Selective depletion of the Type I, Type II, and Type III isozymes of hexokinase in mammalian cells using small interfering RNAs*1

ABSTRACT Severe complications of Zika virus (ZIKV) infection might be caused by inflammation, but how ZIKV induces proinflammatory cytokines is not understood. In this study, we show opposite regulatory effects of the ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate type II IFN signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but it had no influence on STAT1 stability or nuclear translocation. The recruitment of STAT1-STAT2-IRF9 to IFN-β-stimulated genes was compromised when NS5 was expressed. Concurrently, the formation of STAT1-STAT1 homodimers and their recruitment to IFN-γ-stimulated genes, such as the gene encoding the proinflammatory cytokine CXCL10, were augmented. Silencing the expression of an IFN-γ receptor subunit or treatment of ZIKV-infected cells with a JAK2 inhibitor suppressed viral replication and viral induction of IFN-γ-stimulated genes. Taken together, our findings provide a new mechanism by which the ZIKV NS5 protein differentially regulates IFN signaling to facilitate viral replication and cause diseases. This activity might be shared by a group of viral IFN modulators. IMPORTANCE Mammalian cells produce three types of interferons to combat viral infection and to control host immune responses. To replicate and cause diseases, pathogenic viruses have developed different strategies to defeat the action of host interferons. Many viral proteins, including the Zika virus (ZIKV) NS5 protein, are known to be able to suppress the antiviral property of type I and type III interferons. Here we further show that the ZIKV NS5 protein can also boost the activity of type II interferon to induce cellular proteins that promote inflammation. This is mediated by the differential effect of the ZIKV NS5 protein on a pair of cellular transcription factors, STAT1 and STAT2. NS5 induces the degradation of STAT2 but promotes the formation of STAT1-STAT1 protein complexes, which activate genes controlled by type II interferon. A drug that specifically inhibits the IFN-γ receptor or STAT1 shows an anti-ZIKV effect and might also have anti-inflammatory activity.

Download Full-text

Labelling of non-A, non-B hepatitis infected chimpanzee hepatocytes with nuclease-gold conjugates

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111367 ◽

1984 ◽

Vol 42 ◽

pp. 250-251

Author(s):

G. D. Gagne ◽

M. F. Miller ◽

D. A. Peterson

Keyword(s):

Endoplasmic Reticulum ◽

Experimental Infection ◽

Uranyl Acetate ◽

Type I ◽

Cellular Injury ◽

Type Ii ◽

Tubular Structures ◽

Type Iii ◽

Type Iv ◽

Infected Chimpanzee

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.

Download Full-text

Perforator preservation technologies (PPT) based on a new neuro-interventional classification in endovascular treatment of perforator involving aneurysms (piANs)

Chinese Neurosurgical Journal ◽

10.1186/s41016-021-00243-3 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Chen Li ◽

Ao-Fei Liu ◽

Han-Cheng Qiu ◽

Xianli Lv ◽

Ji Zhou ◽

...

Keyword(s):

Endovascular Therapy ◽

Saccular Aneurysm ◽

Type I ◽

Type Ii ◽

Fusiform Aneurysm ◽

Type Iii ◽

Perforating Artery ◽

Protection Technology ◽

Perforating Arteries

Abstract Background Treatment of perforator involving aneurysm (piAN) remains a challenge to open and endovascular neurosurgeons. Our aim is to demonstrate a primary outcome of endovascular therapy for piANs with the use of perforator preservation technologies (PPT) based on a new neuro-interventional classification. Methods The piANs were classified into type I: aneurysm really arises from perforating artery, type II: saccular aneurysm involves perforating arteries arising from its neck (IIa) or dome (IIb), and type III: fusiform aneurysm involves perforating artery. Stent protection technology of PPT was applied in type I and III aneurysms, and coil-basket protection technology in type II aneurysms. An immediate outcome of aneurysmal obliteration after treatment was evaluated (satisfactory obliteration: the saccular aneurysm body is densely embolized (I), leaving a gap in the neck (IIa) or dome (IIb) where the perforating artery arising; fusiform aneurysm is repaired and has a smooth inner wall), and successful perforating artery preservation was defined as keeping the good antegrade flow of those perforators on postoperative angiography. The periprocedural complication was closely monitored, and clinical and angiographic follow-ups were performed. Results Six consecutive piANs (2 ruptured and 4 unruptured; 1 type I, 2 type IIa, 2 type IIb, and 1 type III) in 6 patients (aged from 43 to 66 years; 3 males) underwent endovascular therapy between November 2017 and July 2019. The immediate angiography after treatment showed 6 aneurysms obtained satisfactory obliteration, and all of their perforating arteries were successfully preserved. During clinical follow-up of 13–50 months, no ischemic or hemorrhagic event of the brain occurred in the 6 patients, but has one who developed ischemic event in the territory of involving perforators 4 h after operation and completely resolved within 24 h. Follow-up angiography at 3 to 10M showed patency of the parent artery and perforating arteries of treated aneurysms, with no aneurysmal recurrence. Conclusions Our perforator preservation technologies on the basis of the new neuro-interventional classification seem feasible, safe, and effective in protecting involved perforators while occluding aneurysm.

Download Full-text

Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

International Journal of Molecular Sciences ◽

10.3390/ijms22010429 ◽

2021 ◽

Vol 22 (1) ◽

pp. 429

Author(s):

Luca Bini ◽

Domitille Schvartz ◽

Chiara Carnemolla ◽

Roberta Besio ◽

Nadia Garibaldi ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Type I Collagen ◽

Type I ◽

Tandem Mass ◽

Type Ii ◽

Type Iii ◽

Bioinformatic Tools ◽

Proteomic Approach ◽

Fibrillin 1 ◽

Heritable Disorder

Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.

Download Full-text

Brachial supporting structure of Spiriferida (Brachiopoda)

Journal of Paleontology ◽

10.1017/jpa.2020.106 ◽

2020 ◽

pp. 1-15

Author(s):

Zhiwei Yuan ◽

Wen Guo ◽

Dan Lyu ◽

Yuanlin Sun

Keyword(s):

Mantle Cavity ◽

Family Type ◽

Type I ◽

Type Ii ◽

Feeding Apparatus ◽

Single Family ◽

Supporting Structure ◽

Type Iii ◽

Type Iv ◽

Evolutionary Lineages

Abstract The filter-feeding organ of some extinct brachiopods is supported by a skeletal apparatus called the brachidium. Although relatively well studied in Atrypida and Athyridida, the brachidial morphology is usually neglected in Spiriferida. To investigate the variations of brachidial morphology in Spiriferida, 65 species belonging to eight superfamilies were analyzed. Based on the presence/absence of the jugal processes and normal/modified primary lamellae of the spiralia, four types of brachidium are recognized. Type-I (with jugal processes) and Type-II (without jugal processes), both having normal primary lamellae, could give rise to each other by losing/re-evolving the jugal processes. Type-III, without jugal processes, originated from Type-II through evolution of the modified lateral-convex primary lamellae, and it subsequently gave rise to Type-IV by evolving the modified medial-convex primary lamellae. The evolution of brachidia within individual evolutionary lineages must be clarified because two or more types can be present within a single family. Type-III and Type-IV are closely associated with the prolongation of the crura, representing innovative modifications of the feeding apparatus in response to possible shift in the position of the mouth towards the anterior, allowing for more efficient feeding on particles entering the mantle cavity from the anterior gape. Meanwhile, the modified primary lamellae adjusted/regulated the feeding currents. The absence of spires in some taxa with Type-IV brachidium might suggest that they developed a similar lophophore to that in some extant brachiopods, which can extend out of the shell.

Download Full-text

Understanding the Evolution and Applications of Intelligent Systems via a Tri-X Intelligence (TI) Model

Processes ◽

10.3390/pr9061080 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1080

Author(s):

Min Zhao ◽

Zhenbo Ning ◽

Baicun Wang ◽

Chen Peng ◽

Xingyu Li ◽

...

Keyword(s):

Intelligent Systems ◽

Intelligent Manufacturing ◽

Type I ◽

Type Ii ◽

Multiple Perspectives ◽

Ternary Interaction ◽

Physical Systems ◽

Type Iii ◽

Dynamic Level ◽

Systematic Scheme

The evolution and application of intelligence have been discussed from perspectives of life, control theory and artificial intelligence. However, there has been no consensus on understanding the evolution of intelligence. In this study, we propose a Tri-X Intelligence (TI) model, aimed at providing a comprehensive perspective to understand complex intelligence and the implementation of intelligent systems. In this work, the essence and evolution of intelligent systems (or system intelligentization) are analyzed and discussed from multiple perspectives and at different stages (Type I, Type II and Type III), based on a Tri-X Intelligence model. Elemental intelligence based on scientific effects (e.g., conscious humans, cyber entities and physical objects) is at the primitive level of intelligence (Type I). Integrated intelligence formed by two-element integration (e.g., human-cyber systems and cyber-physical systems) is at the normal level of intelligence (Type II). Complex intelligence formed by ternary-interaction (e.g., a human-cyber-physical system) is at the dynamic level of intelligence (Type III). Representative cases are analyzed to deepen the understanding of intelligent systems and their future implementation, such as in intelligent manufacturing. This work provides a systematic scheme, and technical supports, to understand and develop intelligent systems.

Download Full-text

Morphological types of spermatheca in Coreidae: bearing on intra-familial classification and tribal-groupings (Hemiptera: Heteroptera)

Zootaxa ◽

10.11646/zootaxa.4834.4.1 ◽

2020 ◽

Vol 4834 (4) ◽

pp. 451-501

Author(s):

DOMINIQUE PLUOT-SIGWALT ◽

PIERRE MOULET

Keyword(s):

Western Hemisphere ◽

Type I ◽

Type Ii ◽

Type Iii ◽

Spermathecal Duct ◽

Eastern Hemisphere ◽

Intermediate Part ◽

Muscular Pump ◽

Familial Classification

The morphology of the spermatheca is described in 109 species of 86 genera representing all four currently recognised subfamilies of Coreidae, covering the undivided Hydarinae, both tribes of Pseudophloeinae, all three tribes of Meropachyinae and 27 of the 32 tribes of Coreinae. Three types of spermatheca are recognised. Type I is bipartite, consisting only of a simple tube differentiated into distal seminal receptacle and proximal spermathecal duct and lacks the intermediate part present in most Pentatomomorpha, in which it serves as muscular pump. Type II is also bipartite but more elaborate in form with the receptacle generally distinctly wider than the duct. Type III is tripartite, with receptacle, duct and an often complex intermediate part. Four subtypes are recognised within type III. Type I is found only in Hydarinae and type II only in Pseudophloeinae. Type III is found in both Coreinae and Meropachyinae. Subtype IIIA (“Coreus-group”) unites many tribes from the Eastern Hemisphere and only one (Spartocerini) from the Western Hemisphere. Subtypes IIIB (“Nematopus-group”) and IIID (“Anisoscelis-group”) are confined to taxa from the Western Hemisphere and subtype IIIC (“Chariesterus-group”) is found in tribes from both hemispheres. The polarity of several characters of the intermediate part and some of the spermathecal duct is evaluated, suggesting autapomorphies or apomorphies potentially relevant to the classification of Coreidae at the sufamilial and tribal levels. Characters of the intermediate part strongly indicate that the separation of Meropachyinae and Coreinae as currently constituted cannot be substantiated. The tribes Anisoscelini, Colpurini, Daladerini and Hyselonotini are heterogeneous, each exhibiting two subtypes of spermatheca, and probably polyphyletic. Two tribes, Cloresmini and Colpurini, requiring further investigation remain unplaced. This study demonstrates the great importance of characters of the spermatheca, in particular its intermediate part, for research into the phylogeny and taxonomy of Pentatomomorpha.

Download Full-text

Immunological Determined Plasminogen Groups And Its Possible Biological Relevance

10.1055/s-0038-1652204 ◽

1981 ◽

Author(s):

V Sachs ◽

R Dörner ◽

E Szirmai

Keyword(s):

Human Plasma ◽

Type I ◽

Type Ii ◽

Precipitation Line ◽

Gene Frequencies ◽

Type Iii ◽

Different Types ◽

Human Plasminogen ◽

Gel Diffusion ◽

Good Agreement

Anti human plasminogen sera of the rabbit precipitate human plasma in the agar gel diffusion test by means of intra-basin absorption with plasminogenfree human plasma with three different types: type I is represented by one strong precipitation line, type II by two lines, a big one and a small one, and type III by three slight but distinct lines. The following frequencies of the different types have been observed in a sample of 516 human plasmas: type I 65%, type II 33% and type III 2%. Suppose the types are phenotypical groups of a diallelic system where the types I and III represent the homozygous genotypes and the type II the heterozygous the estimated gene frequencies are in good agreement with the expected values. There is also a good agreement of the distribution of plasminogen groups determined by electrofocussing from RAUM et al. and HOBART. The plasminogen groups possibly may have also a biological meaning because the plasmas of type III always have a lesser fibrinolytic activity than the plasmas of the other types.

Download Full-text

The Natural History of Cerebral Dural Arteriovenous Fistulae

Neurosurgery ◽

10.1227/neu.0b013e31825eabdb ◽

2012 ◽

Vol 71 (3) ◽

pp. 594-603 ◽

Cited By ~ 94

Author(s):

Bradley A. Gross ◽

Rose Du

Keyword(s):

Natural History ◽

Significant Risk ◽

Venous Drainage ◽

Type I ◽

Type Ii ◽

Arteriovenous Fistulae ◽

Type Iii ◽

History Of ◽

Venous Ectasia ◽

Cortical Venous Drainage

Abstract BACKGROUND: Hemorrhage from cerebral dural arteriovenous fistulae (dAVF) is a considerable source of neurological morbidity and even mortality. OBJECTIVE: To evaluate the natural history of cerebral dAVF. METHODS: We reviewed our own cohort of 70 dAVF and incorporated results from the literature, synthesizing pooled hemorrhage rates and evaluating risk factors for 395 dAVF in 6 studies. RESULTS: No hemorrhages occurred during 409 lesion-years of follow-up of Borden type I dAVF; however, cortical venous drainage developed in 1.4%. Like type I dAVF, type II dAVF demonstrated a female predilection and were most commonly transverse-sigmoid or cavernous. Eighteen percent of type II dAVF presented with hemorrhage (95% confidence interval [CI]: 8%-36%), and the annual hemorrhage rate was 6% (95% CI: 0.1%-19%). Borden type III dAVF demonstrated a male predilection and were most commonly tentorial or petrosal. Thirty-four percent presented with hemorrhage (95% CI: 0.4%-49%), with an annual hemorrhage rate of 10% (95% CI: 4%-20%), increasing to 21% for those with venous ectasia (95% CI: 4%-66%). The hemorrhage rate decreased to 2% for asymptomatic or minimally symptomatic type II or III dAVF (95% CI: 0.2%-8%), and increased to 10% for those presenting with nonhemorrhagic neurological deficits (95% CI: 0.9%-41%) and to 46% for those presenting with hemorrhage (95% CI: 11%-130%). CONCLUSION: Venous ectasia is a significant risk factor for hemorrhage among dAVF with cortical venous drainage. In addition, those with hemorrhagic presentation, even compared with nonhemorrhagic neurological deficit presentation, as well as Borden type III dAVF compared with type II dAVF demonstrated a trend toward greater hemorrhage rates.

Download Full-text