bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Exploits a Dynamic Multi-aminoacyl-tRNA Synthetase Complex To Enhance Viral Replication
Authors: Duchon Alice A. , St. Gelais Corine , Titkemeier Nathan , Hatterschide Joshua , Wu Li , Musier-Forsyth Karin 
Published: August 2017

ABSTRACT

A hallmark of retroviruses such as human immunodeficiency virus type 1 (HIV-1) is reverse transcription of genomic RNA to DNA, a process that is primed by cellular tRNAs. HIV-1 recruits human tRNA
Lys3
to serve as the reverse transcription primer via an interaction between lysyl-tRNA synthetase (LysRS) and the HIV-1 Gag polyprotein. LysRS is normally sequestered in a multi-aminoacyl-tRNA synthetase complex (MSC). Previous studies demonstrated that components of the MSC can be mobilized in response to certain cellular stimuli, but how LysRS is redirected from the MSC to viral particles for packaging is unknown. Here, we show that upon HIV-1 infection, a free pool of non-MSC-associated LysRS is observed and partially relocalized to the nucleus. Heat inactivation of HIV-1 blocks nuclear localization of LysRS, but treatment with a reverse transcriptase inhibitor does not, suggesting that the trigger for relocalization occurs prior to reverse transcription. A reduction in HIV-1 infection is observed upon treatment with an inhibitor to mitogen-activated protein kinase that prevents phosphorylation of LysRS on Ser207, release of LysRS from the MSC, and nuclear localization. A phosphomimetic mutant of LysRS (S207D) that lacked the capability to aminoacylate tRNA
Lys3
localized to the nucleus, rescued HIV-1 infectivity, and was packaged into virions. In contrast, a phosphoablative mutant (S207A) remained cytosolic and maintained full aminoacylation activity but failed to rescue infectivity and was not packaged. These findings suggest that HIV-1 takes advantage of the dynamic nature of the MSC to redirect and coopt cellular translation factors to enhance viral replication.

IMPORTANCE
Human tRNA
Lys3
, the primer for reverse transcription, and LysRS are essential host factors packaged into HIV-1 virions. Previous studies found that tRNA
Lys3
packaging depends on interactions between LysRS and HIV-1 Gag; however, many details regarding the mechanism of tRNA
Lys3
and LysRS packaging remain unknown. LysRS is normally sequestered in a high-molecular-weight multi-aminoacyl-tRNA synthetase complex (MSC), restricting the pool of free LysRS-tRNA
Lys
. Mounting evidence suggests that LysRS is released under a variety of stimuli to perform alternative functions within the cell. Here, we show that HIV-1 infection results in a free pool of LysRS that is relocalized to the nucleus of target cells. Blocking this pathway in HIV-1-producing cells resulted in less infectious progeny virions. Understanding the mechanism by which LysRS is recruited into the viral assembly pathway can be exploited for the development of specific and effective therapeutics targeting this nontranslational function.
Correlation between baseline retinal microstructures in spectral-domain optic coherence tomography and need for early intervention in central serous chorioretinopathy
Authors: Lai Wei-Yu , Tseng Cheui-Lien , Wu Tsung-Tien , Lin Huey-Shyan , Sheu Shwu-Jiuan 
Published: August 2017

PurposeTo investigate the association between baseline retinal microstructures observed with spectral-domain optical coherence tomography (OCT) and the need for early intervention in central serous chorioretinopathy (CSC).MethodsCases of acute CSC from July 2011 to December 2014 were retrospectively reviewed. OCT images were further classified using six parameters: foveal serous retinal detachment; pigment epithelial detachment; fibrinous exudates in the subretinal space; retinal pigment epithelium bumps; thickened outer retinal layer and hyper-reflective dots in the intraretinal and/or subretinal layer. Correlation among these parameters and the need for intervention was analysed. Receiver operating characteristic (ROC) curves were performed to identify the optimal number of parameters for prediction.ResultsA total of 47 eyes from 47 patients were included. Among these, 25 eyes required treatment. The presence of subretinal hyper-reflective dots was the only OCT factor having significant association with the need for intervention. An ROC curve analysis revealed that the optimal cut-off value (Youden index) was achieved when combining subretinal hyper-reflective dots with aged ≥50 years and female sex for analysis (area under the curve, 0.735; Youden index: 0.425).ConclusionThe presence of subretinal/intraretinal hyper-reflective dots observed with OCT, female and aged ≥50 years might help predict the need for early intervention in acute CSC.
Device-assisted enteroscopy in the UK: description of a large tertiary case series under conscious sedation
Authors: Pattni Vijay , Tate David J , Terlevich Ana , Marden Peter , Hughes Steve 
Published: August 2017

ObjectiveDevice-assisted enteroscopy (DAE) has developed rapidly, particularly with the advent of double-balloon enteroscopy (DBE). This study reports a case series from a UK tertiary centre for DAE across two modalities—DBE and spiral enteroscopy (SE)—under conscious sedation.DesignRetrospective observational study of 257 enteroscopy procedures from 2008 to 2014. Data were collected on demographics, indications, diagnosis, sedation requirements, duration, complications, tolerance, therapy performed and completion rate. Procedures were performed under conscious sedation using a combination of midazolam, pethidine and fentanyl in a solely outpatient setting.ResultsObscure gastrointestinal bleeding (OGIB) was the commonest indication for DAE (n=164, 63.8%). Overall, yield of DAE was 47.2% and varied significantly across the indications (p=0.003). There was a greater likelihood of positive findings if the indication was polyposis syndrome (75%), abnormal capsule endoscopy (67%) or OGIB (53%) and in older patients (mean age normal exam 60.3 vs abnormal exam 67.9 years, p<0.001). Higher mean doses of midazolam were used for DBE from above (5.4 mg, SD 2.24) and SE (5.6 mg, SD 2.9) to DBE from below (4.4 mg, SD 1.8). No serious complications were recorded. Tolerance of DAE was good with the majority (240/257, 93.4%) of procedures tolerated with comfort scores 0 or 1. Therapy was performed in 121/257 (47.1%) of procedures. The strongest predictor indications for therapy to be performed at DAE were abnormal capsule endoscopy (88.9%) and occult gastrointestinal (GI) bleeding (54.9%). Completion rates were higher in DBEb (91.8%) compared to DBEa (76.5%) and SE (81.6%).ConclusionDAE under conscious sedation is safe and well tolerated. DAE has a high yield if performed for recognised indications and may be safely used to provide therapy where a diagnosis has been made using other modalities.
Serum ghrelin is associated with risk of colorectal adenocarcinomas in the ATBC study
Authors: Murphy Gwen , Cross Amanda J , Dawsey Sanford M , Stanczyk Frank Z , Kamangar Farin , Weinstein Stephanie J , Taylor Philip R , Männistö Satu , Albanes Demetrius , Abnet Christian C , Freedman Neal D 
Published: August 2017

BackgroundColorectal cancers are the third most common cancers in women and men in the USA. While dietary and lifestyle factors such as Western diet, physical inactivity and obesity have been linked to an increased risk of this malignancy, the mechanisms for these associations are unclear. GI hormones, including ghrelin, are involved in energy balance by mediating appetite and metabolism; however, the association between ghrelin and colorectal cancer has not been studied.MethodsWe conducted a case–control study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish smokers (aged 50–69 years) to examine serum ghrelin concentration and colorectal cancer risk. Data from 284 colon and 239 rectal cancers and 523 controls (matched on age, date of blood draw and serum availability) were analysed. ORs and 95% CIs were calculated using multivariable (conditional) logistic regression.ResultsOverall, low-serum ghrelin was significantly associated with increased risk of colorectal cancer (Q1 vs Q4: OR:1.57, 95% CI 1.05 to 2.34). For individuals developing tumours within 10 years of blood draw, those in the lowest quartile of serum ghrelin concentrations were statistically significantly more likely to develop colorectal cancers than those with higher serum ghrelin concentrations (OR: 10.86, 95% CI 5.01 to 23.55). However, for individuals with tumours developing more than 20 years after blood draw, low-serum ghrelin concentrations were associated with a decreased risk of colorectal cancer relative to those with the highest serum ghrelin concentrations (OR: 0.26, 95% CI 0.11 to 0.64).ConclusionLow-serum ghrelin was associated with an increased colorectal cancer risk within 10 years of blood draw with a decreased risk for developing colorectal cancer more than 20 years after blood draw. These results suggest that ghrelin concentrations may vary across the carcinogenic process.
Association of cardiovascular disease risk factors with coronary artery calcium volume versus density
Authors: Thomas Isac C , Shiau Brandon , Denenberg Julie O , McClelland Robyn L , Greenland Philip , de Boer Ian H , Kestenbaum Bryan R , Lin Gen-Min , Daniels Michael , Forbang Nketi I , Rifkin Dena E , Hughes-Austin Jan , Allison Matthew A , Jeffrey Carr J , Ix Joachim H , Criqui Michael H 
Published: August 2017

ObjectivesRecently, the density score of coronary artery calcium (CAC) has been shown to be associated with a lower risk of cardiovascular disease (CVD) events at any level of CAC volume. Whether risk factors for CAC volume and CAC density are similar or distinct is unknown. We sought to evaluate the associations of CVD risk factors with CAC volume and CAC density scores.MethodsBaseline measurements from 6814 participants free of clinical CVD were collected for the Multi-Ethnic Study of Atherosclerosis. Participants with detectable CAC (n=3398) were evaluated for this study. Multivariable linear regression models were used to evaluate independent associations of CVD risk factors with CAC volume and CAC density scores.ResultsWhereas most CVD risk factors were associated with higher CAC volume scores, many risk factors were associated with lower CAC density scores. For example, diabetes was associated with a higher natural logarithm (ln) transformed CAC volume score (standardised β=0.44 (95% CI 0.31 to 0.58) ln-units) but a lower CAC density score (β=−0.07 (−0.12 to −0.02) density units). Chinese, African-American and Hispanic race/ethnicity were each associated with lower ln CAC volume scores (β=−0.62 (−0.83to −0.41), −0.52 (−0.64 to −0.39) and −0.40 (−0.55 to −0.26) ln-units, respectively) and higher CAC density scores (β= 0.41 (0.34 to 0.47), 0.18 (0.12 to 0.23) and 0.21 (0.15 to 0.26) density units, respectively) relative to non-Hispanic White.ConclusionsIn a cohort free of clinical CVD, CVD risk factors are differentially associated with CAC volume and density scores, with many CVD risk factors inversely associated with the CAC density score after controlling for the CAC volume score. These findings suggest complex associations between CVD risk factors and these components of CAC.
Ultrasound-detected osteophytes predict the development of radiographic and clinical features of hand osteoarthritis in the same finger joints 5 years later
Authors: Mathiessen Alexander , Slatkowsky-Christensen Barbara , Kvien Tore K , Haugen Ida K , Berner Hammer Hilde 
Published: August 2017

BackgroundStructural pathology may be present in joints without radiographic evidence of osteoarthritis (OA). Ultrasound is a sensitive tool for early detection of osteophytes. Our aim was to explore whether ultrasound-detected osteophytes (in radiographically and clinically normal finger joints) predicted the development of radiographic and clinical hand OA 5 years later.MethodsWe included finger joints without radiographic OA (Kellgren-Lawrence grade (KLG)=0; n=301) or no clinical bony enlargements (n=717) at baseline and examined whether ultrasound-detected osteophytes predicted incident radiographic OA (KLG ≥1, osteophytes or joint space narrowing (JSN)) or incident clinical bony enlargement (dependent variables) in the same joints 5 years later. We applied logistic regression with generalised estimating equations adjusted for age, sex, body mass index and follow-up time.ResultsUltrasound demonstrated osteophytes in 86/301 (28.6%) joints without radiographic OA and 392/717 (54.7%) joints without clinical bony enlargement. These osteophytes were confirmed in the majority of joints where MRI assessment was available. Significant associations were found between ultrasound-detected osteophytes and development of both radiographic OA (OR=4.1, 95% CI 2.0 to 8.1) and clinical bony enlargement (OR=3.5, 95% CI 2.4 to 5.1) and also incident radiographic osteophytes (OR=4.2, 95% CI 2.1 to 8.5) and JSN (OR=5.3, 95% CI 2.1 to 13.4).ConclusionUltrasound-detected osteophytes predicted incident radiographic and clinical hand OA 5 years later. These results support the use of ultrasound for early detection of OA.
Regional volcanism of northern Zealandia: post-Gondwana break-up magmatism on an extended, submerged continent
Authors: Mortimer N. , Gans P. B. , Meffre S. , Martin C. E. , Seton M. , Williams S. , Turnbull R. E. , Quilty P. G. , Micklethwaite S. , Timm C. , Sutherland R. , Bache F. , Collot J. , Maurizot P. , Rouillard P. , Rollet N. 
Published: August 2017

Abstract

Volcanism of Late Cretaceous–Miocene age is more widespread across the Zealandia continent than previously recognized. New age and geochemical information from widely spaced northern Zealandia seafloor samples can be related to three volcanotectonic regimes: (1) age-progressive, hotspot-style, low-K, alkali-basalt-dominated volcanism in the Lord Howe Seamount Chain. The northern end of the chain (
c.
28 Ma) is spatially and temporally linked to the 40–28 Ma South Rennell Trough spreading centre. (2) Subalkaline, intermediate to silicic, medium-K to shoshonitic lavas of >78–42 Ma age within and near to the New Caledonia Basin. These lavas indicate that the basin and the adjacent Fairway Ridge are underlain by continental rather than oceanic crust, and are a record of Late Cretaceous–Eocene intracontinental rifting or, in some cases, speculatively subduction. (3) Spatially scattered, non-hotspot, alkali basalts of 30–18 Ma age from Loyalty Ridge, Lord Howe Rise, Aotea Basin and Reinga Basin. These lavas are part of a more extensive suite of Zealandia-wide, 97–0 Ma intraplate volcanics. Ages of northern Zealandia alkali basalts confirm that a late Cenozoic pulse of intraplate volcanism erupted across both northern and southern Zealandia. Collectively, the three groups of volcanic rocks emphasize the important role of magmatism in the geology of northern Zealandia, both during and after Gondwana break-up. There is no compelling evidence in our dataset for Late Cretaceous–Paleocene subduction beneath northern Zealandia.
Blood pressure and leg deoxygenation are exaggerated during treadmill walking in patients with peripheral artery disease
Authors: Miller Amanda J. , Luck J. Carter , Kim Danielle Jin-Kwang , Leuenberger Urs A. , Proctor David N. , Sinoway Lawrence I. , Muller Matthew D. 
Published: August 2017

The purpose of this study was to investigate blood pressure (BP) and leg skeletal muscle oxygen saturation (Smo2) during treadmill walking in patients with peripheral artery disease (PAD) and healthy subjects. Eight PAD patients (66 ± 8 yr, 1 woman) and eight healthy subjects (65 ± 7 yr, 1 woman) walked on a treadmill at 2 mph (0.89 m/s). The incline increased by 2% every 2 min, from 0 to 15% or until maximal discomfort. BP was measured every 2 min with an auscultatory cuff. Heart rate (HR) was recorded continuously with an ECG. Smo2 in the gastrocnemius muscle was measured on each leg using near-infrared spectroscopy. The change in systolic BP from seated to peak walking time (PWT) was greater in PAD (healthy: 23 ± 9 vs. PAD: 44 ± 19 mmHg, P = 0.007). HR was greater in PAD patients compared with controls at PWT ( P = 0.011). The reduction in Smo2 (PWT − seated) was greater in PAD (healthy: 15 ± 12 vs. PAD: 49 ± 5%, P < 0.001) in the most affected leg and in the least affected leg (healthy: 12 ± 11 vs. PAD: 32 ± 18%, P = 0.003). PAD patients have an exaggerated decline in leg Smo2 during walking compared with healthy subjects, which may elicit the exaggerated rise in BP and HR during walking in PAD. NEW & NOTEWORTHY This is the first study to simultaneously measure skeletal muscle oxygen saturation and blood pressure (BP) during treadmill exercise in patients with peripheral arterial disease. We found that BP and leg deoxygenation responses to slow-paced, graded treadmill walking are greater in patients with peripheral arterial disease compared with healthy subjects. These data may help explain the high cardiovascular risk in patients with peripheral arterial disease.
Increased tissue oxygenation explains the attenuation of hyperemia upon repetitive pneumatic compression of the lower leg
Authors: Messere Alessandro , Ceravolo Gianluca , Franco Walter , Maffiodo Daniela , Ferraresi Carlo , Roatta Silvestro 
Published: August 2017

The rapid hyperemia evoked by muscle compression is short lived and was recently shown to undergo a rapid decrease even in spite of continuing mechanical stimulation. The present study aims at investigating the mechanisms underlying this attenuation, which include local metabolic mechanisms, desensitization of mechanosensitive pathways, and reduced efficacy of the muscle pump. In 10 healthy subjects, short sequences of mechanical compressions ( n = 3–6; 150 mmHg) of the lower leg were delivered at different interstimulus intervals (ranging from 20 to 160 s) through a customized pneumatic device. Hemodynamic monitoring included near-infrared spectroscopy, detecting tissue oxygenation and blood volume in calf muscles, and simultaneous echo-Doppler measurement of arterial (superficial femoral artery) and venous (femoral vein) blood flow. The results indicate that 1) a long-lasting (>100 s) increase in local tissue oxygenation follows compression-induced hyperemia, 2) compression-induced hyperemia exhibits different patterns of attenuation depending on the interstimulus interval, 3) the amplitude of the hyperemia is not correlated with the amount of blood volume displaced by the compression, and 4) the extent of attenuation negatively correlates with tissue oxygenation ( r = −0,78, P < 0.05). Increased tissue oxygenation appears to be the key factor for the attenuation of hyperemia upon repetitive compressive stimulation. Tissue oxygenation monitoring is suggested as a useful integration in medical treatments aimed at improving local circulation by repetitive tissue compression. NEW & NOTEWORTHY This study shows that 1) the hyperemia induced by muscle compression produces a long-lasting increase in tissue oxygenation, 2) the hyperemia produced by subsequent muscle compressions exhibits different patterns of attenuation at different interstimulus intervals, and 3) the extent of attenuation of the compression-induced hyperemia is proportional to the level of oxygenation achieved in the tissue. The results support the concept that tissue oxygenation is a key variable in blood flow regulation.
Muscle proprioceptors in adult rat: mechanosensory signaling and synapse distribution in spinal cord
Authors: Vincent Jacob A. , Gabriel Hanna M. , Deardorff Adam S. , Nardelli Paul , Fyffe Robert E. W. , Burkholder Thomas , Cope Timothy C. 
Published: August 2017

The characteristic signaling and intraspinal projections of muscle proprioceptors best described in the cat are often generalized across mammalian species. However, species-dependent adaptations within this system seem necessary to accommodate asymmetric scaling of length, velocity, and force information required by the physics of movement. In the present study we report mechanosensory responses and intraspinal destinations of three classes of muscle proprioceptors. Proprioceptors from triceps surae muscles in adult female Wistar rats anesthetized with isoflurane were physiologically classified as muscle spindle group Ia or II or as tendon organ group Ib afferents, studied for their firing responses to passive-muscle stretch, and in some cases labeled and imaged for axon projections and varicosities in spinal segments. Afferent projections and the laminar distributions of provisional synapses in rats closely resembled those found in the cat. Afferent signaling of muscle kinematics was also similar to reports in the cat, but rat Ib afferents fired robustly during passive-muscle stretch and Ia afferents displayed an exaggerated dynamic response, even after locomotor scaling was accounted for. These differences in mechanosensory signaling by muscle proprioceptors may represent adaptations for movement control in different animal species.NEW & NOTEWORTHY Muscle sensory neurons signal information necessary for controlling limb movements. The information encoded and transmitted by muscle proprioceptors to networks in the spinal cord is known in detail only for the cat, but differences in size and behavior of other species challenge the presumed generalizability. This report presents the first findings detailing specializations in mechanosensory signaling and intraspinal targets for functionally identified subtypes of muscle proprioceptors in the rat.
Sympathetic Signaling Reactivates Quiescent Disseminated Prostate Cancer Cells in the Bone Marrow
Authors: Decker Ann M. , Jung Younghun , Cackowski Frank C. , Yumoto Kenji , Wang Jingchen , Taichman Russel S. 
Published: August 2017

Abstract
Clinical observations have identified an association between psychologic stress and cancer relapse, suggesting that the sympathetic nervous system/norepinephrine (NE) plays a role in reactivation of dormant disseminated tumor cells (DTC) in the bone marrow niche. Here, the mechanism by which NE regulates prostate cancer DTCs in the marrow is explored. NE directly stimulated prostate cancer cell proliferation through β2-adrenergic receptors (ADRB2). NE also altered prostate cancer proliferation in the marrow niche by indirectly downregulating the secretion of the dormancy inducing molecule growth arrest specific-6 (GAS6) expressed by osteoblasts. These observations were confirmed in cocultures of prostate cancer cells expressing the fluorescent ubiquitination-based cell-cycle reporters (FUCCI) and osteoblasts isolated from GAS6-deficient (GAS6−/−) animals. A novel ex vivo model system, using femurs harvested from GAS6+/+ or GAS6−/− mice, was used to confirm these results. As in coculture, when prostate cancer cells were injected into the marrow cavities of GAS6+/+ femurs, NE altered the prostate cancer cell cycle. However, NE had less of an impact on prostate cancer cells in femur explants isolated from GAS6−/− mice. Together, this study demonstrates that NE reactivates prostate cancer cell cycling through both a direct action on prostate cancer cells and indirectly on adjacent niche cells.
Implications: Identification of mechanisms that target DTCs may provide novel therapeutic approaches to prevent or treat cancer metastases more effectively. Mol Cancer Res; 15(12); 1644–55. ©2017 AACR.
Response to Review Panelists
Authors: Paden William E. 
Published: August 2017

Abstract
This article consists of replies to the reviewers. For Ambasciano I show that his concern about the taint of epistemic phenomenologies can be largely deflected by understanding the exact contextualization of the materials he questions, particularly their place in the function, structure and serialized nature of the argument. Responding to Segal I try to clarify the evolutionary role of functionalism, the relation of Durkheim and Eliade as I am using them, and the role of difference in comparativism. Willard’s questions about the relations of my natural history approach to the cultural evolution model provides a good opportunity to point out their complementarity and differences.