bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-dependent proteolytic cleavage of STAT3α in ES cells, in mammary glands undergoing forced involution and in breast cancer cell lines
Authors: Matthews James R , Watson Susan MR , Tevendale Maxine CL , Watson Christine J , Clarke Alan R 
Published: February 2007

AbstractBackgroundThe STAT (Signal Transducers and Activators of Transcription) transcription factor family mediates cellular responses to a wide range of cytokines. Activated STATs (particularly STAT3) are found in a range of cancers. Further, STAT3 has anti-apoptotic functions in a range of tumour cell lines. After observing a proteolytic cleavage in STAT3α close to a potential apoptotic caspase protease cleavage site we investigated whether STAT3α might be a caspase substrate.MethodsSTAT3α status was investigatedin vitroin several cell systems:- HM-1 murine embryonic stem (ES) cells following various interventions; IOUD2 murine ES cells following induction to differentiate along neural or adipocyte lineages; and in a number of breast cancer cell lines. STAT3α status was also analysedin vivoin wild type murine mammary glands undergoing controlled, forced involution.ResultsImmunoblotting for STAT3α in HM-1 ES cell extracts detected amino and carboxy terminal species of approximately 48 kDa and 43 kDa respectively – which could be diminished dose-dependently by cell treatment with the nitric oxide (NO) donor drug sodium nitroprusside (SNP). UV irradiation of HM-1 ES cells triggered the STAT3α cleavage (close to a potential caspase protease cleavage site). Interestingly, the pan-caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (z-VAD-FMK) and the JAK2 tyrosine kinase inhibitor AG490 both inhibited cleavage dose-dependently, and cleavage was significantly lower in a heterozygousJAK2knockout ES cell clone. STAT3α cleavage also occurredin vivoin normal murine mammary glands undergoing forced involution, coinciding with a pulse of phosphorylation of residue Y705 on full-length STAT3α. Cleavage also occurred during IOUD2 ES cell differentiation (most strikingly along the neural lineage) and in several human breast cancer cell lines, correlating strongly with Y705 phosphorylation.ConclusionThis study documents a proteolytic cleavage of STAT3α into 48 kDa amino and 43 kDa carboxyl terminal fragments in a range of cell types. STAT3α cleavage occurs close to a potential caspase site, and can be inhibited dose-dependently by SNP, AG490 and z-VAD-FMK. The cleavage seems to be caspase-dependent and requires the phosphorylation of STAT3α at the Y705 residue. This highly regulated STAT3α cleavage may play an important role in modulating STAT3 transcriptional activity.
General practice cooperatives: long waiting times for home visits due to long distances?
Authors: Giesen Paul , van Lin Nieke , Mokkink Henk , van den Bosch Wil , Grol Richard 
Published: February 2007

Abstract
Background
The introduction of large-scale out-of-hours GP cooperatives has led to questions about increased distances between the GP cooperatives and the homes of patients and the increasing waiting times for home visits in urgent cases. We studied the relationship between the patient's waiting time for a home visit and the distance to the GP cooperative. Further, we investigated if other factors (traffic intensity, home visit intensity, time of day, and degree of urgency) influenced waiting times.

Methods
Cross-sectional study at four GP cooperatives. We used variance analysis to calculate waiting times for various categories of traffic intensity, home visit intensity, time of day, and degree of urgency. We used multiple logistic regression analysis to calculate to what degree these factors affected the ability to meet targets in urgent cases.

Results
The average waiting time for 5827 consultations was 30.5 min. Traffic intensity, home visit intensity, time of day and urgency of the complaint all seemed to affect waiting times significantly. A total of 88.7% of all patients were seen within 1 hour. In the case of life-threatening complaints (U1), 68.8% of the patients were seen within 15 min, and 95.6% of those with acute complaints (U2) were seen within 1 hour. For patients with life-threatening complaints (U1) the percentage of visits that met the time target of 15 minuts decreased from 86.5% (less than 2.5 km) to 16.7% (equals or more than 20 km).

Discussion and conclusion
Although home visits waiting times increase with increasing distance from the GP cooperative, it appears that traffic intensity, home visit intensity, and urgency also influence waiting times. For patients with life-threatening complaints waiting times increase sharply with the distance.
Public-private delivery of insecticide-treated nets: a voucher scheme in Volta Region, Ghana
Authors: Kweku Margaret , Webster Jayne , Taylor Ian , Burns Susan , Dedzo McDamien 
Published: February 2007

Abstract

Background
Coverage of vulnerable groups with insecticide-treated nets (ITNs) in Ghana, as in the majority of countries of sub-Saharan Africa is currently low. A voucher scheme was introduced in Volta Region as a possible sustainable delivery system for increasing this coverage through scale-up to other regions. Successful scale-up of public health interventions depends upon optimal delivery processes but operational research for delivery processes in large-scale implementation has been inadequate.

Methods
A simple tool was developed to monitor numbers of vouchers given to each health facility, numbers issued to pregnant women by the health staff, and numbers redeemed by the distributors back to the management agent. Three rounds of interviews were undertaken with health facility staff, retailers and pregnant women who had attended antenatal clinic (ANC).

Results
During the one year pilot 25,926 vouchers were issued to eligible women from clinics, which equates to 50.7% of the 51,658 ANC registrants during this time period. Of the vouchers issued 66.7% were redeemed by distributors back to the management agent. Initially, non-issuing of vouchers to pregnant women was mainly due to eligibility criteria imposed by the midwives; later in the year it was due to decisions of the pregnant women, and supply constraints. These in turn were heavily influenced by factors external to the programme: current household ownership of nets, competing ITN delivery strategies, and competition for the limited number of ITNs available in the country from major urban areas of other regions.

Conclusion
Both issuing and redemption of vouchers should be monitored as factors assumed to influence voucher redemption had an influence on issuing, and vice versa. More evidence is needed on how specific contextual factors influence the success of voucher schemes and other models of delivery of ITNs. Such an evidence base will facilitate optimal strategic decision making so that the delivery model with the best probability of success within a given context is implemented. Rigorous monitoring has an important role to play in the successful scaling-up of delivery of effective public health interventions.
Interrupted coding sequences in Mycobacterium smegmatis: authentic mutations or sequencing errors?
Authors: Deshayes Caroline , Perrodou Emmanuel , Gallien Sebastien , Euphrasie Daniel , Schaeffer Christine , Van-Dorsselaer Alain , Poch Olivier , Lecompte Odile , Reyrat Jean-Marc 
Published: February 2007

Abstract
Background
In silico analysis has shown that all bacterial genomes contain a low percentage of ORFs with undetected frameshifts and in-frame stop codons. These interrupted coding sequences (ICDSs) may really be present in the organism or may result from misannotation based on sequencing errors. The reality or otherwise of these sequences has major implications for all subsequent functional characterization steps, including module prediction, comparative genomics and high-throughput proteomic projects.

Results
We show here, using Mycobacterium smegmatis as a model species, that a significant proportion of these ICDSs result from sequencing errors. We used a resequencing procedure and mass spectrometry analysis to determine the nature of a number of ICDSs in this organism. We found that 28 of the 73 ICDSs investigated correspond to sequencing errors.

Conclusion
The correction of these errors results in modification of the predicted amino acid sequences of the corresponding proteins and changes in annotation. We suggest that each bacterial ICDS should be investigated individually, to determine its true status and to ensure that the genome sequence is appropriate for comparative genomics analyses.
Comparison of the Effects of Hypothermia at 33°C or 35°C after Cardiac Arrest in Rats
Authors: Logue Eric S. , McMichael Melissa J. , Callaway Clifton W. 
Published: February 2007

Abstract
Objectives:
Hypothermia of 32°C–34°C induced after resuscitation from cardiac arrest improves neurologic recovery, but the optimal depth of cooling is unknown. Using a rat model, the authors tested the hypothesis that cooling to 35°C between hours 1 and 24 after resuscitation would improve neurologic outcome as much as cooling to 33°C.
Methods:
Halothane‐anesthetized rats (n= 38) underwent 8 minutes of asphyxial cardiac arrest and resuscitation. Cranial temperature was maintained at 37°C before, during, and after arrest. Between one and 24 hours after resuscitation, cranial temperature was maintained at 33°C, 35°C, or 37°C using computer‐controlled cooling fans and heating lamps. Neurologic scores were measured daily, and rats were killed at 14 days for histologic analysis. Neurons per high‐powered field were counted in the CA1 region of the anterior hippocampus using neuronal nuclear antigen staining.
Results:
After 14 days, 12 of 12 rats (100%) cooled to 33°C, 11 of 12 rats (92%) cooled to 35°C, and ten of 14 rats (71%) cooled to 37°C survived, with hazard of death greater in the rats cooled to 37°C than in the combined hypothermia groups. Neurologic scores were worse in the rats cooled to 37°C than in the hypothermia groups on days 1, 2, and 3. Numbers of surviving neurons were similar between the groups cooled to 33°C and 35°C and were higher than in the group cooled to 37°C.
Conclusions:
These data illustrate that hypothermia of 35°C or 33°C over the first day of recovery improves neurologic scores and neuronal survival after cardiac arrest in rats. The benefit of induced hypothermia of 35°C appears to be similar to the benefit of 33°C.
Randomized Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen Sodium (Bcl-2 antisense) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: O'Brien Susan , Moore Joseph O. , Boyd Thomas E. , Larratt Loree M. , Skotnicki Aleksander , Koziner Benjamin , Chanan-Khan Asher A. , Seymour John F. , Bociek R. Gregory , Pavletic Steve , Rai Kanti R. 
Published: February 2007

PurposeExpression of Bcl-2 protein is associated with chemotherapy resistance and decreased survival in chronic lymphocytic leukemia (CLL). We evaluated whether oblimersen would improve response to chemotherapy in patients with relapsed or refractory CLL.Patients and MethodsPatients had received at least one prior fludarabine-containing regimen and were stratified on the basis of prior fludarabine response, number of prior regimens, and duration of response to last prior therapy. Patients were randomly assigned to 28-day cycles of fludarabine 25 mg/m2/d plus cyclophosphamide 250 mg/m2/d administered intravenously for 3 days with or without oblimersen 3 mg/kg/d as a 7-day continuous intravenous infusion (beginning 4 days before chemotherapy) for up to six cycles. The primary end point was the proportion of patients who achieved complete response (CR) or nodular partial response (nPR).ResultsOf 241 patients randomly assigned, CR/nPR was achieved in 20 (17%) of 120 patients in the oblimersen group and eight (7%) of 121 patients in the chemotherapy-only group (P = .025). Achievement of CR/nPR was correlated with both an extended time to progression and survival (P < .0001). In patients who remained sensitive to fludarabine, oblimersen was associated with a four-fold increase in the CR/nPR rate and a significant survival benefit (P = .05). Oblimersen was frequently associated with thrombocytopenia and, rarely, tumor lysis syndrome and cytokine release reactions; the incidence of opportunistic infections and second malignancies was similar in both groups.ConclusionThe addition of oblimersen to fludarabine plus cyclophosphamide significantly increases the CR/nPR rate in patients with relapsed or refractory CLL (particularly fludarabine-sensitive patients), as well as response duration among patients who achieve CR/nPR.
Post-natal development of the electromotor system in a pulse gymnotid electric fish
Authors: Pereira Ana Carolina , Rodríguez-Cattaneo Alejo , Castelló María E. , Caputi Angel A. 
Published: February 2007

SUMMARYSome fish emit electric fields generated by the coordinated activation of electric organs. Such discharges are used for exploring the environment and for communication. This article deals with the development of the electric organ and its discharge in Gymnotus, a pulse genus in which brief discharges are separated by regular silent intervals. It is focused on the anatomo-functional study of fish sized between 10 and 300 mm from the species of Gymnotus, in which electrogenic mechanisms are best known. It was shown that: (1) electroreception and electromotor control is present from early larval stages; (2) there is a single electric organ from larval to adult stages; (3) pacemaker rhythmicity becomes similar to that of the adult when the body length becomes greater than 45 mm and (4) there is a consistent developmental profile of the electric organ discharge in which waveform components are added according to a programmed sequence. The analysis of these data allowed us to identify three main periods in post-natal development of electrogenesis: (1) before fish reach 55 mm in length, when maturation of neural structures is the main factor determining a characteristic sequence of changes observed in the discharge timing and waveform; (2) between 55 and 100 mm in length, when peripheral maturation of the effector cells and changes in post-effector mechanisms due to the fish's growth determine minor changes in waveform and the increase in amplitude of the discharge and (3) beyond 100 mm in length, when homothetic growth of the fish body explains the continuous increase in electric power of the discharge.
Identification and characterization of a salivary adenosine deaminase from the sand fly Phlebotomus duboscqi, the vector of Leishmania major in sub-Saharan Africa
Authors: Kato Hirotomo , Jochim Ryan C. , Lawyer Phillip G. , Valenzuela Jesus G. 
Published: February 2007

SUMMARY
Two transcripts coding for an adenosine deaminase (ADA) were identified by sequencing a Phlebotomus duboscqi salivary gland cDNA library. Adenosine deaminase was previously reported in the saliva of the sand fly Lutzomyia longipalpis but it was not present in the saliva of the sand flies Phlebotomus papatasi, P. argentipes, P. perniciosus and P. ariasi, suggesting that this enzyme is only present in the saliva of sand flies from the genus Lutzomyia. In the present work, we tested the hypothesis that the salivary gland transcript coding for ADA in Phlebotomus duboscqi, a sister species of Phlebotomus papatasi, produces an active salivary ADA.
Salivary gland homogenates of P. duboscqi converted adenosine to inosine, suggesting the presence of ADA activity in the saliva of this species of sand fly; furthermore, this enzymatic activity was significantly reduced when using either salivary glands of recently blood-fed sand flies or punctured salivary glands, suggesting that this enzyme is secreted in the saliva of this insect. This enzymatic activity was absent from the saliva of P. papatasi. In contrast to other Phlebotomus sand flies, we did not find AMP or adenosine in P. duboscqi salivary glands as measured by HPLC-photodiode array. To confirm that the transcript coding for ADA was responsible for the activity observed in the saliva of this sand fly,we cloned this transcript into a prokaryotic expression vector and produced a soluble and active recombinant protein of approximately 60 kDa that was able to convert adenosine to inosine. Extracts of bacteria transformed with control plasmids did not show this activity. These results suggest that P. duboscqi transcripts coding for ADA are responsible for the activity detected in the salivary glands of this sand fly and that P. duboscqiacquired this activity independently from other Phlebotomus sand flies. This is another example of a gene recruitment event in salivary genes of blood-feeding arthropods that may be relevant for blood feeding and,because of the role of ADA in immunity, it may also play a role in parasite transmission.
Morphometry of retinal vasculature in Antarctic fishes is dependent upon the level of hemoglobin in circulation
Authors: Wujcik Jody M. , Wang George , Eastman Joseph T. , Sidell Bruce D. 
Published: February 2007

SUMMARYWe quantitatively assessed ocular vascular patterns of six Antarctic notothenioid fishes that vary in their expression of the circulating oxygen-binding protein, hemoglobin (Hb). Digital image analyses revealed marked differences in vessel morphometries among notothenioid species. Hemoglobinless (–Hb) icefishes display mean vessel length densities that are greater (Chaenocephalus aceratus, 5.51±0.32 mm mm–2; Champsocephalus gunnari, 5.15±0.50 mm mm–2) than those observed in red-blooded (+Hb) species(Gymnodraco acuticeps, 5.20±0.46 mm mm–2; Parachaenichthyes charcoti, 4.40±0.30 mm mm–2; Trematomus hansoni, 3.94±0.08 mm mm–2; Notothenia coriiceps, 2.48±0.21 mm mm–2). –Hb fishes also have mean vessel diameters that are ∼1.5 times greater than vessel diameters of +Hb species (–Hb,0.193±0.006 mm; +Hb, 0.125±0.005 mm). Vascular density index(VDI), a stereological index that is affected by both vessel number and length, is greatest in –Hb C. aceratus (3.51±0.20) and lowest in +Hb N. coriiceps (1.58±0.14). Among four +Hb species, there is a direct relationship between red blood cell content and retinal vasculature. Hematocrit (Hct) is inversely correlated to vascular density (r2=0.934) and positively correlated to intervessel distance (r2= 0.898) over a &gt;2.3-fold range of Hct. These results indicate that anatomical capacity to supply blood to the retina increases to compensate for decreases in oxygen-carrying capacity of the blood.
Phosphoglucose isomerase genotype affects running speed and heat shock protein expression after exposure to extreme temperatures in a montane willow beetle
Authors: Rank Nathan E. , Bruce Douglas A. , McMillan David M. , Barclay Colleen , Dahlhoff Elizabeth P. 
Published: February 2007

SUMMARYEastern Sierra Nevada populations of the willow beetle Chrysomela aeneicollis commonly experience stressfully high and low environmental temperatures that may influence survival and reproduction. Allele frequencies at the enzyme locus phosphoglucose isomerase (PGI) vary across a climatic latitudinal gradient in these populations, with PGI allele 1 being most common in cooler regions and PGI allele 4 in warmer ones. PGI genotypes differ in heat and cold tolerance and in expression of a 70 kDa heat shock protein. Here we examine genetic, behavioral and environmental factors affecting a performance character, running speed, for willow beetles, and assess effects of consecutive cold and heat exposure on running speed and expression of Hsp70 in the laboratory. In nature, running speed depends on air temperature and is higher for males than females. Mating beetles ran faster than single beetles, and differences among PGI genotypes in male running speed depended on the presence of females. In the laboratory, exposure to cold reduced subsequent running speed, but the amount of this reduction depended on PGI genotype and previous thermal history. Effects of exposure to heat also depended on life history stage and PGI genotype. Adults possessing allele 1 ran fastest after a single exposure to stressful temperature, whereas those possessing allele 4 ran faster after repeated exposure. Larvae possessing allele 4 ran fastest after a single stressful exposure, but running speed generally declined after a second exposure to stressful temperature. The ranking of PGI genotypes after the second exposure depended on whether a larva had been exposed to cold or heat. Effects of temperature on Hsp70 expression also varied among PGI genotypes and depended on type of exposure, especially for adults (single heat exposure, two cold exposures: PGI 1-1&gt;1-4&gt;4-4;other multiple extreme exposures: 4-4&gt;1-4&gt;1-1). There was no consistent association between alleles at other polymorphic enzyme loci and running speed or Hsp70 expression. These data suggest that variation at PGI is associated with considerable plasticity in running speed. Differences in Hsp70 expression among PGI genotypes suggest that the heat-shock response may buffer differences in thermal tolerance and performance among genotypes and help maintain the PGI polymorphism in a thermally variable environment.
Cloacal evaporation: an important and previously undescribed mechanism for avian thermoregulation
Authors: Hoffman Ty C.M. , Walsberg Glenn E. , DeNardo Dale F. 
Published: February 2007

SUMMARY
We present the first experimental evidence that a bird is capable of evaporating enough water from the cloaca to be important for thermoregulation. We measured rates of evaporation occurring from the mouth, the skin, and the cloaca of Inca doves Columbina inca Lesson and Eurasian quail Coturnix coturnix Linnaeus. Inca doves showed no significant increase in cutaneous evaporation in response to curtailment of buccopharyngeal evaporation. Cloacal evaporation in doves was negligible at ambient temperatures of 30°, 35° and 40°C. However, at 42°C, the apportionment of total evaporation in doves was 53.4% cutaneous, 25.4%buccopharyngeal and 21.2% cloacal, with cloacal evaporation shedding, on average, 150 mW of heat. In contrast, the evaporative apportionment in quail at 32°C (the highest ambient temperature tolerated by this species) was 58.2% cutaneous, 35.4% buccopharyngeal and 6.4% cloacal. These results suggest that, for some birds, cloacal evaporation can be controlled and could serve as an important emergency tactic for thermoregulation at high ambient temperatures.