Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential Role of Dietary Salmon Nasal Cartilage Proteoglycan on UVB-Induced Photoaged Skin

New supplements with preventive effects against skin photodamage are receiving increasing attention. This study evaluated the anti-photoaging effects of salmon nasal cartilage proteoglycan (SPG), acting as a functional material for skin health. We administered SPG to in vitro and in vivo models exposed to ultraviolet B (UVB) radiation and assessed its moisturizing and anti-wrinkle effects on dorsal mouse skin and keratinocytes and dermal fibroblasts cell lines. These results showed that SPG restored the levels of filaggrin, involucrin, and AQP3 in the epidermis of UVB-irradiated dorsal skin and keratinocytes, thereby enhancing the keratinization process and water flow. Additionally, SPG treatment increased the levels of hyaluronan and skin ceramide, the major components of intercellular lipids in the epidermis. Furthermore, SPG treatment significantly increased the levels of collagen and procollagen type 1 by down-regulating matrix metalloproteinase 1, which play a crucial role in skin fibroblasts, in both in vitro and in vivo models. In addition, SPG strongly inhibited mitogen-activated protein kinase (MAPKs) signaling, the including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. These findings suggest that dietary SPG may be an attractive functional food for preventing UVB-induced photoaging. And this SPG product may provide its best benefit when treating several signs of skin photoaging.
The Relevance of Integrating CYP2C19 Phenoconversion Effects into Clinical Pharmacogenetics

Introduction CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status. Methods Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PC Bousman , PC Hahn&Roll ) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine. Results There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram. Discussion PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.
Chronic Treatment with Serotonin Selective Reuptake Inhibitors Does Not Affect Regrowth of Serotonin Axons Following Amphetamine Injury in the Mouse Forebrain

A current hypothesis to explain the limited recovery following brain and spinal cord trauma stems from the dogma that neurons in the mammalian central nervous system lack the ability to regenerate their axons after injury. Serotonin (5-HT) neurons in the adult brain are a notable exception in that they can slowly regrow their axons following chemical or mechanical lesions. This process of regrowth occurs without intervention over several months and results in anatomical recovery that approximates the preinjured state. During development, serotonin is a trophic factor, playing a role in both cell survival and axon growth. Additionally, some studies have shown that stroke patients treated after injury with serotonin selective reuptake inhibitors (SSRIs) appeared to have improved recovery. To test the hypothesis that serotonin can influence the regrowth of 5-HT axons, mice received a high dose of para-chloroamphetamine (PCA) to induce widespread retrograde degeneration of 5-HT axons. Then, after a short rest period to avoid any interaction with the acute injury phase, SSRIs were administered daily for 6 or 10 weeks. Using immunohistochemistry in 5-HT transporter-GFP BAC transgenic mice, we determined that while PCA led to a rapid initial decrease in total 5-HT axon length in the somatosensory cortex, visual cortex, or area CA1 of the hippocampus, treatment with either fluoxetine or sertraline (two different SSRIs) did not affect the recovery of axon length. These results suggest that chronic SSRI treatment does not affect the regrowth of 5-HT axons and argue against SSRIs as a potential therapy following brain injury.
A novel Bacillus sp. isolated from rotten seaweed: Identification and characterization alginate lyase its produced

Abstract. Zilda DS, Yulianti Y, Sholihah RF, Subaryono S, Fawzya YN, Irianto HE.2019. A novel Bacillus sp. isolated from rotten seaweed: identification and characterization alginate lyase its produced. Biodiversitas 20: 1166-1172. Alginate lyase has been known as potential biocatalyst not only for industrial but also medicinal application especially for the production of oligosaccharides which have distinct bioactivities. An alginate lyase, AlgT513, has been isolated from rotten seaweed bacterium strain T513 and characterized. The bacterium showed low similarity (95%) with Bacillus tequilensis strain 10b based on 16S rDNA sequence indicating that AlgT513may be a novel Bacillus species. The bacterium forms a clear zone on solid medium with 0.5% sodium alginate addition. The optimum temperature and pH were 50ºC and 8 respectively. AlgT513 maintained stability at board pHs of 4-9 and temperature of 45ºC. Metal ions Mg2+, Ca2+ and K+ increase the activity of the enzyme while Zn2+, Co2+ and Li+ strongly inhibit it. NaCl inhibits AlgT513 activity where most of the alginate lyases need it to reach maximum activity. AlgT513 is suggested as a serine metalloenzyme due to inhibition of ethylenediaminetetraacetic acid (EDTA) and phenylmethylsulfonyl fluoride (PMSF).
Addressing unprofessional behaviors in the clinical learning environment: lessons from a multi-year virtual, intergenerational, interdisciplinary workshop

ABSTRACT Introduction Optimizing the clinical learning environment (CLE) is a medical education priority nationwide. Materials and Methods We developed a virtual, one-hour workshop engaging students, housestaff and faculty in small-group discussions of five case scenarios adapted from reported unprofessional behaviors in the CLE, plus didactics regarding mistreatment, microaggressions and bystander interventions. Results Over two sessions (2021–2022), we engaged 340 students and 73 faculty/housestaff facilitators. Post-session surveys showed significant improvement in participants’ ability to recognize and respond to challenges in the CLE. Discussion Our innovative workshop, including scenarios derived from institutional reports of unprofessional behaviors, advanced participants’ knowledge and commitment to improve the CLE.
Exploring the dynamics and structure of PpiB in living Escherichia coli cells using electron paramagnetic resonance spectroscopy

Abstract The combined effects of the cellular environment on proteins led to the definition of a fifth level of protein structural organization termed quinary structure. To explore the implication of potential quinary structure for globular proteins, we studied the dynamics and conformations of Escherichia coli (E. coli) peptidyl‐prolyl cis/trans isomerase B (PpiB) in E. coli cells. PpiB plays a major role in maturation and regulation of folded proteins by catalyzing the cis/trans isomerization of the proline imidic peptide bond. We applied electron paramagnetic resonance (EPR) techniques, utilizing both Gadolinium (Gd(III)) and nitroxide spin labels. In addition to using standard spin labeling approaches with genetically engineered cysteines, we incorporated an unnatural amino acid to achieve Gd(III)‐nitroxide orthogonal labeling. We probed PpiB's residue‐specific dynamics by X‐band continuous wave EPR at ambient temperatures and its structure by double electron–electron resonance (DEER) on frozen samples. PpiB was delivered to E. coli cells by electroporation. We report a significant decrease in the dynamics induced by the cellular environment for two chosen labeling positions. These changes could not be reproduced by adding crowding agents and cell extracts. Concomitantly, we report a broadening of the distance distribution in E. coli, determined by Gd(III)–Gd(III) DEER measurements, as compared with solution and human HeLa cells. This suggests an increase in the number of PpiB conformations present in E. coli cells, possibly due to interactions with other cell components, which also contributes to the reduction in mobility and suggests the presence of a quinary structure.
Association between estimated pulse wave velocity and in-hospital mortality of patients with acute kidney injury: a retrospective cohort analysis of the MIMIC-IV database

Abstract Background Estimated pulse wave velocity (ePWV) has been found to be an independent predictor of cardiovascular mortality and kidney injury, which can be estimated noninvasively. This study aimed to investigate the association between ePWV and in-hospital mortality in critically ill patients with acute kidney injury (AKI). Methods This study included 5960 patients with AKI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan-Meier survival curve to evaluate the differences in survival status. Cox proportional hazards models were used to explore the association between ePWV and in-hospital mortality in critically ill patients with AKI. To further examine the dose-response relationship, we used a restricted cubic spline (RCS) model. Stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups. Results Survival analysis indicated that patients with high ePWV had a lower survival rate than those with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with an increased risk of in-hospital mortality among AKI patients (HR = 1.53, 95% CI = 1.36-1.71, p < 0.001). Analysis using the RCS model confirmed a linear increase in the risk of hospital mortality as the ePWV values increased (P for nonlinearity = 0.602). Conclusions A high ePWV was significantly associated with an increased risk of in-hospital mortality among patients with AKI. Furthermore, ePWV was an independent predictor of in-hospital mortality in critically ill patients with AKI.
Accuracy and Reliability of Remote Categorization of Upper Limb Outcome After Stroke

Background There is an increasing need for motor assessments after stroke that can be performed quickly and remotely. The Fast Outcome Categorization of the Upper Limb after Stroke-4 (FOCUS-4) assessment remotely classifies upper limb outcome into 1 of 4 categories after stroke and was developed via retrospective analysis of Action Research Arm Test (ARAT) scores. Objective The aim of this study was to prospectively evaluate the accuracy and reliability of FOCUS-4 assessments for categorizing upper limb outcome after stroke when administered remotely during a videocall compared to an in-person ARAT. Methods Data were collected from 26 participants at 3 months post-stroke (3M), 27 participants at 6 months post-stroke (6M), and 56 participants at the chronic stage of stroke (>6M). Participants performed an in-person ARAT and a remote FOCUS-4 assessment administered during a videocall, and accuracy was evaluated by comparing the upper limb outcome categories. Participants at the chronic stage of stroke also performed a second remote FOCUS-4 assessment to assess between-day reliability. Results Overall accuracy of the remote FOCUS-4 assessment was 88% at 3M and 96% at 6M. Overall accuracy of the first and second remote FOCUS-4 assessments at the chronic stage was 75% and 79%, respectively. Reliability of the FOCUS-4 assessment at the chronic stage was 82%. The remote FOCUS-4 assessment was most accurate and reliable for participants with mild or severe upper limb functional impairment. Conclusions The remote FOCUS-4 assessment has potential to classify upper limb functional capacity or to screen possible participants for stroke trials, but external validation is required.
The prevalence of adhesion and biofilm genes in Staphylococcus aureus isolates from bovine mastitis: A comprehensive meta‐analysis

Abstract Background Mastitis poses significant challenges to the dairy industry, resulting in economic losses and increased veterinary expenses. Staphylococcus aureus is a common cause of bovine mastitis, relying on efficient adhesion and biofilm formation for infection. Objectives This study aimed to employ meta‐analysis to investigate the occurrence of adhesion and biofilm genes in S. aureus associated with bovine mastitis, as documented in previous studies. Methods This meta‐analysis was done according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses, examined 22 eligible articles and revealed varying prevalence rates of adhesion and biofilm genes in S. aureus isolates from bovine mastitis. Results Among the genes, clfB showed the highest prevalence (p‐estimate = 0.905), followed by fnbA (p‐estimate = 0.689) and fnbB (p‐estimate = 0.502). The icaA and icaD genes also showed a relatively high prevalence (p‐estimate = 0.694 and 0.814, respectively). Conversely, the biofilm‐associated proteins gene had the lowest prevalence (p‐estimate = 0.043). Subgroup analyses based on mastitis types and publication years revealed no significant differences in gene prevalence. Insufficient data hindered the analysis of fib, sasG , eno and bbp genes. Conclusion This study provides valuable insights for managing S. aureus‐induced bovine mastitis. Additionally, larger‐scale research, particularly on less‐studied genes, is necessary to comprehend the molecular roles of adhesion and biofilm genes in S. aureus‐induced bovine mastitis.
Developing ecological site and state-and-transition models for grazed riparian pastures at Tejon Ranch, California

Ecological site descriptions and associated state-and-transition models are useful tools for understanding the variable effects of management and environment on range resources. Models for woody riparian sites have yet to be fully developed. At Tejon Ranch, in the southern San Joaquin Valley of California, we are using ecological site theory to investigate the role of two managed ungulate populations, cattle and feral pigs, on riparian woodland communities. Responses in plant species composition, woody plant recruitment, and vegetation structure will be measured by comparing cattle and feral pig management treatments among and between areas with similar abiotic conditions (ecological sites). Results from the second year of this project highlight the spatial variability of riparian woodland vegetation communities as well as temporally and spatially variable abundances of cattle and feral pigs. Development of riparian ecological site descriptions and state-and-transition models provide both a generalizable framework for evaluating management alternatives in riparian areas, and also specific direction for managing cattle and feral pigs.
Aptamer-Functionalized Interface Nanopores Enable Amino Acid-Specific Peptide Detection

Single-molecule proteomics based on nanopore technology has made significant advances in recent years. However, to achieve nanopore sensing with single amino acid resolution, several bottlenecks must be tackled: controlling nanopore sizes with nanoscale precision and slowing molecular translocation events. Herein, we address these challenges by integrating amino acid-specific DNA aptamers into interface nanopores with dynamically tunable pore sizes. A phenylalanine aptamer was used as a proof-of-concept: aptamer recognition of phenylalanine moieties led to the retention of specific peptides, slowing translocation speeds. Importantly, while phenylalanine aptamers were isolated against the free amino acid, the aptamers were determined to recognize the combination of the benzyl or phenyl and the carbonyl group in the peptide backbone, enabling binding to specific phenylalanine-containing peptides. We decoupled specific binding between aptamers and phenylalanine-containing peptides from nonspecific interactions (e.g., electrostatics and hydrophobic interactions) using optical waveguide lightmode spectroscopy. Aptamer-modified interface nanopores differentiated peptides containing phenylalanine vs. control peptides with structurally similar amino acids (i.e., tyrosine and tryptophan). When the duration of aptamer–target interactions inside the nanopore were prolonged by lowering the applied voltage, discrete ionic current levels with repetitive motifs were observed. Such reoccurring signatures in the measured signal suggest that the proposed method has the possibility to resolve amino acid-specific aptamer recognition, a step toward single-molecule proteomics.
Understanding Australian general practice patients’ decisions to deprescribe antidepressants in the WiserAD trial: a realist informed approach

Objectives To evaluate how an approach to antidepressant deprescribing works, for whom, and in what contexts by (1) examining the experiences and perceptions of the approach for antidepressant users, (2) identifying the mechanisms of the approach and (3) describing what contexts are associated with antidepressant tapering. Design This mixed methods study was informed by the principles of realist evaluation and was conducted in the first 3 months of participation in the WiserAD randomised control trial. Setting General practice, Victoria, Australia. Participants 13 antidepressant users from general practice participating in the WiserAD trial for antidepressant deprescribing. Intervention A patient-facing, web-based structured support tool that consists of a personalised tapering schedule, an action plan for managing withdrawal symptoms, a daily mood, sleep and activity tracker and mental health nurse support. Primary/secondary outcome measures The outcomes of the study were revealed on data analysis as per a realist evaluation approach which tests and refines an initial programme theory. Results The contexts of learnt coping skills, knowledge and perceptions of antidepressants and feeling well were evident. Outcomes were intention to commence, initiation of deprescribing and successful completion of deprescribing. Key mechanisms for antidepressant deprescribing were (1) initiation of the deprescribing discussion; (2) patient self-efficacy; (3) provision of structured guidance; (4) coaching; (5) mood, sleep and activity tracking and (6) feelings of safety during the tapering period. Conclusions The WiserAD approach to antidepressant deprescribing supported participants to commence and/or complete tapering. The refined programme theory presents the WiserAD pragmatic framework for the application of antidepressant deprescribing in clinical practice. Trial registration number ClinicalTrials.gov NCT05355025; ACTRN12622000567729; ISRCTN11562922; Pre-results.
Key interaction networks: Identifying evolutionarily conserved non‐covalent interaction networks across protein families

Abstract Protein structure (and thus function) is dictated by non‐covalent interaction networks. These can be highly evolutionarily conserved across protein families, the members of which can diverge in sequence and evolutionary history. Here we present KIN, a tool to identify and analyze conserved non‐covalent interaction networks across evolutionarily related groups of proteins. KIN is available for download under a GNU General Public License, version 2, from https://www.github. com/kamerlinlab/KIN. KIN can operate on experimentally determined structures, predicted structures, or molecular dynamics trajectories, providing insight into both conserved and missing interactions across evolutionarily related proteins. This provides useful insight both into protein evolution, as well as a tool that can be exploited for protein engineering efforts. As a showcase system, we demonstrate applications of this tool to understanding the evolutionary‐relevant conserved interaction networks across the class A β‐lactamases.
Salmonella enterica serovar Typhimurium remodels mitochondrial dynamics of macrophages via the T3SS effector SipA to promote intracellular proliferation

ABSTRACT Mitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells’ mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.
Sharp Information-Theoretic Thresholds for Shuffled Linear Regression

This paper studies the problem of shuffled linear regression, where the correspondence between predictors and responses in a linear model is obfuscated by a latent permutation. Specifically, we consider the model $y = \Pi_* X \beta_* + w$, where $X$ is an $n \times d$ standard Gaussian design matrix, $w$ is Gaussian noise with entrywise variance $\sigma^2$, $\Pi_*$ is an unknown $n \times n$ permutation matrix, and $\beta_*$ is the regression coefficient, also unknown. Previous work has shown that, in the large $n$-limit, the minimal signal-to-noise ratio ($\mathsf{SNR}$), $\lVert \beta_* \rVert^2/\sigma^2$, for recovering the unknown permutation exactly with high probability is between $n^2$ and $n^C$ for some absolute constant $C$ and the sharp threshold is unknown even for $d=1$. We show that this threshold is precisely $\mathsf{SNR} = n^4$ for exact recovery throughout the sublinear regime $d=o(n)$. As a by-product of our analysis, we also determine the sharp threshold of almost exact recovery to be $\mathsf{SNR} = n^2$, where all but a vanishing fraction of the permutation is reconstructed.
Variations on quantum de Finetti theorems and operator valued Martin boundaries: a Choquet-Deny approach

We revisit the quantum de Finetti theorem. We state and prove a couple of variants thereof. In parallel, we introduce an operator version of the Martin boundary on quantum groups and prove generalizations of Biane's theoresm. Our proof of the de Finetti theorem is new in the sense that it is based on an analogy with the theory of operator valued Martin boundary that we introduce.