bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular inhibitors, repellents, and semaphorin/plexin/MICAL‐mediated actin filament disassembly
Authors: Hung Ruei‐Jiun , Terman Jonathan R. 
Published: July 2011

AbstractMultiple extracellular signals have been identified that regulate actin dynamics within motile cells, but how these instructive cues present on the cell surface exert their precise effects on the internal actin cytoskeleton is still poorly understood. One particularly interesting class of these cues is a group of extracellular proteins that negatively alter the movement of cells and their processes. Over the years, these types of events have been described using a variety of terms and herein we provide an overview of inhibitory/repulsive cellular phenomena and highlight the largest known protein family of repulsive extracellular cues, the Semaphorins. Specifically, the Semaphorins (Semas) utilize Plexin cell‐surface receptors to dramatically collapse the actin cytoskeleton and we summarize what is known of the direct molecular and biochemical mechanisms of Sema‐triggered actin filament (F‐actin) disassembly. We also discuss new observations from our lab that reveal that the multidomain oxidoreductase (Redox) enzyme Molecule Interacting with CasL (MICAL), an important mediator of Sema/Plexin repulsion, is a novel F‐actin disassembly factor. Our results indicate that MICAL triggers Sema/Plexin‐mediated reorganization of the F‐actin cytoskeleton and suggest a role for specific Redox signaling events in regulating actin dynamics. © 2011 Wiley‐Liss, Inc.
Improved outcomes associated with higher surgery rates for older patients with early stage nonsmall cell lung cancer
Authors: Gray Stacy W. , Landrum Mary Beth , Lamont Elizabeth B. , McNeil Barbara J. , Jaklitsch Michael T. , Keating Nancy L. 
Published: July 2011

AbstractBACKGROUND:Although surgery offers the greatest chance of a cure for patients with early stage nonsmall cell lung cancer (NSCLC), older and sicker patients often fail to undergo resection. The benefits of surgery in older patients and patients with multiple comorbidities are uncertain.METHODS:The authors identified a national cohort of 17,638 Medicare beneficiaries aged ≥66 years living in Surveillance, Epidemiology, and End Results (SEER) areas who were diagnosed with stage I or II NSCLC during 2001 to 2005. Areas with high and low rates of curative surgery for early stage lung cancer were compared to estimate the effectiveness of surgery in older and sicker patients. Logistic regression models were used to assess mortality according to the quintile of area‐level surgery rates, adjusting for potential confounders.RESULTS:Less than 63% of patients underwent surgery in low‐surgery areas, whereas >79% underwent surgery in high‐surgery areas. High‐surgery areas operated on more patients of advanced age and patients with chronic obstructive pulmonary disease than low‐surgery areas. The adjusted all‐cause 1 year mortality was 18% in high‐surgery areas versus 22.8% in low‐surgery areas (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.86‐0.93) for each 10% increase in the surgery rate).The 1‐year lung‐cancer‐specific mortality similarly was lower in high‐surgery areas (12%) versus low‐surgery areas (16.9%; adjusted OR, 0.86; 95% CI, 0.82‐0.91) for each 10% increase in the surgery rate.CONCLUSIONS:Higher rates of surgery for stage I/II NSCLC were associated with improved survival, even when older patients and sicker patients underwent resection. The authors concluded that more work is needed to identify and reduce barriers to surgery for early stage NSCLC. Cancer 2012;. © 2011 American Cancer Society.
Breast cancers presenting luminal B subtype features show higher discordant human epidermal growth factor receptor 2 results between immunohistochemistry and fluorescence in situ hybridization
Authors: Park Seho , Park Hyung Seok , Koo Ja Seung , Yang Woo Ick , Kim Seung Il , Park Byeong‐Woo 
Published: July 2011

AbstractBACKGROUND:The aims of this study were to compare human epidermal growth factor receptor 2 (HER2) results between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and to investigate the clinicopathological characteristics and outcomes according to their results.METHODS:Using consecutive tissue microarrays, IHC and FISH were performed as guidelines in 950 invasive breast cancers treated between November 1999 and August 2005. Characteristics and outcomes were retrospectively analyzed using a chi‐square test, the Kaplan‐Meier method, and Cox's model.RESULTS:FISH‐positivity was observed in 2.6%, 4.8%, 28.1%, and 93.8% of IHC 0, 1+, 2+, and 3+, respectively, and the concordance rate between the 2 assays was 95.5%. IHC‐positive or FISH‐positive cases were associated with poorer differentiation, negative expression of hormone receptors, and higher proliferative index. Among IHC‐equivocal or IHC‐negative patients, positive FISH was negatively associated with survival in univariate and multivariate analyses. Among IHC‐negative patients, tumors showing luminal B subtype features such as estrogen receptor (ER)‐positive, grade II/III, and high Ki‐67 presented discordantly high FISH‐positivity. Among IHC‐positive cases, FISH was not related to outcomes.CONCLUSIONS:The result of FISH is significantly related to prognosis of patients with IHC‐negative or IHC‐equivocal result. Therefore, FISH should be performed in IHC‐equivocal cases. FISH assay might be considered for a selected group of patients with IHC‐negative tumors showing luminal B subtype features of ER‐positive, grade II/III, and high Ki‐67 expression. Cancer 2012;. © 2011 American Cancer Society.
Effect of metformin on survival outcomes in diabetic patients with triple receptor‐negative breast cancer
Authors: Bayraktar Soley , Hernadez‐Aya Leonel F. , Lei Xiudong , Meric‐Bernstam Funda , Litton Jennifer K. , Hsu Limin , Hortobagyi Gabriel N. , Gonzalez‐Angulo Ana M. 
Published: July 2011

AbstractBACKGROUND:Recent observational studies have shown that metformin use in diabetic patients decreases both cancer incidence and mortality. Metformin use is also independently predictive of pathologic complete response. In the current study, the authors explored the association between metformin use and survival outcomes in patients with triple receptor‐negative breast cancer (TNBC) who were receiving adjuvant chemotherapy.METHODS:The Breast Cancer Management System database of The University of Texas MD Anderson Cancer Center identified 1448 women who received adjuvant chemotherapy for TNBC between 1995 and 2007. Patients were categorized by diabetes status and metformin use. The Kaplan‐Meier product‐limit method was used to calculate distant metastasis‐free survival (DMFS), recurrence‐free survival (RFS), and overall survival (OS). Cox proportional hazards models were fit to determine the association between metformin use and survival outcomes.RESULTS:The study cohort was comprised of 63 diabetic patients receiving treatment with metformin, 67 diabetic patients not receiving metformin, and 1318 nondiabetic patients. Patients in the diabetic groups tended to be older (P = .005); more diabetic patients were postmenopausal (P = .0007), black (P = .0001), and obese (P < .0001). At a median follow‐up of 62 months, there were no significant differences with regard to 5‐year DMFS (P = .23), RFS (P = .38), and OS (P = .58) between the 3 groups. Compared with the metformin group, patients who did not receive metformin (hazard ratio [HR], 1.63; 95% confidence interval [95% CI], 0.87‐3.06 [P = .13]) and nondiabetic patients (HR, 1.62; 95% CI, 0.97‐2.71 [P = .06]) tended to have a higher risk of distant metastases.CONCLUSIONS:The findings of the current study suggest that metformin use during adjuvant chemotherapy does not significantly impact survival outcomes in diabetic patients with TNBC. Cancer 2012;. © 2011 American Cancer Society.
Peripheral nerve graft with immunosuppression modifies gene expression in axotomized CNS neurons
Authors: Murray Marion , Santi Lauren , Monaghan Rebecca , Houle John D. , Barr Gordon A. 
Published: July 2011

AbstractAdult central nervous system (CNS) neurons do not regenerate severed axons unaided but may regenerate axons into apposed predegenerated peripheral nerve grafts (PNGs). We examined gene expression by using microarray technology in laser‐dissected lateral vestibular (LV) neurons whose axons were severed by a lateral hemisection at C3 (HX) and in lateral vestibular nucleus (LVN) neurons that were hemisected at C3 and that received immunosuppression with cyclosporine A (CsA) and a predegenerated PNG (termed I‐PNG) into the lesion site. The results provide an expression analysis of temporal changes that occur in LVN neurons in nonregenerative and potentially regenerative states and over a period of 42 days. Axotomy alone resulted in a prolonged change in regulation of probe sets, with more being upregulated than downregulated. Apposition of a PNG with immunosuppression muted gene expression overall. Axotomized neurons (HX) upregulated genes commonly associated with axonal growth, whereas axotomized neurons whose axons were apposed to the PNG showed diminished expression of many of these genes but greater expression of genes related to energy production. The results suggest that axotomized LVN neurons express many genes thought to be associated with regeneration to a greater extent than LVN neurons that are apposed to a PNG. Thus the LVN neurons remain in a regenerative state following axotomy but the conditions provided by the I‐PNG appear to be neuroprotective, preserving or enhancing mitochondrial activity, which may provide required energy for regeneration. We speculate that the graft also enables sufficient axonal synthesis of cytoskeletal components to allow axonal growth without marked increase in expression of genes normally associated with regeneration. J. Comp. Neurol. 519:3433–3455, 2011. © 2011 Wiley‐Liss, Inc.
Kisspeptin neurons co‐express met‐enkephalin and galanin in the rostral periventricular region of the female mouse hypothalamus
Authors: Porteous Robert , Petersen Sandra L. , Yeo Shel Hwa , Bhattarai Janardhan P. , Ciofi Philippe , D'anglemont de Tassigny Xavier , Colledge William H. , Caraty Alain , Herbison Allan E. 
Published: July 2011

AbstractIt is now well established that the kisspeptin neurons of the hypothalamus play a key role in regulating the activity of gonadotropin‐releasing hormone (GnRH) neurons. The population of kisspeptin neurons residing in the rostral periventricular region of the third ventricle (RP3V), encompassing the anteroventral periventricular (AVPV) and periventricular preoptic nuclei (PVpo), are implicated in the generation of the preovulatory GnRH surge mechanism and puberty onset in female rodents. The present study examined whether these kisspeptin neurons may express other neuropeptides in the adult female mouse. Initially, the distribution of galanin, neurotensin, met‐enkephalin (mENK), and cholecystokinin (CCK)‐immunoreactive cells was determined within the RP3V of colchicine‐treated mice. Subsequent experiments, using a new kisspeptin‐10 antibody raised in sheep, examined the relationship of these neuropeptides to kisspeptin neurons. No evidence was found for expression of neurotensin or CCK by RP3V kisspeptin neurons, but subpopulations of kisspeptin neurons were observed to express galanin and mENK. Dual‐labeled RP3V kisspeptin/galanin cells represented 7% of all kisspeptin and 21% of all galanin neurons whereas dual‐labeled kisspeptin/mENK cells represented 28–38% of kisspeptin neurons and 58–68% of the mENK population, depending on location within the AVPV or PVpo. Kisspeptin neurons in the arcuate nucleus were also found to express galanin but not mENK. These observations indicate that, like the kisspeptin population of the arcuate nucleus, kisspeptin neurons in the RP3V also co‐express a range of neuropeptides. This pattern of co‐expression should greatly increase the dynamic range with which kisspeptin neurons can modulate the activity of their afferent neurons. J. Comp. Neurol. 519:3456–3469, 2011. © 2011 Wiley‐Liss, Inc.
Genetic and experimental evidence supports the continuum of the central extended amygdala and a mutiple embryonic origin of its principal neurons
Authors: Bupesh Munisamy , Abellán Antonio , Medina Loreta 
Published: July 2011

AbstractThe central extended amygdala is the major output center for telencephalic control of ingestion, fear responses, stress, and anxiety. In spite of the abundant data supporting the similarity in neurochemistry, connections, and function along the extended amygdala, embryological support for this continuum is lacking. By using a combination of in vitro migration assays, in situ hybridization, and immunostaining, here we show that its major components, including central amygdala and lateral bed nucleus of the stria terminalis (BST), are mosaics formed by different proportions of dorsal lateral ganglionic eminence (LGE)‐, ventral LGE‐, and medial ganglionic eminence (MGE)‐derived principal neurons. The dorsal LGE produces Pax6‐expressing neurons that primarily populate lateral parts of the central extended amygdala, including the capsular and part of lateral central amygdala, but also produces a few cells for the lateral BST. Based on correlation with preproenkephalin, many of these cells are likely enkephalinergic. The ventral LGE produces Islet1‐expressing neurons that populate primarily the central and medial parts of the central amygdala but also produces numerous neurons for the lateral BST. Correlation with corticotropin‐releasing factor suggests that these neurons express this neuropeptide. The MGE produces the majority of neurons of the lateral BST, but its ventrocaudal subdivision also produces an important subpopulation of projection neurons containing somatostatin for medial aspects of the central amygdala. Thus, distinct principal neurons originate in different embryonic domains, but the same domains contribute neurons to most subdivisions of the central extended amygdala, which may explain the similarity in neurochemistry and connections along the corridor. J. Comp. Neurol. 519:3507–3531, 2011. © 2011 Wiley‐Liss, Inc.
A novel type of complex ganglion cell in rabbit retina
Authors: Sivyer Benjamin , Venkataramani Sowmya , Taylor W. Rowland , Vaney David I. 
Published: July 2011

AbstractThe 15–20 physiological types of retinal ganglion cells (RGCs) can be grouped according to whether they fire to increased illumination in the receptive‐field center (ON cells), decreased illumination (OFF cells), or both (ON‐OFF cells). The diversity of RGCs has been best described in the rabbit retina, which has three types of ON‐OFF RGCs with complex receptive‐field properties: the ON‐OFF direction‐selective ganglion cells (DSGCs), the local edge detectors, and the uniformity detectors. Here we describe a novel type of bistratified ON‐OFF RGC that has not been described in either physiological or morphological studies of rabbit RGCs. These cells stratify in the ON and OFF sublaminae of the inner plexiform layer, branching at about 30% and 60% depth, between the ON and OFF arbors of the bistratified DSGCs. Similar to the ON‐OFF DSGCs, these cells respond with transient firing to both bright and dark spots flashed in the receptive field but, unlike the DSGCs, they show no directional preference for moving stimuli. We have termed these cells “transient ON‐OFF” RGCs. Area‐response measurements show that both the ON and the OFF spike responses have an antagonistic receptive‐field organization, but with different spatial extents. Voltage‐clamp recordings reveal transient excitatory inputs at light ON and light OFF; this excitation is strongly suppressed by surround stimulation, which also elicits direct inhibitory inputs to the cells at light ON and light OFF. Thus the receptive‐field organization is mediated both within the presynaptic circuitry and by direct feed‐forward inhibition. J. Comp. Neurol. 519:3128–3138, 2011. © 2011 Wiley‐Liss, Inc.
Nuclear factor one X regulates the development of multiple cellular populations in the postnatal cerebellum
Authors: Piper Michael , Harris Lachlan , Barry Guy , Heng Yee Hsieh Evelyn , Plachez Celine , Gronostajski Richard M. , Richards Linda J. 
Published: July 2011

AbstractDevelopment of the cerebellum involves the coordinated proliferation, differentiation, maturation, and integration of cells from multiple neuronal and glial lineages. In rodent models, much of this occurs in the early postnatal period. However, our understanding of the molecular mechanisms that regulate this phase of cerebellar development remains incomplete. Here, we address the role of the transcription factor nuclear factor one X (NFIX), in postnatal development of the cerebellum. NFIX is expressed by progenitor cells within the external granular layer and by cerebellar granule neurons within the internal granule layer. Using NFIX−/− mice, we demonstrate that the development of cerebellar granule neurons and Purkinje cells within the postnatal cerebellum is delayed in the absence of this transcription factor. Furthermore, the differentiation of mature glia within the cerebellum, such as Bergmann glia, is also significantly delayed in the absence of NFIX. Collectively, the expression pattern of NFIX, coupled with the delays in the differentiation of multiple cell populations of the developing cerebellum in NFIX−/− mice, suggest a central role for NFIX in the regulation of cerebellar development, highlighting the importance of this gene for the maturation of this key structure. J. Comp. Neurol. 519:3532–3548, 2011. © 2011 Wiley‐Liss, Inc.
Brainstem galanin‐synthesizing neurons are differentially activated by chemoreceptor stimuli and represent a subpopulation of respiratory neurons
Authors: Spirovski Darko , Li Qun , Pilowsky Paul M. 
Published: July 2011

AbstractThe ventrolateral medulla oblongata (VLM) of the brainstem contains neurochemically heterogeneous neurons that have a critical role in cardiovascular and respiratory regulation. Previous anatomical studies have shown the existence of galanin immunoreactivity in the medulla oblongata, but a detailed characterization is lacking. In this study, we demonstrate three populations of preprogalanin mRNA (PPG)‐expressing neurons in the VLM of the adult, male Sprague‐Dawley rat: a retrotrapezoid nucleus (RTN) group, a group in the rostral ventral respiratory group (rVRG), and a subpopulation of A1 neurons. PPG+ neurons express tyrosine hydroxylase (TH) only in the A1 region of the VLM, where approximately 56% of PPG+ neurons contain TH (79 ± 14; n = 4). PPG+ neurons do not express vesicular acetylcholine transporter (vAChT) in the VLM (n = 3). However, 33% of PPG+ neurons contain neurokinin‐1 receptor (NK1R) in the rVRG (126 ± 12; n = 12), accounting for ∼28% of all NK1R+ neurons in the region. Retrogradely transported cholera toxin B injected into the thoracic spinal cord (T1) revealed that bulbospinal PPG+ neurons are present in the rVRG (n = 3; ∼26% of PPG+ neurons). PPG+ neurons in the RTN and locus coeruleus are selectively activated (Fos) following 2 hours of exposure to hypercapnia, but not by hypoxia. Neurons in the A1, nucleus of the solitary tract, and dorsomedial hypothalamus are activated by both chemoreceptor stimuli. The results suggest that PPG+ neurons represent a population of brainstem neurons that play a critical and differential role in the chemoreflex responses to hypoxia and hypercapnia. J. Comp. Neurol., 2012. © 2011 Wiley Periodicals, Inc.
Neurosensory and neuromuscular organization in tube feet of the sea urchin Strongylocentrotus purpuratus
Authors: Agca Cavit , Elhajj Milad C. , Klein William H. , Venuti Judith M. 
Published: July 2011

AbstractSeveral behavioral and electrophysiological studies indicate that all classes of echinoderms, including Echinoidia, the class to which sea urchins belong, are photosensitive and exhibit complex behavioral responses to light or changes in light intensity. However, no discrete photosensitive structure has been identified in sea urchins. The purpose of this study was to provide new insights into eye evolution by determining whether distinct photosensory structures are present in adult sea urchins. Recently, we showed that the Strongylocentrotus purpuratus genome contains orthologs of many mammalian retinal genes and that these genes are expressed in tube feet, suggesting the presence of photoreceptor neurons. To determine whether this is so, we identified several features of tube feet that relate to a possible invertebrate phototransduction system. We show that rhabdomeric opsin is expressed severalfold higher within the disk region of the tube feet and is the most abundant opsin. Immunostaining identified βIII‐tubulin‐expressing cells at the periphery of disk in the vicinity of the synaptotagmin‐expressing nerve fibers. We also showed that Pax6 expression in the disk was restricted to the periphery, where small clusters of putative sensory neurons reside. Our results reveal neuromuscular organization of the tube foot neuromuscular system. They further support earlier studies suggesting the presence of a photosensory system in tube feet. J. Comp. Neurol. 519:3566–3579, 2011. © 2011 Wiley‐Liss, Inc.
Morphology of mouse subplate cells with identified projection targets changes with age
Authors: Hoerder‐Suabedissen Anna , Molnár Zoltán 
Published: July 2011

AbstractDuring embryonic and early postnatal development subplate neurons integrate into the developing intra‐ and extracortical circuitry in a dynamic fashion. They extend long‐range projections to adjacent cortical regions, the contralateral hemisphere through the corpus callosum, and to subcortical structures through the internal capsule. Here we studied the developmental changes of the somatodendritic morphology of subplate neurons with specified projection target in the mouse. To do so we used carbocyanine dye tracing from the callosum, the internal capsule, or the primary somatosensory cortex. The morphology of subplate cells with projections to any of these targets is very diverse and includes pyramidal, multipolar, and neurogliaform cells. Here we demonstrate that a subpopulation of subplate cells in the mouse cortex undergoes significant changes in somatodendritic morphology during the critical period for experimental modification of the cytoarchitectonic development of the barrel cortex. Between P2 and P7 the mean maximal extent of the primary dendrite decreases significantly for subplate cells with an axon projecting through the internal capsule. Moreover, at P2 some subplate cells extend a primary dendrite to the marginal zone, whereas all dendrites of P7 subplate cells end in or below layer 4. Additionally, by tracing connections from multiple targets with different carbocyanine dyes we identified subplate cells with multiple long‐range projections. J. Comp. Neurol., 2012. © 2011 Wiley Periodicals, Inc.