bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Delivery of STAT-3 Modulator to Breast Cancer Stem-Like Cells Downregulates a Series of Stemness Genes
Authors: Misra Santosh K. , De Arun , Pan Dipanjan
Published: November 2017

Cancer stem cells are known to be controlled by pathways that are dormant in normal adult cells, for example, PTEN, which is a negative regulator of transcription factor STAT3. STAT3 regulates genes that are involved in stem cell self-renewal and thus represents a novel therapeutic target of enormous clinical significance. Studies on breast cancer stem cells (BCSC) have been also significantly correlated with STATs. We describe here for the first time a novel strategy to selectively target CSCs and to induce downregulation of STAT3 downstream target genes reducing expression of series of “stem-ness genes” in treated tumors. In vitro and in vivo experiments were performed to evaluate functional activity with gene and protein expression studies. The results of the study indicate that this targeted delivery approach deactivates STAT3 causing a reduction of CD44+/CD24− CSC populations with aptly tracked gene and protein regulations of “stemness” characteristics. Mol Cancer Ther; 17(1); 119–29. ©2017 AACR.
Ablation of FGFR2 in Fibroblasts Ameliorates Kidney Fibrosis after Ischemia/Reperfusion Injury in Mice
Authors: Xu Zhuo , Dai Chunsun
Published: November 2017

Background: Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes. However, the role and mechanisms of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further investigation. Methods: In this study, a mouse model with fibroblast-specific FGFR2 gene disruption was generated. The knockouts were born normal and no kidney dysfunction or histological abnormality was found within 2 months after birth. A kidney ischemia/reperfusion injury (IRI) model was created. Results: Kidney fibrosis was developed in the control littermates within 2 and 4 weeks after IRI, while in the knockouts, total collagen deposition, fibronectin, and alpha smooth muscle actin expression were decreased compared to those in the control littermates. In addition, the numbers of Ki-67-positive interstitial cells as well as TUNEL-positive interstitial cells were lower in the knockout kidneys at 4 weeks after IRI. Phosphorylated extracellular regulated protein kinase 1/2 was decreased in the knockout kidneys at 2 and 4 weeks after IRI compared to those in the control littermates. Conclusion: These results suggest that FGF/FGFR2 signaling may promote the proliferation and activation of kidney fibroblasts, which contribute to the development of kidney fibrosis.
Roscovitine, a CDK5 Inhibitor, Alleviates Sevoflurane-Induced Cognitive Dysfunction via Regulation Tau/GSK3β and ERK/PPARγ/CREB Signaling
Authors: Liu Jianhui , Yang Junjun , Xu Yinhua , Guo Gang , Cai Li , Wu Heng , Zhao Yanhong , Zhang Xiaoqing
Published: November 2017

Background/Aims: Multiple exposures to anesthesia in children may increase the risk of developing cognitive impairment. Sevoflurane is an anesthetic that is commonly used in children during surgery. Cyclin-dependent kinase (CDK) 5 is involved in the regulation of sevoflurane-induced cognitive dysfunction, but the mechanistic details remain unclear. The present study evaluated the mechanism by which CDK5 mediates sevoflurane-induced cognitive dysfunction in mice. Methods: Hippocampal neurons were isolated from postnatal day 0 C57BL/6 mouse pups. Six-day-old wild-type mice were exposed to sevoflurane and then treated with the CDK5 inhibitor roscovitine. The effects on cognitive function were evaluated with the Morris water maze and neuronal damage in the hippocampus was assessed by immunohistochemical analysis. Results: CDK5 activation increased neuronal damage by inducing Tau/glycogen synthase kinase (GSK) 3β and suppressing extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor (PPAR)γ/cyclic AMP response element-binding protein (CREB) signaling following exposure to sevoflurane. CDK5 inhibition by roscovitine administration alleviated sevoflurane-induced neuronal damage and cognitive impairment. Conclusions: Inhibiting CDK5 with roscovitine has neuroprotective effects against neuronal injury and cognitive dysfunction caused by sevoflurane anesthesia that are exerted via modulation of Tau/GSK3β and ERK/PPARγ/CREB signaling.
β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells
Authors: Yu Wendan , Li Liren , Zheng Fufu , Yang Wenjing , Zhao Shilei , Tian Chunfang , Yin Wenwen , Chen Yiming , Guo Wei , Zou Lijuan , Deng Wuguo
Published: November 2017

Background/Aims: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. Methods: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of β-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. Results: β-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with β-catenin and contributed to β-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/β-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and β-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. Conclusions: Our study has provided new evidence for the role of β-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of β-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.
Clinical Impact of Diabetes Mellitus on Outcomes After Transcatheter Aortic Valve Replacement
Authors: Abramowitz Yigal , Vemulapalli Sreekanth , Chakravarty Tarun , Li Zhuokai , Kapadia Samir , Holmes David , Matsouaka Roland A. , Wang Alice , Cheng Wen , Forrester James S. , Smalling Richard , Thourani Vinod , Mack Michael , Leon Martin , Makkar Raj R.
Published: November 2017

Background—

Diabetes mellitus (DM) adversely affects morbidity and mortality for cardiovascular diseases and procedures. Data evaluating the outcomes of transcatheter aortic valve replacement (TAVR) in diabetic patients are limited by small sample size and contradictory results. We aimed to establish the magnitude of risk and the incremental influence of insulin dependency by examining short- and long-term adverse outcomes according to DM status and therapy in the world’s largest TAVR registry.

Methods and Results—

We analyzed data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. In-hospital mortality, 30-day mortality, and 1-year mortality after TAVR in patients with and without DM were evaluated using multivariate modeling. Among 47 643 patients treated with TAVR from November 2011 through September 2015 at 394 US hospitals, there were 17 849 (37.5%) patients with DM. Overall, 6600 of the diabetic patients were insulin treated (IT). Thirty-day mortality was 5.0% in patients with DM (6.1% in IT DM and 4.4% in non-IT DM;
P
<0.001) versus 5.9% in patients without DM (
P
<0.001). Overall, 1-year mortality was 21.8% in patients with DM (24.8% in IT DM and 20.1% in non-IT DM;
P
<0.001) versus 21.2% in patients without DM (
P
=0.274). In a multivariable model, DM was associated with increased 1-year mortality (hazard ratio, 1.30; 95% confidence interval, 1.13–1.49;
P
<0.001). Subgroup multivariable analysis showed stronger mortality association in IT diabetics (hazard ratio, 1.57; 95% confidence interval, 1.28–1.91;
P
<0.001) than in non-IT diabetics (hazard ratio, 1.17; 95% confidence interval, 1.00–1.38;
P
=0.052).

Conclusions—

Our data establish the magnitude of short- and long-term risk conferred by DM and the incremental risk conferred by insulin dependency in the performance of TAVR.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01737528.
Value of Progression of Coronary Artery Calcification for Risk Prediction of Coronary and Cardiovascular Events
Authors: Lehmann Nils , Erbel Raimund , Mahabadi Amir A. , Rauwolf Michael , Möhlenkamp Stefan , Moebus Susanne , Kälsch Hagen , Budde Thomas , Schmermund Axel , Stang Andreas , Führer-Sakel Dagmar , Weimar Christian , Roggenbuck Ulla , Dragano Nico , Jöckel Karl-Heinz , Meinertz T. , Bode C. , de Feyter P.J. , Güntert B. , Gutzwiller F. , Heinen H. , Hess O. , Klein B. , Löwel H. , Reiser M. , Schmidt G. , Schwaiger M. , Steinmüller C. , Theorell T. , Willich S.N. , Bode C. , Berger K. , Figulla H.R. , Hamm C. , Hanrath P. , Köpcke W. , Ringelstein B. , Dichgans M. , Zeiher A.
Published: November 2017

Background:

Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events.

Methods:

In 3281 participants (45–74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed.

Results:

We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1–Q3, 23–360] versus 8 [0–83],
P
<0.0001; similar for hard/total cardiovascular events). Some progression algorithms added to the predictive value of baseline CT and risk assessment in terms of C-statistic or integrated discrimination index, especially for total cardiovascular events. However, CAC progression did not improve models including CAC
5y
and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CAC
b
=CAC
5y
=0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CAC
b
progressed from 1 to 399 to CAC
5y
≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC
5y
=400. Participants with CAC
b
≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively).

Conclusions:

CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.
Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure])
Authors: Feldman Ted , Mauri Laura , Kahwash Rami , Litwin Sheldon , Ricciardi Mark J. , van der Harst Pim , Penicka Martin , Fail Peter S. , Kaye David M. , Petrie Mark C. , Basuray Anupam , Hummel Scott L. , Forde-McLean Rhondalyn , Nielsen Christopher D. , Lilly Scott , Massaro Joseph M. , Burkhoff Daniel , Shah Sanjiv J.
Published: November 2017

Background:

In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%.

Methods:

REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise.

Results:

A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control (
P
=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group (
P
=0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group (
P
=1.0).

Conclusions:

In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation.

Clinical Trial Registration:

URL:
https://clinicaltrials.gov
. Unique identifier: NCT02600234.
The Dead Sea Scrolls in Their Hellenistic Context
Authors: Hartog Pieter B. , Jokiranta Jutta
Published: November 2017

This introduction aims at situating the contributions of the Thematic Issue into wider debates on Hellenism and Hellenisation and changes taking place in scholarship. Essentialist notions of Hellenism are strongly rejected, but how then to study the Dead Sea Scrolls and the Qumran site during the Hellenistic period? Each contextualisation depends on the (comparative) material selected, and themes here vary from literary genres, textual practices, and forms of producing knowledge, to material culture, networks, and social organizations. All contributors see some embeddedness in ideas and practices attested elsewhere in the Hellenistic empires or taking place because of changes during the Hellenistic period. In this framework, similarities are overemphasized, but some differences are also suggested. Most importantly, the question of Hellenism is a question of relocating Jewish and Judaean evidence in the study of ancient history.
Temple Ideology and Hellenistic Private Associations
Authors: Eckhardt Benedikt
Published: November 2017

Soon after the discovery of 1QS, comparisons with private associations from the Hellenistic and Roman world were suggested. There are clearly some parallels in internal organization. However, scholars using this comparison to explain features of the yaḥad have rarely taken the environment that made associations in the Hellenistic world possible into account. By way of a comparison of attitudes towards temples, this article seeks to reintroduce the social context of private associations into the debate. While Hellenistic associations can be said to have developed temple ideologies not dissimilar to certain features of the yaḥad, the conditions, aims and implications of those respective ideologies were fundamentally different. This has obvious implications for understanding the social identity of members, and should caution against decontextualized comparisons.
Anxious Mobilities in Accra and Beyond
Authors: Toivanen Anna-Leena
Published: November 2017

In Aidoo’s Changes: A Love Story (1991), the characters are constantly on the move: tropes of mobility recur throughout the novel. Cars, hotels, business and leisure travel, modern technologies and the figure of what can be referred to as the Afropolitan avant la lettre play a pivotal role in embodying meanings that pertain to class, gender, globalization, and consumerism marking the postcolonial African condition, and give the novel an articulate contemporary character. This article adopts a wholesale understanding of mobility in order to explore the ways in which Aidoo’s characters employ different forms of mobility in their processes of self-fashioning as modern African subjects. The article draws attention to the anxiety that informs processes of self-fashioning among urban African elites, caught as they are between the tensions of the traditional and the modern.
Mass Migration, Crimmigration and Defiance
Authors: Šalamon Neža Kogovšek
Published: November 2017

The year 2015 saw an unprecedented number of refugees and migrants arriving to Europe through the “Western Balkans migration route”, where the states through which the route passed established the so-called “humanitarian corridor”. The operation of this corridor was outside the European normative framework and was treated by those states as a de facto undeclared “state of exception”. This situation, marked by an exceptionally intensive arrival of refugees and migrants en masse, was governed by ad hoc rules that were changing on a daily basis, creating an extremely unpredictable and uncertain situation for all stakeholders involved, in particular for the migrants and refugees themselves. This article discusses the crimmigration responses to mass migration management that are prevalent in contemporary law and politics, analyses the corridor within the current crimmigration context and demonstrates how the corridor defied the contemporary crimmigration approach to mass migration.
Diagnosing Relationships between Mean State Biases and El Niño Shortwave Feedback in CMIP5 Models
Authors: Ferrett Samantha , Collins Matthew , Ren Hong-Li
Published: November 2017

The rate of damping of tropical Pacific sea surface temperature anomalies (SSTAs) associated with El Niño events by surface shortwave heat fluxes has significant biases in current coupled climate models [phase 5 of the Coupled Model Intercomparison Project (CMIP5)]. Of 33 CMIP5 models, 16 have shortwave feedbacks that are weakly negative in comparison to observations, or even positive, resulting in a tendency of amplification of SSTAs. Two biases in the cloud response to El Niño SSTAs are identified and linked to significant mean state biases in CMIP5 models. First, cool mean SST and reduced precipitation are linked to comparatively less cloud formation in the eastern equatorial Pacific during El Niño events, driven by a weakened atmospheric ascent response. Second, a spurious reduction of cloud driven by anomalous surface relative humidity during El Niño events is present in models with more stable eastern Pacific mean atmospheric conditions and more low cloud in the mean state. Both cloud response biases contribute to a weak negative shortwave feedback or a positive shortwave feedback that amplifies El Niño SSTAs. Differences between shortwave feedback in the coupled models and the corresponding atmosphere-only models (AMIP) are also linked to mean state differences, consistent with the biases found between different coupled models. Shortwave feedback bias can still persist in AMIP, as a result of persisting weak shortwave responses to anomalous cloud and weak cloud responses to atmospheric ascent. This indicates the importance of bias in the atmosphere component to coupled model feedback and mean state biases.
School belonging: Listening to the voices of secondary school students who have undergone managed moves
Authors: Craggs Holly , Kelly Catherine
Published: November 2017

A sense of school belonging has a powerful effect on students’ emotional, motivational, and academic functioning, yet there have been few attempts to listen to students’ views on school belonging, or to seek their opinions on how best to promote it. Managed move protocols to facilitate a move to an alternative school were developed in the UK as a positive alternative to permanently excluding (expelling) students whose place at the school is no longer considered viable by school management. However, the ‘success’ of these protocols has been defined in a manner which does not take full account of their affective impact on this vulnerable group of children and young people (CYP). Previous research has identified a need for greater personalization of the managed move transition process and fuller incorporation of CYP views. This study sought to understand how secondary school students who have undergone a managed move experience school belonging. Data were analysed using interpretative phenomenological analysis (IPA). A sense of school belonging resulted from positive relationships with peers and an attendant sense of safety, security, and acceptance. Participants expressed both the desirability and perceived difficulty of forging relationships in a new school and acknowledged the value of sensitive and subtle support.
Resources for the Provision of Nutrition Support to Children in Educational Environments
Authors: Corrigan Mandy L. , Huang Shirley , Weaver Ann , Keeler David , Rahe Katina , Balint Jane , Marti Michelle , Goodman Brandis , Nagy Traci , DeLano Victoria , Bond Betty ,   for Home and Alternate Site Care Section, American Society for Parenteral and Enteral Nutrition
Published: November 2017

The use of nutrition support outside of institutional settings has contributed to maintaining the health, well‐being, and nutrition status of many medically complex children. As these children grow and enter educational settings, there is a need for awareness of the care that these children require for nutrition support therapy. This document is designed to raise awareness to these needs, provide best practice educational resources for those involved in the supervision or provision of nutrition support to children in an educational environment, and promote safe and effective care. Care of children requiring nutrition support is an ongoing and shared partnership among the educational team, medical team, homecare team, and parents/caregivers. Care is individualized to the specific child and may include provision of nutrition support therapy while in the school setting, maintenance of a nutrition access device, and monitoring to safely prevent or act on signs of potential complications. Suggested roles and responsibilities of those involved with nutrition support care are discussed; however, all interventions and routine care must be in accordance with physician's orders, school nurse privileges and competencies, and state and local regulations.
A cross-sectional study of ethnicity-based differences in treatment seeking for symptoms of acute coronary syndrome
Authors: Iacoe Emma , Ratner Pamela A , Wong Sabrina T , Mackay Martha H
Published: November 2017

Background:

Patient-related delays in acquiring medical care for symptoms of acute coronary syndrome remain unacceptably long. Many clinical and sociodemographic characteristics associated with treatment-seeking delay are known; however, ethnicity has not been extensively evaluated.

Objective:

The purpose of this study was to examine ethnicity-based differences in the time-to-treatment-seeking intervals of patients experiencing symptoms of acute coronary syndrome.

Method:

Data for this descriptive study were collected for the larger Acute Coronary Syndrome Care in Emergency Departments (ASCEND) study. The larger study is a prospective, observational study in which patients presenting to hospital emergency departments and triaged as having symptoms suggestive of acute coronary syndrome are identified. The primary outcome of this study, the time-to-treatment-seeking interval, was defined as the time between symptom onset and treatment seeking. The predictor variable, ethnicity, was measured with self-reported data and categorised as Chinese, South Asian, or ‘Other’ ethnic group. Participants in the ‘Other’ ethnic group were predominantly of European ancestry. Univariate and multivariate analyses were undertaken, along with nonparametric testing.

Results:

The study sample consisted of 419 participants: 36 Chinese, 126 South Asian, and 257 ‘Other’ participants. The median time-to-treatment-seeking interval, for the total sample, was 180 minutes. A Kruskal–Wallis test demonstrated no statistically significant differences in the time-to-treatment-seeking intervals by ethnicity.

Conclusion:

No ethnicity-based differences in the time-to-treatment-seeking intervals for symptoms of acute coronary syndrome were found. It is possible that Chinese and South Asian patients living in western countries are more aware of the potential signs and symptoms of acute coronary syndrome or feel more confident to access healthcare services than they have been previously.
RETRACTED ARTICLE: Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation
Authors: Wadhwa Meetu , Prabhakar Amit , Ray Koushik , Roy Koustav , Kumari Punita , Jha Prabhash Kumar , Kishore Krishna , Kumar Sanjeev , Panjwani Usha
Published: November 2017

Background

Sleep deprivation (SD) leads to cognitive impairment. Neuroinflammation could be a significant contributing factor in the same. An increase in regional brain pro-inflammatory cytokines induces cognitive deficits, however, the magnitude of the effect under SD is not apparent. It is plausible that microglia activation could be involved in the SD-induced cognitive impairment by modulation of neuronal cell proliferation, differentiation, and brain-derived neuronal factor (BDNF) level. The present study aimed to evaluate the possible beneficial effect of minocycline in amelioration of spatial memory decline during SD by its anti-inflammatory and neuroprotective actions. We scrutinized the effect of minocycline on the inflammatory cytokine levels associated with glial cells (microglia and astrocytes) activity and neurogenesis markers crucial for behavioral functions during SD.

Methods

Male Sprague-Dawley rats weighing 230–250 g were sleep deprived for 48 h using automated cage shaking apparatus. The spatial memory was tested using MWM apparatus immediately after completion of SD with and without minocycline. The animals were euthanized, blood was collected, and brain was extracted for neuroinflammation and neurogenesis studies. The set of experiments were also conducted with use of temozolomide, a neurogenesis blocker.

Results

Minocycline treatment increased the body weight, food intake, and spatial memory performance which declined during SD. It reduced the pro-inflammatory and increased the anti-inflammatory cytokine levels in hippocampus and plasma and inhibited the reactive gliosis in the hippocampus evidenced by improved cell count, morphology, and immunoreactivity. Additionally, minocycline administration promoted neurogenesis at different stages: proliferation (BrdU, Ki-67), differentiation (DCX) cells and growth factor (BDNF). However, no significant change was observed in maturation (NeuN) during SD. In addition, molecules related to behavior, inflammation, and neurogenesis were shown to be more affected after temozolomide administration during SD, and changes were restored with minocycline treatment. We observed a significant correlation of neurogenesis with microglial activation, cytokine levels, and spatial memory during SD.

Conclusion

The present study demonstrated that the SD-induced decline in spatial memory, neuronal cells proliferation, differentiation, and BDNF level could be attributed to upregulation of neuroinflammatory molecules, and minocycline may be an effective intervention to counteract these changes.

Graphical abstract

Microglial activation is involved in SD-induced changes in inflammatory molecules, neurogenesis, and spatial memory.
Novel functions of LHX2 and PAX6 in the developing telencephalon revealed upon combined loss of both genes
Authors: Godbole Geeta , Roy Achira , Shetty Ashwin S. , Tole Shubha
Published: November 2017

Patterning of the telencephalic neuroepithelium is a tightly regulated process controlled by transcription factors and signalling molecules. The cortical primordium is flanked by two signalling centres, the hem medially, and the antihem laterally. The hem induces the formation of the hippocampus in adjacent neuroepithelium. Therefore, the position of the hem defines the position of the hippocampus in the brain. The antihem is positioned at the boundary between the dorsal and ventral telencephalon and proposed to provide patterning cues during development.

LIM-homeodomain (LIM-HD) transcription factor LHX2 suppresses both hem and antihem fate in the cortical neuroepithelium. Upon loss of Lhx2, medial cortical neuroepithelium is transformed into hem, whereas lateral cortical neuroepithelium is transformed into antihem. Here, we show that transcription factor PAX6, known to regulate patterning of the lateral telencephalon, restricts this tissue from transforming into hem upon loss of Lhx2. When Lhx2 and Pax6 are both deleted, the cortical hem expands to occupy almost the complete extent of the cortical primordium, indicating that both factors act to suppress hem fate in the lateral telencephalon. Furthermore, the shift in the pallial-subpallial boundary and absence of the antihem, observed in the Pax6 mutant, are both restored in the Lhx2; Pax6 double mutant.

Together, these results not only reveal a novel function for LHX2 in regulating dorsoventral patterning in the telencephalon, but also identify PAX6 as a fundamental regulator of where the hem can form, and therefore implicate this molecule as a determinant of hippocampal positioning.
Compensating Q effects in viscoelastic media by adjoint-based least-squares reverse time migration
Authors: Guo Peng , McMechan George A.
Published: November 2017

Low values of P- and S-wave quality factors [Formula: see text] and [Formula: see text] result in strong intrinsic seismic attenuation in seismic modeling and imaging. We use a linearized waveform inversion approach, by generalizing least-squares reverse time migration (LSRTM) for viscoelastic media ([Formula: see text]-LSRTM), to compensate for the attenuation loss for P- and S-images. We use the first-order particle velocity, stress, and memory variable equations, with explicit [Formula: see text] in the formulations, based on the generalized standard linear solid, as the forward-modeling operator. The linearized two-way viscoelastic modeling operator is obtained with modulus perturbations introduced for the relaxed P- and S-moduli. The viscoelastic adjoint operator and the P- and S-imaging conditions for modulus perturbations are derived using the adjoint-state method and an augmented Lagrangian functional. [Formula: see text]-LSRTM solves the viscoelastic linearized modeling operator for generating synthetic data, and the adjoint operator is used for back propagating the data residual. With the correct background velocity model, and with the inclusion of [Formula: see text] in the modeling and imaging, [Formula: see text]-LSRTM is capable of iteratively updating the P- and S-modulus perturbations, and compensating the attenuation loss caused by [Formula: see text] and [Formula: see text], in the direction of minimizing the data residual between the observed and predicted data. Compared with elastic LSRTM results, the P- and S-modulus perturbation images from [Formula: see text]-LSRTM have stronger (closer to the true modulus perturbation), and more continuous, amplitudes for the structures in and beneath low-[Formula: see text] zones. The residuals in the image space obtained using the correctly parameterized [Formula: see text]-LSRTM are much smaller than those obtained using the incorrectly parameterized elastic LSRTM. However, the data residuals from [Formula: see text]-LSRTM and elastic LSRTM are similar because elastic Born modeling with a weak reflector in the image produces similar reflection amplitudes with viscoelastic Born modeling with a strong reflector.
Rapid isolation and expansion of skin-derived precursor cells from human primary fibroblast cultures
Authors: Budel Leithe , Djabali Karima
Published: November 2017

Skin-derived precursor (SKP) cells have self-renewal and multipotent abilities and are found in the dermis. SKP cells have been isolated previously from pre-established dermal fibroblast cultures. In these procedures, long-term culture and low yield remain the crucial aspects requiring improvement. In this study, we exposed pre-established dermal fibroblasts to 30-min acid stress prior to isolating SKP cells (termed pH-SKP) and compared the yield to the previously published trypsin- and no-stress methods. Spheroid formation was confirmed and analyzed at days 3, 5 and 7. Stemness was investigated by immunohistochemistry for the stem cell markers Nestin, CD9, vimentin and NG2. Multipotency was investigated by differentiation into adipocytes, smooth muscle cells and fibroblasts. The pH-SKP spheroid yield at day 5 was four- and threefold higher than those obtained using trypsin- and no-stress methods, respectively. The expression of stem cell markers Nestin, CD9, vimentin and NG2 were significantly expressed in pH-SKPs compared to the fibroblast origin. Successful pH-SKP spheroid formation and differentiation were achieved and validated in 11 distinct human primary fibroblast lines. These results demonstrate that acute acidic stress treatment of dermal fibroblast cultures greatly improves SKP isolation, growth, yield and multipotency compared to previous methods.
Selector genes display tumor cooperation and inhibition inDrosophilaepithelium in a developmental context-dependent manner
Authors: Gupta Ram Prakash , Bajpai Anjali , Sinha Pradip
Published: November 2017

During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey), and the segment selector, Ultrabithorax (Ubx), readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth), and/or the Zinc-finger protein, Teashirt (Tsh). In non-Hth/Tsh-expressing domains of these imaginal discs, however, gain of Ey in lgl− somatic clones induces neoplastic transformation in the distal wing disc and haltere, but not in the eye imaginal disc. Likewise, gain of Ubx in lgl− somatic clones induces transformation in the eye imaginal disc but not in its endogenous domain, namely, the haltere imaginal disc. Our results reveal that selector genes could behave as tumor drivers or inhibitors depending on the tissue contexts of their gains.
Tropical Drosophila ananassae of wet-dry seasons show cross resistance to heat, drought and starvation
Authors: Lambhod Chanderkala , Pathak Ankita , Munjal Ashok K. , Parkash Ravi
Published: November 2017

Plastic responses to multiple environmental stressors in wet or dry seasonal populations of tropical Drosophila species have received less attention. We tested plastic effects of heat hardening, acclimation to drought or starvation, and changes in trehalose, proline and body lipids in Drosophila ananassae flies reared under wet or dry season-specific conditions. Wet season flies revealed significant increase in heat knockdown, starvation resistance and body lipids after heat hardening. However, accumulation of proline was observed only after desiccation acclimation of dry season flies while wet season flies elicited no proline but trehalose only. Therefore, drought-induced proline can be a marker metabolite for dry-season flies. Further, partial utilization of proline and trehalose under heat hardening reflects their possible thermoprotective effects. Heat hardening elicited cross-protection to starvation stress. Stressor-specific accumulation or utilization as well as rates of metabolic change for each energy metabolite were significantly higher in wet-season flies than dry-season flies. Energy metabolite changes due to inter-related stressors (heat versus desiccation or starvation) resulted in possible maintenance of energetic homeostasis in wet- or dry-season flies. Thus, low or high humidity-induced plastic changes in energy metabolites can provide cross-protection to seasonally varying climatic stressors.
Leucine-rich repeat-containing 8B protein is associated with the endoplasmic reticulum Ca2+ leak in HEK293 cells
Authors: Ghosh Arijita , Khandelwal Nitin , Kumar Arvind , Bera Amal Kanti
Published: November 2017

Leucine-rich repeat-containing 8 (LRRC8) proteins have been proposed to evolutionarily originate from the combination of the channel protein pannexin, and a leucine-rich repeat (LRR) domain. Five paralogs of LRRC8, namely LRRC8A, LRRC8B, LRRC8C, LRRC8D and LRRC8E have been reported. LRRC8A has been shown to be instrumental in cell swelling. Here, we identify LRRC8B as a key player in the cellular Ca2+ signaling network. Overexpression of human LRRC8B in HEK293 cells reduced the Ca2+ level in the endoplasmic reticulum (ER). LRRC8B-overexpressing cells exhibited a lesser release of Ca2+ from the ER in response to ATP, carbachol and intracellular administration of inositol (1,4,5)-trisphosphate (IP3). LRRC8B-knockdown cells showed a slower depletion of the ER Ca2+ stores when sarco-endoplasmic reticulum Ca2+-ATPase was blocked with thapsigargin (TG), while overexpression of LRRC8B had the opposite effect. LRRC8B-overexpressing cells exhibited a higher level of store-operated Ca2+ entry following store-depletion by TG. Collectively, LRRC8B participates in intracellular Ca2+ homeostasis by acting as a leak channel in the ER. This study gives a fundamental understanding of the role of a novel protein in the elemental cellular process of ER Ca2+ leak and expands the known roles for LRRC8 proteins.

This article has an associated First Person interview with the first author of the paper.
Self-education is one of the forms of improving the professional skill of the teacher
Authors: Темняков Дмитрий , Temnyakov Dmitriy
Published: November 2017

The article reveals the specifics and problems of the qualification requirements for the teacher of a higher education institution within the framework of self-education. Features of self-education of teachers of higher educational institutions at the present stage of reforming the educational system in the Russian Federation are considered. The article analyzes traditionally developed approaches to self-education, advantages and disadvantages of forms of enhancing professional skills through self-education. Recommendations for improving the process of self-education of a teacher of higher education are presented.
Know Your Rights
Authors: Bromley Matt
Published: November 2017

SecEd's supply teaching series continues. This week, we offer advice on your rights, entitlements and responsibilities as a supply teacher. We also offer safeguarding advice for supply staff, including practical advice about fulfilling your child protection duties and responsibilities
Abortion Knowledge and Experiences Among U.S. Servicewomen: A Qualitative Study
Authors: Grindlay Kate , Seymour Jane W. , Fix Laura , Reiger Sarah , Keefe‐Oates Brianna , Grossman Daniel
Published: November 2017

CONTEXT

U.S. servicewomen have a higher rate of unintended pregnancy than civilian women, yet the military does not provide or cover abortion, except in limited circumstances. Servicewomen's experiences with abortion care have received little research attention.

METHODS

Twenty‐one in‐depth interviews with servicewomen who had had an abortion during active‐duty service in the prior two years were conducted between January 2015 and July 2016. Women reported on their experiences accessing abortion, as well as their knowledge and opinions of the military's abortion policy. Data were analyzed thematically using inductive and deductive codes.

RESULTS

In regard to their pregnancy and abortion experiences, servicewomen cited concerns about confidentiality, stigma and negative effects on their career, which prevented half of participants from seeking care from the military. Of those who visited a military treatment facility during pregnancy, some reported feeling upset or abandoned by the lack of options counseling and referral. Women reported that the military's abortion policy had negative health and emotional consequences for servicewomen, and negative financial and logistical consequences for both servicewomen and the military. Most did not have accurate knowledge of the abortion policy. Upon learning the law, the majority believed that the military should provide and cover abortion; yet, servicewomen also expressed apprehension about the military's involvement in abortion care, because of concerns about privacy and negative effects on women's careers.

CONCLUSIONS

Policy recommendations to better meet the needs of servicewomen include wider dissemination of the military's abortion policy, establishing abortion referral and support guidelines, and improving confidentiality in military health services.
Facilitating Design to Engage in Social Behaviour Change for Environmental Benefit
Authors: Sharma Satyakam , Siu Kin Wai Michael
Published: November 2017

Social interventions emerging from the field of social psychology and sociology have been quite effective in fostering sustainable behaviour and have thus inspired the interest of designers and creative idealists in exploring social ways of changing behaviour for environmental benefit. Although the significance of the social dimension to behaviour change is well recognized, it lacks in-depth understanding and support, which can enable designers to engage in the process of social behaviour change to meet sustainability objectives. Based on a study of four effectively implemented cases of gamified behaviour change programmes (GBCPs), this article presents insights into the mechanics of social behaviour change, particularly the process through which these (social) game-based interventions prepare, motivate, transform and incubate behaviour under the influence of a social setting. The study provides a breakdown of the entire process of change into its individual elements (phenomena, activities, processes, etc.) and how these elements collectively constitute an influential social environment that motivates participants to adopt and perform desired sustainable actions in a playful way. This understanding of the mechanics of the GBCPs provides some essential touch points for designers and social entrepreneurs to engage in social behaviour change to meet sustainability objectives.
Teaching Biology Practical Lessons in Secondary Schools: A Case Study of Five Mzilikazi District Secondary Schools in Bulawayo Metropolitan Province, Zimbabwe
Authors: Mwangu Edson C. , Sibanda Lwazi
Published: November 2017

The study examined how teachers teach Biology practical lessons at Ordinary Level in Mzilikazi District Secondary Schools of Bulawayo Metropolitan Province. Qualitative approach and case study design were adopted. Data was collected using document analysis and semi-structured interviews conducted with purposively selected five Biology teachers, five Heads of Science Department from five schools, and one Science Subject Inspector. Data were thematically analysed. The study revealed that teachers used both teacher-centred and student-centred methods in teaching Biology practical lessons and various factors constrained the teaching of practical lessons. The study concluded that some Biology teachers in selected schools did not conduct practical lessons in line with the Ministry of Primary and Secondary Education expectations. The study recommends that the Ministry of Primary and Secondary Education should continue equipping teachers with knowledge and skills of teaching Biology practical lessons through workshops and other staff development programmes.
Acute Peritonitis Caused by Propionibacterium Acnes in a Peritoneal Dialysis Patient
Authors: Basic-Jukic Nikolina , Furic-Cunko Vesna , Juric Ivana , Katalinic Lea , Rukavina Ana , Kocman Monika , Knezevic Tamara
Published: November 2017

Propionibacterium acnes is a gram-positive human skin commensal that is involved in the pathogenesis of acne and prefers anaerobic growth conditions. It has been considered as a low virulence pathogen in different clinical conditions. We present the case of acute peritonitis caused by Propionibacterium acnes in a peritoneal dialysis patient.
Factors Influencing Green Roof Development in Recife, Brazil
Authors: Lemos Ana Letícia B. F. , Kauškale Linda
Published: November 2017

In Recife, Brazil, population growth and development of buildings in the Central region generated an increase of almost 70% in the last 20 years due to the large number of companies that have been allocated in the city generating an increase in the local economy and the significant population increase, creating huge heat islands. Due to this, a new technology has been implemented in the real estate market: The green roofs, a technology of sustainable coverage that allows implantation of soil and vegetation in a waterproofed layer on the constructions. The benefits of this technology include the reduction of temperature by consumption of CO2, a good option for storing rainwater for nonpotable purposes and the possibility of growing organic vegetable gardens for own consumption or sale, generating a new form of income. The aim of the research is to evaluate the factors that interfere with the introduction of sustainable coverage technology of green roofs in the present siting of the city. In this article, the factors that interfere with the implementation of green roof technology in the present siting of the city will be evaluated, focusing on the analysis of internal and external influencing factor. Comparison, historical, statistical data analysis, induction, logical access methods and external and internal influencing factor analysis were used in the research besides the practical development of arguments and graphical representation of research results.