Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphoregulation of K+‐Cl− cotransporter 4 during changes in intracellular Cl− and cell volume

It has long been stated that the K+‐Cl− cotransporters (KCCs) are activated during cell swelling through dephosphorylation of their cytoplasmic domains by a protein phosphatase (PP) but that other enzymes are involved by targeting this PP or the KCCs directly. To date, however, the role of signaling intermediates in KCC regulation has been deduced from indirect evidence rather than in vitro phosphorylation studies, and examined after simulation of ion transport through cell swelling or N‐ethylmaleimide treatment. In this study, the oocyte expression system was used to examine the effects of changes in cell volume (CVOL) and intracellular [Cl−] ([Cl−]i) on the activity and phosphorylation levels (PLEV) of KCC4, and determine whether these effects are mediated by PP1 or phorbol myristate acetate (PMA)‐sensitive effectors. We found that (1) low [Cl−]i or low CVOL leads to decreased activity but increased PLEV, (2) high CVOL leads to increased activity but no decrease in PLEV and (3) calyculin A (Cal A) or PMA treatment leads to decreased activity but no increase in PLEV. Thus, we have shown for the first time that one of the KCCs can be regulated through direct phosphorylation, that changes in [Cl−]i or CVOL modify the activity of signaling enzymes at carrier sites, and that the effectors directly involved do not include a Cal A‐sensitive PP in contrast to the widely held view. J. Cell. Physiol. 219: 787–796, 2009. © 2009 Wiley‐Liss, Inc.
Pipe and grain boundary diffusion of He in UO2

Molecular dynamics simulations have been conducted to study the effects of dislocations and grain boundaries on He diffusion in UO2. Calculations were carried out for the {1 0 0}, {1 1 0} and {1 1 1} 〈1 1 0〉 edge dislocations, the screw 〈1 1 0〉 dislocation and Σ5, Σ13, Σ19 and Σ25 tilt grain boundaries. He diffusivity as a function of distance from the dislocation core and grain boundaries was investigated for the temperature range 2300–3000 K. An enhancement in diffusivity was predicted within 20 Å of the dislocations or grain boundaries. Further investigation showed that He diffusion in the edge dislocations follows anisotropic behaviour along the dislocation core, suggesting that pipe diffusion occurs. An Arrhenius plot of He diffusivity against the inverse of temperature was also presented and the activation energy calculated for each structure, as a function of distance from the dislocation or grain boundary.
Plasminogen activator inhibitors regulate cell adhesion through a uPAR‐dependent mechanism

Binding of type‐1 plasminogen activator inhibitor (PAI‐1) to cell surface urokinase (uPA) promotes inactivation and internalization of adhesion receptors (e.g., urokinase receptor (uPAR), integrins) and leads to cell detachment from a variety of extracellular matrices. In this report, we begin to examine the mechanism of this process. We show that neither specific antibodies to uPA, nor active site inhibitors of uPA, can detach the cells. Thus, cell detachment is not simply the result of the binding of macromolecules to uPA and/or of the inactivation of uPA. We further demonstrate that another uPA inhibitor, protease nexin‐1 (PN‐1), also stimulates cell detachment in a uPA/uPAR‐dependent manner. The binding of both inhibitors to uPA leads to the specific inactivation of the matrix‐engaged integrins and the subsequent detachment of these integrins from the underlying extracellular matrix (ECM). This inhibitor‐mediated inactivation of integrins requires direct interaction between uPAR and those integrins since cells attached to the ECM through integrins incapable of binding uPAR do not respond to the presence of either PAI‐1 of PN‐1. Although both inhibitors initiate the clearance of uPAR, only PAI‐1 triggers the internalization of integrins. However, cell detachment by PAI‐1 or PN‐1 does not depend on the endocytosis of these integrins since cell detachment was also observed when clearance of these integrins was blocked. Thus, PAI‐1 and PN‐1 induce cell detachment through two slightly different mechanisms that affect integrin metabolism. These differences may be important for distinct cellular processes that require controlled changes in the subcellular localization of these receptors. J. Cell. Physiol. 220: 655–663, 2009. © 2009 Wiley‐Liss, Inc.
Bronchoscopic Myths and Legends: Flexible Bronchoscopy in Patients With Very Severe Lung Obstruction

It has been well established that flexible bronchoscopy and topical anesthesia can cause a decline in lung function, including a temporary reduction in FEV1 in normal patients and those with lung obstruction. Pulmonologists are asked frequently to evaluate and bronchoscope patients with very severe lung obstruction. We performed a literature search to evaluate the myth that flexible bronchoscopy is unsafe for patients with very severe lung obstruction. Myth: Flexible bronchoscopy is unsafe and should not be performed in patients with severe obstructive lung disease as defined by a Forced Expiratory Volume (FEV1) of <35% predicted.
Selection and evolutionary potential of spring arrival phenology in males and females of a migratory songbird

The timing of annual life‐history events affects survival and reproduction of all organisms. A changing environment can perturb phenological adaptations and an important question is if populations can evolve fast enough to track the environmental changes. Yet, little is known about selection and evolutionary potential of traits determining the timing of crucial annual events. Migratory species, which travel between different climatic regions, are particularly affected by global environmental changes. To increase our understanding of evolutionary potential and selection of timing traits, we investigated the quantitative genetics of arrival date at the breeding ground using a multigenerational pedigree of a natural great reed warbler (Acrocephalus arundinaceus) population. We found significant heritability of 16.4% for arrival date and directional selection for earlier arrival in both sexes acting through reproductive success, but not through lifespan. Mean arrival date advanced with 6 days over 20 years, which is in exact accordance with our predicted evolutionary response based on the breeder's equation. However, this phenotypic change is unlikely to be caused by microevolution, because selection seems mainly to act on the nongenetic component of the trait. Furthermore, demographical changes could also not account for the advancing arrival date. Instead, a strong correlation between spring temperatures and population mean arrival date suggests that phenotypic plasticity best explains the advancement of arrival date in our study population. Our study dissects the evolutionary and environmental forces that shape timing traits and thereby increases knowledge of how populations cope with rapidly changing environments.
Incarceration among young injectors in San Francisco: associations with risk for hepatitis C virus infection

Background: We describe incarceration history (jail or prison) among a community‐based sample of young injection drug users (IDU) (age<30 years) in San Francisco, and examine associations between selected socio‐demographic and behavioral characteristics and hepatitis hepatitis C virus (HCV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV) infections. Methods: Cross‐sectional baseline data from study of street‐recruited young IDU in San Francisco were analyzed. Results: In a sample of 839 young IDU, median age was 22 years, 70% were male, 86% had a lifetime history of incarceration, and 56% had been incarcerated in the prior year. Serologic markers of HBV and HCV infections were significantly higher among those with any history of incarceration (29% and 42% respectively) compared with those with no incarceration history. Variables independently associated with recent incarceration were gender (male), homelessness, increased years of injecting, and a history of having ever borrowed previously used needles for injecting. Variables independently associated with any lifetime history of incarceration included: gender (males), educational level, homelessness, increased years of injecting, and anti‐HCV status. Conclusions: Interventions to increase geographic and social stability, such as safe transitional housing, and clean and safe injecting spaces, may also contribute greatly to reducing both incarceration and bloodborne infection in this young high‐risk population.
NAG7 promotes human nasopharyngeal carcinoma invasion through inhibition of estrogen receptor alpha and up‐regulation of JNK2/AP‐1/MMP1 pathways

The NAG7, an estrogen receptor repressor, is a negative regulator of nasopharyngeal carcinoma cell growth. Here, we report that NAG7 promotes human nasopharyngeal carcinoma invasion, and we identify the mechanisms underlying this function. As a consequence of elevated NAG7 expression, the adhesion, migration, and invasive capabilities of HNE1 cells in vitro and in vivo were enhanced. NAG7 was a significant negative regulator of protein expression of estrogen receptor alpha (ERα), and activated both the JNK2/AP‐1/MMP1 and the upstream H‐Ras/p‐c‐Raf pathways. None of these effects induced by NAG7 over‐expression could be counteracted by estrogen. These observations indicate that NAG7 plays a potential role in promoting nasopharyngeal carcinoma invasion by regulation of ERα and the H‐ras/p‐c‐Raf and JNK2/AP‐1/MMP1 signaling pathways. J. Cell. Physiol. 221: 394–401, 2009. © 2009 Wiley‐Liss, Inc.
Pollination by sexual deception promotes outcrossing and mate diversity in self‐compatible clonal orchids

The majority of flowering plants rely on animals as pollen vectors. Thus, plant mating systems and pollen dispersal are strongly influenced by pollinator behaviour. In Australian sexually deceptive orchids pollinated by male thynnine wasps, outcrossing and extensive pollen flow is predicted due to floral deception, which minimizes multiple flower visitations within patches, and the movement of pollinators under mate‐search rather than foraging behaviours. This hypothesis was tested using microsatellite markers to reconstruct and infer paternity in two clonal, self‐compatible orchids. Offspring from naturally pollinated Chiloglottis valida and C. aff. jeanesii were acquired through symbiotic culture of seeds collected over three seasons. In both species, outcrossing was extensive (tm = 0.924–1.00) despite clone sizes up to 11 m wide. The median pollen flow distance based on paternity for both taxa combined was 14.5 m (n = 18, range 0–69 m), being larger than typically found by paternity analyses in other herbaceous plants. Unexpectedly for orchids, some capsules were sired by more than one father, with an average of 1.35 pollen donors per fruit. This is the first genetic confirmation of polyandry in orchid capsules. Further, we report a possible link between multiple paternity and increased seed fitness. Together, these results demonstrate that deceptive pollination by mate‐searching wasps enhances offspring fitness by promoting both outcrossing and within‐fruit paternal diversity.
Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I. class III β‐tubulin

Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain cancer in adults. Despite advances in molecular biology and genetics of gliomas currently there is no effective treatment or promising molecularly targeted experimental therapeutic strategies for these tumors. In previous studies we have shown aberrant overexpression of the class III β‐tubulin isotype (βIII‐tubulin) in GBM and have proposed that this change may reflect perturbations in microtubule dynamics associated with glioma tumorigenesis, tumor progression and malignant transformation into GBM. This minireview focuses on microtubules and tubulin as emerging targets in potential therapy of GBM using a new class of βIII‐tubulin‐targeted drugs in the light of recent developments concerning the function and potential role of this isotype in clinically aggressive tumor behavior, cancer stem cells, tumor hypoxia and chemoresistance to tubulin binding agents, principally taxanes. J. Cell. Physiol. 221: 505–513, 2009. © 2009 Wiley‐Liss, Inc.
Aurora B expression in post‐puberal testicular germ cell tumours

Aurora/Ipl1‐related kinases are a conserved family of proteins that are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumours and have been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy, and genomic instability. Previous studies of our group have shown that Aurora B expression is restricted to specific germinal cells. In this study, we have evaluated by immunohistochemical analysis Aurora B expression in post‐puberal testicular germ cell tumours (22 seminomas, 2 teratomas, 15 embryonal carcinomas, 5 mixed germinal tumours with a prominent yolk sac tumour component and 1 choriocarcinoma). The Aurora B protein expression was detected in all intratubular germ cell tumours, seminomas and embryonal carcinomas analysed but not in teratomas and yolk sac carcinomas. The immunohistochemical data were further confirmed by Western blot analysis. In addition, the kinase Aurora B was vigorously expressed in GC‐1 cells line derived from murine spermatogonia. The block of Aurora B function induced by a pharmacological inhibitor significantly reduced the growth of GC‐1 cells suggesting that Aurora B is a potential therapeutic target. J. Cell. Physiol. 221: 435–439, 2009. © 2009 Wiley‐Liss, Inc.
Runx2 and bone morphogenic protein 2 regulate the expression of an alternative Lef1 transcript during osteoblast maturation

Lymphoid Enhancer Binding Factor (Lef) 1 is a transcriptional effector of the Wnt/Lrp5/β‐catenin signaling cascade, which regulates osteoblast differentiation, bone density, and skeletal strength. In this study, we describe the expression and function of an alternative Lef1 isoform in osseous cells. Lef1ΔN is a naturally occurring isoform driven by a promoter (p2) within the intron between exons 3 and 4 of Lef1. Lef1ΔN is induced during late osteoblast differentiation. This is converse to the expression pattern of the full‐length Lef1 protein, which as we previously showed, decreases during differentiation. Agonists of osteoblast maturation differentially affected Lef1ΔN expression. BMP2 stimulated Lef1ΔN expression, whereas Wnt3a blocked basal and BMP2‐induced expression of Lef1ΔN transcripts during osteoblast differentiation. We determined that the Lef1ΔN p2 promoter is active in osteoblasts and Runx2 regulates its activity. Stable overexpression of Lef1ΔN in differentiating osteoblasts induced the expression of osteoblast differentiation genes, osteocalcin and type 1 collagen. Taken together, our results suggest Lef1ΔN is a crucial regulator of terminal differentiation in osseous cells. J. Cell. Physiol. 221: 480–489, 2009. © 2009 Wiley‐Liss, Inc.
At the Breast: Ideologies of Breastfeeding and Motherhood in the Contemporary United States

A colleague of Linda Blum advised her against using the word breasts in her book about mothH erhood, breastfeeding, and how our notions of both are inextricably tied to ideologies of genH der, class, and race. While the comment could not have been made in all seriousness, when I read Blum's account of this conversation I couldn't help but feel the same way. Indeed, as I toted the book along with me over the course of several weeks, it was impossible to ignore the stares and questioning looks the book's title incited. The comments ranged from the sarcasH tic to the bemused, but most were some variaH tion on the theme of "What on earth are you reading? " It was through these interactions that the significance of Blum's research was driven home to me. As I explained over and over again what the book was about, my female colleagues, friends, and family members shifted from puzzled to intrigued-with most asking for more details, and some asking to borrow the book. In studying breastfeeding, Blum has clearly found a topic that speaks to women, yet the negative responsH es the book's title received show just how much families which she uses to compare childHrearing beliefs and parenting strategies. Hill juxtaposes childHdevelopment and childHrearing theories that stigmatize black parents as dysfunctional with interviews of black and white parents to show that they have similar values, views of parH enting roles, and discipline strategies. Black parH ents have the additional burden of teaching their children that racism exists but "it is not to be used as a 'crutch"' (p. 94). Hill challenges feminist scholars' claim that race is an issue for black families, but that genH der is not. She notes that black parents have had to teach their children how to survive. Girls could not adhere to traditional gender norms. Rather, they were taught to work and to support themselves. Hill is disappointed by the dearth of information on parents' strategies to raise black males. This problem is quite disturbing given the racial discrimination they face and the violence they encounter or bring to bear on their own communities. Hill is not averse to asking diffiH cult questions: Do family socialization patterns also disadvantage black male children? Do mothers protect their sons more; and if so, do they do so out of fear for their sons' safety? Or do
Ceramide metabolism determines glioma cell resistance to chemotherapy

Tumor cell resistance to chemotherapy constitutes a major problem in the treatment of malignant tumors. We here investigated the role of ceramide metabolism for the resistance of glioma cells to treatment with the chemotherapeutic drug, gemcitabine. Gemcitabine triggers a marked release of ceramide in drug‐sensitive cells, while glioma cells that are resistant to gemcitabine, fail to accumulate ceramide. While the release of ceramide is very similar in gemcitabine‐sensitive and resistant glioma cells upon stimulation, resistant glioma cells rapidly consume ceramide upon gemcitabine treatment or exogenous sphingomyelinase stimulation. Pharmacologic or genetic inhibition of glucosyltransferases prevents ceramide consumption in resistant cells and restores sensitivity of resistant glioma cells to gemcitabine. These data suggest that glioma cell resistance to at least some chemotherapeutic drugs is mediated by rapid consumption of ceramide to prevent cell death. J. Cell. Physiol. 221: 688–695, 2009. © 2009 Wiley‐Liss, Inc.
The hematopoietic stem cell niche: Low in oxygen but a nice place to be

The enormous regenerative capacity of the blood system to sustain functionally mature cells are generated from highly proliferative, short‐lived progenitors, which in turn arise from a rare population of pluripotent and self‐renewing hematopoietic stem cells (HSC). In the bone marrow, these stem cells are kept in a low proliferative, relatively quiescent state in close proximity to stromal cells and osteoblasts, forming specialized niches. The interaction in particular to bone is crucial to prevent exhaustion of HSCs from uncontrolled cell‐cycle entry and to excessive proliferation. In addition, the niche and its components protect stem cells from stress, such as accumulation of reactive oxygen species and DNA damage. One of the key issues is to identify conditions to increase the number of HSCs, either in vivo or during ex vivo growth cultures. This task has been very difficult to resolve and most attempts have been unsuccessful. However, the mechanistic insights to HSC self‐renewal and preservation are gradually increasing and there is now hope that future research will enable scientists and clinicians to modulate the process. In this review, we will focus on the molecular mechanisms of self‐renewal and HSC maintenance in the light of novel findings that HSCs reside at the lowest end of an oxygen gradient. Hypoxia appears to regulate hematopoiesis in the bone marrow by maintaining important HSC functions, such as cell cycle control, survival, metabolism, and protection against oxidative stress. To improve the therapeutic expansion of HSCs we need to learn more about the molecular mechanisms of hypoxia‐mediated regulation. J. Cell. Physiol. 222:17–22, 2010. © 2009 Wiley‐Liss, Inc.
Induction of Th17 differentiation by corneal epithelial‐derived cytokines

This study was to explore a potential role of epithelium‐derived cytokines in Th17 differentiation. Th17 induction was evaluated by murine CD4+ T cells treated with different combinations of five inducing cytokines, or conditioned media of human corneal epithelial cells (HCECs) exposed to a variety of stimuli. Th17 differentiation was determined by measuring Th17 associated molecules, IL‐17A, IL‐17F, IL‐22, CCL‐20, and STAT3 at mRNA and protein levels, and numbers of IL‐17‐producing T cells by real‐time PCR, and cytokine immunobead and ELISPOT assays, respectively. IL‐23 was the strongest inducer for expanding Th17 cells in the presence of TGF‐β1 + IL‐6; and IL‐1β was the strongest Th17 amplifier in the presence of TGF‐β1 + IL‐6 + IL‐23. These inducing cytokines were found to be significantly stimulated in HCECs challenged by hyperosmotic media (450 mOsM), microbial components (polyI:C, flagellin, R837, and other TLR ligands) and TNF‐α. Interestingly, when incubated with conditioned media of HCECs irritated by polyI:C or TNF‐α, CD4+ T cells displayed increased mRNA levels of IL‐17A, IL‐17F, IL‐22, CCL‐20, and STAT3, increased IL‐17 protein in the supernatant, and increased numbers of IL‐17‐producing T cells (Th17 cells). These findings demonstrate for the first time that Th17 differentiation can be promoted by cytokines produced by corneal epithelium that are exposed to hyperosmotic, microbial, and inflammatory stimuli. J. Cell. Physiol. 222:95–102, 2010. © 2009 Wiley‐Liss, Inc.
Macronutrient intake regulates sexual conflict in decorated crickets

Sexual conflict results in a diversity of sex‐specific adaptations, including chemical additions to ejaculates. Male decorated crickets (Gryllodes sigillatus) produce a gelatinous nuptial gift (the spermatophylax) that varies in size and free amino acid composition, which influences a female's willingness to fully consume this gift. Complete consumption of this gift maximizes sperm transfer through increased retention of the sperm‐containing ampulla, but hinders post‐copulatory mate choice. Here, we examine the effects of protein (P) and carbohydrate (C) intake on the weight and amino acid composition of the spermatophylax that describes its gustatory appeal to the female, as well as the ability of this gift to regulate sexual conflict via ampulla attachment time. Nutrient intake had similar effects on the expression of these traits with each maximized at a high intake of nutrients with a P : C ratio of 1 : 1.3. Under dietary choice, males actively regulated their nutrient intake but this regulation did not coincide with the peak of the nutritional landscape for any trait. Our results therefore demonstrate that a balanced intake of nutrients is central to regulating sexual conflict in G. sigillatus, but males are constrained from reaching the optima needed to bias the outcome of this conflict in their favour.