Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential distribution of release‐related proteins in the hippocampal CA3 area as revealed by freeze‐fracture replica labeling

Synaptic vesicle release occurs at a specialized membrane domain known as the presynaptic active zone (AZ). Several membrane proteins are involved in the vesicle release processes such as docking, priming, and exocytotic fusion. Cytomatrix at the active zone (CAZ) proteins are structural components of the AZ and are highly concentrated in it. Localization of other release‐related proteins including target soluble N‐ethylmaleimide‐sensitive‐factor attachment protein receptor (t‐SNARE) proteins, however, has not been well demonstrated in the AZ. Here, we used sodium dodecyl sulfate‐digested freeze‐fracture replica labeling (SDS‐FRL) to analyze quantitatively the distribution of CAZ and t‐SNARE proteins in the hippocampal CA3 area. The AZ in replicated membrane was identified by immunolabeling for CAZ proteins (CAZ‐associated structural protein [CAST] and Bassoon). Clusters of immunogold particles for these proteins were found on the P‐face of presynaptic terminals of the mossy fiber and associational/commissural (A/C) fiber. Co‐labeling with CAST revealed distribution of the t‐SNARE proteins syntaxin and synaptosomal‐associated protein of 25 kDa (SNAP‐25) in the AZ as well as in the extrasynaptic membrane surrounding the AZ (SZ). Quantitative analysis demonstrated that the density of immunoparticles for CAST in the AZ was more than 100 times higher than in the SZ, whereas that for syntaxin and SNAP‐25 was not significantly different between the AZ and SZ in both the A/C and mossy fiber terminals. These results support the involvement of the t‐SNARE proteins in exocytotic fusion in the AZ and the role of CAST in specialization of the membrane domain for the AZ. J. Comp. Neurol. 489:195–216, 2005. © 2005 Wiley‐Liss, Inc.
Protoconch enlargement in Western Atlantic turritelline gastropod species following the closure of the Central American Seaway

Abstract The closure of the late Neogene interoceanic seaways between the Western Atlantic (WA) and Tropical Eastern Pacific (TEP)—commonly referred to as the Central American Seaway—significantly decreased nutrient supply in the WA compared to the TEP. In marine invertebrates, an increase in parental investment is expected to be selectively favored in nutrient‐poor marine environments as prolonged feeding in the plankton becomes less reliable. Here, we examine turritelline gastropods, which were abundant and diverse across this region during the Neogene and serve as important paleoenvironmental proxies, and test whether species exhibit decreased planktotrophy in the WA postclosure as compared to preclosure fossils and extant TEP species. We also test for differences in degree of planktotrophy in extant sister species pairs. Degree of planktotrophy was inferred by measuring the size of protoconchs, the species' larval shell that represents egg size. Protoconch size was compared between extant postclosure WA and TEP species and preclosure fossil species. To compare extant sister species, we reconstructed the phylogeny of available WA and TEP species using one nuclear (H3) and three mitochondrial markers (12S, 16S, and COI). Compared to the preclosure fossils, protoconch size increased in WA species but remained the same in the TEP species. In the two extant sister species pairs recovered in the phylogenetic analysis, the WA species are inferred to be nonplanktotrophic while the TEP species are planktotrophic. This suggests that decreased nutrient availability and primary productivity in the WA may have driven this change in developmental mode, and was the primary selective force resulting in postclosure turritelline extinctions.
ASSESSMENT: USE OF EPIDURAL STEROID INJECTIONS TO TREAT RADICULAR LUMBOSACRAL PAIN: REPORT OF THE THERAPEUTICS AND TECHNOLOGY ASSESSMENT SUBCOMMITTEE OF THE AMERICAN ACADEMY OF NEUROLOGY

ASSESSMENT: USE OF EPIDURAL STEROID INJECTIONS TO TREAT RADICULAR LUMBOSACRAL PAIN: REPORT OF THE THERAPEUTICS AND TECHNOLOGY ASSESSMENT SUBCOMMITTEE OF THE AMERICAN ACADEMY OF NEUROLOGY To the Editor: We read the Report of the Therapeutics and Technology Assessment Subcommittee with interest.1 We believe that the report could confuse physicians and patients. The abstract reports that there is insufficient evidence to recommend the use of epidural steroid injections to treat radicular cervical pain (Level U), even though the focus of the review is the use of epidural steroid injections to treat radicular lumbosacral pain and the studies included in the synthesis related solely to this focus. Principles of evidence-synthesis, and specifically evidence-synthesis and evidence-based interventional pain management have been described.2 Recently, Abdi et al. performed a systematic review that separated lumbar epidural steroid injections into caudal (8 randomized trials), interlaminar (11 randomized trials), and transforaminal (6 randomized trials), as these approaches are distinct techniques with variable effectiveness and separate applications.3 In addition, Abdi et al. included other observational studies and an examination of the methodologies and criteria of both AHRQ and Cochrane reviews. They concluded that there was moderate evidence to support the long-term (i.e., 6 weeks) effectiveness of caudal and transforaminal epidural steroid injections and limited evidence to support the effectiveness of lumbar interlaminar epidural steroid injections. Armon et al. only included four studies considered to have met the predetermined inclusion criteria, although previous studies have included larger numbers of randomized trials in systematic evaluations including the Cochrane review4 and European guidelines.5 For these reasons, the report by Armon et al. may negatively affect the successful conduct of interventional pain management.
Size-Resolved Respiratory-Tract Deposition of Fine and Ultrafine Hydrophobic and Hygroscopic Aerosol Particles During Rest and Exercise

Airborne ultrafine particles (diameter <100 nm) are ubiquitous in the environment and have been associated with adverse health effects. The respiratory-tract deposition of these particles is fundamentally influenced by their hygroscopicity: their ability to grow by condensation of water in the humid respiratory system. Ambient particles are typically hygroscopic, to varying degrees. This article investigates the influence of hygroscopicity, exercise level, gender, and intersubject variability on size-dependent deposition of fine and ultrafine particles during spontaneous breathing. Using a novel and well-characterized setup, respiratory-tract deposition in the range 12–320 nm has been measured for 29 healthy adults (20 men, 9 women). Each subject completed four sessions: rest and light exercise on an ergometer bicycle while inhaling both hydrophobic (diethylhexylsebacate) and hygroscopic (NaCl) particles. The deposited fraction (DF) based on dry diameters was two to four times higher for the hydrophobic ultrafine particles than for the hygroscopic. The DF of hygroscopic ultrafine particles could be estimated by calculating their equilibrium size at 99.5% relative humidity. The differences in average DF due to exercise level and gender were essentially less than 0.03. However, the minute ventilation increased fourfold during exercise and was 18–46% higher for the men than for the women. Consequently the deposited dose of particles was fourfold higher during exercise and considerably increased for the male subjects. Some individuals consistently had a high DF in all four sessions. As an example, the results show that an average person exposed to 100-nm hydrophobic particles during exercise will receive a 16 times higher dose than a relaxed person exposed to an equal amount of hygroscopic (NaCl) particles.
Relationship between mitral annulus function and mitral regurgitation severity and left atrial remodelling in patients with primary mitral regurgitation.

AIMS To explore the relationship between the mitral annular (MA) remodelling and dysfunction, mitral regurgitation (MR) severity, left ventricular (LV) and atrial (LA) size and function in patients with organic MR (OMR). METHODS AND RESULTS A total of 52 patients (57 ± 15 years, 31 men) with mild to severe OMR and 52 controls underwent 3D transthoracic echocardiography acquisitions of the mitral valve (MV), LA, and LV. MA geometry and dynamics, LV and LA volumes, LV ejection fraction (LVEF) and emptying fractions (LAEF) were assessed using dedicated software packages. LA and LV myocardial deformations were assessed using 2D speckle-tracking echocardiography. OMR patients presented larger and more spherical MA than controls during the entire systole (P < 0.001). Although the MA non-planarity at early-systole was similar between OMR and controls (157 ± 13° vs. 153 ± 12°, P = NS), the MA became flatter from mid- to end-systole (153 ± 12 vs. 146 ± 10° and 157 ± 12 vs. 147 ± 8°, P < 0.01) in OMR. MA area fractional change was lower in patients with OMR (22 ± 5% vs. 28 ± 5%, P < 0.001), and correlated with the MR orifice and volume (r = -0.52 and r = -0.55). MA fractional area change correlated with LA minimum and maximum volumes (r = 0.77 and r = 0.70), total and active LAEF (r = 0.72 and r = 0.76), and LA negative strain and strain rate (r = 0.52 and r = 0.57), but not with the LVEF or LV global longitudinal strain. In a multivariate regression model using LAEF and LVEF, solely active LAEF correlated with the MA fractional area change (β = 0.51, P = 0.005). CONCLUSION In patients with OMR, MA reduced function correlates with the MR severity and the LA size and function, but not with the LV function.
Malleability of the approximate number system: effects of feedback and training

Prior research demonstrates that animals and humans share an approximate number system (ANS), characterized by ratio dependence and that the precision of this system increases substantially over human development. The goal of the present research was to investigate the malleability of the ANS (as measured by Weber fraction) in adult subjects in response to feedback and to explore the relationship between ANS acuity and acuity on another magnitude comparison task. We tested each of 20 subjects over six 1-h sessions. The main findings were that (a) Weber fractions rapidly decreased when trial-by-trial feedback was introduced in the second session and remained stable over continued training, (b) Weber fractions remained steady when trial-by-trial feedback was removed in session 6, (c)Weber fractions from the number comparison task were positively correlated with Weber fractions from a line length comparison task, (d) improvement in Weber fractions in response to feedback for the number task did not transfer to the line length task, (e) finally, the precision of the ANS was positively correlated with math, but not verbal, standardized aptitude scores. Potential neural correlates of the perceptual information and decision processes are considered, and predictions regarding the neural correlates of ANS malleability are discussed.
A Split Analysis of Plurality:Evidence from Amharic

The typical syntactic location for plural inflection is Num(ber), the head of a Num(ber)P between DP and NP (see e.g., Ritter 1991 among many others). However, there is a growing body of research on the idiosyncratic/‘lexical’ properties of certain plurals cross-linguistically, and idiosyncratic plurality is often analyzed as the realization of a different head, closer to the noun than Num (see e.g., Lecarme 2002, Lowenstamm 2008, Acquaviva 2008, Wiltschko 2008, Alexiadou 2011). Nevertheless, it remains controversial which exact heads besides Num are capable of carrying plural features, and how idiosyncratic plurality interacts with Num-based plurality within the same language. The intricate plural system of Amharic (Ethiosemitic) is a fertile area for investigating these issues. Amharic contains both regular and idiosyncratic plurality, and I propose that the two types each correspond to a different syntactic head: Num for regular plurality and the nominalizing head n for idiosyncratic plurality. Plural morphology is thus ‘split’ between two terminal nodes. I also develop an analysis where n and Num work together to generate the many different types of Amharic plurals. Overall, Amharic provides further evidence for two sources of syntactic plurality, and allows for one of the first in-depth analyses of the relationship between idiosyncratic plurality and regular plurality. The plan for the paper is as follows. I present the plural system of Amharic in Section 2. In Section 3, I develop the split analysis of plurality, introducing and justifying why plurality is split between Num and n. Section 4 contains the mechanics of the split plurality analysis in Amharic, as well as some thoughts on split plurality across languages. Section 5 concludes.
Use of Colchicine in Cortical Area 1 of the Hippocampus Impairs Transmission of Non-Motivational Information by the Pyramidal Cells

Colchicine, a potent neurotoxin derived from plants, has been recently introduced as a degenerative toxin of small pyramidal cells in the cortical area 1 of the hippocampus (CA1). In this study, the effect of the alkaloid in CA1 on the behaviors in the conditioning task was measured. Injections of colchicine (1,5 µg/rat, intra-CA1) was performed in the male Wistar rats, while the animals were settled and cannulated in a stereotaxic apparatus. In the control group solely injection of saline (1 µl/rat, intra-CA1) was used. One week later, all the animals passed the saline conditioning task using a three-day schedule of an unbiased paradigm. They were administered saline (1 ml/kg, s.c.) twice a day throughout the conditioning phase. To evaluate the possible effects of cell injury by the toxin on the pyramidal cells, both the motivational signals while in the conditioning box and the non-motivational locomotive signs of the treated and control rats were measured. Based on the present study the alkaloid caused no change in the score of place conditioning, but affected both the sniffing and grooming behaviors in the group that received colchicine. However, the alkaloid did not show the significant effect on the rearing or compartment entering in the rats. According to the findings, the intra-CA1 injection of colchicine may impair the neuronal transmission of non-motivational information by the pyramidal cells in the dorsal hippocampus.
Very early neurologic improvement after intravenous thrombolysis.

OBJECTIVE To evaluate whether very early neurologic improvement (VENI) after intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) perfusion in patients with acute ischemic stroke (AIS) predicts favorable outcome at 3 months. DESIGN Retrospective analysis of prospective data. SETTING Stroke registry at the Stroke Unit, Tenon University Hospital. PATIENTS We analyzed consecutive patients with AIS treated with i.v. rt-PA between November 11, 2002, and December 24, 2007. MAIN OUTCOME MEASURES VENI at 1 hour was defined as a National Institute of Health Stroke Scale score of 0 at the end of rt-PA perfusion or an improvement of 5 or more points compared with baseline. Favorable outcome was defined as a modified Rankin Scale score of 1 or less at 3 months. RESULTS Of 120 patients with AIS treated with i.v. rt-PA, 22 (18.3%) had VENI after i.v. rt-PA perfusion. Favorable outcome was observed in 15 patients with VENI (68.2%) and in 29 patients without VENI (29.6%) (P < .001). No symptomatic intracerebral hemorrhage occurred in patients with VENI. Mortality rates were 0% in the patients with VENI and 17.3% in patients without VENI. Baseline scores for VENI (adjusted odds ratio, 6.23; 95% confidence interval, 2.03-19.13; P = .001) and the National Institute of Health Stroke Scale (0.83; 0.76-0.91; P < .001) were the only 2 factors associated with favorable outcome (modified Rankin Scale score of ≤1). CONCLUSIONS VENI at the end of i.v. rt-PA perfusion in patients with AIS independently predicts favorable outcome at 3 months.
A Link between ORC-Origin Binding Mechanisms and Origin Activation Time Revealed in Budding Yeast

Eukaryotic DNA replication origins are selected in G1-phase when the origin recognition complex (ORC) binds chromosomal positions and triggers molecular events culminating in the initiation of DNA replication (a.k.a. origin firing) during S-phase. Each chromosome uses multiple origins for its duplication, and each origin fires at a characteristic time during S-phase, creating a cell-type specific genome replication pattern relevant to differentiation and genome stability. It is unclear whether ORC-origin interactions are relevant to origin activation time. We applied a novel genome-wide strategy to classify origins in the model eukaryote Saccharomyces cerevisiae based on the types of molecular interactions used for ORC-origin binding. Specifically, origins were classified as DNA-dependent when the strength of ORC-origin binding in vivo could be explained by the affinity of ORC for origin DNA in vitro, and, conversely, as ‘chromatin-dependent’ when the ORC-DNA interaction in vitro was insufficient to explain the strength of ORC-origin binding in vivo. These two origin classes differed in terms of nucleosome architecture and dependence on origin-flanking sequences in plasmid replication assays, consistent with local features of chromatin promoting ORC binding at ‘chromatin-dependent’ origins. Finally, the ‘chromatin-dependent’ class was enriched for origins that fire early in S-phase, while the DNA-dependent class was enriched for later firing origins. Conversely, the latest firing origins showed a positive association with the ORC-origin DNA paradigm for normal levels of ORC binding, whereas the earliest firing origins did not. These data reveal a novel association between ORC-origin binding mechanisms and the regulation of origin activation time.
A parallel plate slot-pair array dual polarization antenna for small satellite SAR

A parallel plate slot-pair array antenna panel with dual circular polarization for application in space-based Synthetic Aperture Radar has been designed and fabricated. Multi-objective genetic algorithm is used to find an optimal set of slot-pair linear array power coupling coefficients. HFSS software is used to simulate the structure. The fabricated antenna panel shows aperture efficiency of 50.1% and 49.2% at 9.65 GHz for RHCP and LHCP beams respectively. Frequency dependency of the gain, and beam-shift between RHCP, LHCP beams are studied.
Gulonolactone Addition to Human Hepatocellular Carcinoma Cells with Gene Transfer of Gulonolactone Oxidase Restores Ascorbate Biosynthesis and Reduces Hypoxia Inducible Factor 1

Humans are unable to synthesise ascorbate (Vitamin C) due to the lack of a functional gulonolactone oxidase (Gulo), the enzyme that catalyses the final step in the biosynthesis pathway. Ascorbate is a vital micronutrient required for many biological functions, including as a cofactor for metalloenzymes that regulate the transcription factor hypoxia-inducible factor-1 (HIF-1), which governs cell survival under hypoxia. In most animals, ascorbate is made in liver cells. This study aimed to restore ascorbate synthesis to human hepatocellular carcinoma HepG2 cells and determine the effect of internally produced ascorbate on HIF-1 activation. HepG2 cells were gene-modified with a plasmid encoding the mouse Gulo cDNA, tested for genomic incorporation by PCR and ascorbate synthesis by high performance liquid chromatography. Levels of HIF-1 protein were measured using Western blotting. Gulo-modified HepG2 cells showed increased adherence compared to control HepG2 cells. A PCR-positive clone synthesised ascorbate when the Gulo substrate, l-gulono-1,4-lactone, was supplied. Intracellular ascorbate concentrations reached 5% of saturation levels (6 nmol/106 cells). Addition of ascorbate or gulonolactone reduced HIF-1 accumulation in the Gulo clone, but also in parental HepG2 cells. Our data confirm the requirement for a number of factors in addition to Gulo in the ascorbate biosynthesis pathway in human cells.
Development and multi‐institutional validation of an upgrading risk tool for Gleason 6 prostate cancer

Many patients with low‐risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer‐specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low‐risk PC.
Target Behavior and Financing: How Conclusive is the Evidence?

The notion that firms have a debt ratio target that is a primary determinant of financing behavior is influential in finance. Yet, how definitive is the evidence? We address this issue by generating samples where financing is unrelated to a firm's current debt ratio or a target. We find that much of the available evidence in favor of target behavior based on leverage ratio changes can be reproduced for these samples. Taken together, our findings suggest that a number of existing tests of target behavior have no power to reject alternatives.
Hypermethylation-Modulated Downregulation of Claudin-7 Expression Promotes the Progression of Colorectal Carcinoma

Objective: The expression of tight junction-related transmembrane protein claudin-7 (CLDN7) and its regulatory mechanism were investigated in colorectal carcinomas (CRCs). Methods: Methylation-specific polymerase chain reaction and treatment with the demethylating agent 5-aza-2′-deoxycytidine were conducted to analyze the methylation status at the CLDN7 promoter region in the Colo320 CRC cell line. We used a total of 26 stage 0 CRCs with an adenoma component and 90 invasive CRCs (stage I–IV), as well as their corresponding lymph node metastases, in an immunohistochemical study. Results: In Colo320 (CLDN7-negative) cells, hypermethylation at the CLDN7 promoter was detected and treatment with 5-aza-2′-deoxycytidine restored CLDN7 expression. In CRC tissues, decreased CLDN7 expression was detected in 62% of stage 0 CRCs and 80% of stage I–IV CRCs, compared with their adjacent adenoma lesions and nonneoplastic epithelia, which had a close correlation with the incidence of vessel infiltration and clinicopathologic stage. Hypermethylation at the CLDN7 promoter was detected in 20% of CRCs with low CLDN7 expression. However, CLDN7 expression tended to be re-expressed in their corresponding lymph node metastases. Conclusion: These findings suggest that the CLDN7 gene silencing by promoter hypermethylation and the resultant reduction of CLDN7 expression may play an important role in the progression of CRCs.