bluuebunny/crossref_metadata_2025 huggingface dataset:
The distribution of blood flow in the udder of the sheep and changes brought about by cold exposure and lactation.
Authors: Thompson G E
Published: December 2015

1. Microspheres have been injected into an external iliac artery of conscious female sheep in order to measure the distribution of blood flow in half the udder. Values were obtained from five non‐lactating ewes in a neutral environment and in a cold environment. Values were also obtained from five lactating ewes in a neutral environment 27‐36 days after parturition. 2. In non‐lactating sheep in a neutral environment, blood flow to half the udder averaged 11.7 ml . min‐1 of which 43% was distributed to lobulo‐alveolar tissue, 10% to skin covering the udder, 2% to the teat, 20% to inguinal adipose tissue and 25% to lymph tissue. 3. Cold exposure significantly reduced udder skin and teat blood flow, by approximately the same amount as it reduced leg skin blood flow, but significantly increased blood flow to adipose tissue in the udder, so total blood flow to the udder was not affected. 4. In lactating sheep, blood flow to half the udder was significantly higher, averaging 357 ml . min‐1. Flow to the teat was slightly greater than in non‐lactating sheep in a neutral environment, but flow to lobulo‐alveolar tissue was much greater and accounted for 98% of total blood flow in lactating sheep.
The effect of contrast on the non‐linear response of the Y cell.
Authors: Shapley R M , Victor J D
Published: December 2015

1. Second‐order frequency responses were obtained from cat retinal ganglion cells of the Y type. The cells were stimulated by a spatial sine grating whose contrast was modulated in time by a sum of eight sinusoids. 2. Second‐order frequency responses obtained at higher contrasts have a peak amplitude at higher input temporal frequency, and phase shifts, compared to their low‐contrast counterparts. 3. This change in shape of the second‐order frequency response is a departure from the prediction of the linear/static non‐linear/linear sandwich model of the non‐linear pathway in the cat retina. The departure is analysed by means of the hypothesis that the two filters of the sandwich model are parametric in contrast. 4. Most of the change in shape of the second‐order frequency response with contrast is accounted for in terms of the sandwich model by changes in the transfer characteristics of the filter preceding the static non‐linearity. 5. The effect of contrast on the second‐order responses of Y cells is qualitatively similar in several ways to the effect of contrast on first‐order responses. This suggests that the contrast gain control mechanism acts early in the retina, before linear and non‐linear pathways have diverged.
Multiple receptor types for octopamine in the locust.
Authors: Evans P D
Published: December 2015

1. Three different pharmacological classes of octopamine receptor mediate the actions of octopamine on the locust extensor‐tibiae neuromuscular preparation. A receptor classification scheme is proposed based on the results of detailed studies with agonists and antagonists. 2. Octopamine1 class receptors mediate the slowing of a myogenic rhythm found in a specialized proximal bundle of muscle fibres. Octopamine2A class receptors mediate the increase in amplitude of slow motoneurone twitch tension and octopamine2B class receptors mediate the increase in relaxation rate of twitch tension induced by firing either the fast or the slow motoneurones. 3. Octopamine1 receptors can be distinguished from the 2A and 2B classes since chlorpromazine (and yohimbine) are much better blocking agents than metoclopramide at the former receptors, whereas the converse is true for the latter class. Also clonidine is a more effective agonist than naphazoline for the former receptors and the converse is true for the latter class. 4. Octopamine 2A can be distinguished for octopamine 2B receptors since metoclopramide, mianserin and cyproheptadine show a strong preference for blocking the former class. Also naphazoline is a much better agonist than tolazoline at the former receptors and tolazoline is a much better agonist than clonidine at a latter. 5. The results are discussed in terms of the location of the various classes of octopamine receptors, their possible relationship to vertebrate alpha‐adrenoreceptors, and the significance of the results for studies on octopamine receptors in the vertebrate central nervous system.
How the contrast gain control modifies the frequency responses of cat retinal ganglion cells.
Authors: Shapley R M , Victor J D
Published: December 2015

1. A model is proposed for the effect of contrast on the first‐order frequency responses of cat retinal ganglion cells. The model consists of several cascaded low pass filters ('leaky integrators') followed by a single stage of negative feed‐back. 2. Values of time constants and gain of the components in this model were chosen to approximate (with least‐squared deviation) experimentally measured first‐order frequency responses. In the experiments used for the analysis, the visual stimulus was a sine grating modulated by a sum of sinusoids. 3. For both X cells and Y cells, the over‐all gain and the time constants of the cascade of low pass filters were insensitive to contrast. 4. In all cells, the gain‐bandwidth product of the negative feed‐back loop was markedly increased with increasing contrast. 5. The effect of stimulation in the periphery of the receptive fields on the first‐order frequency response to a centrally placed spot was identical to the effect of increasing contrast in the grating experiments. In all cases, the gain‐bandwidth product of the negative feed‐back loop was the only model parameter affected by peripheral stimulation. 6. A similar effect of non‐linear summation was investigated for two bars located in the receptive field periphery. 7. This analysis of the contrast gain control mechanism is compared with other models of retinal function.
The relationship between response amplitude and contrast for cat striate cortical neurones.
Authors: Dean A F
Published: December 2015

1. The activity of forty‐three neurones in the cat's striate cortex in response to laterally moving sinusoidal gratings of various contrasts was recorded, in order to examine the relationship between response amplitude and contrast. 2. Neurones seemed to exhibit contrast thresholds: stimuli of very low contrast failed to evoke a change in the response amplitude from the concurrent levels of spontaneous activity. 3. The suprathreshold portion of the response‐contrast relation was found to be monotonic. Typically, the relation was adequately described as linear up to contrasts of about 0.3, above which, varying degrees of saturation were evident. 4. The response‐contrast relation had a higher threshold and a shallower slope when the spatial frequency was not optimal for the neurone. 5. The slope, or gain, of the response‐contrast relation for a stimulus of optimal orientation and spatial frequency varied considerably from neurone to neurone. The gains of special complex cells were significantly greater than those of either standard complex cells or simple cells. 6. The distributions of contrast threshold and contrast gain were examined for their dependence on optimal spatial frequency. Contrast threshold was significantly positively correlated with optimal spatial frequency, while contrast gain was significantly negatively correlated with optimal spatial frequency. This behaviour is consistent with an optical contribution to the measured response properties of striate cortical neurones.
Properties of maintained sodium current induced by a toxin from Androctonus scorpion in frog node of Ranvier.
Authors: Benoit E , Dubois J M
Published: December 2015

1. The effects of toxin II from scorpion Androctonus australis Hector (AaH II) on the Na current of frog myelinated nerve fibres were analysed under voltage‐clamp conditions. 2. Like other alpha‐scorpion toxins and Anemonia toxin II, AaH II both increased the inactivation time constants of peak Na current and induced a non‐inactivatable Na current (maintained current). 3. In the presence of AaH II, the slope of the maintained conductance‐voltage curve was less steep than that corresponding to the peak conductance and the maintained current reversed at a voltage about 20 mV more negative than the peak current. 4. When the peak current was inactivated by pre‐depolarizations, 'on' and 'off' relaxation kinetics of the maintained current were an exponential function whose time constant changed with voltage in a bell‐shaped manner. At 0 mV, the time constant was about 10 ms. 5. The effects of AaH II could be decomposed into fast effects (increase in inactivation time constants of the peak current) which developed within about 5 s and slow effects (increase in maintained current and changes in initial amplitudes of fast and slow phases of peak current inactivation) which developed within about 30 s. 6. These two types of AaH II effects could be completely removed by conditioning depolarizations giving rise to outward currents. 7. A model is proposed in which the binding of the toxin with its receptor is modulated by membrane potential and internal cations, the appearance of the maintained current is modulated by the environment of channels and the change in inactivation time constants is modulated by membrane potential. The maintained current would correspond to the transformation of a fraction of channels into a non‐inactivable (late) form.
Slow sodium channel inactivation in rat fast‐twitch muscle.
Authors: Simoncini L , Stühmer W
Published: December 2015

1. Voltage‐clamp Na+ currents (INa) were measured in rat fast‐twitch fibres using the loose‐patch‐clamp technique. Changes in the conditioning membrane potential produced slow changes in the peak INa elicited by short test depolarizations, due to a slow inactivation process. 2. Inactivation was increased by application of steady depolarizing potentials and was reversed by steady hyperpolarizations. These changes in peak INa could be well fitted by single‐exponential functions with time constants in the range of 1‐4 min. 3. The steady‐state values of the maximum peak INa at any potential could be well fitted by a function identical to the one describing the fast inactivation process. This gave a potential of ‐108 mV at which 50% of the channels were closed due to slow inactivation. 4. The maximum peak current densities obtained with the slow inactivation fully removed were as large as 20 mA cm‐2.
Synaptic activation of N‐methyl‐D‐aspartate receptors in the Schaffer collateral‐commissural pathway of rat hippocampus.
Authors: Collingridge G L , Herron C E , Lester R A
Published: December 2015

1. The involvement of N‐methyl‐D‐aspartate (NMDA) receptors in the response to single‐shock (0.033 Hz) stimulation of the Schaffer collateral‐commissural pathway in hippocampal slices has been investigated using current‐ and voltage‐clamp techniques. 2. In the presence of Mg2+ (1 or 2 mM) at membrane potentials near rest, the selective NMDA antagonist D‐2‐amino‐5‐phosphonovalerate (APV) had no effect on the excitatory postsynaptic potential (EPSP) and the biphasic inhibitory postsynaptic potential (IPSP) evoked by Schaffer collateral‐commissural stimulation. The recurrent IPSP evoked by antidromic stimulation of alvear fibres was also unaffected by APV. 3. The introduction of a Mg2+‐free perfusate led, at high stimulus intensity, to an orthodromically evoked epileptiform discharge but little change in the recurrent IPSP. APV suppressed a large proportion of the enhanced response in Mg2+‐free perfusate. 4. EPSPs and excitatory postsynaptic currents (EPSCs) evoked in Mg2+‐free perfusate invariably had both APV‐resistant and APV‐sensitive components. Both synaptic components had similar thresholds and latencies to onset. The APV‐sensitive component had a long time to peak and long duration. 5. Under current‐clamp conditions in Mg2+‐containing medium, an APV‐sensitive component was recorded at membrane potentials of between ‐30 and ‐10 mV, but not at potentials more negative than ‐55 mV. 6. Under voltage‐clamp, but not current‐clamp, conditions in Mg2+‐containing medium, a small APV‐sensitive component was recorded at resting membrane potentials and increased with membrane depolarization. The difference between the current‐ and voltage‐clamp data is attributed to the hyperpolarizing influence of conjointly activated IPSPs. 7. In the presence of Mg2+ and picrotoxin, a dual‐component EPSC was recorded between ‐30 and +30 mV in all cells examined. The APV‐resistant and APV‐sensitive components had similar latencies to onset. They both had reversal potentials of between ‐8 and 0 mV. The APV‐sensitive component had a longer latency to peak and duration than the APV‐resistant component. 8. It is suggested that NMDA receptors can contribute a low‐threshold and long‐duration monosynaptic component of the response evoked by low‐frequency stimulation of the Schaffer collateral‐commissural pathway. However, under physiological conditions significant expression of this component is prevented by concurrently activated IPSPs which rapidly hyperpolarize neurones into a region where Mg2+ substantially blocks NMDA channels.
Baroreceptor inputs to the nucleus tractus solitarius in the cat: postsynaptic actions and the influence of respiration.
Authors: Mifflin S W , Spyer K M , Withington-Wray D J
Published: December 2015

1. The postsynaptic action of carotid sinus nerve (SN), aortic nerve (AN), superior laryngeal nerve (SLN) and vagal nerve (VN) stimulation has been studied on neurones in the nucleus of the tractus solitarius (NTS) in vivo. 2. Three distinct patterns of postsynaptic responses were evoked by SN stimulation, an EPSP, an EPSP‐IPSP sequence and an IPSP, observed separately in individual neurones. This diversity of response was represented in cells proven to receive baroreceptor input by inflation of a balloon‐tipped catheter within the ipsilateral carotid sinus. 3. Virtually none of the neurones identified as baroreceptive exhibited pulse‐related discharge. 4. A variety of influences to AN, SLN and VN stimulation were observed in neurones receiving baroreceptor afferent information. This wide convergence of input implies that this region of the brain stem is important in the integration of cardiovascular reflexes. 5. The hypothesis was tested that respiratory 'gating' of the baroreceptor reflex is produced by synaptic actions within the NTS. There was an absence of any modification of PSPs by lung inflation and by variations in the timing of the stimulation of the afferent nerves within the respiratory cycle. These observations indicate that respiratory modifications of the baroreceptor reflex must occur at later stages in the reflex pathway.
Ventilatory and circulatory responses at the onset of exercise in man following heart or heart‐lung transplantation.
Authors: Banner N , Guz A , Heaton R , Innes J A , Murphy K , Yacoub M
Published: December 2015

1. Ventilatory and cardiovascular responses to the onset of voluntary and electrically induced leg exercise were studied in six patients following heart transplantation and five following heart‐lung transplantation; the results were compared between the patient groups and also with responses from a group of normal subjects. 2. Oxygen consumption, carbon dioxide production and ventilation and its components were measured over two 30 s periods prior to, and two 30 s periods following, the onset of exercise. Relative changes in stroke volume and cardiac output were derived from ensemble‐averaged Doppler measurements of ascending aortic blood velocity over the same 30 s periods. 3. None of the groups of subjects showed any significant differences in responses to voluntary exercise compared to electrically induced exercise of similar work pattern and intensity. 4. Compared to normal controls, the transplanted subjects showed higher resting heart rates which did not increase at the onset of exercise; stroke volume increased, but less than in the normal subjects. The resulting cardiac output increases in the transplanted subjects were minimal compared to the normal subjects. 5. Ventilation and oxygen uptake increased immediately and with similar magnitude in all three groups. 6. These results show that in the same individual it is possible to have an appropriate ventilatory response to the onset of exercise in the presumed absence of a normal corticospinal input to the exercising muscles (electrically induced exercise) and afferent neural information from the lungs and heart, and in the absence of a normal circulatory response to exercise. The mechanisms underlying this ventilatory response remain undetermined.
Innovative Nanostructured Wicks for Heat Pipes
Authors: Tian Bohan , Wilson Corey , Ma H. B.
Published: December 2015

A good wicking structure is necessary for the design of a highly efficient heat pipe. Several unique aluminum oxide nanostructures were developed as wicks for heat pipes. The wicks were manufactured via an anodization process at various anodization voltages and etching times. This allows for the manufacture of spatially variable wicking structures that can be tuned for specific applications. The resulting nanostructures were characterized with a scanning electron microscope. Six distinct wicking structures are shown in Fig. 1. The honeycomb nanostructure is a self-ordered, hexagonal columnar array. The clumped nanotube structure is composed of bundles of nanotubes separated by deep grooves. The teepee nanostructure has a honeycomb bottom covered with a conical structure top. The horizontal nanofiber structure consists of nanofibers laying parallel to the substrate surface. The ridge network nanostructure is a multiscaled structure with nanoporous ridges. The clumped nanofiber structure is formed from long tangled fibers that meet in a thin ridge. Each of these structures has features useful for nucleation, evaporation, and condensation. These wicks will have many applications in the fields of heat pipes and two-phase heat transfer.
Macroscopic acousto-mechanical analogy of a microbubble
Authors: Chaline Jennifer , Jiménez Noé , Mehrem Ahmed , Bouakaz Ayache , Dos Santos Serge , Sánchez-Morcillo Víctor J.
Published: December 2015

Microbubbles, either in the form of free gas bubbles surrounded by a fluid or encapsulated bubbles used currently as contrast agents for medical echography, exhibit complex dynamics under specific acoustic excitations. Nonetheless, considering their micron size and the complexity of their interaction phenomenon with ultrasound waves, expensive and complex experiments and/or simulations are required for their analysis. The behavior of a microbubble along its equator can be linked to a system of coupled oscillators. In this study, the oscillatory behavior of a microbubble has been investigated through an acousto-mechanical analogy based on a ring-shaped chain of coupled pendula. Observation of parametric vibration modes of the pendula ring excited at frequencies between 1 and 5 Hz is presented. Simulations have been carried out and show mode mixing phenomena. The relevance of the analogy between a microbubble and the macroscopic acousto-mechanical setup is discussed and suggested as an alternative way to investigate the complexity of microbubble dynamics.
Draft Genome Sequence of Streptomyces mutabilis TRM45540, Isolated from a Hypersaline Soil Sample
Authors: Luo Xiaoxia , Wan Chuanxing , Zhang Lili
Published: December 2015

We report here the draft genome sequence of
Streptomyces mutabilis
TRM45540, a strain isolated from a soil sample from Xinjiang, China. Analysis of the genome using the bioinformatics tool antiSMASH showed the presence of many unique natural-product biosynthetic pathways.
Draft Genome of the
Arthrobacter
sp. Strain Edens01
Authors: Couger M. B. , Hanafy Radwa A. , Edens Curtis , Budd Connie , French Donald P. , Hoff Wouter D. , Elshahed Mostafa S. , Youssef Noha H.
Published: December 2015

We report the draft genome sequence of
Arthrobacter
sp. strain Edens01, isolated from a leaf surface of a Rosa hybrid plant as part of the Howard Hughes Medical Institute-funded Student Initiated Microbial Discovery (SIMD) project. The genome has a total size of 3,639,179 bp and contig
N
50
of 454,897 bp.
Genome Sequence of Bradyrhizobium viridifuturi Strain SEMIA 690
T
, a Nitrogen-Fixing Symbiont of
Centrosema pubescens
Authors: Helene Luisa Caroline Ferraz , Gomes Douglas Fabiano , Delamuta Jakeline Renata Marçon , Ribeiro Renan Augusto , Souza Renata Carolini , Almeida Luiz Gonzaga Paula , Vasconcelos Ana Tereza Ribeiro , Hungria Mariangela
Published: December 2015

SEMIA 690
T
is a nitrogen-fixing symbiont of
Centrosema pubescens
, and comprises the recently described species
Bradyrhizobium viridifuturi
. Its draft genome indicates that it belongs to the
Bradyrhizobium elkanii
superclade. SEMIA 690
T
carries two copies of the regulatory
nodD
gene, and the
nod
and
nif
operons resemble those of
Bradyrhizobium diazoefficiens
.
Genomic Sequence of a Clinical Vancomycin-Resistant Reference Strain, Enterococcus faecalis ATCC 51299
Authors: Sung Kidon , Khan Saeed , Marasa Bernard , Min Seonggi , Kweon Ohgew , Nawaz Mohamed , Cerniglia Carl
Published: December 2015

In this paper, we present a draft genome sequence of a quality control reference strain,
Enterococcus faecalis
ATCC 51299 (multilocus sequencing type [MLST] ST6), which is sensitive to teicoplanin but resistant to vancomycin. It is used in an agar screening test for streptomycin, gentamicin, and vancomycin resistance and the resistance marker
vanB
.
Unusual cause for gum hypertrophy and skin nodules in a child
Authors: Rajendran Priyadharshini , Karmegaraj Balaganesh , Vij Mukul , Scott Julius Xavier
Published: December 2015

Juvenile hyaline fibromatosis (JHF) is a rare progressive autosomal recessive disease that is characterised by papulonodular skin lesions, soft tissue masses, joint contractures, gingival hypertrophy and osteolytic bone lesions. We present an 18-month-old boy with JHF. This case demonstrates that JHF should be considered in the differential diagnosis when multiple subcutaneous nodules are observed in the face, head and neck. Gum hypertrophy with palatal nodules is unusual in JHF.
Ovarian vein thrombosis in a polytrauma patient
Authors: Toman Emma , Beaven Alastair , Balogun Moji , Porter Keith
Published: December 2015

A young mother presented to a major trauma centre following a road traffic collision. Her admission CT traumagram demonstrated liver and renal lacerations, spinal and pelvic fractures with no abnormalities of the ovarian veins. Her inpatient course was uncomplicated other than a sustained, isolated raised C reactive protein. CT of the abdomen 1 week after injury demonstrated stable solid organ injuries and the additional, unexpected finding of a right ovarian vein thrombosis (OVT). A pragmatic approach was taken towards the management of the OVT given the haemorrhagic risk from her traumatic injuries. A multidisciplinary, consultant-led plan was made to slowly increase enoxaparin to a therapeutic dose under close surveillance and to then switch to warfarin following an outpatient consultation with a consultant haematologist. A MR venogram was performed after 3 months of anticoagulation, and this demonstrated complete resolution of the OVT and normal appearances of the ovary.
Correlation of ERG immunohistochemistry with molecular detection ofTMPRSS2-ERGgene fusion
Authors: Sung Ji-Youn , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Lee Hyun Moo , Choi Han Yong , Kang So Young , Choi Yoon-La , Kwon Ghee Young
Published: December 2015

Aims

TMPRSS2/E26 transformation-specific (ETS) family gene fusion in prostate carcinoma (PCa) can be detected by several methods including immunohistochemistry (IHC) for ETS-related gene (ERG), the diagnostic utility of which has not been clearly defined.

Methods

We exploredTMPRSS2-ERGgene rearrangement status in 132 patients with PCa with four detection methods including fluorescence in situ hybridisation forTMPRSS2-ERGfusion, real-time reverse transcription PCR (RT-qPCR) forERGandTMPRSS-ERGfusion transcript mRNA and IHC for ERG.

Results

Concordant results were found in 126 cases for the four detection methods and the remaining six cases showed discrepancy in one method: two cases in IHC, three cases in RT-qPCR for ERG and one case in RT-qPCR for fusion transcript. In discordant cases, the majority results were determined as final fusion status. Analysis of discrepancy cases for ERG IHC showed that weak immunoreactivity for ERG should be regarded as equivocal and that even strong immunoreactivity can be false positive. The overall incidence ofTMPRSS-ERGgene fusion was 24%.

Conclusions

ERG IHC is a useful surrogate test for the detection ofTMPRSS2-ERGgene fusion, but it needs to be interpreted with caution and definite judgement should not be based on IHC alone. A relatively low incidence ofTMPRSS2-ERGgene fusion was demonstrated in this Korean cohort.
Identification of training status differences using perceived exertion threshold
Authors: Ferreira Guilherme A. , Bertuzzi Romulo , Lima-Silva Adriano E. , Malfatti Carlos , De-Oliveira Fernando R. , Osiecki Raul
Published: December 2015

We investigated if the rate of perceived exertion (RPE) threshold is as sensitive as the lactate threshold to detect training differences. Lactate and RPE thresholds were identified in well-trained cyclists and physically active males. Power output was higher in well-trained cyclists than in physically active individuals for both thresholds (p < 0.05). Our results suggest that RPE threshold is successful in discriminating differences between well-trained cyclists and physically active individuals.
Biocidal activity of chicken defensin-9 against microbial pathogens
Authors: Yacoub Haitham A. , El-Hamidy Salem M. , Mahmoud Maged M. , Baeshen Mohamed Nabih , Almehdar Hussein A. , Uversky Vladimir N. , Redwan Elrashdy M. , Al-Maghrabi Omar A. , Elazzazy Ahmed M.
Published: December 2015

In this study we identified the expression patterns of β-defensin-9 in chickens from Saudi Arabia, evaluated the antimicrobial activities of synthetic chicken β-defensin-9 (sAvBD-9) against pathogenic bacteria and fungi, and investigated the mode of action of sAvBD-9 on bacterial cells. The AvBD-9 gene of Saudi chickens encodes a polypeptide of 67 amino acids, which is highly similar to the polypeptide in duck, quail, and goose (97%, 86%, and 87%, respectively) and shares a low sequence similarity with the mammalian defensins. AvBD-9 is expressed in various organs and tissues of Saudi chickens and inhibits the growth of both Gram-negative and Gram-positive bacteria, as well as showing activity against unicellular and multicellular fungi (Aspergillus flavus, A. niger, and Candida albicans). sAvBD-9 completely inhibited the growth of both Gram-positive and Gram-negative bacterial strains as well as Candida albicans. The haemolytic effects of sAvBD-9 were limited. Morphological analysis by TEM revealed that sAvBD-9 induces shortening and swelling of Staphylococcus aureus and Shigella sonni cells, opens holes and deep craters in their envelopes, and leads to the release of their cytoplasmic content. Our data shed light on the potential applications of sAvBD-9 in the pharmaceutical industry.
Make haste slowly: reproduction in the Zaisan mole vole (Ellobiustancrei)
Authors: Smorkatcheva A.V. , Kumaitova A.R. , Kuprina K.V.
Published: December 2015

Mole voles are the most specialized subterranean members of the subfamily Arvicolinae. We assess the basic reproductive parameters of the Zaisan mole vole (Ellobius tancrei Blasius, 1884) and compare our data with the characteristics reported for other Ellobius species and surface-dwelling voles. In most respects, reproduction of the E. tancrei follows the pattern that is typical for voles. Females undergo postpartum estrus, but rarely combine pregnancy with lactation. The rate of embryonic and postembryonic growth (0.13 and 0.54 g/day, respectively) are slightly lower, whereas the relative neonate and weanling masses (8% and 40% of maternal mass, respectively) are slightly higher than the respective values predicted for non-subterranean arvicolines. The combination of these trends results in the protracted pregnancy and lactation (both ∼30 days). The age at first breeding is delayed (>2.5 months). Despite heavy weanlings, total maternal investment per litter in E. tancrei is low due to small litter size (2.31). Although the species of Ellobius are similar to each other by the parameters of developmental time, they vary by litter size, total investment per litter, and possibly by relative neonate body mass. This is consistent with the idea that when body-size effect is removed, fecundity variables and degree of precociality at birth are dissociated from timing variables.
Opposite companion effect on flight initiation distance in sympatric species: plateau pika (Ochotona curzoniae) and White-rumped Snowfinch (Onychostruthus taczanowskii)
Authors: Zhang He , Li Wenjing , Hu Yanping , Zhang Yanming
Published: December 2015

There are many factors influencing prey’s risk perception and escape decision during predator–prey encounters. The distance at which animals move away from perceived danger (often quantified as flight initiation distance or FID) has been used by behavioral ecologists to understand the economics of antipredator behavior. Using general linear models, we investigated escape decision-making processes in plateau pika (Ochotona curzoniae (Hodgson, 1858)) and White-rumped Snowfinch (Onychostruthus taczanowskii (Prjevalsky, 1876), formerly known as Montifringilla taczanowskii Przewalski, 1876) together and we found that (i) there are significant positive correlations between starting distance and FID in both species; (ii) pika escapes at a longer distance from an approaching intruder when it is far from its burrow; (iii) foraging animals tolerate closer distances than watching ones, both in pikas and in Snowfinches; (iv) conspecifics seem to have no effect on pikas’ escaping behavior, while the appearance of Snowfinches dramatically decreases the FID of pikas. On the contrary, conspecifics significantly decrease the FID of Snowfinches, while the presence of pikas has no effects. These findings provide new evidence, which are consistent with optimal escape theory. These novel results in multispecies interactions prompt us to pay attention to the potential relationship between pikas and Snowfinches, as well as the “bird–pika in one hole” phenomenon.
Development of a high-resolution melting marker for selecting Fusarium crown and root rot resistance in tomato
Authors: Kim Bichseam , Kim Nahui , Kim Jun Young , Kim Byung Sup , Jung Hee-Jeong , Hwang Indoek , Noua Ill-Sup , Sim Sung-Chur , Park Younghoon
Published: December 2015

Fusarium crown and root rot is a severe fungal disease of tomato caused by Fusarium oxysporum f. sp. radicis-lycopersici (FORL). In this study, the genomic location of the FORL-resistance locus was determined using a set of molecular markers on chromosome 9 and an F2population derived from FORL-resistant inbred ‘AV107-4’ (Solanum lycopersicum) × susceptible ‘L3708’ (Solanum pimpinellifolium). Bioassay performed using Korean FORL strain KACC 40031 showed single dominant inheritance of FORL resistance in the F2population. In all, 13 polymerase chain reaction-based markers encompassing approximately 3.6–72.0 Mb of chromosome 9 were developed based on the Tomato-EXPEN 2000 map and SolCAP Tomato single nucleotide polymorphism array analysis. These markers were genotyped on 345 F2plants, and the FORL-resistance locus was found to be present on a pericentromeric region of suppressed chromosomal recombination in chromosome 9. The location of the FORL-resistance locus was further confirmed by testing these markers against diverse commercial tomato and stock cultivars resistant to FORL. A restriction fragment length polymorphism marker, PNU-D4, located at approximately 6.1 Mb of chromosome 9 showed the highest match with the resistance locus and was used for conducting high-resolution melting analysis for marker-assisted selection of FORL resistance.
Theoretical prediction of the minimum height for negligible demagnetization field in a superconducting sample
Authors: Barba-Ortega J. , Joya Miryam R. , de Tarso C. Freire Paulo
Published: December 2015

The limit below which the magnetization curve of a mesoscopic superconducting prism of square cross-section and finite height approximates the characteristic bi-dimensional limit, e.g. long prism, which with both the magnetic induction and the superconducting electron density are invariant along the direction where the magnetic external field is applied, was numerically found. Using the three- and two-dimensional time-dependent Ginzburg–Landau models, we have determined an analytical dependence of this height limit as a function of the lateral size of the sample.
A Conceptual Approach to Promote the Integration of Ecosystem Services in Strategic Environmental Assessment
Authors: Geneletti Davide
Published: December 2015

There is a growing interest in the potential of strategic environmental assessment (SEA) to mainstream ecosystem services (ES) concerns in decision-making. Experiences in this field have begun to emerge, showing the need for comprehensive guidance. This paper addresses this need by proposing a conceptual approach to integrate ES effectively in SEA. The approach is structured in the following four stages, each comprising specific tasks: establish the ES context; determine and assess priority ES; identify alternatives and assess impacts on ES; follow up on ES. The first stage includes the identification and mapping of ES and beneficiaries for the region affected by the strategic action and the identification of links with other strategic actions. The second stage aims at generating detailed information on a limited set of priority ES, which are considered relevant for shaping and informing the development of the strategic action. This requires determining the priority ES, reviewing existing regulations concerning these services and assessing their baseline conditions and trends. In the third stage, possible alternatives to enhance ES, or at least to minimise negative effects on them, are identified and their impacts assessed. Finally, during the fourth stage, the effects on ES are monitored and managed and the overall quality of the SEA process is tested. The paper concludes by discussing how the stages and their tasks require feedback and interactions and how they can contribute to achieve a better inclusion of concerns about ES (and their beneficiaries) into strategic decisions.
Developing a User-Based Decision-Aid Framework for Water Storage Systems in Sub-Saharan Africa: The Case of Blue Nile Basin in Ethiopia
Authors: Xenarios Stefanos , Polatidis Heracles , McCartney Matthew , Nemes Attila
Published: December 2015

The development of water storage schemes in Sub-Saharan Africa (SSA) is considered a major aid for those regions with unequal water distribution, limited accessibility and anticipated climate change impacts. Great attention is given by many SSA countries to set up different water storage schemes that may improve rural and urban development on a national level. The funding for the water storage schemes is often derived from foreign agencies which conduct feasibility studies for the financing of potential investments. Often however, the feasibility studies rely on a single monetary criterion which may not identify the most appropriate water storage in each case. In addition, limited data availability in many SSA countries increases the difficulty of identifying the most suitable storage option. This paper develops a multicriteria framework for the integrated evaluation of water storage strategies in Sub-Saharan African countries. A set of economic, agronomic and opinion-based criteria are assessed through the PROMETHEE II outranking approach. The introduction of crop modeling complements the limited field data available in agronomic criteria and enhances the scientific rigor of the method. Ethiopia is adopted as a representative case of SSA countries where a diverse set of water storage options is currently under construction, often financed by foreign agencies.
Abstract A01: Vascular endothelial growth factor (VEGF) expression in patients with oral squamous cell carcinoma and its effects on tumor cell growth
Authors: Aggarwal Sadhna , Das Satya N. , Sharma Suresh C. , Devaraja K
Published: December 2015

Objective: VEGF plays an important role in tumor growth, development and progression by promoting angiogenesis. However its role in oral carcinogenesis is not established. In the present study we investigated serum and tissue expression of VEGF in oral cancer patients and its correlation with clinicopathological parameters; as well as with tumor cell proliferation using OSCC cell lines.

Materials and Methods: Cell and tissue expression of VEGF was determined by qRT-PCR, western blot and immunofluorescence assay while serum level of VEGF was determined by ELISA. Tumor cell proliferation was assessed by MTT assay.

Results: VEGF mRNA in tissue was significantly upregulated in tumor area compared to normal area of the same specimen as observed by qRT-PCR (R=7.28±1.40; p= 0.029) and western blot assay (p=0.0345). Significantly higher expression of VEGF was observed in sera of oral cancer patients (p<0.0001) as compared to normal controls. Serum VEGF levels further showed positive correlation with clinical stage and lymph node involvement. In ROC analysis serum VEGF level distinguished between patients and normals with a higher sensitivity and specificity of 65.71% and 66.67% respectively. OSCC cell lines showed higher expression of VEGF and significantly higher proliferation in response to exogenous VEGF in in vitro assay.

Conclusion: Result of the present study indicates a significant role of VEGF in development, establishment and distant spread of oral cancer, besides tumor cell proliferation. Hence serum level of VEGF may be useful for diagnostic and prognostic purposes as well as potential target for development of chemopreventive agents for oral cancer.

Note: This abstract was not presented at the conference.

Citation Format: Sadhna Aggarwal, Satya N. Das, Suresh C. Sharma, K Devaraja. Vascular endothelial growth factor (VEGF) expression in patients with oral squamous cell carcinoma and its effects on tumor cell growth. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr A01.
Abstract A14: Use of VEGF-based splicing-sensitive fluorescent reporters to screen for anti-angiogenic molecules
Authors: Star Eleanor , Harper Steven , Bates David , Oltean Sebastian
Published: December 2015

Two vascular endothelial growth factor (VEGF) protein families are generated via alternative splicing of the VEGF gene terminal exon. Use of the canonical proximal 3' splice site results in pro-angiogenic VEGF isoforms (VEGFxxx). Anti-angiogenic (VEGFxxxb) isoforms are produced through usage of a distal 3' splice site. In a quest to discover novel anti-angiogenic compounds we performed a screen using molecular tools designed to mimic VEGF splicing.

Splicing-sensitive fluorescent reporters (SSFRs) can be used to study specific splicing events. A bichromatic SSFR has been engineered to mimic VEGF terminal exon splicing. Endogenous VEGF intron 7 and parts of exon 8 have been inserted into the reporter. These sequences are followed by the coding sequences for two fluorescent proteins. Depending on which alternative 3' splice site is used, a different fluorescent protein is expressed. This splicing reporter allows VEGF alternative splicing to be followed in vitro and in vivo.

Reporter validation was achieved by transfection of the reporter in several cell lines with differential endogenous VEGF splicing as well as by treating stable cell lines expressing the reporter with growth factors or small molecule inhibitors known to alter VEGF alternative splicing. Flow cytometric analysis was used to evaluate the alternative splicing pattern. Following successful validation, several small pilot screens looking for novel regulators of the pro/anti-angiogenic splicing switch were undertaken with growth factors and various chemicals.

Following validation and pilot experiments, a large screen of 1280 pharmacologically active compounds (LOPAC library) was performed. Changes to reporter splicing were measured using a fluorescent plate reader. Hits from the screen were investigated further using flow cytometry to confirm alteration in splicing pattern. Several compounds of interest were identified and their effect on endogenous pro/anti-angiogenic VEGF being confirmed by RTPCR. Anti-angiogenic activity is being assessed by several in vitro and in vivo angiogenic assays.

Citation Format: Eleanor Star, Steven Harper, David Bates, Sebastian Oltean. Use of VEGF-based splicing-sensitive fluorescent reporters to screen for anti-angiogenic molecules. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr A14.
Abstract A19: Potent antitumor activity of Dll4 blockade in ovarian xenografts mediated by blocking stromal Dll4
Authors: Kuhnert Frank , Chen Guoying , Coetzee Sandra , Kirshner Jessica , Thurston Gavin
Published: December 2015

The Notch ligand delta-like 4 (Dll4) has been identified as a promising new target in tumor angiogenesis in preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. We previously demonstrated that pharmacological blockade of the Dll4-Notch axis results in tumor vessel abnormalization and associated reduction of tumor growth. Using VelocImmune® mice, we identified a fully human IgG1 monoclonal antibody, REGN421 (called enoticumab), which binds human Dll4 with sub-nanomolar affinity and potently inhibits Notch signaling. Treatment of immunodeficient mice engineered to express human Dll4 with enoticumab inhibited growth of several human tumor xenografts and induced non-functional tumor blood vessels. In ovarian tumor xenograft models, Dll4 was expressed specifically by tumor endothelium, and blockade of Dll4 with either human- or mouse-specific Dll4 antibodies showed potent anti-tumor activity was entirely dependent on targeting stromal Dll4 but not tumor cell-expressed Dll4. Blockade of Dll4 reduced Notch signaling in both blood vessels and in tumor cells surrounding blood vessels, suggesting that Dll4 on endothelial cells could induce Notch signaling on ovarian tumor cells. The anti-tumor activity of Dll4 blockade in ovarian tumors was markedly augmented by simultaneous inhibition of VEGF signaling. Importantly, the combined blockade of Dll4 and VEGF reversed normal organ vascular changes that were induced by Dll4 blockade alone. These studies lend further support for therapeutic targeting of Dll4 as a promising new angiogenesis-based anticancer strategy in ovarian cancer, in particular in combination with anti-VEGF agents.

Citation Format: Frank Kuhnert, Guoying Chen, Sandra Coetzee, Jessica Kirshner, Gavin Thurston. Potent antitumor activity of Dll4 blockade in ovarian xenografts mediated by blocking stromal Dll4. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr A19.
Abstract B04: Tumor-associated macrophages support tumor angiogenesis via CXCL16 signaling in papillary thyroid carcinoma
Authors: Cho Sun Wook , Sun Hyun Jin , Song Young Shin , Park Young Joo
Published: December 2015

Purpose: Tumor-associated macrophages (TAMs) are an important player in tumor microenvironments. We investigated the role of TAMs in angiogenesis of papillary thyroid cancer (PTC).

Experimental Design: Human endothelial, HUVEC cells were treated with conditioned medium of PTC (BHP10-3SC)/macrophage (THP-1) co-cultures and cell migration potentials and tube formations were evaluated. Conditioned medium were analyzed by cytokine array.

Results: Treatment of BHP10-3SC/THP-1 conditioned medium significantly increased HUVEC cell migrations and tube formation potentials compared to that of BHP10-3SC or THP-1 conditioned mediums. Cytokine array demonstrated that BHP10-3SC/THP-1 conditioned medium contained high level of CXCL16 while it did not expressed in BHP10-3SC alone conditioned medium. Treatment of CXCL16 increased HUVEC cell migrations and tube formation potentials, and blocking CXCL16 signaling using neutralizing antibodies reduced BHP10-3SC/THP-1 conditioned medium effects on HUVEC cell tube formation potentials.

Conclusions: TAM angiogenesis in PTC tumor microenvironment, in part, through CXCL16 signaling.

Citation Format: Sun Wook Cho, Hyun Jin Sun, Young Shin Song, Young Joo Park. Tumor-associated macrophages support tumor angiogenesis via CXCL16 signaling in papillary thyroid carcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B04.
Abstract B17: In-depth proteomics unveils fatty acid oxidation role in controlling vascular permeability
Authors: Patella Francesca , Schug Zachary T. , Persi Erez , Neilson Lisa J. , Erami Zahra , Avanzato Daniele , Maione Federica , Hernandez-Fernaud Juan R. , Mackay Gillian , Zheng Liang , Reid Steven , Frezza Christian , Giraudo Enrico , Pla Alessandra Fiorio , Anderson Kurt , Ruppin Eytan , Gottlieb Eyal , Zanivan Sara
Published: December 2015

Endothelial cells (ECs) play a key role in maintaining vascular functionality. Alterations in vessel stability and permeability are hallmarks of tumor angiogenesis and may affect the efficacy of anti-cancer therapy. Modulating EC metabolism has emerged as a promising strategy to target angiogenesis in pathological conditions, but so far, little is known about the role of EC metabolism in the regulation of vessel stability and permeability.

In this work we took advantage of a simplified in-vitro model of angiogenesis, where HUVECs (human umbilical vein endothelial cells) form a vascular-like network on a tridimensional matrix, to elucidate the role of EC metabolism during this process.

By integrating high resolution proteomic data with a human genome scale metabolic model we built up the first predictive model of metabolic fluxes occurring in ECs forming a complex network and identified increased fluxes for reactions involving fatty acid oxidation (FAO) enzymes when ECs are assembled into a fully formed network. Upon inhibition of CPT1, the FAO rate-limiting enzyme, we disrupted the network and reduced cellular ATP levels and oxygen consumption, which were restored by replenishing the tricarboxylic acid cycle (TCAc). Remarkably, phosphoproteomic changes measured upon CPT1A inhibition evoked those triggered by thrombin, a potent inducer of EC permeability through calcium signaling. Indeed, acute CPT1A inhibition increased EC permeability in-vitro and leakage of fully formed blood vessel in-vivo, which were restored by replenishing the TCAc or inhibiting calcium influx.

FAO emerges as central regulator of blood vessel stability, revealing the possibility of targeting FAO to interfere with tumor vessel permeability.

Citation Format: Francesca Patella, Zachary T. Schug, Erez Persi, Lisa J. Neilson, Zahra Erami, Daniele Avanzato, Federica Maione, Juan R. Hernandez-Fernaud, Gillian Mackay, Liang Zheng, Steven Reid, Christian Frezza, Enrico Giraudo, Alessandra Fiorio Pla, Kurt Anderson, Eytan Ruppin, Eyal Gottlieb, Sara Zanivan. In-depth proteomics unveils fatty acid oxidation role in controlling vascular permeability. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B17.