bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of a nomogram for predicting catheter-related bladder discomfort in patients with end-stage renal disease after renal transplantation: a retrospective study
Authors: Liu Kao , Liu Shengli , Peng Zhiguo , Li Na , Sun Huaibin
Published: June 2024

Background

The incidence of catheter-related bladder discomfort (CRBD) is relatively high in the end-stage renal disease (ESRD) patients who underwent renal transplantation (RT). This study was designed to establish a nomogram for predicting CRBD after RT among ESRD patients.

Methods

In this retrospective study, we collected 269 ESRD patients who underwent RT between September 2019 and August 2023 in our hospital. The patients were divided into training set (n = 215) and test set (n = 54) based on a ratio of 8:2. Univariate and multivariate logistic regression analyses were utilized to identify the risk factors associated with CRBD after RT, and then a nomogram model was constructed. Receiver operating characteristic (ROC) and calibration curve were used to evaluate the predicting efficiency of the established nomogram.

Results

Multivariate logistic regression analysis showed that aberrant body mass index (BMI) (underweight: OR = 5.25; 95% CI [1.25–22.15], P = 0.024; overweight: OR = 2.75; 95% CI [1.17–6.49], P = 0.021), anuria (OR = 2.86; 95% CI [1.33–5.88]) and application of double J (DJ) stent with a diameter of >5Fr (OR = 15.88; 95% CI [6.47–39.01], P < 0.001) were independent risk factors for CRBD after RT. In contrast, sufentanil utilization (>100 µg) [OR = 0.39; 95% CI [0.17–0.88], P = 0.023] was associated with decreased incidence of CRBD. A nomogram was then established based on these parameters for predicting the occurrence of CRBD after RT. Area under the ROC curve (AUC) values and calibration curves confirmed the prediction efficiency of the nomogram.

Conclusion

A nomogram was established for predicting CRBD after RT in ESRD patients, which showed good prediction efficiency based on AUC and calibration curves.
Riccardia dimorpha sp. nov. (Hepaticophyta, Aneuraceae) from Western Nelson, New Zealand, exhibiting sexually-determined morphological dimorphism, an overlooked feature of some liverworts
Authors: Glenny David
Published: June 2024

Riccardia dimorpha is described from 24 collections made in New Zealand between1984 and 2020 from Western Nelson, Westland, and Fiordland ecological provincesin the South Island, and from Stewart Island / Rakiura. These specimens weremisidentified as R. browniae [ R. pusilla (Steph.) E .A.Br., n om. i lleg.], R . asperulataR.M.Schust., R. multicorpora E.A.Br., and R. perspicua E.A.Br., or identified only togenus. Riccardia dimorpha belongs to the Riccardia section Alcicornia Hässel and ischaracterised by having strong striations on the epidermis, a subterete thallus, amonopodial growth form, endomycorrhizae absent from the ventral epidermis, andepidermal cells are the same size as internal cells. Specimens were collected in fireinducedLeptospermum scoparium shrublands, on peat soils at lowland to montaneelevations. Riccardia dimorpha i s s exually d imorphic i n p lant s ize a nd n umber o fbranches (meristematic tip number), and male and female plants differ to the degreethat the sexuality of a plant can be determined without finding sexual branches on aplant. Such dimorphism is rarely reported in liverworts although is common in mosses.
Planetary Health Interventions and the Need for a Unified Global Informatics Tool: A Narrative Review
Authors: Balaji Jyotsna Needamangalam , Prakash Sreenidhi , Joshi Ashish , Surapaneni Krishna Mohan
Published: June 2024

Planetary Health emphasises the sustainability of natural systems for human well-being, linking human health directly with environmental health. This interdisciplinary concept has gained importance as anthropogenic activities have led to climate changes and health impacts. Despite efforts, a cohesive approach to planetary health from local to global levels remains lacking. The present review analysed 24 sources, including grey literature and published studies, identifying 40 interventions aimed at improving planetary health. The majority of research, primarily from the United States, focuses on reducing air pollution and greenhouse gas emissions. Effective strategies highlighted include promoting active transportation, improving diets, increasing physical activity, and engaging with indigenous communities to protect both environmental and human health. However, a significant gap exists in integrating these interventions through a unified informatics tool, which could enhance coordination and implementation of planetary health measures globally. The review underscores the necessity for a more integrated approach and the development of a global database to consolidate and manage planetary health interventions effectively.
Fahr’s Disease Presenting with Non-febrile Epileptic Seizures: Case Report and Systematic Literature Review
Authors: Radi A. , Sarpong E. Abankwah , Laarej A. , Ourrai A. , Hassani A. , Abilkassem R.
Published: June 2024

Fahr's disease is a very rare condition characterized by abnormal, symmetrical, and bilateral deposits of calcifications in the basal ganglia without an identifiable cause. Fahr's disease must be differentiated from Fahr's syndrome, which is also a rare anatomo-clinical entity, characterized by the presence of intracerebral calcifications located in the basal ganglia, most often associated with phosphocalcic metabolism disorders, primarily hypoparathyroidism.
While Fahr's syndrome involves secondary intracerebral calcifications,Fahr's disease is primary or idiopathic with autosomal dominant or recessive inheritance. There are sporadic and familial forms.
The clinical presentations of Fahr's disease vary and can include confusion syndromes, cognitive disorders, cerebellar syndrome, abnormal movements, psychiatric syndrome, or epilepsy. Seizures are very rare clinical presentation of Fahr’s disease. There are also asymptomatic forms.
We report the case of a 13-year-old boy with Fahr's disease revealed by a non-febrile epileptic seizure. The patient’s brother has similar epileptic manifestations. The medical history, clinical, biological and radiological findings were supportive of a familial form of Fahr’s disease.
Influence of Biotic and Abiotic Factors on Pest Incidence and Natural Enemies in Guava (Psidium guajava L)
Authors: Kanna S. Suganya , Nivashini A. , Pavithra I. , Piruthiga B. , Praveenchandran V. , Muthiah C. , Saraswathy S. , Rajangam J.
Published: June 2024

A study on seasonal incidence of insect pests and their natural enemies in different guava varieties was carried out at Horticultural College and Research Institute, Periyakulam during 2022-23. The results revealed that tea mosquito bug (8.75%), fruit borer (0.75%), mealybugs (12.25% and 2.80 %) and aphids (2.40%) were less in L-46. followed by red flash (1.55- 21.35%), L-49 (0.86- 13.50%)in guava ecosystem. The guava variety, Lalit was found to be more susceptible totea mosquito bug (22.60%), fruit borer (2.65%), mealy bug (25.60%), spiraling whitefly (23.45%), scales (5.75%) and papaya Mealybug (12.70%). The coccinellids population was high in lalit (1.80/tree) followed by Allahabad safeda (1.70/tree) and L-49 (1.60/tree), whereas the spiders were found high in red flash guava (0.70/tree) but in lalit it was 0.15 per tree. The fruit fly damage, mealybugs, spiraling whitefly, aphids, scales, papaya mealybug and spiders was more during hot weather and was positively correlated with maximum and minimum temperature whereas they are negatively correlated with other weather parameters viz., rainfall, wind speed and relative humidity. The fruit borer incidence was recorded high during rainy days (0.103) with high wind speed (0.344) and minimum temperature (0.004). The coccinellids beetle were more during cloudy and rainy period (0.765), high wind speed (0.554) and relative humidity (0.338).
Differential Distribution Patterns From Medial Prefrontal Cortex and Dorsal Raphe to the Locus Coeruleus in Rats
Authors: Lu Yuefeng , Simpson Kimberly L. , Weaver Kristin J. , Lin Rick C.S.
Published: June 2012

Locus coeruleus (LC) consists of a densely packed nuclear core and a surrounding plexus of dendritic zone, which is further divided into several subregions. Whereas many limbic‐related structures topographically target specific subregions of the LC, the precise projections from two limbic areas, that is, medial prefrontal cortex (mPFC) and dorsal raphe (DR), have not been investigated. The goal of the present study is to identify and compare the distribution patterns of mPFC and DR afferent terminals to the LC nuclear core as opposed to specific pericoerulear dendritic regions (Peri‐LC). To address these issues, anterograde tracer injections were combined with dopamine‐β‐hydroxylase (DBH) immunofluorescent staining to reveal the distribution patterns around the LC nuclear complex. Our data suggest that both mPFC‐LC and DR‐LC projections exhibit selective afferent terminal patterns. More specifically, mPFC‐LC projecting fibers mainly target the rostromedial Peri‐LC, whereas DR‐LC projecting fibers demonstrate a preference to the caudal juxtaependymal Peri‐LC. Thus, our present findings provide further evidences that afferents to the LC are topographically organized. Understanding the relationship among different inputs to the LC may help to elucidate the organizing principle which likely governs the interactions between the broad afferent sources of the LC and its global efferent targets. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Comparison of Three Methods of Drug Delivery in the Rat Lumbar Spinal Subarachnoid Space
Authors: Chen Liming , Jiang Meng , Pei Lei
Published: June 2012

This study aimed to compare three most widely used surgeries for experimental lumbar spinal drug delivery in rats. The comparison consisted of assessing the effects of the surgeries and evaluating the deficits produced by these three methods. Sprague Dawley rats underwent acute needle puncture, chronic catheterization via laminectomy or nonlaminectomized catheterization. Body weight changes were measured, animals' general and neurological conditions were observed after surgeries, and motor function was examined by Rota Rod test both prior to and post surgery. Furthermore, nociceptive tests were performed to assess the animals' nociception; hematoxylin, and eosin staining of lumbar spinal cord tissue was performed to evaluate local inflammation caused by surgeries; and both lidocaine paralysis detection; and toluidine blue dye assay were used to confirm the exact location of the catheter. Both needle puncture and catheterization via laminectomy had relatively low success rate of surgery and induced various neurological signs; more severe motor dysfunction, hyperalgesia, allodynia, and local inflammation. Nonlaminectomized catheterization had a higher success rate of surgery, and induced only mild agitation, slight cerebral spinal fluid leakage, mild sensory and motor abnormalities, and minimum pathology in the lumbar spinal cord. The nonlaminectomized catheterization used in this study induces a phenotype of less detectable effects on the animal's behavior and is well‐tolerated compared to the acute needle puncture and laminectomized catheterization that are widely used in the literature. Nonlaminectomized catheterization is a safe, accurate and effective way for lumbar drug delivery in rats. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Digit Ratio 2D:4D in Relation to Autism Spectrum Disorders, Empathizing, and Systemizing: A Quantitative Review
Authors: Hönekopp Johannes
Published: June 2012

Prenatal testosterone (PT) effects have been proposed to increase systemizing (the drive to understand lawful input–output relationships), to decrease empathizing (the drive to understand others), and to cause autism via hypermasculinization of the brain. Digit ratio 2D:4D is a putative marker of PT effects in humans. An online study (n = 1896) into the relationship between the Reading the Mind in the Eyes Test (a widely used measure of empathizing) and self‐measured 2D:4D in a nonclinical sample is reported. No evidence for a link between empathizing and 2D:4D in either females or males emerged. Further, three meta‐analyses are presented that look into the relationships of 2D:4D with autism spectrum disorder (ASD), systemizing, and empathizing. 2D:4D was substantially lower (more masculine) in ASD‐affected individuals than in normal controls (d = −0.58, P < 0.001). However, 2D:4D was found to be virtually unrelated to systemizing and empathizing in normal adults. The results support the idea that high PT is a risk factor for autism, but they challenge the view that PT substantially contributes to sex differences in systemizing and empathizing. Possibly, this pattern reflects an interaction effect, whereby PT drives ASD characteristic changes only in brains with a specific damage. Autism Res 2012, 5: 221–230. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.
Same but Different: 9‐Month‐Old Infants at Average and High Risk for Autism Look at the Same Facial Features but Process Them Using Different Brain Mechanisms
Authors: Key Alexandra P. F. , Stone Wendy L.
Published: June 2012

The study examined whether 9‐month‐old infants at average vs. high risk for autism spectrum disorder (ASD) process facial features (eyes, mouth) differently and whether such differences are related to infants' social and communicative skills. Eye tracking and visual event‐related potentials (ERPs) were recorded in 35 infants (20 average‐risk typical infants, 15 high‐risk siblings of children with ASD) while they viewed photographs of a smiling unfamiliar female face. On 30% of the trials, the eyes or the mouth of that face was replaced with corresponding features from a different female. There were no group differences in the number, duration, or distribution of fixations, and all infants looked at the eyes and mouth regions equally. However, increased attention to the mouth was associated with weaker receptive communication skills and increased attention to the eyes correlated with better interpersonal skills. ERP results revealed that all infants detected eye and mouth changes but did so using different brain mechanisms. Changes in facial features were associated with changes in activity of the face perception mechanisms (N290) for the average‐risk group but not for the high‐risk infants. For all infants, correlations between ERP and eye‐tracking measures indicated that larger and faster ERPs to feature changes were associated with fewer fixations on the irrelevant regions of stimuli. The size and latency of the ERP responses also correlated with parental reports of receptive and expressive communication skills, suggesting that differences in brain processing of human faces are associated with individual differences in social‐communicative behaviors. Autism Res 2012, 5: 253–266. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.
Receptor‐interacting protein (RIP) and Sirtuin‐3 (SIRT3) are on opposite sides of anoikis and tumorigenesis
Authors: Kamarajan Pachiyappan , Alhazzazi Turki Y. , Danciu Theodora , D'silva Nisha J. , Verdin Eric , Kapila Yvonne L.
Published: June 2012

BACKGROUND:

Regulating cross‐talk between anoikis and survival signaling pathways is crucial to regulating tissue processes and mitigating diseases like cancer. Previously, the authors demonstrated that anoikis activates a signaling pathway involving the CD95/Fas‐mediated signaling pathway that is regulated by receptor‐interacting protein (RIP), a kinase that shuttles between Fas‐mediated cell death and integrin/focal adhesion kinase (FAK)‐mediated survival pathways. Because it is known that sirtuin‐3 (SIRT3), a nicotinamide adenine dinucleotide‐dependent deacetylase, regulates cell survival, metabolism, and tumorigenesis, the authors hypothesized that SIRT3 may engage in cross‐talk with Fas/RIP/integrin/FAK survival‐death pathways in cancer cell systems.

METHODS:

Using immunohistochemical staining, immunoblotting, human tissue microarrays, and overexpression and suppression approaches in vitro and in vivo, the roles of RIP and SIRT3 were examined in oral squamous cell carcinoma (OSCC) anoikis resistance and tumorigenesis.

RESULTS:

RIP and SIRT3 had opposite expression profiles in OSCC cells and tissues. Stable suppression of RIP enhanced SIRT3 levels, whereas stable suppression of SIRT3 did not impact RIP levels in OSCC cells. The authors observed that, as OSCC cells became anoikis‐resistant, they formed multicellular aggregates or oraspheres in suspension conditions, and their expression of SIRT3 increased as their RIP expression decreased. Also, anoikis‐resistant OSCC cells with higher SIRT3 and low RIP expression induced an increased tumor burden and incidence in mice, unlike their adherent OSCC cell counterparts. Furthermore, stable suppression of SIRT3 inhibited anoikis resistance and reduced tumor incidence.

CONCLUSIONS:

The current results indicted that RIP is a likely upstream, negative regulator of SIRT3 in anoikis resistance, and an anoikis‐resistant orasphere phenotype defined by higher SIRT3 and low RIP expression contributes to a more aggressive phenotype in OSCC development. Cancer 2012. © 2012 American Cancer Society.
Two Adaptive Weighting Methods to Test for Rare Variant Associations in Family‐Based Designs
Authors: Fang Shurong , Sha Qiuying , Zhang Shuanglin
Published: June 2012

Although next‐generation DNA sequencing technologies have made rare variant association studies feasible and affordable, the development of powerful statistical methods for rare variant association studies is still under way. Most of the existing methods for rare variant association studies compare the number of rare mutations in a group of rare variants (in a gene or a pathway) between cases and controls. However, these methods assume that all causal variants are risk to diseases. Recently, several methods that are robust to the direction and magnitude of effects of causal variants have been proposed. However, they are applicable to unrelated individuals only, whereas family data have been shown to improve power to detect rare variants. In this article, we propose two adaptive weighting methods for rare variant association studies based on family data for quantitative traits. Using extensive simulation studies, we evaluate and compare our proposed methods with two methods based on the weights proposed by Madsen and Browning. Our results show that both proposed methods are robust to population stratification, robust to the direction and magnitude of the effects of causal variants, and more powerful than the methods using weights suggested by Madsen and Browning, especially when both risk and protective variants are present. Genet. Epidemiol. 36:499‐507, 2012. © 2012 Wiley Periodicals, Inc.
Identification of seven serum microRNAs from a genome‐wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas
Authors: Yang Cuihua , Wang Cheng , Chen Xi , Chen Sidi , Zhang Yanni , Zhi Feng , Wang Junjun , Li Limin , Zhou Xiaojun , Li Nanyun , Pan Hao , Zhang Junfeng , Zen Ke , Zhang Chen‐Yu , Zhang Chunni
Published: June 2012

The involvement of circulating microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis and prognosis are becoming increasingly appreciated; however, little is known about circulating miRNA profiles in astrocytomas. In our study, we performed genome‐wide serum miRNA analysis by the Solexa sequencing followed by validation conducted in the training and verification sets with a stem‐loop quantitative reverse‐transcription PCR (RT‐qPCR) assay from serum samples of 122 untreated astrocytomas patients (WHO grades III–IV) and 123 normal controls. Identified miRNAs were subsequently examined in 55 grade II, 15 grade I astrocytomas, 11 astrogliosis, 42 other primary brain tumors and 8 tumor tissues from grades II–IV astrocytomas. In addition, paired serum samples before and after operation were collected from 14 malignant astrocytomas to determine the effect of surgery on the miRNAs' levels. A marked difference in serum miRNA profile was observed between high‐grade astrocytomas and normal controls. Seven miRNAs were validated by RT‐qPCR assay to be significantly decreased in grades II–IV patients (p < 0.001), including miR‐15b*, miR‐23a, miR‐133a, miR‐150*, miR‐197, miR‐497 and miR‐548b‐5p, and the seven‐miRNA panel demonstrated a high sensitivity (88.00%) and specificity (97.87%) for malignant astrocytomas prediction. These identified miRNAs also exhibited a global decrease in tumor tissues relative to normal tissues. Furthermore, these miRNAs in serum were markedly elevated after operation (p < 0.001). In addition, some of these serum miRNAs were significantly different between malignant and benign cases, astrogliosis and other primary brain tumors. The seven serum miRNAs identified in our study hold potential as noninvasive biomarker for malignant astrocytomas.
A microRNA expression signature predicts meningioma recurrence
Authors: Zhi Feng , Zhou Guangxin , Wang Suinuan , Shi Yimin , Peng Ya , Shao Naiyuan , Guan Wei , Qu Hongtao , Zhang Yi , Wang Qiang , Yang Changchun , Wang Rong , Wu Sujia , Xia Xiwei , Yang Yilin
Published: June 2012

The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases, including cancer. In our study, we examined the miRNA expression profile of meningiomas, which is a common type of benign intracranial tumor derived from the protective meninges membranes that surround the brain and spinal cord. To define a typical human meningioma miRNA profile, the expression of 200 miRNAs in a training sample set were screened using quantitative reverse transcription polymerase chain reaction analysis, and then significantly altered miRNAs were validated in a secondary independent sample set. Kaplan–Meier and univariate/multivariate Cox proportional hazard regression analyses were performed to assess whether miRNA expression could predict the recurrence of meningioma after tumor resection. After a two‐phase selection and validation process, 14 miRNAs were found to exhibit significantly different expression profiles in meningioma samples compared to normal adjacent tissue (NAT) samples. Unsupervised clustering analysis indicated that the 14‐miRNA profile differed between tumor and NAT samples. Downregulation of miR‐29c‐3p and miR‐219‐5p were found to be associated with advanced clinical stages of meningioma. Kaplan–Meier analysis showed that high expression of miR‐190a and low expression of miR‐29c‐3p and miR‐219‐5p correlated significantly with higher recurrence rates in meningioma patients. Cox proportional hazard regression analysis revealed that miR‐190a expression level is an important prognostic predictor that is independent of other clinicopathological factors. Our results suggest that the use of miRNA profiling has significant potential as an effective diagnostic and prognostic marker in defining the expression signature of meningiomas and in predicting postsurgical outcomes.
Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai women's health study
Authors: Aschebrook‐Kilfoy Briseis , Shu Xiao‐Ou , Gao Yu‐Tang , Ji Bu‐Tian , Yang Gong , Li Hong Lan , Rothman Nathaniel , Chow Wong‐Ho , Zheng Wei , Ward Mary H.
Published: June 2012

Nitrate and nitrite are precursors in the endogenous formation of N‐nitroso compounds and nitrate can disrupt thyroid homeostasis by inhibiting iodide uptake. We evaluated nitrate and nitrite intake and risk of thyroid cancer in the Shanghai Women's Health Study that included 73,317 women, aged 40–70 years enrolled in 1996–2000. Dietary intake was assessed at baseline using a food frequency questionnaire. During approximately 11 years of follow‐up, 164 incident thyroid cancer cases with complete dietary information were identified. We used Cox proportional hazards regression to estimate relative risks (RRs). We determined the nitrate and nitrite contents of foods using values from the published literature and focusing on regional values for Chinese foods. Nitrate intake was not associated with thyroid cancer risk [RRQ4 = 0.93; 95% confidence interval (CI): 0.42–2.07; p for trend = 0.40]. Compared to the lowest quartile, women with the highest dietary nitrite intake had about a twofold risk of thyroid cancer (RRQ4 = 2.05; 95%CI: 1.20–3.51), but there was not a monotonic trend with increasing intake (p for trend = 0.36). The trend with increasing nitrite intake from animal sources was significant (p for trend = 0.02) and was stronger for nitrite from processed meats (RRQ4 = 1.96; 95%CI: 1.28–2.99; p for trend < 0.01). Although we did not observe an association for nitrate as hypothesized, our results suggest that women consuming higher levels of nitrite from animal sources, particularly from processed meat, may have an increased risk of thyroid cancer.
Counseling Issues for Adult Women in Career Transition
Authors: Ronzio Cynthia R.
Published: June 2012

This article addresses current psychosocial issues facing women in career transition and the implications of those issues for career counselors. Specifically, psychosocial developmental trajectories, the roles of family and relationships, the importance of underlying physical and mental health issues, and sociocultural and contextual stressors are relevant for women in the midst of career change. The author discusses how career counselors can prepare for this complexity and addresses clients' current economic and social milieus. A checklist is provided to aid the career counselor in addressing the multiple issues that a new client brings to the 1st counseling encounter.
Naringenin Inhibits Extracellular Matrix Production via Extracellular Signal‐Regulated Kinase Pathways in Nasal Polyp‐Derived Fibroblasts
Authors: Jung Ji Woong , Park Il‐Ho , Cho Jung‐Sun , Lee Heung‐Man
Published: June 2012

Naringenin, a natural predominant flavanone derived from plant food, has antifibrotic activity. The purposes of this study were to determine the effect of naringenin on myofibroblast differentiation and extracellular matrix (ECM) production in nasal polyp‐derived fibroblasts (NPDFs) and to determine the molecular mechanism of the effect of naringenin on NPDFs. NPDFs were incubated and treated with transforming growth factor (TGF)‐β1. The expression of alpha smooth muscle actin (α‐SMA), fibronectin, and collagen type I mRNA was determined by a reverse transcription‐polymerase chain reaction, and the expression of those proteins was determined by immunofluorescence staining or Western blotting. Expression of several signaling molecules of the TGF‐β1 pathway was evaluated by Western blot analysis. Naringenin inhibits expression of an indicator of myofibroblast differentiation (α‐SMA) and ECM production, including collagen type 1 and fibronectin. Naringenin only suppressed the expression of extracellular signal‐regulated protein kinase (pERK)1/2 among evaluated signaling molecules. PD98059 (a specific inhibitor of ERK1/2 kinase) also suppressed the increased expression of fibronectin, collagen type I, and α‐SMA in TGF‐β1‐induced NPDFs. These results suggest the possibility that naringenin may play an inhibitory role in the production of the ECM in the development of nasal polyps. Copyright © 2012 John Wiley & Sons, Ltd.
Astragalus membranaceus Ameliorates Reproductive Toxicity Induced by Cyclophosphamide in Male Mice
Authors: Kim Wonnam , Kim Sung‐Hoon , Park Seong Kyu , Chang Mun Seog
Published: June 2012

The root of Astragalus membranaceus BUNGE (AM) is a medicinal herb that has been capable of reducing the adverse effects of conventional chemotherapy. To investigate the effects of AM on cyclophosphamide (CP)‐induced reproductive toxicity in mouse testes, 5‐week‐old male imprinting control region mice were divided into five groups; CP was treated on the first day of each week for 5 weeks (100 mg/kg, i.p.), and AM was treated for 5 days a week for 5 weeks. At the end of the treatment period, the testes were taken out, cleared of the adhering tissues, and weighed. Epididymis was taken out and used for sperm analysis. Testis samples were frozen for real‐time quantitative PCR and Western blot analysis. AM treatment increased diminished relative testes weight, and sperm count and motility in mice treated with CP. CP treatment has detrimental effects on the expression of cAMP‐responsive element modulator (CREM), a transcription factor that is highly expressed in male germ cells and is crucial to post‐meiotic germ cell differentiation. AM restored CREM at both the mRNA and protein levels. AM has beneficial influences and appears able to ameliorate relative testes weight, sperm parameters, and CREM expression against CP‐induced reproductive toxicity. Copyright © 2012 John Wiley & Sons, Ltd.
Identity exploration in the dating domain: The role of attachment dimensions and parenting practices
Authors: Pittman Joe F. , Kerpelman Jennifer L. , Soto Janet B. , Adler‐Baeder Francesca M.
Published: June 2012

We examined relations among perceived parenting practices (support and psychological control), attachment dimensions for romantic relationships (anxiety and avoidance) and exploration of the dating identity among actively dating adolescents in two high school aged samples. In the all female sample of Study 1 (n = 653) and the gender balanced sample of Study 2 (n = 1003), parenting practices contributed to adolescent exploration of the dating identity. Parent psychological control, but not parental support, also contributed to elevated feeling of avoidance and anxiety in romantic relationships. Avoidance, in turn, was related to less exploration of the dating identity while anxiety seemed to increase it. Gender moderated the model, with parenting practices predicting exploration only for girls and with the links for avoidance and anxiety with exploration stronger for boys than girls. Indirect effects for parenting practices through attachment dimensions on exploration of the dating identity were also noted.
Serotonin activates angiogenic phosphorylation signaling in human endothelial cells
Authors: Zamani Ali , Qu Zhican
Published: June 2012

Serotonin, a known neurotransmitter, also functions as an angiokine to promote angiogenesis. The majority of serotonin in the human body is stored in platelets, and platelet aggregation leads to significant release of serotonin in thrombotic tumor environment. We have investigated serotonin signaling in human endothelial cells. Through G‐protein‐coupled receptors, serotonin at physiologically relevant concentrations activated Src/PI3K/AKT/mTOR/p70S6K phosphorylation signaling, and this activation was similar to that seen with VEGF. This finding provides insight into the overlapping angiogenic signaling pathways stimulated by serotonin in tumor environment, and suggests one of the mechanisms underlying resistance to current VEGF‐targeting antiangiogenic therapy against cancer.
Sadness and consumption
Authors: Garg Nitika , Lerner Jennifer S.
Published: June 2012

Sadness influences consumption, leading individuals to pay more to acquire new goods and to eat more unhealthy food than they would otherwise. These undesirable consumption effects of sadness can occur without awareness, thus representing more than just conscious attempts at “retail therapy.” In an experiment with real food consumption, the present paper examines the hypothesis that sadness' impact on consumption could be attenuated if the choice context counteracted appraisals of helplessness and enhanced a sense of individual control. Results revealed that: (1) sadness elevates self‐reports of helplessness in response to the emotion‐inducing situation, (2) helplessness mediates the sadness–consumption effect, and (3) inducing a sense of control (via choice) attenuates sadness' effect.
Novel synthetic derivatives of the natural product berbamine inhibit Jak2/Stat3 signaling and induce apoptosis of human melanoma cells
Authors: Nam Sangkil , Xie Jun , Perkins Angela , Ma Yuelong , Yang Fan , Wu Jun , Wang Yan , Xu Rong-zhen , Huang Wendong , Horne David A. , Jove Richard
Published: June 2012

Persistent Jak/Stat3 signal transduction plays a crucial role in tumorigenesis and immune development. Activated Jak/Stat3 signaling has been validated as a promising molecular target for cancer therapeutics discovery and development. Berbamine (BBM), a natural bis‐benzylisoquinoline alkaloid, was identified from the traditional Chinese herbal medicine Berberis amurensis used for treatment of cancer patients. While BBM has been shown to have potent antitumor activities with low toxicity in various cancer types, the molecular mechanism of action of BBM remains largely unknown. Here, we determine the antitumor activities of 13 synthetic berbamine derivatives (BBMDs) against human solid tumor cells. BBMD3, which is the most potent in this series of novel BBMDs, exhibits over 6‐fold increase in biological activity compared to natural BBM. Moreover, BBMD3, directly inhibits Jak2 autophosphorylation kinase activity in vitro with IC500.69μM. Autophosphorylation of Jak2 kinase at Tyr1007/1008 sites also was strongly inhibited in the range of 15μM of BBMD3 in human melanoma cells at 4h after treatment. Following inhibition of autophosphorylation of Jak2, BBMD3 blocked constitutive activation of downstream Stat3 signaling in melanoma cells. BBMD3 also down‐regulated expression of the Stat3 target proteins Mcl‐1and Bcl‐xL, associated with induction of apoptosis. In sum, our findings demonstrate that the novel berbamine derivative BBMD3 is an inhibitor of the Jak2/Stat3 signaling pathway, providing evidence for a molecular mechanism whereby BBMD3 exerts at least in part the apoptosis of human melanoma cells. In addition, BBMD3 represents a promising lead compound for development of new therapeutics for cancer treatment.
Multicentennial variability of the Atlantic meridional overturning circulation and its climatic influence in a 4000 year simulation of the GFDL CM2.1 climate model
Authors: Delworth Thomas L. , Zeng Fanrong
Published: June 2012

We investigate decadal to multicentennial variability of Northern Hemisphere surface air temperature in a 4000‐year control simulation of the GFDL CM2.1 climate model. Spectral analysis shows the presence of a distinct multicentennial timescale of temperature variability. The associated spatial pattern is broad, covering the entire Northern Hemisphere extratropics, but with enhanced amplitude in the Atlantic and Arctic sectors. This variability appears to be driven by interhemispheric fluctuations in oceanic heat transport associated with the Atlantic Meridional Overturning Circulation (AMOC). The AMOC variability is associated with century‐scale propagation of salinity anomalies from the Southern Ocean to the subpolar North Atlantic, with out of phase transport variations between the upper ocean and deeper layers of the Atlantic. When positive (negative) upper ocean salinity anomalies reach the subpolar North Atlantic they strengthen (weaken) the AMOC by modulating upper ocean density and vertical stratification. The large‐scale warming also appears to be enhanced by reductions in surface albedo associated with reduced sea‐ice and low‐level cloudiness, thereby increasing the absorption of shortwave radiation and amplifying the warming from AMOC changes. We speculate that such multicentennial variations in the AMOC could contribute to long‐time scale climate fluctuations in the observed paleo record. This could arise purely as internal variability of the climate system, or through radiatively‐induced changes to atmospheric circulation patterns, such as the NAO, that would in turn influence the AMOC.
Degradation of the organic molecules in the shallow subsurface of Mars due to irradiation by cosmic rays
Authors: Pavlov A. A. , Vasilyev G. , Ostryakov V. M. , Pavlov A. K. , Mahaffy P.
Published: June 2012

Detection of the organic matter on Mars is one of the main goals of the future Martian landing missions. Yet, the degradation of organic molecules by cosmic ray irradiation on Mars is often ignored. We calculate the radiation dose accumulation rates from solar and galactic cosmic rays at various depths in the shallow Martian subsurface. We demonstrate that a 1‐billion‐year outcrop on Mars accumulates the dosage of ∼500 MGy in the top 0–2 cm and ∼50 MGy at 5–10 cm depths. We show that the preservation of ancient complex organic molecules in the shallow (∼10 cm depth) subsurface of rocks could be highly problematic if the exposure age of a geologic outcrop would exceed 300 Myr. We demonstrate that more simple organic molecules with masses ∼100 amu should have a good chance to survive in the shallow subsurface of rocks. Implications to the sampling strategy for the oncoming Martian missions are discussed.
Cell cycle- and DNA repair pathway-specific effects of apoptosis on tumor suppression
Authors: Foster Steven S. , De Saurav , Johnson Linda K. , Petrini John H. J. , Stracker Travis H.
Published: June 2012

The DNA damage response comprises DNA repair, cell-cycle checkpoint control, and DNA damage-induced apoptosis that collectively promote genomic integrity and suppress tumorigenesis. Previously, we have shown that the Chk2 kinase functions independently of the Mre11 complex (Mre11, Rad50, and Nbs1) and ATM in apoptosis and suppresses tumorigenesis resulting from hypomorphic alleles of
Mre11
or
Nbs1
. Based on this work, we have proposed that Chk2 limits the oncogenic potential of replication-associated DNA damage. Here we further address the role of Chk2 and damage-induced apoptosis in suppressing the oncogenic potential of chromosome breaks. We show that loss of Chk2 or a mutation in p53 (R172P), which selectively impairs its function in apoptosis, rescued the lethality of mice lacking Lig4, a ligase required for nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks in G0/G1. In contrast to

Lig4
−/−
p53
−/−

mice,

Lig4
−/−
Chk2
−/−

and

Lig4
−/−
p53
R172P/R172P

mice were not prone to organ-specific, rapid tumorigenesis. Although the severe NHEJ deficiency of

Lig4
−/−

was a less potent initiator of tumorigenesis in the

p53
R172P/R172P

and

Chk2
−/−

backgrounds, where p53 cell-cycle functions are largely intact, even mild defects in the intra-S and G2/M checkpoints caused by mutations in
Nbs1
are sufficient to influence malignancy in

p53
R172P/R172P

mice. We conclude that the oncogenic potential of double-strand breaks resulting from NHEJ deficiency is highly restricted by nonapoptotic functions of p53, such as the G1/S checkpoint or senescence, suggesting that the particular facets of the DNA damage response required for tumor suppression are dictated by the proliferative status of the tumor-initiating cell.
Modeling disease mutations by gene targeting in one-cell mouse embryos
Authors: Meyer Melanie , Ortiz Oskar , Hrabé de Angelis Martin , Wurst Wolfgang , Kühn Ralf
Published: June 2012

Gene targeting by zinc-finger nucleases in one-cell embryos provides an expedite mutagenesis approach in mice, rats, and rabbits. This technology has been recently used to create knockout and knockin mutants through the deletion or insertion of nucleotides. Here we apply zinc-finger nucleases in one-cell mouse embryos to generate disease-related mutants harboring single nucleotide or codon replacements. Using a gene-targeting vector or a synthetic oligodesoxynucleotide as template for homologous recombination, we introduced missense and silent mutations into the
Rab38
gene, encoding a small GTPase that regulates intracellular vesicle trafficking. These results demonstrate the feasibility of seamless gene editing in one-cell embryos to create genetic disease models and establish synthetic oligodesoxynucleotides as a simplified mutagenesis tool.
Alternatively activated dendritic cells regulate CD4+T-cell polarization in vitro and in vivo
Authors: Cook Peter C. , Jones Lucy H. , Jenkins Stephen J. , Wynn Thomas A. , Allen Judith E. , MacDonald Andrew S.
Published: June 2012

Interleukin-4 is a cytokine widely known for its role in CD4+T cell polarization and its ability to alternatively activate macrophage populations. In contrast, the impact of IL-4 on the activation and function of dendritic cells (DCs) is poorly understood. We report here that DCs respond to IL-4 both in vitro and in vivo by expression of multiple alternative activation markers with a different expression pattern to that of macrophages. We further demonstrate a central role for DC IL-4Rα expression in the optimal induction of IFNγ responses in vivo in both Th1 and Th2 settings, through a feedback loop in which IL-4 promotes DC secretion of IL-12. Finally, we reveal a central role for RELMα during T-cell priming, establishing that its expression by DCs is critical for optimal IL-10 and IL-13 promotion in vitro and in vivo. Together, these data highlight the significant impact that IL-4 and RELMα can have on DC activation and function in the context of either bacterial or helminth pathogens.
Biomimetic emulsions reveal the effect of mechanical forces on cell–cell adhesion
Authors: Pontani Lea-Laetitia , Jorjadze Ivane , Viasnoff Virgile , Brujic Jasna
Published: June 2012

Cell–cell contacts in tissues are continuously subject to mechanical forces due to homeostatic pressure and active cytoskeleton dynamics. In the process of cellular adhesion, the molecular pathways are well characterized but the role of mechanics is less well understood. To isolate the role of pressure we present a dense packing of functionalized emulsion droplets in which surface interactions are tuned to mimic those of real cells. By visualizing the microstructure in 3D we find that a threshold compression force is necessary to overcome electrostatic repulsion and surface elasticity and establish protein-mediated adhesion. Varying the droplet interaction potential maps out a phase diagram for adhesion as a function of force and salt concentration. Remarkably, fitting the data with our theoretical model predicts binder concentrations in the adhesion areas that are similar to those found in real cells. Moreover, we quantify the dependence of the area of adhesion on the applied force and thus reveal adhesion strengthening with increasing external pressure even in the absence of active cellular processes. This biomimetic approach reveals a physical origin of pressure-sensitive adhesion and its strength across cell–cell junctions.
Charge transport in molecular electronic junctions: Compression of the molecular tunnel barrier in the strong coupling regime
Authors: Sayed Sayed Y. , Fereiro Jerry A. , Yan Haijun , McCreery Richard L. , Bergren Adam Johan
Published: June 2012

Molecular junctions are essentially modified electrodes familiar to electrochemists where the electrolyte is replaced by a conducting “contact.” It is generally hypothesized that changing molecular structure will alter system energy levels leading to a change in the transport barrier. Here, we show the conductance of seven different aromatic molecules covalently bonded to carbon implies a modest range (< 0.5 eV) in the observed transport barrier despite widely different free molecule HOMO energies (> 2 eV range). These results are explained by considering the effect of bonding the molecule to the substrate. Upon bonding, electronic inductive effects modulate the energy levels of the system resulting in compression of the tunneling barrier. Modification of the molecule with donating or withdrawing groups modulate the molecular orbital energies and the contact energy level resulting in a leveling effect that compresses the tunneling barrier into a range much smaller than expected. Whereas the value of the tunneling barrier can be varied by using a different class of molecules (alkanes), using only aromatic structures results in a similar equilibrium value for the tunnel barrier for different structures resulting from partial charge transfer between the molecular layer and the substrate. Thus, the system does not obey the Schottky-Mott limit, and the interaction between the molecular layer and the substrate acts to influence the energy level alignment. These results indicate that the entire system must be considered to determine the impact of a variety of electronic factors that act to determine the tunnel barrier.
Dislocation-mediated growth of bacterial cell walls
Authors: Amir Ariel , Nelson David R.
Published: June 2012

Recent experiments have illuminated a remarkable growth mechanism of rod-shaped bacteria: proteins associated with cell wall extension move at constant velocity in circles oriented approximately along the cell circumference [Garner EC, et al., (2011)
Science
333:222–225], [Domínguez-Escobar J, et al. (2011)
Science
333:225–228], [van Teeffelen S, et al. (2011) PNAS 108:15822–15827]. We view these as dislocations in the partially ordered peptidoglycan structure, activated by glycan strand extension machinery, and study theoretically the dynamics of these interacting defects on the surface of a cylinder. Generation and motion of these interacting defects lead to surprising effects arising from the cylindrical geometry, with important implications for growth. We also discuss how long range elastic interactions and turgor pressure affect the dynamics of the fraction of actively moving dislocations in the bacterial cell wall.
Isomorphism universal varieties of Heyting algebras
Authors: Adams M. E. , Koubek V. , Sichler J.
Published: June 2012

A variety

V

\mathbf {V}

is group universal if every group

G
G

is isomorphic to the automorphism group

Aut

(
A
)

{\operatorname {Aut}}(A)

of an algebra

A
∈

V

A \in \mathbf {V}

; if, in addition, all finite groups are thus representable by finite algebras from

V

\mathbf {V}

, the variety

V

\mathbf {V}

is said to be finitely group universal. We show that finitely group universal varieties of Heyting algebras are exactly the varieties which are not generated by chains, and that a chain-generated variety

V

\mathbf {V}

is group universal just when it contains a four-element chain. Furthermore, we show that a variety

V

\mathbf {V}

of Heyting algebras is group universal whenever the cyclic group of order three occurs as the automorphism group of some

A
∈

V

A \in \mathbf {V}

. The results are sharp in the sense that, for every group universal variety and for every group

G
G

, there is a proper class of pairwise nonisomorphic Heyting algebras

A
∈

V

A \in \mathbf {V}

for which

Aut

(
A
)
≅
G

{\operatorname {Aut}}(A) \cong G

.
On the smoothness of convex envelopes
Authors: Griewank A. , Rabier P. J.
Published: June 2012

We examine differentiability properties of the convex envelope

conv
⁡
E

\operatorname {conv} E

of a given function

E
:

R

n

→
(
−
∞
,
∞
]

E:{{\mathbf {R}}^n} \to ( - \infty ,\infty ]

in terms of properties of

E
E

. It is shown that

C
1

{C^1}

as well as optimal

C

1
,
α

{C^{1,\alpha }}

regularity results,

0
>
α
⩽
1

0 > \alpha \leqslant 1

, can be obtained under general conditions.
On Gel′fand pairs associated with solvable Lie groups
Authors: Benson Chal , Jenkins Joe , Ratcliff Gail
Published: June 2012

Let

G
G

be a locally compact group, and let

K
K

be a compact subgroup of

Aut

(
G
)

{\operatorname {Aut}}(G)

, the group of automorphisms of

G
G

. There is a natural action of

K
K

on the convolution algebra

L
1

(
G
)

{L^1}(G)

, and we denote by

L
K
1

(
G
)

L_K^1(G)

the subalgebra of those elements in

L
1

(
G
)

{L^1}(G)

that are invariant under this action. The pair

(
K
,
G
)

(K,G)

is called a Gelfand pair if

L
K
1

(
G
)

L_K^1(G)

is commutative. In this paper we consider the case where

G
G

is a connected, simply connected solvable Lie group and

K
⊆

Aut

(
G
)

K \subseteq {\operatorname {Aut}}(G)

is a compact, connected group. We characterize such Gelfand pairs

(
K
,
G
)

(K,G)

, and determine a moduli space for the associated

K
K

-spherical functions.