Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-Regulation between a Novel Two-Component Signal Transduction System for Catabolism of Toluene in Pseudomonas mendocina and the TodST System from Pseudomonas putida

ABSTRACT The tmoABCDEF genes encode the toluene-4-monooxygenase from Pseudomonas mendocina KR1. Upstream from the tmoA gene an open reading frame, tmoX, encoding a protein 83% identical to TodX (todX being the initial gene in the todXFC1C2BADEGIH operon from Pseudomonas putida DOT-T1E) was found. The tmoX gene is also the initial gene in the tmoXABCDEF gene cluster. The transcription initiation point from the tmoX promoter was mapped, and the sequence upstream revealed striking identity with the promoter of the tod operon of P. putida. The tod operon is regulated by a two-component signal transduction system encoded by the todST genes. Two novel genes from P. mendocina KR1, tmoST, were rescued by complementation of a P. putida DOT-T1E todST knockout mutant, whose gene products shared about 85% identity with TodS-TodT. We show that transcription from PtmoX and PtodX can be mediated by TmoS-TmoT or TodS-TodT, in the presence of toluene, revealing cross-regulation between these two catabolic pathways.
Somatostatin, Its Receptors and Analogs, in Lung Cancer

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201–995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1–5. Although elevated plasma somatostatin levels may be detected in 14–15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [111In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer.
Obsessive-Compulsive Behavior as a Symptom of Dementia in Progressive Supranuclear Palsy

Aims: To describe obsessive-compulsive symptoms (OCS) as under-recognized behavioral and psychological symptoms of dementia of progressive supranuclear palsy (PSP) and to discuss possible mechanisms based on MRI and SPECT findings. Methods: We studied 74 PSP patients. OCS are defined as persistent and unreasonable, but non-delusional/hallucinatory, ideas and behaviors. Demography, cognition, the widths of middle cerebellar peduncles (MCP) and the inter-caudate distances (ICD), both corrected by the intracranial size (MCP and ICD ratios), and changes on voxel-based SPECT were compared between the subgroups with and without OCS. Finally, the predicative power of various factors to OCS was investigated. Results: We observed OCS in 18 patients (24%). They were obsessed with daily trifles and physical symptoms among other things. OCS was not associated with demography or cognitive levels. OCS-positive patients had significantly smaller MCP and ICD ratios and showed marked uptake decreases in the orbitofrontal cortex, caudate and thalamus. Relative uptake increases in the cerebellum, specifically the tonsils, were milder in OCS-positive than -negative patients. A smaller right MCP, a smaller ICD ratio and lower uptake increases in the right cerebellar were the significant predictors of OCS. Conclusions: OCS are frequent but under-recognized behavioral and psychological symptoms of dementia in PSP. Dysfunction of the fronto-caudate-thalamus-cerebellum circuit may be involved.
The Subcellular Localization of Plant Protein Phosphatase 5 Isoforms Is Determined by Alternative Splicing[w]

Protein serine/threonine phosphatase 5 (PP5) plays an important role in signal transduction in animal cells, but in plants, knowledge about PP5 is scarce. Here, we describe the isolation of a full-length cDNA encoding tomato (Lycopersicon esculentum) PP5 (LePP5) and its expression in Escherichia coli. Biochemical characterization showed that recombinant LePP5 has a low intrinsic protein phosphatase activity. This activity was increased 6- to 10-fold by either removal of the N-terminal tetratricopeptide repeat domain or by addition of fatty acids, indicating that biochemical features specific for PP5 homologs from other species are conserved in tomato. The single-copy LePP5 gene was cloned and shown to encode two mRNA species that arise by alternative pre-mRNA splicing. Similarly, Arabidopsis was found to express two PP5 transcripts, suggesting that alternative splicing of PP5 pre-mRNA is not specific for tomato. Alternative splicing results in a larger transcript containing an additional exon encoding two putative transmembrane domains and, hence, in a larger PP5 isoform. Subcellular fractionation studies on tomato protein lysates indicated that the majority of the 55-kD LePP5 isoform is soluble, whereas the 62-kD isoform is an integral membrane protein. Production of yellow fluorescent protein-PP5 chimeras in plant cells indicated that the 55-kD isoform is localized in both the nucleus and the cytoplasm, whereas the 62-kD isoform is targeted to the endoplasmic reticulum, including the nuclear envelope. Our findings show that alternative splicing generates two LePP5 isoforms with a different subcellular localization.
Phosphoinositide 3-Kinase Dependent Regulation of Kv Channels in Dendritic Cells

The phosphoinositide 3 (PI3) kinase plays a pivotal role in the regulation of dendritic cells (DCs), antigen-presenting cells that are able to initiate primary immune responses and to establish immunological memory. PI3 kinase is an endogenous suppressor of interleukin 12 (IL-12) production in DCs that is triggered by Toll-like receptor signaling. Inhibition of IL-12 production limits T helper 1 (Th1) polarization. On the other hand, PI3 kinase is an important regulator of various ion channels. The present study aimed to explore whether ion channels in DCs are regulated by PI3 kinase and whether they are important for DC function. To this end, DCs were isolated from murine bone marrow and ion channel activity was determined by patch clamp. As a result, DCs express voltage-gated K+ channels (Kv), which are blocked by Stichodactyla helianthus toxin (ShK, 2.5 nM). A significant upregulation of Kv currents was observed upon maturation of DCs as induced by stimulation of the cells with lipopolysaccharide (LPS, 0.1 µg/ml, 48 h). A dramatic increase of Kv current amplitude was observed following preincubation of the cells with LY294002 (100 nM), a specific inhibitor of PI3 kinase. PI3 kinase inhibitor wortmannin (100 nM) similarly increased Kv current. LY294002 treatment was further followed by a significant increase of IL-12 production. ShK (100 nM) significantly blunted the stimulation of IL-12 release by LPS but not when the cells were first pretreated with LY294002. The observations point to Kv channel sensitive and Kv channel insensitive regulation of DC function.
State-Dependent Memory Effects Using Caffeine and Placebo Do Not Extend to Metamemory

Abstract The authors examined the impact of caffeine on human memory and predictions of memory (i.e., metamemory). On Day 1, 83 college students drank a sweetened beverage containing either caffeine (4 mg/kg body weight) or a placebo before they studied 40 pairs of words. While the participants studied, they predicted their future memory performance for each word pair. On Day 2, the participants again received caffeine or a placebo before the memory test. The participants who drank the same beverage on both days (either caffeine or a placebo) recalled more word pairs than did those who drank different beverages (caffeine on 1 day and a placebo on the other day). In contrast, memory predictions were more accurate when the beverages did not match on both days. These data provide evidence for state-dependent memory when caffeine is used, but not for state-dependent metamemory. People's memory and their predictions of memory can be influenced in different ways if they drink caffeine before they study or take a test.
Children with comorbid attention‐deficit‐hyperactivity disorder and tic disorder: Evidence for additive inhibitory deficits within the motor system

For children with attention‐deficit‐hyperactivity disorder (ADHD) or tic disorder (TD), we recently reported deficient inhibitory mechanisms within the motor system by using transcranial magnetic stimulation. These deficits—stated as reduced intracortical inhibition in ADHD and shortened cortical silent period in TD—could be seen as neurophysiological correlates of motor hyperactivity and tics, respectively. To investigate neurophysiological aspects of comorbidity, we measured motor system excitability for the first time also in children with combined ADHD and TD. The findings of a reduced intracortical inhibition as well as a shortened cortical silent period in these comorbid children provide evidence for additive effects at the level of motor system excitability. Ann Neurol 2001;49:393–396
Granulocytic anaplasmosis in 63 dogs: clinical signs, laboratory results, therapy and course of disease

OBJECTIVES To describe the clinical signs, laboratory results, therapy and course of disease in dogs with canine granulocytic anaplasmosis in which co-infections had been excluded. METHODS Medical records of dogs naturally infected with Anaplasma phagocytophilum were retrospectively evaluated with regard to clinical signs and laboratory abnormalities at the time of presentation, therapy and course of disease. RESULTS Nine hundred and seventy-four dogs with clinical signs suspicious for canine granulocytic anaplasmosis were tested for A. phagocytophilum DNA by modified real-time PCR; 72 dogs had a positive result. Nine of the positive dogs were excluded from further evaluation due to other diseases or lack of data. The most common clinical signs in the 63 A. phagocytophilum-positive dogs included in the study were lethargy and reduced activity (83%), fever (67%) and inappetence (63%). Thrombocytopenia was the most common laboratory abnormality (86%), followed by increased liver enzyme activities and hyperbilirubinaemia (77%), anaemia (70%), hypoalbuminaemia (62%) and leucocytosis (27%). Of 36 thrombocytopenic dogs tested for platelet-bound antibodies, 44% were positive. Of the 63 infected dogs, 59 (97%) recovered, two dogs died (epileptic seizures and immune-mediated haemolytic anaemia) and two were lost to follow-up. CLINICAL SIGNIFICANCE In areas where it is endemic, canine granulocytic anaplasmosis should be considered as a potential cause of acute nonspecific clinical signs or immune-mediated disease if tick exposure cannot be excluded.
Antibodies specific for the human retinoblastoma protein identify a family of related polypeptides

Even though the retinoblastoma gene is one of the best-studied tumor suppressor genes, little is known about its functional role. Like all tumor suppressor gene products, the retinoblastoma protein (pRB) is thought to inhibit some aspect of cell proliferation. It also appears to be a cellular target of several DNA tumor virus-transforming proteins, such as adenovirus E1A, human papillomavirus E7, or simian virus 40 large T antigen. To help in the analysis of pRB, we have prepared a new set of anti-human pRB monoclonal antibodies. In addition to being useful reagents for the study of human pRB, these antibodies display several unexpected properties. They can be used to distinguish different subsets of the pRBs on the basis of their phosphorylation states. Some are able to recognize pRB homologs in other species, including mice, chickens, and members of the genus Xenopus. In addition, some of these antibodies can bind directly to other cellular proteins that, like pRB, were originally identified through their association with adenovirus E1A. These immunologically cross-reactive proteins include the p107 and p300 proteins, and their recognition by antibodies raised against pRB suggests that several members of the E1A-targeted cellular proteins form a structurally and functionally related family.
New medications which decrease levothyroxine absorption.

OBJECTIVE Medications may sometimes interfere with the intestinal absorption of levothyroxine, primarily by forming an insoluble complex with the thyroid hormone in the intestinal lumen. The goal of this study was to examine the acute effects of three previously unstudied medications on levothyroxine absorption. DESIGN We studied the effects of three medications on thyroxine absorption in seven normal volunteers. On each study day, the subjects ingested 1 mg levothyroxine sodium, either taken separately or co-administered with sevelamer hydrochloride (Renagel, a phosphate-binding medication used in the treatment of hyperphosphatemia), chromium picolinate (an over-the-counter nutritional supplement), or ezetimibe (Zetia, a drug used in the treatment of hypercholesterolemia). Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. MAIN OUTCOME Sevelamer hydrochloride and chromium picolinate each significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve, while ezetimibe had no effect. CONCLUSION Hypothyroid patients taking sevelamer hydrochloride or chromium picolinate should be advised to separate the time of ingestion of these drugs from their thyroid hormone preparation by several hours.
Re-examining handedness in schizophrenia: now you see it--now you don't.

The present study was designed to examine patterns of handedness across tasks (i.e., those requiring less vs. greater skill) and over time (initially and 1 month later) in 72 schizophrenic patients and 105 normal controls. Two important methodologic advances were introduced: (1) two handedness tasks, varying in skill level (simple vs. complex); and (2) the addition of a retest on both tasks, 1 month later. Results show a higher incidence (43%) of mixed handedness in the schizophrenic sample than in normal controls (14.3%) on tasks requiring less precision in performance. Similar results were obtained when schizophrenic patients were retested 1 month later, RI = . 88. When the more demanding set of tasks was presented, the frequency of mixed handed schizophrenics dropped by 50% at initial testing. Despite these findings, there was no evidence for stability of change over time. For example, each of the most extreme shifters at Time 1 was fully lateralized 1 month later.
Soft tissue masses in patients with multiple myeloma

To the authors' knowledge, the prognostic significance of plasma cell cytology in soft tissue (ST) masses from patients with multiple myeloma (MM) is unknown. Myeloma patients usually are monitored by bone marrow (BM) aspirates and biopsies to assess plasma cell differentiation, tumor burden, and response to treatment. Monitoring of ST lesions by fine‐needle aspiration (FNA) is not performed routinely. The objective of the current study was to examine ST masses in MM patients using FNA and to classify and determine the prognostic significance of MM in these lesions based on cytologic features.
Cluster-Randomized Trial to Increase Hepatitis B Testing among Koreans in Los Angeles

Background: In the United States, Korean immigrants experience a disproportionately high burden of chronic hepatitis B (HBV) viral infection and associated liver cancer compared with the general population. However, despite clear clinical guidelines, HBV serologic testing among Koreans remains persistently suboptimal. Methods: We conducted a cluster-randomized trial to evaluate a church-based small group intervention to improve HBV testing among Koreans in Los Angeles. Fifty-two Korean churches, stratified by size (small, medium, large) and location (Koreatown versus other), were randomized to intervention or control conditions. Intervention church participants attended a single-session small-group discussion on liver cancer and HBV testing, and control church participants attended a similar session on physical activity and nutrition. Outcome data consisted of self-reported HBV testing obtained via 6-month telephone follow-up interviews. Results: We recruited 1,123 individuals, 18 to 64 years of age, across the 52 churches. Ninety-two percent of the sample attended the assigned intervention session and 86% completed the 6-month follow-up. Sample characteristics included were as follows: mean age 46 years, 65% female, 97% born in Korea, 69% completed some college, and 43% insured. In an intent-to-treat analysis, the intervention produced a statistically significant effect (OR = 4.9, P < 0.001), with 19% of intervention and 6% of control group participants reporting a HBV test. Conclusion: Our intervention was successful in achieving a large and robust effect in a population at high risk of HBV infection and sequelae. Impact: The intervention was fairly resource efficient and thus has high potential for replication in other high-risk Asian groups. Cancer Epidemiol Biomarkers Prev; 24(9); 1341–9. ©2015 AACR.
Quantitative analysis of fuel-related hydrocarbons in surface water and wastewater samples by solid-phase microextraction.

Solid-phase microextraction (SPME) parameters were examined on water contaminated with hydrocarbons including benzene and alkylbenzenes, n-alkanes, and polycyclic aromatic hydrocarbons (PAHs). Absorption equilibration times ranged from several minutes for low molecular weight compounds such as benzene to 5 h for high molecular weight compounds such as benzo[a]pyrene. Under equilibrium conditions, SPME analysis with GC/FID was linear over 3-6 orders of magnitude, with linear correlation coefficients (r(2)) greater than 0.96. Experimentally determined FID detection limits ranged from ∼30 ppt (w/w hydrocarbon/sample water) for high molecular weight PAHs (e.g., MW > 202) to ∼1 ppb for low molecular weight aromatic hydrocarbons. Experimental distribution constants (K) were different with 100- and 7-μm poly(dimethylsiloxane) fibers, and poor correlations with previously published values suggest that K depends on the fiber coating thickness and the sorbent preparation method. The sensitivity of SPME analysis is not significantly enhanced by larger sample volumes, since increasing the water volume (e.g., from 1 to 100 mL) has little effect on the number of analyte molecules absorbed by the fiber, especially for compounds with K < 500. Water sample storage should utilize silanized glassware, since hydrocarbon losses up to 70% could be attributed to unsilanized glassware walls when samples were stored for 48 h. Hydrocarbon losses at part-per-billion concentrations also occurred with surface waters due to partitioning onto part-per-thousand concentrations of suspended solids. Quantitative determinations of aromatic and aliphatic hydrocarbons (e.g., in gasoline-contaminated water) can be performed using GC/MS with deuterated internal standard or standard addition calibration as long as the target components or standards had unique ions for quantitation or sufficient chromatographic resolution from interferences. SPME analysis gave good quantitative performance with surface waters having high suspended sediment contents, as well as with coal gasification wastewater which contained matrix organics at 10(6)-fold higher concentrations than the target aromatic hydrocarbons. Good agreement was obtained between a 45-min SPME and methylene chloride extraction for the determination of PAH concentrations in creosote-contaminated water, demonstrating that SPME is a useful technique for the rapid determination of hydrocarbons in complex water matrices.
Somatosensory properties of cuneocerebellar neurones in the main cuneate nucleus of the rat

Cells in the main cuneate nucleus (MCN) are known to provide a direct projection to the cerebellum, but the precise nature of the information these cells transmit to the cerebellum is unknown. The present study employed anatomical and electrophysiological procedures to determine the location of cuneocerebellar cells in the MCN, and their somatosensory properties in the rat. The location of neurones projecting to the cerebellum was determined with injections of the retrograde tracers, horseradish peroxidase or Fluoro-Gold in vermal and paravermal regions of the cerebellum. Topographically, the majority of retrogradely labelled cells in the MCN were found to lie primarily ventrolateral in the nucleus and rostral to the level of the obex. Single unit recordings from 69 well characterized MCN cells, identified as projection cells by antidromic activation from stimulation of the inferior cerebellar peduncle, were classified according to their responses to cutaneous stimulation and manipulation of joints and muscles. A slight majority of cells (37.7%) responded only to manipulation/stimulation of joints, and 30.4% of cells responded only to cutaneous stimulation. The remaining cells received convergent input from joint and cutaneous receptors. Cutaneous responsive cells all rapidly adapted to maintained stimuli, and had large receptive fields (RFs) that were generally located over the joints. These cells could be activated by passive movements of the forelimb that deformed the RF. They only discharged during movements and were silent during maintained limb positions. Cells responsive to punctate mechanical stimuli applied to the joint capsules, responded to passive movements of the forelimb, but typically only discharged towards the limits of joint movement, and adapted within a few seconds. Once adapted, small perturbations of joint position resulted in vigorous dynamic responses. The results indicate that the neurones in the MCN of the rat which project directly to the cerebellum are localized in the rostral half of the nucleus. They transmit predominantly dynamic information from joint and cutaneous receptors that are likely to be normally activated as a result of limb movements. These cells could signal information about evolving movements or disturbances of forelimb posture or stance.