Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and structural analysis of the Schizosaccharomyces pombe SMN complex

Abstract The macromolecular SMN complex facilitates the formation of Sm-class ribonucleoproteins involved in mRNA processing (UsnRNPs). While biochemical studies have revealed key activities of the SMN complex, its structural investigation is lagging behind. Here we report on the identification and structural determination of the SMN complex from the lower eukaryote Schizosaccharomyces pombe, consisting of SMN, Gemin2, 6, 7, 8 and Sm proteins. The core of the SMN complex is formed by several copies of SMN tethered through its C-terminal alpha-helices arranged with alternating polarity. This creates a central platform onto which Gemin8 binds and recruits Gemins 6 and 7. The N-terminal parts of the SMN molecules extrude via flexible linkers from the core and enable binding of Gemin2 and Sm proteins. Our data identify the SMN complex as a multivalent hub where Sm proteins are collected in its periphery to allow their joining with UsnRNA.
High Pressure Adsorption Studies of Ethane and Ethylene on Clay-Based Adsorbent Materials

Bentonite clay is tailored in three different ways to produce porous materials viz. PCH1, PCH2, and PILC, where PCH1 and PCH2 are two different clay heterostructures and PILC is a Zr-oxide pillared clay. Surface characterization materials shows that both of PCHs have a higher surface area than PILC, and have micro and mesoporosity, where PILC is basically a microporous. DRIFT and X-ray techniques were used to investigate the surface-groups and height of micropores in PCHs and PILC, respectively. Adsorption isotherms of ethane and ethylene were measured on these materials up to high pressure (1000 kPa) under different temperatures, and by processing the obtained data these materials were evaluated for their aptness for ethane ethylene separation. Isosteric heats of adsorption were observed higher for ethylene than ethane during initial surface coverage for each material-gas system. Interaction in each material-gas system with gradual increase in pressure was elucidated with the help of isosteric heat curves. Adsorption performances of these materials were compared with already studied materials (reported by other workers for ethane/ethane separation). Comparison was based on selectivity and working capacity, which are the two decisive parameters for screening suitability of any adsorbent material (for PSA application).
Alternate Assembly of Ordered Multilayers of SiO2 and Other Nanoparticles and Polyions

Alternate layer-by-layer assembly of colloidal SiO2 particles with polycations has been investigated by quartz crystal microbalance (QCM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). QCM measurement confirmed the high regularity and reproducibility of the assembling process that depends on particle concentration, particle size, and ionic strength. The individual adsorption step was completed within 15 s. The thickness of adsorbed layers increased with increasing SiO2 concentrations at the three particle sizes used (45, 25, and 78 nm in diameter), unlike the case for other polyion assemblies. It also increased with increasing ionic strength of aqueous SiO2 dispersions. According to SEM observation, the assembled film possessed surprisingly flat surfaces at optimized ionic strengths. AFM observation revealed that SiO2 particles were not closely packed. The neutralization ratio of SiO2 and PDDA was estimated by turbidity measurement. Comparison of turbidity and QCM data indicated t.
Early-stage dynamics of chloride ion–pumping rhodopsin revealed by a femtosecond X-ray laser

Significance Light-driven rhodopsin proteins pump ions across cell membranes. They have applications in optogenetics and can potentially be used to develop solar energy–harvesting devices. A detailed understanding of rhodopsin dynamics and functions may therefore assist research in medicine, health, and clean energy. This time-resolved crystallography study carried out with X-ray free-electron lasers reveals detailed dynamics of chloride ion–pumping rhodopsin (ClR) within 100 ps of light activation. It shows the dissociation of Cl− from the Schiff base binding site upon light-triggered retinal isomerization. This Cl− dissociation is followed by diffusion toward the intracellular direction. The results hint at a common ion-pumping mechanism across rhodopsin families. Chloride ion–pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl− into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation–diffusion process upon light-triggered retinal isomerization.
Beyond avatars and arrows: Testing the mentalising and submentalising hypotheses with a novel entity paradigm

In recent years, there has been a heated debate about how to interpret findings that seem to show that humans rapidly and automatically calculate the visual perspectives of others. In this study, we investigated the question of whether automatic interference effects found in the dot-perspective task are the product of domain-specific perspective-taking processes or of domain-general “submentalising” processes. Previous attempts to address this question have done so by implementing inanimate controls, such as arrows, as stimuli. The rationale for this is that submentalising processes that respond to directionality should be engaged by such stimuli, whereas domain-specific perspective-taking mechanisms, if they exist, should not. These previous attempts have been limited, however, by the implied intentionality of the stimuli they have used (e.g., arrows), which may have invited participants to imbue them with perspectival agency. Drawing inspiration from “novel entity” paradigms from infant gaze–following research, we designed a version of the dot-perspective task that allowed us to precisely control whether a central stimulus was viewed as animate or inanimate. Across four experiments, we found no evidence that automatic “perspective-taking” effects in the dot-perspective task are modulated by beliefs about the animacy of the central stimulus. Our results also suggest that these effects may be due to the task-switching elements of the dot-perspective paradigm, rather than automatic directional orienting. Together, these results indicate that neither the perspective-taking nor the standard submentalising interpretations of the dot-perspective task are fully correct.
Significance of the physician’s and the patient’s sex in hospitalized patients with community-acquired pneumonia

Abstract Background Numerous studies have revealed that the sex of the patient or of the attending physician have impact on patient care, treatment, morbidity and mortality. Community-acquired pneumonia (CAP) is a common cause of hospitalization, antibiotic treatment and intensive care unit (ICU) admission. The purpose of this study was to examine if the patient’s or the attending physicians’ sex may influence the management of hospitalized patients with CAP. Methods Our study included 826 consecutive inpatients with CAP (404 females, and 422 male patients, 429 patients initially treated by a female physician and 397 patients initially treated by a male physician). We examined if the patient’s, or the initial attending physician’s sex, affected treatment and outcome in patients with CAP. Results Patients mean age was 69 years, 30-day mortality 9%. By use of the pneumonia severity index, male patients were found to be more severely ill at admission (p = .0008). Fewer female physicians’ patients were admitted from the emergency department (ED) to the ICU when compared to male physicians’ patients, 5% versus 10% (p = .006), and female physicians’ patients received their first intravenous (IV) antibiotic dose later than male physicians’ patients in the ED (p = .003). Conclusion Our study indicates that the sex of the attending physician may affect the chosen level of care and antibiotic treatment, and that admitted male patients with CAP were more seriously ill than admitted female patients with CAP.
Undergraduate students' perception and satisfaction regarding online learning system amidst COVID-19 Pandemic in Pakistan.

Background During COVID-19 pandemic, to forestall the outspread of contagion, all academic activities where physical presence was mandatory were halted. This prompted the shifting of educational activities to the online learning system. Current investigation aimed to determine the perception of undergraduate students of various disciplines about online learning which has been implemented across all the universities of Pakistan in the wake of COVID-19 lockdown. Methods A cross-sectional descriptive study was conducted and data was collected from ten different medical, engineering and art universities of Pakistan. Utilizing Openepi, the calculated data sample size was 600. Students were asked 23 different questions including a validated and reliable scale (α=0.952) composed of 14 questions to determine the satisfaction level of students from e-learning. Descriptive statistics, independent sample t-test, ANOVA and chi-square test were used to analyse data through SPSS. Results The most broadly embraced teaching methodology was online classes through Zoom Application. According to the developed scale, overall, 78% of students were dissatisfied from online learning. Students also raised concerns over assessment methods, student-instructor communication, fairness of examination and difficulty in understanding concepts. Majority of students preferred classroom teaching and 81% of respondents didn't want to continue with e-learning. Conclusion Results have depicted that students are not satisfied with e-learning and they pointed out some critical defects in the system. HEC and rectors should treat this issue as top-priority for provision of good quality education and to save the future of undergraduate students of Pakistan.
Neoadjuvant Pembrolizumab and High-Dose IFNα-2b in Resectable Regionally Advanced Melanoma

Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma. Patients and Methods: Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m2/day i.v. , 5 days per week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery. Results: A total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2–43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5–85.8], with a 43% (95% CI: 27.3–60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively). Conclusions: Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator. See related commentary by Menzies et al., p. 4133
Untangling the crosstalk between BRCA1 and R-loops during DNA repair

Abstract R-loops are RNA:DNA hybrids assembled during biological processes but are also linked to genetic instability when formed out of their natural context. Emerging evidence suggests that the repair of DNA double-strand breaks requires the formation of a transient R-loop, which eventually must be removed to guarantee a correct repair process. The multifaceted BRCA1 protein has been shown to be recruited at this specific break-induced R-loop, and it facilitates mechanisms in order to regulate R-loop removal. In this review, we discuss the different potential roles of BRCA1 in R-loop homeostasis during DNA repair and how these processes ensure faithful DSB repair.
The interplay between gaze cueing and facial trait impressions

The gaze cueing effect involves the rapid orientation of attention to follow the gaze direction of another person. Previous studies reported reciprocal influences between social variables and the gaze cueing effect, with modulation of gaze cueing by social features of face stimuli and modulation of the observer’s social judgements from the validity of the gaze cues themselves. However, it remains unclear which social dimensions can affect—and be affected by—gaze cues. We used computer-averaged prototype face-like images with high and low levels of perceived trustworthiness and dominance to investigate the impact of these two fundamental social impression dimensions on the gaze cueing effect. Moreover, by varying the proportions of valid and invalid gaze cues across three experiments, we assessed whether gaze cueing influences observers’ impressions of dominance and trustworthiness through incidental learning. Bayesian statistical analyses provided clear evidence that the gaze cueing effect was not modulated by facial social trait impressions (Experiments 1–3). However, there was uncertain evidence of incidental learning of social evaluations following the gaze cueing task. A decrease in perceived trustworthiness for non-cooperative low dominance faces (Experiment 2) and an increase in dominance ratings for faces whose gaze behaviour contradicted expectations (Experiment 3) appeared, but further research is needed to clarify these effects. Thus, this study confirms that attentional shifts triggered by gaze direction involve a robust and relatively automatic process, which could nonetheless influence social impressions depending on perceived traits and the gaze behaviour of faces providing the cues.
Musculoskeletal modelling of the Nile crocodile (Crocodylus niloticus) hindlimb: Effects of limb posture on leverage during terrestrial locomotion

We developed a three‐dimensional, computational biomechanical model of a juvenile Nile crocodile (Crocodylus niloticus) pelvis and hindlimb, composed of 47 pelvic limb muscles, to investigate muscle function. We tested whether crocodiles, which are known to use a variety of limb postures during movement, use limb orientations (joint angles) that optimise the moment arms (leverages) or moment‐generating capacities of their muscles during different limb postures ranging from a high walk to a sprawling motion. We also describe the three‐dimensional (3D) kinematics of the crocodylian hindlimb during terrestrial locomotion across an instrumented walkway and a treadmill captured via X‐ray Reconstruction of Moving Morphology (biplanar fluoroscopy; ‘XROMM’). We reconstructed the 3D positions and orientations of each of the hindlimb bones and used dissection data for muscle lines of action to reconstruct a focal, subject‐specific 3D musculoskeletal model. Motion data for different styles of walking (a high, crouched, bended and two types of sprawling motion) were fed into the 3D model to identify whether any joints adopted near‐optimal poses for leverage across each of the behaviours. We found that (1) the hip adductors and knee extensors had their largest leverages during sprawling postures and (2) more erect postures typically involved greater peak moment arms about the hip (flexion‐extension), knee (flexion) and metatarsophalangeal (flexion) joints. The results did not fully support the hypothesis that optimal poses are present during different locomotory behaviours because the peak capacities were not always reached around mid‐stance phase. Furthermore, we obtained few clear trends for isometric moment‐generating capacities. Therefore, perhaps peak muscular leverage in Nile crocodiles is instead reached either in early/late stance or possibly during swing phase or other locomotory behaviours that were not studied here, such as non‐terrestrial movement. Alternatively, our findings could reflect a trade‐off between having to execute different postures, meaning that hindlimb muscle leverage is not optimised for any singular posture or behaviour. Our model, however, provides a comprehensive set of 3D estimates of muscle actions in extant crocodiles which can form a basis for investigating muscle function in extinct archosaurs.
Exploring the clinical relevance of a dichotomy between affective and non‐affective psychosis: Results from a first‐episode psychosis cohort study

Defining diagnosis is complex in early psychosis, which may delay the introduction of an appropriate treatment. The dichotomy of affective and non‐affective psychosis is used in clinical setting but remains questioned on a scientific basis. In this study, we explore the clinical relevance of this dichotomy on the basis of clinical variables in a sample of first‐episode psychosis patients.
Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab

Objective Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. Design Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. Results Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2–5.6) vs 37.0 (15.2–76.1), p<0.0001). Conclusions Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. Trial registration number ISRCTN45176516.
DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice

More than 65 million people have been confirmed infection with SARS-CoV-2 and more than 1 million have died from COVID-19 and this pandemic remains critical worldwide. Effective vaccines are one of the most important strategies to limit the pandemic. Here, we report a construction strategy of DNA vaccine candidates expressing full length wild type SARS-CoV-2 spike (S) protein, S1 or S2 region and their immunogenicity in mice. All DNA vaccine constructs of pCMVkan-S, -S1 and -S2 induced high levels of specific binding IgG that showed a balance of IgG1/IgG2a response. However, only the sera from mice vaccinated with pCMKkan-S or -S1 DNA vaccines could inhibit viral RBD and ACE2 interaction. The highest neutralizing antibody (NAb) titer was found in pCMVkan-S group, followed by -S1, while -S2 showed the lowest PRNT50 titers. The geometric mean titers (GMTs) were 2,551, 1,005 and 291 for pCMVkan-S, -S1 and -S2, respectively. pCMVkan-S construct vaccine also induced the highest magnitude and breadth of T cells response. Analysis of IFN-γ positive cells after stimulation with SARS-CoV-2 spike peptide pools were 2,991, 1,376 and 1,885 SFC/106 splenocytes for pCMVkan-S, -S1 and -S2, respectively. Our findings highlighted that full-length S antigen is more potent than the truncated spike (S1 or S2) in inducing of neutralizing antibody and robust T cell responses.
Assessing the Bioactive Profile of Antifungal-Loaded Calcium Sulfate against Fungal Biofilms

Calcium sulfate (CS) has been used clinically as a bone- or void-filling biomaterial, and its resorptive properties have provided the prospect for its use as a release mechanism for local antibiotics to control biofilms. Here, we aimed to test CS beads loaded with three antifungal drugs against planktonic and sessile fungal species to assess whether these antifungal beads could be harnessed to provide consistent release of antifungals at biofilm-inhibitory doses. ABSTRACT Calcium sulfate (CS) has been used clinically as a bone- or void-filling biomaterial, and its resorptive properties have provided the prospect for its use as a release mechanism for local antibiotics to control biofilms. Here, we aimed to test CS beads loaded with three antifungal drugs against planktonic and sessile fungal species to assess whether these antifungal beads could be harnessed to provide consistent release of antifungals at biofilm-inhibitory doses. A panel of different fungal species (n = 15) were selected for planktonic broth microdilution testing with fluconazole (FLZ), amphotericin B (AMB), and caspofungin (CSP). After establishing planktonic inhibition, antifungal CS beads were introduced to fungal biofilms (n = 5) to assess biofilm formation and cell viability through a combination of standard quantitative and qualitative biofilm assays. Inoculation of a hydrogel substrate, packed with antifungal CS beads, was also used to assess diffusion through a semidry material, to mimic active infection in vivo. In general, antifungals released from loaded CS beads were all effective at inhibiting the pathogenic fungi over 7 days within standard MIC ranges for these fungi. We observed a significant reduction of pregrown fungal biofilms across key fungal pathogens following treatment, with visually observable changes in cell morphology and biofilm coverage provided by scanning electron microscopy. Assessment of biofilm inhibition also revealed reductions in total and viable cells across all organisms tested. These data show that antifungal-loaded CS beads produce a sustained antimicrobial effect that inhibits and kills clinically relevant fungal species in vitro as planktonic and biofilm cells.