Miracle-dz/UniFAR-FTUs huggingface dataset:
Netrin‐1 receptor in the ventral tegmental area is required for sensitization to amphetamine

Fundamental to neural organization during development, the netrin‐1 guidance cue and its receptor, deleted in colorectal cancer (DCC), continue to be expressed in the adult brain. We have shown recently that adult dcc heterozygous mice do not develop sensitization to the stimulant drug of abuse amphetamine (AMPH) and that repeated exposure to AMPH upregulates DCC expression in adult rats. This upregulation is selective to the ventral tegmental area (VTA), a site critical for the initiation of behavioral plasticity induced by stimulant drugs, and is glutamate‐dependent. Here we demonstrate that the lack of AMPH‐induced sensitization in dcc heterozygotes is associated with a failure of AMPH to upregulate DCC receptor expression in the VTA. Further, we show that, in wild‐type mice, repeated AMPH induces increases in VTA expression of the dendritic spine‐associated protein, spinophilin. Significantly, however, this effect is not observed in dcc heterozygotes. In parallel experiments conducted in adult rats, we show that VTA DCC receptor activation, at the time of AMPH pretreatment, is critical for sensitization to AMPH. Together, these results demonstrate that the DCC netrin‐1 receptor, a protein traditionally known for its role in organizing brain development, plays a critical function in adult brain plasticity, possibly via orchestration of neuronal circuitry reorganization. We propose VTA DCC receptor signaling as a novel mechanism in the series of glutamate‐dependent cellular processes that lead to enduring plasticity by drugs of abuse.
Has Toll-Like Receptor 4 Been Prematurely Dismissed as an Inflammatory Bowel Disease Gene? Association Study Combined With Meta-Analysis Shows Strong Evidence for Association

OBJECTIVES:Published association studies of the TLR4 Asp299Gly polymorphism and inflammatory bowel disease (IBD) in caucasian populations have inconsistent results. We tested two TLR4 variants for association with IBD in the New Zealand caucasian population and assessed the cumulative evidence for association of TLR4 Asp299Gly and IBD.METHODS:The TLR4 Asp299Gly and Thr399Ile polymorphisms were genotyped and tested for case-control frequency differences in a New Zealand white cohort of 389 Crohn's disease (CD) patients, 405 ulcerative colitis (UC) patients, and 416 population controls. Meta-analysis using a random effects model was performed to test whether 299Gly carriage was associated with UC, CD, or phenotypes of CD patients.RESULTS:There were no significant allele or genotype frequency differences between cases and controls or between CD phenotypes in our New Zealand data. Meta-analysis did not identify any significant associations between CD phenotypes and 299Gly carriage. However, meta-analysis demonstrated significantly higher 299Gly carrier frequencies in CD patients (odds ratio 1.45, 95% CI 1.11–1.90) and in IBD patients (odds ratio 1.36, 95% CI 1.01–1.84) compared to controls.CONCLUSIONS:The meta-analysis provides evidence that Asp299Gly is associated with CD and IBD in whites. Only the Asp299Gly polymorphism has been consistently genotyped in previous TLR4 studies with IBD patients, therefore other TLR4 variants with stronger associations with IBD may exist. Additional well-powered studies of Asp299Gly and other TLR4 variants are urgently needed.
A low-power K-band frequency synthesizer using push-push transformer-feedback VCO in 0.18-µm CMOS technology

In this paper, a K-band frequency synthesizer using 0.18-μm CMOS technology is presented. To achieve low-power consumption, a transformer-feedback voltage-controlled oscillator (TF-VCO) with a cascoded current mode logic (CML) frequency divider is proposed. Furthermore, the push-push structure is selected in TF-VCO to overcome the design trade-off between operating frequency and dc power consumption of CML divider. Based on the aforementioned techniques, the measured phase noise of proposed frequency synthesizer is -114 dBc/Hz at 10 MHz offset at 21.5 GHz. The total power consumption is 20.1 mW.
Functional Characterization of the Initiation Enzyme of S-Layer Glycoprotein Glycan Biosynthesis in Geobacillus stearothermophilus NRS 2004/3a

ABSTRACT The glycan chain of the S-layer glycoprotein of Geobacillus stearothermophilus NRS 2004/3a is composed of repeating units [→2)-α-l-Rhap-(1→3)-β-l-Rhap-(1→2)-α-l-Rhap-(1→], with a 2-O-methyl modification of the terminal trisaccharide at the nonreducing end of the glycan chain, a core saccharide composed of two or three α-l-rhamnose residues, and a β-d-galactose residue as a linker to the S-layer protein. In this study, we report the biochemical characterization of WsaP of the S-layer glycosylation gene cluster as a UDP-Gal:phosphoryl-polyprenol Gal-1-phosphate transferase that primes the S-layer glycoprotein glycan biosynthesis of Geobacillus stearothermophilus NRS 2004/3a. Our results demonstrate that the enzyme transfers in vitro a galactose-1-phosphate from UDP-galactose to endogenous phosphoryl-polyprenol and that the C-terminal half of WsaP carries the galactosyltransferase function, as already observed for the UDP-Gal:phosphoryl-polyprenol Gal-1-phosphate transferase WbaP from Salmonella enterica. To confirm the function of the enzyme, we show that WsaP is capable of reconstituting polysaccharide biosynthesis in WbaP-deficient strains of Escherichia coli and Salmonella enterica serovar Typhimurium.
Impact of preoperative radiotherapy on survival in locally advanced rectal cancer: an observational population-based study from the South of Switzerland

Preoperative radiotherapy (RT) followed by surgery is widely accepted in the treatment of locally advanced rectal cancer (LARC). This study aimed to estimate at the population-based level the impact of preoperative RT on overall survival (OS) and cancer-specific survival (CSS) in LARCs diagnosed in Southern Switzerland between 1996 and 2007. All patients with LARC were selected from the Ticino Cancer Registry database. Patients were categorized according to the first administered treatment: preoperative radiotherapy (RT) followed by surgery (RT+) versus surgery (RT−). Clinical–pathological characteristics and 5-year OS and CSS were analysed. Among 384 patients with LARC, 54% underwent preoperative RT, occurring more frequently in the mid-distal part of the rectum compared with the RT− group (74.8 vs. 29.8%, respectively). Both 5-year OS and CSS significantly improved in RT+ patients (OS: 68 vs. 54%, respectively; CSS: 71 vs. 63%, respectively). The adjusted hazard ratio for all death was equal to 0.66 (95% confidence interval: 0.46; 0.97); similarly, the hazard ratio for cancer-specific death was 0.63 (95% confidence interval: 0.39; 0.99). These observational population-based results, after controlling for most important diagnostic and clinical prognostic factors, confirm the benefit of preoperative RT of LARC, even if the magnitude seems greater than expected in clinical trials results. Additional studies are needed, particularly with regard to the possible effect of standardized staging procedure and multidisciplinary discussion on patient outcome.
The Impact of Relationship Dynamics on the Detection and Reporting of Elder Abuse Occurring in Domestic Settings

There is a keen desire to increase the detection and reporting of elder abuse. The purpose of this study was to describe the circumstances under which abuse is detected and reported and to identify the relationship dynamics that might be impacting detection and reporting decisions. Interviews were conducted with 71 Adult Protective Services (APS) caseworkers, 55 of their elderly clients, and 32 third-party adults. Detection and reporting are distinct but related acts. The temporal relationship between detection and reporting generally differed depending on the nature and quality of the relationship between (a) the victim and offender and (b) the victim and reporter. Efforts to increase reporting may benefit from taking into consideration these relationship dynamics. A range of individuals detected and reported elder abuse, including victims, under a range of circumstances, reinforcing the value of public efforts to increase awareness of elder abuse.
Linear- and circular-plasmid copy numbers in Borrelia burgdorferi

Borrelia burgdorferi, the Lyme disease agent, and other members of the spirochetal genus Borrelia have double-stranded linear plasmids in addition to supercoiled circular plasmids. The copy number relative to the chromosome was determined for 49- and 16-kb linear plasmids and a 27-kb circular plasmid of the type strain, B31, of B. burgdorferi. All three plasmids were present in low copy number, about one per chromosome equivalent, as determined by relative hybridizations of replicon-specific DNA probes. The low copy number of Borrelia plasmids suggests that initiation of DNA replication and partitioning are carefully controlled during the cell division cycle. The copy numbers of these three plasmids of strain B31 were unchanged after approximately 7,000 generations in continuous in vitro culture. A clone of B. burgdorferi B31 that did not contain the 16-kb linear plasmid was obtained after exposure of a culture to novobiocin, a DNA gyrase inhibitor. The plasmid-cured strain contains only one linear plasmid, the 49-kb plasmid, and thus has the smallest genome reported to date for B. burgdorferi.
Diagnostic overview of blood‐based dysferlin protein assay for dysferlinopathies

Introduction: Dysferlin deficiency causes dysferlinopathies. Among peripheral blood mononuclear cells (PBMCs), the dysferlin protein is expressed specifically in CD14+ monocytes. Methods: We quantified dysferlin protein levels in PBMC lysates of 77 individuals suspected clinically of having a dysferlinopathy to screen for true positives. Subsequent molecular confirmation was done by Sanger sequencing and comparative genomic hybridization arrays to establish diagnosis. Results: Of the 44 individuals who had significantly reduced dysferlin levels (≤10%), 41 underwent molecular testing. We identified at least 1 mutation in 85% (35 of 41), and 2 mutations, establishing a dysferlinopathy diagnosis, in 61% (25 of 41) of these individuals. Among those with dysferlin protein levels of >10% (33 of 77), only 1 individual (of 14 who underwent molecular testing) had a detectable mutation. Conclusions: Our results suggest that dysferlin protein levels of ≤10% in PBMCs, are highly indicative of primary dysferlinopathies. However, this assay may not distinguish carriers from those with secondary dysferlin reduction. Muscle Nerve 50: 333–339, 2014
Phagosome maturation during endosome interaction revealed by partial rhodopsin processing in retinal pigment epithelium

ABSTRACT Defects in phagocytosis and degradation of photoreceptor outer segments (POS) by the retinal pigment epithelium (RPE) are associated with aging and retinal disease. The daily burst of rod outer segment (ROS) phagocytosis by the RPE provides a unique opportunity to analyse phagosome processing in vivo. In mouse retinae, phagosomes containing stacked rhodopsin-rich discs were identified by immuno-electron microscopy. Early apical phagosomes stained with antibodies against both cytoplasmic and intradiscal domains of rhodopsin. During phagosome maturation, a remarkably synchronised loss of the cytoplasmic epitope coincided with movement to the cell body and preceded phagosome–lysosome fusion and disc degradation. Loss of the intradiscal rhodopsin epitope and disc digestion occurred upon fusion with cathepsin-D-positive lysosomes. The same sequential stages of phagosome maturation were identified in cultured RPE and macrophages challenged with isolated POS. Loss of the cytoplasmic rhodopsin epitope was insensitive to pH but sensitive to protease inhibition and coincided with the interaction of phagosomes with endosomes. Thus, during pre-lysosomal maturation of ROS-containing phagosomes, limited rhodopsin processing occurs upon interaction with endosomes. This potentially provides a sensitive readout of phagosome–endosome interactions that is applicable to multiple phagocytes.
The Hydrangea simulations: galaxy formation in and around massive clusters

We introduce the Hydrangea simulations, a suite of 24 cosmological hydrodynamic zoom-in simulations of massive galaxy clusters (M200c = 1014–1015.4 M⊙) with baryon particle masses of ∼106 M⊙. Designed to study the impact of the cluster environment on galaxy formation, they are a key part of the ‘Cluster–EAGLE’ project. They use a galaxy formation model developed for the EAGLE project, which has been shown to yield both realistic field galaxies and hot gas fractions of galaxy groups consistent with observations. The total stellar mass content of the simulated clusters agrees with observations, but central cluster galaxies are too massive, by up to 0.6 dex. Passive satellite fractions are higher than in the field, and at stellar masses Mstar > 1010 M⊙, this environmental effect is quantitatively consistent with observations. The predicted satellite stellar mass function matches data from local cluster surveys. Normalized to total mass, there are fewer low-mass (Mstar ≲ 1010 M⊙) galaxies within the virial radius of clusters than in the field, primarily due to star formation quenching. Conversely, the simulations predict an overabundance of massive galaxies in clusters compared to the field that persists to their far outskirts (>5 r200c). This is caused by a significantly increased stellar mass fraction of (sub-)haloes in the cluster environment, by up to ∼0.3 dex even well beyond r200c. Haloes near clusters are also more concentrated than equally massive field haloes, but these two effects are largely uncorrelated.
Temporal profile of prolonged, night‐time driving performance: breaks from driving temporarily reduce time‐on‐task fatigue but not sleepiness

Breaks are often used by drivers to counteract sleepiness and time‐on‐task fatigue during prolonged driving. We examined the temporal profile of changes in driving performance, electroencephalogram (EEG) activity and subjective measures of sleepiness and fatigue during prolonged nocturnal driving in a car simulator. In addition, the study examined the impact of regular breaks from driving on performance, sleepiness and fatigue. Healthy volunteers (n = 12, 23–45 years) maintained a regular sleep–wake pattern for 14 days and were then in a laboratory from 21:00 to 08:30 hours. The driving simulator scene was designed to simulate monotonous night‐time rural driving. Participants drove 4 × 2‐h test sessions, with a break from driving of 1 h between each session. During the break participants performed tests assessing sleepiness and fatigue, and psychomotor performance (∼30 mins), and then were permitted to sit quietly. They were monitored for wakefulness, and not permitted to nap or ingest caffeine. EEG was recorded during the driving task, and subjective assessments of sleepiness and fatigue were obtained at the start and completion of each session. We found that driving performance deteriorated (2.5‐fold), EEG delta, theta and alpha activity increased, and subjective sleepiness and fatigue ratings increased across the testing period. Driving performance and fatigue ratings improved following the scheduled breaks from driving, while the breaks did not affect EEG activity and subjective sleepiness. Time‐on‐task effects increased through the testing period, indicating that these effects are exacerbated by increasing sleepiness. Breaks from driving without sleep temporarily ameliorate time‐on‐task fatigue, but provide little benefit to the sleepy driver.
Improved Outcomes in Juvenile Idiopathic Arthritis FollowingAntihistamine Treatment in Patients with Concurrent Allergic Rhinitis

Objective: We aim to assess the influence of antihistamines as an adjunctive therapy in children with JIA who also have co-existing mild to moderate AR. Methods: Fifty-two JIA patients with AR were enrolled and consecutively randomized. The control group comprised 26 patients who were treated with methotrexate (MTX) 10-15 mg/m2/week orally for 12 months and enteric-coated diclofenac sodium 0.5-2 mg/kg/day orally for 12 weeks. The test group comprised 26 patients who received adjunctive therapy with oral and intranasal antihistamines for 12 months, in addition to MTX and diclofenac. The responses were evaluated using American College of Rheumatology (ACR) pediatric (Pedi) 30/50/70 criteria, AR score, 27-joint Juvenile Arthritis Disease Activity Score (JADAS-27), and laboratory variables. Results: At 3 and 6 months follow-up, significantly more patients in the antihistamine treatment group achieved ACR Pedi50 and ACR Pedi70 responses(at 3 months, 73.1% to 19.2%, 38.5% to 7.7%; at 6 months, 96.2% to 53.8%, 76.9% to 19.2%, respectively, all p<0.01). In the antihistamine group the AR score correlated with JADAS-27 at baseline, 3 months and 6 months (r=0.946, r=0.909 and r=0.964, respectively). During 12 months of follow-up, there were significantly fewer JIA flares in the antihistamine group (0.8 ± 0.7 vs. 2.2 ± 1.4, p<0.01). Conclusions: JIA patients with concurrent AR who receive effective antihistamine treatment for their AR may have better outcomes in terms of JIA control.
Association of soluble tumour necrosis factor-related apoptosis-inducing ligand levels with coronary plaque burden and composition

Background Evidence shows that the soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) may play a protective role against atherosclerosis. This study sought to investigate the potential association of sTRAIL levels with intravascular ultrasound (IVUS) and virtual histology characteristics of coronary plaques. Methods Patients with stable angina or positive for ischaemia non-invasive test were submitted to left cardiac catheterisation. Coronary blood samples were collected and sTRAIL was measured. Coronary arteries with at least one 50% or greater stenosis were studied with IVUS. Results 56 coronary arteries were studied with significant coronary artery disease. Plaque volume per unit of arterial length was 63±5 mm3/cm in arteries at the lower quartile of sTRAIL concentration versus 30±4 mm3/cm at the upper quartile (p<0.001; 95% CI of the difference 19.7 to 46.3 mm3/cm). The necrotic core and fibrofatty content of atheromatous plaques were inversely associated with sTRAIL (p<0.001). Thin-cap fibroatheromas (TCFA) were discovered in 16 of the 56 arterial segments. The mean sTRAIL concentration in these segments was 56.8±7.5 pg/ml versus 99.9±5.7 pg/ml in those without TCFA (p<0.001; 95% CI of the difference 22.7 to 63.5 pg/ml). The association of sTRAIL with the presence of TCFA remained significant in the logistic multivariate analysis (p=0.009). Conclusion According to the findings of the present study, in addition to coronary artery disease burden, the sTRAIL concentration is also related to the composition of atheromatous plaques. A significant association is demonstrated between low sTRAIL levels and the presence of TCFA, the IVUS–virtual histology prototype of the vulnerable plaque.
Direct shoot regeneration from leaf and internode explants of Aloysia polystachya [GRIS.] mold. (Verbenaceae)

SummaryAdventitious bud regeneration from leaf and internode explants of Aloysia polystachya was achieved. Shoots from nodal segments grown in vitro were cut into pieces and used as sources of explants. Organogenesis was induced from both explants cultured on quarter-strength Murashige and Skoog (MS) semisolid medium (plus sucrose 5 g l−1) containing different combinations of 6-benzyladenine (BA) and α-naphthaleneacetic acid (NAA) under 116 μmol m−2 s−1 photosynthetic photon flux density (PPFD), 14-h photoperiod, and at a temperature of 27±2°C. The type of explant markedly influenced organogenesis and growth of the regenerated shoots. The regeneration frequencies were higher with leaf explants, while the number of shoots formed per responsive explant was greater with internode explants. However, the growth of regenerated shoots from internodes was seriously affected by vitrification. The number of shoots produced per responsive leaf explant increased from one to seven as the percentage of leaf explants producing shoots increased from 20 to more than 80%. NAA at 0.05 μM in combination with BA at 0. 5μM induced the highest regeneration rate (87±8.8%) after 20 d of culture, yielding 5.9±0.8 shoots per responsive leaf explant. Histological examination confirmed the occurrence of direct organogenesis. The regenerated shoots from the best induction treatment were transferred to a fresh medium without plant growth regulators for 30 d. Finally, the elongated shoots were rooted by pre-treatment in an aqueous solution of NAA at 500 μM for 2 h and transferred to 1/4 MS. All plantlets raised in vitro were phenotypically normal and successfully hardened to ex vitro conditions. An experimental field plot with 2-yr-old in vitro-regenerated plants was established.
Resolution of non‐alcoholic steatohepatitis after growth hormone replacement in a pediatric liver transplant patient with panhypopituitarism

NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency. Refractory NAFLD in panhypopituitarism may be amenable to GH replacement. Here, we report a pediatric case of NASH secondary to panhypopituitarism from craniopharyngioma, which recurred by 11 months after LDLT. Despite low‐dose GH replacement, the patient remained GH deficient. Pubertal dosed GH therapy led to rapid and complete resolution of hepatic steatosis, which we tracked using serial 1H MRS. Pediatric patients with NASH cirrhosis secondary to panhypopituitarism can be good candidates for liver transplantation, but hormone deficiencies predispose to recurrence after transplant. High‐dose GH replacement should be considered in pediatric patients with GH deficiency and recurrent disease. A multidisciplinary team approach is essential for successful outcomes.
Magnetic resonance imaging abnormalities of peripheral nerve and muscle are common in amyotrophic lateral sclerosis and share features with multifocal motor neuropathy

Introduction: Magnetic resonance imaging (MRI) of peripheral nerve and muscle in patients with amyotrophic lateral sclerosis (ALS) may be performed to investigate alternative diagnoses, including multifocal motor neuropathy (MMN). MRI findings of peripheral nerve and muscle are not well described in these conditions, making interpretation of results difficult. Methods: We examined systematically the peripheral nerve and muscle MRI findings in patients with ALS (n = 60) and MMN (n = 8). Results: In patients with ALS and MMN, abnormal MRIs were common (85% and 75%, respectively), but did not correlate with disease severity. Peripheral nerve MRI abnormalities were similar in frequency (ALS 58%, MMN 63%), with most changes being of mild to moderate severity. Muscle MRI changes were more common in ALS (57% vs. 33%), and no muscle atrophy was seen in patients with MMN. Conclusion: MRI abnormalities of peripheral nerve and muscle in ALS and MMN are common and share some features. Muscle Nerve 52: 137–139, 2015