Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitofusin 2-Containing Mitochondrial-Reticular Microdomains Direct Rapid Cardiomyocyte Bioenergetic Responses Via Interorganelle Ca2+ Crosstalk

Rationale: Mitochondrial Ca2+ uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association of mitochondria to the sarcoplasmic reticulum (SR) may explain efficient mitochondrial Ca2+ uptake despite low Ca2+ affinity of the mitochondrial Ca2+ uniporter. However, the existence of such mitochondrial Ca2+ microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic reticulum to mitochondria in noncardiac cells. Objective: To elucidate roles for Mfn1 and 2 in SR-mitochondrial tethering, Ca2+ signaling, and bioenergetic regulation in cardiac myocytes. Methods and Results: Fruit fly heart tubes deficient of the Drosophila Mfn ortholog MARF had increased contraction-associated and caffeine-sensitive Ca2+ release, suggesting a role for Mfn in SR Ca2+ handling. Whereas cardiac-specific Mfn1 ablation had no effects on murine heart function or Ca2+ cycling, Mfn2 deficiency decreased cardiomyocyte SR-mitochondrial contact length by 30% and reduced the content of SR-associated proteins in mitochondria-associated membranes. This was associated with decreased mitochondrial Ca2+ uptake (despite unchanged mitochondrial membrane potential) but increased steady-state and caffeine-induced SR Ca2+ release. Accordingly, Ca2+-induced stimulation of Krebs cycle dehydrogenases during &bgr;-adrenergic stimulation was hampered in Mfn2-KO but not Mfn1-KO myocytes, evidenced by oxidation of the redox states of NAD(P)H/NAD(P)+ and FADH2/FAD. Conclusions: Physical tethering of SR and mitochondria via Mfn2 is essential for normal interorganelle Ca2+ signaling in the myocardium, consistent with a requirement for SR-mitochondrial Ca2+ signaling through microdomains in the cardiomyocyte bioenergetic feedback response to physiological stress.
Cellular Compartmentation and the Redox/Nonredox Functions of NAD.

SIGNIFICANCE Nicotinamide adenine dinucleotide (NAD+) spans diverse roles in biology, serving as both an important redox cofactor in metabolism and a substrate for signaling enzymes that regulate protein post-translational modifications (PTMs). CRITICAL ISSUES Although the interactions between these different roles of NAD+ (and its reduced form NADH) have been considered, little attention has been paid to the role of compartmentation in these processes. Specifically, the role of NAD+ in metabolism is compartment specific (e.g., mitochondrial vs. cytosolic), affording a very different redox landscape for PTM-modulating enzymes such as sirtuins and poly(ADP-ribose) polymerases in different cell compartments. In addition, the orders of magnitude differences in expression levels between NAD+-dependent enzymes are often not considered when assuming the effects of bulk changes in NAD+ levels on their relative activities. Recent Advances: In this review, we discuss the metabolic, nonmetabolic, redox, and enzyme substrate roles of cellular NAD+, and the recent discoveries regarding the interplay between these roles in different cell compartments. FUTURE DIRECTIONS Therapeutic implications for the compartmentation and manipulation of NAD+ biology are discussed.
Outage Probability Analysis in Power-Beacon Assisted Energy Harvesting Cognitive Relay Wireless Networks

We study the performance of the secondary relay system in a power-beacon (PB) assisted energy harvesting cognitive relay wireless network. In our system model, a secondary source node and a relay node first harvest energy from distributed PBs. Then, the source node transmits its data to the destination node with the help of the relay node. Also, fading coefficients of the links from the PBs to the source node and relay node are assumed independent but not necessarily identically distributed (i.n.i.d) Nakagami- random variables. We derive exact expressions for the power outage probability and the channel outage probability. Based on that, we analyze the total outage probability of the secondary relay system. Asymptotic analysis is also performed, which provides insights into the system behavior. Moreover, we evaluate impacts of the primary network on the performance of the secondary network with respect to the tolerant interference threshold at the primary receiver as well as the interference introduced by the primary transmitter at the secondary source and relay nodes. Simulation results are provided to validate the analysis.
A Perception-driven Hybrid Decomposition for Multi-layer Accommodative Displays

Multi-focal plane and multi-layered light-field displays are promising solutions for addressing all visual cues observed in the real world. Unfortunately, these devices usually require expensive optimizations to compute a suitable decomposition of the input light field or focal stack to drive individual display layers. Although these methods provide near-correct image reconstruction, a significant computational cost prevents real-time applications. A simple alternative is a linear blending strategy which decomposes a single 2D image using depth information. This method provides real-time performance, but it generates inaccurate results at occlusion boundaries and on glossy surfaces. This paper proposes a perception-based hybrid decomposition technique which combines the advantages of the above strategies and achieves both real-time performance and high-fidelity results. The fundamental idea is to apply expensive optimizations only in regions where it is perceptually superior, e.g., depth discontinuities at the fovea, and fall back to less costly linear blending otherwise. We present a complete, perception-informed analysis and model that locally determine which of the two strategies should be applied. The prediction is later utilized by our new synthesis method which performs the image decomposition. The results are analyzed and validated in user experiments on a custom multi-plane display.
Measurement of Human Gait Symmetry using Body Surface Normals Extracted from Depth Maps

In this paper, we introduce an approach for measuring human gait symmetry where the input is a sequence of depth maps of subject walking on a treadmill. Body surface normals are used to describe 3D information of the walking subject in each frame. Two different schemes for embedding the temporal factor into a symmetry index are proposed. Experiments on the whole body, as well as the lower limbs, were also considered to assess the usefulness of upper body information in this task. The potential of our method was demonstrated with a dataset of 97,200 depth maps of nine different walking gaits. An ROC analysis for abnormal gait detection gave the best result (AUC=0.958) compared with other related studies. The experimental results provided by our method confirm the contribution of upper body in gait analysis as well as the reliability of approximating average gait symmetry index without explicitly considering individual gait cycles for asymmetry detection.
A Review of the Role of Breast Arterial Calcification for Cardiovascular Risk Stratification in Women

Cardiovascular disease continues to be the leading cause of death among women in the United States. One of the barriers to improving cardiovascular disease outcomes in women is the lack of reliable, effective screening modalities. Breast arterial calcification has emerged as a potential risk stratification tool. Localized deposition in the media of the artery, known as Mönckeberg medial calcific sclerosis, is notably different from the intimal atherosclerotic process commonly associated with coronary artery disease. Nonetheless, studies favor a correlation between breast arterial calcification and cardiovascular risk factors or coronary artery disease, defined as coronary artery calcification on computed tomography scan or both nonobstructive and obstructive lesions on angiography. Since a majority of women over the age of 40 undergo yearly breast cancer screening with mammography, measurement of breast arterial calcification may offer a personalized, noninvasive approach to risk-stratify women for cardiovascular disease at no additional cost or radiation. Mammography has the potential to alter the course of the leading cause of death in women, heart disease, through the evaluation of breast arterial calcification and identification of opportunities for prevention. Current evidence supports the universal reporting of breast arterial calcifications and personalized patient-provider discussions to more aggressively treat cardiac risk factors through targeted medical therapies or healthy lifestyle changes.
Bacteriocins of Gram-positive bacteria having activity spectra extending beyond closely-related species.

Bacteriocins are bacterially-produced antimicrobial peptides that have killing activity principally against other relatively closely-related bacteria. Some bacteriocins of the lactic acid bacteria (LAB) have for many years been extensively applied in food biopreservation. However, especially during the last decade, a number of reports have appeared about unanticipated extensions to the generally rather narrow anti-bacterial activity spectrum of some of the LAB bacteriocins and novel applications have been proposed for bacteriocins ranging from controlling the growth of an increasingly-heterogeneous variety of pathogens, including Gram-negative multidrug resistant bacteria, viruses, yeasts, and in particular, difficult to control Mycobacterium spp. , to their potential application as anticancer agents. How best can we assess this now rapidly-accumulating stream of reports on potential future applications of bacteriocins? Where is the line between realistic, science-based proposals and highly-speculative fiction and what are the 'critical points' that might help us to draw this line? In this review, we have attempted to analyse a selection of the presently-available data concerning relatively 'unorthodox' (i.e. beyond food preservation) applications of bacteriocins, and, by utilising our set of 'critical points', we endeavour to identify essential or/and missing information that appear crucial for success of the proposed applications.
Heat stress decreases metabolic flexibility in skeletal muscle of growing pigs.

Heat-stressed pigs experience metabolic alterations, including altered insulin profiles, reduced lipid mobilization, and compromised intestinal integrity. This is bioenergetically distinct from thermal neutral pigs on a similar nutritional plane. To delineate differences in substrate preferences between direct and indirect (via reduced feed intake) heat stress effects, skeletal muscle fuel metabolism was assessed. Pigs (35.3 ± 0.8 kg) were randomly assigned to three treatments: thermal neutral fed ad libitum (TN; 21°C, n = 8), heat stress fed ad libitum (HS; 35°C, n = 8), and TN, pair-fed/HS intake (PF; n = 8) for 7 days. Body temperature (TB) and feed intake (FI) were recorded daily. Longissimus dorsi muscle was biopsied for metabolic assays on days -2, 3, and 7 relative to initiation of environmental treatments. Heat stress increased TB and decreased FI ( P < 0.05). Heat stress inhibited incomplete fatty acid oxidation and glucose oxidation ( P < 0.05). Metabolic flexibility decreased in HS pigs compared with TN and PF controls ( P < 0.05). Both phosphofructokinase and pyruvate dehydrogenase (PDH) activities increased in PF ( P < 0.05); however, TN and HS did not differ. Heat stress inhibited citrate synthase and β-hydroxyacyl-CoA dehydrogenase (β-HAD) activities ( P < 0.05). Heat stress did not alter PDH phosphorylation or carnitine palmitoyltransferase 1 abundance but reduced acetyl-CoA carboxylase 1 (ACC1) protein abundance ( P < 0.05). In conclusion, HS decreased skeletal muscle fatty acid oxidation and metabolic flexibility, likely involving β-HAD and ACC regulation.
Plexina2 and CRMP2 Signaling Complex Is Activated by Nogo-A-Liganded Ngr1 to Restrict Corticospinal Axon Sprouting after Trauma

After brain or spinal cord trauma, interaction of Nogo-A with neuronal NgR1 limits regenerative axonal sprouting and functional recovery. Cellular signaling by lipid-anchored NgR1 requires a coreceptor but the relevant partner in vivo is not clear. Here, we examined proteins enriched in NgR1 immunoprecipitates by Nogo-A exposure, identifying CRMP2, a cytosolic protein implicated in axon growth inhibition by Semaphorin/Plexin complexes. The Nogo-A-induced association of NgR1 with CRMP2 requires PlexinA2 as a coreceptor. Non-neuronal cells expressing both NgR1 and PlexinA2, but not either protein alone, contract upon Nogo-A exposure. Inhibition of cortical axon regeneration by Nogo-A depends on a NgR1/PlexinA2 genetic interaction because double-heterozygous NgR1+/−, PlexinA2+/− neurons, but not single-heterozygote neurons, are rescued from Nogo-A inhibition. NgR1 and PlexinA2 also interact genetically in vivo to restrict corticospinal sprouting in mouse cervical spinal cord after unilateral pyramidotomy. Greater post-injury sprouting in NgR1+/−, PlexinA2+/− mice supports enhanced neurological recovery of a mixed female and male double-heterozygous cohort. Thus, a NgR1/PlexinA2/CRMP2 ternary complex limits neural repair after adult mammalian CNS trauma. SIGNIFICANCE STATEMENT Several decades of molecular research have suggested that developmental regulation of axon growth is distinct in most regards from titration of axonal regenerative growth after adult CNS trauma. Among adult CNS pathways, the oligodendrocyte Nogo-A inhibition of growth through NgR1 is thought to have little molecular relationship to axonal guidance mechanisms active embryonically. Here, biochemical analysis of NgR1 function uncovered a physical complex with CRMP cytoplasmic mediators, and this led to appreciation of a role for PlexinA2 in concert with NgR1 after adult trauma. The data extend molecular understanding of neural repair after CNS trauma and link it to developmental processes.
Utilization of a Novel, Multi-Durometer Intracranial Distal Access Catheter: Nuances and Experience in 110 Consecutive Cases of Aneurysm Flow Diversion

Background: Coaxial catheter support systems provide a safe and stable foundation in endovascular treatment of intracranial aneurysms. Increasingly, robust distal intracranial support is sought during complex neurointerventions. The AXS Catalyst 5 distal access catheter (Cat5) is a new intracranial catheter designed for improved trackability and stability. We report the first experience using Cat5 for aneurysm treatment by flow diversion. Methods: A single-center aneurysm database was reviewed for cases of aneurysm treatment with the Pipeline embolization device (PED) that utilized Cat5. Data were collected for patient demographics, aneurysm characteristics, procedural details, catheter positions, vessel tortuosity, and catheter related complications. Results: One hundred and ten cases of aneurysm flow diversion were successfully performed using Cat5. Patient age ranged from 21 to 86 years (mean 57 ± 12.5 years) with 84% women. Aneurysm size ranged from 2 to 28 mm (mean 5.7 ± 5.0 mm), with 97% in the anterior circulation. Twenty-four aneurysms (22%) were located beyond the ICA termination. Significant cervical carotid tortuosity was present in 26% of cases, and moderate to severe cavernous tortuosity (cavernous grade ≥2) in 45% of cases. Cat5 was tracked to the intended distal position in all cases with 100% technical success of PED implantation. No iatrogenic catheter-related vessel injury occurred, and major neurological morbidity occurred in 1 patient (1%). Summary: The Cat5 is a novel, multi-durometer cranial distal access catheter designed for use in tri-axial systems. We have demonstrated the utility of Cat5 in 110 successful cases of flow diversion with a wide range of complexity. This catheter is a new tool in the neurointerventionalist's armamentarium to achieve robust and atraumatic distal access.
Evaluation of the overdiagnosis in breast screening programmes using a Monte Carlo simulation tool: a study of the influence of the parameters defining the programme configuration

Objectives To build up and test a Monte Carlo simulation procedure for the investigation of overdiagnosis in breast screening programmes (BSPs). Design A Monte Carlo tool previously developed has been adapted for obtaining the quantities of interest in order to determine the overdiagnosis: the annual and cumulative number of cancers detected by screening, plus interval cancers, for a population following the BSP, and detected clinically for the same population in the absence of screening. Overdiagnosis is obtained by comparing these results in a direct way. Results Overdiagnosis between 7% and 20%, depending on the specific configuration of the programme, have been found. These range of values is in agreement with some of the results available for actual BSPs. In the cases analysed, a reduction of 11% at most has been found in the number of invasive tumours detected by screening in comparison to those clinically detected in the control population. It has been possible to establish that overdiagnosis is almost entirely linked to ductal carcinoma in situ tumours. Conclusions The use of Monte Carlo tools may facilitate the analysis of overdiagnosis in actual BSPs, permitting to address the role played by various quantities of relevance for them.
Real and Illusory Interactions Enhance Presence in Virtual Environments

It has long been argued that the possibility to interact in and with a virtual environment (VE) enhances the sense of presence. On the basis of a three-component model of presence, we specify this hypothesis and argue that the mental representation of possible actions should especially enhance spatial presence, and to a lesser extent the involvement and realness of a VE. We support this hypothesis in three studies. A correlative study showed that self-reported interaction possibilities correlated significantly with spatial presence, but not with the other two factors. A first experimental study showed that possible self-movement significantly increased spatial presence and realness. A second experimental study showed that even the illusion of interaction, with no actual interaction taking place, significantly increased spatial presence.
Complete mitochondrial genome of the Scorpaenopsis cirrhosa (Scorpaeniformes: Scorpaenidae)

Abstract The complete mitochondrial genome of the Scorpaenopsis cirrhosa has been sequenced. The mitochondrial genome is 16 966 bp in length, containing 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1 control region. The gene order and composition of S. cirrhosa mitochondrial genome was similar to that of most other vertebrates. The overall nucleotides base composition of the heavy strand is A (27.91%), G (17.71%), C (28.02%), and T (26.35%). With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The tRNA-Ser2 gene lacked DHC arm and could not fold into a typical clover-leaf secondary structure. Seen from the phylogenetic tree, S. cirrhosa, a stonefish and four rockfishes from the same order (Scorpaeniformes) clustered into one branch.
Health Information Engagement Factors in Malaysia: A Content Analysis of Facebook Use by the Ministry of Health in 2016 and 2017

Health organizations have widely adopted social media for health promotion, public health communication conveyance, and organizational promotion activities. However, little published data exists on the factors that facilitate health information diffusion in South East Asia, especially Malaysia compared with Western countries. This study aimed to investigate factors associated with good engagement rates among internet users on the Facebook (FB) page of Ministry of Health Malaysia. In this observational study, 2123 FB posts were randomly selected. Data dated from 1 November 2016 to 31 October 2017 was gathered from the Facebook Insight. The logistic regression model was applied to identify factors associated with good engagement rates. This study found that a FB post with a good engagement rate was significantly associated with a health education post (Adjusted Odd Ratio (AOR): 3.80, 95% Confidence Interval CI: 3.02–4.78, p < 0.001), a risk communication post (AOR: 1.77, 95% CI: 1.39–2.26, p < 0.001), a post in the afternoon (AOR: 1.76, 95% CI: 1.34–2.31, p < 0.001) or in the evening (AOR: 1.48, 95% CI: 1.20–1.82, p < 0.001), and a video format (AOR: 3.74, 95% CI: 1.44–9.71, p = 0.007). Therefore, we present the first comprehensive analysis of health information engagement among internet users in Malaysia. The growing trends of online health information-seeking behaviors and demand for the availability of validated health information require effective strategies by public health organizations to disseminate health information and achieve better audience engagement on social media.
ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet–associated Colon Cancer

Purpose: Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein–coupled receptors, including CXCR4. Here we investigated CXCR4–ADAM17 crosstalk and examined the role of ADAM17 in tumorigenesis. Experimental Design: We used CXCR4 inhibitor, AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4–ADAM17 crosstalk in colon cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in mice fed Western diet versus standard diet. Separately, mice were treated with marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from primary human colon cancers and adjacent mucosa. Results: CXCL12 treatment activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced this activation. In vivo, Western diet increased CXCL12 in stromal cells and TGFα in colonocytes. Marimastat or AMD3100 caused >50% reduction in EGFR signals (P < 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and inhibited intestinal tumor multiplicity (P < 0.05). In the AOM model, colonocyte ADAM17 deletion reduced EGFR signals and colonic tumor development (P < 0.05). Finally, ADAM17 was upregulated >2.5-fold in human malignant colonocytes. Conclusions: ADAM17 is a Western diet–inducible enzyme activated by CXCL12–CXCR4 signaling, suggesting the pathway: Western diet→CXCL12→CXCR4→ADAM17→TGFα→EGFR. ADAM17 might serve as a druggable target in chemoprevention strategies. Clin Cancer Res; 23(2); 549–61. ©2016 AACR.