Quantitative proteomics identifies proteins that resist translational repression and become dysregulated in ALS-FUS.

Aberrant translational repression is a feature of multiple neurodegenerative diseases. The association between disease-linked proteins and stress granules further implicates impaired stress responses in neurodegeneration. However, our knowledge of the proteins that evade translational repression is incomplete. It is also unclear whether disease-linked proteins influence the proteome under conditions of translational repression. To address these questions, a quantitative proteomics approach was used to identify proteins that evade stress-induced translational repression in arsenite-treated cells expressing either wild-type or amyotrophic lateral sclerosis (ALS)-linked mutant FUS. This study revealed hundreds of proteins that are actively synthesized during stress-induced translational repression, irrespective of FUS genotype. In addition to proteins involved in RNA- and protein-processing, proteins associated with neurodegenerative diseases such as ALS were also actively synthesized during stress. Protein synthesis under stress was largely unperturbed by mutant FUS, although several proteins were found to be differentially expressed between mutant and control cells. One protein in particular, COPBI, was downregulated in mutant FUS-expressing cells under stress. COPBI is the beta subunit of the coat protein I (COPI), which is involved in Golgi to endoplasmic reticulum (ER) retrograde transport. Further investigation revealed reduced levels of other COPI subunit proteins and defects in COPBI-relatedprocesses in cells expressing mutant FUS. Even in the absence of stress, COPBI localization was altered in primary and human stem cell-derived neurons expressing ALS-linked FUS variants. Our results suggest that Golgi to ER retrograde transport may be important under conditions of stress and is perturbed upon the expression of disease-linked proteins such as FUS.

The RNA-binding protein FUS/TLS undergoes calcium-mediated nuclear egress during excitotoxic stress and is required for GRIA2 mRNA processing.

Excitotoxic levels of glutamate represent a physiological stress that is strongly linked to amyotrophic lateral sclerosis (ALS) and other neurological disorders. Emerging evidence indicates a role for neurodegenerative disease-linked RNA-binding proteins (RBPs) in the cellular stress response. However, the relationships between excitotoxicity, RBP function, and disease have not been explored. Here, using primary cortical and motor neurons, we found that excitotoxicity induced the translocation of select ALS-linked RBPs from the nucleus to the cytoplasm within neurons. RBPs affected by excitotoxicity included TAR DNA-binding protein 43 (TDP-43) and, most robustly, fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS). We noted that FUS is translocated through a calcium-dependent mechanism and that its translocation coincides with striking alterations in nucleocytoplasmic transport. Furthermore, glutamate-induced up-regulation of glutamate ionotropic receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type subunit 2 (GRIA2) in neurons depended on FUS expression, consistent with a functional role for FUS in excitotoxic stress. These findings reveal molecular links among prominent factors in neurodegenerative diseases, namely excitotoxicity, disease-associated RBPs, and nucleocytoplasmic transport.

Mechanosensitive PPAP2B Regulates Endothelial Responses to Atherorelevant Hemodynamic Forces.

RATIONALE: PhosPhatidic Acid Phosphatase type 2B (PPAP2B), an integral membrane protein known as lipid phosphate phosphatase (LPP3) that inactivates lysophosphatidic acid, was implicated in coronary artery disease (CAD) by genome-wide association studies. However, it is unclear whether genome-wide association studies-identified coronary artery disease genes, including PPAP2B, participate in mechanotransduction mechanisms by which vascular endothelia respond to local atherorelevant hemodynamics that contribute to the regional nature of atherosclerosis. OBJECTIVE: To establish the critical role of PPAP2B in endothelial responses to hemodynamics. METHODS AND RESULTS: Reduced PPAP2B was detected in vivo in mouse and swine aortic arch (AA) endothelia exposed to chronic disturbed flow, and in mouse carotid artery endothelia subjected to surgically induced acute disturbed flow. In humans, PPAP2B was reduced in the downstream part of carotid plaques where low shear stress prevails. In culture, reduced PPAP2B was measured in human aortic endothelial cells under atherosusceptible waveform mimicking flow in human carotid sinus. Flow-sensitive microRNA-92a and transcription factor KLF2 were identified as upstream inhibitor and activator of endothelial PPAP2B, respectively. PPAP2B suppression abrogated atheroprotection of unidirectional flow; inhibition of lysophosphatidic acid receptor 1 restored the flow-dependent, anti-inflammatory phenotype in PPAP2B-deficient cells. PPAP2B inhibition resulted in myosin light-chain phosphorylation and intercellular gaps, which were abolished by lysophosphatidic acid receptor 1/2 inhibition. Expression quantitative trait locus mapping demonstrated PPAP2B coronary artery disease risk allele is not linked to PPAP2B expression in various human tissues but significantly associated with reduced PPAP2B in human aortic endothelial cells. CONCLUSIONS: Atherorelevant flows dynamically modulate endothelial PPAP2B expression through miR-92a and KLF2. Mechanosensitive PPAP2B plays a critical role in promoting anti-inflammatory phenotype and maintaining vascular integrity of endothelial monolayer under atheroprotective flow.

Regulation of mammalian transcription by Gdown1 through a novel steric crosstalk revealed by cryo-EM.

In mammals, a distinct RNA polymerase II form, RNAPII(G) contains a novel subunit Gdown1 (encoded by POLR2M), which represses gene activation, only to be reversed by the multisubunit Mediator co-activator. Here, we employed single-particle cryo-electron microscopy (cryo-EM) to disclose the architectures of RNAPII(G), RNAPII and RNAPII in complex with the transcription initiation factor TFIIF, all to ~19 Å. Difference analysis mapped Gdown1 mostly to the RNAPII Rpb5 shelf-Rpb1 jaw, supported by antibody labelling experiments. These structural features correlate with the moderate increase in the efficiency of RNA chain elongation by RNAP II(G). In addition, our updated RNAPII-TFIIF map showed that TFIIF tethers multiple regions surrounding the DNA-binding cleft, in agreement with cross-linking and biochemical mapping. Gdown1's binding sites overlap extensively with those of TFIIF, with Gdown1 sterically excluding TFIIF from RNAPII, herein demonstrated by competition assays using size exclusion chromatography. In summary, our work establishes a structural basis for Gdown1 impeding initiation at promoters, by obstruction of TFIIF, accounting for an additional dependent role of Mediator in activated transcription.

EM structure of a helicase-loader complex depicting a 6:2 binding sub-stoichiometry from Geobacillus kaustophilus HTA426.

During DNA replication, bacterial helicase is recruited as a complex in association with loader proteins to unwind the parental duplex. Previous structural studies have reported saturated 6:6 helicase-loader complexes with different conformations. However, structural information on the sub-stoichiometric conformations of these previously-documented helicase-loader complexes remains elusive. Here, with the aid of single particle electron-microscopy (EM) image reconstruction, we present the Geobacillus kaustophilus HTA426 helicase-loader (DnaC-DnaI) complex with a 6:2 binding stoichiometry in the presence of ATPγS. In the 19 Šresolution EM map, the undistorted and unopened helicase ring holds a robust loader density above the C-terminal RecA-like domain. Meanwhile, the path of the central DNA binding channel appears to be obstructed by the reconstructed loader density, implying its potential role as a checkpoint conformation to prevent the loading of immature complex onto DNA. Our data also reveals that the bound nucleotides and the consequently induced conformational changes in the helicase hexamer are essential for active association with loader proteins. These observations provide fundamental insights into the formation of the helicase-loader complex in bacteria that regulates the DNA replication process.

Differential regulation of amyloid precursor protein sorting with pathological mutations results in a distinct effect on amyloid-ß production.

The deposition of amyloid-ß (Aß) peptide, which is generated from amyloid precursor protein (APP), is the pathological hallmark of Alzheimer's disease (AD). Three APP familial AD mutations (D678H, D678N, and H677R) located at the sixth and seventh amino acid of Aß have distinct effect on Aß aggregation, but their influence on the physiological and pathological roles of APP remain unclear. We found that the D678H mutation strongly enhances amyloidogenic cleavage of APP, thus increasing the production of Aß. This enhancement of amyloidogenic cleavage is likely because of the acceleration of APPD678H sorting into the endosomal-lysosomal pathway. In contrast, the APPD678N and APPH677R mutants do not cause the same effects. Therefore, this study indicates a regulatory role of D678H in APP sorting and processing, and provides genetic evidence for the importance of APP sorting in AD pathogenesis. The internalization of amyloid precursor protein (APP) increases its opportunity to be processed by ß-secretase and to produce Amyloid-ß (Aß) that causes Alzheimer's disease (AD). We report a pathogenic APPD678H mutant that enhances APP internalization into the endosomal-lysosomal pathway and thus promotes the ß-secretase cleavage and Aß production. This study provides genetic evidence for the importance of APP sorting in AD pathogenesis.

Associations of Cardiorespiratory Fitness and Muscular Endurance Fitness With Pulmonary Function in Physically Active Young Adults.

RATIONALE: While the beneficial effects of physical fitness on general health are well-documented, the specific relationship between different types of physical fitness, particularly cardiorespiratory fitness (CRF) and muscular endurance fitness (MEF), and lung function in physically active young adults remains less explored. OBJECTIVE: This study investigated the relationship between CRF and MEF, and their correlation with lung function in physically active young adults. METHODS: This cross-sectional study involved a cohort of 1227 physically active young adults without lung diseases. Lung function was assessed using FEV1, FVC, and FEV1/FVC measurements. The 3000-m run was used to assess CRF, and the 2-min push-up and sit-up tests were used to assess MEF. Multivariable linear regression analysis was used to evaluate the relationships between these fitness measures and lung function, adjusting for potential covariates. RESULTS: Enhanced CRF was associated with superior FEV1 and FVC after adjusting for covariates (ß=-.078, p=.015 for FEV1; ß=-.086, p=.009 for FVC). Push-ups were positively associated with FEV1 (ß=.102, p=.014), but not with FVC. In contrast, sit-ups showed no significant correlation with lung function in the fully adjusted model. CONCLUSION: The study demonstrated a clear association between improved physical fitness and better lung function in physically active young adults, with various exercises showing distinct associations with lung metrics. Notably, push-ups were particularly associated with higher FEV1. A future prospective study is necessary to determine whether routine exercises, such as push-ups, might lead to greater lung function.

Comparisons of Various Anthropometric Indices for Incident Hypertension in Military Young Adults: The CHIEF Cohort Study.

AIM: The study aimed to compare the predictive capabilities of the traditional anthropometric indices with the novel anthropometric indices for incident hypertension. BACKGROUND: Some novel anthropometric indices, e.g., the Body Roundness Index (BRI) and A Body Shape Index (ABSI) have been associated with prevalent hypertension. There are a few cohort studies that have examined the association of the novel anthropometric indices with newonset hypertension in young adults. METHODS: This study included 2,448 military male and female young adults, aged 18-39 years, free of hypertension at baseline in Taiwan; they were followed for incidence of hypertension from 2014 till the end of 2020. Blood Pressure (BP) in mmHg was measured twice and averaged to verify hypertension, which was defined as systolic BP ≥130 and/or diastolic BP ≥80 or on antihypertensive medication therapy in each annual health examination. Anthropometric indices included the Body Mass Index (BMI) defined as the weight (kg)/height squared (m2), Waist Girth (WC) in cm, the Waist-to-height Ratio (WHtR), the BRI defined as 364.2 - 365.5 × {1 - [(WC/2π)/(0.5 × height)]2}0.5, as well as ABSI defined as WC/(BMI2/3 × height1/2). Multiple Cox regression analysis and Area Under the Curve (AUC) of the Receiver of Operating Characteristics (ROC) were utilized with adjustments for the baseline potential covariates to determine the association and compare the performance of various indices for incident hypertension. RESULTS: During a median follow-up period of 6.0 years, 920 new-onset hypertension cases (37.6%) developed. Higher BMI, WC, BRI (per each 1-unit increase) and WHtR (per each 0.1- unit increase) were associated with a greater risk of new-onset hypertension [Hazard Ratios (HRs) and 95% confidence intervals: 1.060 (1.035-1.085), 1.021 (1.011-1.030), and 1.178 (1.077-1.288), respectively], whereas there was no association between ABSI and new-onset hypertension. For the ROC, WC was observed with the greatest AUC for incident new-onset hypertension [0.661 (0.638-0.683)], followed by BMI [0.650 (0.628-0.673)], while the ABSI was found with the lowest AUC [0.544 (0.521-0.568)]. CONCLUSION: Most of the anthropometric indices were associated with a higher risk of new-onset hypertension among young adults, except for ABSI. In addition, this study has suggested the traditional indices, such as WC and BMI, to be superior to the latest ones, e.g., BRI and ABSI, for the prediction of new-onset hypertension.

Far-field self-focusing and -defocusing radiation behaviors of the electroluminescent light sources due to negative refraction.

In recent years, researchers have demonstrated negative refraction theoretically and experimentally by pumping optical power into photonic crystal (PhC) or waveguide structures. The concept of negative refraction can be used to create a perfect lens that focuses an object smaller than the wavelength. By inserting two-dimensional PhCs into the peripheral of a semiconductor light emitting structure, this study presents an electroluminescent device with negative refraction in the visible wavelength range. This approach produces polarization dependent collimation behavior in far-field radiation patterns. The modal dispersion of negative refraction results in strong group velocity modulation, and self-focusing and -defocusing behaviors are apparent from light extraction. This study further verifies experimental results by using theoretic calculations based on equifrequency contours.

Simple replacement reaction for the preparation of ternary Fe(1-x)PtRu(x) nanocrystals with superior catalytic activity in methanol oxidation reaction.

The finding of new metal alloyed nanocrystals (NCs) with high catalytic activity and low cost to replace PtRu NCs is a critical step toward the commercialization of fuel cells. In this work, a simple cation replacement reaction was utilized to synthesize a new type of ternary Fe(1-x)PtRu(x) NCs from binary FePt NCs. The detailed structural transformation from binary FePt NCs to ternary Fe(1-x)PtRu(x) NCs was analyzed by X-ray absorption spectroscopy (XAS). Ternary Fe(35)Pt(40)Ru(25), Fe(31)Pt(40)Ru(29), and Fe(17)Pt(40)Ru(43) NCs exhibit superior catalytic ability to withstand CO poisoning in methanol oxidation reaction (MOR) than do binary NCs (FePt and J-M PtRu). Also, the Fe(31)Pt(40)Ru(29) NCs had the highest alloying extent and the lowest onset potential among the ternary NCs. Furthermore, the origin for the superior CO resistance of ternary Fe(1-x)PtRu(x) NCs was investigated by determining the adsorption energy of CO on the NCs' surfaces and the charge transfer from Fe/Ru to Pt using a simulation based on density functional theory. The simulation results suggested that by introducing a new metal into binary PtRu/PtFe NCs, the anti-CO poisoning ability of ternary Fe(1-x)PtRu(x) NCs was greatly enhanced because the bonding of CO-Pt on the NCs' surface was weakened. Overall, our experimental and simulation results have indicated a simple route for the discovery of new metal alloyed catalysts with superior anti-CO poisoning ability and low usage of Pt and Ru for fuel cell applications.

Effective myocardial salvage with percutaneous coronary intervention in late diagnosed acute post-traumatic ST-elevation myocardial infarction.

BACKGROUND: Acute post-traumatic ST-elevation myocardial infarction (STEMI) is rare but potentially disastrous in patients with blunt cardiac injury. Sometimes the diagnosis is delayed. Failed myocardial salvage by percutaneous coronary intervention (PCI) within 9 h after the onset of post-traumatic STEMI has been described. OBJECTIVE: We present a case report of a patient in whom effective myocardial salvage with PCI was obtained in a late diagnosed acute post-traumatic STEMI. CASE REPORT: We report the case of a young man who was involved in a motorcycle crash, who had a delayed diagnosis of post-traumatic STEMI. Diagnostic coronary angiography was performed to guide treatment strategy. An occluded left anterior descending artery due to a dissection, and an intimal flap at the first diagonal branch were found. A PCI was done 18 h after the onset of the event with striking and immediate improvement of the regional left ventricular wall motion and ejection fraction. CONCLUSION: After blunt thoracic injury, there is the possibility of an acute post-traumatic STEMI being present when facing a patient with clues of blunt cardiac injury. If the diagnosis of acute post-traumatic STEMI is clinically strong, the patient should be managed individually according to the clinical scenario. Early recognition and prompt management are vital when dealing with patients suffering post-traumatic STEMI.

Procedural and One-Year Clinical Outcomes of Long 48 mm Xience Xpedition Everolimus-Eluting Stent in Complex Long Diffuse Coronary Artery Lesions.

BACKGROUND AND OBJECTIVES: Long 48 mm drug-eluting stents (DES) used to treat long coronary lesions decreases the number of stents needed and avoids stent overlapping. Disadvantages include difficulty in delivery and size discrepancy between proximal and distal stent landing zones. The present study analyzed the rate of procedural, immediate angiographic, and 1-year clinical outcomes of long diffuse coronary artery lesions treated with 48 mm everolimus-eluting stents (EES) and compared the clinical outcomes with multiple overlapping DES. METHODS: This retrospective analysis included 213 patients with 228 lesions treated with at least one 48 mm EES at 2 hospitals in Taiwan. RESULTS: About 40.4% of the lesions had moderate-severe calcification and 20.2% had acute angulation. The mean lesion length was 49.2 ± 18.1 mm. In 161 lesions requiring a single 48 mm EES, 67.1% had a discrepancy between proximal and distal reference diameter of ≥0.5 mm and 36% had a discrepancy of ≥1.0 mm. The procedural success rate was 98.6%. Target-vessel failure (TVF) rate at 1 year was 4.2%. Cardiac death occurred in 3 patients. The rates of target-vessel myocardial infarction (TV-MI), target-vessel revascularization (TVR) and definite/ probable stent thrombosis were 1.4%, 3.3%, and 0.9%, respectively. After adjusting patient variables by propensity score matching, no significant difference was found for cardiac death, TVF, TV-MI, and clinically driven TVR. CONCLUSION: Use of 48 mm EES to treat long coronary lesions in clinically and anatomically complex patients is safe and effective. In the propensity score-matched analysis, the 48 mm EES and multiple stents have comparable clinical outcomes.

Interactions between ALS-linked FUS and nucleoporins are associated with defects in the nucleocytoplasmic transport pathway.

Nucleocytoplasmic transport (NCT) decline occurs with aging and neurodegeneration. Here, we investigated the NCT pathway in models of amyotrophic lateral sclerosis-fused in sarcoma (ALS-FUS). Expression of ALS-FUS led to a reduction in NCT and nucleoporin (Nup) density within the nuclear membrane of human neurons. FUS and Nups were found to interact independently of RNA in cells and to alter the phase-separation properties of each other in vitro. FUS-Nup interactions were not localized to nuclear pores, but were enriched in the nucleus of control neurons versus the cytoplasm of mutant neurons. Our data indicate that the effect of ALS-linked mutations on the cytoplasmic mislocalization of FUS, rather than on the physiochemical properties of the protein itself, underlie our reported NCT defects. An aberrant interaction between mutant FUS and Nups is underscored by studies in Drosophila, whereby reduced Nup expression rescued multiple toxic FUS-induced phenotypes, including abnormal nuclear membrane morphology in neurons.

Visual Attack on the Moving Prey by Cuttlefish.

Visual attack for prey capture in cuttlefish involves three well characterized sequential stages: attention, positioning, and seizure. This visually guided behavior requires accurate sensorimotor integration of information on the target's direction and tentacular strike control. While the behavior of cuttlefish visual attack on a stationary prey has been described qualitatively, the kinematics of visual attack on a moving target has not been analyzed quantitatively. A servomotor system controlling the movement of a shrimp prey and a high resolution imaging system recording the behavior of the cuttlefish predator, together with the newly developed DeepLabCut image processing system, were used to examine the tactics used by cuttlefish during a visual attack on moving prey. The results showed that cuttlefish visually tracked a moving prey target using mainly body movement, and that they maintained a similar speed to that of the moving prey right before making their tentacular strike. When cuttlefish shot out their tentacles for prey capture, they were able to either predict the target location based on the prey's speed and compensate for the inherent sensorimotor delay or adjust the trajectory of their tentacular strike according to the prey's direction of movement in order to account for any changes in prey position. These observations suggest that cuttlefish use the various visual tactics available to them flexibly in order to capture moving prey, and that they are able to extract direction and speed information from moving prey in order to allow an accurate visual attack.

Reconfigurable liquid pumping in electric-field-defined virtual microchannels by dielectrophoresis.

Dielectrophoresis (DEP), widely used to generate body forces on suspended particles, is investigated to provide surface forces at the liquid-medium interfaces and pump a high-permittivity liquid in a low-permittivity medium along a virtual microchannel defined by an electric field between parallel plates. Because the pumping pressure is proportional to the square of the intensity of the electric field and independent of the channel width, DEP pumping is advantageous as the dimension of the microchannel shrinks down. The absence of the channel walls simplifies the fabrication processes and further increases its feasibility in nanofluidic applications. We demonstrate water pumping in an immiscible silicone oil medium at adjustable velocities by applying voltages above the threshold value whose square is linearly proportional to the cross-sectional aspect ratio (AR), i.e., the height to width ratio, of the microchannel. With a properly designed AR, liquid valve is achieved by appropriate voltage applications. Without the barriers of channel walls, merging multiple streams and capillary filling of the spacing between electric-field-defined virtual microchannels are observed and studied. Moreover, in situ reconfigurable liquid pumping is demonstrated by a four way switching valve on a programmable crossing electrode set.

Phase TEM for biological imaging utilizing a Boersch electrostatic phase plate: theory and practice.

A Boersch electrostatic phase plate (BEPP) used in a transmission electron microscope (TEM) system can provide tuneable phase shifts and overcome the low contrast problem for biological imaging. Theoretically, a pure phase image with a high phase contrast can be obtained using a BEPP. However, a currently available TEM system utilizing a BEPP cannot achieve sufficiently high phase efficiency for biological imaging, owing to the practical conditions. The low phase efficiency is a result of the blocking of partial unscattered electrons by BEPP, and the contribution of absorption contrast. The fraction of blocked unscattered beam is related to BEPP dimensions and to divergence of the illumination system of the TEM. These practical issues are discussed in this paper. Phase images of biological samples (negatively stained ferritin) obtained by utilizing a BEPP are reported, and the phase contrast was found to be enhanced by a factor of approximately 1.5, based on the calculation using the Rose contrast criterion. The low gain in phase contrast is consistent with the expectation from the current TEM/BEPP system. A new generation of phase TEM utilizing BEPP and designed for biological imaging with a high phase efficiency is proposed.

A novel injectable in situ forming gel based on carboxymethyl hexanoyl chitosan/hyaluronic acid polymer blending for sustained release of berberine.

An in situ forming gel based on simply blending carboxymethyl hexanoyl chitosan (CHC) with low molecular weight hyaluronic acid (LMW HA) was developed, without needing cross-linking, photopolymerization or thermal treatments. The CHC/LMW HA blends formed nanoparticles and then rapidly transformed into supermolecular hydrogels under stirring. The gel formation mechanism was examined by Förster resonance energy transfer (FRET). The gels were injectable, cytocompatible and biodegradable, and showed shape-persistent behavior and adhesive property. Berberine, an anti-apoptotic and anti-arthritis naturally occurring compound, was encapsulated within the CHC/LMW HA gels. The gels demonstrated a pH-responsive characteristic which were able to release berberine in a sustained manner at pH 6.0 (simulating inflamed arthritic articular cartilage) and the degradation rates were accelerated at pH 7.4 (simulating healed normal tissue). The berberine-loaded gels effectively protected chondrocytes against sodium nitroprusside-induced apoptosis. The gels may be potentially useful as an injectable system for intra-articular drug delivery and cartilage tissue engineering.

Magnetostructural relationship in the spin-crossover complex t-{Fe(abpt)2[N(CN)2]2}: polymorphism and disorder phenomenon.

t-{Fe(abpt)(2)[N(CN)(2)](2)} [abpt = 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole] is an intriguing spin-crossover system that crystallizes in two polymorphs. Polymorph A is paramagnetic; its crystal structure consists of a single molecule located at the center of inversion symmetry. Polymorph B, on the other hand, exhibits a rather complicated two-step-like spin transition; its crystal structure consists of two symmetry-independent molecules. The crystal structure of polymorph B has been derived in the different spin states: above the high-temperature step (300 K), between the two steps (90 K), below the incomplete low-temperature step (50 K), in the light-induced metastable state (15 K), in the thermally quenched metastable state (15 K), and after relaxation from the quenched state (15 K). The correlation between the structure and magnetic properties is precisely established, allowing the complicated magnetic behavior of polymorph B to be well understood. A unique order-disorder phase transition, resulting in a modulation of the metastable state structures, is detected for the first time on such spin-transition compounds. The modulation of the structure originates from a particular ordering of the dicyanamide ligand at one of the two Fe sites.

Semantic Highlight Retrieval and Term Prediction.

Due to the unprecedented growth of unedited videos, finding highlights relevant to a text query in a set of unedited videos has become increasingly important. We refer this task as semantic highlight retrieval and propose a query-dependent video representation for retrieving a variety of highlights. Our method consists of two parts: 1) "viralets", a mid-level representation bridging between semantic [Fig. 1(a)] and visual [Fig. 1(c)] spaces and 2) a novel Semantic-MODulation (SMOD) procedure to make viralets query-dependent (referred to as SMOD viralets). Given SMOD viralets, we train a single highlight ranker to predict the highlightness of clips with respect to a variety of queries (two examples in Fig. 1), whereas existing approaches can be applied only in a few predefined domains. Other than semantic highlight retrieval, viralets can also be used to associate relevant terms to each video. We utilize this property and propose a simple term prediction method based on nearest neighbor search. To conduct experiments, we collect a viral video dataset including users' comments, highlights, and/or original videos. Among a testing database with 1189 clips (13% highlights and 87% non-highlights), our highlight ranker achieves 41.2% recall at top-10 retrieved clips. It is significantly higher than the state-of-the-art domain-specific highlight ranker and its extension. Similarly, our method also outperforms all baseline methods on the publicly available video highlight dataset. Finally, our simple term prediction method utilizing viralets outperforms the state-of-the-art matrix factorization method (adapted from Kalayeh et al.). Viral videos refer to popular online videos. We focus on user-generated viral videos, which typically contain short highlight marked by users.

Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis.

BACKGROUND: Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. It remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Therefore, we wished to characterize the transcript profiles in the LA and right atrium (RA) in sinus rhythm (SR) and AF respectively. METHODS: Paired LA and RA appendages acquired from patients receiving cardiac surgery were used for ion-channel- and whole-exome-based transcriptome analysis. The ultrastructure was evaluated by immunohistochemistry. RESULTS: Twenty-two and twenty ion-channels and transporters were differentially expressed between the LA and RA in AF and SR, respectively. Among these, 15 genes were differentially expressed in parallel between AF and SR. AF was associated with increased LA/RA expression ratio in 9 ion channel-related genes, including genes related to calcium handling. In microarray, AF was associated with a differential LA/RA gene expression ratio in 309 genes, and was involved in atherosclerosis-related signaling. AF was associated with the upregulation of thrombogenesis-related genes in the LA appendage, including P2Y12, CD 36 and ApoE. Immunohistochemistry showed higher expressions of collagen-1, oxidative stress and TGF-ß1 in the RA compared to the LA. CONCLUSIONS: AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF.