Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanosensitive channel gating by delipidation

Significance Proteins embedded in membranes experience anisotropic forces from their surroundings. Mechanosensors are activated upon changes in the membrane tension and are the basis of important biological functionalities. However, the molecular mechanisms of mechanosensation are only vaguely understood. Hydrophobic mismatch between protein and membrane, amphiphilic sliding helices, or local membrane bending are examples for different concepts explaining mechanosensation in which one or more of these concepts could be implemented in a particular protein. Here, we show that the mechanosensitive channel of small conductance is gated by the extrusion of lipids from hydrophobic pockets independent of the membrane. A cryoelectron microscopy map at 2.3-Å resolution reveals the so-far-neglected role of aliphatic chains at the periplasmatic side in stabilizing the open state. The mechanosensitive channel of small conductance (MscS) protects bacteria against hypoosmotic shock. It can sense the tension in the surrounding membrane and releases solutes if the pressure in the cell is getting too high. The membrane contacts MscS at sensor paddles, but lipids also leave the membrane and move along grooves between the paddles to reside as far as 15 Å away from the membrane in hydrophobic pockets. One sensing model suggests that a higher tension pulls lipids from the grooves back to the membrane, which triggers gating. However, it is still unclear to what degree this model accounts for sensing and what contribution the direct interaction of the membrane with the channel has. Here, we show that MscS opens when it is sufficiently delipidated by incubation with the detergent dodecyl-β-maltoside or the branched detergent lauryl maltose neopentyl glycol. After addition of detergent-solubilized lipids, it closes again. These results support the model that lipid extrusion causes gating: Lipids are slowly removed from the grooves and pockets by the incubation with detergent, which triggers opening. Addition of lipids in micelles allows lipids to migrate back into the pockets, which closes the channel even in the absence of a membrane. Based on the distribution of the aliphatic chains in the open and closed conformation, we propose that during gating, lipids leave the complex on the cytosolic leaflet at the height of highest lateral tension, while on the periplasmic side, lipids flow into gaps, which open between transmembrane helices.
Impact of social isolation and coping strategies in older adults with mild cognitive impairment during the covid-19 pandemic: A qualitative study

ABSTRACT The COVID-19 pandemic imposed a psychological burden on elderly and particularly individuals with cognitive impairment and dementia. Few studies have investigated the quarantine experiences of older adults with mild cognitive impairment (MCI) during the COVID-19 pandemic. Objectives The objective of this study was to explore the experiences and feelings of older adults with MCI during the COVID-19 outbreak in Chile and to know what strategies they used to overcome social isolation. Method A qualitative design was used. Ten participants with a diagnosis of MCI took part in this study. All interviews were recorded and coded using thematic analysis. Results The thematic analysis identified three themes related to the quarantine experience of older adults with MCI diagnosis: (1) Effects of social isolation during the COVID-19 pandemic (2) Believes, feelings and behaviors about the SARS-CoV-2 virus (3) Coping with social isolation/response to difficulties during the pandemic. It was found that older adults with MCI have been mainly psychologically and socially affected by social distancing and isolation, particularly individuals who were alone during COVID-19 outbreak. The only physical dimension negatively affected was the level of activity. Social isolation led to a significant number of negative emotions such as anger, fear of contracting the virus or possibility of contagion for their families, worries and sadness as well as emotional loneliness. It is noteworthy that the majority of participants have used several coping strategies during this challenging time. Conclusion Since social isolation and a sedentary life have been associated with poorer cognition and functionality in people with MCI, a rational plan to both prevent the progression of cognitive decline and to increase social contact, is essential. Special attention must be drawn to maintaining people physically active at home and keeping their daily routine (within the possibilities) and also to ensure social connectedness through technology. Implementation of these measures could potentially reduce negative emotions during the pandemic.
Addition of Trichocladium canadense to an anaerobic membrane bioreactor: evaluation of the microbial composition and reactor performance

Abstract Membrane bioreactors are powerful systems for wastewater treatment and the removal of toxic compounds. However, membrane biofouling stands in the way of their widespread usage. In this study, the saprophytic fungus Trichocladium canadense was used as the bioaugmentor in an anaerobic membrane bioreactor (AnMBR) and its impact on membrane biofouling, biogas production, the microbial communities of the reactor and removal of the common antibiotics erythromycin (ERY), sulfamethoxazole (SMX) and tetracycline (TET) from synthetic wastewater was investigated. The results indicated that through bioaugmentation with 20% T. canadense, membrane biofouling was slowed by 25%, the chemical oxygen demand removal increased by 16% and a higher efficiency removal of ERY and SMX was achieved. The presence of T. canadense significantly increased the abundance and diversity of the biofilm archaeal community and the bacterial phylum Firmicutes, a known bio-foulant. Graphical Abstract
Overcoming Ambivalence about American Cities

This article is addressed to urban scholars, who often have deep doubts about whether cities have a place in a more democratic and redistributive political order. Urbanists are so ambivalent about cities because many mistakenly believe that cities are, politically, inherently untrustworthy and, economically, inherently ineffectual. Rather than entering into the communitarian debate, it is more fruitful to attempt to understand how local government authority, properly conceived, is actually necessary to many left and minority goals regarding politics and economics. The lack of confidence that the left has in cities has not really been recognized or explored in the existing urban political economy literature.
Recent developments in citrus bioflavonoid encapsulation to reinforce controlled antioxidant delivery and generate therapeutic uses: Review

Abstract Citrus fruits contain numerous antioxidative biomolecules including phenolic acids, flavonols, flavanones, polymethoxyflavones (PMFs), and their derivatives. Previous in vitro and in vivo studies thoroughly investigated the antioxidant and therapeutic potential of bioflavonoids extracted from different citrus varieties and fruit fractions. Major bioflavonoids such as hesperidin, naringin, naringenin, and PMFs, had restricted their incorporation into food and health products due to their poor solubility, chemical stability and bioavailability. Considering these limitations, modern encapsulation methodologies such as hydrogelation, liposomal interactions, emulsifications, and nanoparticles have been designed to shield bioflavonoids with improved target distribution for therapeutic enhancements. The size, durability, and binding efficiency of bioflavonoid-loaded encapsulates were acquired by the optimized chemical and instrumental parameters such as solubility, gelation, dispersion, extrusion, and drying. Bioflavonoid-enriched encapsulates have been also proven to be effective against cancer, inflammation, neurodegeneration, and various other illnesses. However, in the future, newer natural binding agents with higher binding capacity might accelerate the encapsulating potential, controlled release, and enhanced bioavailability of citrus bioflavonoids. Overall, these modern encapsulation systems are currently leading to a new era of diet-based medicine, as demand for citrus fruit-based nutritional supplements and edibles grows.
Spatio-Temporal Coordination of Transcription Preinitiation Complex Assembly in Live Cells

Transcription initiation by RNA polymerase II (Pol II) requires preinitiation complex (PIC) assembly at gene promoters. In the dynamic nucleus where thousands of promoters are broadly distributed in chromatin, it is unclear how ten individual components converge on any target to establish the PIC. Here, we use live-cell, single-molecule tracking in S. cerevisiae to document subdiffusive, constrained exploration of the nucleoplasm by PIC components and Mediator’s key functions in guiding this process. On chromatin, TBP, Mediator, and Pol II instruct assembly of a short-lived PIC, which occurs infrequently but efficiently at an average promoter where initiation-coupled disassembly may occur within a few seconds. Moreover, PIC exclusion by nucleosome encroachment underscores regulated promoter accessibility by chromatin remodeling. Thus, coordinated nuclear exploration and recruitment to accessible targets underlies dynamic PIC establishment in yeast. Collectively, our study provides a global spatio-temporal model for transcription initiation in live cells.
Test–Retest Reliability of a Semi-Structured Interview to Aid in Pediatric Traumatic Brain Injury Diagnosis

Abstract Objective: Retrospective self-report is typically used for diagnosing previous pediatric traumatic brain injury (TBI). A new semi-structured interview instrument (New Mexico Assessment of Pediatric TBI; NewMAP TBI) investigated test–retest reliability for TBI characteristics in both the TBI that qualified for study inclusion and for lifetime history of TBI. Method: One-hundred and eight-four mTBI (aged 8–18), 156 matched healthy controls (HC), and their parents completed the NewMAP TBI within 11 days (subacute; SA) and 4 months (early chronic; EC) of injury, with a subset returning at 1 year (late chronic; LC). Results: The test–retest reliability of common TBI characteristics [loss of consciousness (LOC), post-traumatic amnesia (PTA), retrograde amnesia, confusion/disorientation] and post-concussion symptoms (PCS) were examined across study visits. Aside from PTA, binary reporting (present/absent) for all TBI characteristics exhibited acceptable (≥0.60) test–retest reliability for both Qualifying and Remote TBIs across all three visits. In contrast, reliability for continuous data (exact duration) was generally unacceptable, with LOC and PCS meeting acceptable criteria at only half of the assessments. Transforming continuous self-report ratings into discrete categories based on injury severity resulted in acceptable reliability. Reliability was not strongly affected by the parent completing the NewMAP TBI. Conclusions: Categorical reporting of TBI characteristics in children and adolescents can aid clinicians in retrospectively obtaining reliable estimates of TBI severity up to a year post-injury. However, test–retest reliability is strongly impacted by the initial data distribution, selected statistical methods, and potentially by patient difficulty in distinguishing among conceptually similar medical concepts (i.e., PTA vs. confusion).
Establishment of a venovenous extracorporeal membrane oxygenation in a rat model of acute respiratory distress syndrome

Introduction: Venovenous extracorporeal membrane oxygenation (VV ECMO) is now considered a reasonable option to salvage acute respiratory distress syndrome (ARDS). However, we lack a rodent model for experimental studies. This study was undertaken to establish an animal model of VV ECMO in ARDS rats. Methods: A total of 18 Sprague-Dawley (SD) rats (350 ± 50 g) were used in this study. Using a rat model of oleic acid (OA)-induced ARDS, VV ECMO was established through cavoatrial cannulation of the right jugular vein for venous drainage and venous reinfusion with a specially designed three-cavity catheter. Continuous arterial pressure monitoring was implemented by using a catheter through cannulation of the right femoral artery. The central temperature was monitored with a rectal probe. Arterial blood gas monitoring was implemented by a blood gas analyzer at three-time points: at baseline, 1-hour (after OA modeling), and 3.5-hour (after VV ECMO support). Lung tissue and bronchoalveolar lavage fluid were harvested respectively for protein concentration and pulmonary histologic evaluation to confirm the alleviation of lung injury during VV ECMO. Results: Following ARDS induced by OA, ten rats were successfully established on VV ECMO without failure and survived the ECMO procedure. VV ECMO alleviated lung injury and restored adequate circulation for the return of lung function and oxygenation. VV ECMO was associated with decreased lung injury score, wet/dry weight ratio, and ﬂuid leakage into airspaces. Conclusion: We have established a reliable, economical, and functioning ARDS rat model of VV ECMO.
Prophylactic effect of probiotics fortified with Aloe vera pulp nanoemulsion against ethanol-induced gastric ulcer

Abstract The purpose of this study was designed to evaluate the protective effect of probiotics fortified with Aloe vera pulp nanoemulsion on ethanol-induced gastric ulcer (GU). Freshly harvested Aloe vera pulp nanoemulsion was prepared and subsequently inoculated with 2% of the activated yogurt starter culture of Streptococcus thermophilus and Lactobacillus delbreukii subsp. bulgaricus (1:1). Chemical composition and physicochemical characterization of yogurt and the Aloe vera pulp nanoemulsion were assessed. GU was induced by ethanol. Rats were randomly assigned into control, GU, and four prophylactic groups including probiotics fortified with Aloe vera pulp nanoemulsion in the percentage of 0%, 10%, 20%, and 30% respectively. Serum levels of paraoxynase (POX) and tissue levels of malondialdehyde (MDA), nitric oxide (NO), and catalase (CAT) activity were assessed. Serum levels of nuclear factor kappa B (NF-κB), interleukin-1beta (IL-1β), matrix metalloproteinase-9 (MMP-9), ceramide, and homocysteine (Hcy) were evaluated. Results indicated that the Aloe vera pulp nanoemulsion was appeared in spherical nano form with droplets diameter around 330 nm. Ethanol induces GU to cause a significant increase in the levels of MDA, NO, NF-κB, IL-1β, MMP-9, Hcy, and ceramide along with a significant decrease in POX and CAT activities compared to the control group (p < 0.05). Pretreatment with different concentrations of probiotics fortified with Aloe vera pulp nanoemulsion with, especially the 30% concentration, significantly reduce the oxidative stress and ameliorate the release of different inflammatory mediators suggesting it as a promising approach in the protection against GU via scavenging superoxide radicals and inhibiting the activation of the inflammatory signaling cascades.
Functional Roles of α1-, α2-, β1-, and β2-Tubulins in Vegetative Growth, Microtubule Assembly, and Sexual Reproduction of Fusarium graminearum

In this study, we found that F. graminearum contains four different α-/β-tubulin heterodimers (α1-β1, α1-β2, α2-β1, and α2-β2), and they assemble together into a single microtubule. Moreover, α1- and α2-tubulins are functionally interchangeable in microtubule assembly, vegetative growth, and sexual reproduction. ABSTRACT The plant pathogen Fusarium graminearum contains two α-tubulin isotypes (α1 and α2) and two β-tubulin isotypes (β1 and β2). The functional roles of these tubulins in microtubule assembly are not clear. Previous studies reported that α1- and β2-tubulin deletion mutants showed severe growth defects and hypersensitivity to carbendazim, which have not been well explained. Here, we investigated the interaction between α- and β-tubulin of F. graminearum. Colocalization experiments demonstrated that β1- and β2-tubulin are colocalized. Coimmunoprecipitation experiments suggested that β1-tubulin binds to both α1- and α2-tubulin and that β2-tubulin can also bind to α1- or α2-tubulin. Interestingly, deletion of α1-tubulin increased the interaction between β2-tubulin and α2-tubulin. Microtubule observation assays showed that deletion of α1-tubulin completely disrupted β1-tubulin-containing microtubules and significantly decreased β2-tubulin-containing microtubules. Deletion of α2-, β1-, or β2-tubulin had no obvious effect on the microtubule cytoskeleton. However, microtubules in α1- and β2-tubulin deletion mutants were easily depolymerized in the presence of carbendazim. The sexual reproduction assay indicates that α1- and β1-tubulin deletion mutants could not produce asci and ascospores. These results implied that α1-tubulin may be essential for the microtubule cytoskeleton. However, our Δα1-2×α2 mutant (α1-tubulin deletion mutant containing two copies of α2-tubulin) exhibited normal microtubule network, growth, and sexual reproduction. Interestingly, the Δα1-2×α2 mutant was still hypersensitive to carbendazim. In addition, both β1-tubulin and β2-tubulin were found to bind the mitochondrial outer membrane voltage-dependent anion channel (VDAC), indicating that they could regulate the function of VDAC. IMPORTANCE In this study, we found that F. graminearum contains four different α-/β-tubulin heterodimers (α1-/β1-, α1-/β2-, α2-/β1-, and α2-/β2-tubulin heterodimers), and they assemble together into a single microtubule. Moreover, α1- and α2-tubulins are functionally interchangeable in microtubule assembly, vegetative growth, and sexual reproduction. These results provide more insights into the functional roles of different tubulins of F. graminearum, which could be helpful for purification of tubulin heterodimers and development of new tubulin-binding agents.
In vivo potency testing of subretinal rAAV5.hCNGB1 gene therapy in the Cngb1 knockout mouse model of retinitis pigmentosa.

Retinitis pigmentosa type 45 (RP45) is an autosomal-recessively inherited blinding disease caused by mutations in the cyclic nucleotide gated channel subunit beta 1 (CNGB1) gene. In this study, we developed and tested a novel gene supplementation therapy suitable for clinical translation. To this end, we designed a recombinant adeno-associated virus (rAAV) vector carrying a genome that features a novel human rhodopsin promoter (hRHO194) driving rod-specific expression of full-length human CNGB1 (rAAV5.hCNGB1). rAAV5.hCNGB1 was evaluated for efficacy in the Cngb1 knockout (Cngb1-/-) mouse model of RP45. In particular, increasing doses of rAAV5.hCNGB1 were delivered via single subretinal injection in 4-week-old Cngb1-/- mice and the treatment effect was assessed over a follow-up period of 9 months at the level of (i) retinal morphology, (ii) retinal function, (iii) vision-guided behavior, and (iv) transgene expression. We found that subretinal treatment with rAAV5.hCNGB1 resulted in efficient expression of the human CNGB1 protein in mouse rods and was able to normalize the expression of the endogenous mouse CNGA1 subunit, which together with CNGB1 forms the native heterotetrameric cGMP-gated cation channel in rod photoreceptors. The treatment led to a dose-dependent recovery of rod photoreceptor-driven function and preservation of retinal morphology in Cngb1-/- mice. In summary, these results demonstrate the efficacy of hCNGB1 gene supplementation therapy in the Cngb1-/- mouse model of RP45 and support the translation of this approach towards future clinical application.
Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1‐13C]pyruvate magnetic resonance spectroscopy

Hyperpolarized [1‐13C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1‐13C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long‐term left ventricular effects of heart failure medication, and could identify responders to treatment.
Use of Spectroscopic Methods and Their Clinical Applications in Drug Abuse: A Review

Abstract Assurance of substance abuse in plasma and different parts of the body is vital in clinical and legal toxicology. Detection techniques are evaluated for their appropriateness in scientific and clinical sciences, where extraordinary prerequisites must be met. Recognition and affirmation are for the most part done by gas chromatography–Mass spectrometry (GC-MS) or liquid chromatography (LC-MS), Surface-enhanced Raman spectroscopy (SERS), Magnetic resonance imaging, Positron Emission Tomography, Infrared Spectroscopy, and UV Spectroscopy. Progressed spectroscopic techniques provided helpful quantitative or qualitative data about the natural chemistry and science of exploited substances. These spectroscopic techniques are assumed as quick, precise, and some of them are non-damaging investigation apparatus that may be assumed as a substitution for previously used compound investigation. Spectroscopy with its advances in technology is centralized to novel applications in the detection of abused drug substances and clinical toxicology. These techniques have attracted growing interest as forensic tools for the early detection and monitoring of exploited drugs. This review describes the principle, role, and clinical application of various spectroscopic techniques which are utilized for the identification of drug abuse like morphine, cocaine, codeine, alcohol, amphetamines, and their metabolites in whole blood, plasma, hair, and nails.
Evolution of male genitalia in the Drosophila repleta species group (Diptera: Drosophilidae)

The Drosophila repleta group comprises more than one hundred species that inhabit several environments in the Neotropics and use different hosts as rearing and feeding resources. Rather homogeneous in their external morphology, they are generally distinguished by the male genitalia, seemingly their fastest evolving morphological trait, constituting an excellent model to study patterns of genital evolution in the context of a continental adaptive radiation. Although much is known about the evolution of animal genitalia at population level, surveys on macroevolutionary scale of this phenomenon are scarce. This study used a suite of phylogenetic comparative methods to elucidate the macroevolutionary patterns of genital evolution through deep time and large continental scales. Our results indicate that male genital size and some aspects of shape have been evolving by speciational evolution, probably due to the microevolutionary processes involved in species mate recognition. In contrast, several features of the aedeagus shape seemed to have evolved in a gradual fashion, with heterogeneous evolutionary phenotypic rates among clades. In general, the tempo of the evolution of aedeagus morphology was constant from the origin of the group until the Pliocene, when it accelerated in some clades that diversified mainly in this period. The incidence of novel ecological conditions in the tempo of aedeagus evolution and the relationship between species mate recognition and speciation in the Drosophila repleta group are discussed.