bluuebunny/crossref_metadata_2025 huggingface dataset:
Competition alters seasonal resource selection and promotes use of invasive shrubs by an imperiled native cottontail
Authors: Cheeseman Amanda E. , Ryan Sadie J. , Whipps Christopher M. , Cohen Jonathan B.
Published: October 2018

Many ecosystems face multiple invaders, and interactions among invasive and native species may complicate conservation efforts for imperiled species. Examination of fine‐scale resource selection can be used to detect patterns in habitat selection resulting from species interactions and assess the value of specific resources, including invasive plants, to wildlife. We used animal location data with mixed‐effects resource selection models to examine seasonal competitive interactions and species‐specific selection for forage and cover resources by an imperiled native lagomorph, the New England cottontail Sylvilagus transitionalis and its nonnative competitor, the eastern cottontail S. floridanus in the eastern Hudson Valley, NY. We found evidence that resource selection by New England cottontails depended on the relative prevalence of eastern cottontails to New England cottontails. Where eastern cottontails were less prevalent New England cottontail selected for resources characteristic of early successional shrublands. Where eastern cottontails were more prevalent, New England cottontails selected for resources characteristic of later successional shrublands. New England cottontail use of certain invasive shrubs depended on the prevalence of eastern cottontails relative to New England cottontails, suggesting response to invasive plants is confounded by interactions with a nonnative competitor. Our results further emphasize the need for conservation efforts to consider invasive management within the ecosystem context. We demonstrate the utility of resource selection studies to assist in this regard by exploring competitive interactions in the absence of removal studies, while simultaneously assessing the impact of habitat components such as invasive vegetation on species of conservation concern. Synthesis and applications Resource selection studies can be directly applied to inform ongoing species conservation where multiple invaders are present or where species interactions influence resource selection. Fine‐scale assessments of resource selection, similar to those presented here, can be used to selectively manage habitat to benefit desired species within the ecosystem context.
Integrating multiple genetic detection methods to estimate population density of social and territorial carnivores
Authors: Murphy Sean M. , Augustine Ben C. , Adams Jennifer R. , Waits Lisette P. , Cox John J.
Published: October 2018

Spatial capture–recapture models can produce unbiased estimates of population density, but sparse detection data often plague studies of social and territorial carnivores. Integrating multiple types of detection data can improve estimation of the spatial scale parameter (σ), activity center locations, and density. Noninvasive genetic sampling is effective for detecting carnivores, but social structure and territoriality could cause differential detectability among population cohorts for different detection methods. Using three observation models, we evaluated the integration of genetic detection data from noninvasive hair and scat sampling of the social and territorial coyote (Canis latrans). Although precision of estimated density was improved, particularly if sharing σ between detection methods was appropriate, posterior probabilities of σ and posterior predictive checks supported different σ for hair and scat observation models. The resulting spatial capture–recapture model described a scenario in which scat‐detected individuals lived on and around scat transects, whereas hair‐detected individuals had larger σ and mostly lived off of the detector array, leaving hair but not scat samples. A more supported interpretation is that individual heterogeneity in baseline detection rates (λ0) was inconsistent between detection methods, such that each method disproportionately detected different population cohorts. These findings can be attributed to the sociality and territoriality of canids: Residents may be more likely to strategically mark territories via defecation (scat deposition), and transients may be more likely to exhibit rubbing (hair deposition) to increase mate attraction. Although this suggests that reliance on only one detection method may underestimate population density, integrating multiple sources of genetic detection data may be problematic for social and territorial carnivores. These data are typically sparse, modeling individual heterogeneity in λ0and/or σ with sparse data is difficult, and positive bias can be introduced in density estimates if individual heterogeneity in detection parameters that is inconsistent between detection methods is not appropriately modeled. Previous suggestions for assessing parameter consistency of σ between detection methods using Bayesian model selection algorithms could be confounded by individual heterogeneity in λ0in noninvasive detection data. We demonstrate the usefulness of augmenting those approaches with calibrated posterior predictive checks and plots of the posterior density of activity centers for key individuals.
Genetic effects of anthropogenic habitat fragmentation on remnant animal and plant populations: a meta‐analysis
Authors: Schlaepfer Daniel R. , Braschler Brigitte , Rusterholz Hans‐Peter , Baur Bruno
Published: October 2018

Habitat loss and fragmentation are among the biggest threats to biodiversity. Anthropogenic habitat fragmentation leads to small and isolated remnant plant and animal populations. The combination of increased random genetic drift, inbreeding, and reduced gene flow may substantially reduce genetic variation of remnant populations. However, the magnitude of these responses may depend on several poorly understood factors including organism group, habitat type of both the fragment and the surrounding matrix, life‐history traits, and time since fragmentation. We compiled data for 83 plant and 52 animal species and conducted a meta‐analysis following best practices to evaluate how these factors mediate the effects of anthropogenic habitat fragmentation. We calculated 206 effect sizes as correlations between one of four measures of population‐level genetic diversity and fragment area. All analyses were repeated using models of increasing complexity (traditional random‐effects models, multilevel models accounting for non‐independent data, and multilevel models additionally correcting for phylogenetic relatedness). We confirmed that anthropogenic habitat fragmentation has overall negative effects on genetic diversity of organisms. Our meta‐analysis shows, however, that plant species responded in general stronger to fragmentation than animal species and that the largest negative impacts of fragmentation occurred in tropical and temperate forest fragments, surrounded by a non‐forest matrix. In contrast, we found only weak responses in non‐forest fragments. Genetic diversity measured as mean number of alleles (A) showed the strongest response to fragmentation. Expected heterozygosity (He) and percentage of polymorphic loci (PLP) showed similar but weaker responses. In contrast, our meta‐analysis indicated that inbreeding (Fis) was not measurably affected by anthropogenic habitat fragmentation. Additionally, our models revealed that effects on genetic diversity became stronger with age of fragments: We found significant negative responses for fragments older than 50 yr but not for those more recently isolated. Our meta‐analyses also showed that currently animals are underrepresented in the literature on genetic effects of anthropogenic fragmentation, as are certain geographical regions and habitat types. We expect that future field studies using state‐of‐the‐art approaches will provide further evidence of negative genetic effects, which may reinforce the here reported patterns, even for groups not yet studied.
Tier 3 specialist weight management service and pre‐bariatric multicomponent weight management programmes for adults with obesity living in the UK: A systematic review
Authors: Alkharaiji Mohammed , Anyanwagu Uchenna , Donnelly Richard , Idris Iskandar
Published: October 2018

Background

NHS England has recommended a multidisciplinary weight management services (MWMS—Tier 3 services) for patients requiring specialized management of obesity, including bariatric surgery, but clinical and measurable health‐related outcomes from these services remains fragmented. We therefore undertook a systematic review to explore the evidence base of effect on body weight loss and comorbidities outcomes of Tier 3 or UK pre‐bariatric MWMPs.

Methods

AMED, CINAHL, EMBASE, HMIC, MEDLINE, PsycINFO, PubMed, HDAS search and Google Scholar were searched from January 2000 to September 2017 in a free‐text fashion and crossed‐references of included studies to identify potential illegibility. Inclusion criteria were as follows: (a) published Tier 3 original study abstracts/articles; (b) intervention studies with before and after data; (c) studies that included any sort of MWMPs conducted on British residents with obesity; and (d) studies included T2DM measurements in a MWMPs.

Results

In total, 19 studies met the inclusion criteria. The total number of participants analysed was N = 11,735. Baseline accumulative average BMI was calculated at 42.54 kg/m2, weight 117.88 kg and waist circumference 126.9 cm. And at 6 months, 40.73 kg/m2, 112.17 kg and 120.3 cm, respectively. Secondary outcome variables were as improved with reduction in HbA1c, fasting blood sugars, insulin usage and blood pressure. Physical activity increased at 3 months then declined after 6 months with no significant changes in cholesterol levels.

Conclusion

Tier 3 and MWMPs have a short to mid‐ranged positive effect on obese patients (BMI ≥30 kg/m2) living in the UK regarding accumulated reduction in weight, glycaemic control, blood pressure and with subtle improvements in physical activity.
Skin‐homing CD8+ T cells preferentially express GPI‐anchored peptidase inhibitor 16, an inhibitor of cathepsin K
Authors: Lupsa Nikolett , Érsek Barbara , Horváth Andor , Bencsik András , Lajkó Eszter , Silló Pálma , Oszvald Ádám , Wiener Zoltán , Reményi Péter , Mikala Gábor , Masszi Tamás , Buzás Edit I , Pós Zoltán
Published: October 2018

This study sought to identify novel CD8+ T cell homing markers by studying acute graft versus host disease (aGvHD), typically involving increased T cell homing to the skin and gut. FACS‐sorted skin‐homing (CD8β+/CLA+), gut‐homing (CD8β+/integrinβ7+), and reference (CD8β+/CLA–/integrinβ7–) T cells were compared in patients affected by cutaneous and/or gastrointestinal aGVHD. Microarray analysis, qPCR, and flow cytometry revealed increased expression of peptidase inhibitor 16 (PI16) in skin‐homing CD8+ T cells. Robust association of PI16 with skin homing was confirmed in all types of aGvHD and in healthy controls, too. PI16 was not observed on CLA+ leukocytes other than T cells. Induction of PI16 expression on skin‐homing T cells occurred independently of vitamin D3. Among skin‐homing T cells, PI16 expression was most pronounced in memory‐like CD45RO+/CD127+/CD25+/CD69−/granzyme B− cells. PI16 was confined to the plasma membrane, was GPI‐anchored, and was lost upon restimulation of memory CD8+ T cells. Loss of PI16 occurred by downregulation of PI16 transcription, and not by Phospholipase C (PLC)‐ or Angiotensin‐converting enzyme (ACE)‐mediated shedding, or by protein recycling. Inhibitor screening and pull‐down experiments confirmed that PI16 inhibits cathepsin K, but may not bind to other skin proteases. These data link PI16 to skin‐homing CD8+ T cells, and raise the possibility that PI16 may regulate cutaneous cathepsin K.
Cancer‐related chronic pain: Investigation of the novel analgesic drug candidate cebranopadol in a randomized, double‐blind, noninferiority trial
Authors: Eerdekens Marie‐Henriette , Kapanadze Sofia , Koch Erika Dietlind , Kralidis Georg , Volkers Gisela , Ahmedzai Sam Hjelmeland , Meissner Winfried
Published: October 2018

Background

Cancer‐related pain is a growing health problem given the increasing life expectancy of cancer patients. Opioids are commonly used to treat cancer‐related pain, but carry the risk of severe side effects, limiting their use. Cebranopadol is a first‐in‐class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. This trial examined the analgesic efficacy of cebranopadol compared with morphine prolonged release (PR) in patients with moderate‐to‐severe cancer‐related pain.

Methods

This double‐blind, parallel‐group, multiple‐dose trial was designed as noninferiority trial for efficacy of cebranopadol versus morphine PR. Planned with 524 patients, finally 126 patients were treated for up to 7 weeks (low accrual). The primary efficacy endpoint was the average amount of daily rescue medication intake (morphine immediate release) over the last 2 weeks of treatment.

Results

For the primary endpoint, noninferiority of cebranopadol with and superiority over morphine PR were demonstrated (Full Analysis Set: ∆[95%CI] = −7.48 mg [−12.05, −2.92]; Per Protocol Set: ∆[95%CI] = −4.67 mg [−9.25, −0.10]). The vast majority of patients (≥75%, either treatment) had clinically relevant pain reduction, and noninferiority on this secondary endpoint was not shown. Mostly used doses were ≤800 μg cebranopadol or ≤120 mg morphine PR daily. A total of 83.1% of patients on cebranopadol and 82.0% on morphine PR experienced treatment‐emergent adverse events.

Conclusions

Cebranopadol was effective, safe and well tolerated in the dose range tested (200–1,000 μg) in patients suffering from chronic moderate‐to‐severe cancer‐related pain and was superior to morphine PR on the primary endpoint.

Significance

Cebranopadol presents a new approach to treat cancer pain. The drug candidate was easy to titrate, safe and well tolerated, and as effective as morphine PR in patients suffering from chronic moderate‐to‐severe cancer‐related pain
Dielectrophoretic characterization and separation of monocytes and macrophages using 3D carbon‐electrodes
Authors: Elitas Meltem , Yildizhan Yagmur , Islam Monsur , Martinez‐Duarte Rodrigo , Ozkazanc Didem
Published: October 2018

Monocyte heterogeneity and its prevalence are revealed as indicator of several human diseases ranking from cardiovascular diseases to rheumatoid arthritis, chronic kidney diseases, autoimmune multiple sclerosis, and stroke injuries. When monocytes and macrophages are characterized and isolated with preserved genetic, phenotypic and functional properties, they can be used as label‐free biomarkers for precise diagnostics and treatment of various diseases. Here, the dielectrophoretic responses of the monocytes and macrophages were examined. We present 3D carbon‐electrode dielectrophoresis (carbon‐DEP) as a separation tool for U937 monocytes and U937 monocyte‐differentiated macrophages. The carbon‐electrodes advanced the usability and throughput of DEP separation, presented wider electrochemical stability. Using the 3D carbon‐DEP chip, we first identified the selective positive and negative DEP responses and specific crossover frequencies of monocytes and macrophages as their signatures for separation. The crossover frequency of monocytes and macrophages was 17 and 30 kHz, respectively. Next, we separated monocyte and macrophage subpopulations using their specific dielectrophoretic responses. Afterward, we used a fluorescence‐activated cell sorter to confirm our results. Finally, we enriched 70% of monocyte cells from the mixed cell population, in other words, concentration of monocyte cells to macrophage cells was five times increased, using the 30‐kHz, 10‐Vpp electric field and 1 μL/min flow rate.
Electrohydrodynamic transport of non‐symmetric electrolyte through porous wall of a microtube
Authors: Bhattacharjee Saikat , Roy Debashis , Pal Anish , De Sirshendu
Published: October 2018

Transport of salt through the wall of porous microtube is relevant in various physiological microcirculation systems. Transport phenomena based modeling of such system is undertaken in the present study considering a combined driving force consisting of pressure gradient and external electric field. Transport of salt is modeled in two domains, in the flow conduit and in the pores of porous wall of the microtube. The solute transport in the microtube is presented by convective‐diffusive mass balance and it is solved using integral method under the framework of boundary layer analysis. The wall of the microtube is considered to be consisting of series of straight parallel cylindrical pores with charged inner surface. The solute transport through the pores is considered to be composed of diffusive, convective and electric potential gradient governed by Nernst‐Planck equation. Transport in the microtube and pores is coupled through the osmotic pressure model for the solvent and Donnan equilibrium distribution for the solute. The simulated results agree remarkably well with the experimental data conducted by in‐house experimental set up. The charge density of the porous wall is estimated through the minimization of errors involved between the experimental and simulated data for different operating conditions.
Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2016–2018)
Authors: Breadmore Michael C , Grochocki Wojciech , Kalsoom Umme , Alves Mónica N. , Phung Sui Ching , Rokh Masoomeh Tehrani , Cabot Joan M. , Ghiasvand Alireza , Li Feng , Shallan Aliaa I. , Keyon Aemi S. Abdul , Alhusban Ala A. , See Hong Heng , Wuethrich Alain , Dawod Mohamed , Quirino Joselito P
Published: October 2018

One of the most cited limitations of capillary and microchip electrophoresis is the poor sensitivity. This review continues to update this series of biannual reviews, first published in Electrophoresis in 2007, on developments in the field of online/in‐line concentration methods in capillaries and microchips, covering the period July 2016–June 2018. It includes developments in the field of stacking, covering all methods from field‐amplified sample stacking and large‐volume sample stacking, through to isotachophoresis, dynamic pH junction, and sweeping. Attention is also given to online or in‐line extraction methods that have been used for electrophoresis.
Effect of dietary inclusions of bitter kola seed on geotactic behavior and oxidative stress markers in Drosophila melanogaster
Authors: Oboh Ganiyu , Ogunsuyi Opeyemi B. , Ojelade Mopelola T. , Akomolafe Seun F.
Published: October 2018

This study evaluated the effect of dietary inclusions of Garcinia kola (GK) seed on geotactic behavior and some oxidative stress markers in wildߚtype fruit flies (Drosophila melanogaster). Flies were raised on diet supplement with GK seed for 5 days. The negative geotactic behavior of flies which was used to evaluate their locomotor performance was thereafter evaluated. The flies were subsequently homogenized and the reactive oxygen species (ROS) level, acetylcholinesterase (AChE), catalase and glutathioneߚSߚtransferase (GST) activities, as well as nitric oxide (NO) and total thiol contents were assayed. The phytochemical constituents of GK seed were also determined. It was observed that higher dietary inclusions of GK seed reduced the survival rate of D. melanogaster more significantly compared to control flies. Also, higher dietary inclusions of GK seed significantly reduced locomotor performance and AChE activity, while the ROS level was increased compared to the control. Activities of GST and catalase were significantly increased in flies fed diet supplemented with higher GK seed inclusions but their NO content was significantly reduced compared to control. Phytochemical analysis of GK seed revealed abundance of saponin > glycosides > alkaloids > phenols > flavonoids. These results have shown that dietary inclusion of GK seed at higher concentrations reduced survival rate of D. melanogaster and impaired cholinergic system, with elevated activities of some antioxidant enzymes under acute exposure. These observations could be associated with bioactivities of predominant phytochemicals in GK seed such as saponin and glycosides which have been reportedly toxic at high concentration. Therefore, this study suggests that high consumption of GK seed could induce some toxicological effects and moderate consumption is hence recommended.
The status of nutritional knowledge, attitude and practices associated with complementary feeding in a post‐conflict development phase setting: The case of Acholi sub‐region of Uganda
Authors: Nassanga Prossy , Okello‐Uma Ipolto , Ongeng Duncan
Published: October 2018

Inappropriate complementary feeding is an important challenge to proper child nutrition in post‐conflict rural areas in many sub‐Saharan African countries. While in protected areas during conflict situation and soon after during recovery, communities normally receive nutrition education as part of capacity building to improve knowledge, attitude, and practices to enable them manage maternal and child nutrition issues during the post‐conflict development phase. It is largely unknown whether capacity in nutrition provided is maintained and adequately applied in the post‐conflict development situation. Using Acholi sub‐region of Uganda, an area that experienced violent armed conflict for 20 years (mid‐80s–early 2000), as a case study, we examined the status of nutritional knowledge, attitude, and practices associated with complementary feeding among caregivers of 6‐ to 23‐month‐old children in a post‐conflict development phase following return to normalcy nearly 10 years post‐conflict emergency situation. The results showed that a high proportion of caregivers had good knowledge (88%) and attitude (90.1%) toward complementary feeding. However, only a half (50%) of them practiced correct nutrition behavior. Education status of the household head and sex of the child significantly predicted caregiver knowledge on complementary feeding (p ≤ 0.05). Education status of the household head also predicted caregiver attitude toward complementary feeding (p ≤ 0.05). Poverty, food insecurity, and maternal ill health were the major factors that hindered caregivers from practicing good complementary feeding behavior. These results demonstrate that nutrition education on complementary feeding provided to the community during conflict emergency and recovery situation is largely retained in terms of knowledge and attitude but poorly translated into good child feeding practices due to poverty, food insecurity, and maternal ill health. Maternal health, food security, and poverty reduction should be prioritized if adequate complementary feeding is to be achieved among conflict‐affected communities in the post‐conflict development phase.
Orostachys japonicus induce p53‐dependent cell cycle arrest through the MAPK signaling pathway in OVCAR‐3 human ovarian cancer cells
Authors: Lee Kyung‐Sun , Kim Suhng‐Wook , Lee Hyeong‐Seon
Published: October 2018

Orostachys japonicus (O. japonicus) is utilized as a traditional medicine for patients with various diseases. This study investigated the effect of the ethyl acetate fraction from O. japonicus extract (OJE) on the growth inhibition of OVCAR‐3 human ovarian cancer cells demonstrated to inhibit cell growth and arrest the cell cycle in OVCAR‐3 cells by blocking the sub‐G1 phase and decreasing cyclin E1/CDK2 expression. Cell cycle arrest was connected to the increased expression of the cell cycle regulating factors p53 and p21. Apoptosis was initiated through the intrinsic pathway by up‐regulating the expression of the Bcl‐2/Bax ratio and down‐regulating the expression of pro‐caspase‐3. Furthermore, OJE treatment elicited p‐p38 activation and p‐ERK1/2 inhibition. In conclusion, our results demonstrated that OJE reduced the growth of OVCAR‐3 human ovarian cancer cells mediated by arrest of the cell cycle and regulation of MAPK signaling pathways.
Resveratrol: A miraculous natural compound for diseases treatment
Authors: Koushki Mehdi , Amiri‐Dashatan Nasrin , Ahmadi Nayebali , Abbaszadeh Hojjat‐Allah , Rezaei‐Tavirani Mostafa
Published: October 2018

Resveratrol (3, 5, 4′‐trihydroxystilbene) is a nonflavonoid polyphenol that naturally occurs as phytoalexin. It is produced by plant sources such as grapes, apples, blueberries, plums, and peanut. This compound has critical roles in human health and is well known for its diverse biological activities such as antioxidant and anti‐inflammatory properties. Nowadays, due to rising incidence of different diseases such as cancer and diabetes, efforts to find novel and effective disease‐protective agents have led to the identification of plant‐derived compounds such as resveratrol. Furthermore, several in vitro and in vivo studies have revealed the effectiveness of resveratrol in various diseases such as diabetes mellitus, cardiovascular disease, metabolic syndrome, obesity, inflammatory, neurodegenerative, and age‐related diseases. This review presents an overview of currently available studies on preventive properties and essential molecular mechanisms involved in various diseases.
The 70:20:10 framework and the transfer of learning
Authors: Johnson Samantha J. , Blackman Deborah A. , Buick Fiona
Published: October 2018

The capacity of an organization to innovate, change, and be effective depends on the skills and abilities of employees, highlighting the importance of developing individual capabilities. The 70:20:10 framework is used by practitioners to guide them when developing effective learning and development programs. Although the framework has been adopted globally in both private and public sectors, its effectiveness has not been assessed in relation to the transfer of learning. Using qualitative data from the Australian public sector, this study explores how the framework is being implemented and whether it facilitates the transfer of learning to build middle management capability. Results showed that despite middle managers' awareness of, and willingness to take part in, ongoing skill development, attempts to develop capability through learning transfer by implementing the 70:20:10 framework were not achieving the desired outcomes. The research suggests that learning transfer and managerial capability development was hindered through four misconceptions regarding the framework's implementation. These are: an overconfident assumption that unstructured experiential learning automatically results in capability development; a narrow interpretation of social learning; the expectation that managerial behavior would automatically change following formal training and development activities without the need to actively support the process; and a lack of recognition of the requirement of a planned and integrated relationship of all three aspects of the framework. We suggest future research seeks to explicate the role of social learning in supporting the efficacy of both formal and experiential learning.
Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status
Authors: Hesari AmirReza , Azizian Mitra , Sheikhi Alireza , Nesaei Abolfazl , Sanaei Shahin , Mahinparvar Nazanin , Derakhshani Maryam , Hedayt Pegah , Ghasemi Faezeh , Mirzaei Hamed
Published: October 2018

Esophageal cancer is a common malignant tumor with an increasing trend during the past three decades. Currently, esophagectomy, often in combination with neoadjuvant chemo‐ and radiotherapy, is the cornerstone of curative treatment for esophageal cancer. However, esophagostomy is related to significant risks of perioperative mortality and morbidity, as well as lengthy recovery. Moreover, the adjuvant therapies including chemotherapy and radiotherapy are associated with numerous side effects, limiting compliance and outcome. The dietary agent curcumin has been extensively studied over the past few decades and is known to have many biological activities especially in regard to the prevention and potential treatment of cancer. This review summarizes the chemo‐preventive and chemotherapeutic potential of curcumin in esophageal cancer in both preclinical and clinical settings.
Facilitating the emergence of convergent intraverbals in children with autism
Authors: DeSouza Andresa A. , Fisher Wayne W. , Rodriguez Nicole M.
Published: October 2018

Convergent intraverbals represent a specific type of intraverbal in which multiple components of one speaker's verbal behavior control a specific verbal response from another speaker (e.g., Speaker 1: What wooly, horned animal lives in the high country? Speaker 2: Bighorn sheep). To foster the development of advanced language, Sundberg and Sundberg (2011) proposed prerequisite skills that may engender the emergence of novel, convergent intraverbals. We used a multiple‐probe design with both nonconcurrent (across participants) and concurrent (across stimulus sets) components to evaluate the effects of training these prerequisite skills on the emergence of convergent intraverbals with four children with autism. Participants showed the emergence of convergent intraverbals at mastery levels after they displayed mastery performance on all of the prerequisite skills identified by Sundberg and Sundberg, lending support to their characterization as prerequisites. We discuss these findings in terms of operant mechanisms that may facilitate the development of generative language.
Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa‐miR‐2053 and lncRNA‐RP1‐86D1.3 axis expression in malignant pleural mesothelioma
Authors: Matboli Marwa , Shafei Ayman E. , Ali Mahmoud A. , Gaber Ahmed I. , Galal Ahmed , Tarek Osama , Marei Mohamed , Khairy Eman , El‐Khazragy Nashwa , Anber Nahla , Abdel‐Rahman Omar
Published: October 2018

Aim and Background

Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA‐based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM.

Methods

We have selected an MPM‐specific RNA‐based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A (
ARSA) gene expression with their epigenetic regulators microRNA (
miR‐2053) and long noncoding RNA (
lncRNA‐RP1‐86D1.3). Then, quantitative real‐time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.

Results

The expression of serum DRAM1 messenger RNA (mRNA),
ARSA mRNA,
hsa‐miR‐2053 and
lncRNA‐RP1‐86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA‐based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan‐Meier analysis showed that
hsa‐miR‐2053 is an independent prognostic factor of MPM.

Conclusion

Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.
The long noncoding RNA MALAT‐1 functions as a competing endogenous RNA to regulate MSL2 expression by sponging miR‐338‐3p in myasthenia gravis
Authors: Kong Xiaotong , Wang Jianjian , Cao Yuze , Zhang Huixue , Lu Xiaoyu , Wang Yu , Bo Chunrui , Wang Tianfeng , Li Shuang , Tian Kuo , Liu Zhaojun , Wang Lihua
Published: October 2018

Myasthenia gravis (MG) is a cell‐dependent autoimmune disease commonly associated with thymic pathology. Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT‐1) has been associated with gene regulation and alternative splicing. It has shown relationship with proliferation, apoptosis, migration, and invasion. In this study, we found that MALAT‐1 expression was downregulated in MG. The level of the miR‐338‐3p was increased in peripheral blood mononuclear cells from MG patients compared with those from control subjects. MALAT‐1 competed for binding to miR‐338‐3p with male‐specific lethal 2 (MSL2) in luciferase reporter assays. We confirmed the MALAT‐1‐miR‐338‐3p‐MSL2 interaction network in MG in vitro. Thus, MALAT‐1 directly induced MSL2 expression in MG by acting as a competing endogenous RNA for miR‐338‐3p, suggesting that it may serve as a therapeutic target for MG treatment.
High‐density lipoprotein functionality and breast cancer: A potential therapeutic target
Authors: Samadi Sara , Ghayour‐Mobarhan Majid , Mohammadpour Amirhooshang , Farjami Zahra , Tabadkani Mahla , Hosseinnia Mohammad , Miri Mehri , Heydari‐Majd Motahareh , Mehramiz Mehrane , Rezayi Majid , Ferns Gordon A. , Avan Amir
Published: October 2018

Breast cancer is a major cause of death globally, and particularly in developed countries. Breast cancer is influenced by cholesterol membrane content, by affecting the signaling pathways modulating cell growth, adherence, and migration. Furthermore, steroid hormones are derived from cholesterol and these play a key role in the pathogenesis of breast cancer. Although most findings have reported an inverse association between serum high‐density lipoprotein (HDL)‐cholesterol level and the risk of breast cancer, there have been some reports of the opposite, and the association therefore remains unclear. HDL is principally known for participating in reverse cholesterol transport and has an inverse relationship with the cardiovascular risk. HDL is heterogeneous, with particles varying in composition, size, and structure, which can be altered under different circumstances, such as inflammation, aging, and certain diseases. It has also been proposed that HDL functionality might have a bearing on the breast cancer. Owing to the potential role of cholesterol in cancer, its reduction using statins, and particularly as an adjuvant during chemotherapy may be useful in the anticancer treatment, and may also be related to the decline in cancer mortality. Reconstituted HDLs have the ability to release chemotherapeutic drugs inside the cell. As a consequence, this may be a novel way to improve therapeutic targeting for the breast cancer on the basis of detrimental impacts of oxidized HDL on cancer development.
miR‐221‐3p inhibits oxidized low‐density lipoprotein induced oxidative stress and apoptosis via targeting a disintegrin and metalloprotease‐22
Authors: Zhuang Xinyu , Li Ruoshui , Maimaitijiang Alimujiang , Liu Rongchen , Yan Fangying , Hu Haibo , Gao Xiufang , Shi Haiming
Published: October 2018

Oxidized low‐density lipoprotein (ox‐LDL)‐induced oxidative stress and apoptosis are considered as a critical contributor to atherosclerosis. MicroRNAs (miRNAs) have been reported versatile functions in all biological processes via directly suppressing target messenger RNA at a posttranscriptional level. Although miRNA‐221 has been implied to be involved in the regulation of atherosclerosis, the underlying mechanism remains unclear. Here, we showed that ox‐LDL treatment remarkably suppressed the expression of miR‐221‐3p in a concentration‐dependent and time‐dependent manner. Transfection of miR‐221‐3p mimic significantly reduced the foam cell formation and expression of lipid biomarkers, while transfection of the miR‐221‐3p inhibitor showed completely opposite effects. Moreover, miR‐221‐3p was also found to inhibit the process of cell apoptosis in macrophages. A disintegrin and metalloprotease‐22 (ADAM22) is predicted as a direct target of miR‐221‐3p, and silencing AMAM22 resulted in a reduced foam cell formation and cell apoptosis. Furthermore, silencing AMAM22 restored the stimulatory effect of the miR‐221‐3p inhibitor in ox‐LDL‐induced foam cell formation and apoptosis. These findings suggest that miR‐221‐3p inhibits ox‐LDL and apoptosis via directly targeting ADAM22.
miRNA‐155 and miRNA‐181a as prognostic biomarkers for pediatric acute lymphoblastic leukemia
Authors: El‐Khazragy Nashwa , Noshi Mohamed Ahmed , Abdel‐Malak Camelia , Zahran Rasha F. , Swellam Menha
Published: October 2018

Mortality rates of acute lymphoblastic leukemia (ALL) have improved over the past 20 years; however, a significant portion of deaths stems from the lack of prognostic biomarkers, which can direct therapy and overcome drug resistance. microRNA‐155a (miRNA‐155a) and miRNA‐181a are two single‐stranded miRNAs involved in the pathogenesis of many types of leukemia and lymphoma and is linked to drug resistance. We investigated their expression levels in 55 patients, 45 diagnosed with ALL and 10 as a control group. We found that miRNA‐155a and miRNA‐181a were significantly upregulated in the ALL group with both being linked to high levels of minimal residual disease and poor prognosis. miRNA‐155a cutoff value was significant in discriminating between high‐ and low‐risk ALL patients as well as between ALL patients and healthy controls, miRNA‐181a cutoff value, however, was not significant. Both markers levels were significantly downregulated after therapy. We conclude that miR‐155 is correlated with poor prognosis in ALL, whereas we couldn’t link miRNA‐181a to the prognosis in ALL. Moreover, the marked decrease in their expression after therapy could reflect their impact on disease outcome.
Long noncoding RNA XIST participates in bladder cancer by downregulating p53 via binding to TET1
Authors: Hu Bo , Shi Guowei , Li Qian , Li Wei , Zhou Hui
Published: October 2018

Long noncoding RNAs (lncRNAs) have been reported to take part in intracellular RNA regulatory networks and play important roles in a lot of pathological processes. Currently, lncRNA X‐inactive specific transcript (XIST) has been proved to regulate cell migration, proliferation, and apoptosis in a series of cancers. In this study, we explored whether XIST can affect cell proliferation, migration, and apoptosis in bladder cancer. The influences of XIST on the cell proliferation, cell cycle, and apoptosis were detected in bladder cancer cells. The effect of XIST on the migration of bladder cancer cells was examined by cell migration assay. Through RNA immunoprecipitation and chromatin immunoprecipitation assays, the binding relationship between XIST and TET1 and the regulatory mechanism of TET1 on p53 were examined. Western blot was performed to detect p53 after knockdown or overexpression of XIST. We found that knockdown of XIST suppressed cell migration and proliferation in vitro. Mechanistically, we confirmed that lncRNA XIST participates in bladder cancer by downregulating p53 via binding to TET1. In conclusion, our research revealed the potential role of XIST‐TET1‐p53 regulatory network in bladder cancer.
Dative and electron‐sharing bonding in transition metal compounds
Authors: Jerabek Paul , Schwerdtfeger Peter , Frenking Gernot
Published: October 2018

Quantum chemical calculations using density functional theory at the BP86‐D3(BJ)/def2‐TZVPP level of theory are reported for transition metal compounds [TM]‐L in high and low oxidation states involving carbene, carbyne, alkene, and alkyne ligands L. The nature of the [TM]‐L bond is analyzed with the energy decomposition analysis ‐ natural orbitals for chemical valence (EDA‐NOCV) method. The calculations reveal that transition metal compounds with ligands, that are typically classified as donor–acceptor complexes possessing dative bonds (Fischer‐type carbenes and carbynes, alkene, and alkyne complexes) or as TM compounds with electron‐sharing bonds (Schrock‐type carbenes and carbynes, metallacyclopropanes, and metallacyclopropenes), exhibit significant differences between the orbital interactions when closed‐shell or open shell fragments are used. Fischer‐type carbene complexes have much lower orbital interaction (ΔEorb) values when singlet fragments are employed compared to triplet fragments. In contrast, singlet and triplet fragments of Schrock‐type carbene complexes give similar ΔEorb values. The best description for Fischer‐type carbyne complexes is found for neutral fragments in their electronic doublet state, which engage in a mixture of dative bonding (σ donation and π backdonation) and one electron‐sharing π bond. The EDA‐NOCV calculations of Schrock‐type carbynes using open‐shell species in their quartet electronic state give similar ΔEorb values as neutral fragments in their electronic doublet state. Alkene and alkyne complexes, but also metallacyclic species, are best described with singlet fragments, but the difference between the ΔEorb values for dative bonding and electron‐sharing bonding using triplet fragments becomes much smaller for molecules that are considered as metallacycles. © 2018 Wiley Periodicals, Inc.
CHARMM force field for protonated polyethyleneimine
Authors: Beu Titus Adrian , Ailenei Andrada‐Elena , Farcaş Alexandra
Published: October 2018

We present a revised version of our previously published atomistic Chemistry at Harvard Macromolecular Mechanics (CHARMM) force field for polyethyleneimine (PEI). It is based on new residue types (with symmetric CNC backbone), whose integer charges and bonded parameters are derived from ab initio calculations on an enlarged set of model polymers. The force field is validated by extensive molecular dynamics simulations on solvated PEI chains of various lengths and protonation patterns. The profiles of the gyration radius, end‐to‐end distance, and diffusion coefficient fine‐tune our previous results, while the simulated diffusion coefficients excellently reproduce experimental findings. The developed CHARMM force field is suitable for realistic atomistic simulations of size/protonation‐dependent behavior of PEI chains, either individually or composing polyplexes, but also provides reliable all‐atom distributions for deriving coarse‐grained force fields for PEI. © 2018 Wiley Periodicals, Inc.
Design, synthesis, and biological activity of novel 2‐(pyridin‐3‐yl)ethan‐1‐one oxime ethers bearing adamantane moiety
Authors: Liu Si , Qian Ping , Wan Fu‐Xian , Shi Yan‐Hua , Jiang Lin
Published: October 2018

With the aim of discovering a lead compound for pyridine‐based fungicide bearing adamantane moiety, a series of novel O‐alkyl/benzyl‐1‐(adamantan‐1‐yl)‐2‐(pyridin‐3‐yl)ethan‐1‐one oximes were synthesized from 3‐methylpyridine, ethyl (adamantan‐1‐yl)carboxylate, and alkoxyamine or benzoxyamine hydrochloride. The in vitro antifungal activity against four pathogenic fungi was evaluated, and some compounds exhibited good antifungal activity. Compounds 3d and 3f demonstrated strong activity against Sclerotinia sclerotiorum, with EC50 values of 11.25 and 12.87 μg/mL, respectively; 3b, 3c, and 3k had notable activity against Botrytis cinerea, with EC50 values of 12.78, 12.57, and 11.97 μg/mL, respectively. For Rhizoctonia Solani, 3d and 3g showed sufficient activity with EC50 values of 9.66 and 8.90 μg/mL, respectively. In addition, 3d and 3g demonstrated moderate activity against Colletotrichum orbiculare, with EC50 values of 14.32 and 15.83 μg/mL, respectively.
Circulating myeloid‐derived suppressor cells: An independent prognostic factor in patients with breast cancer
Authors: Safarzadeh Elham , Hashemzadeh Shahryar , Duijf Pascal H.G. , Mansoori Behzad , Khaze Vahid , Mohammadi Ali , Kazemi Tohid , Yousefi Mehdi , Asadi Milad , Mohammadi Hamed , Babaie Farhad , Baradaran Behzad
Published: October 2018

Evading immune destruction is a hallmark of cancer. Myeloid‐derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3+ T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA‐DR
– CD33
+ MDSCs in peripheral blood is about 10‐fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA‐DR
– CD33
+ MDSCs and CD3
+ T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient‐derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient‐derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC.
Small interfering RNA–mediated gene suppression as a therapeutic intervention in hepatocellular carcinoma
Authors: Hajiasgharzadeh Khalil , Somi Mohammad Hossein , Shanehbandi Dariush , Mokhtarzadeh Ahad , Baradaran Behzad
Published: October 2018

Hepatocellular carcinoma (HCC) is one of the lethal and difficult‐to‐cure cancers worldwide. Owing to the late diagnosis and drug resistance of malignant hepatocytes, treatment of this cancer by conventional chemotherapy agents is challenging, and researchers are seeking new alternative treatment options to overcome therapy resistance in this neoplasm. RNA interference (RNAi) is a potent and specific approach in targeting gene expression and has emerged as a novel therapeutic tool for many diseases, including cancers. Small interfering RNA (siRNA) is a type of RNAi that is produced intracellularly from exogenous synthetic oligonucleotides and can selectively knock down target gene expression in a sequence‐specific manner. Various factors play roles in the initiation and progression of HCC and provide multiple candidate targets for siRNA intervention. In addition, due to the liver's unique architecture and availability of some hepatic siRNA delivery methods, this organ has received much more attention as a target tissue for such oligonucleotide action. Recent advances in designing nanoparticle systems for the in vivo delivery of siRNAs have markedly enhanced the potency of siRNA‐mediated gene silencing under clinical development for HCC therapy. The utility of siRNAs as anti‐HCC agents is the subject of the current review. siRNA‐based gene therapies could be one of the main feasible approaches for HCC therapy in the future.
MicroRNAs and breast cancer stem cells: Potential role in breast cancer therapy
Authors: Vahidian Fatemeh , Mohammadi Hamed , Ali‐Hasanzadeh Mohammad , Derakhshani Afshin , Mostaan Masoud , Hemmatzadeh Maryam , Baradaran Behzad
Published: October 2018

MicroRNAs (miRNAs) can control cancer and cancer stem cells (CSCs), and this topic has drawn immense attention recently. Stem cells are a tiny population of a bulk of tumor cells that have enormous potential in expansion and metastasis of the tumor. miRNA have a crucial role in the management of the function of stem cells. This role is to either promote or suppress the tumor. In this review, we investigated the function and different characteristics of CSCs and function of the miRNAs that are related to them. We also demonstrated the role and efficacy of these miRNAs in breast cancer and breast cancer stem cells (BCSC). Eventually, we revealed the metastasis, tumor formation, and their role in the apoptosis process. Also, the therapeutic potential of miRNA as an effective method for the treatment of BCSC was described. Extensive research is required to investigate the employment or suppression of these miRNAs for therapeutics approached in different cancers in the future.