bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Genetic Susceptibility of Sheep to Scrapie by Protein Misfolding Cyclic Amplification and Comparison with Experimental Scrapie Transmission Studies
Authors: Bucalossi Cecilia , Cosseddu GianMario , D'Agostino Claudia , Di Bari Michele Angelo , Chiappini Barbara , Conte Michela , Rosone Francesca , De Grossi Luigi , Scavia Gaia , Agrimi Umberto , Nonno Romolo , Vaccari Gabriele 
Published: June 2011

ABSTRACT

The susceptibility of sheep to scrapie is influenced mainly by the prion protein polymorphisms A136V, R154H, and Q171R/H. Here we analyzed the ability of protein misfolding cyclic amplification (PMCA) to model the genetic susceptibility of sheep to scrapie. For this purpose, we studied the efficiency of brain homogenates from sheep with different PrP genotypes to support PrP
Sc
amplification by PMCA using an ARQ/ARQ scrapie inoculum. The results were then compared with those obtained
in vivo
using the same sheep breed, genotypes, and scrapie inoculum. Genotypes associated with susceptibility (ARQ/ARQ, ARQ/AHQ, and AHQ/ARH) were able to sustain PrP
Sc
amplification in PMCA reactions, while genotypes associated with resistance to scrapie (ARQ/ARR and ARR/ARR) were unable to support the
in vitro
conversion. The incubation times of the experimental infection were then compared with the
in vitro
amplification factors. Linear regression analysis showed that the efficiency of
in vitro
PrP
Sc
amplification of the different genotypes was indeed inversely proportional to their incubation times. Finally, the rare ARQK
176
/ARQK
176
genotype, for which no
in vivo
data are available, was studied by PMCA. No amplification was obtained, suggesting ARQK
176
/ARQK
176
as an additional genotype associated with resistance, at least to the isolate tested. Our results indicate a direct correlation between the ability of different PrP genotypes to undergo PrP
C
-to-PrP
Sc
conversion by PMCA and their
in vivo
susceptibility and point to PMCA as an alternative to transmission studies and a potential tool to test the susceptibility of numerous sheep PrP genotypes to a variety of prion sources.
Liposomal Nanocontainers as Models for Viral Infection: Monitoring Viral Genomic RNA Transfer through Lipid Membranes
Authors: Bilek Gerhard , Matscheko Nena M. , Pickl-Herk Angela , Weiss Victor U. , Subirats Xavier , Kenndler Ernst , Blaas Dieter 
Published: June 2011

ABSTRACT

After uptake into target cells, many nonenveloped viruses undergo conformational changes in the low-pH environment of the endocytic compartment. This results in exposure of amphipathic viral peptides and/or hydrophobic protein domains that are inserted into and either disrupt or perforate the vesicular membranes. The viral nucleic acids thereby gain access to the cytosol and initiate replication. We here demonstrate the
in vitro
transfer of the single-stranded positive-sense RNA genome of human rhinovirus 2 into liposomes decorated with recombinant very-low-density lipoprotein receptor fragments. Membrane-attached virions were exposed to pH 5.4, mimicking the
in vivo
pH environment of late endosomes. This triggered the release of the RNA whose arrival in the liposomal lumen was detected via
in situ
cDNA synthesis by encapsulated reverse transcriptase. Subsequently, cDNA was PCR amplified. At a low ratio between virions and lipids, RNA transfer was positively correlated with virus concentration. However, membranes became leaky at higher virus concentrations, which resulted in decreased cDNA synthesis. In accordance with earlier
in vivo
data, the RNA passes through the lipid membrane without causing gross damage to vesicles at physiologically relevant virus concentrations.
Role of TRIM5α RING Domain E3 Ubiquitin Ligase Activity in Capsid Disassembly, Reverse Transcription Blockade, and Restriction of Simian Immunodeficiency Virus
Authors: Kim Jonghwa , Tipper Christopher , Sodroski Joseph 
Published: June 2011

ABSTRACTThe mammalian tripartite motif protein, TRIM5α, recognizes retroviral capsids entering the cytoplasm and blocks virus infection. Depending on the particular TRIM5α protein and retrovirus, complete disruption of the TRIM5α RING domain decreases virus-restricting activity to various degrees. TRIM5α exhibits RING domain-dependent E3 ubiquitin ligase activity, but the specific role of this activity in viral restriction is unknown. We created a panel of African green monkey TRIM5α (TRIM5αAGM) mutants, many of which are specifically altered in RING domain E3 ubiquitin ligase function, and characterized the phenotypes of these mutants with respect to restriction of simian and human immunodeficiency viruses (SIVmacand HIV-1, respectively). TRIM5αAGMubiquitin ligase activity was essential for both the accelerated disassembly of SIVmaccapsids and the disruption of reverse transcription. The levels of SIVmacparticulate capsids in the cytosol of target cells expressing the TRIM5α variants strongly correlated with the levels of viral late reverse transcripts. RING-mediated ubiquitylation and B30.2(SPRY) domain-determined capsid binding independently contributed to the potency of SIVmacrestriction by TRIM5αAGM. In contrast, TRIM5α proteins attenuated in RING ubiquitin ligase function still accelerated HIV-1 capsid disassembly, inhibited reverse transcription, and blocked infection. Replacement of the helix-4/5 loop in the SIVmaccapsid with the corresponding region of the HIV-1 capsid diminished the dependence of restriction on TRIM5α RING function. Thus, ubiquitylation mediated by the RING domain of TRIM5αAGMis essential for blocking SIVmacinfection at the stage of capsid uncoating.
Oncogenic IRFs Provide a Survival Advantage for Epstein-Barr Virus- or Human T-Cell Leukemia Virus Type 1-Transformed Cells through Induction of BIC Expression
Authors: Wang Ling , Toomey Ngoc L. , Diaz Luis A. , Walker Gail , Ramos Juan C. , Barber Glen N. , Ning Shunbin 
Published: June 2011

ABSTRACT

miR-155, processed from the B-cell integration cluster (BIC), is one of the few well-studied microRNAs (miRNAs) and is involved in both innate immunity and tumorigenesis. BIC/miR-155 is induced by distinct signaling pathways, but little is known about the underlying mechanisms. We have identified two conserved potential interferon (IFN) regulatory factor (IRF)-binding/interferon-stimulated response element motifs in the
Bic
gene promoter. Two oncogenic IRFs, IRF4 and -7, in addition to some other members of the family, bind to and significantly transactivate the
Bic
promoter. Correspondingly, the endogenous levels of IRF4 and -7 are correlated with that of the BIC transcript in Epstein-Barr virus (EBV)-transformed cells. However, RNA interference studies have shown that depletion of IRF4, rather than of IRF7, dramatically decreases the endogenous level of BIC by up to 70% in EBV- or human T-cell leukemia virus type 1 (HTLV1)-transformed cell lines and results in apoptosis and reduction of proliferation rates that are restored by transient expression of miR-155. Moreover, the endogenous levels of the miR-155 target, SHIP1, are consistently elevated in EBV- and HTLV1-transformed cell lines stably expressing shIRF4. In contrast, transient expression of IRF4 decreases the SHIP1 level in EBV-negative B cells. Furthermore, the level of IRF4 mRNA is significantly correlated with that of BIC in adult T-cell lymphoma/leukemia (ATLL) tumors. These results show that IRF4 plays an important role in the regulation of BIC in the context of EBV and HTLV1 infection. Our findings have identified
Bic
as the first miRNA-encoding gene for IRFs and provide evidence for a novel molecular mechanism underlying the IRF/BIC pathway in viral oncogenesis.
Nuclear Envelope Breakdown Can Substitute for Primary Envelopment-Mediated Nuclear Egress of Herpesviruses
Authors: Klupp Barbara G. , Granzow Harald , Mettenleiter Thomas C. 
Published: June 2011

ABSTRACT
Herpesvirus nucleocapsids assemble in the nucleus but mature to infectious virions in the cytoplasm. To gain access to this cellular compartment, nucleocapsids are translocated to the cytoplasm by primary envelopment at the inner nuclear membrane and subsequent fusion of the primary envelope with the outer nuclear membrane. The conserved viral pUL34 and pUL31 proteins play a crucial role in this process. In their absence, viral replication is strongly impaired but not totally abolished. We used the residual infectivity of a pUL34-deleted mutant of the alphaherpesvirus pseudorabies virus (PrV) for reversion analysis. To this end, PrV-ΔUL34 was serially passaged in rabbit kidney cells until final titers of the mutant virus PrV-ΔUL34Pass were comparable to those of wild-type PrV. PrV-ΔUL34Pass produced infectious progeny independently of the pUL34/pUL31 nuclear egress complex and the pUS3 protein kinase. Ultrastructural analyses demonstrated that this effect was due to virus-induced disintegration of the nuclear envelope, thereby releasing immature and mature capsids into the cytosol for secondary envelopment. Our data indicate that nuclear egress primarily serves to transfer capsids through the intact nuclear envelope. Immature and mature intranuclear capsids are competent for further virion maturation once they reach the cytoplasm. However, nuclear egress exhibits a strong bias for nucleocapsids, thereby also functioning as a quality control checkpoint which is abolished by herpesvirus-induced nuclear envelope breakdown.
Non-cirrhotic portal fibrosis: one disease with many names? An analysis from morphological study of native explant livers with end stage chronic liver disease
Authors: Nayak Nabeen C , Jain Deepali , Saigal Sanjiv , Soin Arvind S 
Published: June 2011

BackgroundA group of non-cirrhotic chronic liver diseases, all with sustained portal hypertension and clinically mistaken as cirrhosis, have been described under various names, apparently because of differences in pathological features. The pathogenesis is uncertain and they were believed to have a good prognosis until it was recently shown, from study of explant livers, that they had progressed to end stage disease, needing liver transplantation.AimsTo describe detailed morphological features of such end stage non-cirrhotic disease and examine whether the diseases bearing various names are different or represent variable morphological expressions of one entity.MethodsMorphological features of 10 native explant livers from patients with pre-transplant diagnosis of end stage cirrhosis but finally categorised as non-cirrhotic portal fibrosis were analysed along with the relevant clinical information.ResultsBesides absence of criteria for cirrhosis, variable grades of obliterative changes in portal vein branches and portal fibrosis were consistently seen in all livers. Fibrous intimal thickening with luminal compromise in some medium and large sized portal veins was randomly distributed but appeared characteristic of this disease, very likely representing organised mural thrombi. Areas of closely placed nodular hyperplastic parenchyma separated by compressed hepatocytes, megasinusoids and peliotic changes were seen only in a proportion of cases.ConclusionNon-cirrhotic portal fibrosis is a justifiable name for this disease that can progress to end stage liver disease. It represents a single entity that has been considered as different diseases and given various names on the basis of the dominant element in its heterogeneous morphological manifestation.
Comparison of the Effects of the Thrombin Inhibitor r-Hirudin in Four Animal Models of Neointima Formation After Arterial Injury
Authors: Gerdes Christoph , Faber-Steinfeld Verona , Yalkinoglu Özkan , Wohlfeil Stefan 
Published: June 2011

Thrombin has been implicated as a contributing factor to restenosis after vessel reopening procedures. We compared the ability of the direct thrombin inhibitor recombinant (r-) hirudin to reduce neointimal growth in different animal models of arterial injury. Carotid arteries of rats, rabbits, and hypercholesterolemic minipigs were injured by withdrawal of an inflated balloon catheter. In addition, we used a double-lesion model in rabbits, which involved balloon angioplasty of a preexisting lesion induced by carotid denudation 4 weeks earlier. r-Hirudin was given in all four animal models as a short-term application (bolus of 1 mg/kg IV immediately before injury, followed by infusion of 1 mg · kg
−1
· h
−1
for 2 hours, and an injection of 6 mg/kg SC). Additionally, we investigated the effects of prolonged treatment (intravenous infusion for 3 and 14 days) in rats. Inhibition of thrombin was monitored by determination of activated partial thromboplastin time, and histomorphometric analysis of the arteries was performed after 2 (rats) or 4 (rabbits and minipigs) weeks. In rabbits, short-term r-hirudin treatment reduced neointimal area by 59% (single-injury model,
P
=.05) and 44% (double-injury model,
P
=.02). In rats and minipigs no inhibition of neointimal growth was observed after short-term r-hirudin application. A 3- or 14-day infusion of r-hirudin in rats, however, resulted in 25% (
P
=.007) and 27% (
P
=.003) reductions in neointimal area, respectively. In conclusion, there is considerable interspecies variation in the time frame of susceptibility for reduction of neointimal growth by inhibition of thrombin after arterial injury. These results demonstrate the importance of testing potential antirestenotic treatments in an array of different animal models.
Coagulation Abnormalities in Subarachnoid Hemorrhage
Authors: ETTINGER M. G. 
Published: June 2011

Coagulation and fibrinolytic studies were performed in 30 subarachnoid hemorrhage patients and 30 age-matched and sex-matched controls.
Systemic abnormalities were detected in the following tests: recalcification time, fibrinogen, partial thromboplastin time, K value of thromboelastogram and euglobulin lysis time.
The data suggest that subarachnoid hemorrhage patients with fibrinogen values over 400 mg% have a low probability of survival.

Test abnormalities probably reflect tissue damage and/or meningeal reaction to the subarachnoid hemorrhage. Similar abnormalities can be noted in patients with cerebral trauma and in some patients with nonhemorrhagic cerebrovascular disease.
1

Our data reveal that subarachnoid hemorrhage patients may exhibit simultaneously evidence suggesting increased coagulability and activation of fibrinolytic mechanisms. Under these circumstances administration of agents to suppress lytic activity might lead to disastrous consequences such as widespread intervascular coagulation (consumption coagulopathy).
Cardiac Disorders Predisposing to Embolic Stroke
Authors: KANE WALTER C. , ARONSON STANLEY M. 
Published: June 2011

Data from 4,558 consecutive complete necropsies in patients 16 years of age or older were analyzed to ascertain the influence of certain variables upon the frequency of embolic encephalomalacia.
Embolic lesions of the central nervous system occurred more commonly in the female, regardless of age, race, diabetic status, nutritional status or heart size, partly because the cardiovascular lesions responsible for embolic dissemination were more common in women. While affecting only a small percentage of patients at any age, cerebral embolism assumes more importance in strokes of young adulthood. Embolic infarcts demonstrate a predilection for cerebral and cerebellar cortical locations via the long circumferential arterial branches and tend to spare the parasagittal perforating branches supplying the brain stem and diencephalic nuclei.
Certain cardiac states predispose to cerebral embolism. Patients with endocarditis show the greatest risk of embolic lesions, although patients with rheumatic valvular disease of the left heart and mural thrombi of the left ventricle produce numerically more cases of embolic encephalomalacia because these conditions occur far more often than the endocardidites.
Experimental Cerebral Infarction. I. Selective Segmental Occlusion of Intracranial Arteries in the Dog
Authors: MOLINARI GAETANO F. 
Published: June 2011

1. Cylinders of silicone rubber can be molded to any desired diameter and cut to length, yielding a highly pigmented, radio-opaque, elastic bolus suitable for intravascular injection and embolization.
2. Emboli of this type can be localized by x-ray in vivo and at post mortem for clinicopathological correlation studies.
3. Segments of specific vessels of known diameter can be selectively occluded with a high degree of predictability.
4. The caliber of the proximal segment of the middle cerebral artery is remarkably constant in dogs. The extracranial arteries, however, vary proportionately to the body weight of the animal.
5. Proximal segmental occlusion of the middle cerebral artery results in occlusion of the origins of the lenticulostriate vessels. This produces a deep ischemic infarction of basal ganglia and internal capsule. The cerebral cortex is spared due to the integrity of meningocerebral anastomotic network.
Reassessment of Anticoagulant Therapy in Various Types of Occlusive Cerebrovascular Disease
Authors: MILLIKAN CLARK H. 
Published: June 2011

Precise use of categorical terms and definitions is mandatory in discussing the use of anticoagulants in treating occlusive cerebrovascular disease. The components of the temporal profile of the disease are described.
Six reports have appeared which describe the results of anticagulant therapy in transient cerebral ischemic attacks. From these six studies it is concluded that anticoagulant therapy significantly decreased the risk of cerebral infarction in patients who had attacks of transient focal cerebral ischemia.
In the few carefully performed investigations of the use of anticoagulant for acute progressing stroke the evidence points to the lack of progression in patients receiving treatment when compared to individuals not getting such drugs.
There continues to be a definite difference of opinion about the results of anticoagulant therapy in completed stroke. If anticoagulant is to be administered on a long-term basis, it must be considered dangerous and every effort made to control the level of anticoagulant action precisely. Hypertension must be effectively controlled.
The Brain in Hereditary Hemorrhagic Telangiectasia
Authors: REAGAN THOMAS J. , BLOOM WILLIAM H. 
Published: June 2011

While neurological symptoms are often mentioned in reports of families with hereditary hemorrhagic telangiectasia (HHT) and are frequently assumed to be due to vascular anomalies of the central nervous system, documentation of such anomalies is surprisingly rare. Two cases of surgically treated symptomatic cerebral vascular malformations in HHT have been published previously. In addition, there are three descriptions of vascular anomalies discovered at autopsy in the brains of neurologically asymptomatic patients with HHT available in the literature. A complete postmortem examination of a patient with a symptomatic cerebral vascular anomaly associated with HHT has not been recorded previously.
The patient reported in this paper presented with seizures and underwent surgical resection of infarcted brain tissue associated with a venous angioma. He died six months later and, at autopsy, was found to have multiple "cryptic" venous angiomas of the brain. Hypoxic damage to brain tissue related to small venous angiomas is one mechanism whereby these lesions may become symptomatic. Hemorrhage may also occur. Neurological symptoms in patients with HHT cannot be assumed to be due to cerebral vascular anomalies, and consideration must be especially given to the complications of pulmonary arteriovenous fistula such as polycythemia, embolism, and abscess.
Computed tomographic evaluation of bleeding sites in primary pontine hemorrhages.
Authors: Komiyama M , Yasui T , Yagura H , Fu Y 
Published: June 2011

With the aim of identifying common bleeding sites and probable parent vessels in "small" primary pontine hemorrhages, we reviewed computerized tomographic scans of 20 patients with hematomas less than 2.5 cm in diameter.
We used scans depicting the upper and lower pons and plotted the centers of the hematomas, assuming them to be a probable source of bleeding. No predilection sites were found on the axial plane.
Both the paramedian and the long and short circumferential arteries were probable sources of hemorrhage in the present series.
Cardioembolic stroke revealed by increased hemostatic markers associated with intracardiac thrombus.
Authors: Yasaka M , Yamaguchi T 
Published: June 2011

The presence of hemocoagulative disorders in acute ischemic stroke has been reported occasionally. However, the cause of the hemostatic derangement has not been fully elucidated.
A 66-year-old woman with a history of hypertension and myocardial infarction developed pure motor hemiparesis. On admission, she was thought to have a lacunar infarction. However, computed tomography of the brain with contrast medium revealed a small infarct in the cortex of the frontal lobe. Conventional angiography showed no stenotic or occlusive lesions. Sensitive hemocoagulative tests revealed hypercoagulative and hyperfibrinolytic states. Ultrafast computed tomography of the heart with contrast enhancement demonstrated a large left ventricular mural thrombus. There were no further abnormal findings suggestive of other systemic diseases that affect blood coagulability. As a result, the patient was diagnosed as having suffered a cardioembolic stroke.
An intracardiac thrombus could be one of the causes of the hemostatic disorders of acute cardioembolic stroke.
Evidence of somatotopic organization of the sensory thalamus based on infarction in the nucleus ventralis posterior.
Authors: Combarros O , Polo J M , Pascual J , Berciano J 
Published: June 2011

This is to describe a restricted sensory syndrome of unique distribution due to thalamic infarct.
We report a case of pure sensory disturbance involving the left intraoral and perioral regions and the tips of the thumb and forefinger of the left hand. Magnetic resonance imaging revealed a small infarct in the contralateral thalamus, presumably affecting the nucleus ventralis posterior.
This patient provides an excellent correlation between clinical findings and thalamic representation of body surface as established during stereotactic procedures.
The anterior choroidal artery does not supply the corona radiata and lateral ventricular wall.
Authors: Mohr J P , Steinke W , Timsit S G , Sacco R L , Tatemichi T K 
Published: June 2011

We sought first to characterize the clinical syndromes of patients found to have angiographic, computed tomographic, or magnetic resonance imaging scan indexes of anterior choroidal artery territory infarction and then to determine the frequency of involvement of the periventricular corona radiata in such patients.
Sixteen patients were selected based on angiographically, or surgically, documented occlusion of the anterior choroidal artery or based on infarcts whose minimal lesions included the anterior choroidal territory as defined by Kolisko and Beevor. We mapped the lesions using the templates of the Matsui and Hirano atlas and entered them into a computer using a program allowing overlapping diagrams of the cases.
The anatomic distributions were fairly uniform, all involving the lower portion of the posterior limb of the internal capsule, the medial pallidum (75% of cases), cerebral peduncle in 44%, thalamus in 37%, and the medial temporal lobe in 38%. None extended outside these areas to include the upper corona radiata. The clinical picture corresponded to the well-established neurological syndrome featuring motor deficits with varying degrees of visual field and sensory impairments. Only two showed hypesthetic ataxic hemiparesis.
Our findings indicate that the syndrome of anterior choroidal artery infarction is fairly uniform; ataxic hemiparesis occurs infrequently; and lesions in the lateral ventricular wall and the corona radiata are not part of the territory supplied by the anterior choroidal artery.