bluuebunny/crossref_metadata_2025_split huggingface dataset:
A sucrose non‐fermenting‐1‐related protein kinase‐1 gene, IbSnRK1, improves starch content, composition, granule size, degree of crystallinity and gelatinization in transgenic sweet potato
Authors: Ren Zhitong , He Shaozhen , Zhao Ning , Zhai Hong , Liu Qingchang 
Published: May 2018

SummarySucrose non‐fermenting‐1‐related protein kinase‐1 (SnRK1) is an essential energy‐sensing regulator and plays a key role in the global control of carbohydrate metabolism. The SnRK1 gene has been found to increase starch accumulation in several plant species. However, its roles in improving starch quality have not been reported to date. In this study, we found that the IbSnRK1 gene was highly expressed in the storage roots of sweet potato and strongly induced by exogenous sucrose. Its expression followed the circandian rhythm. Its overexpression not only increased starch content, but also decreased proportion of amylose, enlarged granule size and improved degree of crystallinity and gelatinization in transgenic sweet potato, which revealed, for the first time, the important roles of SnRK1 in improving starch quality of plants. The genes involved in starch biosynthesis pathway were systematically up‐regulated, and the content of ADP‐glucose as an important precursor for starch biosynthesis and the activities of key enzymes were significantly increased in transgenic sweet potato. These findings indicate that IbSnRK1 improves starch content and quality through systematical up‐regulation of the genes and the increase in key enzyme activities involved in starch biosynthesis pathway in transgenic sweet potato. This gene has the potential to improve starch content and quality in sweet potato and other plants.
Current and potential therapeutic strategies for the management of vascular calcification in patients with chronic kidney disease including those on dialysis
Authors: Ruderman Irene , Holt Stephen G. , Hewitson Tim D. , Smith Edward R. , Toussaint Nigel D. 
Published: May 2018

AbstractPatients with CKD have accelerated vascular stiffening contributing significantly to excess cardiovascular morbidity and mortality. Much of the arterial stiffening is thought to involve vascular calcification (VC), but the pathogenesis of this phenomenon is complex, resulting from a disruption of the balance between promoters and inhibitors of calcification in a uremic milieu, along with derangements in calcium and phosphate metabolic pathways. Management of traditional cardiovascular risk factors to reduce VC may be influential but has not been shown to significantly improve mortality. Control of mineral metabolism may potentially reduce the burden of VC, although using conventional approaches of restricting dietary phosphate, administering phosphate binders, and use of active vitamin D and calcimimetics, remains controversial because recommended biochemical targets are hard to achieve and clinical relevance hard to define. Increasing time on dialysis is perhaps another therapy with potential effectiveness in this area. Despite current treatments, cardiovascular morbidity and mortality remain high in this group. Novel therapies for addressing VC include magnesium and vitamin K supplementation, which are currently being investigated in large randomized control trials. Other therapeutic targets include crystallization inhibitors, ligand trap for activin receptors and BMP‐7. This review summarizes current treatment strategies and therapeutic targets for the future management of VC in patients with CKD.
Metabolomics 20 years on: what have we learned and what hurdles remain?
Authors: Alseekh Saleh , Fernie Alisdair R. 
Published: May 2018

SummaryThe term metabolome was coined in 1998, by analogy to genome, transcriptome and proteome. The first research papers using the terms metabolomics, metabonomics, metabolic profiling or metabolite profiling were published shortly thereafter. In this short review we reflect on the major achievements brought about by the use of these approaches, and document the knowledge and technology gaps that are currently constraining its further development. Finally, we detail why we think that the time is ripe to refocus our efforts on the understanding of metabolic function.
Transfusions of least‐incompatible blood with intravenous immunoglobulin plus steroids cover in two patients with rare antibody
Authors: Win Nay , Needs Malcolm , Thornton Nicole , Webster Robert , Chang Cherry 
Published: May 2018

BACKGROUNDThe therapeutic value of the use of intravenous immunoglobulin (IVIG) to correct anemia and thrombocytopenia as a result of immunologic causes (hemolytic disease of the fetus and newborn and fetal or neonatal alloimmune thrombocytopenia) have been well established. Few published papers exist regarding the use of IVIG in adult settings. We report two patients with clinically significant antibodies against high‐incidence antigens, who were successfully transfused with incompatible red blood cells (RBCs), in conjunction with IVIG plus steroids and IVIG.CASE REPORTSCase 1 was a 25‐year‐old patient (Hb SC) who was admitted with low hemoglobin (Hb) and low reticulocyte count. A diagnosis of parvovirus‐induced RBC hypoplasia was made. The patient's sample contained anti‐E, anti‐N, and anti‐U. The Hb decreased to 37 g/dL and urgent transfusion was provided with E–, N–, “least‐incompatible” RBC units covered by IVIG and hydrocortisone. Case 2 was a 54‐year‐old patient who was admitted after a road traffic accident. Nonspecific weak antibody was detected. She received 6 units of least‐incompatible RBCs. She was transferred to another hospital and received 2 least‐incompatible units. Hb level decreased further and an additional unit was transfused. Samples were referred to the reference laboratory and strong anti‐Jra detected. As there was clinical and laboratory evidence of hemolysis and Jr(a–) units were not available, IVIG was prescribed and least‐incompatible units were transfused.RESULTSThere were no hemolytic transfusion reactions, hemolysis ceased, and anemia improved in both cases.CONCLUSIONProphylaxis with IVIG plus steroids and IVIG should be considered as a therapeutic option when transfusion of incompatible units is necessary.
Computed tomographic description of the highly variable imaging features of equine oromaxillary sinus and oronasal fistulae
Authors: Hargreaves Laura , Dixon Jonathon J 
Published: May 2018

AbstractOronasal and oromaxillary sinus fistulae are well‐documented complications following removal or loss of a maxillary cheek tooth. Diagnosis is currently based on a combination of oral examination, videoendoscopy, radiography, and computed tomography (CT). The objective of this retrospective, case series study was to describe the CT characteristics of confirmed oronasal and oromaxillary sinus fistulae in a group of horses. Inclusion criteria were a head CT acquired at the authors’ hospital during the period of 2012–2017, a CT diagnosis of oronasal or oromaxillary sinus fistulae, and a confirmed diagnosis based on a method other than CT. Signalment, clinical findings, oral examination findings, presence of a confirmed fistula, and method for confirmation of the diagnosis were recorded. A veterinary radiologist reviewed CT studies for all included horses and recorded characteristics of the fistulae. Seventeen horses were sampled. Fourteen oromaxillary sinus fistulae and three oronasal fistulae were identified. All fistulae appeared as variably sized focal defects in the alveolar bone. Defects frequently contained a linear tract of heterogeneous material interspersed with gas bubbles, considered consistent with food. Computed tomographic attenuation of the material (Hounsfield units, HU) varied widely within and between cases. In 16 of 17 cases, there was evidence of concurrent dental disease in addition to the fistulae. Although the gold standard diagnostic test remains identification of feed material within the sinus or nasal passages, findings from the current study support the use of CT as an adjunctive diagnostic test for assessing the extent of involvement and presurgical planning.
CLAG3 Self-Associates in Malaria Parasites and Quantitatively Determines Nutrient Uptake Channels at the Host Membrane
Authors: Gupta Ankit , Balabaskaran-Nina Praveen , Nguitragool Wang , Saggu Gagandeep S. , Schureck Marc A. , Desai Sanjay A. 
Published: May 2018

ABSTRACT

Malaria parasites increase host erythrocyte permeability to ions and nutrients via a broad-selectivity channel known as the plasmodial surface anion channel (PSAC), linked to parasite-encoded CLAG3 and two associated proteins. These proteins lack the multiple transmembrane domains typically present in channel-forming proteins, raising doubts about their precise roles. Using the virulent human
Plasmodium falciparum
parasite, we report that CLAG3 undergoes self-association and that this protein’s expression determines channel phenotype quantitatively. We overcame epigenetic silencing of
clag3
paralogs and engineered parasites that express two CLAG3 isoforms simultaneously. Stoichiometric expression of these isoforms yielded intermediate channel phenotypes, in agreement with observed trafficking of both proteins to the host membrane. Coimmunoprecipitation and surface labeling revealed formation of CLAG3 oligomers.
In vitro
selections applied to these transfectant lines yielded distinct mutants with correlated changes in channel activity. These findings support involvement of the identified oligomers in PSAC formation and parasite nutrient acquisition.

IMPORTANCE
Malaria parasites are globally important pathogens that evade host immunity by replicating within circulating erythrocytes. To facilitate intracellular growth, these parasites increase erythrocyte nutrient uptake through an unusual ion channel. The parasite CLAG3 protein is a key determinant of this channel, but its lack of homology to known ion channels has raised questions about possible mechanisms. Using a new method that allows simultaneous expression of two different CLAG3 proteins, we identify self-association of CLAG3. The two expressed isoforms faithfully traffic to and insert in the host membrane, while remaining associated with two unrelated parasite proteins. Both the channel phenotypes and molecular changes produced upon selections with a highly specific channel inhibitor are consistent with a multiprotein complex that forms the nutrient pore. These studies support direct involvement of the CLAG3 protein in channel formation and are relevant to antimalarial drug discovery projects targeting parasite nutrient acquisition.
On the boundary flow using pulsed nanosecond DBD plasma actuators
Authors: Zhao Zi-Jie , Cui Y. D. , Li Jiun-Ming , Zheng Jian-Guo , Khoo B. C. 
Published: May 2018

Our previous studies in quiescent air environment [Z. J. Zhao et al., AIAA J. 53(5) (2015) 1336; J. G. Zheng et al., Phys. Fluids 26(3) (2014) 036102] reveal experimentally and numerically that the shock wave generated by the nanosecond pulsed plasma is fundamentally a microblast wave. The shock-induced burst perturbations (overpressure and induced velocity) are found to be restricted to a very narrow region (about 1 mm) behind the shock front and last only for a few microseconds. These results indicate that the pulsed nanosecond dielectric barrier discharge (DBD) plasma actuator has stronger local effects in time and spatial domain. In this paper, we further investigate the effects of pulsed plasma on the boundary layer flow over a flat plate. The present investigation reveals that the nanosecond pulsed plasma actuator generates intense perturbations and tends to promote the laminar boundary over a flat plate to turbulent flow. The heat effect after the pulsed plasma discharge was observed in the external flow, lasting a few milliseconds for a single pulse and reaching a quasi-stable state for multi-pulses.
Quotient and blow-up of automorphisms of graphs of groups
Authors: Ye Kaidi 
Published: May 2018

In this paper, we study the quotient and “blow-up” of graph-of-groups [Formula: see text] and of their automorphisms [Formula: see text]. We show that the existence of such a blow-up of any [Formula: see text], relative to a given family of “local” graph-of-groups isomorphisms [Formula: see text] depends crucially on the [Formula: see text]-conjugacy class of the correction term [Formula: see text] for any edge [Formula: see text] of [Formula: see text], where [Formula: see text]-conjugacy is a new but natural concept introduced here. As an application, we obtain a criterion as to whether a partial Dehn twist can be blown up relative to local Dehn twists, to give an actual Dehn twist. The results of this paper are also used crucially in the follow-up papers [Lustig and Ye, Normal form and parabolic dynamics for quadratically growing automorphisms of free groups, arXiv:1705.04110v2; Ye, Partial Dehn twists of free groups relative to local Dehn twists — A dichotomy, arXiv:1605.04479 ; When is a polynomially growing automorphism of [Formula: see text] geometric, arXiv:1605.07390 ].
Oberlin’s Transfer: Long Term Outcomes
Authors: Verdins Karlis , Kapickis Martins 
Published: May 2018

Background: Brachial plexus injury is very commonly associated with road traffic accidents, and frequently affects young adults, causing significant disability and impact on quality of life. The successful treatment of upper plexus injury with the Oberlin technique to restore elbow flexion with good functional results. Methods: We retrieved the records of all patients with upper plexus injury who underwent Oberlin transfer operation between March 2007 and July 2012. Outcomes were assessed using the Medical Research Council (MRC) power grading system for biceps muscle, Disabilities of the Arm, Shoulder and Hand score (DASH) for patient functional outcomes and the Visual Analogue Scale for daily disability (VAS where 0- no restrictions; 10- significant limitations) for overall patient satisfaction. Follow-up was performed for at least 12 months post-operatively. Results: The average follow up period was 43.6 months. Six cases gained effective elbow flexion, improving to MRC grade 5/5 and four cases improved to MRC grade 4/5 for biceps function. The average DASH score was 27.25. One patient had serious disability with no changes after Oberlin’s transfer operation. No permanent impairment of ulnar nerve function was observed. Seven out of 10 patients had begun daily work, with no discomfort and no functional impact on activities of daily living. Conclusions: We found The Oberlin transfer is a useful salvage procedure and most effective results are for young patients with short interval between injury and operation.
The Role of Selective Peripheral Neurectomy in the Treatment of Upper Limb Spasticity
Authors: Yong Li Yenn , Wong Charis H.L. , Gaston Mark , Lam Wee Leon 
Published: May 2018

Background: Management of upper limb spasticity remains challenging. Selective peripheral neurectomy (SPN) is a relatively recent intervention for cases refractory to medical therapy. The aim of this study was to conduct a systematic review looking at the efficacy and outcomes of SPN, in order to clarify the patient selection criteria and surgical technique. Methods: A search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Collection, Open Grey and CINAHL was conducted. Inclusion criteria included studies comparing pre- and post-operative outcomes for SPN, neurectomy, fasciculotomy and upper limb spasticity. Results: Only case series were reported with no randomised controlled trials found. 7 studies met the inclusion criteria with a total of 174 patients. A meta-analysis was not possible due to the degree of baseline heterogeneity. All studies had no control arm for comparison of outcomes, with a high risk of bias due to poor internal and external validity, as well as design and performance bias. Surgical techniques differ vastly between studies, with percentage of fascicles ablated between 30–80% and length of neurectomy between 5–10 mm. Some advocated removing end branches while others performed fascicular SPN proximally. 13 patients underwent orthopaedic or neurosurgical procedures, which are both confounding factors. All studies reported an improvement in spasticity although functional outcomes were reported with non-standardized measures. Recurrence rates were reported to be 0–16.1% (mean 3.72%). Conclusions: From this systematic review, SPN appeared to be a useful technique in selected cases, but overall no firm conclusions can be drawn regarding the best surgical technique, or the extent of functional improvement.
Novel Richter Syndrome Xenograft Models to Study Genetic Architecture, Biology, and Therapy Responses
Authors: Vaisitti Tiziana , Braggio Esteban , Allan John N. , Arruga Francesca , Serra Sara , Zamò Alberto , Tam Wayne , Chadburn Amy , Furman Richard R. , Deaglio Silvia 
Published: May 2018

Abstract
Richter syndrome represents the evolution of chronic lymphocytic leukemia into an aggressive tumor, most commonly diffuse large B-cell lymphoma. The lack of in vitro and in vivo models has severely hampered drug testing in a disease that is poorly responsive to common chemoimmunotherapeutic combinations as well as to novel kinase inhibitors. Here we report for the first time the establishment and genomic characterization of two patient-derived tumor xenograft (PDX) models of Richter syndrome, RS9737 and RS1316. Richter syndrome xenografts were genetically, morphologically, and phenotypically stable and similar to the corresponding primary tumor. RS9737 was characterized by biallelic inactivation of CDKN2A and TP53, monoallelic deletion of 11q23 (ATM), and mutations of BTK, KRAS, EGR2, and NOTCH1. RS1316 carried trisomy 12 and showed mutations in BTK, KRAS, MED12, and NOTCH2. RNA sequencing confirmed that in both cases &gt;80% of the transcriptome was shared between primary tumor and PDX. In line with the mutational profile, pathway analyses revealed overactivation of the B-cell receptor, NFκB, and NOTCH pathways in both tumors, potentially providing novel tumor targets. In conclusion, these two novel models of Richter syndrome represent useful tools to study biology and response to therapies of this highly aggressive and still incurable tumor.
Significance: Two patient-derived xenograft models of Richter syndrome represent the first ex vivo model to study biology of the disease and to test novel therapeutic strategies. Cancer Res; 78(13); 3413–20. ©2018 AACR.
Optimized Dosing Schedule Based on Circadian Dynamics of Mouse Breast Cancer Stem Cells Improves the Antitumor Effects of Aldehyde Dehydrogenase Inhibitor
Authors: Matsunaga Naoya , Ogino Takashi , Hara Yukinori , Tanaka Takahiro , Koyanagi Satoru , Ohdo Shigehiro 
Published: May 2018

Abstract
Although malignant phenotypes of triple-negative breast cancer (TNBC) are subject to circadian alterations, the role of cancer stem cells (CSC) in defining this circadian change remains unclear. CSC are often characterized by high aldehyde dehydrogenase (ALDH) activity, which is associated with the malignancy of cancer cells and is used for identification and isolation of CSC. Here, we show that the population of ALDH-positive cells in a mouse 4T1 breast tumor model exhibits pronounced circadian alterations. Alterations in the number of ALDH-positive cells were generated by time-dependent increases and decreases in the expression of Aldh3a1. Importantly, circadian clock genes were rhythmically expressed in ALDH-negative cells, but not in ALDH-positive cells. Circadian expression of Aldh3a1 in ALDH-positive cells was dependent on the time-dependent release of Wingless-type mmtv integration site family 10a (WNT10a) from ALDH-negative cells. Furthermore, antitumor and antimetastatic effects of ALDH inhibitor N,N-diethylaminobenzaldehyde were enhanced by administration at the time of day when ALDH activity was increased in 4T1 tumor cells. Our findings reveal a new role for the circadian clock within the tumor microenvironment in regulating the circadian dynamics of CSC. These results should enable the development of novel therapeutic strategies for treatment of TNBC with ALDH inhibitors.
Significance: This seminal report reveals that circadian dynamics of CSC are regulated by the tumor microenvironment and provides a proof of principle of its implication for chronotherapy in TNBC. Cancer Res; 78(13); 3698–708. ©2018 AACR.
Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures Into Future Successes
Authors: Winer Arthur , Adams Sylvia , Mignatti Paolo 
Published: May 2018

Abstract
The matrix metalloproteinases (MMP) are a family of proteolytic enzymes that degrade multiple components of the extracellular matrix. A large body of experimental and clinical evidence has implicated MMPs in tumor invasion, neoangiogenesis, and metastasis, and therefore they represent ideal pharmacologic targets for cancer therapy. From the 1990s to early 2000s, synthetic inhibitors of MMPs (MMPI) were studied in various cancer types. Unexpectedly, despite strongly promising preclinical data, all trials were unsuccessful in reducing tumor burden or improving overall survival; in addition, MMPIs had unforeseen, severe side effects. Two main reasons can explain the failure of MMPIs in clinical trials. It has now become apparent that some MMPs have antitumor effects; therefore, the broad-spectrum MMPIs used in the initial trials might block these MMPs and result in tumor progression. In addition, although MMPs are involved in the early stages of tumor progression, MMPIs were tested in patients with advanced disease, beyond the stage when these compounds could be effective. As more specific MMPIs are now available, MMP targeting could be reconsidered for cancer therapy; however, new trials should be designed to test their antimetastatic properties in early-stage tumors, and endpoints should focus on parameters other than decreasing metastatic tumor burden. Mol Cancer Ther; 17(6); 1147–55. ©2018 AACR.
Evaluating the Experimental High-Resolution Rapid Refresh–Alaska Modeling System Using USArray Pressure Observations
Authors: McCorkle Taylor A. , Horel John D. , Jacques Alexander A. , Alcott Trevor 
Published: May 2018

Abstract
The High-Resolution Rapid Refresh–Alaska (HRRR-AK) modeling system provides 3-km horizontal resolution and 0–36-h forecast guidance for weather conditions over Alaska. This study evaluated the experimental version of the HRRR-AK system available from December 2016 to June 2017, prior to its operational deployment by the National Centers for Environmental Prediction in July 2018. Surface pressure observations from 158 National Weather Service (NWS) stations assimilated during the model’s production cycle and pressure observations from 101 USArray Transportable Array (TA) stations that were not assimilated were used to evaluate 265 complete 0–36-h forecasts of the altimeter setting (surface pressure reduced to sea level). The TA network is the largest recent expansion of Alaskan weather observations and provides an independent evaluation of the model’s performance during this period. Throughout the study period, systematic differences in altimeter setting between the HRRR-AK 0-h forecasts were larger relative to the unassimilated TA observations than relative to the assimilated NWS observations. Upon removal of these initial biases from each of the subsequent 1–36-h altimeter setting forecasts, the model’s 36-h forecast root-mean-square errors at the NWS and TA locations were comparable. The model’s treatment of rapid warming and downslope winds that developed in the lee of the Alaska Range during 12–15 February is examined. The HRRR-AK 0-h forecasts were used to diagnose the synoptic and mesoscale conditions during this period. The model forecasts underestimated the abrupt increases in the temperature and intensity of the downslope winds with smaller errors as the downslope wind events evolved.