Miracle-dz/UniFAR-FTUs huggingface dataset:
A Computational Method to Propose Mutations in Enzymes Based on Structural Signature Variation (SSV)

With the use of genetic engineering, modified and sometimes more efficient enzymes can be created for different purposes, including industrial applications. However, building modified enzymes depends on several in vitro experiments, which may result in the process being expensive and time-consuming. Therefore, computational approaches could reduce costs and accelerate the discovery of new technological products. In this study, we present a method, called structural signature variation (SSV), to propose mutations for improving enzymes’ activity. SSV uses the structural signature variation between target enzymes and template enzymes (obtained from the literature) to determine if randomly suggested mutations may provide some benefit for an enzyme, such as improvement of catalytic activity, half-life, and thermostability, or resistance to inhibition. To evaluate SSV, we carried out a case study that suggested mutations in β-glucosidases: Essential enzymes used in biofuel production that suffer inhibition by their product. We collected 27 mutations described in the literature, and manually classified them as beneficial or not. SSV was able to classify the mutations with values of 0.89 and 0.92 for precision and specificity, respectively. Then, we used SSV to propose mutations for Bgl1B, a low-performance β-glucosidase. We detected 15 mutations that could be beneficial. Three of these mutations (H228C, H228T, and H228V) have been related in the literature to the mechanism of glucose tolerance and stimulation in GH1 β-glucosidase. Hence, SSV was capable of detecting promising mutations, already validated by in vitro experiments, that improved the inhibition resistance of a β-glucosidase and, consequently, its catalytic activity. SSV might be useful for the engineering of enzymes used in biofuel production or other industrial applications.
Genome-Wide Identification and Characterization of the AREB/ABF/ABI5 Subfamily Members from Solanum tuberosum

Abscisic acid (ABA) plays crucial roles in plant development and adaption to environmental stresses. The ABA-responsive element binding protein/ABRE-binding factor and ABA INSENSITIVE 5 (AREB/ABF/ABI5) gene subfamily members, which belong to the basic domain/leucine zipper (bZIP) transcription factors family, participate in the ABA-mediated signaling pathway by regulating the expression of their target genes. However, information about potato (Solanum tuberosum) AREB/ABF/ABI5 subfamily members remains scarce. Here, seven putative AREB/ABF/ABI5 members were identified in the potato genome. Sequences alignment revealed that these members shared high protein sequence similarity, especially in the bZIP region, indicating that they might possess overlapping roles in regulating gene expression. Subcellular localization analysis illustrated that all seven AREB/ABF/ABI5 members were localized in the nucleus. Transactivation activity assays in yeast demonstrated that these AREB/ABF/ABI5 members possessed distinct transcriptional activity. Electrophoretic mobility shift assays (EMSA) confirmed that all of these AREB/ABF/ABI5 members could have an affinity to ABRE in vitro. The expression patterns of these AREB/ABF/ABI5 genes showed that they were in response to ABA or osmotic stresses in varying degrees. Moreover, most AREB/ABF/ABI5 genes were induced during stolon swelling. Overall, these results provide the first comprehensive identification of the potato AREB/ABF/ABI5 subfamily and would facilitate further functional characterization of these subfamily members in future work.
Enhanced ROS scavenging and sugar accumulation contribute to drought tolerance of naturally occurring autotetraploids in Poncirus trifoliata

Summary Tetraploids have been reported to exhibit increased stress tolerance, but the underlying molecular and physiological mechanisms remain poorly understood. In this study, autotetraploid plants were identified by screening natural seedlings of trifoliate orange (Poncirus trifoliata). The tetraploids exhibited different morphology and displayed significantly enhanced drought and dehydration tolerance in comparison with the diploid progenitor. Transcriptome analysis indicated that a number of stress‐responsive genes and pathways were differentially influenced and enriched in the tetraploids, in particular those coding for enzymes related to antioxidant process and sugar metabolism. Transcript levels and activities of antioxidant enzymes (peroxidase and superoxide dismutase) and sucrose‐hydrolysing enzyme (vacuolar invertase) were increased in the tetraploids upon exposure to the drought, concomitant with greater levels of glucose but lower level of reactive oxygen species (ROS). These data indicate that the tetraploids might undergo extensive transcriptome reprogramming of genes involved in ROS scavenging and sugar metabolism, which contributes, synergistically or independently, to the enhanced stress tolerance of the tetraploid. Our results reveal that the tetraploids take priority over the diploid for stress tolerance by maintaining a more robust system of ROS detoxification and osmotic adjustment via elevating antioxidant capacity and sugar accumulation in comparison with the diploid counterpart.
Impact of beta-lactam and daptomycin combination therapy on clinical outcomes in methicillin-susceptible Staphylococcus aureus bacteremia: A propensity score-matched analysis.

Background Mortality rates from Staphylococcus aureus bacteremia are high and have only modestly improved in recent decades. We compared the efficacies of beta-lactam in combination with daptomycin (BL/D-C) and beta-lactam monotherapy (BL-M) in improving clinical outcomes in methicillin-susceptible S. aureus (MSSA) bacteremia. Methods A retrospective cohort study of MSSA bacteremia was performed in a tertiary hospital from January 2011 to December 2017. Patients receiving BL/D-C and BL-M were compared to assess 7-, 30- and 90-day mortality rates. A 1:2 propensity score matching was performed. Differences were assessed using Cox regression models. Results Of the 514 patients with MSSA bacteremia, 164 were excluded as they had received combination therapies other than BL/D-C, had pneumonia or had died within 48 h of admission. Of the remaining 350 patients, 136 and 214 received BL/D-C and BL-M, respectively. BL/D-C patients had higher Pitt scores and persistent bacteremia more often than BL-M patients. In the raw analysis, there were no differences in mortality rates between groups. After propensity score matching, there were no significant differences between the BL/D-C (110 patients) and BL-M (168 patients) groups for all-cause mortality rates at 7 (8.18% vs. 7.74%, P = 1.000), 30 (17.3% vs. 16.1%, P = 0.922) and 90 days (22.7% vs. 23.2%, P = 1.000), even in a sub-analysis of patients with high-risk source of infection and in a subgroup excluding catheter-related bacteremia. Conclusions BL/D-C failed to reduce mortality rates in patients with MSSA bacteremia. Treatment strategies to improve survival in MSSA bacteremia are urgently needed.
Occlusion Aware Facial Expression Recognition Using CNN With Attention Mechanism

Facial expression recognition in the wild is challenging due to various unconstrained conditions. Although existing facial expression classifiers have been almost perfect on analyzing constrained frontal faces, they fail to perform well on partially occluded faces that are common in the wild. In this paper, we propose a convolution neutral network (CNN) with attention mechanism (ACNN) that can perceive the occlusion regions of the face and focus on the most discriminative un-occluded regions. ACNN is an end-to-end learning framework. It combines the multiple representations from facial regions of interest (ROIs). Each representation is weighed via a proposed gate unit that computes an adaptive weight from the region itself according to the unobstructedness and importance. Considering different RoIs, we introduce two versions of ACNN: patch-based ACNN (pACNN) and global–local-based ACNN (gACNN). pACNN only pays attention to local facial patches. gACNN integrates local representations at patch-level with global representation at image-level. The proposed ACNNs are evaluated on both real and synthetic occlusions, including a self-collected facial expression dataset with real-world occlusions, the two largest in-the-wild facial expression datasets (RAF-DB and AffectNet) and their modifications with synthesized facial occlusions. Experimental results show that ACNNs improve the recognition accuracy on both the non-occluded faces and occluded faces. Visualization results demonstrate that, compared with the CNN without Gate Unit, ACNNs are capable of shifting the attention from the occluded patches to other related but unobstructed ones. ACNNs also outperform other state-of-the-art methods on several widely used in-the-lab facial expression datasets under the cross-dataset evaluation protocol.
Understanding Heterogeneity in Biological Phenotypes of ARDS by Leukocyte Expression Profiles.

RATIONALE Two biological phenotypes of ARDS have been identified based on plasma protein markers in four previous studies. We hypothesized that blood leukocyte gene expression is different between the "reactive" and "uninflamed" phenotype. METHODS This is a new study adding blood leukocyte transcriptomics and bioinformatics analysis to an existing patient cohort of ARDS in patients with sepsis admitted to two ICUs during a 1.5 year period. Canonical pathway analysis (CPA) was performed. RESULTS 210 patients with sepsis and ARDS were included of whom 128 had a reactive and 82 an uninflamed phenotype. 3332/11443 (29%) transcripts were significantly different between the phenotypes. CPA showed upregulation of oxidative phosphorylation genes indicative of mitochondrial dysfunction (52% of genes in pathway). The uninflamed phenotype was characterized by upregulation of mitogen-activated protein kinase (MAPK) pathways. CONCLUSION A third of genes are differentially expressed between biological phenotypes of ARDS supporting the observation that the subgroups of ARDS are incomparable in terms of pathophysiology. These data provide additional support for biological heterogeneity in ARDS patients and suggests that a personalized approach to intervention focusing on oxidative phosphorylation is pivotal in this condition.
Topoisomerase II α Gene alteration in Triple Negative Breast Cancer and Its Predictive Role for Anthracycline-Based Chemotherapy (Egyptian NCI Patients)

Objective: Triple negative breast cancer is an aggressive variant of breast cancer; it forms about 15% of breast cancer cases. It lacks the responsiveness to hormonal and targeted therapies. Anthracyclines remain the treatment option for these patients. Anthracyclines are cardiotoxic, so predicting sensitivity of response by biological predictors may have a role in selecting suitable candidates for these drugs. Material and methods: This study included 50 TNBC cases, from National Cancer Institute, Cairo University(NCI-CU), Egypt, who underwent surgery and received adjuvant chemotherapy. Archived blocks were obtained and immunostaining for Ki-67 LI and Fluorescent In situ Hybridization (FISH) technique to assess TOP2A gene copy number and chromosome 17CEP status were done. Analysis of association between TOP2A alterations and CEP17 polysomy as well as Ki-67 LI with other clinicopathological parameters was done. Associations between the biological markers and event free survival (EFS) and overall survival (OS), were also performed. Results: TOP2A alteration was seen in 9/50 cases (5 amplified and 4 deleted). CEP17 Polysomy was detected in 14% of cases. Most of patients (80%) showed Ki-67 LI ≥20%. There was a significant association between TOP2A gene and CEP17 status. Outcome was better with abnormal TOP2A gene status and CEP17 polysomy, radiotherapy and combined anthracyclines and taxanes in the adjuvant setting, however P-values were not significant. Conclusion: TOP2A gene alterations and CEP17 polysomy may have prognostic and predictive role in TNBC treated with adjuvant Anthracyclines.
Toxicity assessment of Lavandula officinalis extracts in Brine Shrimp (Artemia salina)

Abstract The toxicity of extracts of lavender (Lavandula officinalis) leaves and flowers was evaluated. Aqueous ethanolic and acetone extracts had higher tannin content than that in the aqueous solution. Polyphenol and flavonoid contents were measured in aqueous extracts of leaves and flowers. Polyphenol concentration in aqueous leaf and flower extracts was 61.31 and 84.43 mg tannic acid/g, respectively, whereas flavonoid concentration was 194.1 and 109.9 mg quercetin/g, respectively. Saponin content was 7.85% and 6.22% in leaves and flowers extract, respectively, and alkaloids content was 0.2651% and 0.2132% for leaves and flowers extract, respectively. The EC50 (36 h) of hatching success of Artemia salina cysts was 0.301 and 0.915 mg/mL for aqueous extracts of leaves and flowers, respectively, whereas that for aqueous ethanolic extracts of leaves and flowers, it was 0.111 and 0.586 mg/mL, respectively. The EC50 (36 h) was 0.011 mg/mL for tannic acid. Additionally, the LC50 (24 h) for aqueous extracts of leaves and flowers was 0.467 and 0.724 mg/mL, respectively, whereas that of the aqueous ethanolic extracts of leaves and flowers was 0.074 and 0.126 mg/mL, respectively. The LC50 was 0.015 mg/mL for tannic acid. Although aromatherapy using lavender oils or extracts is beneficial to human health, particularly owing to its anxiolytic, analgesic, and antihyperlipidemic effects, we demonstrated that these extracts might exhibit toxicity. Hence, lavender should be used carefully by health practitioners, and lavender therapies should be closely monitored by medical staff to avoid its toxic effects.
The effect of sequential compression device on hypotension in the sitting position during shoulder arthroscopy; a comparison with elastic stocking.

BACKGROUND The sitting position under general anesthesia is associated with hemodynamic instability. The purpose of this study was to compare the efficacy of a sequential compression device (SCD) with that of elastic stockings (ES) in reducing the incidence of hypotension and other hemodynamic instability in the sitting position during shoulder arthroscopy. METHODS Fifty-one patients undergoing shoulder arthroscopy were randomly assigned into one of three groups to receive no treatment (control group, n = 17), SCD (SCD group, n = 17) or ES (ES group, n = 17). Hemodynamic variables were measured 5 min after induction of anesthesia (baseline values), and every 1 min from 1 to 5 min after raising the patient to a 70degrees sitting position (T1-5) with the beach-chair. RESULTS The incidences of hypotension (proportion, 95% CI) were 12/17 (0.71, 0.47-0.87), 5/16 (0.31, 0.14-0.56) and 7/15 (0.47, 0.25-0.70) in the control, SCD and ES group, respectively. The incidence was significantly lower in the SCD group than that in the control group (P = 0.038). At 1 min after sitting position, mean arterial pressure in the control group was significantly lower than that in the SCD group and it was significantly decreased from the baseline value. CONCLUSIONS SCD could significantly reduce the incidence of hypotension with less hemodynamic instability in the sitting position during shoulder arthroscopy. Although the incidence of hypotension was decreased with the elastic stocking, there was no statistical significance.
Comparison of an Er: YAG laser osteotome versus a conventional drill for the use in osteo‐ odonto‐keratoprosthesis (OOKP)

The osteo‐odonto‐kerato‐prosthesis (OOKP) procedure is a complex, multi‐stage, multidisciplinary surgical intervention for the treatment of severe corneal blindness. One step of the OOKP consists of creating a precise hole into a tooth in which an optic cylinder is subsequently inserted; its shape must ensure a perfect watertight fit. The Er: YAG laser (L) used in this study is part of CARLO®, the first laser osteotome that enables surgical planning based on computed tomography data, robot guidance, and a precise execution of laser cuts in teeth and bone tissue, using laser photoablation rather than conventional mechanical methods. The purpose of this study was to assess whether the Er: YAG laser is non‐inferior compared to a conventional drill.
Cognitive costs of reproduction: life‐history trade‐offs explain cognitive decline during pregnancy in women

Life‐history theory predicts that access to limited resources leads to trade‐offs between competing body functions. Women, who face higher costs of reproduction when compared to men, should be especially vulnerable to these trade‐offs. We propose the ‘cognitive costs of reproduction hypothesis’, which states that energy trade‐offs imposed by reproduction may lead to a decline in maternal cognitive function during gestation. In particular, we hypothesize that the decline in cognitive function frequently observed during pregnancy is associated with the allocation of resources between the competing energetic requirements of the mother's brain and the developing foetus. Several distinctive anatomical and physiological features including a high metabolic rate of the brain, large infant size, specific anatomical features of the placenta and trophoblast, and the lack of maternal control over glucose flow through the placenta make the occurrence of these trade‐offs likely.
Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis

Background Mechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously demonstrated that children with CF and parental-reported secondhand smoke exposure (SHSe) have increased susceptibility to bacterial infections. SHSe hinders arachidonic acid (AA) metabolites that mediate immune function in patients without CF, and may influence CF immune dysfunction. We aimed to define SHSe’s impact on inflammation mediators and infection in children with CF. Methods Seventy-seven children with CF <10 years of age (35 infants <1 year; 42 children 1–10 years) were enrolled and hair nicotine concentrations measured as an objective surrogate of SHSe. AA signalling by serum and macrophage lipidomics, inflammation using blood transcriptional profiles and in vitro macrophage responses to bacterial infection after SHSe were assessed. Results Hair nicotine concentrations were elevated in 63% of patients. Of the AA metabolites measured by plasma lipidomics, prostaglandin D2 (PGD2) concentrations were decreased in children with CF exposed to SHSe, and associated with more frequent hospitalisations (p=0.007) and worsened weight z scores (p=0.008). Children with CF exposed to SHSe demonstrated decreased expression of the prostaglandin genes PTGES3 and PTGR2 and overexpression of inflammatory pathways. These findings were confirmed using an in vitro model, where SHSe was associated with a dose-dependent decrease in PGD2 and increased methicillin-resistant Staphylococcus aureus survival in human CF macrophages. Conclusions Infants and young children with CF and SHSe have altered AA metabolism and dysregulated inflammatory gene expression resulting in impaired bacterial clearance. Our findings identified potential therapeutic targets to halt early disease progression associated with SHSe in the young population with CF.
Host cell protein LAMP‐2 is the receptor for Trypanosoma cruzi surface molecule gp82 that mediates invasion

Host cell invasion by Trypanosoma cruzi metacyclic trypomastigote (MT) is mediated by MT‐specific surface molecule gp82, which binds to a still unidentified receptor, inducing lysosome spreading and exocytosis required for the parasitophorous vacuole formation. We examined the involvement of the major lysosome membrane‐associated LAMP proteins in MT invasion. First, human epithelial HeLa cells were incubated with MT in the presence of antibody to LAMP‐1 or LAMP‐2. Antibody to LAMP‐2, but not to LAMP‐1, significantly reduced MT invasion. Next, HeLa cells depleted in LAMP‐1 or LAMP‐2 were generated. Cells deficient in LAMP‐2, but not in LAMP‐1, were significantly more resistant to MT invasion than wild‐type controls. The possibility that LAMP‐2 might be the receptor for gp82 was examined by co‐immunoprecipitation assays. Protein A/G magnetic beads cross‐linked with antibody directed to LAMP‐1 or LAMP‐2 were incubated with HeLa cell and MT detergent extracts. Gp82 bound to LAMP‐2 but not to LAMP‐1. Binding of the recombinant gp82 protein to wild‐type and LAMP‐1‐deficient cells, which was dose dependent and saturable, had a similar profile and was much higher as compared with LAMP‐2‐depleted cells. These data indicate that MT invasion is accomplished through recognition of gp82 by its receptor LAMP‐2.
Northumbria

Pausing by RNA polymerase is a major mechanism that regulates transcription elongation but can cause con ﬂ icts with fellow RNA polymerases and other cellular machineries. Here, we summarize our recent ﬁ nding that misincorporation could be a major source of transcription pausing in vivo , and discuss the role of misincorporation-induced pausing.
Effects of Question Framing on Self-Reported Memory Concerns across the Lifespan

ABSTRACT Background/Study Context: Evidence regarding whether there is an age-related increase in subjective memory concerns is mixed. The goal of this study was to investigate whether calling to mind specific instances of memory failures affects the likelihood that individuals report being concerned about their memory. Methods: Young, middle-aged, and older individuals responded to statements that probed general memory concerns (e.g., I am concerned about my memory) before or after probing the frequency of memory difficulties in specific everyday situations (e.g., I forget appointments). Results: We found no relationship between age and memory concern, and older compared to younger adults reported having fewer everyday memory failures. Furthermore, individuals of all ages were more likely to report being concerned about their memory if asked before relative to after rating the frequency of specific everyday memory failures. Conclusion: Increasing age is associated with fewer reported difficulties with specific everyday memory situations, but people of all ages display anchoring effects on memory concern based on realistic occurrences of remembering. Our findings have implications for the measurement of self-reported memory as they show that the order of questions can influence responding.
Subarachnoid hemorrhage due to systemic lupus erythematosus associated with multiple intracranial artery aneurysms

To the Editor: Systemic lupus erythematosus (SLE) is an autoimmune-mediated systemic inflammatory disease which involves nearly all organs of the body, and it is associated with premature atherosclerosis, vasculitis, and coagulopathy. Cases of subarachnoid hemorrhage (SAH) due to cerebral aneurysm associated with SLE are being reported more frequently. However, SAH due to SLE associated with multiple cerebral artery aneurysms that rapidly develop within only 2 months is rare, and the causal relations between cerebral aneurysm and SLE are not clearly understood. Herein, we reported a case of multiple cerebral artery aneurysms due to SLE, with enough evidence to confirm that the cerebral artery aneurysms were solely due to SLE.