bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune function of a Rab‐related protein by modulating the JAK‐STAT signaling pathway in the silkworm, Bombyx mori
Authors: Chen Chen , Eldein Salah , Zhou Xiaosan , Sun Yu , Gao Jin , Sun Yuxuan , Liu Chaoliang , Wang Lei 
Published: November 2017

AbstractThe Rab‐family GTPases mainly regulate intracellular vesicle transport, and play important roles in the innate immune response in invertebrates. However, the function and signal transduction of Rab proteins in immune reactions remain unclear in silkworms. In this study, we analyzed a Rab‐related protein of silkworm Bombyx mori (BmRABRP) by raising antibodies against its bacterially expressed recombinant form. Tissue distribution analysis showed that BmRABRP mRNA and protein were high expressed in the Malpighian tubule and fat body, respectively. However, among the different stages, only the fourth instar larvae and pupae showed significant BmRABRP levels. After challenge with four pathogenic microorganisms (Escherichia coli, BmNPV, Beauveria bassiana, Micrococcus luteus), the expression of BmRABRP mRNA in the fat body was significantly upregulated. In contrast, the BmRABRP protein was significantly upregulated after infection with BmNPV, while it was downregulated by E. coli, B. bassiana, and M. luteus. A specific dsRNA was used to explore the immune function and relationship between BmRABRP and the JAK‐STAT signaling pathway. After BmRABRP gene interference, significant reduction in the number of nodules and increased mortality suggested that BmRABRP plays an important role in silkworm's response to bacterial challenge. In addition, four key genes (BmHOP, BmSTAT, BmSOCS2, and BmSOCS6) of the JAK‐STAT signaling pathway showed significantly altered expressions after BmRABRP silencing. BmHOP and BmSOCS6 expressions were significantly decreased, while BmSTAT and BmSOCS2 were significantly upregulated. Our results suggested that BmRABRP is involved in the innate immune response against pathogenic microorganisms through the JAK‐STAT signaling pathway in silkworm.
Assessing Parental Capacity when there are Concerns about an Unborn Child: Pre‐Birth Assessment Guidance and Practice in England
Authors: Lushey Clare J. , Barlow Jane , Rayns Gwynne , Ward Harriet 
Published: November 2017

Assessment where there are concerns that an unborn child is likely to suffer significant harm is one of the most difficult tasks that social workers undertake; the legal and ethical context makes the process of assessment and intervention during this period complex. This paper explores pre‐birth assessment guidance and practice in England. Local safeguarding guidance in 147 English localities was accessed and analysed, and interviews were conducted with 22 practitioners involved in pre‐birth assessments. The findings showed that while most local safeguarding guidance was more detailed and explicit than the national guidance, legal and ethical issues were rarely addressed. Interview data showed that, in general, guidance to support social work assessments during the pre‐birth period was insufficient, and that few practitioners used standardised tools to aid assessment. Some practitioners regarded pre‐birth assessments as less urgent than cases involving infants/older children, thereby increasing delays in decision‐making. It is concluded that existing guidance and practice with regard to pre‐birth assessment are inadequate. Copyright © 2017 John Wiley & Sons, Ltd.‘Explores pre‐birth assessment guidance and practice in England’Key Practitioner Messages

Existing guidance regarding pre‐birth assessment are inadequate with regards to providing practitioners with the necessary information about the assessment process or tools with which to undertake the assessment.
Practitioners undertaking pre‐birth assessment should be provided with better training regarding the assessment process.
There is a need for practitioners undertaking pre‐birth assessment to use standardised tools alongside professional judgement.
‘Practitioners undertaking pre‐birth assessment should be provided with better training regarding the assessment process’
Perfluoroalkyltricyanoborate and Perfluoroalkylcyanofluoroborate Anions: Building Blocks for Low‐Viscosity Ionic Liquids
Authors: Landmann Johannes , Sprenger Jan A. P. , Hennig Philipp T. , Bertermann Rüdiger , Grüne Matthias , Würthner Frank , Ignat'ev Nikolai V. , Finze Maik 
Published: November 2017

AbstractInvited for the cover of this issue is the group of Maik Finze at the Julius‐Maximilians University in Würzburg. The image depicts low‐viscosity ionic liquids, flowing from one container to another. Read the full text of the article at 10.1002/chem.201703685.
Relationship between Hammett's parameters and in silico density functional with tandem mass ESI‐CID fragmentation: Dihydropyridines as prototypes
Authors: dos Santos P.R. , Pereira C.M.P. , Ritter M. , de Paula F.R. , Moura S. 
Published: November 2017

AbstractOver the years, with the instrumental analysis evolution, the relationships between the carried‐out results with the data of theoretical analysis in silico and the Hammett's parameters have been reported. They have been very useful for chemical characterization of small organic molecules. Thus, this work aims at showing the feasibility and limitations for Hammett's and density functional theory applications in electrospray ionization–collision‐induced dissociation (ESI‐CID) fragmentation provision. For this, 13 dihydropyrimidinones para, meta, and orto monosubstituted were studied using ESI and CID in positive mode. As a result, it was observed that the main fragmentation includes the isocyanate and ethanol loses at low energy. Nevertheless, at higher energies, radical ions formed by McLafferty rearrangement were observed. The Hammett plots were correlated fragmentation profiles, showing good linearity for the [M + H]+, which does not occur to radical ions and carbocation's. These tendencies had demonstrated that the stability of protonate and activation energy of secondary ions changes with the pKa. The density functional theory studies indicated that, both nitrogen atoms in the dihydropyrimidinone's prototypes are capable of being protonated. However, the activation energy of fragmentation products is not changed. Therefore, this work has shown information, which can be useful to understand tandem mass spectrometry in ESI‐CID conditions for small organic molecules series. This is the first step for normalization of fragmentation pathway.
Effect of fermentation on anthocyanin stability and in vitro bioaccessibility during shalgam (şalgam) beverage production
Authors: Toktaş Betül , Bildik Fatih , Özçelik Beraat 
Published: November 2017

AbstractBACKGROUNDShalgam is a traditional lactic acid fermented beverage highly popular in southern Turkey. The main raw material, black carrot, contains a significant amount of anthocyanins. In this study, changes in polyphenols, including anthocyanins, related total antioxidant capacity (TAC), and in vitro bioaccessibility during shalgam fermentation and main raw material were evaluated.RESULTSCompared with the last 12 days of the fermentation, a higher increase in total phenolic content (TPC), anthocyanins content (AC), and TAC was observed in the first 12 days of the fermentation during shalgam production. Although black carrot exhibited the highest total flavonoid content (TFC), TPC, AC, and TAC values before bioaccessibility tests, the recovery of shalgam beverage was found to be mostly identical with black carrot results in terms of flavonoids, phenolics, and anthocyanins and antioxidant capacity after in vitro digestion. In vitro digestion significantly reduced the recovery of initial samples in terms of TFC, TPC, AC, and TAC analysis. The amount of beneficial compound in the early fermentation stage was significantly lower than with end product. Sixteen different phenolics were detected from shalgam beverage samples in high‐performance liquid chromatography analysis. After performing bioaccessibility tests, only five phenolics were detected. As anthocyanins, only cyanidin content was identified.CONCLUSIONThe degradation of phenolics and anthocyanins was observed after bioaccessibility tests. © 2017 Society of Chemical Industry
Optimizing venous outflow in reconstruction of Gustilo IIIB lower extremity traumas with soft tissue free flap coverage: Are two veins better than one?
Authors: Stranix John T. , Lee Z‐Hye , Anzai Lavinia , Jacoby Adam , Avraham Tomer , Saadeh Pierre B. , Levine Jamie P. , Thanik Vishal D. 
Published: November 2017

PurposeThe dependent nature of the lower extremity predisposes to venous congestion, especially following significant trauma. The benefit of a second venous anastomosis, however, remains unclear in lower extremity trauma free flap reconstruction. This study investigated the effect of an additional venous anastomosis on flap outcomes in lower extremity trauma reconstruction.MethodsRetrospective review between 1979 and 2016 identified 361 soft tissue flaps performed for Gustilo IIIB/C coverage meeting inclusion criteria. Muscle flaps were performed in 287 cases (79.9%) and fasciocutaneous flaps in 72 cases (20.1%). Single‐vein anastomosis was performed in 76% of cases and dual‐vein anastmoses in 24% of cases. Patient demographics, flap characteristics, and outcomes were examined.ResultsFasciocutaneous flaps were more likely to have two veins performed (P < .001). Complications occurred in 143 flaps (39.8%): 45 take‐backs (12.4%), 37 partial losses (10.3%), 31 complete losses (8.6%). Compared to single‐vein flaps, two veins reduced major complications (P = .005), partial flap failures (P = .008), and any flap failure (P = .018). Multivariable regression analysis demonstrated two veins to be protective against complications (RR = 2.58, P = .009). Subset regression analysis by flap type demonstrated an even more significant reduction in complications among muscle flaps (RR = 3.92, P = .005). Additionally, a >1 mm vein size mismatch was predictive of total flap failure (RR = 3.02, P = .038).ConclusionLower extremity trauma free flaps with two venous anastomoses demonstrated a fourfold reduction in complication rates compared to single‐vein flaps. Additionally, venous size mismatch >1 mm was an independent predictor of total flap failure, suggesting beneficial effects of both two‐vein outflow and matched vessel diameter.
Using MRI cell tracking to monitor immune cell recruitment in response to a peptide‐based cancer vaccine
Authors: Tremblay Marie‐Laurence , Davis Christa , Bowen Chris V. , Stanley Olivia , Parsons Cathryn , Weir Genevieve , Karkada Mohan , Stanford Marianne M. , Brewer Kimberly D. 
Published: November 2017

PurposeMRI cell tracking can be used to monitor immune cells involved in the immunotherapy response, providing insight into the mechanism of action, temporal progression of tumor growth, and individual potency of therapies. To evaluate whether MRI could be used to track immune cell populations in response to immunotherapy, CD8+ cytotoxic T cells, CD4+CD25+FoxP3+ regulatory T cells, and myeloid‐derived suppressor cells were labeled with superparamagnetic iron oxide particles.MethodsSuperparamagnetic iron oxide‐labeled cells were injected into mice (one cell type/mouse) implanted with a human papillomavirus‐based cervical cancer model. Half of these mice were also vaccinated with DepoVaxTM (ImmunoVaccine, Inc., Halifax, Nova Scotia, Canada), a lipid‐based vaccine platform that was developed to enhance the potency of peptide‐based vaccines.ResultsMRI visualization of CD8+ cytotoxic T cells, regulatory T cells, and myeloid‐derived suppressor cells was apparent 24 h post‐injection, with hypointensities due to iron‐labeled cells clearing approximately 72 h post‐injection. Vaccination resulted in increased recruitment of CD8+ cytotoxic T cells, and decreased recruitment of myeloid‐derived suppressor cells and regulatory T cells to the tumor. We also found that myeloid‐derived suppressor cell and regulatory T cell recruitment were positively correlated with final tumor volume.ConclusionThis type of analysis can be used to noninvasively study changes in immune cell recruitment in individual mice over time, potentially allowing improved application and combination of immunotherapies. Magn Reson Med 80:304–316, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
RETRACTED: Epigallocatechin‐3‐gallate enhances differentiation of acute promyelocytic leukemia cells via inhibition of PML‐RARα and HDAC1
Authors: Moradzadeh Maliheh , Roustazadeh Abazar , Tabarraei Alijan , Erfanian Saiedeh , Sahebkar Amirhossein 
Published: November 2017

The use of all‐trans retinoic acid (ATRA) has dramatically improved the treatment and survival rate of patients with acute promyelocytic leukemia (APL). However, toxicity and resistance to this drug are major problems in the treatment of APL with ATRA. Earlier studies have suggested that the green tea polyphenol epigallocatechin gallate (EGCG) induces cell death in hematopoietic neoplasms without adversely affecting normal cells. In the present study, the potential therapeutic effect of EGCG in APL and the underlying molecular mechanisms were investigated. EGCG (100 μM) significantly inhibited proliferation and induced apoptosis in HL‐60 and NB4 cells. This effect was associated with decreased expressions of multidrug resistance proteins ABCB1, and ABCC1, whereas the expressions of pro‐apoptotic genes CASP3, CASP8, p21, and Bax/Bcl‐2 ratio were significantly increased. EGCG, at 25 μM concentration, induced differentiation of leukemic cells towards granulocytic pattern in a similar manner to that observed for ATRA (1 μM). Furthermore, EGCG suppressed the expression of clinical marker PML/RARα in NB4 cells and reduced the expression of HDAC1 in leukemic cells. In conclusion, the results suggested that EGCG can be considered as a potential treatment for APL.
What are critical features of science curriculum materials that impact student and teacher outcomes?
Authors: Roblin Natalie Pareja , Schunn Christian , McKenney Susan 
Published: November 2017

AbstractLarge investments are made in curriculum materials with the goal of supporting science education reform. However, relatively little evidence is available about what features of curriculum materials really matter to impact student and teacher learning. To address this need, the current study examined curriculum features associated with student and teacher outcomes. We reviewed sample curriculum materials and documentation reporting on the instructional outcomes of 51 research‐based K–12 science curriculum materials. Our findings reveal that teacher supports, rather than student supports, had positive impacts on both student and teacher outcomes. Specifically, positive student outcomes were associated with curriculum materials with a larger scope and with materials that provide teachers with information about students’ ideas and recommended instructional strategies. Positive teacher outcomes were associated with the presence of information about targeted standards and recommended instructional strategies. Relatively fewer studies reported on teacher outcomes, and evidence about other dimensions of curriculum materials impact (e.g., spread, sustainability) was difficult to find. Overall, these results reveal the broad importance of embedding teacher supports and ensuring sufficient scope of content across coordinated curriculum units to support the development of conceptual understanding over time. Implications for the design of new curriculum materials and further research are discussed.
Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings
Authors: Weinreb Robert N. , Liebmann Jeffrey M. , Martin Keith R. , Kaufman Paul L. , Vittitow Jason L. 
Published: November 2017

Purpose:
To compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) 0.024% with timolol maleate 0.5% in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Patients and Methods:
Pooled analysis of two phase 3, randomized, multicenter, double-masked, parallel-group, noninferiority trials (APOLLO and LUNAR), each with open-label safety extension phases. Adults with OAG or OHT were randomized 2:1 to double-masked treatment with LBN once daily (qd) or timolol twice daily (bid) for 3 months followed by open-label LBN treatment for 3 (LUNAR) or 9 (APOLLO) months. IOP was measured at 8 am, 12 pm, and 4 pm at week 2, week 6, and months 3, 6, 9, and 12.

Results:
Of the 840 subjects randomized, 774 (LBN, n=523; timolol crossover to LBN, n=251) completed the efficacy phase, and 738 completed the safety extension phase. Mean IOP was significantly lower with LBN versus timolol at all 9 evaluation timepoints during the efficacy phase (P<0.001). A significantly greater proportion of LBN-treated subjects attained a mean IOP ≤18 mm Hg and IOP reduction ≥25% from baseline versus timolol-treated subjects (P<0.001). The IOP reduction with LBN was sustained through the safety phase; subjects crossed over from timolol to LBN experienced additional significant IOP lowering (P≤0.009). Both treatments were well tolerated, and there were no safety concerns with long-term LBN treatment.

Conclusions:
In this pooled analysis of subjects with OAG and OHT, LBN 0.024% qd provided greater IOP-lowering compared with timolol 0.5% bid and maintained lowered IOP through 12 months. LBN demonstrated a safety profile comparable to that of prostaglandin analogs.
Rapid, noninvasive, and unsupervised detection of sleep/wake using piezoelectric monitoring for pharmacological studies in narcoleptic mice
Authors: Black Sarah Wurts , Sun Jessica D. , Laihsu Alex , Kimura Nikki , Santiago Pamela , Donohue Kevin D. , O’Hara Bruce F. , Bersot Ross , Humphries Paul S. 
Published: November 2017

AbstractBackgroundAssessment of sleep/wake by electroencephalography (EEG) and electromyography (EMG) is invasive, resource intensive, and not amenable to rapid screening at scale for drug discovery. In the preclinical development of therapeutics for narcolepsy, efficacy tests are hindered by the lack of a non-EEG/EMG based translational test of symptom severity. The current methods study offers proof-of-principle that PiezoSleep (noninvasive, unsupervised piezoelectric monitoring of gross body movement, together with respiration patterns during behavioral quiescence), can be used to determine sleep/wake as applicable to the development of wake-promoting therapeutics. First, the translational wake-maintenance score (WMS, the ratio of time during the first half of the dark period spent in long wake bouts to short sleep bouts) of the PiezoSleep narcolepsy screen was introduced as a means by which to rank narcoleptic orexin/ataxin-3 mice and wild type mice by sleep/wake fragmentation severity. Accuracy of the WMS to detect narcoleptic phenotypes were determined in genotype-confirmed orexin/ataxin-3 mice and wild type colony mates. The WMS was used to identify the most highly symptomatic mice for resource-intensive EEG/EMG studies for further analysis of specific arousal states. Second, PiezoSleep was demonstrated for use in high-throughput screening of wake-promoting compounds using modafinil in orexin/ataxin-3 and wild type mice.ResultsThe WMS detected a narcoleptic phenotype with 89% sensitivity, 92% specificity and 98% positive predictive value. A 15-fold difference in WMS differentiated wild type littermates from the most severely affected orexin/ataxin-3 mice. Follow-up EEG/EMG study indicated 82% of the orexin/ataxin-3 mice with the lowest wake-maintenance scores met or exceeded the cataplexy-occurrence threshold (≥ 3 bouts) for inclusion in therapeutic efficacy studies. In the PiezoSleep dose-response study, the ED50 for wake-promotion by modafinil was approximately 50 mg/kg in both genotypes. Using unsupervised piezoelectric monitoring, the efficacy of wake-promoting compounds can be determined in a 5-arm study with 60 mice in less than one week—a fraction of the time compared to EEG/EMG studies.ConclusionsThe WMS on the PiezoSleep narcolepsy screen quantifies the inability to sustain wakefulness and provides an accurate measure of the narcoleptic phenotype in mice. PiezoSleep offers rapid, scalable assessment of sleep/wake for high-throughput screening in drug discovery.
Associations of stream geomorphic conditions and prevalence of alternative reproductive tactics among sockeye salmon populations
Authors: DeFilippo L. B. , Schindler D. E. , Carter J. L. , Walsworth T. E. , Cline T. J. , Larson W. A. , Buehrens T. 
Published: November 2017

AbstractIn many species, males may exhibit alternative life histories to circumvent the costs of intrasexual competition and female courtship. While the evolution and underlying genetic and physiological mechanisms behind alternative reproductive tactics are well studied, there has been less consideration of the ecological factors that regulate their prevalence. Here, we examine six decades of age composition records from thirty‐six populations of sockeye salmon (Oncorhynchus nerka) to quantify associations between spawning habitat characteristics and the prevalence of precocious sneakers known as ‘jacks’. Jack prevalence was independent of neutral genetic structure among stream populations, but varied among habitat types and as a function of continuous geomorphic characteristics. Jacks were more common in streams relative to beaches and rivers, and their prevalence was negatively associated with stream width, depth, elevation, slope and area, but positively related to bank cover. Behavioural observations showed that jacks made greater use of banks, wood and shallows than guard males, indicating that their reproductive success depends on the availability of such refuges. Our results emphasize the role of the physical habitat in shaping reproductive tactic frequencies among populations, likely through local adaptation in response to variable fitness expectations under different geomorphic conditions.