Downregulation of miRNA-155-5p contributes to the adipogenic activity of 2-ethylhexyl diphenyl phosphate in 3T3-L1 preadipocytes.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a commonly used organophosphorus flame retardant and food packaging material. Because of its high lipophilic and bioaccumulative properties, adipocytes are the primary target of EHDPP. However, the toxicity of EHDPP on preadipocytes and the potential mechanism have not been fully elucidated. MicroRNAs (miRNAs) are thought to be an important mediator that contribute to the toxicity of environmental contaminants. To identify the miRNAs specifically responsible for EHDPP exposure and their role in EGDPP's toxicity in preadipocytes, the adipogenic effects and miRNA expression profiling were performed on 3T3-L1 preadipocytes exposed to EHDPP. EHDPP at concentrations of 1-10 µM promoted adipocyte differentiation, as evidenced by lipid staining, triglyceride content, and expression of adipogenesis markers. MiRNA-seq analysis revealed that 7 differentially expressed miRNAs were recognized under EHDPP exposure, with miR-155-5p being the top down-regulated miRNA. Quantitative reverse transcription PCR (RT-qPCR) analysis showed that miR-155-5p level fell sharply during the first 2 days and continued to fall dose-dependently throughout the EHDPP exposure period. MiR-155-5p inhibition promotes adipocyte differentiation, whereas its overexpression counteracted EHDPP-induced adipogenesis. Luciferase reporter assay identified CCAAT/enhancer-binding protein beta (C/EBPß) as a target of miR-155-5p in 3T3-L1 preadipocytes in response to EHDPP. Taken together, EHDPP exposure down-regulated miR-155-5p, which then increased C/EBPß and peroxisome proliferator-activated receptor γ (PPARγ) expression and promoted adipogenesis in preadipocytes.

AKBA Promotes Axonal Regeneration via RhoA/Rictor to Repair Damaged Sciatic Nerve.

The existing studies by our team demonstrated the pro-recovery effect of 3-Acetyl-11-keto-beta-boswellic acid (AKBA) on a sciatic nerve injury. To further investigate the role of AKBA in peripheral nerve injury repair, The TMT quantitative proteomics technique was used to obtain differentially significant proteins in a Sham group, Model group, and AKBA group. After that, three time points (5, 14, and 28 d) and four groups (Sham + AKBA, Sham, Model, and AKBA) were set up, and immunoblotting, immunofluorescence, and cellular assays were applied to investigate the expression of CDC42, Rac1, RhoA, and Rictor in the sciatic nerve at different time points for each group in more depth. The results showed that AKBA enriched the cellular components of the myelin sheath and axon regeneration after a sciatic nerve injury and that AKBA upregulated CDC42 and Rac1 and downregulated RhoA expression 5 d after a sciatic nerve injury, promoting axon regeneration and improving the repair of a sciatic nerve injury in rats. Rictor is regulated by AKBA and upregulated in PC12 cells after AKBA action. Our findings provide a new basis for AKBA treatment of a peripheral nerve injury.

Genome-Wide Identification and Characterization of the CCT Gene Family in Foxtail Millet (Setaria italica) Response to Diurnal Rhythm and Abiotic Stress.

The CCT gene family plays important roles in diurnal rhythm and abiotic stress response, affecting crop growth and development, and thus yield. However, little information is available on the CCT family in foxtail millet (Setaria italica). In the present study, we identified 37 putative SiCCT genes from the foxtail millet genome. A phylogenetic tree was constructed from the predicted full-length SiCCT amino acid sequences, together with CCT proteins from rice and Arabidopsis as representatives of monocotyledonous and dicotyledonous plants, respectively. Based on the conserved structure and phylogenetic relationships, 13, 5, and 19 SiCCT proteins were classified in the COL, PRR, and CMF subfamilies, respectively. The gene structure and protein conserved motifs analysis exhibited highly similar compositions within the same subfamily. Whole-genome duplication analysis indicated that segmental duplication events played an important role in the expansion of the CCT gene family in foxtail millet. Analysis of transcriptome data showed that 16 SiCCT genes had significant diurnal rhythm oscillations. Under abiotic stress and exogenous hormonal treatment, the expression of many CMF subfamily genes was significantly changed. Especially after drought treatment, the expression of CMF subfamily genes except SiCCT32 was significantly up-regulated. This work provides valuable information for further study of the molecular mechanism of diurnal rhythm regulation, abiotic stress responses, and the identification of candidate genes for foxtail millet molecular breeding.

Molecular detection and genetic characterization of Cryptosporidium in kindergarten children in Southern Xinjiang, China.

Cryptosporidium is a common cause of diarrhea in children globally. However, there is limited information on the prevalence and genetic characteristics of Cryptosporidium in children in Xinjiang, China. This study aimed to assess the genetic characteristics and epidemiological status of Cryptosporidium in kindergarten children in Southern Xinjiang, China. A total of 609 fecal samples were collected from kindergartners aged 2-6 years from 11 counties in Southern Xinjiang, China. We used nested PCR amplification of the partial SSU rDNA gene to screen samples for Cryptosporidium spp. Isolates containing Cryptosporidium parvum and C. hominis were further subtyped for a gene encoding a 60-kDa glycoprotein (gp60). We used MEGA7 to construct a phylogenetic tree to study the genetic relationship between the gp60 subtypes of these two species via the Maximum Likelihood method based on the Tamura-Nei model. Only 1.3% (8/609) of asymptomatic children were confirmed to be infected with Cryptosporidium, with a 2.0% (6/299) infection rate in boys and 0.6% (2/310) infection rate in girls. Three Cryptosporidium species were identified including C. felis (37.5%; 3/8), C. hominis (37.5%; 3/8), and C. parvum (25.0%; 2/8). Three C. hominis subtypes (IbA9G3, IdA14, and IfA12G1) and two C. parvum subtypes (IIdA14G1 and IIdA15G1) were also found. This study is the first to identify the presence of Cryptosporidium in kindergarten children in Southern Xinjiang, China. The presence of zoonotic C. parvum subtypes IIdA14G1 and IIdA15G1 indicates the possible cross-species transmission of Cryptosporidium between children and animals.

Genome-Wide Association Studies Provide Insights Into the Genetic Architecture of Seed Germination Traits in Maize.

Seed germination is an important agronomic trait that affects crop yield and quality. Rapid and uniform seed germination traits are required in agricultural production. Although several genes are involved in seed germination and have been identified in Arabidopsis and rice, the genetic basis governing seed germination in maize remains unknown. Herein, we conducted a genome-wide association study to determine the genetic architecture of two germination traits, germination speed, and consistency, in a diverse panel. We genotyped 321 maize inbred populations with tropical, subtropical, or temperate origins using 1219401 single-nucleotide polymorphism markers. We identified 58 variants that were associated with the two traits, and 12 of these were shared between the two traits, indicating partial genetic similarity. Moreover, 36 candidate genes were involved in seed germination with functions including energy metabolism, signal transduction, and transcriptional regulation. We found that favorable variants had a greater effect on the tropical subpopulation than on the temperate. Accumulation of favorable variants shortened germination time and improved uniformity in maize inbred lines. These findings contribute significantly to understanding the genetic basis of maize seed germination and will contribute to the molecular breeding of maize seed germination.

Self-Powered Acceleration Sensor Based on Multilayer Suspension Structure and TPU-RTV Film for Vibration Monitoring.

In this paper, we designed a triboelectric acceleration sensor with excellent multiple parameters. To more easily detect weak vibrations, the sensor was founded on a multilayer suspension structure. To effectively improve the electrical properties of the sensor, a surface roughening and internal doping friction film, which was refined with a room temperature vulcanized silicone rubber (RTV) and some thermoplastic polyurethanes (TPU) powder in a certain proportion, was integrated into the structure. It was found that the optimization of the RTV film increases the open circuit voltage and short circuit current of the triboelectric nanogenerator (TENG) by 223% and 227%, respectively. When the external vibration acceleration is less than 4 m/s2, the sensitivity and linearity are 1.996 V/(m/s2) and 0.999, respectively. Additionally, when it is in the range between 4 m/s2 and 15 m/s2, those are 23.082 V/(m/s2) and 0.975, respectively. Furthermore, the sensor was placed in a simulated truck vibration environment, and its self-powered monitoring ability validated by experiments in real time. The results show that the designed sensor has strong practical value in the field of monitoring mechanical vibration acceleration.

Geomorphic effects of recurrent outburst superfloods in the Yigong River on the southeastern margin of Tibet.

Landslide dam outburst floods have a significant impact on landform evolution in high mountainous areas. Historic landslide dams on the Yigong River, southeastern Tibet, generated two outburst superfloods > 105 m3/s in 1902 and 2000 AD. One of the slackwater deposits, which was newly found immediately downstream of the historic dams, has been dated to 7 ka BP. The one-dimensional backwater stepwise method gives an estimate of 225,000 m3/s for the peak flow related to the paleo-stage indicator of 7 ka BP. The recurrence of at least three large landslide dam impoundments and super-outburst floods at the exit of Yigong Lake during the Holocene greatly changed the morphology of the Yigong River. More than 0.26 billion m3 of sediment has been aggraded in the dammed lake while the landslide sediment doubles the channel slope behind the dam. Repeated landslide damming may be a persistent source of outburst floods and impede the upstream migration of river knickpoints in the southeastern margin of Tibet.

Simultaneous Tuning Band Gaps of Cu2 O and TiO2 to Form S-Scheme Hetero-Photocatalyst.

Photocatalytic Z or S scheme merits higher redox potentials and faster charge separation. However, heterostructure photocatalysts with band gaps of bulk materials often have a type I band structure leading to poor photocatalytic activity. In view of this, we report simultaneous tuning of band gaps of Cu2 O and TiO2 , where quantum dot Cu2 O nanoparticles were formed on doped TiO2 with Ti3+ . The reduced size of Cu2 O made its conduction band more negative, whereas the introduction of Ti3+ made the absorption edge red shift to the visible light region. The as-formed heterostructure enabled an S-Scheme mechanism with remarkable activity and stability for visible light photodegradation of 4-chlorophenol (4-CP). The as-obtained photocatalysts' activity demonstrated ca. 510-fold increase as compared to individual ones and a mechanical blend. The as-obtained photocatalysts maintained over 80 % for 5 cycles and 2 months exposure to O2 did not decrease the degradation rate. ESR characterization and scavenger experiments proved the S-Scheme mechanism.

Sex determining region Y-box 9 induced microtubule formation and epithelial⁃mesenchymal transition in human oral squamous cell carcinoma CAL27 cells.

OBJECTIVES: This study aimed to explore the effect of sex determining region Y-box 9 (SOX9) on the microtubule formation and epithelial-mesenchymal transition (EMT) of human oral squamous cell carcinoma (OSCC) CAL27 and the underlying mechanism. METHODS: SOX9-shRNA1 and SOX9-shRNA2 were designed and synthesized and then transfected into CAL27 cells. The expression of SOX9 was detected by quantitative real-time polymerase chain reaction. Microtubule formation assay was used to detect the change in the number of microtubule nodules after interfering with SOX9. Immunofluorescence was used to detect the Vimentin content. Western blot was used to detect the protein expression of EMT marker molecules and Wnt/ß-catenin pathway-related proteins, such as E-cadherin, N-cadherin, Fibronectin, Wnt, ß-catenin, T-cell factor-4 (TCF-4). RESULTS: The expression level of SOX9 significantly decreased after transfection with SOX9-shRNA1 and SOX9-shRNA2 in CAL27 cells (F=578.000, P=0.000; F=96.850, P=0.000). Interference with SOX9 inhibited the EMT of OSCC. After interference with SOX9, the number of tubules and Vimentin positive cells decreased significantly (F=169.700, P=0.000). The expression level of E-cadherin significantly increased (F=181.400, P=0.000). The expression levels of N-cadherin, Fibronectin, Wnt, ß-catenin, and TCF-4 proteins significantly decreased (N-cadherin: F=101.400, P=0.000; Fibronectin: F=122.300, P=0.000; Wnt: F=70.290, P=0.000; ß-catenin: F=81.740, P=0.000; TCF-4: F=37.020, P=0.000). CONCLUSIONS: Interference with SOX9 decreased Vimentin content and inhibited the microtubule formation and protein expression of EMT marker molecules, as well as the expression of proteins related to the Wnt/ß-catenin pathway. Thus, SOX9 can induce microtubule formation and EMT in CAL27, which was related to the inhibition of the Wnt/ß-catenin pathway activation.

Identification, expression and enzyme activity of the group III sPLA2 s in Cyprinus carpio L.

Five group III secreted phospholipase (pla2g3s) homologous genes located on different linkage groups were identified from common carp (Cyprinus carpio), which we named Ccpla2g3a1, Ccpla2g3a2, Ccpla2g3b, Ccpla2g3c1 and Ccpla2g3c2. The five genes encode 530, 525, 461, 752 and 753 amino acids, respectively. Sequence analysis showed that the Ccpla2g3as contain seven exons and the others contain four exons. Synteny analysis of fish pla2g3s indicated that pla2g3a and pla2g3b were from the same ancestor gene, and Ccpla2g3a1, Ccpla2g3a2, Ccpla2g3c1 and Ccpla2g3c2 were from the specific genome duplication of common carp. Due to the significant variation of the pla2g3bs from common carp and zebrafish (Danio rerio), they formed a separate group in the phylogenetic tree. The tissue distributions of Ccpla2g3s coincided with their expression profiles during the embryo stages. The expression levels of Ccpla2g3as and Ccpla2g3cs were low at the embryo stages, and they were abundant in the liver and brain, respectively, whereas the expression of Ccpla2g3b was high at 0.5 h after fertilization and in the ovary. We obtained three soluble recombinant proteins of the bee venom-like PLA2 (BVLP) from Ccpla2g3 and evaluated their PLA2 enzyme properties. The optimum pHs of MBP-a1-BVLP, MBP-b-BVLP and MBP-c1-BVLP were 7.5, 7.0 and 8.0, respectively, and specific activities were 7.68 ± 0.66, 4.155 ± 0.158 and 1.93 ± 0.05 U µmol-1 , respectively. The Kd for Ca2+ of MBP-b-BVLP was the lowest (2.6 µM), whereas the values for both MBP-a1-BVLP and MBP-c1-BVLP were about 15 µM. The Km values of three proteins ranged from 31.9 to 41.91 µM.

Identification, expression and pro-inflammatory effect of interleukin-17 N in common carp (Cyprinus carpio L.).

Two interleukin (IL)-17 N genes (CcIL-17Na and b) present on different linkage groups were identified in the common carp (Cyprinus carpio) genome and confirmed by polymerase chain reaction (PCR) and real time (RT)-PCR in this experiment. Synteny analysis revealed that IL-17 N is transcribed by the complement sequence of TOP3B's intron 2. It is flanked by SDF2L and PPM1F in all fish studied to date, except fugu (Takifugu rubripes). The open reading frames of the two CcIL-17Ns are 411 base pairs long and encode 136 amino acids. The amino acid identity/similarity between CcIL-17Na and b is 91.2%/97.1%. The CcIL-17Ns share identity (46.8-90.4%) with their orthologs from other teleosts. Identities/similarities to other members of the IL-17 family in common carp were low at 21.4-30.2%/31.4-51.4%. In the phylogenetic tree, IL-17Ns from spotted gar (Lepisosteus oculatus, the ancestor of teleosts) and coelacanth (Latimeria chalumnae, the ancestor of tetrapods) were grouped within the same branch with a high bootstrap value of 97%, which indicates that IL-17 N is an ancient and conserved gene. Quantitative RT-PCR results showed that CcIL-17Ns were most highly expressed in the brain of healthy individuals. The expression in brain was significantly induced at 6 h post Aeromonas hydrophila infection; at 1 day post infection, expression in liver, muscle, skin, spleen, and head kidney was up-regulated. In addition, the upregulated expression of proinflammatory cytokines IL-1ß, IFN-γ, IL-6, chemokine CCL20, NF - κ B and TRAF6 in kidney tissue by ccIL-17 N recombinant protein also indicate that IL-17 N can promote inflammation through NF-κB pathway and induce the expression of chemokines and inflammatory factors.

Designing electrolytes with polymerlike glass-forming properties and fast ion transport at low temperatures.

In the presence of Lewis acid salts, the cyclic ether, dioxolane (DOL), is known to undergo ring-opening polymerization inside electrochemical cells to form solid-state polymer batteries with good interfacial charge-transport properties. Here we report that LiNO3, which is unable to ring-open DOL, possesses a previously unknown ability to coordinate with and strain DOL molecules in bulk liquids, completely arresting their crystallization. The strained DOL electrolytes exhibit physical properties analogous to amorphous polymers, including a prominent glass transition, elevated moduli, and low activation entropy for ion transport, but manifest unusually high, liquidlike ionic conductivities (e.g., 1 mS/cm) at temperatures as low as -50 °C. Systematic electrochemical studies reveal that the electrolytes also promote reversible cycling of Li metal anodes with high Coulombic efficiency (CE) on both conventional planar substrates (1 mAh/cm2 over 1,000 cycles with 99.1% CE; 3 mAh/cm2 over 300 cycles with 99.2% CE) and unconventional, nonplanar/three-dimensional (3D) substrates (10 mAh/cm2 over 100 cycles with 99.3% CE). Our finding that LiNO3 promotes reversibility of Li metal electrodes in liquid DOL electrolytes by a physical mechanism provides a possible solution to a long-standing puzzle in the field about the versatility of LiNO3 salt additives for enhancing reversibility of Li metal electrodes in essentially any aprotic liquid electrolyte solvent. As a first step toward understanding practical benefits of these findings, we create functional Li||lithium iron phosphate (LFP) batteries in which LFP cathodes with high capacity (5 to 10 mAh/cm2) are paired with thin (50 µm) lithium metal anodes, and investigate their galvanostatic electrochemical cycling behaviors.

Conventional Molecular Dynamics and Metadynamics Simulation Studies of the Binding and Unbinding Mechanism of TTR Stabilizers AG10 and Tafamidis.

Amyloid transthyretin (ATTR) amyloidosis is a widespread and fatal systemic amyloidosis characterized by the misfolding and amyloid aggregation of transthyretin (TTR). Studies suggest that dissociation of the TTR tetramer is the key step for its misfolding. Because of the importance of tetramer dissociation on ATTR amyloidosis, many TTR stabilizers have been discovered to stabilize the tetramer structure. This paper describes the application conventional molecular dynamics and metadynamics simulations to investigate the binding and unbinding mechanisms of two TTR stabilizers, including AG10 and tafamidis. AG10 has been granted an orphan drug designation by the U.S. Food and Drug Administration (FDA), and tafamidis was the first FDA-approved treatment for ATTR cardiomyopathy. The conventional molecular dynamics simulations reveal that both AG10 and tafamidis can stabilize the TTR tetramer through different mechanisms. AG10 stabilizes TTR tetramer by forming H-bonds with S117 to mimic the protective effect of T119M. Tafamidis stabilizes the tetramer by forming H-bond with S52 in the flexible CD loop to increase its structural stability. Despite the strong binding affinity of tafamidis, the free-energy surface constructed from metadynamics simulation suggests that tafamidis unbinds more readily than AG10 with lower free-energy barriers between the binding state and other intermediates. Finally, by performing pharmacophore analysis, we found two common important moieties of the studied compounds for their binding on the pockets, which can provide valuable guidance for future lead compounds' optimization in designing drugs for ATTR amyloidosis.

Molecular identification of Cryptosporidium spp. in alpacas (Vicugna pacos) in China.

Cryptosporidium is a ubiquitous protozoan in human and animals. To investigate the genetic diversity of Cryptosporidium spp. in alpaca (Vicugna pacos) in China, 484 fecal samples from alpacas were collected at nine sites, and Cryptosporidium spp. were screened with PCR amplification of the small subunit ribosome RNA (SSU rRNA) locus. Cryptosporidium spp. infected 2.9% (14/484) of the alpacas. Of the nine collection sites, two were positive for Cryptosporidium, Wensu (3.0%, 3/100) and Qinghe (31.4%, 11/35). Three Cryptosporidium species were identified: C. parvum (n = 2), C. ubiquitum (n = 1), and C. occultus (n = 11). Cryptosporidium parvum and C. ubiquitum were further subtyped with the 60-kDa glycoprotein locus (gp60). The two C. parvum isolates were subtype IIdA15G1, but the one C. ubiquitum isolate was not subtyped successfully. A phylogenetic analysis indicated that the Cryptosporidium isolates clustered with previously identified species. To our knowledge, this is the first report of Cryptosporidium infections in alpacas in China and provides baseline data for the study of Cryptosporidium in alpacas in China.

Prevalence and molecular characterization of Cryptosporidium spp. in pigs in Xinjiang, China.

Cryptosporidium spp. are distributed ubiquitously worldwide, and pigs are considered as one of the main reservoir hosts. Eight hundred one porcine fecal specimens were collected from seven intensive pig farms in Xinjiang Uygur Autonomous Region, China. Cryptosporidium spp. were screened via PCR amplification of the small ribosomal subunit RNA gene, and 143 specimens (17.9%, 143/801) from all seven farms tested positive for Cryptosporidium spp. Cryptosporidium prevalence in the pigs differed significantly among farms (p < 0.01). The highest Cryptosporidium spp. prevalence in post-weaned pigs was 39.5% (111/281), followed by fattening pigs (23.2%, 30/129), pre-weaned pigs (1.2%, 2/169), and sows (0/222). Significant differences were observed between age groups (p < 0.01). C. suis was the predominantly identified species (62.9%, 90/143), followed by C. scrofarum (35.7%, 51/143), and C. parvum (1.4%, 2/143). Two C. parvum specimens were subtyped by analyzing the 60-kDa glycoprotein (gp60) gene sequences and were identified as IIdA14G1 and IIdA15G1. To our knowledge, this is the first report of C. parvum infection in pigs in China. The identification of three Cryptosporidium species, including zoonotic C. parvum in pigs in Xinjiang raises concern for the health of both swine animals and personnel in the pig industry.

Genetic diversity of Blastocystis in kindergarten children in southern Xinjiang, China.

BACKGROUND: Blastocystis is one of the most common intestinal parasites in humans and various animals worldwide. Few studies are available regarding the genetic characterization of Blastocystis infections in humans in China. METHODS: In the present study, 609 fecal samples were collected from two- to six-year-old kindergarten children in southern Xinjiang and were examined by polymerase chain reaction (PCR). RESULTS: The infection rate of Blastocystis was 14.3% (87/609); no significant difference was observed among counties and between sexes. Blastocystis subtypes ST1 (n = 38), ST2 (n = 8), and ST3 (n = 41) were identified by sequence analysis of the small subunit ribosomal RNA gene. Genetic polymorphisms were observed at the intra-subtype level, including seven variations for ST1 (ST1A to ST1G), four for ST2 (ST2A to ST2D), and two for ST3 (ST3A and ST3B); with ST1F and ST2B being new variations. CONCLUSIONS: ST1 and ST3 are the two common Blastocystis subtypes in the study area. More extensive studies in both humans and animals in different regions are needed to better characterize the transmission of Blastocystis.

Molecular detection of Enterocytozoon bieneusi in alpacas (Vicugna pacos) in Xinjiang, China.

Enterocytozoon bieneusi, an obligate intracellular pathogen, can infect a wide variety of hosts. This study aimed to determine the prevalence and molecular characteristics of E. bieneusi in alpacas (Vicugna pacos) in China. A total of 185 alpaca fecal samples were collected from five herds in Tacheng, Wensu, Hejing, Qinghe, and Nilka counties in Xinjiang Uygur Autonomous Region. Enterocytozoon bieneusi was detected by nested PCR of the internal transcribed spacer (ITS) region. Twenty-eight fecal samples (15.1%, 28/185) were positive for E. bieneusi, with the highest prevalence in alpacas from Qinghe (42.9%, 15/35). Four E. bieneusi genotypes were identified, which included two known (P and ALP3) and two novel (ALP7 and ALP8) genotypes. Genotype ALP3 was the dominant genotype (57.1%, 16/28), followed by genotypes P (32.1%, 9/28), ALP7 (7.1%, 2/28), and ALP8 (2.6%, 1/28). Phylogenetic analysis revealed that three genotypes (P, ALP7, and ALP3) clustered into group 1, whereas genotype ALP8 clustered into group 8. This is the first report of E. bieneusi infection and genetic diversity in alpacas from Xinjiang, China.

Root and root canal morphology in maxillary second molar with fused root from a native Chinese population.

INTRODUCTION: Root fusion is an anatomic variation in maxillary second molars (MSMs); however, the nature of this canal morphology as it relates to its root anatomy has not been fully clarified. The purpose of this study was to investigate the relationship between features of fused roots and root canal anatomy in MSMs using micro-computed tomographic imaging. METHODS: One hundred eighty-seven extracted MSMs were scanned with the µCT50 (Scanco Medical, Bassersdorf, Switzerland), and their root and canal morphology was classified and analyzed using the classifications proposed by Yang and Vertucci. The number and position of canals that merged were recorded and compared among different root fusion types. RESULTS: One hundred eight (57.75%) MSMs had 3 separate roots, and 79 (42.25%) had fused roots. Of the 79 fused roots, 22 showed partial canal merging, and 6 had complete canal merging. Canal merging was found with teeth with 3-root fusion more often than in those with 2-root fusion (P < .05). Of 28 merged canals, 16 occurred between mesiobuccal and distobuccal canals and 9 among mesiobuccal, distobuccal, and palatal canals. CONCLUSIONS: MSMs with fused roots may present a complicated root canal system as a result of canal merging.

Past and future implications of near-misses and their emotional consequences.

The Reflection and Evaluation Model (REM) of comparative thinking predicts that temporal perspective could moderate people's emotional reactions to close counterfactuals following near-misses (Markman & McMullen, 2003). The experiments reported in this paper tested predictions derived from this theory by examining how people's emotional reactions to a near-miss at goal during a football match (Experiment 1) or a close score in a TV game show (Experiment 2) depended on the level of perceived future possibility. In support of the theory it was found that the presence of future possibility enhanced affective assimilation (e.g., if the near-miss occurred at the beginning of the game the players who had nearly scored were hopeful of future success) whereas the absence of future possibility enhanced affective contrast (e.g., if the near-miss occurred at the end of the game the players who had nearly scored were disappointed about missing an opportunity). Furthermore the experiments built upon our theoretical understanding by exploring the mechanisms which produce assimilation and contrast effects. In Experiment 1 we examined the incidence of present-oriented or future-oriented thinking, and in Experiment 2 we examined the mediating role of counterfactual thinking in the observed effect of proximity on emotions by testing whether stronger counterfactuals (measured using counterfactual probability estimates) produce bigger contrast and assimilation effects. While the results of these investigations generally support the REM, they also highlight the necessity to consider other psychological mechanisms (e.g., social comparison), in addition to counterfactual thinking, that might contribute to the emotional consequences of near-miss outcomes.

A conformational transition in the adenylyl cyclase catalytic site yields different binding modes for ribosyl-modified and unmodified nucleotide inhibitors.

Adenylyl cyclases (ACs) are promising pharmacological targets for treating heart failure, cancer, and psychosis. Ribose-substituted nucleotides have been reported as a potent family of AC inhibitors. In silico analysis of the docked conformers of such nucleotides in AC permits assembly of a consistent, intuitive QSAR model with strong correlation relative to measured pK(i) values. Energy decomposition suggests that the MANT group effects an AC conformational transition upon ligand binding.