bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiphospholipid Antibodies Enhance Thrombin-Induced Platelet Activation and Thromboxane Formation
Authors: Martinuzzo M E , Maclouf J , Carreras L O , Lévy-Toledano S
Published: July 2018

In a group of 6 patients with lupus anticoagulant (LA) and antiphospholipid (aPL) antibodies detected by ELISA ovemight urine and blood were simultaneously collected. A significantly increased urinary excretion of the platelet-derived thromboxane (TX) metabolite 11-dehydro-TXB2 was found in this group, as compared to 12 healthy individuals. In contrast, a small but significant reduction of the vascular prostacyclin (PGI2) metabolite 2,3-dinor-6-keto-prostaglandin F1α was observed.

To further elucidate the effect of these antibodies on platelet activation we isolated the F(ab’)2 fragments from IgG of the 6 patients and 5 Controls, and we evaluated the effect of these fragments on the responses of isolated normal platelets to thrombin.

Patients’ F(ab’)2 increased platelet aggregation and serotonin release of platelets stimulated by low dose thrombin (0.01 U/ml). At threshold thrombin concentration (0.05 U/ml) an enhanced TXB2 production was also observed.

In summary, our results show, in addition to the altered TXA2/PGI2 balance observed in vivo, a direct stimulatory effect of aPL antibodies on platelet activation in vitro. This effect is related to recognition of phospholipid epitopes on platelets as shown by its neutralization upon preincubation with phospholipids. This phenomenon may be relevant for the thrombotic tendency of these patients.
Compound Heterozygosity in a Family with Protein C Deficiency Illustrating the Complexity of the Underlying Molecular Mechanism
Authors: Gandrille Sophie , Jude Brigitte , Alhenc-Gelas Martine , Millaire Alain , Aiach Martine
Published: July 2018

The association of two missense mutations, a Leu 223 to Phe and an lie 403 to Met, is described in a family presenting with various protein C deficiency phenotypes. In this family, two subjects were compound heterozygotes with protein C levels of about 25%, the other members being heterozygous for only one of the mutations. The Leu 223 to Phe mutation was also found in 9 members of 3 other families and, in all cases but one, resulted in protein C levels below 60% associated with a high incidence of thrombotic complications. The other mutation, an lie 403 to Met, was identified in those of the family’ members who presented with borderline protein C concentrations. In such a family, the genomic DNA analysis represents the only way to differentiate between the genetic status of each family member. The results highlight the importance of the genotype determination and the poor discriminative power of the plasma assays currently used.
Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation
Authors: Carteaux Jean-P , Steiner Beat , Roux Sébastien
Published: July 2018

Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 449883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 ± 4% and 25 ± 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 ± 8% and 54 ± 9%; p <0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 ± 8%) and only slightly decreased at 60 min (80 ± 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.
Modification of Platelet Function by Radical Species Produced During Irradiation of Oxygenated Water
Authors: Krinsky Norman I , Sladdin Danielle G , Levine Peter H , Taub Irwin A , Simic Michael G
Published: July 2018

Gel-filtered platelets in neutral, oxygen-containing solutions irradiated to a dose of 10 krad with γ-rays display a significant inhibition of ADP-induced aggregation. Though the superoxide anion radical (O-
2) and H2O2 are generated in water irradiated under these conditions, only catalase, but not superoxide dismutase (SOD), conveyed protection against this inhibition of platelet function. When the platelets are in the presence of 10-3 M sodium formate, which converts the majority of the radical species formed to O-
2, inhibition of aggregation was again observed. Under these circumstances, the addition of catalase significantly decreased this inhibition, whereas the addition of SOD was without effect.

In order to separate the platelet-inhibition effects of the radical species generated in the medium from a direct effect of irradiation on platelet components, relatively stable quantities of O-
2. were produced in alkaline solutions and reacted with gel-filtered platelets. Again, an inhibition of ADP-induced aggregation was observed. This inhibition was not significantly altered by the addition of SOD, but was abolished by the addition of catalase, either with or without SOD.

Our observation would indicate that O-
2.is without direct effect on platelet function, but serves as the precursor of H2O2, which can inhibit platelet reactions.
Diversity of Primary Structures of the Carboxy-terminal Regions of Mammalian Fibrinogen Aα-Chains
Authors: Murakawa Masahiro , Okamura Takashi , Kamura Takumi , Shibuya Tsunefumi , Harada Mine , Niho Yoshiyuki
Published: July 2018

The partial amino acid sequences of fibrinogen Aα-chains from five mammalian species have been inferred by means of the polymerase chain reaction (PCR). From the genomic DNA of the rhesus monkey, pig, dog, mouse and Syrian hamster, the DNA fragments coding for α-C domains in the Aα-chains were amplified and sequenced. In all species examined, four cysteine residues were always conserved at the homologous positions. The carboxy- and amino-terminal portions of the α-C domains showed a considerable homology among the species. However, the sizes of the middle portions, which corresponded to the internal repeat structures, showed an apparent variability because of several insertions and/or deletions. In the rhesus monkey, pig, mouse and Syrian hamster, 13 amino acid tandem repeats fundamentally similar to those in humans and the rat were identified. In the dog, however, tandem repeats were found to consist of 18 amino acids, suggesting an independent multiplication of the canine repeats. The sites of the α-chain cross-linking acceptor and α2-plasmin inhibitor cross-linking donor were not always evolutionally conserved. The arginyl-glycyl-aspartic acid (RGD) sequence was not found in the amplified region of either the rhesus monkey or the pig. In the canine α-C domain, two RGD sequences were identified at the homologous positions to both rat and human RGD S. In the Syrian hamster, a single RGD sequence was found at the same position to that of the rat. Triplication of the RGD sequences was seen in the murine fibrinogen α-C domain around the homologous site to the rat RGDS sequence. These findings are of some interest from the point of view of structure-function and evolutionary relationships in the mammalian fibrinogen Aα-chains.
Recombinant Pro-Urokinase Requires Heparin for Optimal Clot Lysis and Restoration of Blood Flow in a Canine Femoral Artery Thrombosis Model
Authors: Burke Sandra E , Lubbers Nathan L , Nelson Richard A , Henkin Jack
Published: July 2018

Heparin is often used as an adjunct to thrombolytic therapy in order to prevent reocclusion of the patent vessels in patients with thrombotic disease. Controversy exists as to whether heparin is required for effective clot lysis with tissue-type plasminogen activator, while in vitro data and small scale clinical trials have suggested an enhancement of pro-urokinase efficacy by heparin. The present study was conducted to determine whether heparin pre-treatment is required to produce optimal clot lysis and blood flow restoration in response to recombinant pro-urokinase (r-proUK). In four groups of dogs, blood clots labelled with 125Iodine were formed in the femoral artery and were monitored continuously for loss of counts as an indicator of clot lysis. Femoral artery blood flow was measured simultaneously. Group 1 received vehicle (n = 5), while group 2 was given vehicle + heparin (n = 6; 500 U bolus + 350 U/h). This dose of heparin increased the activated partial thromboplastin time (APTT) by at least 1.5 times the control level for the 4 h observation period. Group 3 received r-proUK alone at a dose of 100,000 U/kg (50% given as a 1-min bolus injection, 50% as a 30 min infusion) (n = 8), while group 4 was treated with the same dose of r-proUK in the presence of heparin as described (n = 8). Clot lysis at 4 h in groups 1 and 2 was 26 ± 3% and 28 ± 5%, respectively; flow was not restored in either group. In group 3, clot lysis was 50 ± 4% while group 4 showed lysis of 85 ± 5% (p <0.05). However, flow was not restored in any dog in group 3, while five of eight dogs in group 4 showed complete restoration of blood flow. In the remaining three dogs, flow was restored to 70–91% of control levels. The data suggest that a regimen of heparin pretreatment with continued infusion markedly increases the efficacy of r-proUK in this model and results in significant restoration of blood flow.
Subunit A of Factor XIII Regulates Subunit B Plasma Concentration
Authors: Rodeghiero F , Morbin M , Barbui T
Published: July 2018

Subunit a of Factor XIII is found absent in homozygotes and reduced in heterozygotes. Since a concomitant reduction of subunit b occurs in these cases, an interaction between the loci controlling the synthesis of the two subunits was suggested. However in the present study we have shown that the administration of subunit a in two totally devoid homozygotes produced an increase of subunit b, reaching the maximum concentration five days after infusion. This strongly suggests that subunit b plasma level is regulated on the subunit a plasma amount.
Rabbit Antibodies Against the Procoagulant Activity (VIII:C) of Human Factor VIII
Authors: Tran T H , Marbet G A , Duckert F
Published: July 2018

The procoagulant activity VIII:C was separated from factor VIII antigen (VIIIR:Ag) by gel filtration in the presence of 0.25 mol/l calcium chloride. Antibodies (anti-VIII:C) were obtained by immunization of rabbits with VIII:C. The last step of the purification procedure of antibodies consists of an adsorption on VIIIR:Ag-Sepharose 2 BCL as immunoadsorbent to remove contaminating traces of antibodies against VIIIR:Ag. The anti- VIII:C titer remains unchanged during this adsorption (29 Bethesda units per mg). In solution, anti-VIII:C neutralies factor VIII activity (in plasma, cryoprecipitate or in purified form) and the fragment VIII:C without reacting with VIIIR:Ag. Once immobilized on a solid matrix, i.e.2% agarose, it loses over 95% of its inhibitory capacity. The immobilized anti-VIIIR:Ag binds stoichiometrically the antigen and the activity of plasma factor VIII. These results together suggest that factor VIII is composed of 2 different entities, but undissociated under physiological conditions. Immunophysical analyses as a function of pH and temperature of anti-VIII:C and its complex with factor VIII show properties similar to those of homologous antibodies. The antigen determinants of VIII:C (VIII:CAg) are destroyed at low pHs or high temperatures, and VIII:C can no more form a complex with anti-VIII:C. Purified anti-VIII:C is also used in a two-stage assay to detect VIII:CAg or cross-reacting material in some severe haemophiliacs.
Fibrinopeptide A (FPA) Level and Fibrinogen Kinetics in Patients with Malignant Disease
Authors: Yoda Yasuhiro , Abe Tsukasa
Published: July 2018

FPA level, fibrinogen turnover rate, and fibrinolytic activity were studied on 18 patients with malignant disease. It was found that the FPA levels were significantly elevated and were correlated with fibrinogen turnover rate (r=0.74, p<0.001) and FDP (r = 0.58, p<0.02). Estimated FPA turnover rate was also correlated with fibrinogen turnover rate (r = 0.70, p<0.001). These results suggest that fibrinogen catabolism in patients with malignant disease is related with thrombin proteolysis. However, ratios of 1/2 FPA turnover rate to fibrinogen turnover rate suggest that intravascular thrombin proteolysis is not the major determinant of fibrinogen catabolism. It is suspected that extravascular thrombin proteolysis is responsible for the elevation of plasma FPA level which is correlated with acceleration of fibrinogen catabolism.
Prothrombin-Activator (Thromboplastin) Generation in the Blood of Water Snake (Natrix piscator)
Authors: Srivastava V M , Dube B , Dube R K , Agarwal G P
Published: July 2018

The generation of prothrombin-activator (thromboplastin) in water snake (Natrix piscator) is clearly delayed, Compared to a mammalian system, but the final activity is well comparable to that in man, when homologous sources of “phospholipid” (erythrocyte-lysate) and of substrate plasma are employed in one stage “thromboplastin generation test”. The use of heterologous source of either of the above reagents resulted in significantly longer clotting times; hence the need for homologous source of above reagents in the test is emphasized for comparative studies on animal haemostasis.
Delayed Elimination of Fibrin from the Lungs in Rats Given α2-Antiplasmin
Authors: Carlin G , Einarsson M , Saldeen T
Published: July 2018

Injection of human α2–antiplasmin resulted in delayed elimination of fibrin from the lungs in rats with thrombin–induced intravascular coagulation. The amount of α2–antiplasmin injected was chosen so as to simulate the posttraumatic increase of this inhibitor in man. By injecting trace amounts only of radiolabelled α2–antiplasmin a specific uptake of this protein in the lungs was noted after the thrombin-induced coagulation. The results may indicate that the posttraumatic increase in α2–antiplasmin is of significance for the delayed elimination of fibrin seen in patients following trauma.
Development and analysis of a novel printed circuit board electrostatic comb system for micro-newton thrust stand calibration
Authors: Wang Yanan , Ding Weidong , Cheng Le , Li Yue , Ge Chongjian , Han Ruoyu , Yan Jiaqi , Zhao Zheng , Sun Anbang
Published: July 2018

An electrostatic calibration technique is highly flexible in producing a wide range of force and it is widely applied for nano-newton to micro-newton thrust stand calibration. This paper proposes a novel method for electrostatic comb implementation and related experiments have been carried out. Based on the printed circuit board and commercial fins, the comb can be realized flexibly with the output force conveniently extended. The force generated by this kind of comb is theoretically analyzed. Different from the traditional comb structure, the conductive area of the comb fixed plate is minimized to improve the force consistency over engagement. The influence of fin length, fin number, applied voltage, and engagement on the output force has been studied experimentally. The final comb system is capable of producing steady force in the range 13-5040 μN with the relative error within 5%. With a high voltage pulse generator, this system could produce calibration impulse bit in the range 1-1000 μN s for which the lowest level can be far more extended to the nanonewton range with a shorter pulse width, a lower voltage, and a reduced number of fins. Moreover, the calibrator has a rather flat force-engagement characteristic when the engagement is in the range of 6 mm–16 mm, while the variation of electrostatic force is within 5%. This calibrator has a wide output range and great consistency, and it is beneficial for the thrust stand calibration.
Remote in situ laser-induced breakdown spectroscopic approach for diagnosis of the plasma facing components on experimental advanced superconducting tokamak
Authors: Zhao Dongye , Li Cong , Hu Zhenhua , Feng Chunlei , Xiao Qingmei , Hai Ran , Liu Ping , Sun Liying , Wu Ding , Fu Cailong , Liu Jiamin , Farid Nazar , Ding Fang , Luo Guang-Nan , Wang Liang , Ding Hongbin
Published: July 2018

The diagnosis of the fuel retention and impurity deposition on the plasma facing components (PFCs) is very important for monitoring plasma-wall interactions and improving the performance of long-pulse operation for tokamak devices. In this study, a remote in situ laser-induced breakdown spectroscopic (RIS-LIBS) system has been developed to be an effective and routine method for the diagnosis of the composition of the PFCs on Experimental Advanced Superconducting Tokamak (EAST). The RIS-LIBS system can be operated between EAST discharges via a remote network control system. This allows a flexible diagnosis for the PFCs at a specific EAST discharge operation or under planned plasma scenarios according to the experimental requirement. Measurements on the fuel retention and impurity deposition of the PFCs have been performed for the test of the RIS-LIBS system, and the depth resolution and the lateral resolution of the RIS-LIBS system have been achieved to be ∼100 nm and ∼3.0 mm, respectively. For the test of detectable elements, the fuel (deuterium) and impurities have been detected and identified clearly. In addition, the measurement of fuel abundance on the first wall as a function of the days of EAST deuterium plasma discharges has been carried out for the first time. These results well manifest a significant prospect of the RIS-LIBS for the diagnosis of the PFCs in the upcoming fusion devices like China Fusion Engineering Test Reactor (CFETR) and ITER.
Marginally turbulent Couette flow in a spanwise confined passage of square cross section
Authors: Owolabi Bayode E. , Lin Chao-An
Published: July 2018

The results of direct numerical simulations to determine the critical conditions for self-sustained turbulence in wall-driven (Couette) square duct flow and its characteristics at relatively low turbulent Reynolds numbers are presented. We focus on the case in which a pair of opposite counter-moving walls translating with the same speed drives the flow. Stabilisation by the side walls is found to play a crucial role in the transition to turbulence, the minimum Reynolds number for maintaining a turbulent state (Rec ≈ 875) being much greater than that in a plane channel. At Reynolds numbers close to the critical, an alternation of the flow field, in time, between two states characterised by a four-vortex secondary flow pattern is observed, one being a mirror reflection of the other, and the flow remains approximately symmetrical about the common bisector of the moving walls. Due to the intermittency, large velocity fluctuations about the long-term mean are observed at different locations in the duct. These findings are consistent with results of previous studies on turbulent pressure-driven (Poiseuille) square duct flow at low Reynolds numbers; hence, the phenomenon is not unique to Poiseuille flows. Instantaneous flow field visualisations reveal the existence of coherent structures which are persistent over the length of the duct, thus indicating that the states are very stable in the streamwise direction. Quadrant analysis of the Reynolds shear stress shows that the secondary motions are closely related to the near-wall ejection and sweeping events.
Small-angle scattering study of tetra-poly(acrylic acid) gels
Authors: Morishima Ken , Li Xiang , Oshima Kazuyuki , Mitsukami Yoshiro , Shibayama Mitsuhiro
Published: July 2018

Tetra-poly(acrylic acid) (tetra-PAA) gels were fabricated by cross-end coupling of azide (—N3) and alkyne (—C≡CH) terminated tetra-arm poly(tert-butyl acrylate)s. The structures of the tetra-PAA gels and their sols (tetra-PAA sols, i.e., tetra-PAA macromer solutions obtained by deprotection of tert-butyl groups) were investigated by small-angle X-ray and small-angle neutron scattering experiments in methanol, salt-free aqueous media, and salt solutions. The scattering functions, I(q), of the tetra-PAA sols in methanol were described by the Ornstein–Zernike (OZ) function, Iq=I(0)/(1+ξ2q2), whereas those of the gels were represented by the sum of the OZ function and a power-law function, Iq∼Aqb. Here, ξ is the correlation length, q is the magnitude of the scattering vector, A is a constant, and b is the scattering exponent. The OZ and the power-law functions represent the concentration fluctuations and cross-link inhomogeneities characteristic of gels, respectively. In salt-free aqueous media, there appeared a characteristic polyelectrolyte peak in the scattering functions, and the polymer concentration, C, dependence of the peak was similar for both sols and gels. In the presence of salt, both the scattering upturn for gels and the polyelectrolyte peak for both gels and sols were suppressed. Upon increasing the salt concentration, Cs, the scattering intensity increased in the low q regions and the scattering functions were well fitted by the OZ function for both gels and sols.
Electrically activated spin-controlled orbital angular momentum multiplexer
Authors: Ruffato Gianluca , Brasselet Etienne , Massari Michele , Romanato Filippo
Published: July 2018

We present and test the integration of a static orbital angular momentum mode multiplexer with a dynamical geometric-phase optical element, enabling on-demand spin-controlled angular momentum multiplexing. A diffractive optic multiplexer fabricated by 3D high-resolution electron beam lithography performs a conformal mapping for the conversion from linear to azimuthal phase gradients. The latter is functionalized by a dynamic spin-orbit add-on that consists of a self-engineered electrically activated liquid crystal optical vortex generator having large clear-aperture and high-resolution. By combining several functionalities based on the optical angular momentum of light in a compact manner, the proposed hybrid device could find applications in next-generation high-dimensional mode switchers and routers based on orbital angular momentum.
226 nm AlGaN/AlN UV LEDs using p-type Si for hole injection and UV reflection
Authors: Liu Dong , Cho Sang June , Park Jeongpil , Gong Jiarui , Seo Jung-Hun , Dalmau Rafael , Zhao Deyin , Kim Kwangeun , Kim Munho , Kalapala Akhil R. K. , Albrecht John D. , Zhou Weidong , Moody Baxter , Ma Zhenqiang
Published: July 2018

Deep ultraviolet (UV) light-emitting diodes (LEDs) at a wavelength of 226 nm based on AlGaN/AlN multiple quantum wells using p-type Si as both the hole supplier and the reflective layer are demonstrated. In addition to the description of the hole transport mechanism that allows hole injection from p-type Si into the wide bandgap device, the details of the LED structure which take advantage of the p-type Si layer as a reflective layer to enhance light extraction efficiency (LEE) are elaborated. Fabricated LEDs were characterized both electrically and optically. Owing to the efficient hole injection and enhanced LEE using the p-type Si nanomembranes (NMs), an optical output power of 225 μW was observed at 20 mA continuous current operation (equivalent current density of 15 A/cm2) without external thermal management. The corresponding external quantum efficiency is 0.2%, higher than any UV LEDs with emission wavelength below 230 nm in the continuous current drive mode. The study demonstrates that adopting p-type Si NMs as both the hole injector and the reflective mirror can enable high-performance UV LEDs with emission wavelengths, output power levels, and efficiencies that were previously inaccessible using conventional p-i-n structures.
Remote control of liquid crystal elastomer random laser using external stimuli
Authors: Tiwari Anjani Kumar , Pattelli Lorenzo , Torre Renato , Wiersma Diederik S.
Published: July 2018

We present a distinct design for a random laser based on a composite material consisting of an elastomeric liquid crystal with embedded TiO2 nanoparticles. Random lasing action can be controlled by an external, non-contact light stimulus; this induces a rearrangement of the elastomeric liquid crystals which moves the laser body in and out of the focal plane of a pump laser, pushing its emission above or below the lasing threshold.
A first look reveals the surprising behavior of droplet reaction forces on a soft superhydrophobic surface
Authors: Leahy Rhys
Published: July 2018

A position-sensing system and high-speed imaging help probe water droplet reaction forces on soft superhydrophobic surfaces. The fascinating dynamics may help industries exploit the superhydrophobic deflection further.
Poled piezo plates kill bacteria resting on their surface
Authors: Majors J. H.
Published: July 2018

The surfaces of a positively poled ferroelectric material prove deadly to E. coli, depolarizing the cells after attracting the extra surface charge used by their membranes for selectivity and function.
Magnets separate mirror-image molecules
Authors: Miller Johanna L.
Published: July 2018

Spin, not shape, underlies a surprising new method for sorting biomolecules from their opposite-handed counterparts.
A Bose–Einstein condensate in an atom
Authors: Smart Ashley G.
Published: July 2018

By embedding the condensate within the far-flung electronic orbit of a Rydberg atom, researchers orchestrated ion–atom collisions at record cold temperatures.
Size-sorted sand creates uncommon length scale in windblown formations
Authors: Berkowitz Rachel
Published: July 2018

A combination of grain-size distribution and critical wind speed is responsible for megaripples.
Concerns about aging plutonium drive need for new weapon cores
Authors: Kramer David
Published: July 2018

Despite multiple scientific studies pointing to existing long lifetimes of the key nuclear weapons components, the US Department of Energy settles on a dual-site modernization plan.
Restoring sight with retinal prostheses
Authors: Palanker Daniel , Goetz Georges
Published: July 2018

By implanting electrodes that transmit visual information to the surviving neurons in a diseased retina, it’s possible to bring the eye’s dormant neural circuitry back to life.
Large amplitude oscillatory shear: Simple to describe, hard to interpret
Authors: Rogers Simon
Published: July 2018

The response of a material to a periodic, large strain manifests the internal mechanisms by which the substance relieves stress. But Nature does not readily reveal her tricks.
Who owns a scientist’s mind?
Authors: O’Reagan Douglas
Published: July 2018

Changes in US law and practice during the 20th century gradually gave businesses more rights to their researchers’ ideas, but controlling knowledge is no easy task.
Engineering puffed rice
Authors: Gulati Tushar , Ukidwe Mayuri , Datta Ashim
Published: July 2018

Sophisticated materials science lies behind the fabrication of the crunchy, low-fat food enjoyed in cereals and snacks worldwide.
An overview of introduced predator management in inhabited landscapes
Authors: Russell James C. , Stanley Margaret C.
Published: July 2018

Predators play a critical role in ecosystems; however, when overly abundant, they can disrupt natural processes and cause extinctions of species. In particular, oceanic islands have endured many impacts of introduced mammalian predators. Whereas knowledge and management of introduced mammalian predators on islands is well advanced in natural landscapes, in inhabited landscapes, spanning rural and urban environments, comparatively less is known. We summarise key issues from the natural and social sciences in the management of introduced mammalian predators in inhabited landscapes of Aotearoa–New Zealand. We describe the shift in focus over the past few decades from management of introduced mammalian herbivores to predators in rural environments, and the growth in management of introduced mammalian predators in urban environments, both seeking to emulate conservation gains made in forested landscapes. We discuss the circumstances around companion animal management at the interface of the natural and social sciences. We summarise surveys of attitudes towards introduced mammalian predators, the role of biodiversity co-management between Māori and Pakeha, and the importance of also considering non-biodiversity benefits from introduced predator management. We describe the rise of community predator control and large landscape projects aspiring for a ‘Predator Free New Zealand’, and how such an aspiration must be concurrent with habitat restoration. We make recommendations for further research on the basic population biology of predators in inhabited landscapes, and more long-term studies. Such studies should be integrated with examination of the motivations for predator management, as well as the biodiversity and social outcomes of such management. We conclude by remarking that introduced predator management is only one component of a robust national strategy for conservation of native biodiversity in New Zealand.
Animal reintroductions in peopled landscapes: moving towards urban-based species restorations in New Zealand
Authors: van Heezik Yolanda , Seddon Philip J.
Published: July 2018

Urban areas are highly modified landscapes that can support significant biodiversity, including threatened species, although native species are usually present at low densities and several native species will be absent. The most powerful tool for increasing urban biodiversity is supporting existing biodiversity through appropriately designed and managed public and private greenspaces, and improving habitat quality. However, if a more proactive strategy is required to overcome recolonisation barriers, then reintroduction is another powerful tool to enhance biodiversity across urban landscapes. The health of cities, in terms of biodiversity, ecosystem services, and the quality of the nature experiences accessed by adults and children largely depends on how much human communities value and know about nature. While community-driven habitat restorations can improve biodiversity and increase human–nature connection, reintroduction of appropriate species could fill ecological gaps that would otherwise remain empty, and further enrich biodiversity in residents’ nearby neighbourhoods. New Zealand is currently a hotspot of reintroduction activity, but these take place in relatively unmodified terrestrial sites, such as national parks, restored offshore islands, and fenced eco-sanctuaries. We review global examples of animal reintroductions taking place within areas modified by human activity, and, using information elicited from 18 experts, consider potential reintroduction candidates, and consider the benefits, opportunities, challenges, and requirements for the reintroduction of native species into New Zealand’s urban areas.
Personalized disease signatures through information-theoretic compaction of big cancer data
Authors: Vasudevan Swetha , Flashner-Abramson Efrat , Remacle F. , Levine R. D. , Kravchenko-Balasha Nataly
Published: July 2018

Significance

Accurate cancer diagnostics is a prerequisite for optimal personalized cancer medicine. We propose an information-theoretic cancer diagnosis that identifies signatures comprising patient-specific oncogenic processes rather than cancer type-specific biomarkers. Such comprehensive transcriptional signatures should allow for more accurate classification of cancer patients and better patient-specific diagnostics. The approach that we describe herein allows decoding of large-scale molecular-level information and elucidating patient-specific transcriptional altered network structures. Thereby, we move from cancer type-associated biomarkers to unbiased patient-specific unbalanced oncogenic processes.
Characterization of a novel hydroxynitrile lyase from Nandina domestica Thunb
Authors: Isobe Kimiyasu , Kitagawa Asuka , Kanamori Kazuma , Kashiwagi Nozomi , Matsui Daisuke , Yamaguchi Takuya , Fuhshuku Ken-ichi , Semba Hisashi , Asano Yasuhisa
Published: July 2018

The leaves of Nandina domestica Thunb. exhibited high hydroxynitrile lyase (HNL) activity in (R)-mandelonitrile synthesis. The specific activity of young leaves was significantly higher than that of mature leaves. We isolated two HNLs with molecular mass of 24.9 kDa (NdHNL-S) and 28.0 kDa (NdHNL-L) from the young leaves. Both NdHNLs were composed of two identical subunits, without FAD and carbohydrates. We purified NdHNL-L and revealed its enzymatic properties. The whole deduced amino acid sequence of NdHNL-L was not homologous to any other HNLs, and the specific activity for mandelonitrile synthesis by NdHNL-L was higher than that by other plant HNLs. The enzyme catalyzed enantioselective synthesis of (R)-cyanohydrins, exhibited high activity at pH 4.0, and high stability in the pH range of 3.5–8.0 and below 55°C. Thus, NdHNL-L is a novel HNL with novel amino acid sequence and has a potential for the efficient production of (R)-cyanohydrins.
Contextual factors on physical demands in professional women's soccer: Female Athletes in Motion study
Authors: Vescovi Jason D. , Falenchuk Olesya
Published: July 2018

The aim of this study was to examine the impact of contextual factors on relative locomotor and metabolic power distances during professional female soccer matches. Twenty‐eight players (forwards, n = 4; midfielders, n = 12; defenders, n = 12) that competed in a 90‐min home and away match (regular season only). The generalised estimating equations (GEE) was used to evaluate relative locomotor and metabolic power distances for three contextual factors: location (home vs. away), type of turf (natural vs. artificial), and match outcome (win, loss and draw). No differences were observed for home vs. away matches. Moderate‐intensity running (20.0 ± 1.0 m min−1 and 16.4 ± 0.9 m min−1), high‐intensity running (8.6 ± 0.4 m min−1 and 7.3 ± 0.4 m min−1) and high‐metabolic power (16.3 ± 0.5 m min−1 and 14.4 ± 0.5 m min−1) distances were elevated on artificial turf compared to natural grass, respectively. Relative sprint distance was greater during losses compared with draws (4.3 ± 0.4 m min−1 and 3.4 ± 0.3 m min−1). Overall physical demands of professional women's soccer were not impacted by match location. However, the elevation of moderate and high‐intensity demands while playing on artificial turf may have implications on match preparations as well as recovery strategies.
Deficits in context-dependent adaptive coding in early psychosis and healthy individuals with schizotypal personality traits
Authors: Kirschner Matthias , Haugg Amelie , Manoliu Andrei , Simon Joe J , Huys Quentin J M , Seifritz Erich , Tobler Philippe N , Kaiser Stefan
Published: July 2018

Adaptive coding of information is a fundamental principle of brain functioning. It allows for efficient representation over a large range of inputs and thereby alleviates the limited coding range of neurons. In the present study, we investigated for the first time potential alterations in context-dependent reward adaptation and its association with symptom dimensions in the schizophrenia spectrum. We studied 27 patients with first-episode psychosis, 26 individuals with schizotypal personality traits and 25 healthy controls. We used functional MRI in combination with a variant of the monetary incentive delay task and assessed adaptive reward coding in two reward conditions with different reward ranges. Compared to healthy controls, patients with first-episode psychosis and healthy individuals with schizotypal personality traits showed a deficit in increasing the blood oxygen level-dependent response slope in the right caudate for the low reward range compared to the high reward range. In other words, the two groups showed inefficient neural adaptation to the current reward context. In addition, we found impaired adaptive coding of reward in the caudate nucleus and putamen to be associated with total symptom severity across the schizophrenia spectrum. Symptom severity was more strongly associated with neural deficits in adaptive coding than with the neural coding of absolute reward outcomes. Deficits in adaptive coding were prominent across the schizophrenia spectrum and even detectable in unmedicated (healthy) individuals with schizotypal personality traits. Furthermore, the association between total symptom severity and impaired adaptive coding in the right caudate and putamen suggests a dimensional mechanism underlying imprecise neural adaptation. Our findings support the idea that impaired adaptive coding may be a general information-processing deficit explaining disturbances within the schizophrenia spectrum over and above a simple model of blunted absolute reward signals.
Revealing a Cortical Circuit Responsive to Predatory Threats and Mediating Contextual Fear Memory
Authors: de Lima Miguel Antonio Xavier , Baldo Marcus Vinicius C , Canteras Newton Sabino
Published: July 2018

The ventral part of the anteromedial thalamic nucleus (AMv) receives substantial inputs from hypothalamic sites that are highly responsive to a live predator or its odor trace and represents an important thalamic hub for conveying predatory threat information to the cerebral cortex. In the present study, we begin by examining the cortico-amygdalar-hippocampal projections of the main AMv cortical targets, namely, the caudal prelimbic, rostral anterior cingulate, and medial visual areas, as well as the rostral part of the ventral retrosplenial area, one of the main targets of the anterior cingulate area. We observed that these areas form a clear cortical network. Next, we revealed that in animals exposed to a live cat, all of the elements of this circuit presented a differential increase in Fos, supporting the idea of a predator threat-responsive cortical network. Finally, we showed that bilateral cytotoxic lesions in each element of this cortical network did not change innate fear responses but drastically reduced contextual conditioning to the predator-associated environment. Overall, the present findings suggest that predator threat has an extensive representation in the cerebral cortex and revealed a cortical network that is responsive to predatory threats and exerts a critical role in processing fear memory.
Antisense lncRNA transcription drives stochastic Protocadherin α promoter choice
Authors: Canzio Daniele , Nwakeze Chiamaka L. , Horta Adan , Rajkumar Sandy M. , Coffey Eliot L. , Duffy Erin E. , Duffié Rachel , Simon Matthew D. , Lomvardas Stavros , Maniatis Tom
Published: July 2018

Stochastic and combinatorial activation of clustered Protocadherin (Pcdh) α, β, and γ gene promoters generates a cell-surface identity code in individual neurons that functions in neural circuit assembly. Here we show that Pcdhα promoter choice requires transcription of a long noncoding RNA (lncRNA) initiated from newly identified promoters located in the protein coding sequence of each Pcdhα exon. Antisense transcription of the lncRNA through the sense promoter results in its activation and in DNA demethylation of the binding sites for the CCCTC-binding protein, CTCF, located in close proximity to both sense and antisense promoters. Increased CTCF binding promotes the assembly of long-range DNA contacts between the activated promoter and a neuron-specific enhancer, thus locking in the epigenetic state of the stochastically chosen Pcdhα promoter. Examination of this hierarchical molecular mechanism in differentiating olfactory sensory neurons, suggests that antisense Pcdhα transcription is a key prerequisite for stochastic Pcdhα promoter choice in vivo.
DEET feet: Aedes aegypti mosquitoes use their tarsi to sense DEET on contact
Authors: Dennis Emily Jane , Vosshall Leslie Birgit
Published: July 2018

DEET (N, N-diethyl-meta-toluamide) is the most effective and broadly used insect repellent, but its mechanism of action is both complex and controversial [1]. Previous work demonstrated that DEET acts both on insect smell [2-6] and taste [7-11] systems. Its olfactory mode of action requires the odorant co-receptor orco [2, 3, 6], while its gustatory repellency is mediated by activation of bitter taste receptors and neurons in the proboscis upon ingestion [8]. Together, these data have led to the assumption that DEET acts only on olfactory and gustatory pathways. We previously observed that orco mutant female Aedes aegypti mosquitoes are strongly attracted to humans even in the presence of DEET, but are rapidly repelled after contacting DEET-treated skin [6]. To understand the basis of this contact chemorepellency, we carried out a series of behavioral experiments and discovered that DEET acts in three distinct ways: through smell, taste, and contact. DEET and bitter tastants are feeding deterrents when ingested, but only DEET is capable of mediating contact repellency on human skin. We show that the repellent touch of DEET is mediated by the tarsal segments of the legs, and not gustatory neurons in the proboscis as previously believed. This work establishes mosquito leg appendages as the actual sensors of DEET, and highlights the existence of an unknown sensory pathway that is independent of bitter taste. These results will inform the search for novel contact-based insect repellents.

Highlights

DEET and bitters are both repellent when ingested by Aedes aegypti female mosquitoes

Only DEET is additionally repellent upon contact

Repellency of DEET on skin is mediated solely by the legs

Any of the three pairs of legs can sense DEET and prevent mosquitoes from biting
DNMT3A-NPM1 mutated acute myeloid leukaemia shows sensitivity to a PARP1 inhibitor combined with daunorubicin in an in vitro model
Authors: Gafencu Grigore , Pileczki Valentina , Jurj Ancuta , Magdo Lorand , Selicean Cristina , Ola Roxana , Ghiaur Gabriel , Berindan-Neagoe Ioana , Tomuleasa Ciprian
Published: July 2018

Acute myeloid leukaemia is a neoplasia in need of new treatment approaches. PARP inhibitors are a class of targeted therapeutics for cancer that disrupts dysfunctional DNA damage response in various neoplasia. MLL-AF9 mutated leukaemias are sensitive to combinations of PARP inhibitors and cytotoxic drugs. Moreover, DNMT3A and NPM1 mutations are linked to dysfunctions in DNA damage response. Therefore, we investigated if DNMT3A-NPM1 mutated AML cell line is sensible to PARP inhibitors combined with anthracyclines. Our results show that DNMT3A-NPM1 mutated AML is as sensible to combinations of PARP inhibitors and anthracyclines as MLL-AF9 mutated leukaemias, in an in vitro setting.
Therapeutic gene editing in hematopoietic progenitor cells from a mouse model of Fanconi anemia
Authors: Pino-Barrio MJ , Gimenez Y , Villanueva M , Hildenbeutel M , Sánchez-Dominguez R , Rodriguez-Perales S , Pujol R , Surrallés J , Rio P , Cathomen T , Mussolino C , Bueren JA , Navarro S
Published: July 2018

The promising ability to genetically modify hematopoietic stem and progenitor cells (HSPCs) by precise gene editing remains challenging due to their sensitivity and poor permissiveness. This represents the first evidence of implementing a gene editing strategy in a murinesafe harborlocus that phenotypically corrects primary cells derived from a mouse model of Fanconi anemia (FA).

By co-delivering TALENs and a donor therapeuticFANCAcassette template to theMbs85locus (ortholog of the hAAVS1 safe harborlocus), we achieved efficient gene targeting (23%) in FA mouse embryonic fibroblasts (MEFs). This resulted in the phenotypic correction of these cells, as revealed by the improvement of their hypersensitivity to mitomycinC. Moreover, robust evidence of targeted integration was observed in murine WT and FA-A hematopoietic progenitor cells (HPC) reaching mean targeted integration values of 20.98% and 16.33% respectively, with phenotypic correction of FA HPCs. Overall, our results demonstrate the feasibility of implementing a therapeutic targeted integration strategy in a murinesafe harborlocus, such as theMbs85gene, of MEFs and murine HPC from a FA mouse model.
Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects
Authors: Annamalai Ramkumar T. , Hong Xiaowei , Schott Nicholas , Benjamin Levi Gopinath Tiruchinapally , Stegemann Jan P.
Published: July 2018

Repair of complex fractures with bone loss requires a potent, space-filling intervention to promote regeneration of bone. We present a minimally-invasive strategy combining mesenchymal stromal cells (MSC) with a chitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.
Multivariate methods for testing hypotheses of temporal community dynamics
Authors: Buckley Hannah L. , Day Nicola J. , Case Bradley S. , Lear Gavin , Ellison Aaron M.
Published: July 2018

For ecological research to make important contributions towards understanding and managing temporally-variable global change processes, such as responses to land-use and climatic change, we must have effective and comparable ways to quantify and analyse compositional change over time in biological communities. These changes are the sum of local colonisation and extinction events, or changes in the biomass and relative abundance of taxa within and among samples. We conducted a quantitative review of currently available methods for the analysis of multivariate datasets collected at temporal intervals. This review identified the need for the application of quantitative, hypothesis-based approaches to understand temporal change in community composition, particularly for small datasets with less than 15 temporal replicates. To address this gap, we: (1) conceptually present how temporal patterns in community dynamics can be framed as specific, testable hypotheses; (2) provide three fully-worked case-studies, complete with R code, demonstrating multivariate analysis methods for temporal hypothesis testing and pattern visualisation; and (3) present a road map for testing specific, quantitative hypotheses relating to the underlying mechanisms of temporal community dynamics.
Infer related genes from large scale gene expression dataset with embedding
Authors: Choy Chi Tung , Wong Chi Hang , Chan Stephen Lam
Published: July 2018

Artificial neural networks (ANNs) have been utilized for classification and prediction task with remarkable accuracy. However, its implications for unsupervised data mining using molecular data is under-explored. We adopted a method of unsupervised ANN, namely word embedding, to extract biologically relevant information from TCGA gene expression dataset. Ground truth relationship, such as cancer types of the input sample and semantic meaning of genes, were showed to retain in the resulting entity matrices. We also demonstrated the interpretability and usage of these matrices in shortlisting candidates from a long gene list. This method is feasible to mine big volume of biological data, and would be a valuable tool to discover novel knowledge from omics data. The resulting embedding matrices mined from TCGA gene expression data are interactively explorable online (http://bit.ly/tcga-embedding-cancer) and could serve as an informative reference.