bluuebunny/crossref_metadata_2025 huggingface dataset:
The G-Protein-Coupled Serotonin Receptor SER-1 Regulates Egg Laying and Male Mating Behaviors inCaenorhabditis elegans
Authors: Carnell Lucinda , Illi Julie , Hong Swung Woo , McIntire Steven L.
Published: November 2005

Serotonin (5-HT) is a neuromodulator that regulates many aspects of animal behavior, including mood, aggression, sex drive, and sleep. In vertebrates, most of the behavioral effects of 5-HT appear to be mediated by G-protein-coupled receptors (GPCRs). Here, we show that SER-1 is the 5-HT GPCR responsible for the stimulatory effects of exogenous 5-HT in two sexually dimorphic behaviors ofCaenorhabditis elegans, egg laying and male ventral tail curling. Loss ofser-1function leads to decreased egg laying in hermaphrodites and defects in the turning step of mating behavior in males.ser-1is expressed in muscles that are postsynaptic to serotonergic neurons and are known to be required for these behaviors. Analysis of theser-1mutant also reveals an inhibitory effect of 5-HT on egg laying that is normally masked by SER-1-dependent stimulation. This inhibition of egg laying requires MOD-1, a 5-HT-gated chloride channel. Loss ofmod-1function in males also produces defects in ventral tail curling and enhances the turning defects inser-1mutant males. Sustained elevations in 5-HT levels result in behavioral adaptation to both the stimulatory and inhibitory actions of the neurotransmitter, indicating that both SER-1 and MOD-1 signaling can be modulated. Removal of wild-type animals from high levels of exogenous 5-HT produces a SER-1-dependent withdrawal response in which egg laying is significantly decreased. These studies provide insight into the role of 5-HT in behavior and the regulation of 5-HT2receptor function.
Neurological and Neurodegenerative Alterations in a Transgenic Mouse Model Expressing Human α-Synuclein under Oligodendrocyte Promoter: Implications for Multiple System Atrophy
Authors: Shults Clifford W. , Rockenstein Edward , Crews Leslie , Adame Anthony , Mante Michael , Larrea Gabriel , Hashimoto Makoto , Song David , Iwatsubo Takeshi , Tsuboi Kyoko , Masliah Eliezer
Published: November 2005

Multiple system atrophy (MSA) is a progressive, neurodegenerative disease characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of α-synuclein (α-syn) in oligodendrocytes. To better understand the mechanisms of neurodegeneration and the role of α-syn accumulation in oligodendrocytes in the pathogenesis of MSA, we generated transgenic mouse lines expressing human (h) α-syn under the control of the murine myelin basic protein promoter. Transgenic mice expressing high levels of hα-syn displayed severe neurological alterations and died prematurely at 6 months of age. Furthermore, mice developed progressive accumulation of hα-syn-immunoreactive inclusions in oligodendrocytes along the axonal tracts in the brainstem, basal ganglia, cerebellum, corpus callosum, and neocortex. The inclusions also reacted with antibodies against phospho-serine (129) hα-syn and ubiquitin, and hα-syn was found in the detergent-insoluble fraction. In high-expresser lines, the white matter tracts displayed intense astrogliosis, myelin pallor, and decreased neurofilament immunostaining. Accumulation of hα-syn in oligodendrocytes also leads to prominent neurodegenerative changes in the neocortex with decreased dendritic density and to loss of dopaminergic fibers in the basal ganglia. The oligodendrocytic inclusions were composed of fibrils and accompanied by mitochondrial alterations and disruption of the myelin lamina in the axons. Together, these studies support the contention that accumulation of α-syn in oligodendrocytes promotes neurodegeneration and recapitulates several of the key functional and neuropathological features of MSA.
Lamina Propria and Olfactory Bulb Ensheathing Cells Exhibit Differential Integration and Migration and Promote Differential Axon Sprouting in the Lesioned Spinal Cord
Authors: Richter Miranda W. , Fletcher Patrick A. , Liu Jie , Tetzlaff Wolfram , Roskams A. Jane
Published: November 2005

Olfactory bulb-derived (central) ensheathing cell (OB OEC) transplants have shown significant promise in rat models of spinal cord injury, prompting the use of lamina propria-derived (peripheral) olfactory ensheathing cells (LP OECs) in both experimental and clinical trials. Although derived from a common embryonic precursor, both sources of OECs reside in different nervous system compartments postnatally, and their ability to promote regeneration and efficacy after transplantation may differ depending on both their source and mode of transplantation. Here, we have purified green fluorescent protein-expressing LP and OB OECs, assayed their biological differencesin vitro, and transplanted them acutely either directly into or rostral and caudal to a dorsolateral funiculus crush. LP and OB OECs exhibit multiple morphological and antigenic similaritiesin vitro, and, after transplantation, they both attenuate lesion and cavity formation and promote angiogenesis, endogenous Schwann cell infiltration, and axonal sprouting. However, an increased mitotic rate and migratory ability of LP OECsin vitrowas reflectedin vivoby their superior ability to migrate within the spinal cord, reduce cavity formation and lesion size, and differentially stimulate outgrowth of axonal subpopulations compared with OB OECs. An undesired behavior (autotomy) was also significantly enhanced by LP OEC, over OB OEC, transplantation. These results suggest that LP and OB OECs exhibit intrinsic biological differences that, after transplantation into the lesioned CNS, result in differences in postlesion spinal cord neuropathology and anatomical and behavioral regeneration outcomes that also vary depending on direct versus rostrocaudal transplantation.
Do We Know What the Early Visual System Does?
Authors: Carandini Matteo , Demb Jonathan B. , Mante Valerio , Tolhurst David J. , Dan Yang , Olshausen Bruno A. , Gallant Jack L. , Rust Nicole C.
Published: November 2005

We can claim that we know what the visual system does once we can predict neural responses to arbitrary stimuli, including those seen in nature. In the early visual system, models based on one or more linear receptive fields hold promise to achieve this goal as long as the models include nonlinear mechanisms that control responsiveness, based on stimulus context and history, and take into account the nonlinearity of spike generation. These linear and nonlinear mechanisms might be the only essential determinants of the response, or alternatively, there may be additional fundamental determinants yet to be identified. Research is progressing with the goals of defining a single “standard model” for each stage of the visual pathway and testing the predictive power of these models on the responses to movies of natural scenes. These predictive models represent, at a given stage of the visual pathway, a compact description of visual computation. They would be an invaluable guide for understanding the underlying biophysical and anatomical mechanisms and relating neural responses to visual perception.
Critical Role of Calcitonin Gene-Related Peptide 1 Receptors in the Amygdala in Synaptic Plasticity and Pain Behavior
Authors: Han Jeong S. , Li Weidong , Neugebauer Volker
Published: November 2005

The role of neuropeptides in synaptic plasticity is less well understood than that of classical transmitters such as glutamate. Here we report the importance of the G-protein-coupled calcitonin gene-related peptide (CGRP1) receptor as a critical link between amygdala plasticity and pain behavior. A key player in emotionality and affective disorders, the amygdala has been implicated in the well documented, but mechanistically unexplained, relationship between pain and affect. Our electrophysiological and pharmacologicalin vitro(patch-clamp recordings) andin vivo(extracellular single-unit recordings) data show that selective CGRP1 receptor antagonists (CGRP8-37and BIBN4096BS) in the amygdala reverse arthritis pain-related plasticity through a protein kinase A (PKA)-dependent postsynaptic mechanism that involves NMDA receptors. CGRP1 receptor antagonists inhibited synaptic plasticity in the laterocapsular division of the central nucleus of the amygdala (CeLC) in brain slices from arthritic rats compared with normal controls. The effects were accompanied by decreased neuronal excitability and reduced amplitude, but not frequency, of miniature EPSCs; paired-pulse facilitation was unaffected. The antagonist effects were occluded by a PKA inhibitor. CGRP1 receptor blockade also directly inhibited NMDA-evoked, but not AMPA-evoked, membrane currents. Together, these data suggest a postsynaptic site of action. At the systems level, the antagonists reversed the sensitization of nociceptive CeLC neurons in anesthetized rats in the arthritis pain model. Importantly, CGRP1 receptor blockade in the CeLC inhibited spinal (hindlimb withdrawal reflexes) and supraspinal pain behavior of awake arthritic rats, including affective responses such as ultrasonic vocalizations. This study provides direct evidence for the critical dependence of pain behavior on CGRP1-mediated amygdala plasticity.
Extraction of silver from nitric acid medium by certain quinoline derivatives
Authors: Ali A. M. I.
Published: November 2005

Three new quinoline derivatives were synthesised and characterized. These compounds were found to be insoluble in water and different acids such as HNO3, HCl until 6 M and soluble in NaOH at 2 M concentration. Chloroform was found to be the suitable solvent for quinoline derivatives. The extraction of Ag from nitric acid by 8-methyl-2,4-dithiol-quinoline (1H) (MDTQ), 4-chloro-8-methyl-quinoline (1H) thione (CMTQ) and 3-formyl-4-hydroxy N-methyl 2(H) quinoline (FHMQ) has been investigated.

The effects of shaking time, nitric acid concentration, metal ion concentration and the concentration of extractant were studied. The results showed that the distribution ratio of Ag decreased with increase in the nitric acid and metal concentration, and increased by increasing the extractant concentration. It was found that an equilibrium time of 10 min was required to reach equilibrium. The results showed that (MDTQ) is very selective for the separation of Ag.
Radiobromination of closo-dodecaborate anion. Aspects of labelling chemistry in aqueous solution using Chloramine-T
Authors: Tolmachev Vladimir , Bruskin A. , Sivaev Igor , Lundqvist Hans , Sjöberg Stefan
Published: November 2005

Closo-dodecaborate dianion is a three-dimensional aromatic inorganic molecule, which can be easily halogenated forming a stable halogen-boron bond. Derivatives of closo-dodecaborate were considered as a convenient chemical form of delivery of enriched 10B to malignant tumors for boron neutron capture therapy (BNCT). Some properties of closo-dodecaborate (hydrophilicity, strength of halogen-boron bond, charge at lysosomal pH) make it attractive as a potential prosthetic group for attachment of radioactive halogens to tumor-targeting proteins. Bromine radioisotopes possess a variety of useful nuclear characteristics, and can be used in different areas of clinical diagnostics and therapy. In this work, a basic chemistry of closo-dodecaborate radiobromination was studied. It was found, that di(triethylamonium) dodecahydro-closo-dodecaborate can be labelled in high yield, more then 90%, in a wide pH range. By decreasing the pH, the bromination can be directed to closo-dodecaborate in the presence of phenolic compounds. The results of the study indicate a possibility of using the radioactive bromine label for investigation of pharmacokinetics of boronated compounds for BNCT.
Disparate Clinical Presentation of Neonatal Hemochromatosis in Twins
Authors: Ekong Udeme D. , Kelly Susan , Whitington Peter F.
Published: November 2005

Neonatal hemochromatosis (NH) is a rare disease of gestation that results in fetal liver injury and extrahepatic siderosis. The etiology of NH is not fully understood. However, the rate of recurrence of NH in the pregnancy after an affected one is ∼80%. A spectrum of liver disease has been recognized, spanning from liver failure in the fetus or neonate to infants that survive with medical therapy. Here we report on 2 sets of fraternal twins, each set with a gross disparity in the severity of presentation: 1 infant with liver failure and the other nearly unaffected. These findings suggest a need to look carefully for subclinical disease in the siblings of patients with NH by using sensitive tests such as those for ferritin and α-fetoprotein. They also suggest that affected infants may be missed when using routine clinical testing, which would lead to the apparent rate of recurrence, understating the actual recurrence rate.
Tenofovir Disoproxil Fumarate and an Optimized Background Regimen of Antiretroviral Agents as Salvage Therapy for Pediatric HIV Infection
Authors: Hazra Rohan , Gafni Rachel I. , Maldarelli Frank , Balis Frank M. , Tullio Antonella N. , DeCarlo Ellen , Worrell Carol J. , Steinberg Seth M. , Flaherty John , Yale Kitty , Kearney Brian P. , Zeichner Steven L.
Published: November 2005

Objectives. Highly active antiretroviral therapy has altered the course of HIV infection among children, but new antiretroviral agents are needed for treatment-experienced children with drug-resistant virus. Tenofovir disoproxil fumarate (DF) is a promising agent for use in pediatric salvage therapy, because of its tolerability, efficacy, and resistance profile. We designed this study to provide preliminary pediatric safety and dosing information on tenofovir DF, while also providing potentially efficacious salvage therapy for heavily treatment-experienced, HIV-infected children.

Methods. Tenofovir DF, alone and in combination with optimized background antiretroviral regimens, was studied among 18 HIV-infected children (age range: 8.3–16.2 years) who had progressive disease with ≥2 prior antiretroviral regimens, in a single-center, open-label trial. Tenofovir DF monotherapy for 6 days was followed by the addition of individualized antiretroviral regimens. Subjects were monitored with HIV RNA reverse transcription-polymerase chain reaction, flow cytometry, and routine laboratory studies; monitoring for bone toxicity included measurement of lumbar spine bone mineral density (BMD) with dual-energy x-ray absorptiometry. Subjects were monitored through 48 weeks.

Results. Two subjects developed grade 3 elevated hepatic transaminase levels during monotherapy and were removed from the study. The remaining 16 subjects had a median of 4 antiretroviral agents (range: 3–5 agents) added to tenofovir DF. HIV plasma RNA levels decreased from a median pretreatment level of 5.4 log10 copies per mL (range: 4.1–5.9 log10 copies per mL) to 4.21 log10 copies per mL at week 48 (n = 15), with 6 subjects having <400 copies per mL, including 4 with <50 copies per mL. The overall median increases in CD4+ T cell counts were 58 cells per mm3 (range: −64 to 589 cells per mm3) at week 24 and 0 cells per mm3 (range: −274 to 768 cells per mm3) at week 48. The CD4+ cell responses among the virologic responders were high and sustained. The major toxicity attributed to tenofovir DF was a >6% decrease in BMD for 5 of 15 subjects evaluated at week 48, necessitating the discontinuation of tenofovir DF therapy for 2; all 5 subjects experienced >2 log10 copies per mL decreases in HIV plasma RNA levels.

Conclusions. Tenofovir DF-containing, individualized, highly active antiretroviral therapy regimens were well tolerated and effective among heavily treatment-experienced, HIV-infected children. Loss of BMD may limit tenofovir DF use among prepubertal patients.
Reflexivity, contraction functions and minimum-norm elements
Authors: Aizpuru A. , García-Pacheco F. J.
Published: November 2005

Here we present a new proof of Blatter's result: a normed space is complete if every bounded closed convex subset has an element of minimum norm. We also present geometrical conditions for the existence of minimum-norm elements in bounded closed convex sets. Also, we characterize reflexivity in the class of Banach spaces by means of contraction functions. Furthermore, we study what happens if we remove the completeness hypothesis.
Characterizations of nonsmooth generalized polarly cone-monotone maps
Authors: Ivanov Vsevolod Ivanov
Published: November 2005

In this paper we consider different types of generalized cone-mono-tone maps: polarly C-monotone, strictly polarly C-monotone, strongly polarly C-monotone, polarly C-pseudomonotone, strictly polarly C-pseudomonotone and polarly C-quasimonotone maps, where C is a cone in a finite-dimensional space Rm. We characterize these maps in the case when they are radially continuous with respect to the positive polar cone C+ of the cone C, generalizing some well known results. In the obtained theorems we use first and higher-order lower Dini directional derivatives.
DH‐I‐180‐3‐Mediated Photodynamic Therapy: Biodistribution and Tumor Vascular Damage
Authors: Lim Dae‐Seog , Kol Si‐Hwan , Lee Chang‐Hee , Ahn Woong‐Shick , Lee Won‐Young
Published: November 2005

An important goal of photodynamic therapy (PDT) for treatment of various cancers is to shorten PDT‐performing time and simultaneously enhance PDT efficacy. Here, we investigated the nontumor tissue distribution of and the tumor vascular damage caused by a new photosensitizer, DH‐I‐180–3, in mice with implanted EMT6 mammary tumor cells. In addition, we performed cell‐based assays to evaluate the basic antitumor effect of DH‐I‐180–3PDT in EMT6 cells. After administration of PDT, the type of cell death was characterized to be apoptosis, and a change in the mitochondrial membrane potential was also observed within minutes. On the other hand, tumor growth was remarkably retardedin vivoin mice that received DH‐I‐180–3/PDT, compared with mice in the control group, which were exposed to light irradiation alone. Finally, tumors in some mice nearly healed. The antitumor drug reached a maximum concentration approximately 3 h after administration. However, PDT was most effective when there was substantial accumulation of DH‐I‐180–3 in the tumor vasculature and in healthy tissue. The histological demonstration provided further evidence of tumor vascular damage. On the basis of these findings, we suggest that PDT with the photosensitizer DH‐I‐180–3 induces vascular damage with blood vessel shutdown, in addition to direct killing of tumor cells, in mice.
Hygienic quality of stem fractions of mechanically processed fibre hemp and linseed
Authors: KYMÄLÄINEN H-R. , NYKTER M. , HAUTALA M.
Published: November 2005

Bast fibre is the most important fraction of bast fibre plants for technical products, i.e. thermal insulations and packaging materials. The hygienic quality of the various fractions of bast fibre plants is of interest in thermal insulations, because it may affect the quality of indoor air. Packaging materials may be associated e.g. with foodstuffs, which highlights the importance of hygienic quality. The aim of this study was to screen the hygienic quality, determined as microbial content, of mechanically fractionated fibre hemp and linseed plants harvested in the autumn before frost, after early frost and in spring. In addition, the possible correlation between microbes and ash was investigated. Two plant species, fibre hemp and linseed were studied. The plants were cultivated in Siuntio in southern Finland during the years 2002 and 2003, harvested in autumn or in spring and mechanically fractionated. The microbial contents of the fractions were examined by measuring the total number of microbes using Hygicult® growing slides. The microbial content of fractions of fibre hemp and linseed varied between 103 and 109 cfu/gdw. The fibre of hemp harvested after early frost or in spring had the lowest amount of moulds, but during winter and spring the amounts of bacteria and yeasts increased in hemp. Mechanically separated fibre and shive contained less microbes than the stalk. Ash contents of all examined samples of stems and stem fractions varied between 1% and 14%. The fibre after fractionating had a lower ash content (2.33.3%) than that of stems (4.46.9%) harvested in the autumn. The ash content of stem and shive decreased to 1.6% during winter, the ash content of fibre being even somewhat lower (0.9%). No correlation was observed between the contents of microbes and ash.;
Forward hedging under price and production risk of wheat
Authors: LIU X. , PIETOLA K.
Published: November 2005

This paper estimates optimal hedging ratios for a Finnish spring wheat producer under price and yield uncertainty. The contract available for hedging fixes the price and quantity at the time of sowing for a delivery at harvest. Autoregressive models are used to obtain point forecasts for the conditional mean price and price volatility at harvest. Expected yield and yield volatility are estimated from the field experiment data. A range of coefficients of absolute risk aversion are used in the computations. The results suggest that yield volatility is large and it dominates the price volatility in the optimal hedging decisions of the Finnish wheat producers. The point estimate for the price and yield correlation is negative and has a large magnitude. Thus, a negative correlation between the price and the yield, as signalled by the point estimate, will decrease the optimal hedging ratio since the Finnish farmers do not have access to selling put options when they enter in a forward contract.;
Weed flora and weed management of field peas in Finland
Authors: SALONEN J. , HYVÖNEN T. , JALLI H.
Published: November 2005

The composition of the weed flora of dry pea (Pisum sativum L.) fields and cropping practices were investigated in southwestern Finland. Surveys were done in 20022003 in 119 conventionally cropped fields and 64 fields under organic cropping. Herbicides were applied to 92% of conventionally cropped fields where they provided relatively good control but were costly. Weeds were controlled mechanically only in five fields under organic production. A total of 76 weed species were recorded, of which 29 exceeded the 10% frequency level of occurrence. The average number of weed species per field was 10 under conventional cropping and 18 under organic cropping. The most frequent weed species in both cropping practices were Chenopodium album, Stellaria media and Viola arvensis. Elymus repens was the most frequent grass species. The difference in species composition under conventional and organic cropping was detected with Redundancy Analysis. Under conventional cropping, features of crop stand and weed control explained 38.7% and 37.6% of the variation respectively. Under organic cropping the age of crop stand and field location (y co-ordinate) respectively explained best the variation. Weeds could be efficiently managed with herbicides under conventional cropping, but they represented a significant problem for organic production. Mixed cultivation of pea with cereals is recommended, particularly for organic cropping, as it favours crop competition against weeds.;
Depletion of Endogenous Germ Cells in Male Pigs and Goats in Preparation for Germ Cell Transplantation
Authors: Honaramooz Ali , Behboodi Esmail , Hausler Carl L. , Blash Stephen , Ayres Sandra , Azuma Chieko , Echelard Yann , Dobrinski Ina
Published: November 2005

ABSTRACT: The efficiency of germ cell transplantation, the procedure of transferring germ cells from a donor male into the testes of recipient males, can be greatly increased by reduction of endogenous germ cells in recipient animals. To develop effective methods for suppression of endogenous spermatogenesis in potential pig and goat recipients, we either administered busulfan to pregnant sows or irradiated the testes of immature goats. Piglets from sows treated twice with busulfan (7.5 mg/kg) at days 98 and 108 of gestation showed reduced gonocyte numbers at 2, 4, and 8 weeks of age and reduced initiation of spermatogenesis at 16 weeks of age. For goats, groups of 3 kids at 1, 5, or 9.5 weeks of age received fractionated irradiation of the testes with 3 doses of 2 Gy on 3 consecutive days. At 2 months after irradiation, 5%‐10% of seminiferous tubule cross sections contained pachytene spermatocytes, compared with 50%‐100% in controls. At 3 months after irradiation, spermatozoa appeared in 20% of tubule cross sections in all treated goats and in 100% of tubules in control goats. By 6 months after irradiation, spermatogenesis had recovered in 60% of tubules in goats treated at 5 or 9.5 weeks of age but in only 29% of tubules after treatment at 1 week of age. Therefore, late gestation in utero treatment of pigs with low doses of busulfan and testicular irradiation of goats at 1 week of age will result in a reduction in the endogenous germ cell population that could facilitate donor cell colonization after germ cell transplantation.
Monoclonal Antibody From Vasectomized Mouse Identifies a Conserved Testis‐Specific Antigen TSA70
Authors: Wakle Monali S. , Joshi Saurabh A. , Khole Vrinda V.
Published: November 2005

ABSTRACT: Vasectomy results in the occlusion of testicular outflow, leading to autoimmunity characterized by the production of antisperm antibodies (ASA). Reports on the rise in ASA following vasectomy in several species are available; however, not much is known about the specific sperm autoantigens to which postvasectomy antibodies are directed. In the present study, monoclonal antibodies were generated using a vasectomized mouse. One of the monoclonal antibodies, D5E5, identified an approximately 70‐kd antigen localized on the principal piece of the tail and also on the tip of the acrosome of mouse sperm. The cognate antigen was expressed postmeiotically in a stage‐specific manner during spermiogenesis, starting from step 8 of elongating spermatids during spermiogenesis up to mature spermatozoa. The protein was conserved across the species, as observed by its presence in rat, bull, marmoset, and human sperm. Following capacitation, the antigen on the head was seen to shift to the acrosomal region and was lost after the acrosome reaction. However, the localization on tip of the acrosome still persisted, which indicates that the antigen may play a role post‐acrosome reaction in sperm egg interaction. Resistance to Triton X‐100 solubilization indicates that TSA70 could be an acrosomal matrix protein. In addition, we observed a significant reduction in forward progressive motility of mouse sperm treated in vitro with D5E5. In view of its testis specificity, acrosome and tail localization, and conserved nature, TSA70 is likely to play an important role in sperm function.
DNA Integrity Is Compromised in Protamine‐Deficient Human Sperm
Authors: Aoki Vincent W. , Moskovtsev Sergey I. , Willis Jennifer , Liu Lihua , Mullen J. Brendan M. , Carrell Douglas T.
Published: November 2005

ABSTRACT:The objective of this study was to examine the relationship between DNA integrity and protamines in human sperm. One hundred forty‐nine male infertility patients were included in an Institutional Review Board‐approved study. Sperm were evaluated for DNA fragmentation using the DNA Integrity Assay, a test equivalent to the sperm chromatin structure assay (SCSA). Additionally, nuclear proteins were extracted and the protamine‐1/protamine‐2 ratio (P1/P2), protamine‐1 (P1), protamine‐2 (P2), and total protamine concentrations were evaluated. We identified 37 patients with abnormally low P1/P2 ratios, 99 patients with normal P1/P2 ratios, and 13 patients with abnormally high P1/P2 ratios. DNA fragmentation was significantly elevated in patients with low P1/P2 ratios (37.1 ± 6.02) vs those with normal and high P1/P2 ratios (26.7 ± 1.9 and 23.8 ± 3.2, respectively; P < .05) and was inversely correlated with the P1/P2 ratio (Rs−0.18, P < .05), P1 concentration (Rs−0.29, P < .001), P2 concentration (Rs− 0.24, P < .005), and total protamine concentration (Rs−0.28, P < .001). Furthermore, χ2 analysis revealed a significant increase in the incidence of marked DNA fragmentation in patients with diminished levels of either P1 or P2. The present study is the first to report that human sperm protamine content is significantly related to DNA fragmentation. In particular, sperm P1 and P2 concentrations inversely correlate with DNA fragmentation, indicating a protective role of the protamines against sperm DNA damage. In light of recent studies highlighting the negative effect of sperm DNA damage on ART outcomes, these findings indicate a possible clinical significance for human sperm protamine levels.
Single‐Nucleotide Polymorphisms and Mutation Analyses of the TNP1 and TNP2 Genes of Fertile and Infertile Human Male Populations
Authors: Miyagawa Yasushi , Nishimura Hiromi , Tsujimura Akira , Matsuoka Yasuhiro , Matsumiya Kiyomi , Okuyama Akihiko , Nishimune Yoshitake , Tanaka Hiromitsu
Published: November 2005

ABSTRACT: Previously, we examined the relationship between protamine gene variations and human male infertility. In this study, we show specific variability in the transition nuclear protein genes (TNPs) of sterile male patients. Transition nuclear proteins (TPs) are major nuclear proteins that replace nuclear histones, leading to eventual substitution by protamines during human spermiogenesis. Analysis of the human TNP1 and TNP2 gene sequences in 282 sterile male patients and 270 (TNP1) and 266 (TNP2) proven‐fertile male volunteers revealed 5 amino acid substitution‐causing single nucleotide polymorphisms (SNPs) in the open‐reading frame of the TNP2 gene. On the other hand, a deletion of 15 nucleotides, which encompassed the recognition site for the cAMP response element (CRE) transcription factor, was found in the 5′‐promoter region of the TNP1 gene in infertile men. This deletion reduces TNP1 expression and may cause human male infertility.
Corruption and reforms: A case of Poland’s medical sector
Authors: Leven Bozena
Published: November 2005

This study focuses on the effects of Poland’s reforms in the period 1990e2005 on corruption in the health care system. In the last 15 years Poland has transformed its economy drastically, introducing market-oriented reforms into almost every aspect of its economy. In this study we consider how different reforms changed incentives and mechanisms facilitating corruption in the medical care sector. Our conclusion is that corruption in Poland’s medical sector has worsened since the onset of the marketization reforms. We support this conclusion primarily by analyzing changes in incentives for corruption and the number of mechanisms facilitating it. In addition, where available, quantitative data are provided, though we recognize that numerical estimates of corruption are subject to substantial error. We focus on three major forms of corruption: patient payments to secure medical treatment or improve its quality, payments from industry (mostly pharmaceutical and medical equipment producers), and the use by physicians of free public facilities for private patients.
Intervention in a family of Boolean networks
Authors: Choudhary Ashish , Datta Aniruddha , Bittner Michael L. , Dougherty Edward R.
Published: November 2005

Motivation: Intervention in a gene regulatory network is used to avoid undesirable states, such as those associated with a disease. Several types of intervention have been studied in the framework of a probabilistic Boolean network (PBN), which is a collection of Boolean networks in which the gene state vector transitions according to the rules of one of the constituent networks and where network choice is governed by a selection distribution. The theory of automatic control has been applied to find optimal strategies for manipulating external control variables that affect the transition probabilities to desirably affect dynamic evolution over a finite time horizon. In this paper we treat a case in which we lack the governing probability structure for Boolean network selection, so we simply have a family of Boolean networks, but where these networks possess a common attractor structure. This corresponds to the situation in which network construction is treated as an ill-posed inverse problem in which there are many Boolean networks created from the data under the constraint that they all possess attractor structures matching the data states, which are assumed to arise from sampling the steady state of the real biological network.

Results: Given a family of Boolean networks possessing a common attractor structure composed of singleton attractors, a control algorithm is derived by minimizing a composite finite-horizon cost function that is a weighted average over all the individual networks, the idea being that we desire a control policy that on average suits the networks because these are viewed as equivalent relative to the data. The weighting for each network at any time point is taken to be proportional to the instantaneous estimated probability of that network being the underlying network governing the state transition. The results are applied to a family of Boolean networks derived from gene-expression data collected in a study of metastatic melanoma, the intent being to devise a control strategy that reduces the WNT5A gene's action in affecting biological regulation.

Availability: The software is available on request.

Contact:  edward@ee.tamu.edu

Supplementary information: The supplementary Information is available at
POLITICAL ECONOMY AND THE EFFICIENCY OF COMPENSATION FOR TAKINGS
Authors: BRENNAN TIMOTHY J. , BOYD JAMES
Published: November 2005

To assess compensation for regulation‐induced “takings,” the authors model political support for regulation as a function of externalities, landowner wealth, and tax burdens. When competing social interests have equal influence on political outcomes, compensation should not be paid. However, when environmentalists and property owners have unequal influence, the model yields several counterintuitive implications. For example, disenfranchised environmentalists should support takings compensation, since it reduces landowner opposition to regulation. The authors also show how compensation rules can limit the deadweight social costs of income transfers, while recognizing their effects on regulator and landowner behavior. (JELK11,D72,L51)
IS THERE A CASE FOR LOW INFLATION‐INDUCED PRODUCTIVITY GROWTH IN SELECTED ASIAN ECONOMIES?
Authors: MAHADEVAN RENUKA , ASAFU‐ADJAYE JOHN
Published: November 2005

The authors examine the evidence on the relationship between inflation and productivity growth for nine Asian economies using causality analysis in a multivariate model with money supply as a possible effective monetary policy tool. The inflation‐productivity growth relationship is found to be non‐uniform, as the evidence of uni‐directional, bi‐directional, and no causality between the two variables is varied and significant for some countries and insignificant for others. An attempt is made to explain the inflation‐productivity nexus for these countries and to discuss implications for anti‐inflationary policies such as inflation targeting. (JEL E31, O47, C32)
Functional Genomic Analysis of theAUXIN/INDOLE-3-ACETIC ACIDGene Family Members inArabidopsis thaliana [W]
Authors: Overvoorde Paul J. , Okushima Yoko , Alonso José M. , Chan April , Chang Charlie , Ecker Joseph R. , Hughes Beth , Liu Amy , Onodera Courtney , Quach Hong , Smith Alison , Yu Guixia , Theologis Athanasios
Published: November 2005

Auxin regulates various aspects of plant growth and development. The AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) genes encode short-lived transcriptional repressors that are targeted by the TRANSPORT INHIBITOR RESPONSE1/AUXIN RECEPTOR F-BOX proteins. The Aux/IAA proteins regulate auxin-mediated gene expression by interacting with members of the AUXIN RESPONSE FACTOR protein family. Aux/IAA function is poorly understood; herein, we report the identification and characterization of insertion mutants in 12 of the 29 Aux/IAA family members. The mutants show no visible developmental defects compared with the wild type. Double or triple mutants of closely related Aux/IAA genes, such as iaa8-1 iaa9-1 or iaa5-1 iaa6-1 iaa19-1, also exhibit wild-type phenotypes. Global gene expression analysis reveals that the molecular phenotypes of auxin-treated and untreated light-grown seedlings are unaffected in the iaa17-6 and iaa5-1 iaa6-1 iaa19-1 mutants. By contrast, similar analysis with the gain-of-function axr3-1/iaa17-1 mutant seedlings reveals dramatic changes in basal and auxin-induced gene expression compared with the wild type. Expression of several type-A ARABIDOPSIS RESPONSE REGULATOR genes and a number of genes involved in cell wall biosynthesis and degradation is repressed in axr3-1/iaa17-1. The data suggest extensive functional redundancy among Aux/IAA gene family members and that enhanced stability of the AXR3/IAA17 protein severely alters the molecular phenotype, resulting in developmental defects.
Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension
Authors: Tji-Joong Gan C. , Lankhaar Jan-Willem , Marcus J. Tim , Westerhof Nico , Marques Koen M. , Bronzwaer Jean G. F. , Boonstra Anco , Postmus Pieter E. , Vonk-Noordegraaf Anton
Published: November 2005

The aim of this study was to investigate the contribution of direct right-to-left ventricular interaction to left ventricular filling and stroke volume in 46 patients with pulmonary arterial hypertension (PAH) and 18 control subjects. Stroke volume, right and left ventricular volumes, left ventricular filling rate, and interventricular septum curvature were measured by magnetic resonance imaging and left atrial filling by transesophageal echocardiography. Stroke volume, left ventricular end-diastolic volume, and left ventricular peak filling rate were decreased in PAH patients compared with control subjects: 28 ± 13 vs. 41 ± 10 ml/m2( P < 0.001), 46 ± 14 vs. 61 ± 14 ml/m2( P < 0.001), and 216 ± 90 vs. 541 ± 248 ml/s ( P < 0.001), respectively. Among PAH patients, stroke volume did not correlate to right ventricular end-diastolic volume or mean pulmonary arterial pressure but did correlate to left ventricular end-diastolic volume ( r = 0.62, P < 0.001). Leftward interventricular septum curvature was correlated to left ventricular filling rate ( r = 0.64, P < 0.001) and left ventricular end-diastolic volume ( r = 0.65, P < 0.001). In contrast, left atrial filling was normal and not correlated to left ventricular end-diastolic volume. In PAH patients, ventricular interaction mediated by the interventricular septum impairs left ventricular filling, contributing to decreased stroke volume.
Releasing First-World Wealth for Global Mission: What Levers Can be Pulled Today?
Authors: Ross Kenneth
Published: November 2005

There has been a lively debate about whether first-world wealth is a benefit or a handicap to worldwide Christian mission. Nonetheless it remains a matter of concern that formidable obstacles stand in the path of a flow of resources from wealthy countries to support missionary work. Church decline in the West, a new parochialism, a consumerist lifestyle, project orientation, soteriological relativism and more sophisticated models of mission are some of the forces which have acted to reduce Western financial support for cross-cultural mission worldwide. Nonetheless there are levers, both old and new, which can be pulled to revive and consolidate such support. The uncancelled mandate of the Great Commission, the cry for justice for the poor, the appeal of catholicity and mutuality and the potential of local initiative and direct involvement of local church members are some of the levers which can propel renewed support for Christian mission worldwide. Many missionary initiatives will stand or fall depending on how effectively these levers can be pulled.
Decreased expression of cytochrome P450 protein in non-malignant colonic tissue of patients with colonic adenoma
Authors: Bergheim Ina , Bode Christiane , Parlesak Alexandr
Published: November 2005

Background

Cytochrome P450 (CYP) enzymes in epithelial cells lining the alimentary tract play an important role in both the elimination and activation of (pro-)carcinogens. To estimate the role of cytochrome P450 in carcinogenesis of the colon, expression patterns and protein levels of four representative CYPs (CYP2C, CYP2E1, CYP3A4 and CYP3A5) were determined in colon mucosa of normal and adenomatous colonic tissue of patients with adenomas and disease-free controls.

Methods

Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 in colon mucosa of normal and adenomatous colonic tissue of patients with adenoma and disease-free controls was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot.

Results

With the exception of CYP3A5, expression of CYP mRNA was similar among groups and tissues (e.g. normal colon mucosa and adenoma). CYP3A5 mRNA expression was significantly higher in adenoma in comparison to normal tissue of patients with adenoma (~48%). When comparing protein concentrations of CYPs measured in adenomas with neighboring normal colonic mucosa no differences were found. However, in normal tissue of patients with adenomas, protein levels of CYP2C8, CYP3A4 and CYP3A5, but not that of CYP2E1, were significantly lower than in biopsies obtained from disease-free controls. Specifically, in normal colonic mucosa of patients protein concentrations of CYP2C8, CYP3A4, and CYP3A5 were ~86%, ~69%, and ~54%, respectively, lower than in disease-free controls.

Conclusion

In conclusion, among other factors, the altered protein levels of certain CYPs (e.g. CYP2C8, CYP3A4 and CYP3A5) in colon mucosa might contribute to the development of neoplasia in the colon.
Increased risk of cancer among relatives of patients with lung cancer in China
Authors: Jin Yongtang , Xu Yingchun , Xu Ming , Xue Saoli
Published: November 2005

Background

Genetic factors were considered as one of the risk factors for lung cancer or other cancers. The aim of this work was to determine whether a genetic predisposition accounts for such familial aggregation of cancer among relatives of lung cancer probands.

Methods

A case-control study was conducted in 800 case families identified by lung cancer patients (probands), and in 800 control families identified by the probands'spouses. The data were analysed with logistic regression analysis model.

Results

The data revealed a significantly greater overall risk of cancer (OR = 1.82, P < 0.01) in the proband group. The relatives of lung cancer probands maintained an increased risk of non-lung cancer (P < 0.05) after adjusting for confounder factors. The crude odds ratio of a proband family having one family member with cancer was 1.67 compared with control families. Proband families were 2.56 times more likely to have two other family members with cancer. For three cancers and four or more cancers, the risk increased to 3.50 and 5.91, respectively. The most striking differences in cancer prevalence between proband and control families were noted for cancer risk among female relatives. The strongest effects were for not only lung cancer in any female relatives (OR 2.17, 95%CI 1.60–3.64) and mothers (OR 2.78, 95%CI 1.23–5.12) and sisters (OR 2.03, 95%CI 1.26–3.97), but also non-lung cancer in females and mothers (OR 2.00, 95%CI 1.26–3.01, and OR 2.34, 95%CI 1.28–4.40, respectively).

Conclusion

These data support the hypothesis of a genetic susceptibility to cancer in families with lung cancer, and the female genetic susceptibility to cancer might be greater than male.
Biochemical characterization of the Arctic char (Salvelinus alpinus) ovarian progestin membrane receptor
Authors: Berg A Håkan , Thomas Peter , Olsson Per-Erik
Published: November 2005

Membrane progestin receptors are involved in oocyte maturation in teleosts. However, the maturation-inducing steroid (MIS) does not appear to be conserved among species and several progestins may fulfill this function. So far, complete biochemical characterization has only been performed on a few species. In the present study we have characterized the membrane progestin receptor in Arctic char (Salvelinus alpinus) and show that the 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) receptor also binds several xenobiotics, thus rendering oocyte maturation sensitive to environmental pollutants. We identified a single class of high affinity (Kd, 13.8 ± 1.1 nM), low capacity (Bmax, 1.6 ± 0.6 pmol/g ovary) binding sites by saturation and Scatchard analyses. Receptor binding displayed rapid association and dissociation kinetics typical of steroid membrane receptors, with t1/2 s of less than 1 minute. The 17,20beta-P binding also displayed tissue specificity with high, saturable, and specific 17,20beta-P binding detected in ovaries, heart and gills while no specific binding was observed in muscle, brain or liver. Changes in 17,20beta-P binding during oocyte maturation were consistent with its identity as the oocyte MIS membrane receptor. Incubation of fully-grown ovarian follicles with gonadotropin induced oocyte maturation, which was accompanied by a five-fold increase in 17,20beta-P receptor binding. In addition, competition studies with a variety of steroids revealed that receptor binding is highly specific for 17,20beta-P, the likely maturation-inducing steroid (MIS) in Arctic char. The relative-binding affinities of all the other progestogens and steroids tested were less than 5% of that of 17,20beta-P for the receptor. Several ortho, para derivatives of DDT also showed weak binding affinity for the 17,20beta-P receptor supporting the hypothesis that xenobiotics may bind steroid receptors on the oocyte's surface and might thereby interfere with oocyte growth and maturation.
Supply-demand balance in outward-directed networks and Kleiber's law
Authors: Painter Page R
Published: November 2005

Background

Recent theories have attempted to derive the value of the exponent α in the allometric formula for scaling of basal metabolic rate from the properties of distribution network models for arteries and capillaries. It has recently been stated that a basic theorem relating the sum of nutrient currents to the specific nutrient uptake rate, together with a relationship claimed to be required in order to match nutrient supply to nutrient demand in 3-dimensional outward-directed networks, leads to Kleiber's law (b = 3/4).

Methods

The validity of the supply-demand matching principle and the assumptions required to prove the basic theorem are assessed. The supply-demand principle is evaluated by examining the supply term and the demand term in outward-directed lattice models of nutrient and water distribution systems and by applying the principle to fractal-like models of mammalian arterial systems.

Results

Application of the supply-demand principle to bifurcating fractal-like networks that are outward-directed does not predict 3/4-power scaling, and evaluation of water distribution system models shows that the matching principle does not match supply to demand in such systems. Furthermore, proof of the basic theorem is shown to require that the covariance of nutrient uptake and current path length is 0, an assumption unlikely to be true in mammalian arterial systems.

Conclusion

The supply-demand matching principle does not lead to a satisfactory explanation for the approximately 3/4-power scaling of mammalian basal metabolic rate.