Real-time Automatic M-mode Echocardiography Measurement with Panel Attention from Local-to-Global Pixels

Motion mode (M-mode) recording is an essential part of echocardiography to measure cardiac dimension and function. However, the current diagnosis cannot build an automatic scheme, as there are three fundamental obstructs: Firstly, there is no open dataset available to build the automation for ensuring constant results and bridging M-mode echocardiography with real-time instance segmentation (RIS); Secondly, the examination is involving the time-consuming manual labelling upon M-mode echocardiograms; Thirdly, as objects in echocardiograms occupy a significant portion of pixels, the limited receptive field in existing backbones (e.g., ResNet) composed from multiple convolution layers are inefficient to cover the period of a valve movement. Existing non-local attentions (NL) compromise being unable real-time with a high computation overhead or losing information from a simplified version of the non-local block. Therefore, we proposed RAMEM, a real-time automatic M-mode echocardiography measurement scheme, contributes three aspects to answer the problems: 1) provide MEIS, a dataset of M-mode echocardiograms for instance segmentation, to enable consistent results and support the development of an automatic scheme; 2) propose panel attention, local-to-global efficient attention by pixel-unshuffling, embedding with updated UPANets V2 in a RIS scheme toward big object detection with global receptive field; 3) develop and implement AMEM, an efficient algorithm of automatic M-mode echocardiography measurement enabling fast and accurate automatic labelling among diagnosis. The experimental results show that RAMEM surpasses existing RIS backbones (with non-local attention) in PASCAL 2012 SBD and human performances in real-time MEIS tested. The code of MEIS and dataset are available at https://github.com/hanktseng131415go/RAME

Structural insights into the electron/proton transfer pathways in the quinol:fumarate reductase from Desulfovibrio gigas

The membrane-embedded quinol:fumarate reductase (QFR) in anaerobic bacteria catalyzes the reduction of fumarate to succinate by quinol in the anaerobic respiratory chain. The electron/proton-transfer pathways in QFRs remain controversial. Here we report the crystal structure of QFR from the anaerobic sulphate-reducing bacterium Desulfovibrio gigas (D. gigas) at 3.6 Å resolution. The structure of the D. gigas QFR is a homo-dimer, each protomer comprising two hydrophilic subunits, A and B, and one transmembrane subunit C, together with six redox cofactors including two b-hemes. One menaquinone molecule is bound near heme b_L in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane. Armed with these structural insights, we propose electron/proton-transfer pathways in the quinol reduction of fumarate to succinate in the D. gigas QFR

Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas

Guan, H., Hsieh, Y., Lin, P. et al. Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas. Sci Rep 8, 14935 (2018) doi:10.1038/s41598-018-33193-

Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas

The membrane-embedded quinol: fumarate reductase (QFR) in anaerobic bacteria catalyzes the reduction of fumarate to succinate by quinol in the anaerobic respiratory chain. The electron/protontransfer pathways in QFRs remain controversial. Here we report the crystal structure of QFR from the anaerobic sulphate-reducing bacterium Desulfovibrio gigas (D. gigas) at 3.6 Å resolution. The structure of the D. gigas QFR is a homo-dimer, each protomer comprising two hydrophilic subunits, A and B, and one transmembrane subunit C, together with six redox cofactors including two b-hemes. One menaquinone molecule is bound near heme bL in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane. Armed with these structuralinsights, we propose electron/proton-transfer pathways in the quinol reduction of fumarate to succinate in the D. gigas QFR.Guan, H., Hsieh, Y., Lin, P. et al. Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas. Sci Rep 8, 14935 (2018) doi:10.1038/s41598-018-33193-

The atomic structures of shrimp nodaviruses reveal new dimeric spike structures and particle polymorphism

Shrimp nodaviruses, including Penaeus vannamei (PvNV) and Macrobrachium rosenbergii nodaviruses (MrNV), cause white-tail disease in shrimps, with high mortality. The viral capsid structure determines viral assembly and host specificity during infections. Here, we show cryo-EM structures of T = 3 and T = 1 PvNV-like particles (PvNV-LPs), crystal structures of the protrusion-domains (P-domains) of PvNV and MrNV, and the crystal structure of the ∆N-ARM-PvNV shell-domain (S-domain) in T = 1 subviral particles. The capsid protein of PvNV reveals five domains: the P-domain with a new jelly-roll structure forming cuboid-like spikes; the jelly-roll S-domain with two calcium ions; the linker between the S- and P-domains exhibiting new cross and parallel conformations; the N-arm interacting with nucleotides organized along icosahedral two-fold axes; and a disordered region comprising the basic N-terminal arginine-rich motif (N-ARM) interacting with RNA. The N-ARM controls T = 3 and T = 1 assemblies. Increasing the N/C-termini flexibility leads to particle polymorphism. Linker flexibility may influence the dimeric-spike arrangement

Evaluation of Oral Antiretroviral Drugs in Mice With Metabolic and Neurologic Complications

Antiretroviral (ART) drugs has previously been associated with lipodystrophic syndrome, metabolic consequences, and neuropsychiatric complications. ART drugs include three main classes of protease inhibitors (PIs), nucleoside analog reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our previous work demonstrated that a high risk of hyperlipidemia was observed in HIV-1-infected patients who received ART drugs in Taiwan. Patients receiving ART drugs containing either Abacavir/Lamivudine (Aba/Lam; NRTI/NRTI), Lamivudine/Zidovudine (Lam/Zido; NRTI/NRTI), or Lopinavir/Ritonavir (Lop/Rit; PI) have the highest risk of hyperlipidemia. The aim of this study was to investigate the effects of Aba/Lam (NRTI/NRTI), Lam/Zido (NRTI/NRTI), and Lop/Rit (PI) on metabolic and neurologic functions in mice. Groups of C57BL/6 mice were administered Aba/Lam, Lam/Zido, or Lop/Rit, orally, once daily for a period of 4 weeks. The mice were then extensively tested for metabolic and neurologic parameters. In addition, the effect of Aba/Lam, Lam/Zido, and Lop/Rit on lipid metabolism was assessed in HepG2 hepatocytes and during the 3T3-L1 preadipocyte differentiation. Administration with Aba/Lam caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in leptin serum levels. Administration with Lop/Rit also caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in serum levels of total cholesterol, and HDL-c. Treatment of mice with Aba/Lam and Lop/Rit enhanced the lipid accumulation in the liver, and the decrease in AMP-activated protein kinase (AMPK) phosphorylation and/or its downstream target acetyl-CoA carboxylase (ACC) protein expression. In HepG2 hepatocytes, Aba/Lam, Lam/Zido, and Lop/Rit also enhanced the lipid accumulation and decreased phosphorylated AMPK and ACC proteins. In 3T3-L1 pre-adipocyte differentiation, Aba/Lam and Lop/Rit reduced adipogenesis by decreasing expression of transcription factor CEBPb, implicating the lipodystrophic syndrome. Our results demonstrate that daily oral administration of Aba/Lam and Lop/Rit may produce cognitive, motor, and metabolic impairments in mice, regardless of HIV-1 infection

The atomic structures of shrimp nodaviruses reveal new dimeric spike structures and particle polymorphism

Shrimp nodaviruses, including Penaeus vannamei (PvNV) and Macrobrachium rosenbergii nodaviruses (MrNV), cause white-tail disease in shrimps, with high mortality. The viral capsid structure determines viral assembly and host specificity during infections. Here, we show cryo-EM structures of T = 3 and T = 1 PvNV-like particles (PvNV-LPs), crystal structures of the protrusion-domains (P-domains) of PvNV and MrNV, and the crystal structure of the ∆N-ARM-PvNV shell-domain (S-domain) in T = 1 subviral particles. The capsid protein of PvNV reveals five domains: the P-domain with a new jelly-roll structure forming cuboid-like spikes; the jelly-roll S-domain with two calcium ions; the linker between the S- and P-domains exhibiting new cross and parallel conformations; the N-arm interacting with nucleotides organized along icosahedral two-fold axes; and a disordered region comprising the basic N-terminal arginine-rich motif (N-ARM) interacting with RNA. The N-ARM controls T = 3 and T = 1 assemblies. Increasing the N/C-termini flexibility leads to particle polymorphism. Linker flexibility may influence the dimeric-spike arrangement

The atomic structures of shrimp nodaviruses reveal new dimeric spike structures and particle polymorphism

Shrimp nodaviruses, including Penaeus vannamei (PvNV) and Macrobrachium rosenbergii nodaviruses (MrNV), cause white-tail disease in shrimps, with high mortality. The viral capsid structure determines viral assembly and host specificity during infections. Here, we show cryo-EM structures of T = 3 and T = 1 PvNV-like particles (PvNV-LPs), crystal structures of the protrusion-domains (P-domains) of PvNV and MrNV, and the crystal structure of the ∆N-ARM-PvNV shell-domain (S-domain) in T = 1 subviral particles. The capsid protein of PvNV reveals five domains: the P-domain with a new jelly-roll structure forming cuboid-like spikes; the jelly-roll S-domain with two calcium ions; the linker between the S- and P-domains exhibiting new cross and parallel conformations; the N-arm interacting with nucleotides organized along icosahedral two-fold axes; and a disordered region comprising the basic N-terminal arginine-rich motif (N-ARM) interacting with RNA. The N-ARM controls T = 3 and T = 1 assemblies. Increasing the N/C-termini flexibility leads to particle polymorphism. Linker flexibility may influence the dimeric-spike arrangement

Augmented TLR2 Expression on Monocytes in both Human Kawasaki Disease and a Mouse Model of Coronary Arteritis

BACKGROUND: Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. METHODS: Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. RESULTS: Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. CONCLUSION: This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14+ monocytes