Nitriles

Publication Title: 
Human Reproduction Update

BACKGROUND: Here we describe the consensus guideline methodology, summarise the evidence-based recommendations we provided to the World Health Organisation (WHO) for their consideration in the development of global guidance and present a narrative review on the management of anovulatory infertility in women with polycystic ovary syndrome (PCOS). OBJECTIVE AND RATIONALE: The aim of this paper was to present an evidence base for the management of anovulatory PCOS.

Author(s): 
Balen, Adam H.
Morley, Lara C.
Misso, Marie
Franks, Stephen
Legro, Richard S.
Wijeyaratne, Chandrika N.
Stener-Victorin, Elisabet
Fauser, Bart C. J. M.
Norman, Robert J.
Teede, Helena
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one of the leading genetic causes of death in childhood. SMA is caused by a mutation of the survival-of-motor-neuron 1 (SMN1) gene, leading to a quantitative defect in the survival-motor-neuron (SMN) protein expression. All patients retain one or more copies of the SMN2 gene, which modulates the disease severity by producing a small amount of stable SMN protein.

Author(s): 
Branchu, Julien
Biondi, Olivier
Chali, Farah
Collin, Thibault
Leroy, Felix
Mamchaoui, Kamel
Makoukji, Joelle
Pariset, Claude
Lopes, Philippe
Massaad, Charbel
Chanoine, Christophe
Charbonnier, FrÈdÈric
Publication Title: 
The Journal of Biological Chemistry

Estrogen receptors (ER alpha/ER beta) are expressed in neuronal cells and exhibit a variety of activities in the central nervous system. ER activity is regulated in a ligand-dependent manner and by co-regulatory factors. Caveolin-1 is a recently identified co-activator of ER alpha mediating the ligand-independent activation of this steroid receptor. Here the influence of ERs on caveolin expression in human neuroblastoma SK-N-MC cells as well as in rodent brain was investigated.

Author(s): 
Zschocke, J¸rgen
Manthey, Dieter
Bayatti, Nadhim
van der Burg, Bart
Goodenough, Sharon
Behl, Christian
Publication Title: 
The Journal of Biological Chemistry

The roles of MEK, ERK, the epsilon and alpha isoforms of protein kinase C (PKC), and caveolin-1 in regulating collagen expression were studied in normal lung fibroblasts. Knocking down caveolin-1 gave particularly striking results. A 70% decrease caused a 5-fold increase in MEK/ERK activation and collagen expression. The combined data reveal a branched signaling pathway. In its central portion MEK activates ERK, leading to increased collagen expression. Two branches converge on MEK/ERK. In one, increased PKCepsilon leads to MEK/ERK activation.

Author(s): 
Tourkina, Elena
Gooz, Pal
Pannu, Jaspreet
Bonner, Michael
Scholz, Dimitri
Hacker, Sharon
Silver, Richard M.
Trojanowska, Maria
Hoffman, Stanley
Publication Title: 
Toxicology and Applied Pharmacology

CD40 is a costimulatory molecule linking innate and adaptive immune responses to bacterial stimuli, as well as a critical regulator of functions of other costimulatory molecules. The mechanisms regulating lipopolysaccharide (LPS)-induced CD40 expression have not been adequately characterized in human monocytic cells. In this study we used a human monocytic cell line, THP-1, to investigate the possible mechanisms of CD40 expression following LPS exposure. Exposure to LPS resulted in a dose- and time-dependent increase in CD40 expression.

Author(s): 
Wu, Weidong
Alexis, Neil E.
Chen, Xian
Bromberg, Philip A.
Peden, David B.
Publication Title: 
The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry

OBJECTIVES: Amyloid senile plaques and tau neurofibrillary tangles are neuropathologic hallmarks of Alzheimer disease, which may be associated with mild cognitive impairment (MCI) or mood and anxiety symptoms years before the dementia diagnosis.

Author(s): 
Lavretsky, Helen
Siddarth, Prabha
Kepe, Vladimir
Ercoli, Linda M.
Miller, Karen J.
Burggren, Alison C.
Bookheimer, Susan Y.
Huang, Sung-Cheng
Barrio, Jorge R.
Small, Gary W.
Publication Title: 
PloS One

Estrogens produce biological effects by interacting with two estrogen receptors, ERalpha and ERbeta. Drugs that selectively target ERalpha or ERbeta might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERbeta-selective compounds have been identified. One class of ERbeta-selective agonists is represented by ERB-041 (WAY-202041) which binds to ERbeta much greater than ERalpha.

Author(s): 
Paruthiyil, Sreenivasan
Cvoro, Aleksandra
Zhao, Xiaoyue
Wu, Zhijin
Sui, Yunxia
Staub, Richard E.
Baggett, Scott
Herber, Candice B.
Griffin, Chandi
Tagliaferri, Mary
Harris, Heather A.
Cohen, Isaac
Bjeldanes, Leonard F.
Speed, Terence P.
Schaufele, Fred
Leitman, Dale C.
Publication Title: 
Pancreas

OBJECTIVES: Prostaglandin E2 (PGE2) is a product of cyclooxygenase (COX) and PGE synthase (PGES) and deactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH). Down-regulation of PGDH contributes to PGE2 accumulation in lung and colon cancers but has not been identified in pancreatic cancer.

Author(s): 
Pham, Hung
Chen, Monica
Li, Aihua
King, Jonathan
Angst, Eliane
Dawson, David W.
Park, Jenny
Reber, Howard A.
Hines, O. Joe
Eibl, Guido
Publication Title: 
PloS One

Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic.

Author(s): 
Zhang, Lili
Blackman, Brigitte E.
Schonemann, Marcus D.
Zogovic-Kapsalis, Tatjana
Pan, Xiaoyu
Tagliaferri, Mary
Harris, Heather A.
Cohen, Isaac
Pera, Renee A. Reijo
Mellon, Synthia H.
Weiner, Richard I.
Leitman, Dale C.
Publication Title: 
PloS One

BACKGROUND: During inflammation, adhesion molecules regulate recruitment of leukocytes to inflamed tissues. It is reported that vascular cell adhesion molecule-1 (VCAM-1) activates extracellular regulated kinases 1 and 2 (ERK1/2), but the mechanism for this activation is not known. Pharmacological inhibitors of ERK1/2 partially inhibit leukocyte transendothelial migration in a multi-receptor system but it is not known whether VCAM-1 activation of ERK1/2 is required for leukocyte transendothelial migration (TEM) on VCAM-1.

Author(s): 
Abdala-Valencia, Hiam
Berdnikovs, Sergejs
Cook-Mills, Joan M.

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