bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalytic Asymmetric Amination of N‐Nonsubstituted α‐Alkoxycarbonyl Amides: Concise Enantioselective Synthesis of Mycestericin F and G
Authors: Berhal Farouk , Takechi Sho , Kumagai Naoya , Shibasaki Masakatsu 
Published: January 2011

AbstractIn an attempt to explore the synthetic utility of a ternary asymmetric catalyst comprising La(NO3)3⋅6H2O, amide‐based ligand (R)‐L1, and D‐valine tert‐butyl ester H‐D‐Val‐OtBu, we investigated a catalytic, asymmetric amination of functionalized N‐nonsubstituted α‐alkoxycarbonyl amides using di‐tert‐butyl azodicarboxylate as an electrophilic aminating reagent. A highly functionalized, cyclic N‐nonsubstituted α‐alkoxycarbonyl amide delivered the desired amination product in up to 96 % enantiometric excess, with the requisite functionalities of the polar heads of sphingosines with the appropriate stereochemical arrangement. The rapid asymmetric assembly of these functional groups allowed a concise enantioselective synthetic route to sphingosines to be established with a broad flexibility towards derivative synthesis. These studies have culminated in an efficient catalytic enantioselective total synthesis of immunosuppressive fungal metabolites mycestericin F (3 a) and G (3 b).
Allosteric Inhibitor Development Targeting HIV‐1 Integrase
Authors: Al‐Mawsawi Laith Q. , Neamati Nouri 
Published: January 2011

AbstractHIV‐1 integrase (IN) is one of three essential enzymes for viral replication, and is a focus of ardent antiretroviral drug discovery and development efforts. Diligent research has led to the development of the strand‐transfer‐specific chemical class of IN inhibitors, with two compounds from this group, raltegravir and elvitegravir, advancing the farthest in the US Food and Drug Administration (FDA) approval process for any IN inhibitor discovered thus far. Raltegravir, developed by Merck & Co., has been approved by the FDA for HIV‐1 therapy, whereas elvitegravir, developed by Gilead Sciences and Japan Tobacco, has reached phase III clinical trials. Although this is an undoubted success for the HIV‐1 IN drug discovery field, the emergence of HIV‐1 IN strand‐transfer‐specific drug‐resistant viral strains upon clinical use of these compounds is expected. Furthermore, the problem of strand‐transfer‐specific IN drug resistance will be exacerbated by the development of cross‐resistant viral strains due to an overlapping binding orientation at the IN active site and an equivalent inhibitory mechanism for the two compounds. This inevitability will result in no available IN‐targeted therapeutic options for HIV‐1 treatment‐experienced patients. The development of allosterically targeted IN inhibitors presents an extremely advantageous approach for the discovery of compounds effective against IN strand‐transfer drug‐resistant viral strains, and would likely show synergy with all available FDA‐approved antiretroviral HIV‐1 therapeutics, including the IN strand‐transfer‐specific compounds. Herein we review the concept of allosteric IN inhibition, and the small molecules that have been investigated to bind non‐active‐site regions to inhibit IN function.
Glomerular nucleus of the weakly electric fish, Gymnotus sp.: Cytoarchitecture, histochemistry, and fiber connections—Insights from neuroanatomy to evolution and behavior
Authors: Giassi Ana Catarina Casari , Maler Leonard , Moreira Jorge E. , Hoffmann Anette 
Published: January 2011

AbstractThe present study provides a detailed description of morphological and hodological aspects of the glomerular nucleus in the weakly electric fish Gymnotus sp., and explores the evolutionary and functional implications flowing from this analysis. The glomerular nucleus of Gymnotus shows numerous morphological similarities with the glomerular nucleus of percomorph fish, although cytoarchitectonically simpler. In addition, congruence of the histochemical acetylcholinesterase (AChE) distribution with cytoarchitectonic data suggests that the glomerular nucleus, together with the ventromedial cell group of the medial subdivision of the preglomerular complex (PGm‐vmc) rostrally, and the subglomerular nucleus (as identified by Maler et al. [1991] J Chem Neuroanat 4:1–38) caudally, may form a distinct longitudinally organized glomerular complex. Our results show that an important source of sensory afferents to the glomerular nucleus originates in the pretectal and electrosensorius nuclei. The glomerular nucleus in turn projects to the hypothalamus (inferior lobe and anterior hypothalamus), to the anterior tuberal nucleus, and to the medial region of the preglomerular nucleus (PGm). These data suggest that visual and electrosensory information reach the glomerular nucleus and are relayed to the hypothalamus and, via PGm, to the pallium. Such connections are similar to those of the glomerular nucleus in percomorphs and the posterior pretectal nucleus in osteoglossomorph, esocids, and salmonids, where they comprise one component of a visual processing pathway. In Gymnotiform fish, however, the pretectal region that projects to the glomerular nucleus is dominated by electrosensory input (visual input is minor), which is consistent with the dominant role of electroreception in these fish. J. Comp. Neurol. 519:1658–1676, 2011. © 2011 Wiley‐Liss, Inc.
Neuronal organization of a fast‐mediating cephalothoracic pathway for antennal‐tactile information in the cricket (Gryllus bimaculatus DeGeer)
Authors: Schöneich Stefan , Schildberger Klaus , Stevenson Paul A. 
Published: January 2011

AbstractCrickets use their long antennae as tactile sensors. Confronted with obstacles, conspecifics, or predators, antennal contacts trigger short‐latency motor responses. To reveal the neuronal pathway underlying these antennal‐guided locomotory reactions we identified descending interneurons that rapidly transmit antennal‐tactile information from the head to the thorax in the cricket Gryllus bimaculatus. Antennae were stimulated with forces approximating those of naturally occurring antennal contacts. Responding interneurons were individually identified by intracellular axon recordings in the pro‐mesothoracic connective and subsequent tracer injection. Simultaneous with the intracellular recordings, the overall spike response in the neck connectives was recorded extracellularly to reveal the precise response‐timing of each individual neuron within the collective multiunit response. Here we describe four descending brain neurons and two with the soma in the subesophageal ganglion. All antennal‐touch elicited action potentials apparent in the neck connective recordings within 10 ms after antennal‐contact are generated by these six interneurons. Their dendrites ramify in primary antennal‐mechanosensory neuropils of the head ganglia. Each of them consistently generated action potentials in response to antennal touching and three of them responded also to different visual stimulation (light‐off, movement). Their descending axons conduct action potentials with 3–5 m/s to the thoracic ganglia where they send off side branches in dorsal neuropils. Their physiological and anatomical properties qualify them as descending giant fibers in the cricket and suggest an involvement in evoking fast locomotory reactions. They form a fast‐mediating cephalo‐thoracic pathway for antennal‐tactile information, whereas all other antennal‐tactile interneurons had response latencies exceeding 40 ms. J. Comp. Neurol. 519:1677–1690, 2011. © 2011 Wiley‐Liss, Inc.
Fezf1 and Fezf2 are required for olfactory development and sensory neuron identity
Authors: Eckler Matthew J. , McKenna William L. , Taghvaei Sahar , McConnell Susan K. , Chen Bin 
Published: January 2011

AbstractThe murine olfactory system consists of main and accessory systems that perform distinct and overlapping functions. The main olfactory epithelium (MOE) is primarily involved in the detection of volatile odorants, while neurons in the vomeronasal organ (VNO), part of the accessory olfactory system, are important for pheromone detection. During development, the MOE and VNO both originate from the olfactory pit; however, the mechanisms regulating development of these anatomically distinct organs from a common olfactory primordium are unknown. Here we report that two closely related zinc‐finger transcription factors, FEZF1 and FEZF2, regulate the identity of MOE sensory neurons and are essential for the survival of VNO neurons respectively. Fezf1 is predominantly expressed in the MOE while Fezf2 expression is restricted to the VNO. In Fezf1‐deficient mice, olfactory neurons fail to mature and also express markers of functional VNO neurons. In Fezf2‐deficient mice, VNO neurons degenerate prior to birth. These results identify Fezf1 and Fezf2 as important regulators of olfactory system development and sensory neuron identity. J. Comp. Neurol. 519:1829–1846, 2011. © 2011 Wiley‐Liss, Inc.
Glutamatergic neuronal populations in the forebrain of the sea lamprey, Petromyzon marinus: An in situ hybridization and immunocytochemical study
Authors: Villar‐Cerviño Verona , Barreiro‐Iglesias Antón , Mazan Sylvie , Rodicio Maria Celina , Anadón Ramón 
Published: January 2011

AbstractDespite the importance of glutamate as a major excitatory neurotransmitter in the brain, the distribution of glutamatergic populations in the brain of most vertebrates is still unknown. Here, we studied for the first time the distribution of glutamatergic neurons in the forebrain of the sea lamprey (Petromyzon marinus), belonging to the most ancient group of vertebrates (agnathans). For this, we used in situ hybridization with probes for a lamprey vesicular glutamate transporter (VGLUT) in larvae and immunofluorescence with antiglutamate antibodies in both larvae and adults. We also compared glutamate and γ‐aminobutyric acid (GABA) immunoreactivities in sections using double‐immunofluorescence methods. VGLUT‐expressing neurons were observed in the olfactory bulb, pallium, septum, subhippocampal lobe, preoptic region, thalamic eminence, prethalamus, thalamus, epithalamus, pretectum, hypothalamus, posterior tubercle, and nucleus of the medial longitudinal fascicle. Comparison of VGLUT signal and glutamate immunoreactivity in larval forebrain revealed a consistent distribution of positive cells, which were numerous in most regions. Glutamate‐immunoreactive cell populations were also found in similar regions of the adult forebrain. These include mitral‐like cells of the olfactory bulbs and abundant cells in the lateral pallium, septum, and various diencephalic regions, mainly in the prethalamus, thalamus, habenula, pineal complex, and pretectum. Only a small portion of the glutamate‐immunoreactive cells showed colocalization with GABA, which was observed mainly in the olfactory bulb, telencephalon, hypothalamus, ventral thalamus, and pretectum. Comparison with glutamatergic cells observed in rodent forebrains suggests that the regional distribution of glutamatergic cells does not differ greatly in lampreys and mammals. J. Comp. Neurol. 519:1712–1735, 2011. © 2011 Wiley‐Liss, Inc.
Transportin 1 in the mouse brain: Appearance in regions of neurogenesis, cerebrospinal fluid production/sensing, and circadian clock
Authors: Sato Miho , Mizoro Yasutaka , Atobe Yuta , Fujimoto Yoshito , Yamaguchi Yoshiaki , Fustin Jean‐Michel , Doi Masao , Okamura Hitoshi 
Published: January 2011

AbstractTransportin1 (Tnpo1) is a carrier protein belonging to the importin‐β family, which transports substrates between the cytoplasm and the nucleus. To gain insight into the role of Tnpo1 gene in the brain, we investigated the localization of Tnpo1‐, Tnpo2‐, and Tnpo3‐expressing cells by in situ hybridization histochemistry. Tnpo1 mRNA‐positive cells were distributed throughout the brain from the olfactory bulb to the medulla oblongata. The cells in the subventricular zone of the lateral ventricle, where neurogenesis occurs even in the adult, and its progeny neurons in the granular cells of the olfactory bulb and the islands of Calleja were strongly labeled. It is also noteworthy that cerebrospinal fluid (CSF)‐generating epithelial cells in the choroid plexus and CSF‐contacting and ‐sensing circumventricular organs, including organum vasculosum lamina terminalis, subfornical organ, and subcommissural organ, expressed high amounts of Tnpo1. The strongest signals were found in the suprachiasmatic nucleus (SCN), where the biological clock resides, which prompted us to examine the circadian characteristics of Tnpo1. Under constant‐dark conditions, the circadian expression profiles of Tnpo1 mRNA in the SCN showed a peak in the subjective night and a trough in the subjective day. Tnpo2 and Tnpo3 showed similar patterns of expression, except in the choroids plexus, the subventricular zone, and the SCN, where the expression was notably weaker. These findings suggest that Tnpo1 is involved in a variety of functions in the adult brain, including neurogenesis, CSF production and sensing, and circadian rhythms. J. Comp. Neurol. 519:1770‐1780, 2011. © 2011 Wiley‐Liss, Inc.
Patterned expression of a cocaine‐ and amphetamine‐regulated transcript peptide reveals complex circuit topography in the rodent cerebellar cortex
Authors: Reeber Stacey L. , Sillitoe Roy V. 
Published: January 2011

AbstractThe cerebellum (Cb) of mammals and birds consists of an evolutionarily conserved map defined by Purkinje cell (PC) protein expression. In mice, ZebrinII/aldolaseC is expressed in a striking array of stripes in lobules I–V (anterior zone; AZ) and VIII–anterior IX (posterior zone; PZ), whereas the small heat shock protein 25 (HSP25) is expressed in stripes in lobules VI–VII (central zone, CZ) and posterior IX–X (nodular zone, NZ). Little is known about whether molecularly defined afferent subsets terminate within specific PC stripes or whether their topography is conserved across species. Using immunohistochemistry, we demonstrate in adult mice and rats that cocaine‐ and amphetamine‐regulated transcript (CART) expression can be used to partition sensory‐motor projections into complex topographic maps. We found that in mice CART was expressed in climbing fiber bands that generally corresponded to the pattern of HSP25‐expressing PCs in the CZ/NZ. In contrast, CART was expressed in climbing fiber bands in all four transverse zones of the rat Cb. Within the rat AZ/PZ, climbing fibers terminated selectively within the dendrites of ZebrinII‐immunoreactive PCs. In additional experiments, we observed CART expression in loose clusters of spinocerebellar mossy fibers in the mouse AZ/PZ, whereas in rat CART immunoreactive mossy fibers terminated predominantly in the CZ/NZ. We conclude that, although the overall topography of CART‐expressing afferents is restricted within a conserved map of PC stripes and transverse zones, their termination patterns also reflect species‐specific compartmental features. J. Comp. Neurol. 519:1781–1796, 2011. © 2011 Wiley‐Liss, Inc.
A Novel Pyrene‐Based Fluorescing Amphiphile with Unusual Bulk and Interfacial Properties
Authors: Salonen Anniina , Knyazev Anton , von Bandel Nicolas , Degrouard Jéril , Langevin Dominique , Drenckhan Wiebke 
Published: January 2011

AbstractWe have synthesised a new, pyrene‐based, low‐molecular‐mass, amphiphilic molecule that displays a wealth of properties of potential interest for aggregation and interfacial applications. In order to elucidate some of the key properties of this molecule, which consists of a pyrene‐containing hydrophobic head and a short PEG‐based hydrophilic tail, we investigate herein some aspects of its concentration‐dependent behaviour in aqueous solutions. We show that the inclusion of the hydrophobic pyrene group not only provides the molecule with intriguing bulk and interfacial properties down to low concentrations, but also with various means of assessing its aggregation behaviour by means of its well‐characterised fluorescence properties. Combining a range of fluorescence techniques with microscopic imaging (optical and Cryo‐TEM), interfacial tension measurements and foaming studies, we have been able to identify and characterise three concentration‐dependant regimes. At low concentrations, the molecule is dissolved in monomeric form. At intermediate concentrations, labile aggregates are formed, which, at higher concentrations, give way to aggregates containing pre‐associated pyrenes. Our measurements strongly imply that the latter aggregates are hexagonally close‐packed tubular micelles. In this latter regime we also find a range of micron‐sized precipitates. Additionally, the molecule displays strong interfacial activity, yet a surprisingly slow dynamics of interfacial adsorption. Finally, we demonstrate the possibility of using it to visualize interfaces and also create reasonably stable (1 hour) and fluorescing foams.
Efficient Conversion of Furfuryl Alcohol into Alkyl Levulinates Catalyzed by an Organic–Inorganic Hybrid Solid Acid Catalyst
Authors: Zhang Zehui , Dong Kun , Zhao Zongbao (Kent) 
Published: January 2011

AbstractA clean, facile, and environment‐friendly catalytic method has been developed for the conversion of furfuryl alcohol into alkyl levulinates making use of the novel solid catalyst methylimidazolebutylsulfate phosphotungstate ([MIMBS]3PW12O40). The solid catalyst is an organic–inorganic hybrid material, which consists of an organic cation and an inorganic anion. A study for optimizing the reaction conditions such as the reaction time, the temperature and the catalyst loading has been performed. Under optimal conditions, a high n‐butyl levulinate yield of up to 93 % is obtained. Furthermore, the kinetics of the reaction pathways and the mechanism for the alcoholysis of furfuryl alcohol are discussed. This method is environmentally benign and economical for the conversion of biomass‐based derivatives into fine chemicals.
Advances in kidney transplant immunosuppression: Emerging biologics
Authors: Kumar Vineeta , Gaston Robert S. 
Published: January 2011

AbstractThere remains a need in solid‐organ transplantation for an immunosuppressive agent with a novel mechanism of action and fewer adverse consequences to replace current immunosuppressive drugs and improve long‐term patient and graft survival. There are several agents on the horizon, both small molecules and biologics, offering this promise along with ease and consistency of long‐term administration. We discuss three biologic agents currently in advanced stages of clinical trials in kidney transplantation.
The three‐signal hypothesis of lymphocyte activation/targets for immunosuppression
Authors: Goral Simin 
Published: January 2011

AbstractKidney transplantation is the preferred mode of renal replacement therapy for most patients with end‐stage renal disease. Despite the increasing success of transplantation over the years, allograft rejection remains a major problem. Recently, there has been considerable improvement in understanding the role of the immune system in rejection. In the setting of transplantation, T cells have proved to be crucial players in the immune response, and their activation has been shown to be a very tightly regulated process involving numerous interactions of receptors including the T‐cell receptor (TCR):CD3 complex, co‐stimulatory receptors, and appropriate signaling molecules, resulting in production of cytokines as well as clonal expansion and differentiation of effector T lymphocytes. In this review, current knowledge of the mechanisms of lymphocyte activation as well as potential targets for various immunosuppressive agents are discussed.
New targets for immunosuppression in kidney transplantation: Focus on recent clinical trials
Authors: Wojciechowski David , Vincenti Flavio 
Published: January 2011

AbstractSigniﬁcant advances have been made in post‐kidney transplantation immunosuppression. The introduction of calcineurin inhibitors (CNIs) has led to a reduction in acute rejection and improved 1‐year outcomes. However, long‐term allograft survival has not improved. This may in part be due to the chronic nephrotoxicity of CNIs and negative effects on the cardiovascular and metabolic risk proﬁle via worsening hypertension, diabetes, and dyslipidemia. New drug development now focuses on maintaining low rejection rates but maximizing long‐term allograft survival and modulating the cardio‐metabolic side effects seen with CNIs. Two small molecules are currently undergoing Phase 2 investigation. CP‐690550 (tasocitinib) is a JAK 3 inhibitor, and AEB‐071 (sotrastaurin) is a protein kinase C inhibitor. Two biologic agents are also undergoing development. Belatacept is a humanized antibody that blocks the T‐cell co‐stimulation pathway and has had promising results in both Phase 2 and 3 investigation. Alefacept is a humanized antibody that inhibits T‐cell adhesion and is currently undergoing Phase 2 investigation. This article will review the mechanisms of these drugs and outline the available trial data results.
The role of mTOR inhibition in renal transplant immune suppression
Authors: Patel Samir J. , Dawson Kyle L. , Knight Richard J. , Abdellatif Abdul , Achkar Katafan , Gaber Lillian W. , Gaber A. Osama 
Published: January 2011

AbstractThe mammalian target of rapamycin inhibitors (mTOR‐Is) sirolimus and everolimus represent a class of proliferation signal inhibitors with a wide spectrum of activities, including suppression of T‐cell proliferation and reduction of tumor growth. In solid‐organ transplantation, mTOR inhibitors are an option for maintenance immune suppression due to their relative lack of nephrotoxicity compared with the current backbone of most regimens, the calcineurin inhibitors (CNIs). This property, in conjunction with their unique pharmacology, allows mTOR‐Is to be used as an adjunct or alternative to CNIs. Earlier studies of their use in de novo renal transplantation have delineated potential strategies for use of this class of drugs in groups of patients in whom mTOR inhibition may be useful. From recent kidney studies it appears that the time for introduction of mTOR‐I therapy may be prior to the development of proteinuria or signiﬁcant graft deterioration. Consideration should also be given to the use of mTOR‐Is in patients with or at high risk of post‐transplant malignancy. Due to potential toxicities, knowledge of the adverse effects and pharmacokinetic proﬁles of mTOR‐Is is necessary for proper management of patients receiving these agents.
Belatacept in renal transplantation
Authors: Yost Sarah E. , Ranga K. Vinay , Kaplan Bruce 
Published: January 2011

AbstractBelatacept is a novel agent that prevents CD28 signaling and inhibits T‐cell activation by costimulation blockade. It was developed from abatacept (CTLA‐4 Ig), the ﬁrst recombinant immunoglobulin fusion protein that contains extracellular portion of CTLA‐4, and the Fc domain of IgG. Early studies have shown that belatacept recipients show comparable patient and graft survival, superior renal function and renal biopsy data compared with cyclo‐sporine‐treated patients. Newer biologic agents such as belatacept offer the promise of real change—due to their lack of mechanism‐related toxic effects—and help monitor drug administration, thereby improving compliance. Belatacept is a potential option for maintenance biologic therapy without a calcineurin inhibitor, accompanied by excellent mid‐term results with yet unknown long‐term safety and efﬁcacy. The increased rate of TCMR and possibly central nervous system post‐transplantation lymphoproliferative disorder are worrisome and need to be further elucidated.