NCACO-score: An effective main-chain dependent scoring function for structure modeling

<p>Abstract</p> <p>Background</p> <p>Development of effective scoring functions is a critical component to the success of protein structure modeling. Previously, many efforts have been dedicated to the development of scoring functions. Despite these efforts, development of an effective scoring function that can achieve both good accuracy and fast speed still presents a grand challenge.</p> <p>Results</p> <p>Based on a coarse-grained representation of a protein structure by using only four main-chain atoms: N, Cα, C and O, we develop a knowledge-based scoring function, called NCACO-score, that integrates different structural information to rapidly model protein structure from sequence. In testing on the Decoys'R'Us sets, we found that NCACO-score can effectively recognize native conformers from their decoys. Furthermore, we demonstrate that NCACO-score can effectively guide fragment assembly for protein structure prediction, which has achieved a good performance in building the structure models for hard targets from CASP8 in terms of both accuracy and speed.</p> <p>Conclusions</p> <p>Although NCACO-score is developed based on a coarse-grained model, it is able to discriminate native conformers from decoy conformers with high accuracy. NCACO is a very effective scoring function for structure modeling.</p

Transcriptome analysis reveals the molecular basis of the response to acute hypoxic stress in blood clam Scapharca broughtonii

Hypoxia tolerance and adaptive regulation are important for aquatic animals, especially for species with poor mobility, such as most bivalves. Previous studies have confirmed that the blood clam Scapharca broughtonii has strong hypoxia resistance. However, the molecular mechanism supporting its hypoxic tolerance is still largely limited. To further screen the genes and their potential regulation of hypoxia tolerance, the transcriptome changes of S. broughtonii after acute hypoxic stress were explored by RNA sequencing. In this study, the average value of Q30 is 92.89%, indicating that the quality of sequencing is relatively high. The Unigenes obtained were annotated using four databases, namely Interpo, KEGG, Swisspro and TrEMBL. The annotation rates in these four databases were 71.82%, 75.95%, 92.98%, and 79.26%, respectively. And also, there were 649 DEGs in group B (dissolved oxygen (DO) of 2.5 mg/L) compared with group D (DO of 7.5 mg/L), among which 252 were up-regulated, and 397 were down-regulated. There were 965 DEGs in group A (DO of 0.5 mg/L), 2.5 mg/L, and 7.5 mg/L, compared with group B, among which 530 were up-regulated, and 435 were down-regulated. Meanwhile, there were 2,040 DEGs in group A compared with group D, among which 901 were up-regulated, and 1,139 were down-regulated. The main metabolic-related pathways of KEGG enriched in this study included Insulin secretion, Insulin signaling pathway, MAPK signal transduction pathway, and PPAR signaling pathway. These pathways may be critical metabolic pathways to solve energy demand and rebuild energy balance in S. broughtonii under hypoxic conditions. This study preliminarily clarified the response of S. broughtonii to hypoxia stress on the molecular levels, providing a reference for the following study on the response laws of related genes and pathways under environmental stress of S. broughtonii

Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of H3K27 Deacetylation and Methylation

Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of brown adipocyte thermogenic program. HDAC1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing HDAC1 profoundly blocks, whereas deleting HDAC1 significantly enhances β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes. β-adrenergic activation in brown adipocytes results in a dissociation of HDAC1 from promoters of BAT-specific genes, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α), leading to increased acetylation of histone H3 lysine 27 (H3K27), an epigenetic mark of gene activation. This is followed by dissociation of the polycomb repressive complexes, including the H3K27 methyltransferase enhancer of zeste homologue (EZH2), suppressor of zeste 12 (SUZ12), and ring finger protein 2 (RNF2) from, and concomitant recruitment of H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) to UCP1 and PGC1α promoters, leading to decreased H3K27 trimethylation, a histone transcriptional repression mark. Thus, HDAC1 negatively regulates brown adipocyte thermogenic program, and inhibiting HDAC1 promotes BAT-specific gene expression through a coordinated control of increased acetylation and decreased methylation of H3K27, thereby switching transcriptional repressive state to active state at the promoters of UCP1 and PGC1α. Targeting HDAC1 may be beneficial in prevention and treatment of obesity by enhancing BAT thermogenesis

Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of H3K27 Deacetylation and Methylation

Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of brown adipocyte thermogenic program. HDAC1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing HDAC1 profoundly blocks, whereas deleting HDAC1 significantly enhances β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes. β-adrenergic activation in brown adipocytes results in a dissociation of HDAC1 from promoters of BAT-specific genes, including uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α), leading to increased acetylation of histone H3 lysine 27 (H3K27), an epigenetic mark of gene activation. This is followed by dissociation of the polycomb repressive complexes, including the H3K27 methyltransferase enhancer of zeste homologue (EZH2), suppressor of zeste 12 (SUZ12), and ring finger protein 2 (RNF2) from, and concomitant recruitment of H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) to UCP1 and PGC1α promoters, leading to decreased H3K27 trimethylation, a histone transcriptional repression mark. Thus, HDAC1 negatively regulates brown adipocyte thermogenic program, and inhibiting HDAC1 promotes BAT-specific gene expression through a coordinated control of increased acetylation and decreased methylation of H3K27, thereby switching transcriptional repressive state to active state at the promoters of UCP1 and PGC1α. Targeting HDAC1 may be beneficial in prevention and treatment of obesity by enhancing BAT thermogenesis

Efficient wide-bandgap perovskite solar cells with open-circuit voltage deficit below 0.4 V via hole-selective interface engineering

Wide-bandgap mixed-halide perovskite solar cells (WBG-PSCs) are promising top cells for efficient tandem photovoltaics to achieve high power conversion efficiency (PCE) at low cost. However, the open-circuit voltage (VOC) of WBG-PSCs is still unsatisfactory as the VOC-deficit is generally larger than 0.45 V. Herein, we report a buried interface engineering strategy that substantially improves the VOC of WBG-PSCs by inserting amphophilic molecular hole-selective materials featuring with a cyanovinyl phosphonic acid (CPA) anchoring group between the perovskite and substrate. The assembly and redistribution of CPA-based amphiphilic molecules at the perovskite-substrate buried interface not only promotes the growth of a low-defect crystalline perovskite thin film, but also suppresses the photo-induced halide phase separation. The energy level alignment between wide-bandgap perovskite and the hole-selective layer is further improved by modulating the substituents on the triphenylamine donor moiety (methoxyls for MPA-CPA, methyls for MePA-CPA, and bare TPA-CPA). Using a 1.68 eV bandgap perovskite, the MePA-CPA-based devices achieved an unprecedentedly high VOC of 1.29 V and PCE of 22.3% under standard AM 1.5 sunlight. The VOC-deficit (&lt;0.40 V) is the lowest value reported for WBG-PSCs. This work not only provides an effective approach to decreasing the VOC-deficit of WBG-PSCs, but also confirms the importance of energy level alignment at the charge-selective layers in PSCs.</p

Security Proofs for Key-Alternating Ciphers with Non-Independent Round Permutations

This work studies the key-alternating ciphers (KACs) whose round permutations are not necessarily independent. We revisit existing security proofs for key-alternating ciphers with a single permutation (KACSPs), and extend their method to an arbitrary number of rounds. In particular, we propose new techniques that can significantly simplify the proofs, and also remove two unnatural restrictions in the known security bound of 3-round KACSP (Wu et al., Asiacrypt 2020). With these techniques, we prove the first tight security bound for t-round KACSP, which was an open problem. We stress that our techniques apply to all variants of KACs with non-independent round permutations, as well as to the standard KACs

Characteristics and outcomes of fetal ventricular aneurysm and diverticulum: combining the use of a new technique, fetal HQ

ObjectivesCongenital ventricular aneurysms or diverticulum (VA/VD) are rare cardiac anomalies with lack prenatal evaluation data. The present study aimed to provide the prenatal characteristics and outcomes from a tertiary center and the use of new techniques to evaluate the shape and contractility of these fetuses.MethodsTen fetuses were diagnosed with VA or VD, and 30 control fetuses were enrolled. Fetal echocardiography was performed to make the diagnosis. The prenatal echo characteristics and follow-up data were carefully reviewed. The shape and contractility measurements of the four-chamber view (4CV) and both ventricles were measured and computed using fetal fetal heart quantification (HQ).ResultsA total of 10 fetuses were enrolled, including 4 cases of left ventricular diverticulum, 5 cases of left ventricular aneurysm, and 1 case of right ventricular aneurysm (RVA). Four cases chose to terminate the pregnancy. The RVA was associated with a perimembranous ventricular septal defect. Two cases had fetal arrhythmia, and one case had pericardial effusion. After birth, one case underwent surgical resection at five years old. The 4CV global sphericity index (SI) of free-wall located ventricular outpouching (VO) was significantly lower than the apical ones and the control group (p &lt; 0.01). Four of five apical left VOs had significant higher (&gt;95th centile) SI in base segments, and three of four left VOs in the free-wall had significant lower (&lt; 5th centile) SI in the majority of 24 segments. Compared to the control group, the left ventricle (LV) global longitudinal strain, ejection fraction, and fractional area change were significantly decreased (p &lt; 0.01), while the LV cardiac output of the cases was in the normal range. The transverse fraction shortening of the affected segments of ventricles was significantly lower than the other ventricle segments (p &lt; 0.01).ConclusionsFetal HQ is a promising technique to evaluate the shape and contractility of congenital ventricular aneurysm and diverticulum