism. The aim of the present study was to investigate the effects of hypoxia and PGK1 on glycolysis, stem cell-like properties and epithelial-mesenchymal transition (EMT) in OSCC cells. Cell Counting Kit-8 assays were performed to examine tumor cell viability under hypoxic conditions. Sphere formation, immunohistochemistry, western blotting, Transwell assays and mouse xenograft studies were performed to assess the biological effects of PGK1. Under hypoxic conditions, phosphoglycerate PGK1 expression was found to be upregulated, which resulted in the potentiation of stem cell-like properties and enhancement of EMT. However, PGK1 knockdown reversed hypoxia-mediated glycolysis, stem cell-like properties, EMT in addition to inhibiting OSCC cell invasion and migration. PGK1 knockdown also inhibited tumour growth, whilst the overexpression of PGK1 was demonstrated to promote tumour growth in mouse xenograft models in vivo. Downstream, activation of the AKT signalling pathway reversed the series of changes induced by PGK1 knockdown. PGK1 expression was found to be upregulated in human OSCC tissues, which was associated with the pathological differentiation of tumours and lymph node metastasis. To conclude, results from the present study demonstrate that hypoxia can increase PGK1 expression, resulting in the promotion of glycolysis, enhancing stem cell-like properties and EMT by activating AKT signalling in OSCC.
Phylogenetic analysis of the Enenterinae (Digenea, Lepocreadiidae) and discussion of the evolution of the digenean fauna of kyphosid fishes

Species allocated to the digenean genera Enenterum Linton, 1910 ; Jeancadenatia Dollfus, 1946 ; Cadenatella Dollfus, 1946 ; and Koseiria form a clade within the Lepocreadiidae whose sister group is a clade comprising Neoallolepidapedon Yamaguti, 1965, Callogonotrema, Oshmarin, 1965, Allolepidapedon Yamaguti, 1940, and Bulbocirrus Oshmarin, 1965. Phylogenetic analysis of the Enenterinae based on comparative morphology, produced one most parsimonious tree with a consistency index of 0.72. Cadenatella is paraphyletic. Only 15.3% of character changes are evolutionary losses, supporting earlier reports that parasitic platyhelminths have experienced little secondary simplification during their evolutionary history. The Enenterinae appears to have originated in the Pacific Ocean, becoming associated with kyphosid fishes as a result of an ancient host switch. Subsequent evolutionary diversification reflects widespread geographical dispersal, consistent with the natural history of kyphosids.
The crystal structures of a chloride-pumping microbial rhodopsin and its proton-pumping mutant illuminate proton transfer determinants

Microbial rhodopsins are versatile and ubiquitous retinal-binding proteins that function as light-driven ion pumps, light-gated ion channels, and photosensors, with potential utility as optogenetic tools for altering membrane potential in target cells. Insights from crystal structures have been central for understanding proton, sodium, and chloride transport mechanisms of microbial rhodopsins. Two of three known groups of anion pumps, the archaeal halorhodopsins (HRs) and bacterial chloride-pumping rhodopsins, have been structurally characterized. Here we report the structure of a representative of a recently discovered third group consisting of cyanobacterial chloride and sulfate ion-pumping rhodopsins, the Mastigocladopsis repens rhodopsin (MastR). Chloride-pumping MastR contains in its ion transport pathway a unique Thr-Ser-Asp (TSD) motif, which is involved in the binding of a chloride ion. The structure reveals that the chloride-binding mode is more similar to HRs than chloride-pumping rhodopsins, but the overall structure most closely resembles bacteriorhodopsin (BR), an archaeal proton pump. The MastR structure shows a trimer arrangement reminiscent of BR-like proton pumps and shows features at the extracellular side more similar to BR than the other chloride pumps. We further solved the structure of the MastR-T74D mutant, which contains a single amino acid replacement in the TSD motif. We provide insights into why this point mutation can convert the MastR chloride pump into a proton pump but cannot in HRs. Our study points at the importance of precise coordination and exact location of the water molecule in the active center of proton pumps, which serves as a bridge for the key proton transfer.
Simulation-based training and assessment of mobile pre-hospital SARS-CoV-2 diagnostic teams in Styria, Austria

Supplemental Digital Content is available in the text Abstract The World Health Organization has declared coronavirus disease 2019 (COVID-19) a pandemic. Polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the diagnostic gold standard of COVID-19. We have developed a simulation-based training program for mobile prehospital diagnostic teams in the province of Styria, Austria, and performed a prospective observational study on its applicability and effectivity. The 1-day curriculum uses theoretical instruction, technical skills training, and simulator-based algorithm training to teach and train prehospital patient identification and communication, donning the personal protective equipment, collection of naso-/oropharyngeal swabs for SARS-CoV-2 polymerase chain reaction testing, doffing the personal protective equipment, and sample logistics. Trainings were conducted at the SIM CAMPUS simulation hospital, Eisenerz, using high-fidelity patient simulation. To ensure achievement of predefined learning outcomes, participants had to undergo a final simulator-based objective structured clinical examination. In March 2020, 45 emergency medical assistants and 1 physician of the Austrian Red Cross participated on a voluntary basis. Forty-five of the 46 participants (97.8%) completed the curriculum successfully, with mean objective structured clinical examination ratings of 98.6%. Using several proven educational concepts, we have successfully drafted and implemented a training program for mobile prehospital SARS-CoV-2 diagnostic teams. Based on simulation-based objective structured examinations, it has prepared participants effectively for preclinical duties.
Swallowing-related quality of life among oral-feeding Chinese patients with Parkinson’s disease – a preliminary study using Chinese SWAL-QOL

Abstract Purpose The objective of the present study is to evaluate swallowing-related quality of life in Chinese patients with Parkinson’s disease (PD) using the validated Chinese version of the Swallowing Quality-of-Life Questionnaire (C-SWAL-QOL) and factors associated with swallowing-related quality of life, including age, disease duration, and severity of depression by 15-item Geriatric Depression Scale in Chinese version (GDS-C). Methods C-SWAL-QOL was administered to 67 Chinese patients with PD. Upon completion of C-SWAL-QOL, they completed the 15-item GDS-C. Spearman’s Rho correlation analyses were performed to examine the relationship between the 10-subscale scores of C-SWAL-QOL and (1) age, (2) disease duration, and (3) depression. Results Among the subscales in C-SWAL-QOL, sleep, fatigue, eating duration, and communication were the most severely affected. Significant relationships existed between composite C-SWAL-QOL score, total C-SWAL-QOL score, Dysphagia Symptom Battery (DSB) core, and depression. Significant relationships were also observed between depression and the following subscales: communication, fear, mental health, social functioning, and fatigue. Yet, no relationships existed between score of C-SWAL-QOL and age or disease duration in PD. Conclusions Considering the goal of dysphagia intervention is to improve swallowing safety and efficiency and ultimately enhance patients’ QOL, clinicians should consider using C-SWAL-QOL in clinical practice to measure swallowing outcomes and to better understand treatment effectiveness. Implications for rehabilitation Dysphagia-related patient-reported outcome (PRO) measures such as Swallowing Quality-of-Life Questionnaire (SWAL-QOL) are the cornerstone to systematically collecting patient-centered data and monitoring rehabilitation outcomes. Based on the scores of Chinese Parkinson’s disease (PD) patients in an oral feeding population indicated in the current study, treatment goal and rehabilitation plan can be set. Chinese patients with Parkinson's disease might benefit from a rehabilitation program focusing on the most severely affected subscales in C-SWAL-QOL.
Co-expression of peripheral olfactory receptors with SARS-CoV-2 infection mediators: Potential implications beyond loss of smell as a COVID-19 symptom

Severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) enters into human host cells via mechanisms facilitated mostly by angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). New loss of smell (anosmia/hyposmia) is now recognized as a COVID-19 related symptom, which may be caused by SARS-CoV-2 infection and damage of the olfactory receptor (OR) cells in the nasal neuroepithelium and/or central involvement of the olfactory bulb. ORs are also expressed peripherally (e.g., in tissues of the gastrointestinal and respiratory systems) and it is possible that their local functions could also be impaired by SARS-CoV-2 infection of these tissues. Using Gene Expression Profiling Interactive Analysis, The Cancer Genome Atlas, Genotype-Tissue Expression, cBioPortal and Shiny Methylation Analysis Resource Tool, we highlight the expression of peripheral ORs in both healthy and malignant tissues, and describe their co-expression with key mediators of SARS-CoV-2 infection, such as ACE2 and TMPRSS2, as well as cathepsin L (CTSL; another cellular protease mediating SARS-CoV-2 infection of host cells). A wide expression profile of peripheral ORs was noted, particularly in tissues such as the prostate, testis, thyroid, brain, liver, kidney and bladder, as well as tissues with known involvement in cardio-metabolic disease (e.g., the adipose tissue, pancreas and heart). Among these, OR51E2, in particular, was significantly upregulated in prostate adenocarcinoma (PRAD) and co-expressed primarily with TMPRSS2. Functional networks of this OR were further analysed using the GeneMANIA interactive tool, showing that OR51E2 interacts with a plethora of genes related to the prostate. Further in vitro and clinical studies are clearly required to elucidate the role of ORs, both at the olfactory level and the periphery, in the context of COVID-19.
Modern approach to the treatment of dry eye, a complex multifactorial disease: a P.I.C.A.S.S.O. board review

Dry eye disease (DED) is a growing public health concern affecting quality of life and visual function, with a significant socio-economic impact. It is characterised by the loss of homoeostasis, resulting in tear film instability, hyperosmolarity and inflammation of the ocular surface. If the innate immune response is unable to cope with internal bodily or environmental adverse conditions, the persistent, self-maintaining vicious circle of inflammation leads to the chronic form of the disease. Treatment of DED should be aimed at the restoration of the homoeostasis of the ocular surface system. A proper diagnostic approach is fundamental to define the relevance and importance of each of the DED main pathogenic factors, namely tear film instability, epithelial damage and inflammation. Consideration also needs to be given concerning two other pathogenic elements: lid margin changes and nerve damage. All the factors that maintain the vicious circle of DED in the patient’s clinical presentation have to be considered and possibly treated simultaneously. The treatment should be long-lasting and personalised since it has to be adapted to the different clinical conditions observed along the course of the disease. Since DED treatment is frequently unable to provide fast and complete relief from symptoms, empathy with patients and willingness to explain to them the natural history of the disease are mandatory to improve patients’ compliance. Furthermore, patients should be instructed about the possible need to increase the frequency and/or change the type of treatment according to the fluctuation of symptoms, following a preplanned rescue regimen.
Solvation Shell of the Nitrite Ion in Water: An Ab Initio Molecular Dynamics Study.

We performed ab initio molecular dynamics simulation of a nitrite ion in water to investigate the structural and dynamical properties of its hydration shell. The nitrite ion is found to exhibit strong asymmetry toward hydrogen bonding due to its two different types of hydrogen bond acceptor sites. This difference is better captured through further partitioning of the hydration shell into its proximal and distal regions. The frequency shifts of the stretch modes of hydration shell water reveal that the nitrogen site forms a stronger hydrogen bond than its oxygen sites with the latter forming hydrogen bonds which are similar in strength to that between a pair of water molecules. The escape dynamics of water from the hydration shell is found to be rather slow which seems to classify the nitrite ion as a structure-maker. However, the dynamics of orientational and hydrogen bond relaxation reveal a faster mobility of water molecules in the hydration shell than bulk water in-spite of strong ion-water interactions. It is found that the nitrite ion can hold water molecules in its solvation shell and still make them rotate fast in its vicinity through switching of their hydrogen bonds between its nitrogen and oxygen acceptor sites. The dipole moment of the solute in water is also calculated in the present study.
Complement C5 inhibition in patients with COVID-19 - a promising target?

Citation: Regis Peffault de Latour, Anne Bergeron, Etienne Lengline, Thibault Dupont, Armance Marchal, Lionel Galicier, Nathalie de Castro, Louise Bondeelle, Michael Darmon, Clairelyne Dupin, Guillaume Dumas, Pierre Leguen, Isabelle Madelaine, Sylvie Chevret, Jean-Michel Molina, Elie Azoulay, and Veronique Fremeaux-Bacchi. Collaborative Groups: CORE GROUP). Complement C5 inhibition in patients with COVID-19 a promising target? Haematologica. 2020; 105:xxx doi:10.3324/haematol.2020. 260117
Tumor necrosis factor-alpha and interleukin-1 beta play a critical role in the resistance against lethal herpes simplex virus encephalitis.

BACKGROUND The innate immune response after herpes simplex type 1 (HSV-1) encephalitis could be protective or, paradoxically, implicated in neuronal damage. We investigated the role of the innate immune response in such infection using a C57BL/6 mouse knockout (KO) model for tumor necrosis factor (TNF)-alpha and/or interleukin (IL)-1beta. METHODS Encephalitis was induced by intranasal infection with a clinical strain of HSV-1 in 1-month-old KO or wild-type (WT) mice. Mice were monitored for survival, brain viral load was quantified by real-time polymerase chain reaction, and the inflammatory response was assessed by in situ hybridization in groups of mice killed on days 3-7. RESULTS WT mice had a significantly higher mean life expectancy (P=.0001, log-rank test) than other groups. IL-1beta and TNF-alpha KO mice had a similar mean life expectancy, and encephalitis was lethal to all TNF-alpha /IL-1beta-deficient mice. Brain viral loads were lower in WT than in KO mice that had disseminated viral replication in the pons and medulla. Moreover, TNF- alpha and IL-1beta KO mice failed to initiate an adequate immune response, as shown by the virtual absence of expression of proinflammatory molecules in the brain. CONCLUSION These data clearly demonstrate the importance of TNF-alpha and IL-1beta in protection against HSV-1 encephalitis in this mouse model.