bluuebunny/crossref_metadata_2025 huggingface dataset:
Human umbilical vein endothelial cell vaccine therapy in patients with recurrent glioblastoma
Authors: Tanaka Minoru , Tsuno Nelson Hirokazu , Fujii Tomoyuki , Todo Tomoki , Saito Nobuhito , Takahashi Koki
Published: October 2012

We aimed to assess the clinical efficacy of glutaraldehyde‐fixed human umbilical vein endothelial cell (HUVEC) vaccine for the treatment of patients with recurrent glioblastoma. Patients of a HUVEC vaccine group received intradermal injections of 5 × 107 HUVEC weekly during the first month, and every 2 weeks from the second month, until progression of the disease was observed. Salvage treatment consisted of multimodal chemotherapy, radiation, including gamma‐knife therapy, and/or repeated surgery, when feasible. Hazard ratios for death were calculated using a Cox model. A total of 17 patients with recurrent glioblastoma were enrolled in this study. All the patients received the initial treatment consisting of maximal safe surgical resection, followed by radiotherapy of 50–80 Gy or more, with concomitant and adjuvant chemotherapy consisting of temozolomide or nimustine (ACNU). A total of 352 vaccinations were performed for the patients of the HUVEC vaccine group (median number of vaccination = 11 doses; range 3–122 doses). The median progression‐free survival and overall survival were 5.5 and 11.4 months, respectively. The median overall survival from the diagnosis was 24.3 months. The HUVEC vaccine therapy significantly prolonged the tumor doubling time and contributed to reducing the tumor growth rate. Hematological adverse reactions due to chemotherapy were recognized: one patient experienced grade III leukocytopenia and one showed grade II lymphocytopenia. Associated with the HUVEC vaccine therapy, a delayed‐type hypersensitivity‐like skin reaction developed at the injection site. The HUVEC vaccine therapy effectively controlled disease progression, without evident adverse effects, except for a delayed‐type hypersensitivity‐like skin reaction at the injection site.
Getting the closer object? An information‐based dissociation between vision for perception and vision for movement in early infancy
Authors: van Wermeskerken Margot , van der Kamp John , Savelsbergh Geert J.P. , von Hofsten Claes
Published: October 2012

In human adults two functionally and neuro‐anatomically separate systems exist for the use of visual information in perception and the use of visual information to control movements (Milner & Goodale,,). We investigated whether this separation is already functioning in the early stages of the development of reaching. To this end, 6‐ and 7‐month‐old infants were presented with two identical objects at identical distances in front of an illusory Ponzo‐like background that made them appear to be located at different distances. In two further conditions without the illusory background, the two objects were presented at physically different distances. Preferential reaching outcomes indicated that the allocentric distance information contained in the illusory background affected the perception of object distance. Yet, infants' reaching kinematics were only affected by the objects' physical distance and not by the perceptual distance manipulation. These findings were taken as evidence for the two‐visual systems, as proposed by Milner and Goodale (), being functional in early infancy. We discuss the wider implications of this early dissociation.
Responses of the functional structure of soil microbial community to livestock grazing in the Tibetan alpine grassland
Authors: Yang Yunfeng , Wu Linwei , Lin Qiaoyan , Yuan Mengting , Xu Depeng , Yu Hao , Hu Yigang , Duan Jichuang , Li Xiangzhen , He Zhili , Xue Kai , van Nostrand Joy , Wang Shiping , Zhou Jizhong
Published: October 2012

Microbes play key roles in various biogeochemical processes, including carbon (C) and nitrogen (N) cycling. However, changes of microbial community at the functional gene level by livestock grazing, which is a global land‐use activity, remain unclear. Here we use a functional gene array, GeoChip 4.0, to examine the effects of free livestock grazing on the microbial community at an experimental site of Tibet, a region known to be very sensitive to anthropogenic perturbation and global warming. Our results showed that grazing changed microbial community functional structure, in addition to aboveground vegetation and soil geochemical properties. Further statistical tests showed that microbial community functional structures were closely correlated with environmental variables, and variations in microbial community functional structures were mainly controlled by aboveground vegetation, soil C/N ratio, and NH4+‐N. In‐depth examination of N cycling genes showed that abundances of N mineralization and nitrification genes were increased at grazed sites, but denitrification and N‐reduction genes were decreased, suggesting that functional potentials of relevant bioprocesses were changed. Meanwhile, abundances of genes involved in methane cycling, C fixation, and degradation were decreased, which might be caused by vegetation removal and hence decrease in litter accumulation at grazed sites. In contrast, abundances of virulence, stress, and antibiotics resistance genes were increased because of the presence of livestock. In conclusion, these results indicated that soil microbial community functional structure was very sensitive to the impact of livestock grazing and revealed microbial functional potentials in regulating soil N and C cycling, supporting the necessity to include microbial components in evaluating the consequence of land‐use and/or climate changes.
In vitro direct plant regeneration and Agrobacterium‐mediated transformation of lucerne (Medicago sativa L.)
Authors: Kumar S. , Tiwari R. , Chandra A. , Sharma A. , Bhatnagar R. K.
Published: October 2012

In vitro direct plant regeneration of lucerne was achieved by simultaneous application of thidiazuron (TDZ) and 6‐benzyladenine (BA) in Murashige and Skoog (MS) medium. Seedlings were germinated and grown for 6 d on growth regulator–containing MS medium. The shoot tip, consisting of the apical meristem along with parts of the cotyledonary leaves and hypocotyl, was then cultured on a medium containing the growth regulator(s). Adventitious budding of the shoot tip was promoted synergistically by treatment with TDZ and BA, and a maximum of thirty‐five shoots per explant was obtained on a medium supplemented with 2 mg L−1 TDZ and 1 mg L−1 BA. Plant regeneration frequency varied from 67 to 93%, and five Indian lucerne cultivars responded well to the regeneration protocol. The Agrobacterium‐mediated transformation frequency from co‐cultivated explants was 13% following multiple shoot induction. Southern analysis of the T0 plants and T1 progenies confirmed stable inheritance of the hpt marker gene. Agrobacterium infection of the explant caused a significant reduction in the plant regeneration frequency (23%) and the number of shoots induced (11) when compared with uninfected explants. A single shoot tip provided sufficient material to regenerate and establish twenty‐seven lucerne plants, whereas only nine plants could be regenerated from an Agrobacterium co‐cultivated explant. This transformation protocol could represent a valuable improvement over existing ones for lucerne.
Different parasite inocula determine the modulation of the immune response and outcome of experimental Trypanosoma cruzi infection
Authors: Borges Diego C. , Araújo Natalia M. , Cardoso Cristina R. , Lazo Chica Javier E.
Published: October 2012

During infection, the host response develops effector mechanisms to combat the parasite. However, this response can become uncontrolled or regulated by mechanisms that modulate the inflammatory reaction. The number of parasites that infects the host, such as trypomastigotes in Chagas disease, may also influence immune activation and disease pathology. We evaluated the inflammation and immune regulation that follows Trypanosoma cruzi infection with low (300), intermediate (3000) or high (30 000) parasite loads. Our results showed that the load of parasite inoculum influenced disease outcome: the higher the number of parasites in the inoculum, the lower were the survival rates. There was a strong association between parasitism and inflammatory infiltrate in the heart and the parasite inoculum determined cytokine interplay in this tissue, as shown by increased interferon‐γ, tumour necrosis factor‐α, interleukin‐17 (IL‐17) and IL‐23 in the 300 and 30 000 inoculum groups, higher IL‐4 and IL‐10 in the intermediate‐inoculum mice, and elevated IL‐6 production in the heart of mice in the 3000 and 30 000 groups. The number of T cells and antigen‐presenting cells was augmented in the infected groups, especially for the splenic CD4+ CD25+ regulatory T cells expressing CD45RBlow, GITR, PD‐1 and FoxP3 in the group with the highest inoculum. Interestingly, these mice also presented an apparent decrease in CD4+ CD25+ FoxP3+ cells in the cardiac infiltrate, in contrast to the intermediate inoculum group, which showed elevated numbers of these regulatory leucocytes in the heart. Finally, our results demonstrated that parasite load during T. cruzi infection is linked to the response pattern that will result in parasite/inflammation control or tissue damage.
The phagocytic capacity and immunological potency of human dendritic cells is improved by α2,6‐sialic acid deficiency
Authors: Cabral M. Guadalupe , Silva Zélia , Ligeiro Dário , Seixas Elsa , Crespo Hélio , Carrascal Mylène A. , Silva Mariana , Piteira Ana R. , Paixão Paulo , Lau Joseph T. , Videira Paula A.
Published: October 2012

Dendritic cells (DCs) play an essential role in immunity against bacteria by phagocytosis and by eliciting adaptive immune responses. Previously, we demonstrated that human monocyte‐derived DCs (MDDCs) express a high content of cell surface α2,6‐sialylated glycans. However, the relative role of these sialylated structures in phagocytosis of bacteria has not been reported. Here, we show that treatment with a sialidase significantly improved the capacity of both immature and mature MDDCs to phagocytose Escherichia coli. Desialylated MDDCs had a significantly more mature phenotype, with higher expression of MHC molecules and interleukin (IL)‐12, tumour necrosis factor‐α, IL‐6 and IL‐10 cytokines, and nuclear factor‐κB activation. T lymphocytes primed by desialylated MDDCs expressed more interferon‐γ when compared with priming by sialylated MDDCs. Improved phagocytosis required E. coli sialic acids, indicating a mechanism of host–pathogen interaction dependent on sialic acid moieties. The DCs harvested from mice deficient in the ST6Gal.1 sialyltransferase showed improved phagocytosis capacity, demonstrating that the observed sialidase effect was a result of the removal of α2,6‐sialic acid. The phagocytosis of different pathogenic E. coli isolates was also enhanced by sialidase, which suggests that modifications on MDDC sialic acids may be considered in the development of MDDC‐based antibacterial therapies. Physiologically, our findings shed new light on mechanisms that modulate the function of both immature and mature MDDCs, in the context of host–bacteria interaction. Hence, with particular relevance to DC‐based therapies, the engineering of α2,6‐sialic acid cell surface is a novel possibility to fine tune DC phagocytosis and immunological potency.
Differential requirements of CD4+T‐cell signals for effector cytotoxic T‐lymphocyte (CTL) priming and functional memory CTL development at higher CD8+T‐cell precursor frequency
Authors: Umeshappa Channakeshava S. , Nanjundappa Roopa H. , Xie Yufeng , Freywald Andrew , Xu Qingyong , Xiang Jim
Published: October 2012

Increased CD8+ T‐cell precursor frequency (PF) precludes the requirement of CD4+ helper T (Th) cells for primary CD8+ cytotoxic T‐lymphocyte (CTL) responses. However, the key questions of whether unhelped CTLs generated at higher PF are functional effectors, and whether unhelped CTLs can differentiate into functional memory cells at higher PF are unclear. In this study, ovalbumin (OVA) ‐pulsed dendritic cells (DCOVA) derived from C57BL/6, CD40 knockout (CD40−/−) or CD40 ligand knockout (CD40L−/−) mice were used to immunize C57BL/6, Iab−/−, CD40−/− or CD40L−/− mice, whose PF was previously increased with transfer of 1 × 106 CD8+ T cells derived from OVA‐specific T‐cell receptor (TCR) transgenic OTI, OTI(CD40−/−) or OTI(CD40L−/−) mice. All the immunized mice were then assessed for effector and memory CTL responses. Following DC immunization, relatively comparable CTL priming occurred without CD4+ T‐cell help and Th‐provided CD40/CD40L signalling. In addition, the unhelped CTLs were functional effectors capable of inducing therapeutic immunity against established OVA‐expressing tumours. In contrast, the functional memory development of CTLs was severely impaired in the absence of CD4+ T‐cell help and CD40/CD40L signalling. Finally, unhelped memory CTLs failed to protect mice against lethal tumour challenge. Taken together, these results demonstrate that CD4+ T‐cell help at higher PF, is not required for effector CTL priming, but is required for functional memory CTL development against cancer. Our data may impact the development of novel preventive and therapeutic approaches in cancer patients with compromised CD4+ T‐cell functions.
Potential cotton aphid, Aphis gossypii, population suppression by arthropod predators in upland cotton
Authors: Shrestha Ram B. , Parajulee Megha N.
Published: October 2012

The cotton aphid, Aphis gossypii Glover, predation rate of convergent lady beetle, Hippodamia convergens Guerin‐Meneville, was determined by assigning a single predator randomly to each of four prey density treatments in the laboratory. Prey densities included 25, 50, 100, and 200 aphids per Petri dish arena. Predation response was recorded at 1, 4, 8, 16, 24, and 48 h after assigning predators to their prey treatments. Rate of consumption increased through time, with all 25 aphids consumed during the first 4 h of the experiment. At the highest density, adult lady beetle consumed on average 49, 99, 131, 163, 183, and 200 aphids within 1, 4, 8, 16, 24 and 48 h, respectively. Predators showed a curvilinear feeding response in relation to total available time, indicating that convergent lady beetles have the potential to suppress larger populations of aphids through continuous feeding by regulating their predation efficiency during feeding. The analysis of age‐specific mortality in absence of prey revealed that lady beetles could survive for an extended period of time (more than 2 weeks) without prey. The ability of a predator to survive without prey delays or prevents the rebound of pest populations that is a significant factor in natural biological control. A two‐year field sampling of 10 cotton arthropod predator species showed that spiders (27%) were the most dominant foliage dwelling predators in the Texas High Plains cotton followed by convergent lady beetles (23.5%), hooded beetles (13.5%), minute pirate bugs (11%), green lacewings (9.5%), bigeyed bugs (7.5%), scymnus beetles (3%), soft‐winged flower beetles (2%), damsel bugs (1.5%), and assassin bugs (1.5%). A field cage study showed that one H. convergens adult per plant released at prey density of one aphid per leaf kept the aphid population below economic threshold for the entire growing season.
Priming of antiherbivore defensive responses in plants
Authors: Kim Jinwon , Felton Gary W.
Published: October 2012

Defense priming is defined as increased readiness of defense induction. A growing body of literature indicates that plants (or intact parts of a plant) are primed in anticipation of impending environmental stresses, both biotic and abiotic, and upon the following stimulus, induce defenses more quickly and strongly. For instance, some plants previously exposed to herbivore‐inducible plant volatiles (HIPVs) from neighboring plants under herbivore attack show faster or stronger defense activation and enhanced insect resistance when challenged with secondary insect feeding. Research on priming of antiherbivore defense has been limited to the HIPV‐mediated mechanism until recently, but significant advances were made in the past three years, including non‐HIPV‐mediated defense priming, epigenetic modifications as the molecular mechanism of priming, and others. It is timely to consider the advances in research on defense priming in the plant–insect interactions.
Locomotion behavior of cao vit gibbon (Nomascus nasutus) living in karst forest in Bangliang Nature Reserve, Guangxi, China
Authors: FAN Pengfei , SCOTT Matthew B. , FEI Hanlan , MA Changyong
Published: October 2012

The cao vit gibbon is a critically endangered species. Only approximately 110 individuals remain in degraded karst forest along the China‐Vietnam border. Karst forest is unusual gibbon habitat. Currently, the canopy height of cao vit gibbon habitat is approximately 10 m. Research on the locomotor behavior of gibbons living in this particular forest type might provide important insight into locomotor stability and variability of gibbons. We used 5 min scan samples to record the locomotion mode, support use and canopy strata of gibbons in 3 groups for 2096 h between January 2008 and December 2009. Although cao vit gibbon habitat has a lower canopy in comparison to that of other forests inhabited by gibbons, cao vit gibbons displayed a similar overall locomotor pattern to other gibbon species (Symphalangus syndactylus, Hylobates lar and Hylobates agilis) in which brachiation dominate their locomotor behavior. Cao vit gibbons spent most of their time travelling on inclined branches (2–10 cm) in the middle stratum through the forest canopy. Adult females appear to more often employ safer modes of locomotion (bridging more often and brachiation less), while adult males choose riskier modes (leaping more and climbing less). As gibbons increased in body weight, as they grew from infant to adult, they tended to use larger supports. This research documented that locomotor behavior in Hylobatidae is strongly determined by anatomical characters, but cao vit gibbons also show the ability to use various supports, enabling them to survive in karst forest.
Melanoma epidemiology, prognosis and trends in Latvia
Authors: Azarjana K. , Ozola A. , Ruklisa D. , Cema I. , Rivosh A. , Azaryan A. , Pjanova D.
Published: October 2012

Background Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma.

Objectives The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence.

Methods We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma.

Results The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15‐2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22–1.81; P < 0.001).

Conclusions There is a steady increase in melanoma incidence in Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival.
Unique gene alterations are induced in FACS‐purified Fos‐positive neurons activated during cue‐induced relapse to heroin seeking
Authors: Fanous Sanya , Guez‐Barber Danielle H. , Goldart Evan M. , Schrama Regina , Theberge Florence R. M. , Shaham Yavin , Hope Bruce T.
Published: October 2012

Cue‐induced heroin seeking after prolonged withdrawal is associated with neuronal activation and altered gene expression in prefrontal cortex (PFC). However, these previous studies assessed gene expression in all neurons regardless of their activity state during heroin seeking. Using Fos as a marker of neural activity, we describe distinct molecular alterations induced in activated versus non‐activated neurons during cue‐induced heroin seeking after prolonged withdrawal. We trained rats to self‐administer heroin for 10 days (6 h/day) and assessed cue‐induced heroin seeking in extinction tests after 14 or 30 days. We used fluorescent‐activated cell sorting (FACS) to purify Fos‐positive and Fos‐negative neurons from PFC 90 min after extinction testing. Flow cytometry showed that Fos‐immunoreactivity was increased in less than 10% of sparsely distributed PFC neurons. mRNA levels of the immediate early genes fosB, arc, egr1, and egr2, as well as npy and map2k6, were increased in Fos‐positive, but not Fos‐negative, neurons. In support of these findings, double‐label immunohistochemistry indicated substantial coexpression of neuropeptide Y (NPY)‐ and Arc‐immunoreactivity in Fos‐positive neurons. Our data indicate that cue‐induced relapse to heroin seeking after prolonged withdrawal induces unique molecular alterations within activated PFC neurons that are distinct from those observed in the surrounding majority of non‐activated neurons.
Protease‐activated receptor‐1 modulates hippocampal memory formation and synaptic plasticity
Authors: Almonte Antoine G. , Qadri Laura H. , Sultan Faraz A. , Watson Jennifer A. , Mount Daniel J. , Rumbaugh Gavin , Sweatt J. David
Published: October 2012

Protease‐activated receptor‐1 (PAR1) is an unusual G‐protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. Although previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. Here, we used PAR1−/− mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1−/− mice have deficits in hippocampus‐dependent memory. We also show that while PAR1−/− mice have normal baseline synaptic transmission at Schaffer collateral‐CA1 synapses, they exhibit severe deficits in N‐methyl‐d‐aspartate receptor (NMDAR)‐dependent long‐term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR‐mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR‐dependent processes subserving memory formation and synaptic plasticity.
Conversion to enteric‐coated mycophenolate sodium from mycophenolate mofetil in stable renal transplant patients: Results of an Asia–Pacific study
Authors: Lee Po‐Huang , Vathsala Anantharaman , Han Duck Jong , Chan Tak‐Mao , Wong Hin‐Seng , Woodcock Chad , Kurstjens Nicol ,   Asia Pacific MyPROMS Study Investigators, Sivaraman Pary , Chu Sheng‐Hsien , Hsieh Hwei‐Ho , Hsu Kuo‐Hsiung , Lee Po‐Chang , Lian Jong‐Da , Yang Wu‐Chang , Morad Zaki , Tan Si‐Yen , Han Duck Jong , Park Ki Il , Siu Yui‐Pong , Tsang Wai Kay
Published: October 2012

This study enrolled 112 patients from 16 Asian centres in Asian countries demonstrating that enteric‐coated mycophenolate sodium is a safe and effective alternative to mycophenolate mofetil. The incidence of gastrointestinal upset was reduced.
Variance in Coronary Venous Anatomy: A Critical Determinant in Optimal Candidate Selection for Cardiac Resynchronization Therapy
Authors: RANDHAWA ARPANDEEP , SAINI ABHIMANYU , AGGARWAL ANJALI , ROHIT MANOJ K. , SAHNI DAISY
Published: October 2012

Background

Knowledge of coronary sinus (CS) anatomy and its variations is one of the important factors determining the final position of left ventricle pacing lead during cardiac resynchronization therapy.

Methods

Coronary venous system anatomy, including number, diameter, and opening angles of tributaries, was studied in 50 normal formalin‐fixed adult cadaveric hearts.

Results

Thebesian valve (TV) and Vieussens valve were present in 64% and 60% cases, respectively. CS ostium coverage of ≥75% by TV was seen in 25% (8/32) cases. Number of prominent tributaries lying between anterior interventricular vein and middle cardiac vein varied from 1–4. In 28% of hearts, only one prominent tributary was present. Midlateral vein (average diameter 1.75 ± 0.66 mm) with an average distance of 43.5 ± 12.2 mm from coronary ostium was present in 58% (29/50) hearts, of which it formed an acute angle with CS axis in four (13.39%) cases. Posterolateral vein (average diameter 1.62 ± 0.45 mm) with an average distance of 33.4 ± 11.7 mm from coronary ostium was found in 72% (36/50) cases and formed an acute angle with CS in three (8.33%) cases.

Conclusions

Restrictive TV covering ≥75% CS ostium (25% cases), presence of single prominent tributary (28% cases), and formation of acute angle of tributary with CS axis (1/4 cases with anterolateral vein, 4/29 cases with midlateral vein, 3/36 cases with posterolateral vein, and 3/28 cases with posterior veins of the left ventricle) can impede successful cannulation of CS.

(PACE 2013; 36:94–102)
Palaeoceanography of Lower Cretaceous Alpine platform carbonates
Authors: FÖllmi Karl B. , Godet Alexis
Published: October 2012

Shallow‐water carbonate platforms evolve in an interplay of local, regional and global dynamics, thereby generating a detailed record of environmental conditions. Platform sediments constitute important archives of past environmental change and, as such, they are increasingly analysed for the information they contain on wider‐scale patterns. The integration of this information with palaeoceanographic data obtained from deeper‐water sediments provides a powerful tool to develop a more diverse and complete image of past environmental change. In this contribution, the remains of the northern Tethyan carbonate platform of Early Cretaceous age cropping out in the western Swiss Jura and the Helvetic Alps are used to illustrate the advantage of a palaeoceanographic approach in their interpretation. The tools applied are biostratigraphy and chemostratigraphy (carbon and strontium isotopes) in order to obtain a precise age model for correlation with (hemi‐)pelagic sediments in adjacent basins, sequence stratigraphy as a means to reconstruct the impact of sea‐level change, phosphorus stratigraphy as a proxy for trophic levels, facies and microfacies analyses as a gateway to gain better insight into the carbonate factory, and the detailed analysis of platform‐drowning unconformities as an indicator of wider‐scale palaeoenvironmental change. It is shown that changes from periods of predominantly photozoan to predominantly heterozoan carbonate production near the Berriasian–Valanginian boundary and middle early Aptian coincided with substantial increases in phosphorus burial rates and major carbon‐isotope excursions. Furthermore, the majority of the platform‐drowning episodes occurred just prior to and during episodes of major palaeoenvironmental change and, last but not least, the platform itself may have influenced the chemistry of adjacent basins and the carbon‐isotope composition of associated carbonates by the export of periplatform ooze.
Association of phosphate with rhyolite glass in marine Neogene tuffs from Patagonia, Argentina
Authors: Rubinstein Nora , Fazio Ana M. , Scasso Roberto A. , Carey Steven
Published: October 2012

The precipitation/replacement of Ca‐phosphate is a complex process that commonly takes place during the early diagenesis in marine sediments. The unusual occurrence of shallow marine, early diagenetic phosphatic deposits associated with glassy tuffs in the Neogene Gaiman Formation, in the Chubut Province, Patagonia, Argentina, constitutes a good case example for the study of replacement and precipitation of Ca‐phosphate on an unstable substrate. Isocon diagrams illustrate that chemical changes during glass diagenesis include gains in loss on ignition and Ca, and losses of K. These changes are the result of glass hydration during sea water–glass interaction, together with adsorption and diffusion of ions into the bulk shard; combined, these represent an incipient process of volcanic glass replacement by Ca‐phosphate. Subsequent early diagenetic P enrichment in the pore solutions led to phosphate precipitation, associated with pitting on the glass shards and pumice. The associated development of a reactive surface promoted the incorporation of P and Ca into their margins. Lastly, precipitation of calcium phosphate filled the vesicles and other open cavities, inhibiting further glass dissolution. The high porosity and reactivity of the volcanic glass provided an appropriate substrate for phosphate precipitation, leading to the development of authigenic apatite concretions in the volcanic‐glass bearing strata of the Gaiman Formation. This research is of significance for those concerned with marine phosphatic deposits and sheds light on the processes of early diagenetic phosphate precipitation by replacement of an atypical, unstable substrate like hydrated volcanic glass.
The pollen tube: a soft shell with a hard core
Authors: Vogler Hannes , Draeger Christian , Weber Alain , Felekis Dimitris , Eichenberger Christof , Routier‐Kierzkowska Anne‐Lise , Boisson‐Dernier Aurélien , Ringli Christoph , Nelson Bradley J. , Smith Richard S. , Grossniklaus Ueli
Published: October 2012

Plant cell expansion is controlled by a fine‐tuned balance between intracellular turgor pressure, cell wall loosening and cell wall biosynthesis. To understand these processes, it is important to gain in‐depth knowledge of cell wall mechanics. Pollen tubes are tip‐growing cells that provide an ideal system to study mechanical properties at the single cell level. With the available approaches it was not easy to measure important mechanical parameters of pollen tubes, such as the elasticity of the cell wall. We used a cellular force microscope (CFM) to measure the apparent stiffness of lily pollen tubes. In combination with a mechanical model based on the finite element method (FEM), this allowed us to calculate turgor pressure and cell wall elasticity, which we found to be around 0.3 MPa and 20–90 MPa, respectively. Furthermore, and in contrast to previous reports, we showed that the difference in stiffness between the pollen tube tip and the shank can be explained solely by the geometry of the pollen tube. CFM, in combination with an FEM‐based model, provides a powerful method to evaluate important mechanical parameters of single, growing cells. Our findings indicate that the cell wall of growing pollen tubes has mechanical properties similar to rubber. This suggests that a fully turgid pollen tube is a relatively stiff, yet flexible cell that can react very quickly to obstacles or attractants by adjusting the direction of growth on its way through the female transmitting tissue.
Detailed Heat Transfer Distributions in Engine Similar Cooling Channels for a Turbine Rotor Blade With Different Rib Orientations
Authors: LeBlanc Christopher , Ekkad Srinath V. , Lambert Tony , Rajendran Veera
Published: October 2012

Detailed Nusselt number distributions are presented for a gas turbine engine similar internal channel geometry used for cooling a modern first stage rotor blade. The cooling design has one leading edge channel and a three-pass channel that covers the rest of the blade. The simulated model, generated from the midspan section of an actual cooling circuit, was studied for wall heat transfer coefficient measurements using the transient liquid crystal technique. The model wall inner surfaces were sprayed with thermochromic liquid crystals, and a transient test was used to obtain the local heat transfer coefficients from the measured color change. Results are presented for a nominal channel inlet leading edge channel Reynolds number of 10,700 and a channel inlet three-pass channel Reynolds number of 25,500. Detailed heat transfer measurements are presented for the simulated leading edge, first pass, second pass and third pass interior walls for different rib configurations. The channels were studied for smooth, 90 deg ribs, and angled ribs geometries in addition to ribs on the divider walls between adjacent passages. Overall pressure drop measurements were also obtained for each passage. Some of these results are compared with the predicted heat transfer from standard correlations used in design practices. Results show very complicated heat transfer behavior in these realistic channels compared to results obtained in simplistic geometry channels from published studies. In some cases, the Nusselt numbers predicted by correlations are 50–60% higher than obtained from the current experiments.
The Effects of Radially Distorted Incident Flow on Performance of Axial-Flow Fans With Forward-Skewed Blades
Authors: Yang B. , Gu Ch. G.
Published: October 2012

In this study, experiments and numerical simulations were carried out to evaluate the effects of radially distorted incident flow on the performance of axial-flow fans, which were equipped with three kinds of forward-skewed blades. Loss coefficient and velocity components at exit section as well as overall performance are discussed, both at the design point and the lower mass flow rate point. Furthermore, rotating stall was also observed by use of three dynamic pressure sensors. All results reveal that there are beneficial effects of forward-skewed blades on the fan performance, but the fan performance and its unsteady aerodynamic characteristics are quite affected by the radially distorted incident flow.
Akt-Mediated Regulation of Autophagy and Tumorigenesis Through Beclin 1 Phosphorylation
Authors: Wang Richard C. , Wei Yongjie , An Zhenyi , Zou Zhongju , Xiao Guanghua , Bhagat Govind , White Michael , Reichelt Julia , Levine Beth
Published: October 2012

Getting Autophagy to Akt

The protein kinase Akt is often activated in human cancers and is thought to promote tumor formation. One way in which it may do so is to inhibit autophagy (a process by which the cell digests its own proteins or organelles, especially damaged ones).

Wang
et al.

(p.
956
, published online 25 October; see the Perspective by

Koren and Kimchi

) provide a direct molecular mechanism by which Akt regulates autophagy. Beclin, a component of the autophagy machinery, appears to be a direct target of phosphorylation by Akt. Such phosphorylation enhanced interaction of Beclin with intermediate filaments of the cyto skeleton and inhibited autophagy. Expression of a modified Beclin 1 molecule that could not be phosphorylated by Akt inhibited Akt-induced transformation of cells in culture and tumor formation in a mouse model.
Binary Millisecond Pulsar Discovery via Gamma-Ray Pulsations
Authors: Pletsch H. J. , Guillemot L. , Fehrmann H. , Allen B. , Kramer M. , Aulbert C. , Ackermann M. , Ajello M. , de Angelis A. , Atwood W. B. , Baldini L. , Ballet J. , Barbiellini G. , Bastieri D. , Bechtol K. , Bellazzini R. , Borgland A. W. , Bottacini E. , Brandt T. J. , Bregeon J. , Brigida M. , Bruel P. , Buehler R. , Buson S. , Caliandro G. A. , Cameron R. A. , Caraveo P. A. , Casandjian J. M. , Cecchi C. , Çelik Ö. , Charles E. , Chaves R. C. G. , Cheung C. C. , Chiang J. , Ciprini S. , Claus R. , Cohen-Tanugi J. , Conrad J. , Cutini S. , D’Ammando F. , Dermer C. D. , Digel S. W. , Drell P. S. , Drlica-Wagner A. , Dubois R. , Dumora D. , Favuzzi C. , Ferrara E. C. , Franckowiak A. , Fukazawa Y. , Fusco P. , Gargano F. , Gehrels N. , Germani S. , Giglietto N. , Giordano F. , Giroletti M. , Godfrey G. , Grenier I. A. , Grondin M.-H. , Grove J. E. , Guiriec S. , Hadasch D. , Hanabata Y. , Harding A. K. , den Hartog P. R. , Hayashida M. , Hays E. , Hill A. B. , Hou X. , Hughes R. E. , Jóhannesson G. , Jackson M. S. , Jogler T. , Johnson A. S. , Johnson W. N. , Kataoka J. , Kerr M. , Knödlseder J. , Kuss M. , Lande J. , Larsson S. , Latronico L. , Lemoine-Goumard M. , Longo F. , Loparco F. , Lovellette M. N. , Lubrano P. , Massaro F. , Mayer M. , Mazziotta M. N. , McEnery J. E. , Mehault J. , Michelson P. F. , Mitthumsiri W. , Mizuno T. , Monzani M. E. , Morselli A. , Moskalenko I. V. , Murgia S. , Nakamori T. , Nemmen R. , Nuss E. , Ohno M. , Ohsugi T. , Omodei N. , Orienti M. , Orlando E. , de Palma F. , Paneque D. , Perkins J. S. , Piron F. , Pivato G. , Porter T. A. , Rainò S. , Rando R. , Ray P. S. , Razzano M. , Reimer A. , Reimer O. , Reposeur T. , Ritz S. , Romani R. W. , Romoli C. , Sanchez D. A. , Parkinson P. M. Saz , Schulz A. , Sgrò C. , do Couto e Silva E. , Siskind E. J. , Smith D. A. , Spandre G. , Spinelli P. , Suson D. J. , Takahashi H. , Tanaka T. , Thayer J. B. , Thayer J. G. , Thompson D. J. , Tibaldo L. , Tinivella M. , Troja E. , Usher T. L. , Vandenbroucke J. , Vasileiou V. , Vianello G. , Vitale V. , Waite A. P. , Winer B. L. , Wood K. S. , Wood M. , Yang Z. , Zimmer S.
Published: October 2012

Exotic Pulsations

The launch of the Fermi Gamma-ray Space Telescope in 2008 enabled the detection of large numbers of pulsars. Millisecond pulsars, neutron stars with millisecond periods, are much more difficult to find in gamma-ray data. In a computational tour de force,

Pletsch
et al.

(p.
1314
, published online 25 October) detected gamma-ray pulsations from a formerly unidentified gamma-ray source in the Fermi Large Area Telescope Second Source Catalog. The pulsating neutron star orbits a companion star more rapidly than any other such neutron star known, and the system may belong to an exotic class of binary systems where the neutron star is systematically destroying its companion.
Food-Grade Bacteria Expressing Elafin Protect Against Inflammation and Restore Colon Homeostasis
Authors: Motta Jean-Paul , Bermúdez-Humarán Luis G. , Deraison Céline , Martin Laurence , Rolland Corinne , Rousset Perrine , Boue Jérôme , Dietrich Gilles , Chapman Kevin , Kharrat Pascale , Vinel Jean-Pierre , Alric Laurent , Mas Emmanuel , Sallenave Jean-Michel , Langella Philippe , Vergnolle Nathalie
Published: October 2012

Lactic acid–producing bacteria engineered to produce the antiprotease Elafin restore colon homeostasis in mice with colitis and protect human tissue from inflammation.
A Window into Metastasis
Authors: Brucker David , Herms Jochen
Published: October 2012

A glass window constructed by Ritsma, Steller
et al.
(this issue) allows chronic, high-resolution imaging of metastasis in the mouse abdomen.
"Honey, Have You Taken Your Polyphenols Today?"
Authors: Skarke Carsten
Published: October 2012

Resveratrol, a nutritional polyphenol commonly found in grape skins, berries, and nuts, might have therapeutic value in stroke management.
Science Translational Medicine
Podcast: 31 October 2012
Authors: Onaral Banu , LaMarco Kelly
Published: October 2012

A conversation with Banu Onaral about innovation partnerships between emerging and developed economies.
Identification of the Enzyme Responsible forN-Acetylation of Norfloxacin by Microbacterium sp. Strain 4N2-2
Authors: Kim Dae-Wi , Feng Jinhui , Chen Huizhong , Kweon Ohgew , Gao Yuan , Yu Li-Rong , Burrowes Vanessa J. , Sutherland John B.
Published: October 2012

Microbacteriumsp. 4N2-2, isolated from a wastewater treatment plant, converts the antibacterial fluoroquinolone norfloxacin toN-acetylnorfloxacin and three other metabolites. BecauseN-acetylation results in loss of antibacterial activity, identification of the enzyme responsible is important for understanding fluoroquinolone resistance. The enzyme was identified as glutamine synthetase (GS);N-acetylnorfloxacin was produced only under conditions associated with GS expression. The GS gene (glnA) was cloned, and the protein (53 kDa) was heterologously expressed and isolated. Optimal conditions and biochemical properties (KmandVmax) of purified GS were characterized; the purified enzyme was inhibited by Mn2+, Mg2+, ATP, and ADP. The contribution of GS to norfloxacin resistance was shown by using a norfloxacin-sensitiveEscherichia colistrain carryingglnAderived fromMicrobacteriumsp. 4N2-2. The GS ofMicrobacteriumsp. 4N2-2 was shown to act as anN-acetyltransferase for norfloxacin, which produced low-level norfloxacin resistance. Structural and docking analysis identified potential binding sites for norfloxacin at the ADP binding site and for acetyl coenzyme A (acetyl-CoA) at a cleft in GS. The results suggest that environmental bacteria whose enzymes modify fluoroquinolones may be able to survive in the presence of low fluoroquinolone concentrations.
n
-Alkane Chain Length Alters Dietzia sp. Strain DQ12-45-1b Biosurfactant Production and Cell Surface Activity
Authors: Wang Xing-Biao , Nie Yong , Tang Yue-Qin , Wu Gang , Wu Xiao-Lei
Published: October 2012

Upon growth on
n
-hexadecane (C
16
),
n
-tetracosane (C
24
), and
n
-hexatriacontane (C
36
),
Dietzia
sp. strain DQ12-45-1b could produce different glycolipids, phospholipids, and lipopeptides. Interestingly, cultivation with C
36
increased cell surface hydrophobic activity, which attenuated the negative effect of the decline of the emulsification activity. These results suggest that the mechanisms of biosurfactant production and cell surface hydrophobicity are dependent upon the chain lengths of the
n
-alkanes used as carbon sources.
Bacterial Chitinolytic Communities Respond to Chitin and pH Alteration in Soil
Authors: Kielak Anna M. , Cretoiu Mariana Silvia , Semenov Alexander V. , Sørensen Søren J. , van Elsas Jan Dirk
Published: October 2012

Chitin amendment is a promising soil management strategy that may enhance the suppressiveness of soil toward plant pathogens. However, we understand very little of the effects of added chitin, including the putative successions that take place in the degradative process. We performed an experiment in moderately acid soil in which the level of chitin, next to the pH, was altered. Examination of chitinase activities revealed fast responses to the added crude chitin, with peaks of enzymatic activity occurring on day 7. PCR-denaturing gradient gel electrophoresis (DGGE)-based analyses of 16S rRNA and
chiA
genes showed structural changes of the phylogenetically and functionally based bacterial communities following chitin addition and pH alteration. Pyrosequencing analysis indicated (i) that the diversity of
chiA
gene types in soil is enormous and (i) that different
chiA
gene types are selected by the addition of chitin at different prevailing soil pH values. Interestingly, a major role of Gram-negative bacteria versus a minor one of
Actinobacteria
in the immediate response to the added chitin (based on 16S rRNA gene abundance and
chiA
gene types) was indicated. The results of this study enhance our understanding of the response of the soil bacterial communities to chitin and are of use for both the understanding of soil suppressiveness and the possible mining of soil for novel enzymes.
Fluorometric Quantification of Polyphosphate in Environmental Plankton Samples: Extraction Protocols, Matrix Effects, and Nucleic Acid Interference
Authors: Martin Patrick , Van Mooy Benjamin A. S.
Published: October 2012

Polyphosphate (polyP) is a ubiquitous biochemical with many cellular functions and comprises an important environmental phosphorus pool. However, methodological challenges have hampered routine quantification of polyP in environmental samples. We tested 15 protocols to extract inorganic polyphosphate from natural marine samples and cultured cyanobacteria for fluorometric quantification with 4′,6-diamidino-2-phenylindole (DAPI) without prior purification. A combination of brief boiling and digestion with proteinase K was superior to all other protocols, including other enzymatic digestions and neutral or alkaline leaches. However, three successive extractions were required to extract all polyP. Standard addition revealed matrix effects that differed between sample types, causing polyP to be over- or underestimated by up to 50% in the samples tested here. Although previous studies judged that the presence of DNA would not complicate fluorometric quantification of polyP with DAPI, we show that RNA can cause significant interference at the wavelengths used to measure polyP. Importantly, treating samples with DNase and RNase before proteinase K digestion reduced fluorescence by up to 57%. We measured particulate polyP along a North Pacific coastal-to-open ocean transect and show that particulate polyP concentrations increased toward the open ocean. While our final method is optimized for marine particulate matter, different environmental sample types may need to be assessed for matrix effects, extraction efficiency, and nucleic acid interference.
Carboxyethylarginine Synthase Genes Show Complex Cross-Regulation in Streptomyces clavuligerus
Authors: Kwong Thomas , Tahlan Kapil , Anders Cecilia L. , Jensen Susan E.
Published: October 2012

Carboxyethylarginine synthase is the first dedicated enzyme of clavam biosynthesis in
Streptomyces clavuligerus
and is present in two isoforms encoded by two separate genes. When grown on a liquid soy medium, strains with
ceaS1
deleted showed only a mild reduction of clavam biosynthesis, while disruption of
ceaS2
abolished all clavam biosynthesis. Creation of an in-frame
ceaS2
deletion mutant to avoid polarity did not restore clavam production, nor did creation of a site-directed mutant altered only in a single amino acid residue important for activity. Reverse transcriptase PCR analyses of these mutants indicated that the failure to produce clavam metabolites could be traced to reduced or abolished transcription of
ceaS1
in the
ceaS2
mutants, despite the location of
ceaS1
on a replicon completely separate from that of
ceaS2
. Western analyses further showed that the CeaS1 protein (as well as the CeaS2 protein) was absent from the
ceaS2
mutants. Complementation experiments were able to restore clavam production partially, but only by virtue of restoring CeaS2 production. CeaS1 was still absent from the complemented strains. While this dependence of CeaS1 production on the expression of
ceaS2
from its native chromosomal location was seen in all of the
ceaS2
mutants, the effect was limited to growth in liquid medium. When the same mutants were grown on solid soy medium, clavam production was restored and CeaS1 was produced, albeit at low levels compared to the wild type.
Invertase SUC2 Is the Key Hydrolase for Inulin Degradation in Saccharomyces cerevisiae
Authors: Wang Shi-An , Li Fu-Li
Published: October 2012

Specific
Saccharomyces cerevisiae
strains were recently found to be capable of efficiently utilizing inulin, but genetic mechanisms of inulin hydrolysis in yeast remain unknown. Here we report functional characteristics of invertase SUC2 from strain JZ1C and demonstrate that SUC2 is the key enzyme responsible for inulin metabolism in
S. cerevisiae
.