Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition

Pannexins are large-pore forming channels responsible for ATP release under a variety of physiological and pathological conditions. Although predicted to share similar membrane topology with other large-pore forming proteins such as connexins, innexins, and LRRC8, pannexins have minimal sequence similarity to these protein families. Here, we present the cryo-EM structure of a frog pannexin 1 (Panx1) channel at 3.0 Å. We find that Panx1 protomers harbor four transmembrane helices similar in arrangement to other large-pore forming proteins but assemble as a heptameric channel with a unique constriction formed by Trp74 in the first extracellular loop. Mutating Trp74 or the nearby Arg75 disrupt ion selectivity, whereas altering residues in the hydrophobic groove formed by the two extracellular loops abrogates channel inhibition by carbenoxolone. Our structural and functional study establishes the extracellular loops as important structural motifs for ion selectivity and channel inhibition in Panx1.
Occupancy spectrum distribution: application for coalescence simulation with generic mergers

MOTIVATION As the density of sampled population increases, especially as studies incorporate aspects of the spatial landscape to study evolutionary processes, efficient simulation of genetic data under the coalescent becomes a primary challenge. Beyond the computational demands, coalescence-based simulation strategies have to be reconsidered because traditional assumptions about the dynamics of coalescing lineages within local populations may be violated (e.g., more than two daughter lineages may coalesce to a parent at low population densities). Specifically, to efficiently assign n lineages to m parents, the order relation between n and m strongly affects the relevant algorithm for the coalescent simulator (e.g., only when $$ n \lt \sqrt{2m} $$, is it reasonable to assume that two lineages, at most, can be assigned to the same parent). Controlling the details of the simulation model as a function of n and m is then crucial to represent accurately and efficiently the assignment process, but current implementations make it difficult to switch between different types of lineage mergers at run-time or even compile-time. RESULTS With the described occupancy spectrum and algorithm that generates the support of the joint probability distribution of the occupancy spectrum, computation is much faster than realizing the whole assignment process under the coalescent. Using general definitions of lineage merges, which also makes the codebase resusable, we implement several variants of coalescent mergers, including an approximation where low probability spectrums are discarded. Comparison of runtimes and performance of the different C ++ highly reusable coalescence mergers (binary, multiple, hybrids) are given and we illustrate their potential utility with example applications. AVAILABILITY All components are integrated into Quetzal, an open-source C ++ library for coalescence available at https://becheler.github. io/pages/quetzal.html. SUPPLEMENTARY INFORMATION Algorithms, details of application, as well as performance metrics are available at Bioinformatics online.
An Investigative Review for Pharmaceutical Analysis of 1,4-Dihydropyridine-3,5-Dicarboxylic Acid Derivative: Cilnidipine

Abstract Hypertension is commonly a quiet condition, and it expands the risk of heart diseases and stroke. Calcium delivers a substantial role in cardiovascular functions and hence is essential for cardiac automaticity and functioning. Calcium channel antagonists are the choice of drugs for the management of cardiovascular diseases; they precisely stop the introduction of calcium through L-type calcium channels are existing channels in the heart. Cilnidipine belongs to the class 4th generation calcium channel blockers as a foremost therapeutic agent used in the treatment of hypertension and heart diseases. This review article focuses on an inclusive account of crucial analytical methodologies used for the pharmaceutical analysis of cilnidipine in pure forms, biological samples and pharmaceuticals. According to literature reports several analytical techniques such as hyphenated techniques, high-performance thin-layer chromatography, high-performance liquid-chromatography, capillary electrophoresis, voltammetry, UV/Vis-spectrophotometry, and Fourier-transform infrared spectroscopy approaches have been used for determination of cilnidipine alone or in the combined dosage form. We have also discussed the pharmacopeial assay methods, physicochemical properties, and also depict the stacked column chart for year wise publication count for cilnidipine. From literature, concluded that the high-performance liquid-chromatography and UV/Vis-spectrophotometry methods are the most prevailing methods for the analysis of cilnidipine. The data presented in this review may provide a very significant base for further studies on cilnidipine in the area of drug analysis.
A Hybrid Speller Design Using Eye Tracking and SSVEP Brain–Computer Interface

Steady-state visual evoked potentials (SSVEPs) have been extensively utilized to develop brain–computer interfaces (BCIs) due to the advantages of robustness, large number of commands, high classification accuracies, and information transfer rates (ITRs). However, the use of several simultaneous flickering stimuli often causes high levels of user discomfort, tiredness, annoyingness, and fatigue. Here we propose to design a stimuli-responsive hybrid speller by using electroencephalography (EEG) and video-based eye-tracking to increase user comfortability levels when presented with large numbers of simultaneously flickering stimuli. Interestingly, a canonical correlation analysis (CCA)-based framework was useful to identify target frequency with a 1 s duration of flickering signal. Our proposed BCI-speller uses only six frequencies to classify forty-eight targets, thus achieve greatly increased ITR, whereas basic SSVEP BCI-spellers use an equal number of frequencies to the number of targets. Using this speller, we obtained an average classification accuracy of 90.35 ± 3.597% with an average ITR of 184.06 ± 12.761 bits per minute in a cued-spelling task and an ITR of 190.73 ± 17.849 bits per minute in a free-spelling task. Consequently, our proposed speller is superior to the other spellers in terms of targets classified, classification accuracy, and ITR, while producing less fatigue, annoyingness, tiredness and discomfort. Together, our proposed hybrid eye tracking and SSVEP BCI-based system will ultimately enable a truly high-speed communication channel.
Efficiency of timed pregnancies in C57BL/6 and BALB/c mice by mating one male with up to four females

For a wide range of biomedical approaches, an accurate estimate of the age of embryos or pups is important. Overnight mating is the method that is mostly used to establish timed pregnancies. The oestrus cycle in mice repeats every four to five days. So, not all females will get pregnant because they are not in oestrus. Therefore, the aim of this study was to analyse whether polygamous mating could increase the rate of timed pregnancies per breeding cage and female. We compared overnight timed mating regimes with up to four females per male, using C57BL/6 and BALB/c mice as well as F1 hybrids of these two strains. The number of vaginal plugs, number of females that gave birth and weaned litter (including size and weaning weight) were recorded. Our results showed that the plug and pregnancy rate decreased, but the productivity per breeding cage increased for polygamous mating regimes. The proportion of females with vaginal plugs and females that gave birth was significantly higher in monogamous mating. The proportion of plugged females that gave birth, as well as litter size and weaning weight, were not influenced by the mating regime. After analysing 513 breeding cages with a total of 1090 females, we found that polygamous mating with up to three females per male can increase the number of timed pregnancies. However, in the mating regime with more than three females, the rate of timed pregnancy as well as number of pups per female declined.
Doing our work better, together: a relationship-based approach to defining the quality improvement agenda in trauma care

Background Trauma care represents a complex patient journey, requiring multidisciplinary coordinated care. Team members are human, and as such, how they feel about their colleagues and their work affects performance. The challenge for health service leaders is enabling culture that supports high levels of collaboration, co-operation and coordination across diverse groups. We aimed to define and improve relational aspects of trauma care at Gold Coast University Hospital. Methods We conducted a mixed-methods collaborative ethnography using the relational coordination survey—an established tool to analyse the relational dimensions of multidisciplinary teamwork—participant observation, interviews and narrative surveys. Findings were presented to clinicians in working groups for further interpretation and to facilitate co-creation of targeted interventions designed to improve team relationships and performance. Findings We engaged a complex multidisciplinary network of ~500 care providers dispersed across seven core interdependent clinical disciplines. Initial findings highlighted the importance of relationships in trauma care and opportunities to improve. Narrative survey and ethnographic findings further highlighted the centrality of a translational simulation programme in contributing positively to team culture and relational ties. A range of 16 interventions—focusing on structural, process and relational dimensions—were co-created with participants and are now being implemented and evaluated by various trauma care providers. Conclusions Through engagement of clinicians spanning organisational boundaries, relational aspects of care can be measured and directly targeted in a collaborative quality improvement process. We encourage healthcare leaders to consider relationship-based quality improvement strategies, including translational simulation and relational coordination processes, in their efforts to improve care for patients with complex, interdependent journeys.
Mechanistic dissection of macro- and micronucleophagy

ABSTRACT Nucleophagy, the mechanism for autophagic degradation of nuclear material, occurs in both a macro- and micronucleophagic manner. Upon nitrogen deprivation, we observed, in an in-depth fluorescence microscopy study, the formation of micronuclei: small parts of superfluous nuclear components surrounded by perinuclear ER. We identified two types of micronuclei associated with a corresponding autophagic mode. Our results showed that macronucleophagy degraded these smaller micronuclei. Engulfed in Atg8-positive phagophores and containing cargo receptor Atg39, macronucleophagic structures revealed finger-like extensions when observed in 3-dimensional reconstitutions of fluorescence microscopy images, suggesting directional growth. Interestingly, in the late stages of phagophore elongation, the adjacent vacuolar membrane showed a reduction of integral membrane protein Pho8. This change in membrane composition could indicate the formation of a specialized vacuolar domain, required for autophagosomal fusion. Significantly larger micronuclei formed at nucleus vacuole junctions and were identified as a substrate of piecemeal microautophagy of the nucleus (PMN), by the presence of the integral membrane protein Nvj1. Micronuclei sequestered by vacuolar invaginations also contained Atg39. A detailed investigation revealed that both Atg39 and Atg8 accumulated between the vacuolar tips. These findings suggest a role for Atg39 in micronucleophagy. Indeed, following the degradation of Nvj1, an exclusive substrate of PMN, in immunoblots, we could confirm the essential role of Atg39 for PMN. Our study thus details the involvement of Atg8 in both macronucleophagy and PMN and identifies Atg39 as the general cargo receptor for nucleophagic processes. Abbreviations: DIC: Differential interference contrast, FWHM: Full width at half maximum, IQR: Interquartile range, MIPA: Micropexophagy-specific membrane apparatus, NLS: Nuclear localization signal, NVJ: Nucleus vacuole junction, PMN: Piecemeal microautophagy of the nucleus, pnER: Perinuclear ER.
From formulation to in vivo model: A comprehensive study of a synergistic relationship between vancomycin, carvacrol, and cuminaldehyde against Enterococcus faecium

Vancomycin‐resistant Enterococcus faecium (VRE) has become endemic in healthcare settings, reducing treatment options for enterococcal infections. New antimicrobials for VRE infections are a high priority, but the development of novel antibiotics is time‐consuming and expensive. Essential oils (EOs) synergistically enhance the activity of some existing antibiotics, suggesting that EO–antibiotic combinations could resensitise resistant bacteria and maintain the antibiotic repertoire. The mechanism of resensitisation of bacteria to antibiotics by EOs is relatively understudied. Here, the synergistic interactions between carvacrol (1.98 mM) and cuminaldehyde (4.20 mM) were shown to reestablish susceptibility to vancomycin (0.031 mg/L) in VRE, resulting in bactericidal activity (4.73 log10 CFU/ml reduction). Gene expression profiling, coupled with β‐galactosidase leakage and salt tolerance assays, suggested that cell envelope damage contributes to the synergistic bactericidal effect against VRE. The EO–vancomycin combination was also shown to kill clinical isolates of VRE (2.33–5.25 log10 CFU/ml reduction), and stable resistance did not appear to develop even after multiple passages. The in vivo efficacy of the EO–vancomycin combination was tested in a Galleria mellonella larvae assay; however, no antimicrobial action was observed, indicating that further drug development is required for the EO–vancomycin combination to be clinically useful for treatment of VRE infections.
Alzheimer Disease and Related Dementia Resources: Perspectives of African American and Caucasian Family Caregivers in Northwest Louisiana

We examined knowledge of Alzheimer’s disease and related dementias (ADRD), resources, and research opportunities among older African American (AA) and Caucasian caregivers. A mixed methods design integrated qualitative (focus group) and quantitative (survey) data from Northwest Louisiana. Eight focus groups (59 adults, 92% female, 78% AA, 25% rural) revealed limited knowledge. Quantitative findings from 117 ADRD caregivers (83% female, 72% AA, 30% limited heath literacy, 27% low income) indicated participants obtained information from providers (54%), friends and relatives (32%), and the internet (37%). Barriers to care were cost (24%) and lack of family agreement (17%). Few families used adult daycare (8%) or support groups (28%). Concerns about research participation were violation of privacy (30%) and fear of patient distress (27%). Distrust of doctors was minimal (3%). Findings did not vary by race. There is a need for clear, literacy-appropriate information about ADRD, caregiver resources, and clinical trials.
Low Lactic Acid-Producing Strain of Lachancea thermotolerans as a New Starter for Beer Production

Growing consumer interest in new beer flavors is contributing to the application of innovative materials and non-Saccharomyces yeast in brewing. The goal of this study was to test the impact of the low lactic acid-producing Lachancea thermotolerans MN477031 strain on the process of fermenting beer wort, with two different concentrations of bitter compounds, and on the quality of the beer produced. Qualify factors were broadly analyzed, including ethanol content, apparent degree of fermentation, sugars, organic acids, free amino nitrogen, glycerol, volatile compounds, ions and so on. It was proven that the L. thermotolerans MN477031 strain demonstrated a high capacity for rapid initiation of wort fermentation, and a tolerance to hop-derived compounds. As a result, the alcohol content in beer from this method of production was approximately 20% lower, while the content of the real extract was significantly higher in comparison to commercial Safbrew T-58. This strain stands out from many strains of L. thermotolerans due to the low lactic acid production and only marginal influence on pH decrease compared to Saccharomyces cerevisiae. Therefore, the potential of MN477031 in the production of different types of beer (not only sour) is very high. The composition of volatile compounds in L. thermotolerans beer differs—not only in terms of the use of the strain, but also in hop variety.
Temperature-Dependent Luminescence of Red-Emitting Ba2Y5B5O17: Eu3+ Phosphors with Efficiencies Close to Unity for Near-UV LEDs

Solid state white light sources based on a near-UV LED chip are gaining more and more attention. This is due to the increasing efficiency of near-UV-emitting LED chips and wider phosphors selection if compared to devices based on blue LED chips. Here, a brief overview is given of the concepts of generating white light employing near-UV LED and some optical properties of the available phosphors are discussed. Finally, the synthesis and optical properties of very efficient red-emitting Ba2Y5B5O17:Eu3+ phosphor powder and ceramics is reported and discussed in terms of possible application as a red component in near-UV LED-based white light sources.
Directed Self-Assembly of Polystyrene Nanospheres by Direct Laser-Writing Lithography

In this work, we performed a systematic study on the effect of the geometry of pre-patterned templates and spin-coating conditions on the self-assembling process of colloidal nanospheres. To achieve this goal, large-scale templates, with different size and shape, were generated by direct laser-writer lithography over square millimetre areas. When deposited over patterned templates, the ordering dynamics of the self-assembled nanospheres exhibits an inverse trend with respect to that observed for the maximisation of the correlation length ξ on a flat surface. Furthermore, the self-assembly process was found to be strongly dependent on the height (H) of the template sidewalls. In particular, we observed that, when H is 0.6 times the nanospheres diameter and spinning speed 2500 rpm, the formation of a confined and well ordered monolayer is promoted. To unveil the defects generation inside the templates, a systematic assessment of the directed self-assembly quality was performed by a novel method based on Delaunay triangulation. As a result of this study, we found that, in the best deposition conditions, the self-assembly process leads to well-ordered monolayer that extended for tens of micrometres within the linear templates, where 96.2% of them is aligned with the template sidewalls.
The small molecule BI-2852 induces a nonfunctional dimer of KRAS

In Kessler et al. (1), the small molecule BI-2852 is shown to bind—at nanomolar affinity—to KRAS between switch I and II, inhibiting interactions with effectors. Here, we identify an alternative explanation for the inhibitory activity. While investigating the BI-2852 KRAS complex (Protein Data Bank [PDB] code 6GJ8), we noticed, by revealing the molecules in the neighboring unit cell, BI-2852 induces a KRAS dimer with rotational symmetry. This dimer complex consists of four molecules (two of BI-2852 and two of KRAS; Fig. 1 A ). Fig. 1. Dimer of KRAS with BI-2852. ( A ) Cartoon of BI-2852 KRAS dimer. Lig1 (cyan) and Lig2 (magenta) interact with both Ras1 (beige) and Ras2 (orange). ( B ) KRAS (ribbons) and key side chains are shown. ( C ) Zoom-in of the binding site: salt–bridge interactions shown (dashed lines). ( D ) Lid (green) and Basin (purple) are indicated on Ras1. Both Lig1 and Lig2 are shown on Ras1. The indole rings, colored green and purple, engage the Lid and Basin, respectively. ( E ) Absorbance A 280 plotted as a function of elution volume: … [↵][1]1To whom correspondence may be addressed. Email: trent.balius{at}nih.gov. [1]: #xref-corresp-1-1
Breastfeeding and postnatal depression in Sabah, Malaysia

iii Abbreviations v List of Tables vi List of Figures ix CHAPTER 1: INTRODUCTION 1.1 Background of the study 1 1.2 Significance of the study 2 1.3 Description of Sabah, Malaysia 4 1.4 Aim and objectives of the study 5 1.4. 1 Research questions 6 1.4. 2 Specific objectives 6 1.5 Scope and outline of the thesis 6 1.6 The definition of terms used in this study 7 1.7 Limitations 8 CHAPTER 2: REVIEW OF THE LITERATURE 2.1 Breastfeeding 9 2.1.1 Breastfeeding in Asia 12 2.1.2 Breastfeeding in Malaysia 19 2.1.2.1 Breastfeeding Promotion Programme 19 2.1.2.2 Breastfeeding initiation and duration 20 2.1.2.3 Reasons for breastfeeding discontinuation 29 2.1.3 Predictors of initiation and duration of breastfeeding 32 xi 2.2 Postpartum depression 42 2.2.1 Antenatal depression 45 2.2.2 Predictors of Postpartum Depression 47 2.3 Postpartum depression and breastfeeding 51 2.4 Postpartum depression and cultural factors 62 CHAPTER 3: METHODOLOGY 3.1 Study location 68 3.2 Study design and data collection procedure 69 3.2.1 Sample size calculation 69 3.3 Research instruments 70 3.3.1 Demographic and breastfeeding Information 70 3.3.2 Iowa Infant Feeding Scale 70 3.3.3 Edinburgh Postpartum Depression Scale (EPDS) – Malay version 71 3.4 Statistical analysis 73 3.4. 1 Descriptive and Univariate Analysis 73 3.4. 2 Generalised Logistic Estimating Equations (GEE) 73 3.4. 3 Cox Proportional Hazards Regression Analysis 74 3.5 Ethical Considerations 75
Lignans from medicinal plants and their anticancer effect.

Since early times, various plants have been used as remedies for treating different kinds of diseases and lesions with satisfying results. The phenolic compounds are secondary metabolites from medicinal plants which include a wide category of compounds such as phenolic acids, flavonoids, tannins, stilbenes, curcuminoids, xanthones, coumarins, lignans, etc. Between these, lignans are considered important in cancer prevention and treatment, besides others beneficial health effects, e.g. antioxidant, anticarcinogenic, antimutagenic and anti-estrogenic effects. This review summarizes the most recent literature and the most important results concerning plant lignans and their derivatives in cancer prevention and treatment, both in vitro and in vivo assessments. The mechanistic aspects will be also highlighted.
Association of rs699947 (−2578 C/A) and rs2010963 (−634 G/C) Single Nucleotide Polymorphisms of the VEGF Gene, VEGF-A and Leptin Serum Level, and Cardiovascular Risk in Patients with Excess Body Mass: A Case–Control Study

Background: Two single nucleotide polymorphisms (SNPs) of the VEGF gene, rs699947 and rs2010963, are responsible for differentiated gene expression. A mutual dependence between VEGF and leptin serum level has been observed. This study investigated the associations between the rs699947 and rs2010963 SNPs of VEGF gene, VEGF-A, and leptin serum concentrations, and cardiometabolic risk of body mass excess. Methods: In this case–control study, 212 subjects with excess body mass and 145 normal-weight controls gave blood samples and underwent anthropometric and pulse wave analysis. Genotyping of VEGF gene was carried out to analyze the rs699947 (−2578 C/A) and rs2010963 (−634 G/C) SNPs. (ClinicalTrials.gov ID: NCT04077554). Results: This study showed a significant positive correlation between serum levels of VEGF-A and leptin in individuals with excess body mass possessing the CC genotype of the rs699947 variant of the VEGF gene. It has been registered that an increase in VEGF-A serum level correlates with an increase in arterial stiffness in excess body mass patients harboring AA genotype of the rs699947 (−2578 C/A) variant of the VEGF gene. No differences in VEGF-A and leptin serum concentrations were noted between particular genotypes. Conclusions: The CC genotype of the rs699947 variant of the VEGF gene promotes a positive interdependency between leptin and VEGF-A serum levels in subjects with excess body mass.