bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Role of Lanthanides in Enzymatic Activity and Transcriptional Regulation of Pyrroloquinoline Quinone-Dependent Alcohol Dehydrogenases in
Pseudomonas putida
KT2440
Authors: Wehrmann Matthias , Billard Patrick , Martin-Meriadec Audrey , Zegeye Asfaw , Klebensberger Janosch 
Published: June 2017

ABSTRACT

The oxidation of alcohols and aldehydes is crucial for detoxification and efficient catabolism of various volatile organic compounds (VOCs). Thus, many Gram-negative bacteria have evolved periplasmic oxidation systems based on pyrroloquinoline quinone-dependent alcohol dehydrogenases (PQQ-ADHs) that are often functionally redundant. Here we report the first description and characterization of a lanthanide-dependent PQQ-ADH (PedH) in a nonmethylotrophic bacterium based on the use of purified enzymes from the soil-dwelling model organism
Pseudomonas putida
KT2440. PedH (PP_2679) exhibits enzyme activity on a range of substrates similar to that of its Ca
2+
-dependent counterpart PedE (PP_2674), including linear and aromatic primary and secondary alcohols, as well as aldehydes, but only in the presence of lanthanide ions, including La
3+
, Ce
3+
, Pr
3+
, Sm
3+
, or Nd
3+
. Reporter assays revealed that PedH not only has a catalytic function but is also involved in the transcriptional regulation of
pedE
and
pedH
, most likely acting as a sensory module. Notably, the underlying regulatory network is responsive to as little as 1 to 10 nM lanthanum, a concentration assumed to be of ecological relevance. The present study further demonstrates that the PQQ-dependent oxidation system is crucial for efficient growth with a variety of volatile alcohols. From these results, we conclude that functional redundancy and inverse regulation of PedE and PedH represent an adaptive strategy of
P. putida
KT2440 to optimize growth with volatile alcohols in response to the availability of different lanthanides.

IMPORTANCE
Because of their low bioavailability, lanthanides have long been considered biologically inert. In recent years, however, the identification of lanthanides as a cofactor in methylotrophic bacteria has attracted tremendous interest among various biological fields. The present study reveals that one of the two PQQ-ADHs produced by the model organism
P. putida
KT2440 also utilizes lanthanides as a cofactor, thus expanding the scope of lanthanide-employing bacteria beyond the methylotrophs. Similar to the system described in methylotrophic bacteria, a complex regulatory network is involved in lanthanide-responsive switching between the two PQQ-ADHs encoded by
P. putida
KT2440. We further show that the functional production of at least one of the enzymes is crucial for efficient growth with several volatile alcohols. Overall, our study provides a novel understanding of the redundancy of PQQ-ADHs observed in many organisms and further highlights the importance of lanthanides for bacterial metabolism, particularly in soil environments.
e-Biologics: Fabrication of Sustainable Electronics with “Green” Biological Materials
Authors: Lovley Derek R. 
Published: June 2017

ABSTRACT
The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial components as the guide for synthesis, are a potential green solution. Some e-biologics can be fabricated from renewable feedstocks with relatively low energy inputs, often while avoiding the harsh chemicals used for synthesizing more traditional electronic materials. Several are completely free of toxic components, can be readily recycled, and offer unique features not found in traditional electronic materials in terms of size, performance, and opportunities for diverse functionalization. An appropriate investment in the concerted multidisciplinary collaborative research required to identify and characterize e-biologics and to engineer materials and devices based on e-biologics could be rewarded with a new “green age” of sustainable electronic materials and devices.
Landing-related ankle injuries do not occur in plantarflexion as once thought: a systematic video analysis of ankle injuries in world-class volleyball
Authors: Skazalski Christopher , Kruczynski Jacek , Bahr Martin Aase , Bere Tone , Whiteley Rod , Bahr Roald 
Published: June 2017

BackgroundAnkle injuries are prevalent in elite volleyball and suggested to result from player contact at the net. Traditionally, ankle sprains are thought to happen in a plantarflexed position, but case studies suggest plantarflexion may not be involved.AimDescribe the injury situations and mechanisms of ankle injuries in world-class volleyball based on systematic video analysis of injuries reported through the Fédération Internationale de Volleyball (FIVB) Injury Surveillance System.MethodsVideos of 24 injuries from major FIVB tournaments were included for analysis (14 men, 10 women). Five analysts reviewed the videos to determine specific situations and mechanisms leading to injuries.ResultsThe majority of injuries occurred during two volleyball situations, blocking (n=15) and attacking (n=6). Injuries to blockers were the result of landing on an opponent (n=11) or teammate (n=4). Attacking injuries most frequently occurred when a back-row player landed on a front-row teammate (n=4 of 6). When landing on an opponent under the net, the attacker landed into the opponent’s court in 11 of 12 situations but without violating the centre line rule. Injuries mostly resulted from rapid inversion without any substantial plantarflexion.ConclusionsThe majority of injuries occur while blocking, often landing on an opponent. The attacker is overwhelmingly to blame for injuries at the net secondary to crossing the centre line. Injuries while attacking often result from a back-row player landing on a front-row teammate. Landing-related injuries mostly result from rapid inversion with the absence of plantarflexion.
Improving door to CT scanner times for potential stroke thrombolysis candidates – The Emergency Department's role
Authors: Barbour Victoria , Thakore Shobhan 
Published: June 2017

Stroke thrombolysis is an important treatment in the management of acute strokes. Its' effectiveness is reliant on prompt administration after stroke onset. Disability free survival at 3-6 months increases by 10% when administered within 3 hours. There is also an economic benefit from early administration with reduced institutional care. New Scottish care standards have been introduced which suggest a target that 50% of suitable patients should receive thrombolysis within 30 minutes, and 80% within one hour 6.Processes in the Emergency Department play a key role in determining the time a patient waits between arrival and reaching the CT scanner. The project team looked at Ninewells Emergency Department times to CT scanner between May and August 2015 and found that only 20% of patients had their scan within 20 minutes, and 70% within 45 minutes. The team went on to conduct a quality improvement project. This involved initial patient mapping and short interviews with staff. A multi action approach was developed involving education in the form of emails, presentations and visual charts, and the final step was to simplify the paperwork involved. The project was conducted over 11 months and successfully reduced the times to CT, with 60% having had their CT scan within 20 minutes, and 100% within 45 minutes, with a very noticeable reduction in variation around the mean. It is hoped to take this approach forward and apply it to other processes in the department.
Error analysis for pesticide detection performed on paper-based microfluidic chip devices
Authors: Yang Ning , Shen Kai , Guo Jianjiang , Tao Xinyi , Xu Peifeng , Mao Hanping 
Published: June 2017

Paper chip is an efficient and inexpensive device for pesticide residues detection. However, the reasons of detection error are not clear, which is the main problem to hinder the development of pesticide residues detection. This paper focuses on error analysis for pesticide detection performed on paper-based microfluidic chip devices, which test every possible factor to build the mathematical models for detection error. In the result, double-channel structure is selected as the optimal chip structure to reduce detection error effectively. The wavelength of 599.753 nm is chosen since it is the most sensitive detection wavelength to the variation of pesticide concentration. At last, the mathematical models of detection error for detection temperature and prepared time are concluded. This research lays a theory foundation on accurate pesticide residues detection based on paper-based microfluidic chip devices.
An experimental study of dolomite dissolution kinetics at conditions relevant to CO
2
geological storage
Authors: Baritantonaki Angeliki , Bolourinejad Panteha , Herber Rien 
Published: June 2017

The kinetics of dolomite dissolution have been experimentally investigated under subsurface conditions characteristic of the Rotliegend gas fields in the NE of The Netherlands. Experiments were performed in closed, stirred, batch reactors at far from equilibrium conditions, with dolomite powders of different grain sizes. The experiments were repeated for all grain sizes at 25°C and an experiment was also conducted in deionized water. The rates were derived from the measured concentrations of Mg
2+
or Ca
2+
released from dolomite dissolution and were normalized by the surface area of the minerals at each time interval.

Regression of the rates with the pH resulted in the kinetic rate constants of: log
k
1
= −8.16 ± 0.06 at 25°C and log
k
2
= −7.61 ± 0.05 at 100°C (300 – 350 μm), log
k
3
= −7.88 ± 0.20 at 25°C, log
k
4
= −7.45 at 100°C (75 – 100 μm), log
k
5
= −6.62 ± 0.50 at 25°C and log
k
6
= −5.96 ± 1 at 100°C (20 – 25 μm).

The results obtained in this study indicate that in an acidic regime the dissolution of dolomite in brine is a factor of 2 faster than in deionized water. It was also shown that the dissolution rates, when normalized by surface area, increase with decreasing grain size.
Impaired visuomotor generalization by inconsistent attentional contexts
Authors: Wang Tony S. L. , Song Joo-Hyun 
Published: June 2017

In daily life, people are constantly presented with situations in which they have to learn and acquire new motor skills in complex environments, where attention is often distracted by other events. Being able to generalize and perform the acquired motor action in different environments is a crucial part of visuomotor learning. The current study examined whether attentional distraction impairs generalization of visuomotor adaptation or whether consistent distraction can operate as an internal cue to facilitate generalization. Using a dual-task paradigm combining visuomotor rotational adaptation and an attention-demanding secondary task, we showed that switching the attentional context from training (dual-task) to generalization (single-task) reduced the range of transfer of visuomotor adaptation to untrained directions. However, when consistent distraction was present throughout training and generalization, visuomotor generalization was equivalent to without distractions at all. Furthermore, this attentional context-dependent generalization was evident even when sensory modality of distractions differed between training and generalization. Therefore, the general nature of the dual tasks, rather than the specific stimuli, is associated with visuomotor memory and serves as a critical cue for generalization. Taken together, we demonstrated that attention plays a critical role during sensorimotor adaptation in selecting and associating multisensory signals with motor memory. This finding provides insight into developing learning programs that are generalizable in complex daily environments. NEW & NOTEWORTHY Learning novel motor actions in complex environments with attentional distraction is a critical function. Successful motor learning involves the ability to transfer the acquired skill from the trained to novel environments. Here, we demonstrate attentional distraction does not impair visuomotor adaptation. Rather, consistency in the attentional context from training to generalization modulates the degree of transfer to untrained locations. The role of attention and memory must, therefore, be incorporated into existing models of visuomotor learning.
Impact of glutamatergic and serotonergic neurotransmission on diaphragm muscle activity after cervical spinal hemisection
Authors: Mantilla Carlos B. , Gransee Heather M. , Zhan Wen-Zhi , Sieck Gary C. 
Published: June 2017

Incomplete cervical spinal cord hemisection at C2 (SH) disrupts descending excitatory drive to phrenic motoneurons, paralyzing the ipsilateral diaphragm muscle. Spontaneous recovery over time is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-d-aspartate (NMDA) and serotonergic 5-HT2A receptors. We hypothesized that NMDA and 5-HT2A receptor-mediated neurotransmission play a role in ipsilateral diaphragm muscle activity post-SH. Adult male Sprague-Dawley rats were implanted with bilateral diaphragm EMG electrodes for chronic EMG recordings up to 28 days post-SH (SH 28D). The extent of recovery was calculated by peak root-mean-square (RMS) EMG amplitude. In all animals, absence of ipsilateral activity was verified at 3 days post-SH. Diaphragm EMG activity was also recorded during exposure to hypoxia-hypercapnia (10% O2-5% CO2). In SH animals displaying recovery of ipsilateral diaphragm EMG activity at SH 28D, cervical spinal cord segments containing the phrenic motor nucleus (C3–C5) were surgically exposed and either the NMDA receptor antagonist d-2-amino-5-phosphonovalerate (d-AP5; 100 mM, 30 μl) or 5-HT2A receptor antagonist ketanserin (40 mM, 30 μl) was instilled intrathecally. Following d-AP5, diaphragm EMG amplitude was reduced ipsilaterally, during both eupnea (42% of pre-d-AP5 value; P = 0.007) and hypoxia-hypercapnia (31% of pre-d-AP5 value; P = 0.015), with no effect on contralateral EMG activity or in uninjured controls. Treatment with ketanserin did not change ipsilateral or contralateral RMS EMG amplitude in SH animals displaying recovery at SH 28D. Our results suggest that spinal glutamatergic NMDA receptor-mediated neurotransmission plays an important role in ipsilateral diaphragm muscle activity after cervical spinal cord injury. NEW & NOTEWORTHY Spontaneous recovery following C2 spinal hemisection (SH) is associated with increased phrenic motoneuron expression of glutamatergic and serotonergic receptors. In this study, we show that pharmacological inhibition of glutamatergic N-methyl-d-aspartate (NMDA) receptors blunts ipsilateral diaphragm activity post-SH. In contrast, pharmacological inhibition of serotonergic 5-HT2A receptors does not change diaphragm EMG activity post-SH. Our results suggest that NMDA receptor-mediated glutamatergic neurotransmission plays an important role in enhancing rhythmic respiratory-related diaphragm activity after spinal cord injury.
Pharmacokinetics and Pharmacodynamics-Based Mathematical Modeling Identifies an Optimal Protocol for Metronomic Chemotherapy
Authors: Ciccolini Joseph , Barbolosi Dominique , Meille Christophe , Lombard Aurélie , Serdjebi Cindy , Giacometti Sarah , Padovani Laetitia , Pasquier Eddy , André Nicolas 
Published: June 2017

Abstract
Metronomic chemotherapy is usually associated with better tolerance than conventional chemotherapy, and encouraging response rates have been reported in various settings. However, clinical development of metronomic chemotherapy has been hampered by a number of limitations, including the vagueness of its definition and the resulting empiricism in protocol design. In this study, we developed a pharmacokinetic/pharmacodynamic mathematical model that identifies in silico the most effective administration schedule for gemcitabine monotherapy. This model is based upon four biological assumptions regarding the mechanisms of action of metronomic chemotherapy, resulting in a set of 6 minimally parameterized differential equations. Simulations identified daily 0.5–1 mg/kg gemcitabine as an optimal protocol to maximize antitumor efficacy. Both metronomic protocols (0.5 and 1 mg/kg/day for 28 days) were evaluated in chemoresistant neuroblastoma-bearing mice and compared with the standard MTD protocol (100 mg/kg once a week for 4 weeks). Systemic exposure to gemcitabine was 14 times lower in the metronomic groups compared with the standard group. Despite this, metronomic gemcitabine significantly inhibited tumor angiogenesis and reduced tumor perfusion and inflammation in vivo, while standard gemcitabine did not. Furthermore, metronomic gemcitabine yielded a 40%–50% decrease in tumor mass at the end of treatment as compared with control mice (P = 0.002; ANOVA on ranks with Dunn test), while standard gemcitabine failed to significantly reduce tumor growth. Stable disease was maintained in the metronomic groups for up to 2 months after treatment completion (67%–72% reduction in tumor growth at study conclusion, P &lt; 0.001; ANOVA on ranks with Dunn test). Collectively, our results confirmed the superiority of metronomic protocols in chemoresistant tumors in vivo. Cancer Res; 77(17); 4723–33. ©2017 AACR.
A Small-Molecule Inhibitor of WEE1, AZD1775, Synergizes with Olaparib by Impairing Homologous Recombination and Enhancing DNA Damage and Apoptosis in Acute Leukemia
Authors: Garcia Tamara B. , Snedeker Jonathan C. , Baturin Dmitry , Gardner Lori , Fosmire Susan P. , Zhou Chengjing , Jordan Craig T. , Venkataraman Sujatha , Vibhakar Rajeev , Porter Christopher C. 
Published: June 2017

Abstract
Although some patients with acute leukemia have good prognoses, the prognosis of adult and pediatric patients who relapse or cannot tolerate standard chemotherapy is poor. Inhibition of WEE1 with AZD1775 has been shown to sensitize cancer cells to genotoxic chemotherapies, including cytarabine in acute myeloid leukemia (AML) and T-ALL. Inhibition of WEE1 impairs homologous recombination by indirectly inhibiting BRCA2. Thus, we sought to determine whether AZD1775 could sensitize cells to the PARP1/2 inhibitor olaparib. We found that combined treatment with AZD1775 and olaparib was synergistic in AML and ALL cells, and this combination impaired proliferative capacity upon drug withdrawal. AZD1775 impaired homologous recombination in olaparib-treated cells, resulting in enhanced DNA damage accumulation and apoptosis induction. This combination enhanced disease control and increased survival in a murine AML model. Furthermore, we demonstrated that combined treatment with AZD1775 and olaparib reduces proliferation and colony formation and increases apoptosis in AML patient samples. In aggregate, these studies raise the possibility of rational combinations of targeted agents for leukemia in patients for whom conventional chemotherapeutics may not be effective or well tolerated. Mol Cancer Ther; 16(10); 2058–68. ©2017 AACR.
Inhibition of Androgen Receptor Nuclear Localization and Castration-Resistant Prostate Tumor Growth by Pyrroloimidazole-based Small Molecules
Authors: Masoodi Khalid Z. , Xu Yadong , Dar Javid A. , Eisermann Kurtis , Pascal Laura E. , Parrinello Erica , Ai Junkui , Johnston Paul A. , Nelson Joel B. , Wipf Peter , Wang Zhou 
Published: June 2017

AbstractThe androgen receptor (AR) is a ligand-dependent transcription factor that controls the expression of androgen-responsive genes. A key step in androgen action, which is amplified in castration-resistant prostate cancer (CRPC), is AR nuclear translocation. Small molecules capable of inhibiting AR nuclear localization could be developed as novel therapeutics for CRPC. We developed a high-throughput screen and identified two structurally-related pyrroloimidazoles that could block AR nuclear localization in CRPC cells. We show that these two small molecules, 3-(4-ethoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (EPPI) and 3-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (CPPI) can inhibit the nuclear localization and transcriptional activity of AR and reduce the proliferation of AR-positive but not AR-negative prostate cancer cell lines. EPPI and CPPI did not inhibit nuclear localization of the glucocorticoid receptor or the estrogen receptor, suggesting they selectively target AR. In LNCaP tumor xenografts, CPPI inhibited the proliferation of relapsed LNCaP tumors. These findings suggest that EPPI and CPPI could serve as lead structures for the development of therapeutic agents for CRPC. Mol Cancer Ther; 16(10); 2120–9. ©2017 AACR.
ADA-07 Suppresses Solar Ultraviolet–Induced Skin Carcinogenesis by Directly Inhibiting TOPK
Authors: Gao Ge , Zhang Tianshun , Wang Qiushi , Reddy Kanamata , Chen Hanyong , Yao Ke , Wang Keke , Roh Eunmiri , Zykova Tatyana , Ma Weiya , Ryu Joohyun , Curiel-Lewandrowski Clara , Alberts David , Dickinson Sally E. , Bode Ann M. , Xing Ying , Dong Zigang 
Published: June 2017

Abstract
Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell–originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843–54. ©2017 AACR.