bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVOLUTION OF DAILY TORPOR AND HIBERNATION IN BIRDS AND MAMMALS: IMPORTANCE OF BODY SIZE
Authors: Geiser Fritz 
Published: June 2007

SUMMARY1. The evolution of hibernation and daily torpor in mammals and birds remains a controversial subject. The original view was that use of torpor reflects a primitive thermoregulation, as it occurs in ancestral groups of mammals.2. This view is no longer widely supported. However, the interpretation of a polyphyletic derivation of torpor also has been challenged because of the astonishing similarity of torpor patterns among various orders and even the two classes.3. A recent argument is that mutations required for torpor and hibernation are unlikely to occur simultaneously and that torpor must be plesiomorphic (ancestral), although it is not functionally primitive. Homeothermy is interpreted as a loss of the ability to enter torpor in those groups that could survive without the requirement of heterothermic periods for energy conservation.4. Interestingly, while torpor in mammals occurs in the phylo‐genetically old groups, lending support to the hypothesis of an ancestral derivation of torpor, the opposite is the case for birds. Modern bird groups and ancestral mammal groups contain mainly small species that often rely on fluctuating food supply, whereas modern mammalian orders and ancient bird orders contain the largest species with low energy requirements for maintenance and thermoregulation.5. It is, therefore, possible that not phylogenetic position but size and diet determine the occurrence of heterothermy. Moreover, because endothermy and torpor in birds has apparently evolved separately from that in mammals and because it is possible that daily torpor and hibernation represent two distinct torpor patterns that evolved separately, a convergent evolution of torpor in endotherms cannot be excluded.
EVOLUTION OF THE HUMAN BRAIN: IS BIGGER BETTER?
Authors: Henneberg Maciej 
Published: June 2007

SUMMARY1. The hominid brain has increased approximately three times in size since the Pliocene, but so has the brain of equids. The tripling of hominid brain size has been considered as an indicator of increased mental abilities, as it coincided with the production of tools, weapons and other artefacts of increasing sophistication. No indicators of the increase in equid intelligence are known. Intraspecific correlation between brain size and variously measured ‘intelligence’ is, in modern humans, very weak if not completely absent. With the exception of size, there are no major differences between the anatomy of ape and human brains.2. A study of 297 estimates of body height, 626 estimates of body weight and 276 estimates of the cranial capacity of hominids dated at various periods over the past 5 million years shows that the increase in hominid brain size was paralleled by an increase in body size.3. In a sample of 45 variously dated fossil hominids, brain size correlates isometrically with body size.4. Since the Late Pleistocene (approximately 30000 years ago), human brain size decreased by approximately 10%; yet again, this decrease was paralleled by a decrease in body size.5. Therefore, it may be concluded that the gross anatomy of the hominid brain is not related to its functional capabilities. The large human brain:body size ratio may be a result of the structural reduction of the size of the gastrointestinal tract and, consequently, its musculoskeletal supports. It is related to richer, meat‐based diets and extra‐oral food processing rather than the exceptional increase in the size of the cerebrum. The exceptional mental abilities of humans may be a result of functional rather than anatomical evolution.
LOCATION OF GANGLIOSIDE GM2 ACTIVATOR PROTEIN GENE EXPRESSION IN SHEEP
Authors: Butkus A. , Coghlan JP 
Published: June 2007

SUMMARY1. The present study was aimed at characterizing and establishing the site of production of a ‘novel’ protein isolated in 1988 during the course of studies on sheep renal morphology. This protein has subsequently been identified as the GM2 activator protein (GM2AP).2. The ‘novel’ protein, with an apparent molecular weight of 18–22 kDa and a pi between 4.7 and 4.9, was isolated from enriched granular fractions of sheep kidney cortex using two‐dimensional (2‐D) polyacrylamide gel electrophoresis. Following electroelution, the N‐terminal amino acid sequence was determined and, applying the preferred codon usage formula, an oligodeoxy ribonucleotide probe was constructed for examination of sites of expression of this novel protein using northern analyses and hybridization histochemistry.3. Western blots of the 2‐D gels onto nitrocellulose membranes permitted us to select the appropriate spots for injection into rabbits for production of polyclonal antibodies. The antibodies were used to confirm the sites of protein production using immunohistochemistry.4. Northern analyses revealed that GM2AP mRNA has a widespread distribution in ovine tissues. In the kidney, GM2 was expressed in all major renal arteries and arterioles. In the liver, the expression of the gene was prominent in the hepatic vein and ducts. Antibodies raised against the GM2AP confirmed that the protein was present at the same sites as the mRNA.5. These are the first studies showing the location of GM2 activator gene expression in normal mammalian tissues. The arterial site of production has implications for local action or an important role in membrane integrity throughout the kidney.
STRUCTURE‐FUNCTION RELATIONSHIPS OF ALDOSTERONE SYNTHASE AND 11β‐HYDROXYLASE ENZYMES: IMPLICATIONS FOR HUMAN HYPERTENSION
Authors: Fisher Angela , Davies Eleanor , Fraser Robert , Connell John MC 
Published: June 2007

SUMMARY1. The genes encoding aldosterone synthase (CYP11B2) and 11β‐hydroxylase (CYP11B1) are very similar at the nucleotide level (> 95% homology). Despite this and the corresponding similarity of amino acid sequence, there are considerable differences in functional and substrate specificity of the two enzymes. In the present study we have examined the role of two amino acids that differ between the two enzymes (147 and 248) to determine the difference between aldosterone synthase and 11β‐hydroxylase capacity to 11‐hydroxylate 11‐deoxycorticosterone (DOC).2. Plasmids containing cDNA encoding wild‐type aldosterone synthase, wild‐type 11β‐hydroxylase and mutated forms of aldosterone synthase (D147E and I248T), in which the codons for residues 147 (aspartate exon 3) or 248 (isoleucine exon 4) had been altered to encode the corresponding amino acids (gluta‐mate and threonine respectively) from 11β‐hydroxylase were transiently expressed in non‐steroidogenic COS‐7 cells. All trans‐fections were cotransfected with bovine adrenodoxin. Cells were then incubated with [3H]‐DOC for 48 h and the production of corticosterone (B), 18‐hydroxycorticosterone (18‐OHB) and aldosterone measured by measuring tritriated products using thin layer chromatography.3. Compared with wild‐type aldosterone synthase, the mutated form (D147E) encoding amino acid 147 from lip‐hydroxylase was more efficient in 11β‐hydroxylation of deoxycorticosterone (B:DOC ratio 0.53 ± 0.05 (wild type) to 3.05 ± 0.37 (mutant); P < 0.001). However, 18‐hydroxylation of B and conversion of this steroid into aldosterone were unaffected. There was a 20% increase in the production of aldosterone from DOC (P < 0.05). However, in comparison with wild‐type 11β‐hydroxylase, the mutated aldosterone synthase (D147E) was still less efficient (B:DOC ratio 6.2 ± 0.41). The mutated aldosterone synthase (I248T) encoding amino acid 248 from 11β‐hydroxylase showed no changes in conversion of DOC to B or in the production of aldosterone.4. These data demonstrate that position 147 has an important effect on the efficiency of 11β‐hydroxylation of DOC and indicate that this is a key difference between the two enzymes in determining functional specificity. However, other residues must also contribute to efficiency of 11 ‐hydroxylation of 11β‐hydroxylase. In contrast, amino acid 248, which is one of the few differences between the two enzymes in exon 4, does not affect enzyme efficiency. As altered activity of aldosterone synthase and 11β‐hy‐droxylase has been proposed as an important intermediate phenotype in essential hypertension, such studies will help our understanding of the structure‐function relationships that will be necessary in order to understand how genetic changes may contribute to observed differences in phenotype.
HAEMORPHIN PEPTIDES MAY BE ENDOGENOUS LIGANDS FOR BRAIN ANGIOTENSIN AT4 RECEPTORS
Authors: Moeller Ingrid , Chai Siew Yeen , Smith Ian , Lew Rebecca , Mendelsohn Frederick AO 
Published: June 2007

SUMMARY1. Angiotensin IV (AngIV), the (3–8) fragment of AngII, was previously believed to be an inactive metabolite. However, specific binding sites, termed AT4 receptors, have been identified in the brain and peripheral organs and the peptide has been reported to enhance memory recall in passive avoidance studies and to dilate pial and renal cortical vessels.2. AT4 receptors are distinct from AngII AT1 and AT2 receptors with respect to function, ligand specificity and distribution.3. In the brain, AT4 receptors are abundant in cerebral and cerebellar cortex, hippocampal formation and cholinergic systems, as well as sensory and motor systems. However, the peptide AngIV is low or undetectable in the central nervous system. This led us to search for an alternative peptide ligand of the AT4 receptor.4. The decapeptide LVVYPWTQRF was isolated from cerebral cortex and binds with high affinity to brain AT4 receptors. This peptide sequence corresponds to an internal sequence of (i‐globin and has previously been named LVV‐haemorphin 7.5. Haemorphin may represent a new class of endogenous neuropeptides, some of which interact potently with the brain AT4 receptor to elicit a range of actions.
EFFECTS OF DIURETICS ON RENAL KALLIKREIN GENE EXPRESSION IN RATS
Authors: Penschow Jennifer D. , Bulmer Bronwyn 
Published: June 2007

SUMMARY1. To determine the effects of diuresis and changes in electrolyte balance on kallikrein gene expression, renal kallikrein mRNA levels were correlated with urine volumes, urinary electrolyte levels, haematocrit and plasma electrolyte levels in rats treated with substances with a range of diuretic activities.2. Furosemide and related compounds, benzyl furosemide and isofurosemide, as well as amiloride hydrochloride, chlorothiazide or the vehicle (saline) were administered twice daily for 24 or 72 h to rats housed in metabolic cages.3. Diuresis occurred after each treatment with furosemide, after the initial treatment with benzyl furosemide and did not occur after isofurosemide, amiloride hydrochloride or chlorothiazide.4. Kallikrein gene expression in kidney was increased after 72 h treatment with furosemide, after 24 or 72 h treatment with benzyl furosemide or amiloride hydrochloride and was unchanged after 24 or 72 h treatment with isofurosemide or chlorothiazide, compared with vehicle‐treated controls.5. Plasma urea levels were elevated after 72 h treatment with furosemide, benzyl furosemide and chlorothiazide and plasma chloride was decreased after 24 and 72 h benzyl furosemide. Haematocrits were unchanged. There were no changes in urinary electrolyte levels 72 h after treatment with any of the diuretics.6. Neither diuresis nor measurable changes in plasma or urinary electrolytes correlate with changes in renal kallikrein gene expression after diuretic treatment of rats.
5‐FLUOROURACIL: A PHARMACOLOGICAL PARADIGM IN THE USE OF CYTOTOXICS
Authors: Thomas DM , Zalcberg JR 
Published: June 2007

SUMMARY1. Painstaking progress in drug development is well illustrated by 5‐fluorouracil (5FU), originally designed 40 years ago as a fluorinated analogue of the naturally occurring base uracil. Innovative pharmacokinetic and pharmacodynamic strategies have seen significant clinical improvements for cancer patients over the past decade.2. 5‐Fluorouracil acts by three main mechanisms. Principally, the intermediate metabolite fluorodeoxj uridine monophosphate inhibits a key enzyme in pyrimidine biosynthesis, namely thymidylate synthase (TS). Additionally, 5FU is metabolized to ribo‐ and deoxy‐ribonucleotides, which act as false bases for incorporation into RNA and DNA.3. Biomodulation of 5FU has been attempted with methotrexate (MTX), folinic acid, interferons, cisplatin and radiotherapy. Methotrexate augments the actions of 5FU by inhibiting dihy‐drofolate reductase and decreasing the folate pool required for pyrimidine biosynthesis, inhibiting TS via MTX‐polyglutamate and directly inhibiting purine biosynthesis. Interferons increase steady state concentrations of 5FU. 5‐Fluorouracil enhances the cytotoxicity of cisplatin and radiotherapy by inhibiting DNA repair. Folinic acid enhances TS inhibition by increasing the intracellular pool of folates that stabilize the 5FU‐TS complex.4. S‐Fluorouracil has a short plasma half‐life. Thymidylate synthase inhibition is limited to the S‐phase of the cell cycle and only a small fraction of most cancer cells are in S‐phase at any one time. Increased response rates seen with infusional protocols may reflect the effective recruitment of additional mechanisms of cytotoxicity, not dependent on cell cycle, including effects on RNA synthesis.5. Patients with localized metastatic disease may benefit from locoregional treatments. These include hepatic intra‐arterial therapy with related compounds, such as floxuridine, which reach high concentrations at sites of tumour, while systemic toxicities are minimized by efficient hepatic clearance.6. Recent developments include orally bioavailable formulations, such as ftorafur, capecitabine and the combination of 5FU with the dihydropyrimidine phosphate dehydrogenase inhibitor ethynyluracil. Recognition of diurnal variation in the activity of such key enzymes as DPD has led to the administration of 5FU at regulated, variable infusion rates (chronomodu‐lation). These promising pharmacological approaches may further improve clinical outcomes in common cancers.
CAPTOPRIL INHIBITS BOTH DOPAMINERGIC AND CHOLINERGIC NEUROTRANSMISSION IN THE CENTRAL NERVOUS SYSTEM
Authors: Tsuda Kazushi , Tsuda Seiko , Nishio Ichiro , Masuyama Yoshiaki , Goldstein Menek 
Published: June 2007

SUMMARY 1. The present study was performed to investigate the effects of captopril on both dopaminergic and cholinergic neurotransmission in the rat central nervous system. 2. Slices of rat striatum were prepared and prelabelled with [3H]‐dopamine or [3H]‐choline. Slices were continuously super‐fused with Krebs'‐Ringer solution and electrical stimulation (1 Hz) was performed. 3. Captopril significantly inhibited stimulation‐evoked [3H]‐dopamine release from rat striatal slices in a concentration‐dependent manner (S2/S1 ratios: control 0.83S±0.018 (n= 6); 1×10−5 mol/L captopril 0.597±0.035 (n= 6; P<0.05); 5 × 10−5 mol/L captopril 0.561 ± 0.041 (n = 6; P<0.05)). However, the basal release of [3H]‐dopamine was not affected by captopril. 4. Captopril also reduced stimulation‐evoked [3H]‐acetyl‐choline release in the striatum (S2/S1 ratios: control 0.891 ±0.016 (n= 6); 1 × 10−5 mol/L captopril 0.794±0.011 (n= 6; P<0.05)). 5. These results show that captopril inhibits the release of both dopamine and acetylcholine in the rat striatum. Although the mechanisms underlying the neurosuppressive effects of captopril remain to be determined, the findings suggest that the inhibition of dopaminergic and cholinergic neurotransmission may be related to the central action of the angiotensin‐converting enzyme inhibitor.
RESPIRATORY MECHANICS AND SURFACTANT IN THE ACUTE RESPIRATORY DISTRESS SYNDROME
Authors: Bersten AD , Davidson K , Nicholas TE , Doyle IR 
Published: June 2007

SUMMARY 1. Although abnormalities in pulmonary surfactant were initially implicated in the pathogenesis of the acute respiratory distress syndrome (AROS) 30 years ago, most subsequent research has focused on mediators of the parenchymal acute lung injury (ALI) and the associated increase in alveolocapillary permeability. 2. Surfactant is essential for normal breathing and the severity of ALI correlates with surfactant dysfunction and abnormalities in surfactant composition; however, no relationship has been shown with respiratory system compliance. In neonates and most animal models, respiratory system compliance will directly reflect the elastic properties of the lung. However, the greater vertical height of the chest wall in adults, in combination with the increase in lung density due to ALI, results in dependent collapse of alveoli. Because simple, global measurement of compliance is strongly influenced by the volume of aerated lung, alternative measures of respiratory mechanics may reflect surfactant dysfunction. 3. Using a dynamic, volume‐dependent model of respiratory mechanics to indirectly reflect this heterogeneous inflation, we have found direct relationships with surfactant composition in patients with ARDS. A failure of surfactant to increase surface tension in large alveoli may also explain why lung overdistension occurs at relatively low pressures. Furthermore, surfactant dysfunction will exaggerate heterogeneous lung inflation, augmenting regional overinflation, and is essential for ALI secondary to repetitive opening and closing of alveoli during tidal ventilation. 4. Ventilation‐induced ALI has also been shown to result in massive increases in pro‐inflammatory cytokines within the lung. Because ALI itself fails to compartmentalize cytokines, with spillover into the systemic circulation resulting in distant organ dysfunction, surfactant dysfunction may have widespread implications.
RESPIRATORY SINUS DYSRHYTHMIA PERSISTS IN TRANSPLANTED HUMAN HEARTS FOLLOWING AUTONOMIC BLOCKADE
Authors: Slovut David P , Wenstrom John C , Moeckel Richard B , Wilson Robert F , Osborn John W , Abrams Jerome H 
Published: June 2007

SUMMARY1. The present study was performed to test whether beat‐to‐beat cardiovascular control in cardiac allograft recipients resides in cholinergic and/or adrenergic nerves that are intrinsic to the heart.2. Heart rate (HR) fluctuations synchronous with respiration during spontaneous, double tidal volume and metronome‐synchronized breathing were quantified in 13 human heart transplant recipients. We also examined the effects of sequential cholinergic and β‐adrenoceptor (combined) autonomic blockade on respiratory sinus arrythmia (RSA). We computed RSA amplitude and the correlation between respiration and changes in HR (cardiopulmonary synchronization; CPS). Group means were compared using repeated‐measures analysis of variance. Transplant recipients served as their own controls.3. In the basal state, moderate RSA amplitude and CPS were observed. During cholinergic and combined blockade, we observed no significant change in RSA amplitude, whereas CPS increased significantly during combined blockade (P<0.05). The amplitude of RSA increased during respiration at double baseline tidal volume, but not at any of the other breathing manoeuvres (P<0.01). In contrast, CPS increased significantly during both patterned breathing manoeuvres. No significant correlation was seen between mean right atrial pressure and RSA amplitude. In 23% of subjects with low CPS, HR oscillated with arterial pressure. These oscillations were independent of respiration. During all three patterns of respiration, a significant inverse correlation was observed between CPS and pulse pressure (r= ‐0.53 to ‐0.73). Thus, as the amplitude of pulse pressure increased, respiration accounted for a smaller percentage of HR variation.4. In conclusion, RSA persists and the magnitude of CPS increases following combined autonomic blockade. These studies suggest that while RSA after cardiac transplantation is not cholinergically or adrenergically mediated, it may be related to mechanical stretch of the sinus node caused by changes in intrathoracic pressure and perfusion pressure.
MODULATION OF ELECTRICALLY EVOKED RESPONSES IN RAT DUODENUM BY ACTIVATION OF NICOTINIC CHOLINOCEPTORS
Authors: Sotirov Emil S , Itzev Dimitar E , Papasova Maria P 
Published: June 2007

SUMMARY1. The effect of activation of nicotinic cholinoceptors in rat duodenal segments following electrical field stimulation (EFS) was investigated.2. Electrical field stimulation elicited a two‐component response: transient relaxation followed by contraction. The EFS‐evoked response was tetrodotoxin (TTX; 1 μmol/L) sensitive. The relaxation component was NG‐nitro‐L‐arginine (L‐NNA; 100 μmol/L) sensitive, while the contractile response was atropine (1 μmol/L) sensitive.3. 1,1‐Dimethyl‐4‐phenyl‐piperazinium iodide (DMPP; 20 μmol/L) induced relaxation of spontaneously active preparations that was L‐NNA sensitive. L‐Arginine (1mmol/L) reversed the effects of L‐NNA on DMPP‐induced relaxation.4. When EFS was applied, DMPP increased the amplitude of the relaxation component of the response and reduced the contractile component.5. In the presence of L‐NNA, the effect of DMPP on the relaxation component of the response to EFS was reduced, but the contractile response was not affected. L‐Arginine partly reduced this effect of l‐NNA.6. Neither propranolol (1 μmol/L) nor yohimbine (1 μmol/L) had any effect on the actions of DMPP on EFS‐evoked responses, but prazosin (1 μmol/L) strongly reduced the effect of DMPP on the contractile component of the response to EFS and slightly reduced the effect of DMPP on the relaxation response.7. Histochemical studies demonstrated that, in the myenteric plexus of the rat duodenum, there are many reduced nicotinamide adenine dinucleotide phosphate‐diaphorase (N ADPH‐d)‐positive neurons and that their number decreased after treatment with L‐NNA. In the presence of L‐arginine and L‐NNA, the number of NADPH‐d‐positive neurons was similar to that found in control samples.8. The data suggest that activation of nicotinic cholinoceptors modulates EFS‐evoked responses in the rat duodenum as a result of the potentiation of nitrergic and adrenergic neurotransmission.
Infants hospitalised with pertussis: Estimating the true disease burden
Authors: Somerville Rebecca L , Grant Cameron C , Grimwood Keith , Murdoch David , Graham David , Jackson Pamela , Meates‐Dennis Maud , Nicholson Ross , Purvis Diana 
Published: June 2007

Aim:  New Zealand (NZ) has a large pertussis disease burden compared with other developed countries. Accurate ascertainment of disease burden is fundamental to controlling pertussis and informing immunisation policy. Disease burden estimates are primarily from passive surveillance, which underestimates disease incidence. The aim of this study is to use active surveillance to determine pertussis disease burden in infants hospitalised in NZ.Methods:  Using the NZ Paediatric Surveillance Unit, active surveillance from 08/2004 to 07/2005 for infants <12 months old, hospitalised with pertussis.Results:  110 infants identified (196 per 100 000), including six with complications, eight intensive care admissions and one death. The hospitalisation rate (per 100 000) varied with ethnicity, being higher for Maori (296) and Pacific (358) compared with European/other (117). Twenty‐four per cent were too young to be immunised. Of infants 6 weeks and older 46% had received no immunisations. Despite being more likely to be immunised Pacific infants had a higher hospitalisation rate owing to a larger proportion acquiring pertussis prior to age 6 weeks. Cyanosis and apnoea were frequent symptoms in young infants. Under‐identification, estimated using capture–recapture analysis, was modest for both active surveillance (16%) and passive notification (19%).Conclusions:  Infant pertussis hospitalisation rates are three to six times greater than rates in the USA, England and Australia. Underestimation of disease burden by passive notification in hospitalised infants is modest, suggesting a high degree of clinical awareness by paediatricians in NZ. New immunisation strategies are needed to protect infants from a younger age.