Miracle-dz/UniFAR-FTUs huggingface dataset:
BCL: : MolAlign: Three-Dimensional Small Molecule Alignment for Pharmacophore Mapping

Small molecule flexible alignment is a critical component of both ligand- and structure-based methods in computer-aided drug discovery. Despite its importance, the availability of high-quality flexible alignment software packages is limited. Here, we present BCL::MolAlign, a freely available property-based molecular alignment program. BCL::MolAlign accommodates ligand flexibility through a combination of pregenerated conformers and on-the-fly bond rotation. BCL::MolAlign converges on alignment poses by sampling the relative orientations of mutually matching atom pairs between molecules through Monte Carlo Metropolis sampling. Across six diverse ligand data sets, BCL::MolAlign flexible alignment outperforms MOE, ROCS, and FLEXS in recovering native ligand binding poses. Moreover, the BCL::MolAlign alignment score is more predictive of ligand activity than maximum common substructure similarity across 10 data sets. Finally, on a recently published benchmark set of 20 high quality congeneric ligand-protein complexes, BCL::MolAlign is able to recover a larger fraction of native binding poses than maximum common substructure-based alignment and RosettaLigand. BCL::MolAlign can be obtained as part of the Biology and Chemistry Library (BCL) software package freely with an academic license or can be accessed via Web server at http://meilerlab.org/index.php/servers/molalign .
Delineation of pentatricopeptide repeat codes for target RNA prediction

Abstract Members of the pentatricopeptide repeat (PPR) protein family are sequence-specific RNA-binding proteins that play crucial roles in organelle RNA metabolism. Each PPR protein consists of a tandem array of PPR motifs, each of which aligns to one nucleotide of the RNA target. The di-residues in the PPR motif, which are referred to as the PPR codes, determine nucleotide specificity. Numerous PPR codes are distributed among the vast number of PPR motifs, but the correlation between PPR codes and RNA bases is poorly understood, which hinders target RNA prediction and functional investigation of PPR proteins. To address this issue, we developed a modular assembly method for high-throughput construction of designer PPRs, and by using this method, 62 designer PPR proteins containing various PPR codes were assembled. Then, the correlation between these PPR codes and RNA bases was systematically explored and delineated. Based on this correlation, the web server PPRCODE (http://yinlab.hzau.edu.cn/pprcode) was developed. Our study will not only serve as a platform for facilitating target RNA prediction and functional investigation of the large number of PPR family proteins but also provide an alternative strategy for the assembly of custom PPRs that can potentially be used for plant organelle RNA manipulation.
Thermal transport in thermoelectric materials with chemical bond hierarchy

Chemical bond hierarchy (CBH) depicts a unique structural type of solids, in which fractions of the materials are loosely bonded in a relatively rigid framework. The weak bonding in materials with CBH induces special atomic vibrational motions and has a significant influence on the thermoelectric transport properties. The architecture of compounds with CBH was first proposed by Slack in his ‘phonon glass electron crystal’ paradigm and has led to the discovery of numerous new thermoelectric compounds over the years. This review covers various types of thermoelectric materials with different levels of CBH, focusing on their lattice thermal conductivities (κLs). Caged compounds, with foreign impurities in the cages as the rattlers, are the first type of compounds stimulating the study of CBH. The fillers in both the clathrates and the filled skutterudites greatly reduce the κL accompanied by abnormal temperature dependence. As reviewed herein, the reduced κL is attributed to different mechanistic sources, i.e., the resonant scattering or the enhanced anharmonic phonon scatterings. Both may contribute to the κL reductions. In recent years, more materials with different types of CBH have been discovered, some containing complex atomic clusters as the rattlers, and others having flowing atoms that cause multiple equilibrium sites and even liquid-like behaviors. All CBHs strongly interfere with the heat transport of the corresponding materials. Future perspectives and possible research directions for thermal transport in thermoelectric materials with CBH have also been summarized herein.
Effect of Advanced HIV Infection on the Respiratory Microbiome.

RATIONALE Previous work found the lung microbiome in healthy subjects infected with HIV was similar to that in uninfected subjects. We hypothesized the lung microbiome from subjects infected with HIV with more advanced disease would differ from that of an uninfected control population. OBJECTIVES To measure the lung microbiome in an HIV-infected population with advanced disease. METHODS 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from 30 subjects infected with HIV with advanced disease (baseline mean CD4 count, 262 cells/mm(3)) before and up to 3 years after starting highly active antiretroviral therapy (HAART) and compared with 22 uninfected control subjects. MEASUREMENTS AND MAIN RESULTS The lung microbiome in subjects infected with HIV with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared with uninfected BAL. Differences improved with HAART, but still persisted up to 3 years after starting therapy. Population dispersion in the group infected with HIV was significantly greater than in the uninfected cohort and declined after treatment. There were differences in the relative abundance of some bacteria between the two groups at baseline and after 1 year of therapy. After 1 year on HAART, HIV BAL contained an increased abundance of Prevotella and Veillonella, bacteria previously associated with lung inflammation. CONCLUSIONS The lung microbiome in subjects infected with HIV with advanced disease is altered compared with an uninfected population both in diversity and bacterial composition. Differences remain up to 3 years after starting HAART. We speculate an altered lung microbiome in HIV infection may contribute to chronic inflammation and lung complications seen in the HAART era.
Small variations in nanoparticle structure dictate differential cellular stress responses and mode of cell death

Abstract For optimal exploitation of nanoparticles (NPs) in biomedicine, and to predict nanotoxicity, detailed knowledge of the cellular responses to cell-bound or internalized NPs is imperative. The final outcome of NP-cell interaction is dictated by the type and magnitude of the NP insult and the cellular response. Here, this has been systematically studied by using poly(alkylcyanoacrylate) (PACA) particles differing only in their alkyl side chains; butyl (PBCA), ethylbutyl (PEBCA), or octyl (POCA), respectively. Surprisingly, these highly similar NPs induced different stress responses and modes of cell death in human cell lines. The POCA particles generally induced endoplasmic reticulum stress and apoptosis. In contrast, PBCA and PEBCA particles induced oxidative stress and lipid peroxidation depending on the level of the glutathione precursor cystine and transcription of the cystine transporter SLC7A11. The latter was induced as a protective response by the transcription factors ATF4 and Nrf2. PBCA particles strongly activated ATF4 downstream of the eIF2α kinase HRI, whereas PEBCA particles more potently induced Nrf2 antioxidant responses. Intriguingly, PBCA particles activated the cell death mechanism ferroptosis; a promising option for targeting multidrug-resistant cancers. Our findings highlight that even minor differences in NP composition can severely impact the cellular response to NPs. This may have important implications in therapeutic settings.
Toward a Core Outcome Measurement Set for Polymyalgia Rheumatica: Report from the OMERACT 2018 Special Interest Group

Objective. To report the progress of the Outcome Measures in Rheumatology (OMERACT) Polymyalgia Rheumatica (PMR) Working Group in selecting candidate instruments for a core outcome measurement set. Methods. A systematic literature review identified outcomes measured and instruments used in PMR studies, and a respondent survey and raw data analysis assessed their domain match and feasibility. Results. Candidate instruments were identified for pain [visual analog scale/numerical rating scale (VAS/NRS)], stiffness (VAS/NRS and duration), and physical function (Health Assessment Questionnaire–Disability Index/modified Health Assessment Questionnaire). Domain match and feasibility assessments were favorable; however, validation in PMR was lacking. Conclusion. Further assessment of candidate instruments is required prior to recommending a PMR core outcome measurement set.
Essential Elements as a Distinguishing Factor between Mycorrhizal Potentials of Two Cohabiting Truffle Species in Riparian Forest Habitat in Serbia

True truffles (Tuber sp.) that establish ectomycorrhizal symbiosis (ECM) with trees in the Mediterranean and temporal regions have species specific abilities to assimilate soil born elements. Suitable habitats are usually inhabited by few truffle species, while distinguishing their symbiotic potentials appeared very difficult. Two species that commonly inhabit riparian forests in Serbia are the most prized one, Tuber magnatum Pico (Piedmont white truffle) and not so highly valued Tuber brumale Vitt. In order to assess potential differences between their assimilation and accumulation abilities, the differences between contents of elements that may be the subjects of the symbiotic trade between the host plant and fungi were evaluated in accumulation target (ascocarps) and their source (the soil). Essential (K, Na, Ca, Mg, Fe, P, S, and Zn) and essential trace elements (Co, Cr, Cu, Mn, and Se) in truffles and soil samples were determined by means of inductively coupled plasma with optical emission spectrometry (ICP‐OES). Their concentrations (mg/kg) in ascocarps were in the range from 1.364±0.591 (Cr) to 10760.862±16.058 (K), while in soil ranged from 23.035±0.010 (Cr) to 20809.300±122.934 (Fe). Element accumulation potential (bioaccumulation factor) was calculated in the system truffle/soil. The statistical approaches were used for establishing the differences, while the possible differentiation between symbiotic potentials of two mycelia in the defined soil conditions was discussed.
In vivo actions of SCTR/AT1aR heteromer in controlling Vp expression and release via cFos/cAMP/CREB pathway in magnocellular neurons of PVN

With an increasing body of evidence regarding GPCR oligomerization and its clinical implications over the last decade, the modulation and dynamics of GPCR homo‐ and hetero‐oligomers has more recently become an area of intense research focus. Previously, our lab showed in vitro heteromer formation between angiotensin II receptor type 1 subtype a (AT1aR) and secretin receptor (SCTR), which is involved in in vivo control of hyperosmolality‐induced water drinking behavior. Because the secretin (SCT)/SCTR axis is crucial to the central actions of angiotensin II (ANGII) and both SCT and ANGII are capable of triggering vasopressin (Vp) release from hypothalamus, we investigated here the in vivo role of SCTR‐AT1aR heteromer in regulating Vp release in hypothalamus using transmembrane peptides as tools. We showed that SCTR‐AT1aR heteromer mediates stimulatory actions of both SCT and ANGII in hypothalamic Vp expression and release as well as neuronal activities via the immediate early gene cFos. The results from this study not only are consistent with our hypothesis that SCT and ANGII interact at the receptor level to mediate their water homeostatic activities but also provide evidence for in vivo functions of cross‐class GPCR heteromers. —Mak, S. O. K. , Zhang, L. , Chow, B. K. C. In vivo actions of SCTR/AT1aR heteromer in controlling Vp expression and release via cFos/cAMP/CREB pathway in magnocellular neurons of PVN. FASEB J. 33, 5389–5398 (2019). www.fasebj. org
Benefit of directional microphones for unilateral, bilateral and bimodal cochlear implant users

Objective: To compare the standard T-Mic setting to UltraZoom and StereoZoom in 10 unilateral cochlear implant (CI) users, 10 bimodal device users and 10 bilateral CI users as well as a normal hearing (NH) reference group (n = 10). Method: Speech reception thresholds were measured using the Oldenburg sentence test in noise. Speech was presented from the front at 0°, noise was presented from five loudspeakers spaced at ±60°, ±120°, 180° (setup A) or from four loudspeakers in the front hemisphere at ±30°, ±60° and one at 180° (setup B). Results: There was a significant advantage for UltraZoom and StereoZoom for all groups in both setups. The largest advantage was for StereoZoom in the bilateral group (setup A, 5.2 dB, P < 0.001 and B, 3.4 dB, P < 0.001) There was a significant advantage for StereoZoom over UltraZoom in the bimodal group (setup A, P < 0.01 and B, P < 0.05) and in the bilateral group (P < 0.01, setup B only). The bilateral group performed as well as the normally hearing group in both setups and the bimodal group performed as well in setup A. There was a significant benefit of 1.8 dB for ClearVoice over UltraZoom alone for the unilateral group. Conclusions: UltraZoom and StereoZoom provided a clinically and statistically significant benefit over the T-Mic condition. The largest gain was shown for StereoZoom in the bimodal and bilateral groups. The use of StereoZoom enabled the bilateral group to perform as well as the normally hearing group in both the challenging speaker setups. However, real life environments might provide an even greater challenge than the conditions tested here.
Visemenet

We present a novel deep-learning based approach to producing animator-centric speech motion curves that drive a JALI or standard FACS-based production face-rig, directly from input audio. Our three-stage Long Short-Term Memory (LSTM) network architecture is motivated by psycho-linguistic insights: segmenting speech audio into a stream of phonetic-groups is sufficient for viseme construction; speech styles like mumbling or shouting are strongly co-related to the motion of facial landmarks; and animator style is encoded in viseme motion curve profiles. Our contribution is an automatic real-time lip-synchronization from audio solution that integrates seamlessly into existing animation pipelines. We evaluate our results by: cross-validation to ground-truth data; animator critique and edits; visual comparison to recent deep-learning lip-synchronization solutions; and showing our approach to be resilient to diversity in speaker and language.
Crosstalk between Autophagy and Type I Interferon Responses in Innate Antiviral Immunity

Autophagy exhibits dual effects during viral infections, promoting the clearance of viral components and activating the immune system to produce antiviral cytokines. However, some viruses impair immune defenses by collaborating with autophagy. Mounting evidence suggests that the interaction between autophagy and innate immunity is critical to understanding the contradictory roles of autophagy. Type I interferon (IFN-I) is a crucial antiviral factor, and studies have indicated that autophagy affects IFN-I responses by regulating IFN-I and its receptors expression. Similarly, IFN-I and interferon-stimulated gene (ISG) products can harness autophagy to regulate antiviral immunity. Crosstalk between autophagy and IFN-I responses could be a vital aspect of the molecular mechanisms involving autophagy in innate antiviral immunity. This review briefly summarizes the approaches by which autophagy regulates antiviral IFN-I responses and highlights the recent advances on the mechanisms by which IFN-I and ISG products employ autophagy against viruses.
Effectiveness of extracorporeal shock-wave therapy for frozen shoulder

Background: This systematic review aims to explore the effectiveness and safety of extracorporeal shock-wave therapy (ESWT) for patients with frozen shoulder. Methods: The sources of Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and Websites of Clinical Trials Registry will be searched. All databases and other sources will be searched from inception to the date of the search will be run. Only randomized controlled trials of ESWT for frozen shoulder will be considered for inclusion in this systematic review. Two authors independently screen the studies, extract the data, and evaluate the methodology quality for included trials. If sufficient trials will be included with fair heterogeneity, the data will be pooled, and the meta-analysis will be performed by using RevMan 5.3 software. Results: This systematic review will assess the effectiveness and safety of ESWT for frozen shoulder. The primary outcome includes pain intensity. The secondary outcomes consist of shoulder function, quality of life, and also the adverse events. Conclusion: Its findings may provide latest evidence of ESWT for the treatment of frozen shoulder. Ethics and dissemination: No research ethics approval is required in this study, because it is a systematic review and will not use individual data. The results of this study are expected to publish at peer-reviewed journals.
Azospirillum brasilense inoculation counteracts the induction of nitrate uptake in maize plants

Nitrogen (N) represents one of the limiting factors for crop growth and productivity and to date has been widely supplied via external application of fertilizers. However, the use of plant growth-promoting rhizobacteria (PGPR) might represent a valuable tool to further improve plant nutrition. This study examines the influence of Azospirillum brasilense strain Cd on nitrate uptake in maize (Zea mays) plants, focusing on the high-affinity transport system (HATS). Plants were induced with nitrate (500 µM) and either inoculated or not with Azospirillum. Inoculation decreased the nitrate uptake rate in induced plants, suggesting that Azospirillum may negatively affect HATS in the short term. The expression dynamics of ZmNF-YA and ZmLBD37 suggested that Azospirillum affected the N balance in the plants, most probably by supplying them with reduced N, i.e. NH4+. This was further corroborated by measurements of total N and the expression of ammonium transporter genes. Overall, our data demonstrate that Azospirillum can counteract the plant response to nitrate induction, albeit without compromising N nutrition. This suggests that the agricultural application of microbial inoculants requires fine-tuning of external fertilizer inputs.
Cancer cells in the tumor core exhibit spatially coordinated migration patterns

ABSTRACT In the early stages of metastasis, cancer cells exit the primary tumor and enter the vasculature. Although most studies have focused on the tumor invasive front, cancer cells from the tumor core can also potentially metastasize. To address cell motility in the tumor core, we imaged tumor explants from spontaneously forming tumors in mice in real time using long-term two-photon microscopy. Cancer cells in the tumor core are remarkably dynamic and exhibit correlated migration patterns, giving rise to local ‘currents’ and large-scale tissue dynamics. Although cells exhibit stop-and-start migration with intermittent pauses, pausing does not appear to be required during division. Use of pharmacological inhibitors indicates that migration patterns in tumors are actively driven by the actin cytoskeleton. Under these conditions, we also observed a relationship between migration speed and correlation length, suggesting that cells in tumors are near a jamming transition. Our study provides new insight into the dynamics of cancer cells in the tumor core, opening new avenues of research in understanding the migratory properties of cancer cells and later metastasis. This article has an associated First Person interview with the first author of the paper. Summary: Tissue explant imaging reveals that cancer cells in the tumor core migrate in a coordinated manner that is actively driven by the actin cytoskeleton.
Paternal height has an impact on birth weight of their offspring in a Japanese population: the Japan Environment and Children’s Study

Abstract This study examines the relationship between paternal height or body mass index (BMI) and birth weight of their offspring in a Japanese general population. The sample included 33,448 pregnant Japanese women and used fixed data, including maternal, paternal and infant characteristics, from the Japan Environment and Children’s Study (JECS), an ongoing nationwide birth cohort study. Relationships between paternal height or BMI and infant birth weight [i.e., small for gestational age (SGA) and large for gestational age (LGA)] were examined using a multinomial logistic regression model. Since fetal programming may be a sex-specific process, male and female infants were analyzed separately. Multivariate analysis showed that the higher the paternal height, the higher the odds of LGA and the lower the odds of SGA in both male and female infants. The effects of paternal BMI on the odds of both SGA and LGA in male infants were similar to those of paternal height; however, paternal height had a stronger impact than BMI on the odds of male LGA. In addition, paternal BMI showed no association with the odds of SGA and only a weak association with the odds of LGA in female infants. This cohort study showed that paternal height was associated with birth weight of their offspring and had stronger effects than paternal BMI, suggesting that the impact of paternal height on infant birth weight could be explained by genetic factors. The sex-dependent effect of paternal BMI on infant birth weight may be due to epigenetic effects.
Parental Decision Making about the HPV Vaccine

Background: Prophylactic human papillomavirus (HPV) vaccines are available, but uptake is suboptimal. Information on factors influencing parental decisions regarding vaccination will facilitate the development of successful interventions. Methods: Parents of girls ages 9 to 17 years (n = 476; cooperation rate = 67%) from a panel of U.S. households completed online surveys between September 2007 and January 2008, documenting vaccine knowledge, attitudes, and intentions. Results: Among those aware of the vaccine, 19% had already vaccinated their daughter(s), 34% intended to, 24% were undecided, and 24% had decided against vaccination. Awareness of HPV was high but knowledge levels were suboptimal (mean 72%, SEM 0.8%). Black and Hispanic parents were significantly less likely to be aware of the vaccine compared with White parents. In multivariate analyses, compared with parents who opposed vaccination, those who had already vaccinated their daughter(s) or who intended to do so had more positive attitudes, reported fewer barriers, and were more likely to perceive that family and friends would endorse vaccination. They also reported higher levels of trust in pharmaceutical companies that produce the vaccine. Conclusions: Despite limited knowledge, most parents had decided to vaccinate their daughter(s). Given evidence of diminished access to information among Black and Hispanic parents, programs should focus on reaching these groups. Interventions should address parental concerns about behavioral consequences, reduce structural barriers, and promote the perception that vaccination is endorsed by significant others. Moreover, interventions may need to address mistrust of pharmaceutical companies. Impact Statement: This study documents factors associated with parental decisions about HPV vaccination for their daughter(s) and provides direction for intervention development. Cancer Epidemiol Biomarkers Prev; 19(9); 2187–98. ©2010 AACR.