Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional dissection and evidence for intercellular transfer of the heterocyst‐differentiation PatS morphogen

The formation of a diazotrophic cyanobacterial filament represents a simple example of biological development. In Anabaena, a non‐random pattern of one nitrogen‐fixing heterocyst separated by about 10 photosynthetic vegetative cells results from lateral inhibition elicited by the cells differentiating into heterocysts. Key to this process is the patS gene, which has been shown to produce an inhibitor of heterocyst differentiation that involves the C‐terminal RGSGR pentapeptide. Complementation of a ΔpatS Anabaena mutant with different versions of PatS, including point mutations or tag fusions, showed that patS is translated into a 17‐amino acid polypeptide. Alterations in the N‐terminal part of PatS produced inhibition of heterocyst differentiation, thus this part of the peptide appears necessary for proper processing and self‐immunity in the producing cells. Alterations in the C‐terminal part of PatS led to over‐differentiation, thus supporting its role in inhibition of heterocyst differentiation. A polypeptide, produced in proheterocysts, consisting of a methionine followed by the eight, but not the five, terminal amino acids of PatS recreated the full activity of the native peptide. Immunofluorescence detection showed that an RGSGR‐containing peptide accumulated in the cells adjacent to the producing proheterocysts, illustrating intercellular transfer of a morphogen in the cyanobacterial filaments.
Testosterone metabolism to 5α‐dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator‐activated receptor ligand linoleic acid in human sebocytes

Background Despite the clinical evidence that androgens stimulate sebaceous lipids, androgens in vitro have shown no similar effects. This contradiction led to the assumption that cofactors may be required for lipid regulation and peroxisome proliferator‐activated receptor (PPAR) ligands were suggested to be adequate candidates.
Global Synthesis and Critical Evaluation of Pharmaceutical Data Sets Collected from River Systems

Pharmaceuticals have emerged as a major group of environmental contaminants over the past decade but relatively little is known about their occurrence in freshwaters compared to other pollutants. We present a global-scale analysis of the presence of 203 pharmaceuticals across 41 countries and show that contamination is extensive due to widespread consumption and subsequent disposal to rivers. There are clear regional biases in current understanding with little work outside North America, Europe, and China, and no work within Africa. Within individual countries, research is biased around a small number of populated provinces/states and the majority of research effort has focused upon just 14 compounds. Most research has adopted sampling techniques that are unlikely to provide reliable and representative data. This analysis highlights locations where concentrations of antibiotics, cardiovascular drugs, painkillers, contrast media, and antiepileptic drugs have been recorded well above thresholds known to cause toxic effects in aquatic biota. Studies of pharmaceutical occurrence and effects need to be seen as a global research priority due to increasing consumption, particularly among societies with aging populations. Researchers in all fields of environmental management need to work together more effectively to identify high risk compounds, improve the reliability and coverage of future monitoring studies, and develop new mitigation measures.
Treponema rectale sp. nov., a spirochete isolated from the bovine rectum.

A Gram-stain-negative, obligatory anaerobic spirochete, CHPAT, was isolated from the rectal tissue of a Holstein-Friesian cow. On the basis of 16S rRNA gene comparisons, CHPAT was most closely related to the human oral spirochete, Treponema parvum, with 88.8 % sequence identity. Further characterisation on the basis of recA gene sequence analysis, cell morphology, pattern of growth and physiological profiling identified marked differences with respect to other recognised species of the genus Treponema. Microscopically, the helical cells measured approximately 1-5 µm long and 0.15-0.25 µm wide, with two to five irregular spirals. Transmission electron microscopy identified four periplasmic flagella in a 2 : 4 : 2 arrangement. CHPAT grew independently of serum, demonstrated no evidence of haemolytic activity and possessed an in vitro enzyme activity profile that is unique amongst validly named species of the genus Treponema, exhibiting C4 esterase, α-galactosidase and β-galactosidase activity. Taken together, these data indicate that CHPAT represents a novel species of the genus Treponema, for which the name Treponema rectale is proposed. The type strain of Treponema rectale is CHPAT (=DSM 103679T=NCTC 13848T).
N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A) interaction with LYS 3.28(192) is crucial for its inverse agonism at the cannabinoid CB1 receptor.

In superior cervical ganglion neurons, N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A) competitively antagonizes the Ca(2+) current effect of the cannabinoid (CB) agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55212-2), and behaves as an inverse agonist by producing opposite current effects when applied alone. In contrast, in neurons expressing CB1 with a K-->A mutation at residue 3.28(192) (i.e., K3.28A), SR141716A competitively antagonizes the effects of WIN55212-2, but behaves as a neutral antagonist by producing no current effects itself. Receptor modeling studies suggested that in the CB1 inactive (R) state, SR1417A16A stabilizes transmembrane helix 6 in its inactive conformation via aromatic stacking with F3.36/W6.48. In this binding site, SR141716A would exhibit higher affinity for CB1 R due to a hydrogen bond between the SR141716A C3 substituent and K3.28(192), a residue available to SR141716A only in R. To test this hypothesis, a "mutant thermodynamic cycle" was constructed that combined the evaluation of SR141716A affinity at WT CB1 and K3.28A with an evaluation of the wild-type CB1 and K3.28A affinities of an SR141716A analog, 5-(4-chlorophenyl)-3-[(E)-2-cyclohexylethenyl]-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole (VCHSR), that lacks hydrogen bonding potential at C3. Binding affinities suggested that K3.28 is involved in a strong interaction with SR141716A in WT CB1, but does not interact with VCHSR. Thermodynamic cycle calculations indicated that a direct interaction occurs between the C3 substituent of SR141716A and K3.28 in WT CB1. Consistent with these results, VCHSR acted as a neutral antagonist at WT CB1. These results support the hypothesis that hydrogen bonding of the SR141716A C3 substituent with K3.28 is responsible for its higher affinity for the inactive R state, leading to its inverse agonism.
An alternative architecture for on-chip global interconnect: segmented bus power modeling

On-chip interconnect power consumption has become an important issue as technology quickly scales down and the industry embraces system-on-a-chip (SOC). The simple bus structure may became a serious bottleneck in reducing the total chip power consumption and increasing performance due to transmission line effects. Alternative interconnect structures should be considered under this circumstances. This paper models the power consumption of both a global data bus and the proposed segmented bus for a commercial chip at the behavioral level. The chip is an integration of a 16-bit DSP and a 32-bit RISC microcontroller. The power measurements of both bus structures at different technology feature size levels are reported for a set of standard signal processing benchmarks.
Distinct patterns of dystrophin organization in myocyte sarcolemma and transverse tubules of normal and diseased human myocardium.

BACKGROUND Genetic mutations of dystrophin and associated glycoproteins underlie cell degeneration in several inherited cardiomyopathies, although the precise physiological role of these proteins remains under discussion. We studied the distribution of dystrophin in relation to the force-transducing vinculin-rich costameres in left ventricular cardiomyocytes from normal and failing human hearts to further elucidate the function of this protein complex. METHODS AND RESULTS Single- and double-label immunoconfocal microscopy and parallel high-resolution immunogold fracture-label electron microscopy were used to localize dystrophin and vinculin in human left ventricular myocytes from normal (n=6) and failing hearts (idiopathic dilated cardiomyopathy, n=7, or ischemic heart disease, n=5). In control cardiomyocytes, dystrophin had a continuous distribution at the peripheral sarcolemma, with concentrated bands corresponding to the vinculin-rich costameres. Intracellular labeling extended along transverse (T) tubule membranes. Fracture-label confirmed this distribution, showing significantly greater label on plasma membrane fractures overlying I-bands (I-band 4.1+/-0.3 gold particles/micrometer A-band 3.3+/-0.2 gold particles/micrometer mean+/-SE, P=0.02). Hypertrophied myocytes from failing hearts showed maintenance of this surface distribution except in degenerating cells; there was a clear increase in intracellular dystrophin label reflecting T-tubule hypertrophy. CONCLUSIONS Dystrophin partially colocalizes with costameric vinculin in normal and hypertrophied myocytes, a distribution lost in degenerating cells. This suggests a primarily mechanical role for dystrophin in maintenance of cell membrane integrity in normal and hypertrophied myocytes. The presence of dystrophin in the cardiac T-tubule membrane, in contrast to its known absence in skeletal muscle T-tubules, implies additional roles for dystrophin in membrane domain organization.
Myeloma impairs mature osteoblast function but causes early expansion of osteo‐progenitors: temporal changes in bone physiology and gene expression in the KMS12BM model

Myeloma bone disease results from an uncoupling of osteoclastic resorption and osteoblastic bone formation, but early changes in osteogenic function remain poorly defined. We used the KMS12BM xenograft model to investigate cellular and molecular events at early and late stages of disease. Lytic lesions and changes in osteoblast and osteoclast numbers occur late (8 weeks), however, micro‐computed tomography of femora revealed significant reduction in bone volume at earlier disease stages (3 weeks) when tumour burden is low. Calcein labelling demonstrated reduced mineralization and bone formation at 3 weeks, suggesting functional impairment despite preserved osteoblast numbers. Osteo‐progenitors from compact bone increased early (1 week), but fell at 3 weeks and were profoundly suppressed by 8 weeks. Exposure of osteoblast progenitors to multiple myeloma (MM) cells in vitro induced cell cycling, suggesting a mechanistic basis for early expansion of osteo‐progenitors. We observed temporal changes in chemokine, osteogenic and osteoclastogenic genes in the stromal compartment. Notably, an early rise in CCL3 may underlie functional changes in mature osteoblasts at 3 weeks. Our data indicate that MM has distinct effects on mature osteoblasts and immature osteo‐progenitors. Our findings argue for early clinical intervention to prevent bone changes that ultimately lead to the development of osteolytic disease.
Natural Genetic Exchanges between Vaccine and Wild Poliovirus Strains in Humans

ABSTRACT In a previous study of poliovirus vaccine-derived strains isolated from patients with vaccine-associated paralytic poliomyelitis (VAPP) (9, 11), we reported that a high proportion (over 50%) of viruses had a recombinant genome. Most were intertypic vaccine/vaccine recombinants. However, some had restriction fragment length polymorphism (RFLP) profiles different from those of poliovirus vaccine strains. We demonstrate here that five such recombinants, of 88 VAPP strains examined, carried sequences of wild (nonvaccine) origin. To identify the parental wild donor of these sequences, we used RFLP profiles and nucleotide sequencing to look for similarity in the 3D polymerase-coding region of 61 wild, cocirculating poliovirus isolates (43 type 1, 16 type 2, and 2 type 3 isolates). In only one case was the donor identified, and it was a wild type 1 poliovirus. For the other four vaccine/wild recombinants, the wild parent could not be identified. The possibility that the wild sequences were of a non-poliovirus-enterovirus origin could not be excluded. Another vaccine/wild recombinant, isolated in Belarus from a VAPP case, indicated that the poliovirus vaccine/wild recombination is not an isolated phenomenon. We also found wild polioviruses (2 of 15) carrying vaccine-derived sequences in the 3′ moiety of their genome. All these results suggest that genetic exchanges with wild poliovirus and perhaps with nonpoliovirus enteroviruses, are also a natural means of evolution for poliovirus vaccine strains.
Untersuchungen zur postkolostralen Immunglobulin-G-Versorgung neugeborener Saugferkel mittels unterschiedlicher ELISA-Nachweissysteme

Zusammenfassung Gegenstand und Ziel: Überprüft werden sollte die Anwenderfreundlichkeit, Praxistauglichkeit und Vergleichbarkeit der Ergebnisse des Colostrum Quality Counter (CQC), einer neuen Untersuchungsmethode für die postkolostrale Immunglobulin-G-(IgG-)Versorgung beim Saugferkel. Material und Methode: Blutproben von insgesamt 219 Saugferkeln aus vier Betrieben wurden mit drei verschiedenen ELISA-Testsystemen auf ihre IgG-Konzentrationen untersucht. Bei 30 Saugferkeln wurden darüber hinaus die IgG-Konzentrationen aus zentralvenös und peripher entnommenem Blut mit zwei Testsystemen bestimmt und verglichen. Zum Einsatz kamen der Colostrum Quality Counter (CQC, FarmulaONE, NL-Best), der interne IgG-ELISA des eigenen Lehrstuhls (MUC) und ein kommerziell erhältlicher IgG-ELISA (NAT; NatuTec, Frankfurt/Main). Ergebnisse: Die Einzelwerte aller drei Tests wichen deutlich voneinander ab, wobei MUC und NAT deutlich höhere Korrelationen zueinander aufwiesen als zum CQC. Die Messwerte des CQC lagen insgesamt deutlich höher und wiesen eine wesentlich größere Streuung auf. Die aus zentralvenösem und peripherem Blut ermittelten Messwerte differierten nicht signifikant. Klinische Relevanz: Der CQC ermöglicht eine einfache Probennahme auch bei größeren Strichprobenzahlen. Die Ergebnisse waren individuell sehr unterschiedlich mit einigen ungewöhnlich hohen Werten. MUC und NAT lieferten miteinander vergleichbare Messresultate und die bestimmten IgG-Konzentrationen zeigten eine deutliche Korrelation zueinander.
The effects of bradykinin on afferent units in intra-abdominal sympathetic nerve trunks.

The effects of intra-arterial injections of bradykinin on afferent discharges in the splanchnic and hypogastric nerves have been studied. All units which were excited by the peptide were mechanosensitive. Following i.a. bradykinin, the slowly adapting mechanoreceptors associated with the bladder showed increased discharge rates which appear to be related to changes in intravesical pressure. When the effects of bradykinin on the bladder were blocked by cord cooling, the afferents were not excited. It is concluded that bradykinin causes discharges in the slowly adapting mechanoreceptors around the bladder because it causes bladder contractions, and not because of any chemosensitivity of the nerve ending.
The clinical and biological role of CD20 membrane antigen modulation under immunotherapy with anti-CD20 monoclonal antibody rituximab in lymphoprolipherative neoplastic disorders

Immunotherapy using an antibody (rituximab) targeting CD20 antigen in combination with chemotherapy has been recently associated with significantly improved response rate and survival in patients with various types of CD20-positive B-cell lymphoproliferative disorders. This treatment may induce the disappearance of CD20 surface expression on neoplastic B-cells. Several mechanisms have been proposed to explain CD20 loss after rituximab therapy, while the clinical significance (if any) of this phenomenon is still not clear. We have produced a brief overview of the biological aspects of CD20 modulation after rituximab treatment and its possible clinical implications.
Perinatal depression screening, prevention and early intervention: recent advances in Portugal

Perinatal depression (PD) is a significant public health concern, needing a more efficient detection, prevention and treatment. Experts in the area recently recommended universal psychosocial assessment programs that combine the evaluation of PD symptoms and psychosocial risk factors. Within a new research project, our team has been exploring this avenue to try to reduce the high negative impact of PD. Our aims are: (1) to analyze the predictive ability of a new instrument (Perinatal Depression Screening and Prevention Tool/PDSPTool) to assess both PD symptoms and risk factors previously validated/identified by our team; (2) to test the efficacy of prevention and/or early intervention program —Mother in Me (MIM), focused on psychoeducational and psychotherapy sessions focusing on Cognitive-Behavioral Therapy (CBT) and on exercises from the third generation CBT. The new instrument (PDSPT), includes the short version of the Postpartum Depression Screening Scale (adapted and validated for pregnancy) and other valid self-report questionnaires to assess the PD risk factors in Portuguese women: lifetime history of depression, prenatal insomnia and prenatal negative affect. The PDSPTool and the Diagnostic interview for Psychological Distress have been administered to pregnant women (third trimester), recruited in the primary health care centers and maternity hospitals, where the vast majority of Portuguese women have their pregnancy and puerperium followed. The effectiveness of the program will be tested at 5 weeks, 3 and 6 months postpartum, based on the PDSS cutoff points and on the administration of the interview.
The AML 1 / ETO ( MTG 8 ) and AML 1 / Evi1 Leukemia-Associated Chimeric

AML1, a gene on chromosome 21 encoding a transcription factor, is disrupted in the (8;21)(q22;q22) and (3;21)(q26;q22) chromosomal translocations associated with myelogenous leukemias; as a result, chimeric proteins AML1/ETO(MTG8) and AML1/Evi-1 are generated, respectively. To clarify the roles of AML1/ETO(MTG8) and AML1/Evi-1 in leukemogenesis, we investigated subcellular localization of these chimeric proteins by immunofluorescence labeling and subcellular fractionation of COS-7 cells that express these chimeric proteins. AML1/ETO(MTG8) and AML1/Evi-1 are nuclear proteins, as is wild-type AML1. Polyomavirus enhancer binding protein (PEBP)2b(core binding factor [CBF]b), a heterodimerizing partner of AML1 that is located mainly in the cytoplasm, was translocated into the nucleus with dependence on the runt domain of AML1/ETO(MTG8) or AML1/ Evi-1 when coexpressed with these chimeric proteins. When a comparable amount of wild-type AML1 or the chimeric proteins was coexpressed with PEBP2b(CBFb), more of the cells expressing the chimeric proteins showed the nuclear accumulation of PEBP2b(CBFb), as compared with the cells expressing wild-type AML1. We also showed that the chimeric proteins associate with PEBP2b(CBFb) more effectively than wild-type AML1. These data suggest that the chimeric proteins are able to accumulate PEBP2b(CBFb) in the nucleus more efficiently than wild-type AML1, probably because of the higher affinities of the chimeric proteins for PEBP2b(CBFb) than that of wild-type AML1. These effects of the chimeric proteins on the cellular distribution of PEBP2b(CBFb) possibly cause the dominant negative properties of the chimeric proteins over wild-type AML1 and account for one of the mechanisms through which these chimeric proteins contribute to leukemogenesis. r 1998 by The American Society of Hematology.
A simple method for the collision avoidance of telerobotic manipulators

In this article a fast and simple method for the motion planning of telerobotic manipulators is presented. It is based on solving numerically a linear system of equations that includes a simple null space vector for obstacle avoidance, and an efficient procedure for the appropriate damping of the pseudoinverse matrix. This approach enables the pursuance simultaneously, of both collision avoidance and singularities prevention on-line in a sensor based environment. These properties also make it suitable for entirely autonomous operations. <<ETX>>
Regulation and Accounting Conservatism

This study documents an increase in conservatism in response to the Securities and Exchange Commission’s Staff Accounting Bulletin No. 101, which altered the regulation concerning revenue recognition for registrants. We further illustrate the increase in conservatism primarily relates to companies that were forced to delay cash revenues. Given the benefits of conservatism surround the asymmetric recognition of hard-to-verify gains versus losses, the deferral of easily verifiable cash revenues calls into question the contracting benefits resulting from the regulation. Instead, we suggest the regulation may have primarily served to benefit the reputation of the Securities and Exchange Commission as a conservative regulatory body, especially in light of the corporate scandals that followed soon after the issuance of the regulation in 1999. Our results illustrate the influence of regulation on conservatism providing some initial evidence called for by Watts (2003b).
LncRNA HMlincRNA 717 is down-regulated in non-small cell lung cancer and associated with poor prognosis

Introduction: Long non coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. The lncRNA HMlincRNA717, a newly identified lncRNA, was demonstrated to be down-regulated in gastric cancer. However, little is known about its role in non small cell lung cancer (NSCLC). Methods: Expression of lncRNA HMlincRNA717 in tumor and their matched non-tumor tissues was determined by quantitative real-time PCR (qRT-PCR) in NSCLC patients. Then, we analyzed the potential relationship between lncRNA HMlincRNA717 expression levels in tumor tissues and clinicopathological features of NSCLC, and clinical outcome. Results: lncRNA HMlincRNA717 expression level was significantly decreased in NSCLC tissues in comparison to adjacent non-tumor tissues. It was also proved that HMlincRNA717 expression was to be associated with NSCLC histological grade, and lymph node metastasis. In addition, survival analysis proved that down-regulated HMlincRNA717 expression was associated with poor overall survival of NSCLC patients. Multivariate survival analysis also proved that HMlincRNA717 was an independent prognostic factor for NSCLC patients. Conclusions: The present study showed the down-regulation of HMlincRNA717 and its association with tumor progression in human NSCLC. It also provided that HMlincRNA717 expression was an independent prognostic factor for patients with NSCLC, which might be a potential prognostic biomarker and therapeutic target for NSCLC.