Miracle-dz/UniFAR-FTUs huggingface dataset:
Coupling of ETB Endothelin Receptor to Mitogen‐Activated Protein Kinase Stimulation and DNA Synthesis in Primary Cultures of Rat Astrocytes

Abstract: Astrocytes have been shown to express endothelin (ET) receptors functionally coupled, via different heterotrimeric G proteins, to several intracellular pathways. To assess the relative contribution of each subtype in the astrocytic responses to ET‐1, effects of BQ123, an antagonist selective for the ET receptor subtype A (ETA‐R), and IRL1620, an agonist selective for the ET receptor subtype B (ETB‐R), were investigated in primary cultures of rat astrocytes. Binding experiments indicated that the ETB‐R is the predominant subtype in these cells. Inhibition of forskolin‐stimulated cyclic AMP production was observed under ETB‐R stimulation. Bordetella pertussis toxin (PTX) pretreatment completely abolished this effect, indicating that this pathway is coupled to the ETB‐R via Gi protein. Increases of tyrosine phosphorylation of cellular proteins, stimulation of mitogen‐activated protein kinase (MAPK), and DNA synthesis were also found to be mediated by the ETB‐R, but through PTX‐insensitive G protein. IRL1620‐induced MAPK activation involved the adapter proteins Shc and Grb2 and the serine/threonine kinase Raf‐1. This study reveals that the various effects of ET‐1 in astrocytes are mediated by the ETB‐R, which couples to multiple signaling pathways including the MAPK cascade.
Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization.

BACKGROUND The importance of early and aggressive management of trauma- related coagulopathy remains poorly understood. We hypothesized that a trauma exsanguination protocol (TEP) that systematically provides specified numbers and types of blood components immediately upon initiation of resuscitation would improve survival and reduce overall blood product consumption among the most severely injured patients. METHODS We recently implemented a TEP, which involves the immediate and continued release of blood products from the blood bank in a predefined ratio of 10 units of packed red blood cells (PRBC) to 4 units of fresh frozen plasma to 2 units of platelets. All TEP activations from February 1, 2006 to July 31, 2007 were retrospectively evaluated. A comparison cohort (pre-TEP) was selected from all trauma admissions between August 1, 2004 and January 31, 2006 that (1) underwent immediate surgery by the trauma team and (2) received greater than 10 units of PRBC in the first 24 hours. Multivariable analysis was performed to compare mortality and overall blood product consumption between the two groups. RESULTS Two hundred eleven patients met inclusion criteria (117 pre-TEP, 94 TEP). Age, sex, and Injury Severity Score were similar between the groups, whereas physiologic severity (by weighted Revised Trauma Score) and predicted survival (by trauma-related Injury Severity Score, TRISS) were worse in the TEP group (p values of 0.037 and 0.028, respectively). After controlling for age, sex, mechanism of injury, TRISS and 24-hour blood product usage, there was a 74% reduction in the odds of mortality among patients in the TEP group (p = 0.001). Overall blood product consumption adjusted for age, sex, mechanism of injury, and TRISS was also significantly reduced in the TEP group (p = 0.015). CONCLUSIONS We have demonstrated that an exsanguination protocol, delivered in an aggressive and predefined manner, significantly reduces the odds of mortality as well as overall blood product consumption.
Regional Management Plan for the West Indian Manatee, Trichechus manatus

As truly aquatic herbivorous mammals, West Indian manatees (Trichechus manatus) occupy a specialized niche in the ecosystem. The uniqueness of their niche render them susceptible to over-exploitation. Manatees are long-lived, but reproductive processes are slow. Their naturally low population growth and present mortality levels hamper the increase of potential populations, and may actually be accelerating their decline. Manatees are present in nineteen (19) countries of the Wider Caribbean but most populations are estimated at below one hundred (100) individuals. Heavily hunted in the past, they have always played an important role in the folklore and traditions of indigenous peoples of the Wider Caribbean. Ecologically, they may play a role in the cycle of nutrients and in the clearing of water ways by feeding exclusively on aquatic plants. Socio-economic factors affect manatee conservation in the Wider Caribbean. West Indian manatees occur in areas inhabited by some of the most impoverished peoples of the Western Hemisphere. Manatee preferred habitats correspond to areas usually favored by humans for settlement, and more recently by larger enterprises for services, industrial, and development projects. Manatees are susceptible to anthropogenic and natural disturbances, including environmental catastrophes, harassment, and pollution. Although hunting tradition is dwindling, manatees are still taken throughout the Caribbean for subsistence, and newer threats are emerging. Major hazards vary slightly with the country, but incidental take, hunting, and habitat alteration are the most prevalent. The extent of manatees' range hinders continuity of law enforcement activities, and environmental education programmes to stimulate an ecological consciousness are limited in number and scope of action. Manatees in Florida exhibit flexible behaviour patterns and adapt quickly to actions taken on their behalf. If left alone some populations have the potential to slowly recover. The keys to manatee conservation in individual countries consist of estimating distribution and abundance, conserving manatee habitats and launching an integrated education/conservation/law enforcement programme to ensure the immunity of those populations to human-related threats. As individual manatees may move along the territorial waters of several countries, their ultimate conservation will be highly dependent on international co-operation. Some systems (e.g. in Belize, Guatemala, and Venezuela) are identified as potential sources of manatees to more depleted areas, but this will be true only if manatees are granted and assured immediate protection throughout their range. This document is divided in three sections: I) a review of the biology of the species in the Wider Caribbean, II) status of scientific knowledge and conservation efforts in each country and III) a set of recommended activities to be undertaken by individual countries and the region as a whole.
Deletion of 3p25.3 in a patient with intellectual disability and dysmorphic features with further definition of a critical region

Several recent reports of interstitial deletions at the terminal end of the short arm of chromosome 3 have helped to define the critical region whose deletion causes 3p deletion syndrome. We report on an 11‐year‐old girl with intellectual disability, obsessive–compulsive tendencies, hypotonia, and dysmorphic facial features in whom a 684 kb interstitial 3p25.3 deletion was characterized using array‐CGH. This deletion overlaps with interstitial 3p25 deletions reported in three recent case reports. These deletions share a 124 kb overlap region including only three RefSeq annotated genes, THUMPD3, SETD5, and LOC440944. The current patient had phenotypic similarities, including intellectual disability, hypotonia, depressed nasal bridge, and long philtrum, with previously reported patients, while she did not have the cardiac defects, seizures ormicrocephaly reported in patients with larger deletions. Therefore, this patient furthers our knowledge of the consequences of 3p deletions, while suggesting genotype–phenotype correlations. © 2013 Wiley Periodicals, Inc.
Diffusion‐weighted spectroscopy: A novel approach to determine macromolecule resonances in short‐echo time 1H‐MRS

Quantification of short‐echo time proton magnetic resonance spectroscopy results in >18 metabolite concentrations (neurochemical profile). Their quantification accuracy depends on the assessment of the contribution of macromolecule (MM) resonances, previously experimentally achieved by exploiting the several fold difference in T1. To minimize effects of heterogeneities in metabolites T1, the aim of the study was to assess MM signal contributions by combining inversion recovery (IR) and diffusion‐weighted proton spectroscopy at high‐magnetic field (14.1 T) and short echo time (=8 msec) in the rat brain. IR combined with diffusion weighting experiments (with δ/Δ = 1.5/200 msec and b‐value = 11.8 msec/μm2) showed that the metabolite nulled spectrum (inversion time = 740 msec) was affected by residuals attributed to creatine, inositol, taurine, choline, N‐acetylaspartate as well as glutamine and glutamate. While the metabolite residuals were significantly attenuated by 50%, the MM signals were almost not affected (<8%). The combination of metabolite‐nulled IR spectra with diffusion weighting allows a specific characterization of MM resonances with minimal metabolite signal contributions and is expected to lead to a more precise quantification of the neurochemical profile. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Montara: 2011 Shallow Reef Surveys at Ashmore, Cartier and Seringapatam Reefs

In response to the triggering of the Coral Reefs (S6) component of the PTTEP Australasia (Ashmore Cartier) Pty Ltd (PTTEPAA)/Dept. of SEWPaC Monitoring Plan for the Montara Well Release Timor Sea, PTTEP commissioned the Australian Institute of Marine Science (AIMS) to conduct surveys of shallow reef benthic habitats in the vicinity of the Montara well head platform in April 2010. Ashmore Reef and Cartier Islet were the principal emergent reefs of interest, as they were closest to the Montara Well Head platform. To provide a control location, the same sampling was conducted at Seringapatam Reef, a similar emergent reef in the same bioregion, but several hundred kilometres to the south-west and well away from modelled spill trajectories.The condition of the benthic communities at Ashmore and Cartier Reefs in the previous survey in 2010 was consistent with surveys conducted before the uncontrolled release. Although there was no evidence of recent major disturbance that could be attributable to any uncontrolled release,there was evidence of a recent coral bleaching event that was most likely caused by elevated water temperatures (Heyward et al. 2010). Notwithstanding the lack of a major impact, more subtle potential effects from hydrocarbons could not be ruled out and there remained knowledge gaps regarding coral reproduction and the recovery or otherwise of the bleached corals. Consequently, a follow up survey was commissioned by PTTEPAA in 2011 (Coral Reefs S6B), and the results of the surveys are presented here.The most recent 2011 survey enabled a repeated assessment of the shallow reef benthos to ascertain the ongoing state of the coral communities. In addition, an extended and more diverse selection of sampling was undertaken to see if processes of ongoing coral population renewal via sexual reproduction and recruitment were occurring. The 2011 surveys were broader in scope than the 2010 assessment, including comprehensive assessment of the fish communities associated withthe benthic sites, as well as a re-sampling of reef sediments to follow up on the status of hydrocarbon detections noted in the 2010 report.
Outer membrane protein P1 is the CEACAM‐binding adhesin of Haemophilus influenzae

Haemophilus influenzae is a Gram‐negative pathogen colonizing the upper respiratory tract mucosa. H. influenzae is one of several human‐restricted bacteria, which bind to carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs) on the epithelium leading to bacterial uptake by the eukaryotic cells. Adhesion to CEACAMs is thought to be mediated by the H. influenzae outer membrane protein (OMP) P5. However, CEACAMs still bound to H. influenzae lacking OMP P5 expression, and soluble CEACAM receptor ectodomains failed to bind to OMP P5, when heterologously expressed in Escherichia coli. Screening of a panel of H. influenzae OMP mutants revealed that lack of OMP P1 completely abrogated CEACAM binding and supressed CEACAM‐mediated engulfment of H. influenzae by epithelial cells. Moreover, ectopic expression of OMP P1 in E. coli was sufficient to induce CEACAM binding and to promote attachment to and internalization into CEACAM‐expressing cells. Interestingly, OMP P1 selectively recognizes human CEACAMs, but not homologs from other mammals and this binding preference is preserved upon expression in E. coli. Together, our data identify OMP P1 as the bona fide CEACAM‐binding invasin of H. influenzae. This is the first report providing evidence for an involvement of the major OMP P1 of H. influenzae in pathogenesis.
High-content analysis of Rab protein function at the ER-Golgi interface

ABSTRACT The Rab family of small GTPases play fundamental roles in the regulation of trafficking pathways between intracellular membranes in eukaryotic cells. In this short commentary we highlight a recent high-content screening study that investigates the roles of Rab proteins in retrograde trafficking from the Golgi complex to the endoplasmic reticulum, and we discuss how the findings of this work and other literature might influence our thoughts on how the architecture of the Golgi complex is regulated.
CD40 ligand is a critical effector of Epstein–Barr virus in host cell survival and transformation

Epstein–Barr virus (EBV), implicated in numerous human diseases, including lymphoid malignancies, persistently infects peripheral B cells and transforms them into lymphoblastoid cell lines. Here we found that EBV equally infected B cells from patients with X-linked hyper IgM syndrome and those from healthy donors; however, it hardly transformed X-linked hyper IgM syndrome B cells, because of the dysfunctional gene of CD40 ligand (CD40L) of the patients. Unlike CD40, CD40L is not usually expressed on B cells. However, we found that EBV infection of normal B cells induced CD40L expression as a critical effector in host cell transformation and survival. Moreover, chronic active EBV infection of peripheral T cells, implicated in T cell malignancies, was associated with ectopic expression of CD40, and, in Jurkat T cells, EBV infection induced CD40 expression. These results suggest that EBV infection induces CD40L/CD40 signaling in host cells, which appears to play an essential role in its persistent infection and malignancies of lymphocytes.
The Continuous Service Usage Intention in the Web Analytics Services

The World Wide Web (WWW) has continued to grow at very rapid speed in both the sheer volume of traffic and size, complexity of web sites. Web analytics industry also has been growing rapidly. Web analytics is to analyze web log files to discover accessing patterns of web pages. In our work described in this paper, we identify factors which can affect the continuous usage intention of a firm using services in Web Analytics service and empirically validate the relationships between the identified factors. For this purpose, we analyze 174 Korea firms. The analysis results show that the satisfaction is significantly associated with service quality and switching cost and the service usage period is not significantly associated with continuous service usage intention. We measure service quality using SERVQUAL. It turn out that two dimensions of SERVQUAL, reliability and empathy are significantly associated with satisfaction, but another dimension of SERVQUAL, responsibility, is not. Finally, satisfaction is significantly associated with continuous service usage intention.
Quarternary Structure and Enzymological Properties of the Different Hormone-Sensitive Lipase (HSL) Isoforms

Background Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of energy in the form of fatty acids from intracellular stores of neutral lipids. The enzyme has been shown to exist in different isoforms with different molecular masses (84 kDa, 89 kDa and 117 kDa) expressed in a tissue-dependent manner, where the predominant 84 kDa form in adipocytes is the most extensively studied. Methodology/Principal Findings In this study we employed negative stain electron microscopy (EM) to analyze the quarternary structure of the different HSL isoforms. The results show that all three isoforms adopt a head-to-head homodimeric organization, where each monomer contains two structural domains. We also used enzymatic assays to show that despite the variation in the size of the N-terminal domain all three isoforms exhibit similar enzymological properties with regard to psychrotolerance and protein kinase A (PKA)-mediated phosphorylation and activation. Conclusions/Significance We present the first data on the quaternary structure and domain organization of the three HSL isoforms. We conclude that despite large differences in the size of the N-terminal, non-catalytic domain all three HSL isoforms exhibit the same three-dimensional architecture. Furthermore, the three HSL isoforms are very similar with regard to two unique enzymological characteristics of HSL, i.e., cold adaptation and PKA-mediated activation.
Oxygen migration pathways in NO-bound truncated hemoglobin.

Atomistic simulations of dioxygen (O(2)) dynamics and migration in nitric oxide-bound truncated Hemoglobin N (trHbN) of Mycobacterium tuberculosis are reported. From more than 100 ns of simulations the connectivity network involving the metastable states for localization of the O(2) ligand is built and analyzed. It is found that channel I is the primary entrance point for O(2) whereas channel II is predominantly an exit path although access to the protein active site is also possible. For O(2) a new site compared to nitric oxide, from which reaction with the heme group can occur, was found. As this site is close to the heme iron, it could play an important role in the dioxygenation mechanism as O(2) can remain there for hundreds of picoseconds after which it can eventually leave the protein, while NO is localized in Xe2. The present study supports recent experimental work which proposed that O(2) docks in alternative pockets than Xe close to the reactive site. Similar to other proteins, a phenylalanine residue (Phe62) plays the role of a gate along the access route in channel I. The most highly connected site is the Xe3 pocket which is a "hub" and free energy barriers between the different metastable states are ≈1.5 kcal mol(-1) which allows facile O(2) migration within the protein.
MYCOTIC CORNEAL ULCERS*

CORNEAL ulcers present one of the major ophthalmic problems of India. Mitsui and Hanabusa (1955), Ley (1956), and Ley and Sanders (1956) considered that antibiotic and/or corticosteroid therapy might convert non-pathogenic into pathogenic fungi. Seligmann (1953), Mankowski and Littleton (1954), and Vogel, Michael, and Timpe (1955) have reported the systemic dissemination of fungus infection after systemic cortisone therapy. Conant, Smith, Baker, Callaway, and Martin (1954) stated that mycotic keratitis was mainly due to potentially pathogenic fungi. Leber (1879), Berliner (1882), Schirmer (1896), Uhthoff (1897), Stern and Kulvin (1950), Thygeson, Hogan, and Kimura (1953), Pautler, Roberts, and Beamer (1955), Anderson, Roberts, Gonzalez, and Chick (1959), and Barsky (1959) have reported clinical cases of mycotic infection of the cornea, and Fazakas (1953), Ley (1956), Hirose, Yoshioka, Abe, Kanemitsu, and Kiya (1957), and Montana and Sery (1958) have produced mycotic keratitis experimentally. Some of our recent cases of corneal ulcer, in spite of suitable antibiotic and other therapy, progressed relentlessly and ended in blindness. We assumed that, besides bacteria, other pathogens were complicating these ulcers and we were able in a few to isolate fungi. We therefore attempted to produce experimental fungal keratitis in rabbits and to study the corneal ulcers thus obtained.
TRANSFER OF DELAYED HYPERSENSITIVITY TO DIPHTHERIA TOXIN IN MAN

Simultaneous transfer of delayed hypersensitivity to diphtheria toxin and to tuberculin has been accomplished in eight consecutive instances in man using extracts from washed leucocytes taken from the peripheral blood of tuberculin-positive, Schick-negative donors who were highly sensitive (i.e., pseudoreactors) to purified diphtheria toxin and toxoid. The leucocyte extracts used for transfer contained no detectable antitoxin. The recipient subjects were Schick-positive (<0.001 unit antitoxin per ml. serum) and tuberculin-negative at the time of transfer. All the recipients remained Schick-positive for at least 2 weeks following transfer and in every case their serum contained less than 0.001 units antitoxin at the time when they exhibited maximal skin reactivity to toxoid. Evidence is presented which indicates that the transfer factor may be released from leucocyte suspensions under mild conditions in which most of the cells appear to remain morphologically intact. Four adult Schick-positive subjects have been sensitized to diphtheria toxoid by intradermal injection of a few micrograms of purified toxoid in the form of a washed toxoid-antitoxin precipitate. Two of these sensitized individuals showed severe delayed skin reactions specifically directed against diphtheria toxin (or toxoid) at a time when their serum antitoxin level was less than 0.001 units/ml.
Two dimensional projective point matching

Point matching is the task of finding a set of correspondences between two sets of points under some geometric transformation. A local search algorithm for point matching is presented, and shown to be effective at solving problems where the point sets are related by a projective transformation. Random starts local search is shown to be capable of solving. very difficult point matching problems, and a heuristic key feature algorithm is presented which can substantially improve the effectiveness of local search in most cases.
Territorial behaviour in southern red-backed and Ozark zigzag salamanders: effects of sex, species and ownership

When both males and females are territorial, spatial and aggressive behaviour can vary between the sexes. We examined differences in exploratory and competitive behaviour between males and females and residents and intruders of two species, the Ozark zigzag (P. angusticlavius) and southern red-backed (P. serratus) salamanders. For exploratory behaviour, males and females differed in distance traveled based on species, but females of both species were significantly more cautious than males about leaving territories. In competition trials, male and female territory residents (owners) did not differ in defensive behaviour, but female intruders were more aggressive than male intruders. Overall, P. angusticlavius showed more aggressive behaviour, explored more, and were less cautious about leaving territories than P. serratus. Female intruders of both species fight harder, potentially to gain territories, and are more cautious about leaving territories, which may indicate that the cost of not having a territory is greater for females.