bluuebunny/crossref_metadata_2025 huggingface dataset:
Stoichiometric estimates of the biochemical conversion efficiencies in tsetse metabolism
Authors: Custer Adrian V
Published: August 2005

Background

The time varying flows of biomass and energy in tsetse (Glossina) can be examined through the construction of a dynamic mass-energy budget specific to these flies but such a budget depends on efficiencies of metabolic conversion which are unknown. These efficiencies of conversion determine the overall yields when food or storage tissue is converted into body tissue or into metabolic energy. A biochemical approach to the estimation of these efficiencies uses stoichiometry and a simplified description of tsetse metabolism to derive estimates of the yields, for a given amount of each substrate, of conversion product, by-products, and exchanged gases. This biochemical approach improves on estimates obtained through calorimetry because the stoichiometric calculations explicitly include the inefficiencies and costs of the reactions of conversion. However, the biochemical approach still overestimates the actual conversion efficiency because the approach ignores all the biological inefficiencies and costs such as the inefficiencies of leaky membranes and the costs of molecular transport, enzyme production, and cell growth.

Results

This paper presents estimates of the net amounts of ATP, fat, or protein obtained by tsetse from a starting milligram of blood, and provides estimates of the net amounts of ATP formed from the catabolism of a milligram of fat along two separate pathways, one used for resting metabolism and one for flight. These estimates are derived from stoichiometric calculations constructed based on a detailed quantification of the composition of food and body tissue and on a description of the major metabolic pathways in tsetse simplified to single reaction sequences between substrates and products. The estimates include the expected amounts of uric acid formed, oxygen required, and carbon dioxide released during each conversion. The calculated estimates of uric acid egestion and of oxygen use compare favorably to published experimental measurements.

Conclusion

This biochemical analysis provides reasonable first estimates of the conversion efficiencies for the major pathways used by tsetse metabolism. These results now enable a deeper analysis of tsetse ecology based on the construction of a dynamic mass-energy budget for tsetse and their populations.
Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers
Authors: Songisepp Epp , Kals Jaak , Kullisaar Tiiu , Mändar Reet , Hütt Pirje , Zilmer Mihkel , Mikelsaar Marika
Published: August 2005

Background

In persons without clinical symptom it is difficult to assess an impact of probiotics regarding its effect on health. We evaluated the functional efficacy of the probiotic Lactobacillus fermentum ME-3 in healthy volunteers by measuring the influence of two different formulations on intestinal lactoflora, fecal recovery of the probiotic strain and oxidative stress markers of blood and urine after 3 weeks consumption.

Methods

Two 3-week healthy volunteer trials were performed. Open placebo controlled (OPC) study participants (n = 21) consumed either goat milk or by L. fermentum ME-3 fermented goat milk (daily dose 11.8 log CFU (Colony Forming Units). Double blind randomised placebo controlled (DBRP) study participants (n = 24) received either capsules with L. fermentum ME-3 (daily of dose 9.2 CFU) or placebo capsules.

The faecal lactoflora composition, faecal ME-3 recovery, effect of the consumption on intestinal lactoflora, and oxidative stress markers of blood (total antioxidative activity; total antioxidative status and glutathione red-ox ratio) was measured.

Results

ME-3 was well tolerated and a significant increase in total faecal lactobacilli yet no predominance of ME-3 was detected in all study groups. Faecal recovery of ME-3 was documented by molecular methods only in fermented milk group, however the significant improvement of blood TAA (Total Antioxidative Activity) and TAS (Total Antioxidative Status) indices was seen both in case of fermented goat milk and capsules", yet glutathione re-ox ratio values decreased only in case of fermented by ME-3 goat milk.

Conclusion

The functional efficacy of both consumed formulations of an antioxidative probiotic L. fermentum ME-3 is proved by the increase of the intestinal lactobacilli counts providing putative defence against enteric infections and by reduction of the oxidative stress indices of blood and urine of healthy volunteers. In non-diseased host the probiotic health claims can be assessed by improvement of some measurable laboratory indices of well-established physiological functions of host, e.g. markers of antioxidative defence system.
Cocaine in surface waters: a new evidence-based tool to monitor community drug abuse
Authors: Zuccato Ettore , Chiabrando Chiara , Castiglioni Sara , Calamari Davide , Bagnati Renzo , Schiarea Silvia , Fanelli Roberto
Published: August 2005

Background

Cocaine use seems to be increasing in some urban areas worldwide, but it is not straightforward to determine the real extent of this phenomenon. Trends in drug abuse are currently estimated indirectly, mainly by large-scale social, medical, and crime statistics that may be biased or too generic. We thus tested a more direct approach based on 'field' evidence of cocaine use by the general population.

Methods

Cocaine and its main urinary metabolite (benzoylecgonine, BE) were measured by mass spectrometry in water samples collected from the River Po and urban waste water treatment plants of medium-size Italian cities. Drug concentration, water flow rate, and population at each site were used to estimate local cocaine consumption.

Results

We showed that cocaine and BE are present, and measurable, in surface waters of populated areas. The largest Italian river, the Po, with a five-million people catchment basin, steadily carried the equivalent of about 4 kg cocaine per day. This would imply an average daily use of at least 27 ± 5 doses (100 mg each) for every 1000 young adults, an estimate that greatly exceeds official national figures. Data from waste water treatment plants serving medium-size Italian cities were consistent with this figure.

Conclusion

This paper shows for the first time that an illicit drug, cocaine, is present in the aquatic environment, namely untreated urban waste water and a major river. We used environmental cocaine levels for estimating collective consumption of the drug, an approach with the unique potential ability to monitor local drug abuse trends in real time, while preserving the anonymity of individuals. The method tested here – in principle extendable to other drugs of abuse – might be further refined to become a standardized, objective tool for monitoring drug abuse.
Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: A comprehensive review
Authors: Utian Wulf H
Published: August 2005

Many women experience vasomotor symptoms at or around the time of menopause. Hot flushes and night sweats are considered primary menopausal symptoms that may also be associated with sleep and mood disturbances, as well as decreased cognitive function. All of these symptoms may lead to social impairment and work-related difficulties that significantly decrease overall quality of life. Hot flushes have shown a great deal of variability in their frequency and severity in women. In some women, hot flushes persist for several months; in others, they may last for more than 10 years. Traditionally vasomotor symptoms were reported to begin 5 to 10 years prior to the cessation of the final menstrual cycle, corresponding with the initial decline in circulating gonadal hormones; however, night sweats in particular most often begin in perimenopause. The pathogenesis of hot flushes has not yet been fully elucidated, but the circuitry involving estrogen and neurotransmitters, norepinephrine and serotonin specifically, are hypothesized to play a major role in the altered homeostatic thermoregulatory mechanisms underlying these events.

Menopause-associated vasomotor symptoms are associated with significant direct and indirect costs. Overall costs of traditional pharmacotherapy or complementary and alternative medicine modalities, including over-the-counter treatments and dietary supplements, for managing menopause-related vasomotor symptoms are substantial and include initial and follow-up physician visits and telephone calls. Additional costs include laboratory testing, management of adverse events, loss of productivity at work, and personal and miscellaneous costs. Pharmacoeconomic analyses, including those that consider risks identified by the Women's Health Initiative, generally support the cost-effectiveness of hormonal therapy for menopause-associated vasomotor symptoms, which have been the mainstay for the management of these symptoms for more than 50 years. However, because many women now want to avoid hormone therapy, there is a need for additional targeted therapies, validated by results from controlled clinical trials that are safe, efficacious, cost-effective, and well tolerated by symptomatic menopausal women.
HBx M130K and V131I (T-A) mutations in HBV genotype F during a follow-up study in chronic carriers
Authors: León Bernal , Taylor Lizeth , Vargas Minor , Luftig Ronald B , Albertazzi Federico , Herrero Libia , Visona Kirsten
Published: August 2005

Background

Around 400 million people worldwide are chronically infected with Hepatitis B virus (HBV). An estimated 10% of these chronic patients develop progressive liver damage including cirrhosis and Hepatocellular Carcinoma (HCC). The HBx gene encodes a protein of 154 amino acids which is a transactivator and has been associated with HBV pathogenesis. A change in the amino acid sequences at positions 130 and 131 in the HBV-X protein (M130K and V131I) produced by T-A point mutations at the nucleic acids level has been associated with severe liver damage and HCC in patients from China and Africa. Further, such changes have been proposed as a prognostic marker for progressive liver damage and HCC. The purpose of this study was to determine if T-A mutations are present in HBV chronic carriers with genotype F (the major genotype in Costa Rica) and further, if these mutations are associated with HBV disease progression in Costa Rica HBV patients from 1972 to 1985.

Results

Serum samples from 50 HBV positive individuals were amplified and directly sequenced, 48 belonged to genotype F, 1 from genotype D and another was classified as D or E.

T-;A mutations were absent in 17 acute patients who recovered, but was present in 12 of 29 chronic carrier samples (42.8%), in one sample the T-A mutations were detected as early as 29 days after clinical onset of disease. In 17 carriers with available liver biopsies, T-;A mutations were found in 8 sera of 13 (61.5%) classified as moderate or severe, and none in 4 biopsies with mild liver damage. However, it was not possible to demonstrate a statistical association between the presence of T-A mutations and moderate/severe liver damage, using a Fischer exact test, 1 tail, p = 0.05.

In 4 patients HCC was diagnosed, and 2 of them presented the T-A mutations in their sera.

Conclusion

T-A mutations were found in HBV genotype F in chronic carriers but not in patients who recovered from acute infection. These mutations could be developing early during infection although the possibility of infection with the mutant virus could not be excluded.

More studies are necessary to establish if the T-A mutation can be used as a prognostic marker for severity of liver disease in patients infected with HBV.
Effect of stroke location on the laryngeal cough reflex and pneumonia risk
Authors: Addington W Robert , Stephens Robert E , Widdicombe John G , Rekab Kamel
Published: August 2005

Background

The purpose of this study was to evaluate the risk of developing pneumonia in acute stroke patients comparing the early anatomical stroke location and laryngeal cough reflex (LCR) testing.

Methods

A prospective study of 818 consecutive acute stroke patients utilizing a reflex cough test (RCT), which assesses the neurological status of the LCR compared to magnetic resonance imaging or computerized tomography for stroke location and subsequent pneumonia outcome. Stroke diagnosis and stroke location were made by a neurologist and clinical radiologist, respectively; both were blinded to the RCT results.

Results

Brainstem (p-value < .007) and cerebral strokes (p-value < .005) correlated with the RCT results and pneumonia outcome. Of the 818 patients, 35 (4.3%) developed pneumonia. Of the 736 (90%) patients who had a normal RCT, 26 (3.5%) developed pneumonia, and of the 82 (10%) patients with an abnormal RCT, 9 (11%) developed pneumonia despite preventive interventions (p-value < .005). The RCT had no serious adverse events.

Conclusion

The RCT acted as a reflex hammer or percussor of the LCR and neurological airway protection and indicated pneumonia risk. Despite stroke location, patients may exhibit "brainstem shock," a global neurological condition involving a transient or permanent impairment of respiratory drive, reticular activating system or LCR. Recovery of these functions may indicate emergence from brainstem shock, and help predict morbidity and mortality outcome.
Organic compatible solutes of halotolerant and halophilic microorganisms
Authors: Roberts Mary F
Published: August 2005

Microorganisms that adapt to moderate and high salt environments use a variety of solutes, organic and inorganic, to counter external osmotic pressure. The organic solutes can be zwitterionic, noncharged, or anionic (along with an inorganic cation such as K+). The range of solutes, their diverse biosynthetic pathways, and physical properties of the solutes that effect molecular stability are reviewed.
HIV-1 gp120-induced TNF-α production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways
Authors: Lee Chuhee , Tomkowicz Brian , Freedman Bruce D , Collman Ronald G
Published: August 2005

Human immunodeficiency virus type 1 (HIV-1) infection is initiated by binding of the viral envelope glycoprotein gp120 to CD4 followed by a chemokine receptor, but these interactions may also take place independently from infection. gp120 stimulation of primary human macrophages is known to trigger production of cytokines implicated in pathogenesis, particularly tumor necrosis factor α (TNF-α), but the mechanisms have not been determined. We sought to define the pathways responsible for TNF-α secretion by monocyte-derived macrophages (MDM) following HIV-1 gp120 stimulation. MDM exposure to recombinant macrophage-tropic (R5) gp120 led to dose- and donor-dependent release of TNF-α, which was cyclohexamide-sensitive and associated with up-regulated message. Pretreatment with specific inhibitors of the mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinase 1/2 (ERK-1/2; PD98059, U0126) and p38 (SB202190, PD169316) inhibited the secretion of TNF-α. gp120-elicited TNF-α production was also blocked by phosphatidylinositol-3 kinase (PI-3K) inhibitors (wortmannin, LY294002). Moreover, PI-3K inhibition ablated gp120-induced phosphorylation of p38 and ERK-1/2. The response was inhibited by a CC chemokine receptor 5 (CCR5)-specific antagonist, indicating that CCR5 was in large part responsible. These results indicate that gp120-elicited TNF-α production by macrophages involves chemokine receptor-mediated PI-3K and MAPK activation, that PI-3K is an upstream regulator of MAPK in this pathway, and that p38 and ERK-1/2 independently regulate TNF-α production. These gp120-triggered signaling pathways may be responsible for inappropriate production of proinflammatory cytokines by macrophages, which are believed to play a role in immunopathogenesis and in neurological sequelae of AIDS.
The effects of CpG DNA on HMGB1 release by murine macrophage cell lines
Authors: Jiang Weiwen , Li Jianhua , Gallowitsch-Puerta Margot , Tracey Kevin J , Pisetsky David S
Published: August 2005

DNA containing cytosine-guanine dinucleotide (CpG) motifs (CpG DNA) has potent immunostimulatory activities that resemble those of lipopolysaccharide (LPS) in its effects on the innate immune system. Among its activities, LPS can induce the release of high mobility group protein (HMGB1) by macrophages, a dual function molecule that can mediate the late effects of LPS. To determine whether CpG DNA can also induce HMGB1 release, the effects of a synthetic CpG oligonucleotide (ODN) on HMGB1 release from RAW 264.7 and J774A.1 cells were assessed by Western blotting of culture supernatants. Under conditions in which the CpG ODN activated the cell lines, as assessed by stimulation of tumor necrosis factor α and interleukin-12, it failed to cause HMGB1 release into the media. Although unable to induce HMGB1 release by itself, the CpG ODN nevertheless potentiated the action of LPS. With RAW 264.7 cells, lipoteichoic acid and polyinosinic-polycytidylic acid, like LPS, stimulated HMGB1 release as well as cytokine production. These results indicate that the effects of CpG DNA on macrophages differ from other ligands of Toll-like receptors and may lead to a distinct pattern of immune cell activation in the context of infection or its use as an immunomodulatory agent.
Blockade of CTLA-4 (CD152) enhances the murine antibody response to pneumococcal capsular polysaccharides
Authors: Boudewijns Michaël , Jeurissen Axel , Wuyts Margaretha , Moens Leen , Boon Louis , Van Neerven Joost J , Kasran Ahmad , Overbergh Lut , Lenaerts Caroline , Waer Marc , Mathieu Chantal , Ceuppens Jan L , Bossuyt Xavier
Published: August 2005

The capsular polysaccharides (caps-PS) of Streptococcus pneumoniae are classified as thymus-independent antigens. Nevertheless, T lymphocytes can modulate the antibody response to caps-PS. In this study, we show that anticytotoxic T lymphocyte-associated antigen 4 (CTLA-4) treatment, along with administration of caps-PS to BALB/c mice, resulted in a dose-dependent generation of a strong caps-PS-specific antibody response. Anti-CTLA-4 treatment had no effect on the immunoglobulin G (IgG) antibody production in athymic nu/nu mice. Anti-CTLA-4 treatment stimulated the IgG antibody production in severe combined immunodeficiency (SCID)/SCID mice reconstituted with CTLA-4−/− B lymphocytes and wild-type T lymphocytes. This excluded the possibility that anti-CTLA-4 enhanced antibody production by direct interaction with B lymphocytes. Anti-CTLA-4 treatment enhanced the antibody production in SCID/SCID mice reconstituted with B lymphocytes and CD4(+) and CD8(+) T lymphocytes but not in SCID/SCID mice reconstituted with B lymphocytes in the absence of CD4(+) and/or CD8(+) cells. Administration of anti-CTLA-4 in BALB/c mice but not in nu/nu mice resulted in a markedly increased production of interleukin (IL)-2, IL-4, and interferon-γ. Taken together, these data strongly suggest a role of T lymphocytes and CTLA-4 in the regulation of the antibody response to caps-PS.
The role of TNF in hepatic histopathological manifestations and hepatic CD8+ T cell alloresponses in murine MHC class I disparate GVHD
Authors: El-Hayek Jihad M , Rogers Thomas E , Brown Geri R
Published: August 2005

Transfer of B6 T cells to major histocompatibility complex (MHC) class I disparate bm1 × B6 F1 mice leads to the development of hepatic graft-versus-host disease (GVHD) characterized by an active hepatitis with portal and lobular inflammation as well as bile duct inflammation and venulitis. The present studies determined the role of tumor necrosis factor (TNF) in hepatic GVHD. B6 responder cells were cultured with irradiated MHC class I disparate bm1 or syngeneic spleen cells (SpC) in the presence or absence of TNF receptor inhibitor [TNFR-immunoglobulin (Ig)]. Recipient bm1 × B6 F1 mice were irradiated (600 cGy) and reconstituted with 5 × 106 T cell-depleted B6 bone marrow cells and 1 × 107 B6 SpC. Mice were injected with an adenovirus encoding TNFR-Ig [TNF inhibitor-encoding adenovirus (Adv-TNFi)] or β-galactosidase (Adv-βgal). Severity of liver GVHD was assessed by a composite histopathological score consisting of the sum of scores for venulitis, lobular hepatitis, and bile duct inflammation. Addition of TNFR-Ig reduced cell proliferation in mixed lymphocyte cultures using B6 responder SpC by 71% ± 12.8% and interferon-γ responses by 78% ± 18%. GVHD-induced “wasting disease” was reduced in Adv-TNFi recipients [4.4%±5.2% weight loss (n=11)] compared with Adv-βgal recipients [16.1%±7.6% weight loss (n=11; P=0.0004)] 9 days post-transplant. Composite histopathological scores and individual venulitis scores were reduced with the addition of Adv-TNFi. Hepatic CD8+ T cells in the recipients of Adv-TNFi were reduced as compared with recipients of Adv-βgal. In conclusion, Adv-TNFi reduces MHC class I disparate alloproliferative responses and hepatic GVHD.
Task Decomposition Through Competition in a Modular Connectionist Architecture: The What and Where Vision Tasks
Authors: Jacobs Robert A. , Jordan Michael I. , Barto Andrew G.
Published: August 2005

A novel modular connectionist architecture is presented in which the networks composing the architecture compete to learn the training patterns. An outcome of the competition is that different networks learn different training patterns and, thus, learn to compute different functions. The architecture performs task decomposition in the sense that it learns to partition a task into two or more functionally independent tasks and allocates distinct networks to learn each task. In addition, the architecture tends to allocate to each task the network whose topology is most appropriate to that task. The architecture's performance on “what” and “where” vision tasks is presented and compared with the performance of two multilayer networks. Finally, it is noted that function decomposition is an underconstrained problem, and, thus, different modular architectures may decompose a function in different ways. A desirable decomposition can be achieved if the architecture is suitably restricted in the types of functions that it can compute. Finding appropriate restrictions is possible through the application of domain knowledge. A strength of the modular architecture is that its structure is well suited for incorporating domain knowledge.
Dominant Role of Mitochondria in Calcium Homeostasis of Single Rat Pituitary Corticotropes
Authors: Lee Andy K. , Tse Amy
Published: August 2005

The rise in cytosolic free Ca2+ concentration ([Ca2+]i) is the major trigger for secretion of ACTH from pituitary corticotropes. To better understand the shaping of the Ca2+ signal in corticotropes, we investigated the mechanisms regulating the depolarization-triggered Ca2+ signal using patch-clamp techniques and indo-1 fluorometry. The rate of cytosolic Ca2+ clearance was unaffected by inhibitors of Na+/Ca2+ exchanger or plasma membrane Ca2+-ATPase (PMCA), slightly slowed by sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, but dramatically slowed by mitochondrial uncouplers or inhibitor of mitochondrial uniporter. Measurements with rhod-2 revealed that depolarization-triggered increase in mitochondrial Ca2+ concentration. Thus, mitochondria have a dominant role in cytosolic Ca2+ clearance. Using the Mn2+ quench technique, we found the presence of a continuous basal Ca2+ influx in corticotropes. This basal Ca2+ influx was balanced by the combined actions of mitochondrial uniporter and PMCA and SERCA pumps. Inhibition of the mitochondrial uniporter or PMCA or SERCA pumps elevated basal [Ca2+]i. Using membrane capacitance measurement, we found that the change in the shape of the depolarization-triggered Ca2+ signal after mitochondrial inhibition was associated with enhancement of the exocytotic response. Thus, mitochondria have a dominant role in the regulation of Ca2+ signal and exocytosis in corticotropes.
Growth Hormone-Releasing Peptide Hexarelin Reduces Neonatal Brain Injury and Alters Akt/Glycogen Synthase Kinase-3β Phosphorylation
Authors: Brywe Katarina G. , Leverin Anna-Lena , Gustavsson Malin , Mallard Carina , Granata Riccarda , Destefanis Silvia , Volante Marco , Hagberg Henrik , Ghigo Ezio , Isgaard Jörgen
Published: August 2005

Hexarelin (HEX) is a peptide GH secretagogue with a potent ability to stimulate GH secretion and recently reported cardioprotective actions. However, its effects in the brain are largely unknown, and the aim of the present study was to examine the potential protective effect of HEX on the central nervous system after injury, as well as on caspase-3, Akt, and extracellular signal-regulated protein kinase (ERK) signaling cascades in a rat model of neonatal hypoxia-ischemia. Hypoxic-ischemic insult was induced by unilateral carotid ligation and hypoxic exposure (7.7% oxygen), and HEX treatment was administered intracerebroventricularly, directly after the insult. Brain damage was quantified at four coronal levels and by regional neuropathological scoring. Brain damage was reduced by 39% in the treatment group, compared with vehicle group, and injury was significantly reduced in the cerebral cortex, hippocampus, and thalamus but not in the striatum. The cerebroprotective effect was accompanied by a significant reduction of caspase-3 activity and an increased phosphorylation of Akt and glycogen synthase kinase-3β, whereas ERK was unaffected. In conclusion, we demonstrate for the first time that HEX is neuroprotective in the neonatal setting in vivo and that increased Akt signaling is associated with downstream attenuation of glycogen synthase kinase-3β activity and caspase-dependent cell death.
Transforming Growth Factor β-Activated Kinase 1 Is a Key Mediator of Ovine Follicle-Stimulating Hormone β-Subunit Expression
Authors: Safwat Nedal , Ninomiya-Tsuji Jun , Gore A. Jesse , Miller William L.
Published: August 2005

FSH, a key regulator of gonadal function, contains a β-subunit (FSHβ) that is transcriptionally induced by activin, a member of the TGFβ-superfamily. This study used 4.7 kb of the ovine FSHβ-promoter linked to luciferase (oFSHβLuc) plus a well-characterized activin-responsive construct, p3TPLuc, to investigate the hypothesis that Smad3, TGFβ-activated kinase 1 (TAK1), or both cause activin-mediated induction of FSH. Overexpression of either Smad3 or TAK1 induced oFSHβLuc in gonadotrope-derived LβT2 cells as much as activin itself. Induction of p3TPLuc by activin is known to require Smad3 activation in many cell types, and this was true in LβT2 cells, where 10-fold induction by activin (2–8 h after activin treatment) was blocked more than 90% by two dominant negative (DN) inhibitors of Smad3 [DN-Smad3 (3SA) and DN-Smad3 (D407E)]. By contrast, 6.5-fold induction of oFSHβLuc by activin (10–24 h after activin treatment) was not blocked by either DN-Smad inhibitor, suggesting that activation of Smad3 did not trigger induction of oFSHβLuc. By contrast, inhibition of TAK1 by a DN-TAK1 construct led to a 50% decrease in activin-mediated induction of oFSHβLuc, and a specific inhibitor of TAK1 (5Z-7-Oxozeanol) blocked induction by 100%, indicating that TAK1 is necessary for activin induction of oFSHβLuc. Finally, inhibiting p38-MAPK (often activated by TAK1) blocked induction of oFSHβLuc by 60%. In conclusion, the data presented here indicate that activation of TAK1 (and probably p38-MAPK), but not Smad3, is necessary for triggering induction of oFSHβ by activin.
Reduction in Adiposity Affects the Extent of Afferent Projections to Growth Hormone-Releasing Hormone and Somatostatin Neurons and the Degree of Colocalization of Neuropeptides in Growth Hormone-Releasing Hormone and Somatostatin Cells of the Ovine Hypothalamus
Authors: Iqbal Javed , Manley Tim R. , Ciofi Philippe , Clarke Iain J.
Published: August 2005

Various neuropeptides and neurotransmitters affect GH secretion by acting on GHRH and somatostatin (SRIF) cells. GH secretion is also affected by alteration in adiposity, which could be via modulation of GHRH and SRIF cells. We quantified colocalization of neuropeptides in GHRH and SRIF cells and afferent projections to these cells in lean (food restricted) and normally fed sheep (n = 4/group). The number of GHRH-immunoreactive (IR) cells in the arcuate nucleus was higher in lean animals, but the number of SRIF-IR cells in the periventricular nucleus was similar in the two groups. A subpopulation of GHRH-IR cells colocalized neuropeptide Y in lean animals, but this was not seen in normally fed animals. GHRH/galanin (GAL) colocalization was higher in lean animals with no difference in numbers of GHRH/tyrosine hydroxylase or GHRH/GAL-like peptide cells. SRIF/enkephalin colocalization was lower in lean animals. The percentage of GHRH neurons receiving SRIF input was similar in lean and normally fed animals, but more GHRH cells received input from enkephalin afferents in normally fed animals. The percentage of SRIF cells receiving GHRH, neuropeptide Y, GAL, and orexin afferents was higher in lean animals. These findings provide an anatomical evidence of central mechanism(s) by which appetite-regulating peptides and dopamine could regulate GH secretion. Increased input to SRIF cells in lean animals may be inhibitory and permissive of increased GH. The appearance of NPY in GHRH cells of lean animals may be a mechanism for regulation of increasing GH secretion with reduced adiposity.
Somatostatin Increases Voltage-Gated K+ Currents in GH3 Cells through Activation of Multiple Somatostatin Receptors
Authors: Yang Seung-Kwon , Parkington Helena C. , Blake Allan D. , Keating Damien J. , Chen Chen
Published: August 2005

The secretion of GH by somatotropes is inhibited by somatostatin (SRIF) through five specific membrane receptors (SSTRs). SRIF increases both transient outward (IA) and delayed rectifying (IK) K+ currents. We aim to clarify the subtype(s) of SSTRs involved in K+ current enhancement in GH3 somatotrope cells using specific SSTR subtype agonists. Expression of all five SSTRs was confirmed in GH3 cells by RT-PCR. Nystatin-perforated patch clamp was used to record voltage-gated K+ currents. We first established the presence of IA and IK type K+ currents in GH3 cells using different holding potentials (−40 or −70 mV) and specific blockers (4-aminopirimidine and tetraethylammonium chloride). SRIF (200 nm) increased the amplitude of both IA and IK in a fully reversible manner. Various concentrations of each specific SRTR agonist were tested on K+ currents to find the maximal effective concentration. Activation of SSTR2 and SSTR4 by their respective agonists, L-779,976 and L-803,087 (10 nm), increased K+ current amplitude without preference to IA or IK, and abolished any further increase by SRIF. Activation of SSTR1 and SSTR5 by their respective agonists, L-797,591 or L-817,818 (10 nm), increased K+ current amplitude, but SRIF evoked a further increase. The SSTR3 agonist L-797,778 (10 nm) did not affect the K+ currents or the response to SRIF. These results indicate that SSTR1, -2, -4, and -5 may all be involved in the enhancement of K+ currents by SRIF but that only the activation of SSTR2 or -4 results in the full activation of K+ current caused by SRIF.
A Positive Feedback Loop that Regulates Cyclooxygenase-2 Expression and Prostaglandin F2α Synthesis via the F-Series-Prostanoid Receptor and Extracellular Signal-Regulated Kinase 1/2 Signaling Pathway
Authors: Jabbour Henry N. , Sales Kurt J. , Boddy Sheila C. , Anderson Richard A. , Williams Alistair R. W.
Published: August 2005

Cyclooxygenase (COX) enzymes catalyze the biosynthesis of eicosanoids, including prostaglandin (PG) F2α. PGF2α exerts its autocrine/paracrine function by coupling to its G protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of COX-2 and FP receptor colocalized together within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF2α-FP receptor interaction in modulating COX-2 expression and PGF2α biosynthesis using an endometrial adenocarcinoma cell line stably transfected with the FP receptor cDNA (FPS cells). PGF2α-FP receptor activation rapidly induced COX-2 promoter, mRNA, and protein expression in FPS cells. These effects of PGF2α on the expression of COX-2 could be abolished by treatment of FPS cells with an FP receptor antagonist (AL8810) and chemical inhibitor of ERK1/2 kinase (PD98059), or by inactivation of ERK1/2 signaling with dominant-negative mutant isoforms of Ras or ERK1/2 kinase. We further confirmed that elevated COX-2 protein in FPS cells could biosynthesize PGF2αde novo to promote a positive feedback loop to facilitate endometrial tumorigenesis. Finally, we have shown that PGF2α could potentiate tumorigenesis in endometrial adenocarcinoma explants by inducing the expression of COX-2 mRNA.
Physicochemical Properties of New Gelators Based on a Chromen-2-one Core
Authors: Zhang Fusheng , Morita Yuki , Kawabe Kosuke , Tasaka Takeyasu , Okamoto Hiroaki , Takenaka Shunsuke , Kita Hidetoshi
Published: August 2005

Homologous series of 2-oxochromen-6-yl 4-alkoxybenzoates (1-n, n = 2–10) and 4-alkoxybiphenyl-4′-carboxylates (2-n, n = 5–8) can gelate various organic solvents, where the gel–sol transition temperatures are ca. 60 and 90 °C, respectively.
Surfactant-Based Homogeneous Assay for the Measurement of Triglyceride Concentrations in VLDL and Intermediate-Density Lipoprotein
Authors: Okada Masahiko , Saito Tomohiro , Yoshimura Hajime , Noguchi Yasuhiko , Ito Taeko , Sasaki Hiroko , Hama Hitoshi
Published: August 2005

Background: Existing studies have demonstrated the clinical significance of triglyceride content in VLDL (VLDL-TG) and intermediate-density lipoprotein (IDL-TG). We developed a homogeneous assay protocol to directly measure VLDL-TG.

Methods: Possible reagents and conditions for measuring VLDL-TG were comprehensively tested, and the “best” combination was determined. Healthy persons were instructed to consume a fatty meal after 15-h overnight fasting. Serum VLDL-TG + IDL-TG concentrations were measured using the proposed method. Patients with serum LDL-cholesterol concentrations ≥3.62 mmol/L (140 mg/dL) were administered simvastatin at a daily dose of 5 mg, and serum VLDL-TG concentrations were then measured.

Results: The combination of 2 nonionic surfactants played an important role in differentiating VLDL and IDL from other lipoproteins, probably via specific interactions with phospholipids and apolipoproteins. The regression line of the proposed method (y) and the ultracentrifugal assay (x) was: y = 0.98x + 0.31 mmol/L (r = 0.98; n = 73; P <0.05). The difference between postprandial total TG and VLDL-TG concentrations was statistically significant (P <0.05). After 8 weeks of therapy with simvastatin, total TG and LDL-cholesterol concentrations were 13.6% and 26.3% lower, respectively (P <0.05), whereas VLDL-TG did not show any significant decrease.

Conclusion: Our homogeneous method can measure TG content in VLDL and IDL.
Measuring Shear Wave Velocity Using Bender Elements
Authors: Leong EC , Yeo SH , Rahardjo H
Published: August 2005

The use of bender element to measure shear wave velocity is popular due to its simplicity. However, there are still some uncertainties in the interpretation of the bender element test. In this paper, the use of bender elements in the determination of shear wave velocities of dry, unsaturated, and saturated soil specimens is examined with respect to the characteristics of the bender elements, waveform, magnitude, and frequency of the applied voltage to the transmitter bender element and method of travel time determination. The interpretation of the bender element test can be improved if two performance criteria are adopted: (1) a signal-to-noise ratio of at least 4 dB for the receiver signal, and (2) a wave path length to wavelength ratio of at least 3.33. Procedures to estimate the strain level associated with the shear wave velocity measurement using bender element are also described.
A Laboratory Device to Test the Pull-Out Behavior of Soil Nails
Authors: Chu L-M , Yin J-H
Published: August 2005

Soil nailing is an in situ soil reinforcing technique adopted for stabilizing existing slopes in Hong Kong and in many other countries and regions. For the design of a soil nail system, pull-out capacity of a soil nail is an important design parameter. Field pull-out tests are then carried out to verify the pull-out resistance assumed at the design stage. However, the pull-out capacity of a soil nail in the field is influenced by a number of factors, such as variation in the soil properties, variation in the installation procedures, types of soil nail, and stress levels. Thus, field testing has a number of limitations. To overcome the limitations, a new laboratory pull-out testing apparatus was developed to investigate the interface shear strength behavior of the soil nails and surrounding soil. A numerical analysis was carried out to assess the initial stress conditions in the laboratory pull-out test box. A series of laboratory pull-out tests was performed with a cement grouted nail in a Completely Decomposed Granite (CDG) soil. It is aimed at studying the influence of overburden pressure, soil degree of saturation, and surface roughness of soil nail on the interface shear strength. The results indicate that the curves for pull-out tests exhibit a significant peak and post-peak shear strength behavior. And the interface shear strength between the nail and soil is shown to be dependent on the normal stress, the soil degree of saturation, and the surface roughness of the nail. A correlation of the interface shear strength with major influencing factors is then derived for practice design applications. The findings in this study may be a useful reference for geotechnical engineering in soil nailing design and constructions and for better understanding of the soil nail pull-out performance in the soil.
Saturated Hydraulic Conductivity of Compacted Recycled Asphalt Pavement
Authors: Trzebiatowski BD , Benson CH
Published: August 2005

Tests were conducted to determine the saturated hydraulic conductivity of three recycled asphalt pavement (RAP) materials being used as base course aggregate for pavement construction. Comparative tests were also conducted on a compacted crushed rock aggregate (Lodi gravel) that is used for base course in Wisconsin. All four are granular materials. The RAPs have saturated hydraulic conductivities ranging from 2.4 × 10−5 to 9.0 × 10−5 m/s when compacted with standard Proctor effort and from 4.5 × 10−8 to 1.7 × 10−6 m/s when compacted with modified Proctor effort. The Lodi gravel is less permeable, having saturated hydraulic conductivities of 5.8 × 10−7 m/s (standard Proctor effort) and 2.4 × 10−9 m/s (modified Proctor effort). Three conventional methods of predicting the saturated hydraulic conductivity of coarse-grained soils were evaluated in terms of their ability to predict the saturated hydraulic conductivity of RAP: Hazen's equation, Kenney's equation, and the Kozeny-Carmen equation. Each of these equations overpredict the hydraulic conductivity of RAP. Two empirical equations to predict the hydraulic conductivity of RAP were developed from the saturated hydraulic conductivity data. The empirical equations were found to work well for RAP as well as the Lodi gravel. However, the empirical equations are based on a small data set. Updating of the equations is encouraged as more data become available.
Heat-induced Dimensional Changes in Bone and their Consequences for Forensic Anthropology
Authors: Thompson TJU
Published: August 2005

An understanding of heat-induced transformation of hard tissue is vital before a full interpretation of burned human remains can be successfully achieved. Samples of modern sheep (n = 60) were analyzed resulting in 5440 data points. An experimental approach was undertaken that explored the bi-variable impact of heating temperature and duration of burning. Subsequent heat-induced bone changes included the progression of color from natural through to blue-white, the significant loss of weight, the reduction in mechanical strength, the development of distinct fracture patterns, alterations in the microscopic porosity, substantial alterations in crystalline structure and reduction and expansion in size. Collation and integration of this information demanded a revision of the four stages of heat-induced degradation of bone previously presented by Mayne Correia (1) and Thompson (2). The results demonstrate that heat-induced shrinkage is also accompanied by expansion and that both can be statistically significant. This suggests that anthropological techniques applied to burned bone will likely be detrimentally affected and accuracy will be reduced.
Maternal Death Due to Non-Traumatic Fat Embolism
Authors: Karayel F , Arican N , Kavas G , Akcay Turan A , Pakis I
Published: August 2005

The aim of this report is to document a case of non-traumatic fat embolism (NTFE) and to address the need for considerition of fat embolism in suspicious deaths resulting from respiratory distress in the postpartum period. A 28-years-old woman autopsied at the Morgue Department of the Council of Forensic Medicine is included to the study. This female became unconscious and developed respiratory distress 4 h after delivery, and this was followed by respiratory arrest. External examination revealed resuscitation marks and normal postmortem changes. Light microscopy revealed massive fat embolization involving most of the alveolar capillaries on several sections. Only in one particular area was a bone marrow embolus. Pathological diagnosis of the lung was diffuse pulmonary fat embolism. There was no evidence of other organ involvement with emboli. Other visceral organs showed no striking findings other than mild congestion. The cause of death was considered to be respiratory insufficiency resulting from severe fat embolism of the lungs.
The Effects of Skeletal Preparation Techniques on DNA from Human and Non-Human Bone
Authors: Rennick SL , Fenton TW , Foran DR
Published: August 2005

The forensic pathologist increasingly relies on the forensic anthropologist to be the consulting expert in human identification. Likewise, if identification is not possible from visual inspection of skeletal remains, the forensic biologist may be called upon to conduct DNA analysis. The possibility of downstream DNA testing needs to be considered when skeletal preparation techniques are employed to deflesh human remains, as they have the potential to strongly impact genetic analyses and subsequent identification. In this study, three cleaning techniques, boiling bone in water, in bleach, and in powdered detergent/sodium carbonate, were tested for their effect on nuclear and mtDNA recovery from a variety of human and non-human bones. A statistically significant reduction in DNA yields occurred in non-human bones cleaned with bleach, and DNA degradation was apparent electrophoretically. The human bones also showed much lower yields from bleach cleaning, while the detergent/carbonate method allowed the largest segments of DNA to be amplified, indicating it may have a less degradative effect on bone DNA than either of the other cleaning processes.
Abnormally High Concentrations of Amphetamine in Blood of Impaired Drivers
Authors: Jones AW , Holmgren A
Published: August 2005

We present a case series (N = 46) of individuals apprehended in Sweden for driving under the influence of drugs (DUID). These cases were selected because the concentrations of amphetamine in blood were abnormally high (>5.0 mg/L), the highest being 17 mg/L. In comparison, the median blood-amphetamine concentration in a population of DUID offenders (N = 6,613) was 0.70 mg/L. Among the DUID suspects with extremely high blood-amphetamine concentrations there were 38 men (83%) with mean age of 37.8 y (SD 6.8 y) and 8 women (17%) with a mean age of 34.1 y (SD 4.3 y). All had previously been registered in our database (mean 12 times, median 9 times) for drug-related offences, including DUID. The concentration of amphetamine in blood of female offenders was slightly higher than the concentration in male offenders (6.6 mg/L vs. 5.8 mg/L), although this difference was not statistically significant (p > 0.05). The drugs other than amphetamine most frequently encountered in the blood samples were tetrahydrocannabinol and benzodiazepines (diazepam and nordiazepam). The commonest signs of drug use reported by the arresting police officers were bloodshot and glazed (watery) eyes, restlessness, talkativeness, exaggerated reflexes and slurred speech. Unsteady gait and dilated pupils were observed in some but not all individuals. These very high concentrations of amphetamine were tolerated without any fatalities indicating a pronounced adaptation to the pharmacologic effects of this central stimulant. Anecdotal information indicated that those with the very highest concentrations of amphetamine in blood had swallowed the drug to prevent being apprehended in possession of an illicit substance.
Expression of Seminal Vesicle-Specific Antigen in Serum of Lung Tumor Patients
Authors: Berti A , Virgili A , D'Errico G , Vespi G , Lago G , Cavazzana A
Published: August 2005

Protein markers are commonly used in forensic medicine to establish the origin of human fluids detected in crime scenes. Semenogelins, the major protein constituents of semen coagulum, are the most effective markers for semen detection. Recently, it has been demonstrated that semenogelins are also ectopically expressed in small cell lung carcinomas (SCLC) and in a minority of non-small cell lung carcinomas (NSCLC). This finding prompted us to look for semenogelin expression in the serum of lung cancer patients. A set of 13 serum samples (3 from SCLC and 10 from NSCLC patients) was screened by enzyme—linked immunosorbent assay (ELISA), using a commercially available kit. Four of the NSCLC cases showed positive results. Ectopic expression of marker proteins in individuals affected by cancer could represent a potential source of forensic pitfalls.
Characterization of Ballpoint Pen Inks by Thermal Desorption and Gas Chromatography-Mass Spectrometry
Authors: Bügler JH , Buchner H , Dallmayer A
Published: August 2005

The characterization of ink on paper is of importance for dating and comparing questioned ink entries in forensic document examination. Inks are commonly characterized by their colorant profile that is identified by well-established analytical methods. Numerous ink formulations show identical colorant profiles, though. In order to differentiate inks that are not distinguishable by colorant analysis, a method for the characterization of colorless ink ingredients, namely binders, solvents and additives is necessary. In this paper, we propose a technique for the analysis of colorless compounds in ballpoint inks using direct thermal desorption of the ink on paper followed by chemical analysis of the desorbed volatile compounds by gas chromatography-mass spectrometry. As compared to liquid extraction and subsequent analysis of the extracts, the technique avoids possible contamination risks. Sensitivity is very high due to the enrichment of volatile components by thermal desorption. Even from old samples, the chromatograms obtained by the method enable the determination of binder polymers, solvents and additives. Pure binders as used by ink manufacturers were analyzed for unambiguous assignment of analytical results to specific polymers. To prove the practical applicability, we analyzed 121 ballpoint pens, not all having the same colorant profile, and grouped the pens into resin and solvent categories.