bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute cholecystitis – early laparoskopic surgery versus antibiotic therapy and delayed elective cholecystectomy: ACDC-study
Authors: Weigand Kilian , Köninger Jörg , Encke Jens , Büchler Markus W , Stremmel Wolfgang , Gutt Carsten N
Published: October 2007

Background

Acute cholecystitis occurs frequently in the elderly and in patients with gall stones. Most cases of severe or recurrent cholecystitis eventually require surgery, usually laparoscopic cholecystectomy in the Western World. It is unclear whether an initial, conservative approach with antibiotic and symptomatic therapy followed by delayed elective surgery would result in better morbidity and outcome than immediate surgery. At present, treatment is generally determined by whether the patient first sees a surgeon or a gastroenterologist. We wish to investigate whether both approaches are equivalent. The primary endpoint is the morbidity until day 75 after inclusion into the study.

Design

A multicenter, prospective, randomized non-blinded study to compare treatment outcome, complications and 75-day morbidity in patients with acute cholecystitis randomized to laparoscopic cholecystectomy within 24 hours of symptom onset or antibiotic treatment with moxifloxacin and subsequent elective cholecystectomy. For consistency in both arms moxifloxacin, a fluorquinolone with broad spectrum of activity and high bile concentration is used as antibiotic. Duration: October 2006 – November 2008

Organisation/Responsibility

The trial was planned and is being conducted and analysed by the Departments of Gastroenterology and General Surgery at the University Hospital of Heidelberg according to the ethical, regulatory and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and the Good Clinical Practice guideline (GCP).

Trial Registration

ClinicalTrials.gov NCT00447304
Genetic subtraction profiling identifies genes essential for Arabidopsisreproduction and reveals interaction between the female gametophyte and the maternal sporophyte
Authors: Johnston Amal J , Meier Patrick , Gheyselinck Jacqueline , Wuest Samuel EJ , Federer Michael , Schlagenhauf Edith , Becker Jörg D , Grossniklaus Ueli
Published: October 2007

Background

The embryo sac contains the haploid maternal cell types necessary for double fertilization and subsequent seed development in plants. Large-scale identification of genes expressed in the embryo sac remains cumbersome because of its inherent microscopic and inaccessible nature. We used genetic subtraction and comparative profiling by microarray between the Arabidopsis thaliana wild-type and a sporophytic mutant lacking an embryo sac in order to identify embryo sac expressed genes in this model organism. The influences of the embryo sac on the surrounding sporophytic tissues were previously thought to be negligible or nonexistent; we investigated the extent of these interactions by transcriptome analysis.

Results

We identified 1,260 genes as embryo sac expressed by analyzing both our dataset and a recently reported dataset, obtained by a similar approach, using three statistical procedures. Spatial expression of nine genes (for instance a central cell expressed trithorax-like gene, an egg cell expressed gene encoding a kinase, and a synergid expressed gene encoding a permease) validated our approach. We analyzed mutants in five of the newly identified genes that exhibited developmental anomalies during reproductive development. A total of 527 genes were identified for their expression in ovules of mutants lacking an embryo sac, at levels that were twofold higher than in the wild type.

Conclusion

Identification of embryo sac expressed genes establishes a basis for the functional dissection of embryo sac development and function. Sporophytic gain of expression in mutants lacking an embryo sac suggests that a substantial portion of the sporophytic transcriptome involved in carpel and ovule development is, unexpectedly, under the indirect influence of the embryo sac.
Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity
Authors: Choi Seung-Chul , Kim Kwang Dong , Kim Jong-Tae , Kim Jae Wha , Lee Hee Gu , Kim Jin-Man , Jang Yong-Suk , Yoon Do-Young , Kim Keun Il , Yang Young , Cho Dae Ho , Lim Jong-Seok
Published: October 2007

We reported previously that N-myc downstream-regulated gene 2 (NDRG2), a member of a new family of differentiation-related genes, is expressed specifically in dendritic cells (DC) differentiated from monocytes, CD34+ progenitor cells, and the myelomonocytic leukemic cell line. In this study, we demonstrate that NDRG2 protein expression is detected, not only in in vitro-differentiated DC but also in primary DC from lymph nodes, thymus, and skin when anti-NDRG2 antibodies are used. As predicted from previous studies investigating the mRNA expression pattern of several types of cell lines, progenitor cells, and DC, NDRG2 protein was expressed strongly in DC. Its expression was detected at significant levels after differentiation from progenitor cells. RNA interference of NDRG2 demonstrated that activated leukocyte cell adhesion molecule (ALCAM) expression is down-regulated specifically in DC differentiated from NDRG2 small interfering RNA (siRNA)-transfected monocytes. This was consistent with our observation that U937 cells transfected with NDRG2 became resistant to the GM-CSF/IL-4-induced ALCAM reduction. Furthermore, DC, which had differentiated from NDRG2 siRNA-transfected monocytes, showed a reduced ability to induce T cell proliferation. Taken together, our results indicate that NDRG2 is able to preserve ALCAM expression during DC differentiation from monocytes under cytokine culture conditions and that its expression helps DC maintain costimulatory signals necessary for T cell stimulation.
Expression of Delta-Like Protein 4 in the Human Endometrium
Authors: Mazella J. , Liang S. , Tseng L.
Published: October 2007

Activation of Delta-Notch signaling pathway promotes the development of the vascular system in embryo, normal adult tissues, and cancerous lesions. Delta and Notch genes are known to be expressed in endothelial cells, and little is known of their expression beyond the vascular system. The purpose of this study was to investigate whether Delta gene would be expressed in cells of the uterine endometrium. In this study, we found that the human endometrial cells expressed one of the Delta ligands, Delta-like 4 protein (Dll4). Dll4 was expressed in human endometrium in a spatiotemporal fashion. Immunohistochemistry studies showed the cytoplasm as well as membrane staining with apical localization both in the luminal and glandular epithelium and moderate diffuse staining in the cytoplasm of the stromal cells. Western blot analysis showed that the size of the endometrial Dll4 was identical to that in the human umbilical endothelial cells. The expression of Dll4 mRNA in human endometrial cells was quantitatively determined by real-time PCR. Dll4 mRNA expressed in the glandular epithelium showed large variations, and it was significantly elevated in the mid and late proliferative and early secretory endometrium. Endometrial stromal cells contained less Dll4 mRNA and had no clear correlation with the menstrual cycle. The effect of hormones was studied in the primary culture of isolated glandular epithelial and stromal cells. In glandular cells, estradiol had little effect, and medroxyprogesterone acetate significantly reduced the mRNAs compared with that of control. Relaxin induced the Dll4 mRNA. In stromal cells, both estradiol and medroxyprogesterone acetate reduced the Dll4 mRNA. To our knowledge, this is the first report of the expression of Dll4 in the endometrium. We propose that endometrial Dll4 may enhance the development of the endometrial microvascular system and facilitate the implantation of blastocyst in a fertile cycle.
Contraction in Human Myometrium Is Associated with Changes in Small Heat Shock Proteins
Authors: MacIntyre David A. , Tyson Elisa K. , Read Mark , Smith Roger , Yeo George , Kwek Kenneth , Chan Eng-Cheng
Published: October 2007

The myometrium undergoes substantial remodeling at the time of labor including rearrangement of the cellular contractile machinery. The regulation of this process in human myometrium at the time of labor is poorly defined, but evidence in other muscle types suggests modulation by small heat shock proteins (sHSP). The aim of this study was to investigate whether similar changes in sHSP occur in the myometrium at labor. Using a quantitative proteomic approach (two-dimensional difference gel electrophoresis), we found a 69% decrease in the sHSP αB-crystallin in the myometrium at labor plus multiple isoforms of HSP27. Immunoblotting using phosphospecific HSP27 antibodies (HSP27-serine15, -78, and -82) detected marked changes in HSP27 phosphorylation at labor. Although total HSP27 levels were unchanged, HSP27-Ser15 was 3-fold higher at labor. Coimmunoprecipitation studies showed that HSP27 coprecipitates with αB-crystallin and also smooth muscle α-actin. Coimmunofluorescence studies demonstrated a relocation of HSP27 from the perinuclear region to the actin cytoskeleton at labor. The functional significance of these changes was demonstrated in vitro where myometrial strips stimulated to contract with oxytocin exhibited increased HSP27-Ser15 phosphorylation. Our findings provide data consistent with a novel pathway regulating human myometrial contraction at labor and identify HSP27 and αB-crystallin as potential targets for future tocolytic design.
Exogenous Ghrelin Attenuates the Progression of Chronic Hypoxia-Induced Pulmonary Hypertension in Conscious Rats
Authors: Schwenke Daryl O. , Tokudome Takeshi , Shirai Mikiyasu , Hosoda Hiroshi , Horio Takeshi , Kishimoto Ichiro , Kangawa Kenji
Published: October 2007

Chronic exposure to hypoxia, a common adverse consequence of most pulmonary disorders, can lead to a sustained increase in pulmonary arterial pressure (PAP), right ventricular hypertrophy, and is, therefore, closely associated with heart failure and increased mortality. Ghrelin, originally identified as an endogenous GH secretagogue, has recently been shown to possess potent vasodilator properties, likely involving modulation of the vascular endothelium and its associated vasoactive peptides. In this study we hypothesized that ghrelin would impede the pathogenesis of pulmonary arterial hypertension during chronic hypoxia (CH). PAP was continuously measured using radiotelemetry, in conscious male Sprague Dawley rats, in normoxia and during 2-wk CH (10% O2). During this hypoxic period, rats received a daily sc injection of either saline or ghrelin (150 μg/kg). Subsequently, heart and lung samples were collected for morphological, histological, and molecular analyses. CH significantly elevated PAP in saline-treated rats, increased wall thickness of peripheral pulmonary arteries, and, consequently, induced right ventricular hypertrophy. In these rats, CH also led to the overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA within the lung. Exogenous ghrelin administration attenuated the CH-induced overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA. Consequently, ghrelin significantly attenuated the development of pulmonary arterial hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy. These results demonstrate the therapeutic benefits of ghrelin for impeding the pathogenesis of pulmonary hypertension and right ventricular hypertrophy, particularly in subjects prone to CH (e.g. pulmonary disorders).
Gonadotropin-Releasing Hormone-1 Neuronal Activity Is Independent of Cyclic Nucleotide-Gated Channels
Authors: Constantin Stéphanie , Wray Susan
Published: October 2007

Pulsatile release of GnRH-1 is essential for secretion of gonadotropin hormones. The frequency of GnRH-1 pulses is regulated during the reproductive cycle by numerous neurotransmitters. Cyclic nucleotide-gated (CNG) channels have been proposed as a mechanism to integrate the cAMP signal evoked by many neurotransmitters. This study reports the expression of the CNGA2 subunit in GnRH-1 neurons obtained from mouse nasal explants and shows the ability of GnRH-1 neurons to increase their activity in response to forskolin (activator of adenylyl cyclases), or 3-isobutyl-1-methylxanthine (inhibitor of phosphodiesterases) even after removal of γ-aminobutyric acid (A)-ergic input. Next, the endogenous activity of adenylyl cyclases was evaluated as a component of the oscillatory mechanism of GnRH-1 neurons. Inhibition of endogenous activity of adenylyl cyclases did not alter GnRH-1 activity. The potential involvement of CNGA2 subunit in basal or induced activity was tested on GnRH-1 neurons obtained from CNGA2-deficient mice. Without up-regulation of CNGA1 or CNGA3, the absence of functional CNGA2 did not alter either the endogenous GnRH-1 neuronal activity or the response to forskolin, negating CNG channels from cAMP-sensitive mechanisms leading to changes in GnRH-1 neuronal activity. In addition, the potential role of CNGA2 subunit in the synchronization of calcium oscillations previously described was evaluated in GnRH-1 neurons from CNGA2-deficient explants. Synchronized calcium oscillations persisted in CNGA2-deficient GnRH-1 neurons. Taken together, these results indicate that CNGA2 channels are not necessary for either the response of GnRH-1 neurons to cAMP increases or the basal rhythmic activity of GnRH-1 neurons.
Lack of Mutations in the Thyroid Hormone Receptor (TR) α and β Genes but Frequent Hypermethylation of the TRβ Gene in Differentiated Thyroid Tumors
Authors: Joseph Biju , Ji Meiju , Liu Dingxie , Hou Peng , Xing Mingzhao
Published: October 2007

Context: It remains inconclusive whether mutations in thyroid hormone receptor (TR) genes naturally occur in thyroid cancer and whether these genes could be suppressors of this cancer.

Objectives: Our objectives were to examine further mutations of TRα and TRβ genes in thyroid cancer and also to examine their methylation as an epigenetic silencing mechanism in thyroid cancer.

Experimental Design: Instead of using a cDNA sequencing approach used in previous studies, we used genomic DNA to sequence directly the coding regions of the TRα and TRβ genes to search mutations in various differentiated thyroid tumors and used methylation-specific PCR to analyze promoter methylation of these genes. Allelic zygosity status at TRβ was also analyzed.

Results: We found no TRα gene mutation in 17 papillary thyroid cancers (PTCs) and 11 follicular thyroid cancers (FTCs), and no TRβ gene mutation in 16 PTCs and 12 FTCs. We also found no methylation of the TRα gene in 33 PTCs, 31 FTCs, 20 follicular thyroid adenomas (FTAs), and 10 thyroid tumor cell lines. In contrast, we found hypermethylation of the TRβ gene in 10 of 29 (34%) PTCs, 22 of 27 (81%) FTCs, five of 20 (25%) follicular thyroid adenomas, and three of 10 (30%) thyroid tumor cell lines, with the highest prevalence in FTC. We additionally examined loss of heterozygosity at TRβ and found it in three of nine (33%) PTCs and three of nine (33%) FTCs.

Conclusions: Mutation is not common in TR genes, whereas hypermethylation of the TRβ gene as an alternative gene silencing mechanism is highly prevalent in thyroid cancer, particularly FTC, consistent with a possible tumor suppressor role of this gene for FTC.
ArabidopsisPOT1A interacts with TERT-V(I8), an N-terminal splicing variant of telomerase
Authors: Rossignol Pascale , Collier Sarah , Bush Max , Shaw Peter , Doonan John H.
Published: October 2007

Chromosome integrity is maintained via the actions of ribonucleoprotein complexes that can add telomeric repeats or can protect the chromosome end from being degraded. POT1 (protection of telomeres 1), a class of single-stranded-DNA-binding proteins, is a regulator of telomeric length. The Arabidopsis genome contains three POT1 homologues: POT1A, POT1B and POT1C. Using yeast two-hybrid assays to identify components of a potential POT1A complex, we retrieved three interactors: the N-terminus of the telomerase, a protein kinase and a plant-specific protein. Further analysis of the interaction of POT1 proteins with telomerase showed that this interaction is specific to POT1A, suggesting a specific role for this paralogue. The interaction is specific to the N-terminal region of the telomerase, which can be encoded by splicing variants. This interaction indicates possible mechanisms for telomerase regulation by alternative splicing and by POT1 proteins.
The long and winding road: influences of intracellular metabolite diffusion on cellular organization and metabolism in skeletal muscle
Authors: Kinsey Stephen T. , Hardy Kristin M. , Locke Bruce R.
Published: October 2007

A fundamental principle of physiology is that cells are small in order to minimize diffusion distances for O2 and intracellular metabolites. In skeletal muscle, it has long been recognized that aerobic fibers that are used for steady state locomotion tend to be smaller than anaerobic fibers that are used for burst movements. This tendency reflects the interaction between diffusion distances and aerobic ATP turnover rates, since maximal intracellular diffusion distances are ultimately limited by fiber size. The effect of diffusion distance on O2 flux in muscle has been the subject of quantitative analyses for a century, but the influence of ATP diffusion from mitochondria to cellular ATPases on aerobic metabolism has received much less attention. The application of reaction–diffusion mathematical models to experimental measurements of aerobic metabolic processes has revealed that the extreme diffusion distances between mitochondria found in some muscle fibers do not necessarily limit the rates of aerobic processes per se, as long as the metabolic process is sufficiently slow. However, skeletal muscle fibers from a variety of animals appear to have intracellular diffusion distances and/or fiber sizes that put them on the brink of diffusion limitation. Thus, intracellular metabolite diffusion likely influences the evolution of muscle design and places limits on muscle function.
Reappraisal of the comparative cost of human locomotion using gait-specific allometric analyses
Authors: Rubenson Jonas , Heliams Denham B. , Maloney Shane K. , Withers Philip C. , Lloyd David G. , Fournier Paul A.
Published: October 2007

The alleged high net energy cost of running and low net energy cost of walking in humans have played an important role in the interpretation of the evolution of human bipedalism and the biomechanical determinants of the metabolic cost of locomotion. This study re-explores how the net metabolic energy cost of running and walking (J kg–1m–1) in humans compares to that of animals of similar mass using new allometric analyses of previously published data. Firstly, this study shows that the use of the slope of the regression between the rate of energy expenditure and speed to calculate the net energy cost of locomotion overestimates the net cost of human running. Also, the net energy cost of human running is only 17% higher than that predicted based on their mass. This value is not exceptional given that over a quarter of the previously examined mammals and birds have a net energy cost of running that is 17% or more above their allometrically predicted value. Using a new allometric equation for the net energy cost of walking, this study also shows that human walking is 20%less expensive than predicted for their mass. Of the animals used to generate this equation, 25% have a relatively lower net cost of walking compared with their allometrically predicted value. This new walking allometric analysis also indicates that the scaling of the net energy cost of locomotion with body mass is gait dependent. In conclusion, the net costs of running and walking in humans are moderately different from those predicted from allometry and are not remarkable for an animal of its size.
Phonotactic walking paths of field crickets in closed-loop conditions and their simulation using a stochastic model
Authors: Mhatre Natasha , Balakrishnan Rohini
Published: October 2007

Field cricket females localize one of many singing males in the field in closed-loop multi-source conditions. To understand this behaviour, field cricket phonotaxis was investigated in a closed-loop walking phonotaxis paradigm, in response to two simultaneously active speakers playing aphasic calling songs. Female phonotactic paths were oriented towards the louder sound sources, but showed great inter-individual variability. Decisions made in the initial phases were correlated with the overall directions of the paths. Interestingly, the sound pressure levels of stimuli did not greatly influence several features of phonotactic paths such as sinuosity, walking bout lengths and durations. In order to ascertain the extent of our understanding of walking phonotaxis, a stochastic model was used to simulate the behaviour observed in the experiment. The model incorporated data from the experiment and our current understanding of field cricket auditory physiology. This model, based on stochastic turning towards the louder side, successfully recaptured several qualitative and quantitative features of the observed phonotactic paths. The simulation also reproduced the paths observed in a separate outdoor field experiment. Virtual crickets that were unilaterally deafened or had poor ear directionality exhibited walking paths similar to those observed in previous experiments.
Environmental stress affects the expression of a carotenoid-based sexual trait in male zebra finches
Authors: Eraud Cyril , Devevey Godefroy , Gaillard Maria , Prost Josiane , Sorci Gabriele , Faivre Bruno
Published: October 2007

Abiotic factors including thermal stress are suggested to exert constrains on sexual ornaments through trade-offs between sexual displays and physiological functions related to self-maintenance. Given the health properties of carotenoid pigments, carotenoid-based ornaments offer a relevant context in which to investigate the effect of environmental stress, such as ambient temperature, on the production and maintenance of secondary sexual traits and, also, to explore the proximate mechanisms shaping their expression. In this study, we exposed male zebra finches (Taeniopygia guttata) to environmental stress by exposing them to two temperature regimes (6 and 26°C) over a 4 week period. Simultaneously, half of the males in each temperature group were supplemented with carotenoids, whereas the other half were not. The expression of a carotenoid-based sexual trait(bill colour) and the amount of circulating carotenoids were assessed before and at the end of the experiment. Carotenoid-supplemented males developed a redder bill, but the effect of supplementation was reduced under cold exposure. However, we found evidence that birds facing a cold stress were carotenoid limited, since supplemented males developed redder bills than the non-supplemented ones. Interestingly, while cold-exposed and non-supplemented males developed duller bills, they circulated a higher amount of carotenoids at the end of the experiment compared to the pre-experimental values. Together, these results suggest that ambient temperature might contribute to the modulation of the expression of carotenoid-based ornaments. Our findings suggest that carotenoids are a limiting resource under cold exposure and that they might be prioritized for self-maintenance at the expense of the ornament. The physiological functions related to self-maintenance that might have benefited from carotenoid saving are discussed.
Natural variation in food acquisition mediatedviaaDrosophilacGMP-dependent protein kinase
Authors: Kaun Karla R. , Riedl Craig A. L. , Chakaborty-Chatterjee Munmun , Belay Amsale T. , Douglas Scott J. , Gibbs Allen G. , Sokolowski Marla B.
Published: October 2007

In natural environments where food abundance and quality can change drastically over time, animals must continuously alter their food acquisition strategies. Although genetic variation contributes to this plasticity, the specific genes involved and their interactions with the environment are poorly understood. Here we report that natural variation in the Drosophilagene, foraging (for), which encodes a cGMP-dependent protein kinase (PKG), affects larval food acquisition in an environmentally dependent fashion. When food is plentiful, the wild-type rover(forR) allele confers lower food intake and higher glucose absorption than both the wild-type sitter (fors) allele and the mutant fors2 allele. When food is scarce, forR, fors and fors2 larvae increase food intake to a common maximal level, but forRlarvae retain their increased absorption efficiency. Changes in forexpression can induce corrective behavioral modifications in response to food deprivation. When reared in environments with low food levels, forR larvae have higher survivorship and faster development than fors and fors2larvae. Together, these results show that natural variation in forhas far reaching implications affecting a suite of phenotypes involved in the regulation of food acquisition.
Spectral and spatial properties of polarized light reflections from the arms of squid (Loligo pealeii) and cuttlefish (Sepia officinalisL.)
Authors: Chiou Tsyr-Huei , Mäthger Lydia M. , Hanlon Roger T. , Cronin Thomas W.
Published: October 2007

On every arm of cuttlefish and squid there is a stripe of high-reflectance iridophores that reflects highly polarized light. Since cephalopods possess polarization vision, it has been hypothesized that these polarized stripes could serve an intraspecific communication function. We determined how polarization changes when these boneless arms move. By measuring the spectral and polarizing properties of the reflected light from samples at various angles of tilt and rotation, we found that the actual posture of the arm has little or no effect on partial polarization or the e-vector angle of the reflected light. However, when the illumination angle changed, the partial polarization of the reflected light also changed. The spectral reflections of the signals were also affected by the angle of illumination but not by the orientation of the sample. Electron microscope samples showed that these stripes are composed of several groups of multilayer platelets within the iridophores. The surface normal to each group is oriented at a different angle, which produces essentially constant reflection of polarized light over a range of viewing angles. These results demonstrate that cuttlefish and squid could send out reliable polarization signals to a receiver regardless of arm orientation.
A chymotrypsin-like serine protease interacts with the chitin synthase from the midgut of the tobacco hornworm
Authors: Broehan Gunnar , Zimoch Lars , Wessels Anton , Ertas Beyhan , Merzendorfer Hans
Published: October 2007

The chitin portion of the peritrophic matrix in the midgut of the tobacco hornworm, Manduca sexta, is produced by chitin synthase 2 (CHS2), a transmembrane family II glycosyltransferase, located at the apical tips of brush border microvilli. To look for proteins that potentially interact with CHS2, we performed yeast two-hybrid screening, identifying a novel chymotrypsin-like protease (CTLP1) that binds to the extracellular carboxyterminal domain of CHS2. The occurrence of this interaction in vivo is supported by co-localization and co-immunoprecipitation data. Based on our findings we propose that chitin synthesis is controlled by an intestinal proteolytic signalling cascade linking chitin synthase activity to the nutritional state of the larvae.
Sex and flow: the consequences of fluid shear for sperm–egg interactions
Authors: Riffell Jeffrey A. , Zimmer Richard K.
Published: October 2007

Fertilization is a complex interaction among biological traits of gametes and physical properties of the fluid environment. At the scale of fertilization (0.01–1 mm), sperm encounter eggs while being transported within a laminar (or viscous) shear flow. Varying laminar-shear in a Taylor-Couette flow tank, our experiments simulated important aspects of small-scale turbulence within the natural habitats of red abalone(Haliotis rufescens), a large marine mollusk and external fertilizer. Behavioral interactions between individual cells, sperm–egg encounter rates, and fertilization success were quantified, simultaneously, using a custom-built infrared laser and computer-assisted video imaging system. Relative to still water, sperm swam faster and moved towards an egg surface,but only in comparatively slow flows. Encounter rate, swim speed and orientation, and fertilization success each peaked at the lowest shear tested(0.1 s–1), and then decayed as shear increased beyond 1.0 s–1. The decay did not result, however, from damage to either sperm or eggs. Analytical and numerical models were used to estimate the propulsive force generated by sperm swimming (Fswim) and the shear force produced by fluid motion within the vicinity of a rotating egg(Fshear). To first order, male gametes were modeled as prolate spheroids. The ratio Fswim/Fshear was useful in explaining sperm–egg interactions. At low shears where Fswim/Fshear>1, sperm swam towards eggs, encounter rates were pronounced, and fertilization success was very high; behavior overpowered fluid motion. In contrast, sperm swimming,encounter rate and fertilization success all decayed rapidly when Fswim/Fshear<1; fluid motion dominated behavior. The shears maximizing fertilization success in the lab typically characterized natural flow microenvironments of spawning red abalone. Gamete behavior thus emerges as a critical determinant of sexual reproduction in the turbulent sea.
Male accessory glands of Drosophila melanogaster make a secreted angiotensin I-converting enzyme (ANCE), suggesting a role for the peptide-processing enzyme in seminal fluid
Authors: Rylett Caroline M. , Walker Michael J. , Howell Gareth J. , Shirras Alan D. , Isaac R. Elwyn
Published: October 2007

Angiotensin I-converting enzyme (ACE) expressed on the surface of endothelial cells is responsible for the last step in the synthesis of circulating angiotensin II and the inactivation of bradykinin. Mammalian ACE is also expressed in the prostate with other components of the renin–angiotensin system, and in developing spermatids, where the peptidase activity is known to be critical for normal sperm function. The importance of an ACE gene to male fertility has also been demonstrated in Drosophila melanogaster, where Ance is expressed in spermatids, and hypomorphic alleles of Ance cause a defect in spermiogenesis. Here we show that ANCE, which shares many enzymatic properties with mammalian ACE, is also a product of the male accessory gland of D. melanogaster. It is expressed in the secondary cells and is associated with the electron dense granule within the large vesicles of these cells. ACE proteolytic activity is lost from the accessory glands during mating,consistent with transfer to the mated female in the seminal fluid. The accessory gland ACE-like activity might have an evolutionarily conserved function processing biologically active peptides with a role in male fertility.
The acoustic mechanics of stick–slip friction in the California spiny lobster (Panulirus interruptus)
Authors: Patek S. N. , Baio J. E.
Published: October 2007

The dynamic interplay between static and sliding friction is fundamental to many animal movements. One interesting example of stick–slip friction is found in the sound-producing apparatus of many spiny lobster species(Palinuridae). The acoustic movements of the spiny lobster's plectrum over the file are generated by stick–slip friction between the two surfaces. We examined the microscopic anatomy, kinematics, acoustics and frictional properties of the California spiny lobster (Panulirus interruptus)toward the goal of quantitatively characterizing the frictional and acoustic mechanics of this system. Using synchronous high-speed video and sound recordings, we tested whether plectrum kinematics are correlated with acoustic signal features and found that plectrum velocity is positively correlated with acoustic amplitude. To characterize the frictional mechanics of the system, we measured frictional forces during sound production using excised plectrums and files. Similar to rubber materials sliding against hard surfaces, the static coefficient of friction in this system was on average 1.7. The change in the coefficient of friction across each stick–slip cycle varied substantially with an average change of 1.1. Although driven at a constant speed, the plectrum slipped at velocities that were positively correlated with the normal force between the two surfaces. Studies of friction in biological systems have focused primarily on adhesion and movement, while studies of stick–slip acoustics have remained under the purview of musical acoustics and engineering design. The present study offers an integrative analysis of an unusual bioacoustic mechanism and contrasts its physical parameters with other biological and engineered systems.
Kinematics of jumping in leafhopper insects (Hemiptera, Auchenorrhyncha,Cicadellidae)
Authors: Burrows Malcolm
Published: October 2007

The jumping movements and performance of leafhopper insects (Hemiptera,Auchenorrhyncha, Cicadellidae) were analysed from high-speed sequences of images captured at rates up to 5000 frames s–1. The propulsion for a jump was delivered by rapid and synchronous movements of the hind legs that are twice the length of the other legs, almost as long as the body, and represent 3.8% of the body mass. The wings were not moved before take-off, but the jump frequently launched a flight. The front and middle legs set the attitude of the body in preparation for a jump but were usually raised from the ground before take-off. The movements of the hind legs occurred in three distinct phases. First, a levation phase of 15–30 ms, in which both hind legs were moved forward and medially so that they were positioned directly beneath the body with their tibio-tarsal joints pressed against each other. Second, a holding phase lasting 10–200 ms, in which the hind legs remained stationary in the fully levated position. Third, a rapid jump phase,in which both hind legs were simultaneously depressed about their coxo-trochanteral joints and extended at their femoro-tibial joints. This phase lasted 5–6 ms on average, with the fastest movements accomplished in 2.75 ms and involving rotations of the coxo-trochanteral joints of 44 000 deg. s–1. In the best jumps by Aphrodes, a peak take-off velocity of 2.9 m s–1 was achieved by an acceleration of 1055 m s–2, equivalent to 108 times gravity. This jumping performance required an energy output of 77 μJ, a power output of 28 mW and exerted a force of 19 mN, or 100 times its body mass.
Cross-modal effects on learning: a seismic stimulus improves color discrimination learning in a jumping spider
Authors: VanderSal Nicole D. , Hebets Eileen A.
Published: October 2007

The production of multimodal signals during animal displays is extremely common, and the function of such complex signaling has received much attention. Currently, the most frequently explored hypotheses regarding the evolution and function of complex signaling focus on the signal and/or signaler, or the signaling environment, while much less attention has been placed on the receivers. However, recent studies using vertebrates suggest that receiver psychology (e.g. learning and memory) may play a large role in the evolution of complex signaling. To date, the influence of multimodal cues on receiver learning and/or memory has not been studied in invertebrates. Here, we test the hypothesis that the presence of a seismic (vibratory)stimulus improves color discrimination learning in the jumping spider Habronattus dossenus. Using a heat-aversion learning experiment, we found evidence for a cross-modal effect on color learning. Over a series of training trials, individuals exposed to a seismic stimulus jumped onto the heated color less frequently and remained there for less time than did individuals not exposed to a seismic stimulus. In addition, in a final no-heat test trial, individuals from the seismic-present treatment were more likely to avoid the previously heated color than were individuals from the seismic-absent treatment. This is the first study to demonstrate a cross-modal influence on learning in an invertebrate.
Echolocation in air: Biological systems, technical challenges, and transducer design
Authors: Waters D A
Published: October 2007

Echolocation systems used by bats may be used by engineers wishing to emulate the performance of these biological systems. Comparisons are made between biosonar systems based on water and air, the signal structures used by animals echolocating in air, and the limits on resolution. The current thinking in how biological systems operate are discussed, as are the engineering challenges of replicating the performance levels demonstrated by echolocating animals.
Mass production of bio-inspired structured surfaces
Authors: Abbott S J , Gaskell P H
Published: October 2007

Bio-inspired surface structures offer significant commercial potential for the creation of antireflective, self-cleaning and drag reducing surfaces, as well as new types of adhesive systems. The current article explores how the current understanding of the basic science of the biological structures occurring on the surface of moth eyes, leaves, sharkskin, and the feet of reptiles can be transferred to functional man-made materials, some of the drawbacks of which are shown to offer a long-term challenge to engineers. Explored also is the related topic of how such surfaces can be mass-produced, encompassing the important areas of current surface replication techniques and the associated acquisition of good master structures.
Development of Electrochemical Standards for Corrosion Testing
Authors: Dean Sheldon W.
Published: October 2007

Although the understanding that corrosion is an electrochemical process has been known for almost a century, the exploitation of electrochemical techniques for corrosion testing has largely occurred in the past four decades. The development of standard conventions in ASTM G 3 and calculation procedures in ASTM G 102 have stimulated the development of electrochemical test methods. The development of reference test methods G 5, G 59, G 61, G 100, and G 106 that allow the verification of both equipment and procedures has been an important contribution to the development and expansion of these test methods. The availability of reliable electrometers, potentiostatic power supplies and recording equipment has also made these methods simpler to use. This paper reviews the development of these standards and discusses three electrochemical test methods. It also outlines several areas for new standards development and provides ideas for improvements to existing standards.
Bim Expression Indicates the Pathway to Retinal Cell Death in Development and Degeneration
Authors: Doonan Francesca , Donovan Maryanne , Gomez-Vicente Violeta , Bouillet Philippe , Cotter Thomas G.
Published: October 2007

Programmed cell death (PCD) during development of the mouse retina involves activation of the mitochondrial pathway. Previous work has shown that the multidomain Bcl-2 family proteins Bax and Bak are fundamentally involved in this process. To induce mitochondrial membrane permeabilization, Bax and Bak require that prosurvival members of the family be inactivated by binding of “BH3-only” members. We showed previously that the BH3-only protein BimEL is highly expressed during postnatal retinal development but decreases dramatically thereafter. The purpose of this study was to investigate a possible role for Bim, in retinal development and degeneration, upstream of Bax and Bak.Bim−/−mice analyzed for defective retinal development exhibit an increase in retinal thickness and a delay in PCD, thereby confirming a role for Bim. We also demonstrate that in response to certain death stimuli,bim+/+retinal explants upregulate BimEL leading to caspase activation and cell death, whereasbim−/−explants are resistant to apoptosis. Finally, we analyzed Bim expression in the retinal degeneration (rd) mouse, anin vivomodel of retinal degeneration. Bim isoforms, which decrease during development, are not reexpressed during retinal degeneration and ultimately photoreceptor cells die by a caspase-independent mechanism. Thus, we conclude that in cases in which BimEL is reexpressed during pathological cell death, developmental cell death pathways are reactivated. However, the absence of BimEL expression correlates with caspase-independent death in the rd model.
State-Dependent Enhancement of Subthreshold A-Type Potassium Current by 4-Aminopyridine in Tuberomammillary Nucleus Neurons
Authors: Jackson Alexander C. , Bean Bruce P.
Published: October 2007

A-type potassium current (IA) both activates and inactivates at subthreshold voltages. We asked whether there is steady-stateIAat subthreshold voltages, using dissociated mouse tuberomammillary nucleus neurons, pacemaking neurons with largeIAcurrents in which subthresholdIAmight regulate firing frequency. With slow depolarizing voltage ramps (20 mV/s), there was no discernible component of steady-state outward current in the range of −70 to −40 mV. However, faster ramps of 50–100 mV/s, similar to the rate of spontaneous depolarization during pacemaking, did evoke subthreshold outward currents. Ramp-evoked current at subthreshold voltages was unaffected by 10 mmtetraethylammonium and likely representsIA, because its voltage dependence overlaps that ofIAactivation (midpoint near −44 mV) and inactivation (midpoint near −85 mV). However, although 4-aminopyridine (4-AP) inhibited peakIAactivated by step depolarizations as expected (IC50, ∼1 mm), ramp-evoked current was instead dramatically enhanced (current at −40 mV evoked by 50 mV/s ramp enhanced >15-fold by 10 mm4-AP). In cell-attached recordings of spontaneous pacemaking, 10 mm4-AP slowed rather than speeded firing, consistent with enhancement of subthresholdIA. Also consistent with such enhancement, 4-AP also greatly increased the latency to first spike after long hyperpolarizations. The striking enhancement ofIAduring depolarizing ramps can be explained by a model in which 4-AP binds tightly to closed channels but must unbind before channels can inactivate. Thus, the state dependence of 4-AP binding to the channels underlyingIAcan result in effects on firing patterns opposite to those expected from simple block ofIA.
Brain-Derived Neurotrophic Factor Expression and Respiratory Function Improve after Ampakine Treatment in a Mouse Model of Rett Syndrome
Authors: Ogier Michael , Wang Hong , Hong Elizabeth , Wang Qifang , Greenberg Michael E. , Katz David M.
Published: October 2007

Rett syndrome (RTT) is caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Although MeCP2 is thought to act as a transcriptional repressor of brain-derived neurotrophic factor (BDNF),Mecp2null mice, which develop an RTT-like phenotype, exhibit progressive deficits in BDNF expression. These deficits are particularly significant in the brainstem and nodose cranial sensory ganglia (NGs), structures critical for cardiorespiratory homeostasis, and may be linked to the severe respiratory abnormalities characteristic of RTT. Therefore, the present study usedMecp2null mice to further define the role of MeCP2 in regulation of BDNF expression and neural function, focusing on NG neurons and respiratory control. We find that mutant neurons express significantly lower levels of BDNF than wild-type cellsin vitro, asin vivo, under both depolarizing and nondepolarizing conditions. However, BDNF levels in mutant NG cells can be increased by chronic depolarizationin vitroor by treatment ofMecp2null mice with CX546, an ampakine drug that facilitates activation of glutamatergic AMPA receptors. Ampakine-treatedMecp2null mice also exhibit marked functional improvement, characterized by restoration of normal breathing frequency and minute volume. These data demonstrate that BDNF expression remains plastic inMecp2null mice and raise the possibility that ampakine compounds could be of therapeutic value in the treatment of RTT.
Enhanced Astrocytic Ca2+Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus
Authors: Ding Shinghua , Fellin Tommaso , Zhu Yingzi , Lee So-Young , Auberson Yves P. , Meaney David F. , Coulter Douglas A. , Carmignoto Giorgio , Haydon Philip G.
Published: October 2007

Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca2+signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal deathin vivo. Using two-photon microscopyin vivo, we show that status epilepticus enhances astrocytic Ca2+signals for 3 d and that the period of elevated glial Ca2+signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca2+signalsin vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca2+chelators selectively into astrocytes after status epilepticus. We demonstrate that the selective attenuation of glial Ca2+signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target.
NMDA Receptor Contribution to the Climbing Fiber Response in the Adult Mouse Purkinje Cell
Authors: Piochon Claire , Irinopoulou Theano , Brusciano Daniel , Bailly Yannick , Mariani Jean , Levenes Carole
Published: October 2007

Among integrative neurons displaying long-term synaptic plasticity, adult Purkinje cells seemed to be an exception by lacking functional NMDA receptors (NMDA-Rs). Although numerous anatomical studies have shown both NR1 and NR2 NMDA-R subunits in adult Purkinje cells, patch-clamp studies failed to detect any NMDA currents. Using more recent pharmacological and immunodetection tools, we demonstrate here that Purkinje cells from adult mice respond to exogenous NMDA application and that postsynaptic NMDA-Rs carry part of the climbing fiber-mediated EPSC (CF-EPSC), with undetectable contribution from presynaptic or polysynaptic NMDA currents. We also detect NR2-A/B subunits in adult Purkinje cells by immunohistochemistry. The NMDA-mediated CF-EPSC is barely detectable before 3 weeks postnatal. From the end of the third week, the number of cells displaying the NMDA-mediated CF-EPSC rapidly increases. Soon, this EPSC becomes detectable in all the Purkinje cells but is still very small. Its amplitude continues to increase until 12 weeks after birth. In mature Purkinje cells, we show that the NMDA-Rs contribute to the depolarizing plateau of complex spikes and increase their number of spikelets. Together, these observations demonstrate that mature Purkinje cells express functional NMDA receptors that become detectable in CF-EPSCs at ∼21 d after birth and control the complex spike waveform.