bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection against Lethal Damage Induced by Ultraviolet Radiation.*
Authors: SCHOENBORN HENRY W.
Published: May 2007

SUMMARY. Sodium pyruvate, glutathione, potassium cyanide, dextrose, sucrose, 3 nucleic acid derivatives, 11 B‐vitamins, and 22 amino acids were tested for their ability to protect Astasia longa against the lethal damage induced by ultraviolet radiation. Compounds which protected when added to a cell suspension just before irradiation were cystine, phenylalanine, tryptophan, tyrosine, adenine, cytidylic acid, uracil, and sodium pyruvate. None of these compounds protected when added immediately after irradiation. Except for phenylalanine, solutions of these compounds afforded protection when used as filters between the ultraviolet source and the flagellates. Cysteine failed to protect when added just before irradiation, but gave good protection when cells were grown in its presence.
Photomotion in Euglena gracilis* I. Photokinesis II. Phototaxis
Authors: WOLKEN J. J. , SHIN E.
Published: May 2007

SYNOPSIS. Photokinesis or the non‐directed rate of swimming of Euglena gracilis for various light intensities was studied. The rate of swimming in white light was found to increase with light intensity until it reaches 0.16 mm./sec. at a saturation of 40 ft. candles, and then decreased with increasing light intensities. Polarized light appeared to be more effective (0.18 mm./sec. at 13 ft. candles) than non‐polarized light.

The action spectrum for photokinesis showed two peaks, a major one near 465 mμ, and another in the neighborhood of 630 mμ, having the values of 0.18 mm./sec. and 0.16 mm./sec. respectively at an intensity of 4 ft. candles.

The action spectrum for phototaxis, or directed orientation, had a peak near 420 mμ and showed a maximum near 490 mμ. Both dark‐grown and dark‐adapted Euglena showed spectral peaks similar to those of the light‐grown cells. For polarized light, the action spectrum had two additional peaks at 468 mμ and 508 mμ. The polarized light effect may indicate more than one light‐absorbing pigment within the “eye spot” or that other pigments within Euglena were absorbing.
A Factual Analysis of Chromosomal Movement in Barbulanympha
Authors: CLEVELAND L. R.
Published: May 2007

SYNOPSIS. The role of eleven different types of achromatic figures in chromosomal movement of Barbulanympha is analyzed. When only one pole is present, no chromosomes are ever connected with it, and hence they do not move. The chromosomes go through their usual life cycle including pairing, but remain in the parent nucleus, which, of course, does not divide. When two poles are present with only one pole near the nucleus, the poles, which are the distal ends of the elongate centrioles, do not cooperate in the formation of a central spindle and the chromosomal behavior is just as if there were only one pole—no movement. The same is true when more than two poles are present with only one near the nucleus.

Unless a central spindle is present, movement of chromosomes never occurs. However, when many central spindles are present, sister chromosomes may separate and move to poles which are not directly connected by a central spindle. In other words, sisters may separate without moving along a central spindle.

In binucleate cells with one central spindle the chromosomes of one nucleus move to the poles, but those of the other do not. Movement always occurs in the nucleus that has its nuclear membrane depressed by the central spindle. When two or more central spindles are present, the chromosomes of both nuclei may move to the poles.
Coprozoic Protozoa from Wyoming Mammals
Authors: NOBLE GLENN A.
Published: May 2007

SYNOPSIS. Coprozoic protozoa from elk, bison, bear, moose, coyote, marmot, cattle, horse, sheep and man were kept in feces at 4° C. for 2–6 months. During that time in most of the samples there developed the flagellates Cercomonas sp., Copromonas ruminantium and Monas communis; the amoebae Vahlkampfia sp. and Sappinia diploidea, and ciliates of the Nyctotherus type, and an unidentified smaller species. There was a correlation between numbers of protozoa and bacteria. The same species of protozoa in soil or in soil mixed with boiled feces failed to live. Coprozoic protozoa may require certain essential metabolites from bacteria as do true parasites. The wide variation in appearance of cysts made it practically impossible to identify the protozoa with certainty in that stage. Reliance had to be on motile forms which readily developed in the cold cultures.
Euryhaline Chrysomonads: Nutrition and Toxigenesis in Prymnesium parvum, with Notes on Isochrysis galbana and Monochrysis lutheri
Authors: McLAUGHLIN J. J. A.
Published: May 2007

SYNOPSIS. The nutritional requirements of 3 isolates of Prymnesium parvum (2 Israeli, 1 Scottish) included vitamin B12 and thiamine. For comparison, 2 other brackish chrysomonads were studied: Monochrysis lutheri isolated by Droop in Scotland and Isochrysis galbana purified by McLaughlin from a culture obtained from the Plymouth laboratory.

The isolates of Prymnesium parvum and Isochrysis galbana had a molecular B12 specificity like Ochromonas malhamensis: no response to Factor B, pseudovitamin B12, Factor A or Factor H. M. lutheri, in contrast, responded to pseudovitamin B12, Factor H, and Factor A.

Thiamine was essential; 1.0 μg.% allowed full growth of P. parvum. The NaCl concentration for good growth was 0.3–5.0%; growth was possible from 6–12%. Dark growth was not achieved.

Ammonia, as suggested from its use in suppressing outbreaks of P. parvum, was sharply inhibitory, less so at high concentrations of NaCl or at acid pH.

Nitrate, ammonia, arginine, asparagine, methionine, histidine, alanine, glycine, serine, proline, leucine, isoleucine, tyrosine, aspartic and glutamic acids, acetylurea, and creatine served as nitrogen sources in both acid and alkaline media.

The phosphate requirement of P. parvum and M. lutheri and Isochrysis galbana was satisfied by inorganic phosphate, commercial glycerophosphate, yeast adenylic acid, cytidylic acid, monoethyl phosphate, and riboflavin monophosphate.

Laboratory cultures in defined media of the isolates of P. parvum were toxigenic to Lebistes and Gambusia. Culture fluids from alkaline media were more toxic than those from acid media, as previously noted in Israel.

Culture media suitable for production of large quantities of these organisms were developed.
On the Parasitic Protozoa of Liberia. I. Coccidia of Some Small Mammals.
Authors: BRAY R. S.
Published: May 2007

SYNOPSIS. Four new species of Eimeria are described from small mammals in Liberia. These are: E. levinei, sp. nov. from a free‐tailed bat, E. firestonei, sp. nov., and E. milleri, sp. nov., from a shrew, and E. putevelata, sp. nov., from a striped grass mouse.
A Study of the Regeneration Pattern of Euplotes eurystomus*
Authors: YOW FRANCIS W.
Published: May 2007

SYNOPSIS. Euplotes eurystomus Wrzesniowski was cultured on bacterial media with Tetrahymena pyriformis serving as the food organism. Animals were injured with various types of operations using the Chambers' micromanipulator. These animals were followed during the course of their regeneration using various nuclear stains, silver impregnation techniques and vital staining methods. It was found that two cirral fields arose as a result of injury removing one or more of the locomotor organelles and that the posterior field was soon resorbed, while the anterior one replaced all of the old cirri of the regenerating animal. In addition, in response to this sort of injury, complete nuclear reorganization took place. Animals which were injured in a manner not affecting the locomotor organelles directly, responded by proliferating a fine network in the area of injury. This network seemed to reinforce the injured area and persisted until the next binary fission of the animal. No nuclear reorganization took place in these cases.
Stentor introversus, n.sp.*
Authors: TARTAR VANCE
Published: May 2007

SYNOPSIS. A new species of Stentor is described, a fresh water form, medium sized, with cerulean blue pigment, and characterized by retractable feeding organelles.
Notes on the biology of Trypanosoma ambystomae Lehmann, 1954. II. The Life Cycle in the Invertebrate Host.
Authors: LEHMANN DONALD L.
Published: May 2007

SYNOPSIS. The leech, Erpobdella sp., is a suitable invertebrate host for Trypanosoma ambystomae. The developmental cycle involves a mononucleate, rounded body derived from the bloodstream form; this body then transforms into a large plump crithidia. Subsequent divisions yield medium crithidia, small crithidia, and ultimately, metacyclic trypanosomes.
Photographs of Fertilization in the Smaller Species of Trichonympha
Authors: CLEVELAND L. R.
Published: May 2007

SYNOPSIS. The photographs illustrate male and female gametes before fertilization, several progressive stages in the entrance of the male gamete into the cytoplasm of the female, cytoplasmic fusion of gametes, loss of extranuclear organelles of male gamete, retention of extranuclear organelles of female gamete, movement of pronucleus of male gamete to that of female, progressive stages in fusion of pronuclei, and the formation of the zygote which possesses the extranuclear organelles of the female gamete. Some abortive attempts at fertilization, resulting from failure of gametes to differentiate, are shown.
A Malaria Parasite of the Hippopotamus
Authors: GARNHAM P. C. C.
Published: May 2007

SYNOPSIS. A new species of Hepatocystis (H. hippopotami) is described from the blood and liver of a Rhodesian hippopotamus (Hippopotamus amphibius). Its relationship with other members of the genus is briefly discussed.
Early computerized tomography accurately determines the presence or absence of scaphoid and other fractures
Authors: Cruickshank Jaycen , Meakin Alex , Breadmore Ross , Mitchell David , Pincus Steven , Hughes Thomas , Bently Bronwyn , Harris Mark , Vo Austin
Published: May 2007

Objective:  To validate the use of early CT in predicting scaphoid fracture and other fractures in patients with suspected scaphoid fracture.

Method:  A prospective observational study of adult patients with a diagnosis of clinical scaphoid fracture presenting to a regional ED. Patients were immobilized in a scaphoid plaster and had a CT (wrist and carpals) same or next day. The gold standard used was the diagnosis on Day 10 with clinical examination and X‐rays, with MRI performed in patients with persistent tenderness but normal X‐rays.

Results:  Forty‐seven patients completed the study protocol from September 2004 until February 2006. For all fractures, early CT had a 96.8% negative predictive value and 100% positive predictive value (94.4% sensitive, 100% specific). No scaphoid fracture was missed by early CT. One patient had a trapezium fracture on CT, with a coexistent subtle capitate fracture only detected on MRI.

Conclusion:  Early CT scans show promise in the diagnosis of scaphoid and other fractures of the wrist and carpals. Further study is warranted to validate early CT in clinical scaphoid fracture as an alternative to other early advanced imaging, or plaster immobilization and 2 week review.
High-Level Production of Beta-Carotene in
Saccharomyces cerevisiae
by Successive Transformation with Carotenogenic Genes from
Xanthophyllomyces dendrorhous
Authors: Verwaal René , Wang Jing , Meijnen Jean-Paul , Visser Hans , Sandmann Gerhard , van den Berg Johan A. , van Ooyen Albert J. J.
Published: May 2007

To determine whether
Saccharomyces cerevisiae
can serve as a host for efficient carotenoid and especially β-carotene production, carotenogenic genes from the carotenoid-producing yeast
Xanthophyllomyces dendrorhous
were introduced and overexpressed in
S. cerevisiae
. Because overexpression of these genes from an episomal expression vector resulted in unstable strains, the genes were integrated into genomic DNA to yield stable, carotenoid-producing
S. cerevisiae
cells. Furthermore, carotenoid production levels were higher in strains containing integrated carotenogenic genes. Overexpression of
crtYB
(which encodes a bifunctional phytoene synthase and lycopene cyclase) and
crtI
(phytoene desaturase) from
X. dendrorhous
was sufficient to enable carotenoid production. Carotenoid production levels were increased by additional overexpression of a homologous geranylgeranyl diphosphate (GGPP) synthase from
S. cerevisiae
that is encoded by
BTS1
. Combined overexpression of
crtE
(heterologous GGPP synthase) from
X. dendrorhous
with
crtYB
and
crtI
and introduction of an additional copy of a truncated 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene (
tHMG1
) into carotenoid-producing cells resulted in a successive increase in carotenoid production levels. The strains mentioned produced high levels of intermediates of the carotenogenic pathway and comparable low levels of the preferred end product β-carotene, as determined by high-performance liquid chromatography. We finally succeeded in constructing an
S. cerevisiae
strain capable of producing high levels of β-carotene, up to 5.9 mg/g (dry weight), which was accomplished by the introduction of an additional copy of
crtI
and
tHMG1
into carotenoid-producing yeast cells. This transformant is promising for further development toward the biotechnological production of β-carotene by
S. cerevisiae
.
Localization of RHO-4 Indicates Differential Regulation of Conidial versus Vegetative Septation in the Filamentous Fungus
Neurospora crassa
Authors: Rasmussen Carolyn G. , Glass N. Louise
Published: May 2007

rho-4
mutants of the filamentous fungus
Neurospora crassa
lack septa and asexual spores (conidia) and grow slowly. In this report, localization of green fluorescent protein-tagged RHO-4 is used to elucidate the differences in factors controlling RHO-4 localization during vegetative growth versus asexual development. RHO-4 forms a ring at incipient vegetative septation sites that constricts with the formation of the septum toward the septal pore; RHO-4 persists around the septal pore after septum completion. During the formation of conidia, RHO-4 localizes to the primary septum but subsequently is relocalized to the cytoplasm after the placement of the secondary septum. Cytoplasmic localization and inactivation of RHO-4 are mediated by a direct physical interaction with RDI-1, a RHO guanosine nucleotide dissociation inhibitor. Inappropriate activation of the cyclic AMP-dependent protein kinase A pathway during vegetative growth causes mislocalization of RHO-4 away from septa to the cytoplasm, a process which was dependent upon RDI-1. An adenylate cyclase
cr-1
mutant partially suppresses the aconidial defect of
rho-4
mutants but only rarely suppresses the vegetative septation defect, indicating that conidial septation is negatively regulated by CR-1. These data highlight the differences in the regulation of septation during conidiation versus vegetative septation in filamentous fungi.
Histidine Auxotrophy in Commensal and Disease-Causing Nontypeable
Haemophilus influenzae
Authors: Juliao Patricia C. , Marrs Carl F. , Xie Jingping , Gilsdorf Janet R.
Published: May 2007

Histidine biosynthesis is one of the best studied metabolic pathways in bacteria. Although this pathway is thought to be highly conserved within and between bacterial species, a previous study identified a genetic region within the histidine operon (
his
) of nontypeable strains of
Haemophilus influenzae
(NTHI) that was more prevalent among otitis media strains than among throat commensal NTHI strains. In the present study, we further characterized this region and showed that genes in the complete his operon (
hisG
, -
D
, -
C
, -
NB
, -
H
, -
A
, -
F
, and -
IE
) are >99% conserved among four fully sequenced NTHI strains, are present in the same location in these four genomes, and are situated in the same gene order. Using PCR and dot blot hybridization, we determined that the
his
operon was significantly more prevalent in otitis media NTHI strains (106/121; 87.7%) than in throat strains (74/137; 54%) (prevalence ratio, 1.62;
P
< 0.0001), suggesting a possible role in middle ear survival and/or acute otitis media. NTHI strains lacking the
his
operon showed attenuated growth in histidine-restricted media, confirming them as
his
-negative auxotrophs. Our results suggest that the ability to make histidine is an important factor in bacterial growth and survival in the middle ear, where nutrients such as histidine may be found in limited amounts. Those isolates lacking the histidine pathway were still able to survive well in the throat, which suggests that histidine is readily available in the throat environment.
Low Concentrations of Bile Salts Induce Stress Responses and Reduce Motility inBacillus cereusATCC 14570
Authors: Kristoffersen Simen M. , Ravnum Solveig , Tourasse Nicolas J. , Økstad Ole Andreas , Kolstø Anne-Brit , Davies William
Published: May 2007

Tolerance to bile salts was investigated in fortyBacillus cereusstrains, including 17 environmental isolates, 11 dairy isolates, 3 isolates from food poisoning outbreaks, and 9 other clinical isolates. Growth of all strains was observed at low bile salt concentrations, but no growth was observed on LB agar plates containing more than 0.005% bile salts. Preincubation of theB. cereustype strain, ATCC 14579, in low levels of bile salts did not increase tolerance levels.B. cereusATCC 14579 was grown to mid-exponential growth phase and shifted to medium containing bile salts (0.005%). Global expression patterns were determined by hybridization of total cDNA to a 70-mer oligonucleotide microarray. A general stress response and a specific response to bile salts were observed. The general response was similar to that observed in cultures grown in the absence of bile salts but at a higher (twofold) cell density. Up-regulation of several putative multidrug exporters and transcriptional regulators and down-regulation of most motility genes were observed as part of the specific response. Motility experiments in soft agar showed that motility decreased following bile salts exposure, in accordance with the transcriptional data. Genes encoding putative virulence factors were either unaffected or down-regulated.
Two ABC Transporter Operons and the Antimicrobial Resistance Gene
mtrF
Are
pilT
Responsive in
Neisseria gonorrhoeae
Authors: Friedrich Alexandra , Arvidson Cindy G. , Shafer William M. , Lee Eun-Hee , So Magdalene
Published: May 2007

Retraction of type IV pili is mediated by PilT. We show that loss of
pilT
function leads to upregulation of
mtrF
(
m
ultiple
t
ransferable
r
esistance) and two operons encoding putative ABC transporters in
Neisseria gonorrhoeae
MS11. This effect occurs indirectly through the transcriptional regulator FarR, which until now has been shown to regulate only
farAB
.
l
-Glutamine can reverse
pilT
downregulation of the ABC transporter operons and
mtrF
.
Identical, Independent, and Opposing Roles of ppGpp and DksA in
Escherichia coli
Authors: Magnusson Lisa U. , Gummesson Bertil , Joksimović Predrag , Farewell Anne , Nyström Thomas
Published: May 2007

The recent discovery that the protein DksA acts as a coregulator of genes controlled by ppGpp led us to investigate the similarities and differences between the relaxed phenotype of a ppGpp-deficient mutant and the phenotype of a strain lacking DksA. We demonstrate that the absence of DksA and ppGpp has similar effects on many of the observed phenotypes but that DksA and ppGpp also have independent and sometimes opposing roles in the cell. Specifically, we show that overexpression of DksA can compensate for the loss of ppGpp with respect to transcription of the promoters P

uspA

, P

livJ

, and P

rrnBP1

as well as amino acid auxotrophy, cell-cell aggregation, motility, filamentation, and stationary phase morphology, suggesting that DksA can function without ppGpp in regulating gene expression. In addition, ppGpp and DksA have opposing effects on adhesion. In the course of our analysis, we also discovered new features of the relaxed mutant, namely, defects in cell-cell aggregation and motility.
Global Transcriptional Analysis of
Streptococcus mutans
Sugar Transporters Using Microarrays
Authors: Ajdić Dragana , Pham Vi T. T.
Published: May 2007

The transport of carbohydrates by
Streptococcus mutans
is accomplished by the phosphoenolpyruvate-phosphotransferase system (PTS) and ATP-binding cassette (ABC) transporters. To undertake a global transcriptional analysis of all
S. mutans
sugar transporters simultaneously, we used a whole-genome expression microarray. Global transcription profiles of
S. mutans
UA159 were determined for several monosaccharides (glucose, fructose, galactose, and mannose), disaccharides (sucrose, lactose, maltose, and trehalose), a β-glucoside (cellobiose), oligosaccharides (raffinose, stachyose, and maltotriose), and a sugar alcohol (mannitol). The results revealed that PTSs were responsible for transport of monosaccharides, disaccharides, β-glucosides, and sugar alcohol. Six PTSs were transcribed only if a specific sugar was present in the growth medium; thus, they were regulated at the transcriptional level. These included transporters for fructose, lactose, cellobiose, and trehalose and two transporters for mannitol. Three PTSs were repressed under all conditions tested. Interestingly, five PTSs were always highly expressed regardless of the sugar source used, presumably suggesting their availability for immediate uptake of most common dietary sugars (glucose, fructose, maltose, and sucrose). The ABC transporters were found to be specific for oligosaccharides, raffinose, stachyose, and isomaltosaccharides. Compared to the PTSs, the ABC transporters showed higher transcription under several tested conditions, suggesting that they might be transporting multiple substrates.
QseA and GrlR/GrlA Regulation of the Locus of Enterocyte Effacement Genes in EnterohemorrhagicEscherichia coli
Authors: Russell Regan M. , Sharp Faith C. , Rasko David A. , Sperandio Vanessa
Published: May 2007

Transcription of the locus of enterocyte effacement (LEE) genes in enterohemorrhagicEscherichia coli(EHEC) is regulated by the LEE-encoded Ler and GrlR/GrlA proteins as well as the non-LEE-encoded regulator QseA. This work demonstrates that GrlR/GrlA activateLEE2transcription in a Ler-independent fashion, whereas transcription ofgrlRAis activated by QseA in both Ler-dependent and -independent manners.
Nitric oxide synthase-derived plasma nitrite predicts exercise capacity
Authors: Rassaf Tienush , Lauer Thomas , Heiss Christian , Balzer Jan , Mangold Sarah , Leyendecker Thorsten , Rottler Jessica , Drexhage Christine , Meyer Christian , Kelm Malte
Published: May 2007

Background:

Nitrite is the main oxidation product of nitric oxide (NO) in plasma. It sensitively reflects changes in endothelial NO synthase (eNOS) activity under fasting conditions and serves as an endocrine NO donor, contributing to the regulation of blood flow through reaction with haemoglobin. As NO is necessary to maintain an adequate vascular response to the increased demands of blood flow, it is believed to be important for vasodilation induced by exercise.

Objective:

To investigate whether the capacity of the vasculature to produce nitrite is associated with exercise performance.

Design:

With the use of chemiluminescence detection, nitrite concentrations in 55 healthy subjects (mean (SEM) age 40 (2) years; 22 men) were studied before and after an exercise test, and endothelial function was determined by measuring flow-mediated dilation of the brachial artery using high-resolution ultrasound. In a subset of subjects, the NOS inhibitor,NG-monomethyl-l-arginine, was applied to elucidate the effect of eNOS on changes in nitrite.

Results:

Exercise significantly (p<0.001) increased plasma nitrite from 97 (6) to 125 (8) nM. The relative increase in plasma nitrite was related to flow-mediated dilation (6.1 (0.3)%; r = 0.36; p = 0.01).NG-Monomethyl-l-arginine blocked increases in nitrite. Post-exercise nitrite concentration correlated with exercise performance, as determined by maximally reached stress power (r = 0.37; p<0.007), and inversely with age. Multivariate analysis showed that both age and post-exercise nitrite concentration were independent predictors of stress endurance and power.

Conclusion:

The results suggest a role for plasma nitrite in the adaptation of haemodynamics during exercise. An impaired increase in plasma nitrite may limit exercise capacity.
Systemic α-adrenergic and nitric oxide inhibition on basal limb blood flow: effects of endurance training in middle-aged and older adults
Authors: Sugawara Jun , Komine Hidehiko , Hayashi Koichiro , Yoshizawa Mutsuko , Otsuki Takeshi , Shimojo Nobutake , Miyauchi Takashi , Yokoi Takashi , Maeda Seiji , Tanaka Hirofumi
Published: May 2007

Endurance training improves endothelium-dependent vasodilation, yet it does not increase basal blood flow in the legs. We determined the effects of a 3-mo aerobic exercise intervention on basal leg blood flow and α-adrenergic vasoconstriction and nitric oxide (NO) release in seven apparently healthy middle-aged and older adults (60 ± 3 yr). Basal femoral artery blood flow (via Doppler ultrasound) (pretraining: 354 ± 29; posttraining: 335 ± 34 ml/min) and vascular conductance did not change significantly with the exercise training. Before the exercise intervention, femoral artery blood flow increased 32 ± 16% with systemic α-adrenergic blockade (with phentolamine) ( P < 0.05), and the addition of nitric oxide synthase (NOS) inhibition using NG-monomethyl-l-arginine (l-NMMA) did not affect femoral artery blood flow. After training was completed, femoral artery blood flow increased 47 ± 7% with α-adrenergic blockade ( P < 0.01) and then decreased 18 ± 7% with the subsequent administration of l-NMMA ( P < 0.05). Leg vascular conductance showed a greater α-adrenergic blockade-induced vasodilation (+1.7 ± 0.5 to +3.0 ± 0.5 units, P < 0.05) as well as NOS inhibition-induced vasoconstriction (−0.8 ± 0.4 to −2.7 ± 0.7 units, P < 0.05) after the exercise intervention. Resting plasma norepinephrine concentration significantly increased after the training. These results suggest that regular aerobic exercise training enhances NO bioavailability in middle-aged and older adults and that basal limb blood flow does not change with exercise training because of the contrasting influences of sympathetic nervous system activity and endothelium-derived vasodilation on the vasculature.
Inhibition of p38 MAPK and AMPK restores adenosine-induced cardioprotection in hearts stressed by antecedent ischemia by altering glucose utilization
Authors: Jaswal Jagdip S. , Gandhi Manoj , Finegan Barry A. , Dyck Jason R. B. , Clanachan Alexander S.
Published: May 2007

p38 mitogen-activated protein kinase (MAPK) and 5′-AMP-activated protein kinase (AMPK) are activated by metabolic stresses and are implicated in the regulation of glucose utilization and ischemia-reperfusion (IR) injury. This study tested the hypothesis that inhibition of p38 MAPK restores the cardioprotective effects of adenosine in stressed hearts by preventing activation of AMPK and the uncoupling of glycolysis from glucose oxidation. Working rat hearts were perfused with Krebs solution (1.2 mM palmitate, 11 mM [3H/14C]glucose, and 100 mU/l insulin). Hearts were stressed by transient antecedent IR (2 × 10 min I/5 min R) before severe IR (30 min I/30 min R). Hearts were treated with vehicle, p38 MAPK inhibitor (SB-202190, 10 μM), adenosine (500 μM), or their combination before severe IR. After severe IR, the phosphorylation (arbitrary density units) of p38 MAPK and AMPK, rates of glucose metabolism (μmol·g dry wt−1·min−1), and recovery of left ventricular (LV) work (Joules) were similar in vehicle-, SB-202190- and adenosine-treated hearts. Treatment with SB-202190 + adenosine versus adenosine alone decreased p38 MAPK (0.03 ± 0.01, n = 3 vs. 0.48 ± 0.10, n = 3, P < 0.05) and AMPK (0.00 ± 0.00, n = 3 vs. 0.26 ± 0.08, n = 3 P < 0.05) phosphorylation. This was accompanied by attenuated rates of glycolysis (1.51 ± 0.40, n = 7 vs. 3.95 ± 0.65, n = 7, P < 0.05) and H+production (2.12 ± 0.76, n = 7 vs. 6.96 ± 1.48, n = 7, P < 0.05), and increased glycogen synthesis (1.91 ± 0.25, n = 6 vs. 0.27 ± 0.28, n = 6, P < 0.05) and improved recovery of LV work (0.81 ± 0.08, n = 7 vs. 0.30 ± 0.15, n = 8, P < 0.05). These data indicate that inhibition of p38 MAPK abolishes subsequent phosphorylation of AMPK and improves the coupling of glucose metabolism, thereby restoring adenosine-induced cardioprotection.
Microvascular network remodeling in dura mater of ovariectomized pigs: role for angiopoietin-1 in estrogen-dependent control of vascular stability
Authors: Glinskii Olga V. , Abraha Tsghe W. , Turk James R. , Rubin Leona J. , Huxley Virginia H. , Glinsky Vladislav V.
Published: May 2007

Estrogen is a key regulator of vascular responses and angioadaptation in multiple organs and tissues, including brain. However, the consequences of a loss of ovarian steroid hormone secretion on the status of microvascular networks in brain and meninges are largely unknown. Here, using the perfused dura mater model coupled with high-resolution digital epifluorescence and laser scanning confocal microscopy and computer-assisted morphometric analysis, we demonstrate that cessation of ovarian hormone production causes dramatic vascular remodeling in meningeal microvascular networks characterized by a threefold decrease in microvessel density and capillary rarefaction and an almost fourfold increase in vascular permeability. These changes were accompanied by a significant decrease in angiopoietin-1 (Ang-1) expression and Ang-1/Tie-2 ratio (1.4-fold, P < 0.01, and 1.5-fold, P < 0.05, respectively) in ovariectomized animals compared with intact females, but no changes were detected in the expression of estrogen receptors (ER)-α and -β. We conclude that estrogen-dependent control of Ang-1 expression plays an important role in stabilizing meningeal microvessel and maintaining healthy microvascular networks.
Lipid A fraction of LPS induces a discrete MAPK activation in acute lung injury
Authors: Fang Wen-Feng , Cho Jae Hwa , He Qianbin , Lin Meng-Chih , Wu Chao-Chien , Voelkel Norbert F. , Douglas Ivor S.
Published: May 2007

Lipopolysaccharide (LPS) induces acute lung injury (ALI) via Toll-like receptor 4 (TLR4)-mediated MAPK activation. The lipid A fraction of LPS is considered to be the active moiety, but whether the lipid A-TLR4 interaction accounts completely for ALI-associated MAPK activation in vivo has not been determined. The lipid A fraction of LPS induces a discrete MAPK activation pattern in murine ALI. Mice (C57BL/6J, C3H/HeJ) were treated with intratracheal instillations of purified lipid A or LPS (10, 30, and 100 μg per mouse) or vehicle. ALI was assessed by histology. Chromogenic myeloperoxidase (MPO) activity was measured in lung homogenates. MAPK expression was quantified by immunoblotting. In vitro ERK inhibitor studies using thioglycollate-elicited macrophages were also performed. MPO increased in a dose- and time-responsive fashion. Notably, MPO was 2.4-fold greater after lipid A compared with LPS and vehicle at 6 h after instillation (lipid A, 0.88 ± 0.25 vs. LPS, 0.37 ± 0.21 optical density units·min−1·mg−1; P < 0.05). However, ALI scores were comparable at 6 and 24 h between LPS and lipid A. MPO was also comparable in vehicle-treated or C3H/HeJ mice treated with LPS or lipid A at 6 and 24 h. Phospho-ERK activation was pronounced at 6 and 24 h after lipid A but not LPS treatment. In vitro studies confirmed the relationship between phospho-ERK activation and cytokine expression in macrophage stimulated with either LPS or lipid A. Compared with whole LPS, the lipid A fraction is associated with amplified whole lung MPO and ERK activation 6 h after intratracheal instillation in mice.
Northern Purgatives, Southern Restoratives: Ming Medical Regionalism
Authors: Hanson Marta E.
Published: May 2007

Physicians during the Ming dynasty (1368—1644) understood that the Chinese empire was geographically diverse. They observed that their patients were corporeally and physiologically heterogeneous. They interpreted this ecological and human diversity within the reunited Ming Empire according to both an ancient northwest-southeast axis and a new emphasis on north versus south. The geographic distinctions—northern and southern (nanbei 南北) as well as northwestern (xibei 西北) and southeastern (dongnan 東南)—similarly helped explain doctrinal and therapeutic divergences within the literate sector of Chinese medicine. They thought about ecological, climatic, and human variation within the framework of a uniquely Chinese northwest-southeast polarity with roots in Chinese mythology and the Inner Canon ef the Yellow Emperor. They also thought in terms of a north-em and southern split in medicine, which the Yuan scholar Dai Liang 戴良 (1317—1383) explicitly mentioned in his writings. The Ming physicians who discussed medical regionalism mostly asserted, however, the opposite; namely their own impartiality as medical authorities for all of China. Nevertheless, their essays on regionalism reveal considerable tensions, fissures, and conflicts in the literate sector of Ming medicine.
Going Beyond Elite Medical Traditions: The Case of Chandshi
Authors: Mukharji Projit Bihari
Published: May 2007

The historian's overwhelming reliance on textual sources has kept the tradition of 'Chandshi' outside the view of the rich corpus of South Asian medical historiography that has developed of late. By supplementing the scant textual evidence by personal interviews and sittings in the clinics of these physicians, I seek to re-construct the history of this little-known, nontextual medical tradition practised by members of a socially dis-privileged caste group. By studying the present modes of self-presentation, I suggest that the search for status and legitimacy may have, in the past, led physicians of this system to speak of themselves as ayurvedic rather than Chandshipractitioners.
Preservation and Progress: Using Tibet an Medicine as a Model to Define a Progressive Role for Traditional Asian Medicine in Modern Healthcare
Authors: Tokar Eliot
Published: May 2007

The history of Tibetan medicine's development provides an excellent model for planning the appropriate utilisation of 'foreign' medical systems and traditions within a new culture that incorporates progressive approaches for the use of both medical pluralism and integration. This history takes on increasing relevance in the modern world as the practice of Tibetan medicine and other forms of traditional Asian medicine have been spreading in the West where they have been faced with commoditisation and the hegemony of biomedicine. In the face of modern globalization, certain key questions have yet to be sufficiently addressed. How can systems of traditional Asian medicine be incorporated into western cultures in a manner that permits them to contribute to our understanding of health and disease while allowing them to retain their own integrity? How can they be utilised to aid in the solution of public health problems that exist in the West? What should be the proper interaction between traditional Asian medical systems (e.g., Tibetan medicine) and biomedicine? To determine the answer to these and other vital questions, we must take into account the many cultural, political, economic and scientific issues that affect the state of both public health and individual healthcare.
Buddhism and the Historicising of Medicine in Thirteenth-Century Tibet
Authors: Garrett Frances
Published: May 2007

This article considers a Tibetan anthology, the Eighteen Additional Practices (Cha lag bco brgyad), that includes some of the earliest indigenous Tibetan medical works still extant, and examines more closely its first text, a history of the Four Tantras. Several of these works display an explicit concern to show medicine to be part of Buddhist history. Other texts in the collection exhibit the heavy influence of what we might call religious practice on the work of medical healing. The anthology's first text articulates an explicit connection between Tibetan medical literature and Indian Buddhism. This article compares this work's structure and content to other Tibetan medical histories and addresses its role in early medical history.
Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia
Authors: O'Hare Thomas , Eide Christopher A. , Deininger Michael W. N.
Published: May 2007

Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism of acquired imatinib resistance in patients with chronic myeloid leukemia (CML). Here we examine predisposing factors underlying acquisition of KD mutations, evidence for acquisition of mutations before and during therapy, and whether the detection of a KD mutation universally implies resistance. We also provide a perspective on how the second-line Abl inhibitors dasatinib and nilotinib are faring in the treatment of imatinib-resistant CML, especially in relation to specific KD mutations. We discuss the growing importance of the multi-inhibitor–resistant 315T>I mutant and the therapeutic potential that a 315T>I inhibitor would have. Last, we assess the potential of Abl kinase inhibitor combinations to induce stable responses even in advanced CML and interpret the emerging data in the context of CML pathogenesis.
Interleukin-6–dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer
Authors: Löffler Dennis , Brocke-Heidrich Katja , Pfeifer Gabriele , Stocsits Claudia , Hackermüller Jörg , Kretzschmar Antje K. , Burger Renate , Gramatzki Martin , Blumert Conny , Bauer Kay , Cvijic Helena , Ullmann A. Kerstin , Stadler Peter F. , Horn Friedemann
Published: May 2007

Signal transducer and activator of transcription 3 (Stat3) is implicated in the pathogenesis of many malignancies and essential for IL-6–dependent survival and growth of multiple myeloma cells. Here, we demonstrate that the gene encoding oncogenic microRNA-21 (miR-21) is controlled by an upstream enhancer containing 2 Stat3 binding sites strictly conserved since the first observed evolutionary appearance of miR-21 and Stat3. MiR-21 induction by IL-6 was strictly Stat3 dependent. Ectopically raising miR-21 expression in myeloma cells in the absence of IL-6 significantly reduced their apoptosis levels. These data provide strong evidence that miR-21 induction contributes to the oncogenic potential of Stat3.
Demographic changes and marker properties affect detection of human population differentiation
Authors: Listman Jennifer B , Malison Robert T , Sughondhabirom Atapol , Yang Bao-Zhu , Raaum Ryan L , Thavichachart Nuntika , Sanichwankul Kittipong , Kranzler Henry R , Tangwonchai Sookjaroen , Mutirangura Apiwat , Disotell Todd R , Gelernter Joel
Published: May 2007

Background

Differentiating genetically between populations is valuable for admixture and population stratification detection and in understanding population history. This is easy to achieve for major continental populations, but not for closely related populations. It has been claimed that a large marker panel is necessary to reliably distinguish populations within a continent. We investigated whether empirical genetic differentiation could be accomplished efficiently among three Asian populations (Hmong, Thai, and Chinese) using a small set of highly variable markers (15 tetranucleotide and 17 dinucleotide repeats).

Results

Hmong could be differentiated from Thai and Chinese based on multi-locus genotypes, but Thai and Chinese were indistinguishable from each other. We found significant evidence for a recent population bottleneck followed by expansion in the Hmong that was not present in the Thai or Chinese. Tetranucleotide repeats were less useful than dinucleotide repeat markers in distinguishing between major continental populations (Asian, European, and African) while both successfully distinguished Hmong from Thai and Chinese.

Conclusion

Demographic history contributes significantly to robust detection of intracontinental population structure. Populations having experienced a rapid size reduction may be reliably distinguished as a result of a genetic drift -driven redistribution of population allele frequencies. Tetranucleotide markers, which differ from dinucleotide markers in mutation mechanism and rate, are similar in information content to dinucleotide markers in this situation. These factors should be considered when identifying populations suitable for gene mapping studies and when interpreting interpopulation relationships based on microsatellite markers.
Human immunodeficiency virus type 1 efficiently binds to human fetal astrocytes and induces neuroinflammatory responses independent of infection
Authors: Li Jinliang , Bentsman Galina , Potash Mary Jane , Volsky David J
Published: May 2007

Background

HIV-1 infects human astrocytesin vitroandin vivobut the frequency of infected cells is low and its biological significance is unknown. In studiesin vitro, recombinant gp120 alone can induce profound effects on astrocyte biology, suggesting that HIV-1 interaction with astrocytes and its functional consequences extend beyond the limited levels of infection in these cells. Here we determined the relative efficiencies of HIV-1 binding and infection in human fetal astrocytes (HFA), mainly at the single cell level, using HIV-1 tagged with green fluorescence protein (GFP)-Vpr fusion proteins, termed HIV-GFP, to detect virus binding and HIV-1 expressing Rev and NefGFP fusion proteins to detect productive infection.

Results

Essentially all HFA in a population bound HIV-GFP specifically and independently of CCR5 and CXCR4. The dynamics of this binding at 37°C resembled binding of an HIV fusion mutant to CD4-positive cells, indicating that most of HIV-GFP arrested infection of HFA at the stage of virus-cell fusion. Despite extensive binding, only about 1% of HFA were detectably infected by HIV-RevGFP or HIV-NefGFP, but this proportion increased to the majority of HFA when the viruses were pseudotyped with vesicular stomatitis virus envelope glycoprotein G, confirming that HFA impose a restriction upon HIV-1 entry. Exposure of HFA to HIV-1 through its native proteins rapidly induced synthesis of interleukin-6 and interleukin-8 with increased mRNA detected within 3 h and increased protein detected within 18 h of exposure.

Conclusion

Our results indicate that HIV-1 binding to human astrocytes, although extensive, is not generally followed by virus entry and replication. Astrocytes respond to HIV-1 binding by rapidly increased cytokine production suggesting a role of this virus-brain cell interaction in HIV-1 neuropathogenesis.
Surfactant protein Bpolymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma
Authors: Puthothu Beena , Forster Johannes , Heinze Jessica , Heinzmann Andrea , Krueger Marcus
Published: May 2007

Background

Surfactant proteins (SP) are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma.

Methods

We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses.

Results

The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034).

Conclusion

Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.
Spontaneous metastasizing mucinous adenocarcinoma in the ileum of a Sprague-Dawley rat
Authors: Chandra M. , Frith C. H.
Published: May 2007

Spontaneous tumours of the rat small intestine are extremely rare. A control Sprague-Dawley male rat from a carcinogenicity bioassay had a mucinous adenocarcinoma in the ileum. Tumour metastasis was observed in the mesenteric lymph node, lung, and seminal vesicles. Gross and histopathological features of this neoplasm are described and discussed.
Bleeding of pulmonate snails
Authors: Cooper J. E.
Published: May 2007

A technique for removing blood (haemolymph) by syringe from African land snails ( Achatina spp.) is described. The method avoids the need for shell perforation or incision of soft tissues and appears to have few adverse effects on the snail.
Helminthic infestation complicated by intussusception in baboons (Papio hamadryas)
Authors: Hennessy A. , Phippard A. F. , Harewood W. J. , Horam C. J. , Horvath J. S.
Published: May 2007

Two juvenile baboons presented with diarrhoea, which did not resolve completely following antibiotic therapy. Ileal intussusception was identified at autopsy in both cases. Trichuris was the only gastrointestinal pathogen for which evidence could be found. This helminth is well-recognized as a cause of intussusception in human infants, but the complication has not been reported previously in non-human primates. It is likely to be fatal if undiagnosed.
Refinement of animal use-assessment and alleviation of pain and distress
Authors: Flecknell P. A.
Published: May 2007

The refinement of experimental techniques represents an important opportunity to improve the welfare of laboratory animals. Objective methods for the assessment of pain and distress in animals are needed before procedures that are claimed to be refinements can be evaluated. The methods currently used for assessment of pain and distress are unsatisfactory, and are often based on uncritical anthropomorphic assumptions. Future developments may enable the establishment of well validated clinical scoring systems, or identification of biochemical or physiological indices of pain or distress. If reliable methods of pain assessment can be developed, then a critical evaluation of the methods available for the alleviation of pain and distress can be undertaken. This article reviews methods of clinical pain assessment in animals, with reference to the techniques used in man. Techniques for pain alleviation are briefly reviewed.
Blood sampled in rats from right ventricle may not always be truly representative of a mixed venous sample
Authors: Guitart R. , Alfaro V. , Roca-Acín J. , Palacios L.
Published: May 2007

Blood samples from the right ventricle (RV) in rats are usually assumed to be representative of mixed venous blood. However, results presented here suggest that this assumption may not be true in all experimental circumstances. Nineteen male Wistar rats were anaesthetized with urethane and mechanically ventilated. The six gases used in the multiple inert gas elimination technique (MIGET) were administered continuously and samples of mixed expired air and blood from the left carotid artery and RV were simultaneously withdrawn. While inert gas concentrations in arterial blood and mixed expired air were almost homogeneous, those obtained from RV blood showed a high variability, specially evident for the less soluble gases in blood. As inert gases are cleared in the lungs according to their solubility in blood and they are only replaced through the lower systemic circulation, higher or lower concentrations found in RV samples than those expected suggests a preferential collection of blood from the lower or upper systemic circulation, respectively.