bluuebunny/crossref_metadata_2025 huggingface dataset:
Repetition suppression of ventromedial prefrontal activity during judgments of self and others
Authors: Jenkins Adrianna C. , Macrae C. Neil , Mitchell Jason P.
Published: March 2008

One useful strategy for inferring others' mental states (i.e., mentalizing) may be to use one's own thoughts, feelings, and desires as a proxy for those of other people. Such self-referential accounts of social cognition are supported by recent neuroimaging observations that a single brain region, ventromedial prefrontal cortex (vMPFC), is engaged both by tasks that require introspections about self and by tasks that require inferences about the minds of others perceived to be similar to self. To test whether people automatically refer to their own mental states when considering those of a similar other, we examined repetition-related suppression of vMPFC response during self-reflections that followed either an initial reflection about self or a judgment of another person. Consistent with the hypothesis that perceivers spontaneously engage in self-referential processing when mentalizing about particular individuals, vMPFC response was suppressed when self-reflections followed either an initial reflection about self or a judgment of a similar, but not a dissimilar, other. These results suggest that thinking about the mind of another person may rely importantly on reference to one's own mental characteristics.
Close correspondence between quantitative- and molecular-genetic divergence times for Neandertals and modern humans
Authors: Weaver Timothy D. , Roseman Charles C. , Stringer Chris B.
Published: March 2008

Recent research has shown that genetic drift may have produced many cranial differences between Neandertals and modern humans. If this is the case, then it should be possible to estimate population genetic parameters from Neandertal and modern human cranial measurements in a manner analogous to how estimates are made from DNA sequences. Building on previous work in evolutionary quantitative genetics and on microsatellites, we present a divergence time estimator for neutrally evolving morphological measurements. We then apply this estimator to 37 standard cranial measurements collected on 2,524 modern humans from 30 globally distributed populations and 20 Neandertal specimens. We calculate that the lineages leading to Neandertals and modern humans split ≈311,000 (95% C.I.: 182,000 to 466,000) or 435,000 (95% C.I.: 308,000 to 592,000) years ago, depending on assumptions about changes in within-population variation. These dates are quite similar to those recently derived from ancient Neandertal and extant human DNA sequences. Close correspondence between cranial and DNA-sequence results implies that both datasets largely, although not necessarily exclusively, reflect neutral divergence, causing them to track population history or phylogeny rather than the action of diversifying natural selection. The cranial dataset covers only aspects of cranial anatomy that can be readily quantified with standard osteometric tools, so future research will be needed to determine whether these results are representative. Nonetheless, for the measurements we consider here, we find no conflict between molecules and morphology.
Myosin V and Kinesin act as tethers to enhance each others' processivity
Authors: Ali M. Yusuf , Lu Hailong , Bookwalter Carol S. , Warshaw David M. , Trybus Kathleen M.
Published: March 2008

Organelle transport to the periphery of the cell involves coordinated transport between the processive motors kinesin and myosin V. Long-range transport takes place on microtubule tracks, whereas final delivery involves shorter actin-based movements. The concept that motors only function on their appropriate track required further investigation with the recent observation that myosin V undergoes a diffusional search on microtubules. Here we show, using single-molecule techniques, that a functional consequence of myosin V's diffusion on microtubules is a significant enhancement of the processive run length of kinesin when both motors are present on the same cargo. The degree of run length enhancement correlated with the net positive charge in loop 2 of myosin V. On actin, myosin V also undergoes longer processive runs when kinesin is present on the same cargo. The process that causes run length enhancement on both cytoskeletal tracks is electrostatic. We propose that one motor acts as a tether for the other and prevents its diffusion away from the track, thus allowing more steps to be taken before dissociation. The resulting run length enhancement likely contributes to the successful delivery of cargo in the cell.
HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimen
Authors: Li Nainong , Zhao Dongchang , Kirschbaum Mark , Zhang Chunyan , Lin Chia-Lei , Todorov Ivan , Kandeel Fouad , Forman Stephen , Zeng Defu
Published: March 2008

In allogeneic hematopoietic cell transplantation (HCT), donor T cell-mediated graft versus host leukemia (GVL) and graft versus autoimmune (GVA) activity play critical roles in treatment of hematological malignancies and refractory autoimmune diseases. However, graft versus host disease (GVHD), which sometimes can be fatal, remains a major obstacle in classical HCT, where recipients are conditioned with total body irradiation or high-dose chemotherapy. We previously reported that anti-CD3 conditioning allows donor CD8
+
T cells to facilitate engraftment and mediate GVL without causing GVHD. However, the clinical application of this radiation-free and GVHD preventative conditioning regimen is hindered by the cytokine storm syndrome triggered by anti-CD3 and the high-dose donor bone marrow (BM) cells required for induction of chimerism. Histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) are known to induce apoptosis of cancer cells and reduce production of proinflammatory cytokines by nonmalignant cells. Here, we report that SAHA inhibits the proliferative and cytotoxic activity of anti-CD3-activated T cells. Administration of low-dose SAHA reduces cytokine production and ameliorates the cytokine storm syndrome triggered by anti-CD3. Conditioning with anti-CD3 and SAHA allows induction of chimerism with lower doses of donor BM cells in old nonautoimmune and autoimmune lupus mice. In addition, conditioning with anti-CD3 and SAHA allows donor CD8
+
T cell-mediated GVA activity to reverse lupus glomerulonephritis without causing GVHD. These results indicate that conditioning with anti-CD3 and HDAC inhibitors represent a radiation-free and GVHD-preventative regimen with clinical application potential.
Surprising migration and population size dynamics in ancient Iberian brown bears (
Ursus arctos
)
Authors: Valdiosera Cristina E. , García-Garitagoitia José Luis , Garcia Nuria , Doadrio Ignacio , Thomas Mark G. , Hänni Catherine , Arsuaga Juan-Luis , Barnes Ian , Hofreiter Michael , Orlando Ludovic , Götherström Anders
Published: March 2008

The endangered brown bear populations (
Ursus arctos
) in Iberia have been suggested to be the last fragments of the brown bear population that served as recolonization stock for large parts of Europe during the Pleistocene. Conservation efforts are intense, and results are closely monitored. However, the efforts are based on the assumption that the Iberian bears are a unique unit that has evolved locally for an extended period. We have sequenced mitochondrial DNA (mtDNA) from ancient Iberian bear remains and analyzed them as a serial dataset, monitoring changes in diversity and occurrence of European haplogroups over time. Using these data, we show that the Iberian bear population has experienced a dynamic, recent evolutionary history. Not only has the population undergone mitochondrial gene flow from other European brown bears, but the effective population size also has fluctuated substantially. We conclude that the Iberian bear population has been a fluid evolutionary unit, developed by gene flow from other populations and population bottlenecks, far from being in genetic equilibrium or isolated from other brown bear populations. Thus, the current situation is highly unusual and the population may in fact be isolated for the first time in its history.
Monolayer purification: A rapid method for isolating protein complexes for single-particle electron microscopy
Authors: Kelly Deborah F. , Dukovski Danijela , Walz Thomas
Published: March 2008

Visualizing macromolecular complexes by single-particle electron microscopy (EM) entails stringent biochemical purification, specimen preparation, low-dose imaging, and 3D image reconstruction. Here, we introduce the “monolayer purification” method, which employs nickel-nitrilotriacetic acid (Ni-NTA) functionalized lipids for simultaneously purifying His-tagged complexes directly from cell lysates while producing specimens suitable for single-particle EM. The method was established by using monolayers containing Ni-NTA lipid to specifically adsorb His-tagged transferrin–transferrin receptor (Tf-TfR) complexes from insect and mammalian cell extracts. The specificity and sensitivity of the method could be improved by adding imidazole to the extracts. The monolayer-purified Tf-TfR samples could be vitrified and used to calculate a 3D reconstruction of the complex. Monolayer purification was then used to rapidly isolate ribosomal complexes from bacteria by overexpressing a single His-tagged ribosomal subunit. The resulting monolayer samples allowed calculation of a cryo-EM 3D reconstruction of the
Escherichia coli
50S ribosomal subunit.
Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1α and oxidative phosphorylation
Authors: Arany Zoltan , Wagner Bridget K. , Ma Yanhong , Chinsomboon Jessica , Laznik Dina , Spiegelman Bruce M.
Published: March 2008

The transcriptional coactivator PGC-1α is a potent regulator of several metabolic pathways, including, in particular, the activation of oxidative phosphorylation and mitochondrial biogenesis. Recent evidence suggests that increasing PGC-1α activity may have beneficial effects in various conditions, including muscular dystrophy, diabetes, and neurodegenerative diseases. We describe here a high-throughput screen to identify small molecules that induce PGC-1α expression in skeletal muscle cells. A number of drug classes are identified, including glucocorticoids, microtubule inhibitors, and protein synthesis inhibitors. These drugs induce PGC-1α mRNA, and the expression of a number of genes known to be regulated by PGC-1α. No induction of these target genes is seen in PGC-1α −/− cells, demonstrating that the drugs act through PGC-1α. These data demonstrate the feasibility of high-throughput screening for inducers of PGC-1α. Moreover, the data identify microtubule inhibitors and protein synthesis inhibitors as modulators of PGC-1α and oxidative phosphorylation.
Shift in language policy in Malaysia
Authors: Gill Saran Kaur
Published: March 2008

Malaysia experienced a major shift in language policy in 2003 for the subjects of science and maths. This meant a change in the language of education for both national and national-type schools. For national schools, this resulted in a shift from Bahasa Malaysia, the national language to English. Parallel with this, to ensure homogeneity of impact of change, the State persuaded the national-type schools, which have been utilizing the language of community, Mandarin and Tamil respectively, as medium of instruction since independence in 1957, to shift to English for the teaching of science and maths.

This paper aims to unravel the socio-political reasons underlying the shift with a focus on the Chinese community’s responses to the change. This will be carried out by examining the discourses of the debate contested by members of the Chinese community, juxtaposed against the reasons for the change, set forth by the State, as articulated by the former Prime Minister of Malaysia, Mahathir Mohamad. This multi-pronged approach will be used to unravel the underlying ideologies for the change and the reluctant compromise that was reached by the Chinese community.
Calcium Transport Mechanisms of PC12 Cells
Authors: Duman Joseph G. , Chen Liangyi , Hille Bertil
Published: March 2008

Many studies of Ca2+ signaling use PC12 cells, yet the balance of Ca2+ clearance mechanisms in these cells is unknown. We used pharmacological inhibition of Ca2+ transporters to characterize Ca2+ clearance after depolarizations in both undifferentiated and nerve growth factor-differentiated PC12 cells. Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA), plasma membrane Ca2+ ATPase (PMCA), and Na+/Ca2+ exchanger (NCX) account for almost all Ca2+ clearance in both cell states, with NCX and PMCA making the greatest contributions. Any contribution of mitochondrial uniporters is small. The ATP pool in differentiated cells was much more labile than that of undifferentiated cells in the presence of agents that dissipated mitochondrial proton gradients. Differentiated PC12 cells have a small component of Ca2+ clearance possessing pharmacological characteristics consistent with secretory pathway Ca2+ ATPase (SPCA), potentially residing on Golgi and/or secretory granules. Undifferentiated and differentiated cells are similar in overall Ca2+ transport and in the small transport due to SERCA, but they differ in the fraction of transport by PMCA and NCX. Transport in neurites of differentiated PC12 cells was qualitatively similar to that in the somata, except that the ER stores in neurites sometimes released Ca2+ instead of clearing it after depolarization. We formulated a mathematical model to simulate the observed Ca2+ clearance and to describe the differences between these undifferentiated and NGF-differentiated states quantitatively. The model required a value for the endogenous Ca2+ binding ratio of PC12 cell cytoplasm, which we measured to be 268 ± 85. Our results indicate that Ca2+ transport in undifferentiated PC12 cells is quite unlike transport in adrenal chromaffin cells, for which they often are considered models. Transport in both cell states more closely resembles that of sympathetic neurons, for which differentiated PC12 cells often are considered models. Comparison with other cell types shows that different cells emphasize different Ca2+ transport mechanisms.
Probabilistic and numerical validation of homology computations for nodal domains
Authors: Day Sarah , Kalies William , Mischaikow Konstantin , Wanner Thomas
Published: March 2008

Homology has long been accepted as an important computable tool for quantifying complex structures. In many applications these structures arise as nodal domains of real-valued functions and are therefore amenable only to a numerical study, based on suitable discretizations. Such an approach immediately raises the question of how accurate the resulting homology computations are. In this paper we present a probabilistic approach to quantifying the validity of homology computations for nodal domains of random Fourier series in one and two space dimensions, which furnishes explicit probabilistic a-priori bounds for the suitability of certain discretization sizes. In addition, we introduce a numerical method for verifying the homology computation using interval arithmetic.
Modification and the cohomology groups of compact solvmanifolds
Authors: Guan Daniel
Published: March 2008

In this note we give a modification theorem for a compact homogeneous solvmanifold such that a certain Mostow type condition will be satisfied. An application of this result is a simpler way to calculate the cohomology groups of compact quotients of real solvable Lie group over a cocompact discrete subgroup. Furthermore, we apply the second result to obtain a splitting theorem for compact complex homogeneous manifolds with symplectic structures. In particular, we are able to classify compact complex homogeneous spaces with pseudo-Kählerian structures.
Spatial distribution of chaetognaths off the northern Bicol Shelf, Philippines (Pacific coast)
Authors: Noblezada Mary Mar P. , Campos Wilfredo L.
Published: March 2008

Noblezada, M. M. P., and Campos, W. L. 2008. Spatial distribution of chaetognaths off the northern Bicol Shelf, Philippines (Pacific coast). – ICES Journal of Marine Science, 65: 484–494. The composition, abundance, and distribution of chaetognaths off the northern Bicol Shelf, Philippines (Pacific coast), from 31 stations along transects perpendicular to the coast were analysed. Samples were collected in April, 2001. In all, 26 species belonging to 14 genera were identified. Flaccisagitta enflata was the most abundant and frequently captured species at all stations, and constituted 41.9% of the total specimens. Most of the smallest diversity values were observed from areas affected by upwelling, although the greatest densities were observed at stations located within the upwelling zones. The occurrence of mesopelagic and bathypelagic species (Decipisagitta decipiens, Caecosagitta macrocephala, and Eukrohnia fowleri), in samples collected from upper water layers, could be explained by vertical transport caused by upwelling.
Seroprevalence of the enteroaggregative Escherichia coli virulence factor dispersin among USA travellers to Cuernavaca, Mexico: a pilot study
Authors: Huang David B. , Brown Eric L. , DuPont Herbert L. , Cerf Jing , Carlin Lily , Flores Jose , Belkind-Gerson Jaime , Nataro James P. , Okhuysen Pablo C.
Published: March 2008

This pilot study examined the change in the seroprevalence of the enteroaggregative Escherichia coli (EAEC) virulence factor dispersin in USA students during a short stay in Cuernavaca, Mexico, between June and August 2004. One hundred and ninety-five students provided paired serum samples – one on arrival to Mexico (pre-serum) and a second on departure from Mexico (post-serum) after a mean stay of 19 days. Serum samples were tested for IgG antibody to a recombinant purified dispersin protein by ELISA. For all travellers, with and without diarrhoea, the mean±sd pre-serum absorbance value (read at 450 and 570 nm) was 0.340±0.212 and the mean post-serum value was 0.513±0.316 (P<0.00001). Both travellers who developed diarrhoea and those who did not develop diarrhoea had an increase in IgG antibody to dispersin from the time of arrival to the time of departure from Cuernavaca (diarrhoea group 0.323±0.197 to 0.501±0.311, P<0.00001, and the asymptomatic group 0.354±0.224 to 0.525±0.321, P<0.00001). The pre-serum absorbance value (read at 450 and 570 nm) for IgG antibody to dispersin was not associated with protection against the development of diarrhoeal illness. These results indicate that USA travellers to Mexico show seroconversion for the EAEC virulence factor dispersin. Further studies are needed to characterize in more detail the host clinical and immunological responses to the dispersin protein.
Development of an in-house loop-mediated isothermal amplification (LAMP) assay for detection of Mycobacterium tuberculosis and evaluation in sputum samples of Nepalese patients
Authors: Pandey Basu Dev , Poudel Ajay , Yoda Tomoko , Tamaru Aki , Oda Naozumi , Fukushima Yukari , Lekhak Binod , Risal Basista , Acharya Bishnu , Sapkota Bishwa , Nakajima Chie , Taniguchi Tooru , Phetsuksiri Benjawan , Suzuki Yasuhiko
Published: March 2008

A number of nucleic acid amplification assays (NAAs) have been employed to detect tubercle bacilli in clinical specimens for tuberculosis (TB) diagnosis. Among these, loop-mediated isothermal amplification (LAMP) is an NAA possessing superior isothermal reaction characteristics. In the present study, a set of six specific primers targeting the Mycobacterium tuberculosis 16S rRNA gene with high sensitivity was selected and a LAMP system (MTB-LAMP) was developed. Using this system, a total of 200 sputum samples from Nepalese patients were investigated. The sensitivity of MTB-LAMP in culture-positive samples was 100 % (96/96), and the specificity in culture-negative samples was 94.2 % (98/104, 95 % confidence interval 90.5–97.9 %). The positive and negative predictive values of MTB-LAMP were 94.1 and 100 %, respectively. These results indicate that this MTB-LAMP method may prove to be a powerful tool for the early diagnosis of TB.
Spondylodiscitis due to Aerococcus viridans
Authors: Nasoodi A. , Ali A. G. , Gray W. J. , Hedderwick S. A.
Published: March 2008

Aerococcus viridans is a microaerophilic, Gram-positive, catalase-negative coccus, found singly or in tetrads. To date, no case of spondylodiscitis due to this organism has been reported. We report what we believe to be the first case of spondylodiscitis caused by A. viridans, in a patient with decompensated liver failure, and discuss the possible pathogenesis of this rather uncommon pathogen in this case.
Virulence of Listeria monocytogenes isolated from the cheese dairy environment, other foods and clinical cases
Authors: Neves Elsa , Silva Ana Carla , Roche Sylvie M. , Velge Philippe , Brito Luisa
Published: March 2008

The virulence potential of 51 Listeria monocytogenes isolates, including strains from cheese, cheese production environments and from human cases of listeriosis, was evaluated in this study. The isolates were used to infect HT-29 cell monolayers in an in vitro test of virulence, based on a plaque-forming assay (PFA). Fifteen selected isolates were used for subcutaneous footpad inoculation in mice and subsequent recovery of the bacterium from the spleen 3 days after inoculation. In the PFA, two isolates from milk (serovar 1/2a) were not significantly different (P<0.05) from the low-virulence strain (442) used as reference. Thirty-three isolates were not significantly different (P<0.05) from the virulent strain (EGDe) used as reference. Nine isolates were significantly more virulent (highly virulent) than the EGDe strain and seven isolates were significantly less virulent. The nine highly virulent isolates were either from humans (four), from cheese dairy environments (two isolates of a strain were found persistently in two dairies), from cheese (one), from milk (one) and the reference strain for serovar 1/2b (CECT 936). The two milk isolates with low virulence in the PFA were found to be virulent in mice. In conclusion, all the isolates from food and food-related environments were potentially virulent or highly virulent. These results stress the risk of listeriosis associated with the consumption of cheese contaminated with L. monocytogenes, and once more emphasize the importance of good manufacturing practices (GMPs) together with sanitation standard operating procedures (SSOPs) throughout the food chain.
A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility
Authors: Keller Mark P. , Choi YounJeong , Wang Ping , Belt Davis Dawn , Rabaglia Mary E. , Oler Angie T. , Stapleton Donald S. , Argmann Carmen , Schueler Kathy L. , Edwards Steve , Steinberg H. Adam , Chaibub Neto Elias , Kleinhanz Robert , Turner Scott , Hellerstein Marc K. , Schadt Eric E. , Yandell Brian S. , Kendziorski Christina , Attie Alan D.
Published: March 2008

Insulin resistance is necessary but not sufficient for the development of type 2 diabetes. Diabetes results when pancreatic beta-cells fail to compensate for insulin resistance by increasing insulin production through an expansion of beta-cell mass or increased insulin secretion. Communication between insulin target tissues and beta-cells may initiate this compensatory response. Correlated changes in gene expression between tissues can provide evidence for such intercellular communication. We profiled gene expression in six tissues of mice from an obesity-induced diabetes-resistant and a diabetes-susceptible strain before and after the onset of diabetes. We studied the correlation structure of mRNA abundance and identified 105 co-expression gene modules. We provide an interactive gene network model showing the correlation structure between the expression modules within and among the six tissues. This resource also provides a searchable database of gene expression profiles for all genes in six tissues in lean and obese diabetes-resistant and diabetes-susceptible mice, at 4 and 10 wk of age. A cell cycle regulatory module in islets predicts diabetes susceptibility. The module predicts islet replication; we found a strong correlation between 2H2O incorporation into islet DNA in vivo and the expression pattern of the cell cycle module. This pattern is highly correlated with that of several individual genes in insulin target tissues, including Igf2, which has been shown to promote beta-cell proliferation, suggesting that these genes may provide a link between insulin resistance and beta-cell proliferation.
Stimulation of Monocyte Procoagulant Activity by Adherence to Different Surfaces
Authors: van Ginkel C. J. W. , van Aken W. G. , Oh J. I. H. , Vreeken J.
Published: March 2008

Summary. During in vitro incubation for several hours human circulating blood leucocytes developed procoagulant activity (PCA) which was identified as tissue thromboplastin‐like activity and which remained specifically associated with monocytes. Adherence of monocytes to glass stimulated these cells to generate PCA. When cuprophane was used, both the degree of adherence of monocytes and PCA generation by these cells was significantly less. In addition, when the monocytes were incubated upon a monolayer of cultured endothelial cells only minor PCA generation was detectable. After incubation on glass the non‐adherent monocytes had negligible PCA in comparison to the adherent monocytes. Protein synthesis inhibitors (cycloheximide and actinomycin D) inhibited PCA generation but did not affect monocyte adherence. These results demonstrate that adherence of monocytes is a stimulus for the generation of PCA.
Binding of Thrombin to Functionally Defective Platelets: a Hypothesis on the Nature of the Thrombin Receptor
Authors: Ganguly P.
Published: March 2008

Summary. The initial step in the interaction of thrombin with human platelets is binding of thrombin to specific structures on the platelet surface. Data are presented which show that platelets from thrombasthenic patients bind thrombin similar to controls. In contrast, platelets from a patient with Bernard‐Soulier syndrome had lower thrombin binding capacity. It is suggested that glycoprotein one (GP‐I) on the platelet surface might be the receptor for thrombin.
MALE PSEUDOHERMAPHRODITISM WITH HYPERTENSION DUE TO A 17α‐HYDROXYLATION DEFICIENCY
Authors: TOURNIAIRE JACQUES , AUDI‐PARERA LAURA , LORAS BERNADETTE , BLUM JACQUES , CASTELNOVO PAUL , FOREST MAGUELONE G.
Published: March 2008

A case of male pseudohermaphroditism aged 48 years with systemic hypertension and hypokalaemic alkalosis is described. Results of metabolic studies point to a 17α‐hydroxylase deficiency deficiency demonstrated by low cortisol (0.56 mg/24 h), high corticosterone (270 mg/24 h) and 11‐deoxycorticosterone (5 mg/24 h) secretion rates. Adrenocorticotrophin and gonadotrophin levels were markedly raised but plasma androstenedione (3 ng/ dl), testosterone (17 ng/dl), oestrone (3 ng/dl) and oestradiol (1.8 ng/dl) were all low.

Plasma aldosterone levels and secretion rates in urine were low and were surprisingly unaffected by dexamethasone therapy although low renin levels rose with a marked return of the erect posture effect. Therapeutic levels of dexamethasone were, however, followed by incipient renal failure.
CALCIUM ION AS SECOND MESSENGER
Authors: RASMUSSEN HOWARD , JENSEN PAMELA , LAKE WILLIAM , GOODMAN DAVID B. P.
Published: March 2008

The role of calcium as an intracellular messenger in the activation of eukaryotic cells is discussed. Particular emphasis is devoted to: (1) the interrelationship between cell activation by chemical stimuli and alterations in intracellular calicum metabolism, and (2) the interrelated roles of calcium and the cyclic nucleotides, cyclic AMP and cyclic GMP, in achieving the final intergrated, co‐ordinated cellular response.
MODES OF INACTIVATION OF NEUROHYPOPHYSIAL HORMONES: SIGNIFICANCE OF PLASMA DISAPPEARANCE RATE FOR THEIR PHYSIOLOGICAL RESPONSES
Authors: PLIŜKA VLADIMIR , RUDINGER JOSEF
Published: March 2008

Analogues of oxytocin and deaminooxytocin with 4‐glutamine replaced by 4‐glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4‐glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the ‘oil‐bath’technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these ‘rapidly inactivated’analogues can be used as proof of some predictions of the three‐compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed.
THE ASSAY OF 1α, 25‐DIHYDROXYVITAMIN D3: PHYSIOLOGIC AND PATHOLOGIC MODULATION OF CIRCULATING HORMONE LEVELS
Authors: HAUSSLER M. R. , BAYKLINK D. J. , HUGHES M. R. , BRUMBAUGH P. F. , WERGEDAL J. E. , SHEN F. H. , NIELSEN R. L. , COUNTS S. J. , BURSAC K. M. , McCAIN T. A.
Published: March 2008

A sensitive radioreceptor assay for 1α,25‐dihydroxyvitamin D3 (1α,25‐(OH)2D3) is utilized to quantitate the circulating concentration of this sterol in experimental animals and humans. When weanling rats are grown for 2 weeks on low calcium or low phosphate diets, limited availability of either ion elicits a five‐fold increase in the plasma level of 1α,25‐(OH)2D3. The enhancement of 1α,25‐(OH)2D3 in calcium deficiency is dependent upon the presence of the parathyroid and/or thyroid glands, which is consistent with parathyroid hormone (PTH) mediation of this effect. In contrast, the response to phosphate deficiency is independent of these glands and may result from a direct action of low phosphate on the renal synthesis of 1α,25‐(OH)2D3. Studies in humans indicate that the normal level of 1α,25‐(OH)2D is 2.1‐4.5 ng/100 ml plasma. Patients with chronic renal failure have markedly lower circulating 1α,25‐(OH)2D and this kidney hormone is undectectable in anephirc subjects, but returns to normal within 1 day after successful renal transplantation. Hypoparathyroidism and pseudohypoparatghyroidism are associated with reduced plasma 1α,25‐(OH)2D while patients with primary hyperparathyroidism have significantly elevated sterol hormone levels. Thus, from measurements in rats and humans, it appears that circulating 1α,25‐(OH)2D3 is regulated by PTH and/or phosphate and that abnormal plasma 1α,25‐(OH)2D3 is a part of the pathophysiology of renal osteodystrophy and parathyroid disorders.
FURTHER INVESTIGATIONS ON INTESTINAL HORMONAL POLYPEPTIDES
Authors: MUTT VIKTOR
Published: March 2008

Attempts are described to identify additional polypeptides of hormonal nature in a concentrate of intestinal polypeptides shown previously to contain secretin, cholecystokinin‐pancreozymin (CCK), motilin, gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP), enteroglucagon and chymodenin. The probable amino acid sequence of a variant form of CCK is discolsed. The possibility of using characteristic fragments of polypeptides for the quantitation of the polypeptides themselves in crude preparations is briefly discussed.
EVIDENCE FOR SECRETION OF VASOACTIVE INTESTINAL PEPTIDE BY TUMOURS OF PANCREAS, ADRENAL MEDULLA, THYROID AND LUNG: SUPPORT FOR THE UNIFYING APUD CONCEPT
Authors: SAID SAMI I.
Published: March 2008

Levels of vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay in plasma or tissue from thirty‐five patients with watery diarrhoea, and in plasma of twenty‐five normal controls. Plasma levels were between 0.6 and 11.0 ng/ml in thirty‐one of the thirty‐three patients in whom it was measured and too low to measure (<200 pg/ml) in the other two. Peptide levels were <200 pg/ml in twenty‐three of the controls, but higher in the remaining two. All tissues from patients were ‘rich’in VIP (10 ng to 35 μg per g). The aetiologic diagnoses included pancreatic islet‐cell adenoma or adenocarcinoma, islet‐cell hyperplasia, bronchogenic carcinoma, pheochromocytoma, ganglioneuroblastoma, medullary thyroid carcinoma, and retroperitoneal histocytoma. The findings support the conclusions that: (1) VIP is a likely mediator of the watery‐diarrhoea syndrome; (2) the syndrome may result from a variety of tumours; (3) this or a related peptide hormone may be secreted by these tumours; and (4) these tumours may have a common embryonic origin.
GUT ENDOCRINOLOGY: CORRELATION OF PHYSIOLOGY AND MORPHOLOGY
Authors: POLAK J. M. , BLOOM S. R. , PEARSE A. G. E.
Published: March 2008

The gastrointestinal tract is a large and complex endocrine organ. Elucidation of its nature, and the actions of its individual hormonal components, has advanced in recent years following the purification and sequencing of six probable hormones and the subsequent development of radioimmunoassay techniques for their measurement and immunocytochemistry for the determination of their cellular origin. Immunoassay and immunocytochemistry are clearly complimentary to each other in providing a fuller understanding of the dynamics of endocrine function at the cellular level. This is illustrated in the examples described in this paper.
SYNTHESIS AND BIOLOGICAL ACTIVITY OF α‐AZAPEPTIDES: α‐AZA‐ANALOGUES OF LUTEINIZING HORMONE RELEASING HORMONE
Authors: DUTTA A. S. , FURR B. J. A. , GILES M. B. , MORLEY J. S.
Published: March 2008

The term ‘α‐azapeptides’is applied to analogues derived by change of one or more of the α‐CHs of amino‐acid residues in peptides by N; in such analogues the overall polarity of the molecule and the spacing of side‐chain residues is preserved, but stability towards peptidases may be increased because of the changed conformational situation at the residue or residues involved in the change. Three α‐aza‐analogues of LHRH, i.e. azaglycine6‐, azalanine10‐LHRH, and two α‐aza‐analogues of des‐His‐LHRH, i.e. azalglycine6‐and azalanine 6‐des‐His‐LHRH in inducing ovulation in androgen‐sterilized, constant‐oestrus rats, but less potent than LHRH in causing LH release in immature male rats. Evidence of increased duration of action was not obtained. The two aza‐analogues of des‐His‐LHRH were neither agonists nor antagonists in these two test systems.
CHEMISTRY AND PHYSIOLOGY OF PARATHYROID HORMONE
Authors: POTTS, Jr JOHN T.
Published: March 2008

Many recent studies, only a few of which are reviewed here (see Habener & Pots, 1976, for a detailed summary) have led to considerable clarification concerning critical features of the chemistry, biosynthesis, secretion and mode of action of parathyroid hormone. Certain of the confusion recently experienced in measurements of parathyroid hormone in blood is clearly explained by the heterogeneity arising from various forms of parathyroid hormone arising during biosynthesis and metabolism. Ultimately, as critical featrues of biosynthesis and metabolism of PTH as well as chemical definition of various molecular forms are achieved, considerable refinement in immunoassays should result. These advances in turn should provide better insights into the role of parathyroid dysfunction in various disorders of calcium and skeletal metabolism. From the physiological viewpoint, a clearer appreciation of the homeostatic role of parathyroid hormone in calcium metabolism is emerging as the essential features of biosynthesis, release, metabolism and action of the hormone are uncovered.
Storage of Escherichia coli Strains Containing Plasmid DNA in Liquid Nitrogen
Authors: BREESE M. D. , SHARP R. J.
Published: March 2008

The stability of plasmids and lysogenic bacteriophage in 16 strains of Escherichia coli was studied following storage in liquid nitrogen for periods up to 2 years. A comparison was made with cultures which had undergone lyophilization. Plasmid loss was detected by plating on selective media containing antibiotics to which resistance was conferred by plasmid DNA. Loss of plasmid DNA was not evident following storage in liquid nitrogen or lyophilization.
Enumeration of Vital and Thermally Stressed Staphylococcus aureus in Foods Using Baird‐Parker Pig Plasma Agar (BPP)
Authors: IDZIAK E. S. , MOSSEL D. A. A.
Published: March 2008

Baird‐Parker (BP), modified BP medium (egg yolk replaced with pig plasma, BPP) and modified Vogel and Johnson agar (phosphatidyl choline, deoxyribonucleic acid, with catalase added, PCVJ) were equally efficient for enumerating both non‐stressed and thermally‐stressed populations of Staphylococcus aureus from pure cultures and naturally contaminated foods. Vogel and Johnson agar was inferior. All colonies exhibiting coagulase activity on BPP were subsequently confirmed as Staph. aureus; this was not the case with presumptive colonies from BP and PCVJ. Based on selectivity, definitive diagnostic characterization of colonies and increased sensitivity (more sample plated), BPP should be considered as the reference method for the routine enumeration of Staph. aureus in foods.
The Structure and Function of the Spore Outer Membrane in Dormant and Germinating Spores of Bacillus megaterium
Authors: CRAFTS‐LIGHTY ANITA , ELLAR D. J.
Published: March 2008

Attempts to demonstrate the presence of the spore outer membrane in mature, dormant spores of a strain of Bacillus megaterium are described. The outer, integument, layers of this organism were found to contain one‐third of the total spore cytochrome content, several enzymes of the electron transport chain (specifically NADH oxidase, dehydrogenase, cytochrome c reductase and NADPH dehydrogenase) and a large number of polypeptides extractable with sodium dodecylsulphate in the presence of dithiothreitol and protease inhibitors. These all suggest the presence of a membraneous element. Electron microscopic evidence is presented on the structure of the dormant integument enzymes. Changes in the integument enzymes and in the gel electrophoresis profile of the extractable integument polypeptides which occur during spore gemination, are described and compared with those that take place in the spore inner membrane. The heat sensitivity of the integument enzymes is compared with that of the inner membrane enzymes and the implications for theories of spore heat resistance discussed.
Inhibition of bongkrek acid and toxoflavin production in tempe bongkrek containing Pseudomonas cocovenenans
Authors: Buckle K.A. , Kartadarma E.
Published: March 2008

Tempe bongkrek was prepared from partially defatted coconut by fermentation with the mould Rhizopus oligosporus. The addition of 2% sodium chloride decreased but did not inhibit formation of bongkrek acid by Pseudomonas cocovenenans strain ITB in either coconut culture medium (CCM) or tempe bongkrek, while 2% sodium chloride or acidification of CCM to pH 4.5 with acetic acid inhibited formation of toxoflavin. Toxin formation by three strains of Ps. cocovenenans in tempe bongkrek was inhibited by the combination of 2% sodium chloride and reduction of pH to 4.5 with acetic acid. Mycelial growth of R. oligosporus was sometimes affected by toxin production by Ps. cocovenenans, but not by the addition of 2% sodium chloride and/or acidification of CCM to pH 4.5 with acetic acid.
Are Hormonal Responses to Exercise in Young Men with Down’s Syndrome Related to Reduced Endurance Performance?
Authors: Bricout V‐A. , Guinot M. , Faure P. , Flore P. , Eberhard Y. , Garnier P. , Favre Juvin A.
Published: March 2008

The aim of the present study was to analyse whether hormonal responses could explain an exercise limitation in Down’s syndrome (DS). Fourteen young men with DS (mean age 22.5 ± 0.7 years) and 15 controls (CONT, mean age 22.5 ± 0.3 years) participated in the study. During a treadmill submaximal incremental test, blood samples were collected for determination of hormonal and metabolic variables. Compared to CONT, DS individuals showed lower VO2max (P < 0.05), and lower duration of submaximal incremental exercise (P < 0.001). At rest, DS individuals showed greater catecholamines, insulin and leptin values (P < 0.05), but lower testosteronemia and cortisolemia (P < 0.05), compared to CONT. During submaximal incremental tests, catecholamines and cortisol were not increased, whereas the insulin concentration of DS individuals was significantly higher (P < 0.01) compared to CONT. Glycaemia increased significantly at the end of submaximal incremental test for CONT but not for DS individuals (P < 0.01). Maximal fat oxidation was lower (P < 0.01), whereas non‐esterified fatty acids concentrations rose significantly during submaximal exercise in DS individuals. These results indicate an altered hormonal response to exercise in DS individuals. This endocrine profile at rest and during exercise may limit endurance performance in DS individuals.
Activation of A‐Type γ‐Amino Butyric Acid Receptors Excites Gonadotrophin‐Releasing Hormone Neurones Isolated from Adult Rats
Authors: Yin C. , Ishii H. , Tanaka N. , Sakuma Y. , Kato M.
Published: March 2008

Gonadotrophin‐releasing hormone (GnRH) neurones represent the final output neurones in the neuroendocrine control of reproduction, and γ‐amino butyric acid (GABA) is one of the major players in the regulation of GnRH neurones. GABA inhibits a large proportion of brain neurones in adult animals by acting on A‐type GABA receptors (GABAARs). Two contradictory reports on the action of GABA in the GnRH neurones of adult mice have been published. DeFazio et al. (Mol Endocrinol 2002; 16: 2872) demonstrated that activation of GABAARs excites the GnRH neurones of adult mice, whereas Han et al. (Endocrinology 2002; 143: 1459) showed that the response to GABA on GnRH neurones switches from depolarisation to hyperpolarisation around puberty in female mice. Therefore, we examined the reversal potential of GABAAR currents by means of perforated patch‐clamp recording with gramicidin in overnight‐cultured GnRH neurones isolated from adult GnRH‐enhanced green fluorescent protein transgenic rats. The reversal potential was −26 ± 1.4 mV (mean ± SEM, n = 42) in GnRH neurones, whereas it was −57 ± 2.7 mV (n = 34) in unidentified neurones, and GABA depolarised the GnRH neurones in current‐clamp condition. The GABAAR currents in rat GnRH neurones were augmented by neurosteroids, allopregnanolone and 3α,21‐dihydroxy‐5α‐pregnan‐20‐one, at submicromolar concentrations. In addition, the expression patterns of GABAAR subunit mRNAs were determined by multi‐cell reverse transcription‐polymerase chain reaction, which revealed that the α2, β3, γ1 and γ2 subunits were dominant and the α6 and γ3 subunits were negative in rat GnRH neurones. These results indicate that GABAARs in the soma of rat GnRH neurones are comprised mainly of α2, β3 and γ1 or γ2 subunits and that they are sensitive to neurosteroids; moreover, they suggest that activation of these receptors depolarises GnRH neurones. Thus, GABA and neurosteroids influence the electrical activity of GnRH neurones.
Fast Effects of Glucocorticoids on Memory‐Related Network Oscillations in the Mouse Hippocampus
Authors: Weiss E. K. , Krupka N. , Bähner F. , Both M. , Draguhn A.
Published: March 2008

Transient or lasting increases in glucocorticoids accompany deficits in hippocampus‐dependent memory formation. Recent data indicate that the formation and consolidation of declarative and spatial memory are mechanistically related to different patterns of hippocampal network oscillations. These include gamma oscillations during memory acquisition and the faster ripple oscillations (approximately 200 Hz) during subsequent memory consolidation. We therefore analysed the effects of acutely applied glucocorticoids on network activity in mouse hippocampal slices. Evoked field population spikes and paired‐pulse responses were largely unaltered by corticosterone or cortisol, respectively, despite a slight increase in maximal population spike amplitude by 10 μm corticosterone. Several characteristics of sharp waves and superimposed ripple oscillations were affected by glucocorticoids, most prominently the frequency of spontaneously occurring sharp waves. At 0.1 μm, corticosterone increased this frequency, whereas maximal (10 μm) concentrations led to a reduction. In addition, gamma oscillations became slightly faster and less regular in the presence of high doses of corticosteroids. The present study describes acute effects of glucocorticoids on sharp wave‐ripple complexes and gamma oscillations in mouse hippocampal slices, revealing a potential background for memory deficits in the presence of elevated levels of these hormones.
Biology of Post‐Traumatic Stress Disorder in Childhood and Adolescence
Authors: Pervanidou P.
Published: March 2008

Diverse patterns of cortisol secretion with consistently high circulating catecholamines have been reported in post‐traumatic stress disorder (PTSD), an anxiety state that develops after exposure to traumatic life events. Indeed, peripheral cortisol levels have been reported to be low or normal in the majority of adult chronic PTSD studies, whereas, in most paediatric studies, high cortisol values have been documented. Longitudinal studies on PTSD biology, including the transition from childhood to adulthood, may shed light on these discrepancies. In children, elevated evening salivary cortisol in the aftermath of the trauma was predictive of PTSD development 6 months later, whereas plasma interleukin‐6 correlated positively with evening cortisol and was equally predictive of later PTSD. Longitudinal assessment of PTSD children 1 and 6 months later revealed progressive normalisation of cortisol levels, whereas noradrenaline concentrations became gradually higher. We hypothesise that, in adults with chronic PTSD, low cortisol levels, together with high catecholamines, may reflect a late event in the natural history of the disorder, months or years after the trauma. The progressive divergence of cortisol and noradrenaline concentrations over time may be responsible for PTSD maintenance in children and explain the differences between the child and adult PTSD endophenotypes. In adults studied immediately after the trauma, and by contrast to children, low cortisol levels are predictive of later PTSD development. Our hypothesis that low cortisol levels may reflect a previous trauma, earlier in development, is supported by the well established observation that prior trauma is a risk factor for a new PTSD diagnosis. The developmental stage of an individual in relation to previous exposure to trauma and PTSD vulnerability are crucial variables that may determine clinical and biological PTSD phenotypes and explain the discrepancies between adults and children in reported cortisol levels.
Hepatic artery reconstruction with inferior mesenteric vein graft in pediatric living donor liver transplantation
Authors: Margreiter Christian , Aigner Felix , Orozco Hector , Wechselberger Gottfried , Öllinger Robert , Bösmüller Claudia , Sucher Robert , Mark Walter , Margreiter Raimund
Published: March 2008

Abstract:  We report a transplant of the left lateral liver segments with two arteries for a pediatric recipient from a live donor. A six‐month‐old female patient was diagnosed with liver cirrhosis secondary to biliary atresia and scheduled for LDLT (father as donor). Left lateral hepatectomy was performed at the donor site. The dissection of the left HA, which divided immediately after its origin, showed two branches for segments II and III. The artery for segment III was anastomosed to the recipient HA. The artery for segment II was too short for direct anastomosis with the gastroduodenal artery. After an unsuccessful attempt to use of the recipient’s saphenous vein, the recipient’s IMV was used as an interposition graft. No post‐operative complications were observed. The outcome of this case demonstrates that left lateral segments with two arteries can be successfully used if proper surgical techniques are applied. From this experience we can recommend the IMV as an alternative to the saphenous vein for an interposition graft.