bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Novel Chemical Probe for the Selective Enrichment of Phosphorylated Serine‐ and Threonine‐Containing Peptides
Authors: van der Veken Pieter , Dirksen Eef H. C. , Ruijter Eelco , Elgersma Ronald C. , Heck Albert J. R. , Rijkers Dirk T. S. , Slijper Monique , Liskamp Rob M. J. 
Published: October 2005

AbstractGaining insight into phosphoproteomes is of the utmost importance for understanding regulation processes such as signal transduction and cellular differentiation. While the identification of phosphotyrosine‐containing amino acid sequences in peptides and proteins is now becoming possible, mainly because of the availability of high‐affinity antibodies, no general and robust methodology allowing the selective enrichment and analysis of serine‐ and threonine‐phosphorylated proteins and peptides is presently available. The method presented here involves chemical modification of phosphorylated serine or threonine residues and their subsequent derivatization with the aid of a multifunctional probe molecule. The designed probe contains four parts: a reactive group that is used to bind specifically to the modified phosphopeptide, an optional part in which heavy isotopes can be incorporated, an acid‐labile linker, and an affinity tag for the selective enrichment of modified phosphopeptides from complex mixtures. The acid‐cleavable linker allows full recovery from the affinity‐purified material and removal of the affinity tag prior to MS analysis. The preparation of a representative probe molecule containing a biotin affinity tag and its applicability in phosphoproteome analysis is shown in a number of well‐defined model systems of increasing degrees of complexity. Amounts of phosphopeptide as low as 1 nmol can be modified and enriched from a mixture of peptides. During the development of the β‐elimination/nucleophilic addition protocol, special attention was paid to the different experimental parameters that might affect the chemical‐modification steps carried out on phosphorylated residues.
Solid Film versus Solution‐Phase Charge‐Recombination Dynamics of exTTF–Bridge–C60 Dyads
Authors: Handa Samantha , Giacalone Francesco , Haque Saif A. , Palomares Emilio , Martín Nazario , Durrant James R. 
Published: October 2005

AbstractThe charge‐recombination dynamics of two exTTF–C60 dyads (exTTF=9,10‐bis(1,3‐dithiol‐2‐ylidene)‐9,10‐dihydroanthracene), observed after photoinduced charge separation, are compared in solution and in the solid state. The dyads differ only in the degree of conjugation of the bridge between the donor (exTTF) and the acceptor (C60) moieties. In solution, photoexcitation of the nonconjugated dyad C60–BN–exTTF (1) (BN=1,1′‐binaphthyl) shows slower charge‐recombination dynamics compared with the conjugated dyad C60–TVB–exTTF (2) (TVB=bisthienylvinylenebenzene) (lifetimes of 24 and 0.6 μs, respectively), consistent with the expected stronger electronic coupling in the conjugated dyad. However, in solid films, the dynamics are remarkably different, with dyad 2 showing slower recombination dynamics than 1. For dyad 1, recombination dynamics for the solid films are observed to be tenfold faster than in solution, with this acceleration attributed to enhanced electronic coupling between the geminate radical pair in the solid film. In contrast, for dyad 2, the recombination dynamics in the solid film exhibit a lifetime of 7 μs, tenfold slower than that observed for this dyad in solution. These slow recombination dynamics are assigned to the dissociation of the initially formed geminate radical pair to free carriers. Subsequent trapping of the free carriers at film defects results in the observed slow recombination dynamics. It is thus apparent that consideration of solution‐phase recombination data is of only limited value in predicting the solid‐film behaviour. These results are discussed with reference to the development of organic solar cells based upon molecular donor–acceptor structures.
Electron‐Rich Tetrathiafulvalene–Triarylamine Conjugates: Synthesis and Redox Properties
Authors: Li Hongchao , Lambert Christoph 
Published: October 2005

AbstractBy combining tetrathiafulvalenes (TTFs) and triarylamines, four TTF–triarylamine conjugates bridged by an annulated pyrrole ring were designed and synthesized by an N‐arylation reaction. Electrochemical and photophysical investigations suggest that these novel conjugates possess very strong electron‐donating ability with very high HOMO energy levels of around −4.70 eV; the HOMOs are mainly located on the TTF moiety. We observed significant electronic coupling between the TTF moieties and the triarylamine groups. However, no evidence for such electronic communication between end‐capping TTF units (conjugates 5 and 7) or between two terminal triarylamine groups (conjugate 9) could be found. Differential scanning calorimetry (DSC) measurements together with PM3‐optimized geometries suggest that conjugates 5 and 7, which adopt three‐dimensional propeller‐shaped structures, may easily pack and crystallize in the solid state because of the large rigid planar blades consisting of TTF and one of the phenyl rings of the triarylamine moiety. However, conjugate 9, with two bulky end‐capping triarylamine groups, forms an amorphous material with a glass transition at 74.5 °C.
The Hit‐to‐Lead Process at Schering AG: Strategic Aspects
Authors: Steinmeyer Andreas 
Published: October 2005

AbstractModern organizations conducting drug‐discovery programs frequently apply high‐throughput screening to generate novel hit structures for the indications of interest. Systematic hit‐to‐lead processes have been established at most pharmaceutical companies to ensure a smooth conversion of hits into high‐quality lead structures. At Schering AG, a hit‐to‐lead process with distinct selection criteria was introduced in 1999 to identify the best leads possible. The thorough evaluation of hits and lead candidates allows risk assessments, which facilitate the assignment of valuable resources to those lead‐discovery projects with the most chances of success. A dedicated hit‐to‐lead team has been formed to oversee the process and to provide guidance to the respective project teams.
Unitary hypothesis for multiple triggers of the pain and strain of migraine
Authors: Burstein Rami , Jakubowski Moshe 
Published: October 2005

AbstractMigraine headache is triggered by and associated with a variety of hormonal, emotional, nutritional, and physiological changes. The perception of migraine headache is formed when nociceptive signals originating in the meninges are conveyed to the somatosensory cortex through the trigeminal ganglion, medullary dorsal horn, and thalamus. Is there a common descending pathway accounting for the activation of meningeal nociceptors by different migraine triggers? We propose that different migraine triggers activate a wide variety of brain areas that impinge on parasympathetic neurons innervating the meninges. According to this hypothesis, migraine triggers such as perfume, stress, or awakening activate multiple hypothalamic, limbic, and cortical areas, all of which contain neurons that project to the preganglionic parasympathetic neurons in the superior salivatory nucleus (SSN). The SSN, in turn, activates postganglionic parasympathetic neurons in the sphenopalatine ganglion, resulting in vasodilation and local release of inflammatory molecules that activate meningeal nociceptors. Are there ascending pathways through which the trigeminovascular system can induce the wide variety of migraine symptoms? We propose that trigeminovascular projections from the medullary dorsal horn to selective areas in the midbrain, hypothalamus, amygdala, and basal forebrain are functionally positioned to produce migraine symptoms such as irritability, loss of appetite, fatigue, depression, or the quest for solitude. Bidirectional trafficking by which the trigeminovascular system can activate the same brain areas that have triggered its own activity in the first place provides an attractive network of perpetual feedback that drives a migraine attack for many hours and even days. J. Comp. Neurol. 493:9–14, 2005. © 2005 Wiley‐Liss, Inc.
Relevance of an evidence‐based ejaculation time cutoff point for neurobiological research of premature ejaculation
Authors: Waldinger Marcel D. 
Published: October 2005

AbstractThe Diagnostic and Statistical Manual (DSM)‐IV definition of premature ejaculation is not based on evidence‐based studies. In particular, the absence of a well‐defined quantitative measure of the intravaginal ejaculation latency time (IELT) makes the DSM definition inadequate. Therefore, the DSM‐IV definition should be replaced by a medical definition that incorporates both quantitative as qualitative parameters of premature ejaculation. An evidence‐based medical definition should include a cutoff point of the IELT at the 0.5 and 2.5 percentiles of the IELT distribution in the general male population. Such a definition has recently been proposed on the basis of a stopwatch study of the IELT in 491 men from five different countries. Similarly, a cutoff point of ejaculation frequency in laboratory rats enhances the probability to distinguish genuine rapid‐ejaculator rats. Only by the strict application of these cutoff points is the probability enhanced that human and animal neurobiological research can prove whether these sexual endophenotypes differ in brain activation, have particular genetic genotypes (polymorphisms), are strictly under genetic control, or are dependent on environmental conditions and/or genotypic/environmental interactions. J. Comp. Neurol. 493:46–50, 2005. © 2005 Wiley‐Liss, Inc.
Role of Barrington's nucleus in micturition
Authors: Sasaki Mitsuyoshi 
Published: October 2005

AbstractBarrington's nucleus is a central component of the micturition circuit. This nucleus projects axons to the sacral parasympathetic nucleus, where preganglionic neurons innervating the urinary bladder are located. To clarify the functional role of this nucleus, the firing properties of Barrington's neurons that project axons to the spinal cord were examined. Based on these studies, a model begins to emerge that places Barrington's nucleus in the micturition pathway that is involved in increasing bladder pressure rapidly and strongly, while also maintaining high bladder pressure. In addition, Barrington's neurons are suggested to have another role, that is, increasing the probability of micturition contraction by activating a spinal excitatory pathway or disinhibiting a spinal inhibitory mechanism. In contrast to the excitatory role of Barrington's nucleus, this nucleus does not seem to trigger bladder relaxation. J. Comp. Neurol. 493:21–26, 2005. © 2005 Wiley‐Liss, Inc.
Generalized arousal of mammalian central nervous system
Authors: Pfaff Donald , Westberg Lars , Kow Lee‐Ming 
Published: October 2005

AbstractA fundamental capacity of the mammalian CNS is becoming amenable to study with the techniques of functional genomics. Emphasized in this review are ascending connections from the medullary reticular formation and descending connections from the paraventricular nucleus of the hypothalamus. In particular, sex hormone effects on neurons allow us to relate generalized arousal to a specific form of arousal which is required for reproductive behaviors. J. Comp. Neurol. 493:86–91, 2005. © 2005 Wiley‐Liss, Inc.
Neural mechanisms of freezing and passive aversive behaviors
Authors: Jhou Thomas 
Published: October 2005

AbstractCues that predict aversive outcomes often produce marked inhibitions of behavior known as freezing, but it is unknown exactly what neural pathways cause this inhibition. The amygdala and bed nucleus of the stria terminalis, along with their projections to the periaqueductal gray, are strongly implicated in freezing, but it is not known how these structures inhibit motor output. The median raphe nucleus (MRN), which contains a major population of serotonin neurons, has also been implicated in freezing, but the serotonin neurons themselves do not seem to be involved, leaving it uncertain which neurons in this area promote freezing. Our recent work suggests that GABAergic neurons just lateral to the MRN, but not within the MRN, regulate freezing via projections to midbrain dopamine neurons. Because freezing pathways may control a variety of other passive aversive behaviors, their elucidation may help understand the mechanisms of addictions and compulsions, which involve a failure of aversive outcomes to inhibit behavior. J. Comp. Neurol. 493:111–114, 2005. © 2005 Wiley‐Liss, Inc.
Free will versus survival: Brain systems that underlie intrinsic constraints on behavior
Authors: Price Joseph L. 
Published: October 2005

AbstractThis article discusses the neuroanatomical systems involved in the related functions of fear and discernment of the consequences of one's actions, two internal constraints on free will and action. Both mechanisms are related to a system for control and modulation of visceral function stretching from the spinal cord to the ventromedial prefrontal cortex, including the ventral striatum, ventral pallidum, and mediodorsal thalamus, the amygdala, the hypothalamus, the periaqueductal gray (PAG), and the brainstem reticular formation and autonomic nuclei. Reflexes at the lower levels provide rapid visceral and somatic reactions to threatening stimuli, while the PAG and hypothalamus coordinate these to produce more concerted responses. The amygdala interacts with the cortical sensory systems in the assessment of fear‐related stimuli and modulates the reflex responses through projections to the hypothalamus and brainstem. The ventromedial prefrontal cortex, especially the “medial prefrontal network,” is connected to the amygdala, hypothalamus, and PAG, and allows cortical control over the system in relation to a wider set of emotions. This cortical region is involved both in the assessment of reward and in mood disorders and it plays a central role in the ability to discern the consequences of one's actions and make appropriate behavioral choices. It also forms an interconnected circuit with specific cortical areas in the rostral superior temporal cortex, posterior parahippocampal cortex, and retrosplenial/posterior cingulate cortex. The overall function of this circuit is unclear, but may be involved in introspective monitoring of the individual. J. Comp. Neurol. 493:132–139, 2005. © 2005 Wiley‐Liss, Inc.
Intrinsic brain activity sets the stage for expression of motivated behavior
Authors: Raichle Marcus E. , Gusnard Debra A. 
Published: October 2005

AbstractResearch in many species has provided increasingly detailed information on relevant, primarily subcortical brain systems supporting the expression of basic appetites and drives. While basic appetites and drives are essential for adaptation and survival in any environment, they are naturally constrained by an organism's inherent biology and modulated as circumstances dictate. The brain mechanisms which serve to constrain and modulate them, however, remain much less well understood. We suggest that the manner in which such constraint and potential modulation is achieved likely involves processes that emerge from the coordinated behavior of multiple brain systems, and functional brain imaging techniques such as PET and fMRI are beginning to help us understand aspects of such coordination. In this review we argue that, in pursuit of this understanding, we must focus not only on changes evoked in brain systems during various behaviors, but also on the ongoing and very costly intrinsic activity within these systems, for the latter may be at least as important as the evoked activity in terms of brain function in general and the constraint and modulation of basic appetites and drives in particular. Distinguishing intrinsic from evoked activity in the context of functional brain imaging experiments is challenging, however. Here we review some evolving strategies for doing so. J. Comp. Neurol. 493:167–176, 2005. © 2005 Wiley‐Liss, Inc.
Immunohistochemical localization of GAD67‐expressing neurons and processes in the rat brainstem: Subregional distribution in the nucleus tractus solitarius
Authors: Fong Angelina Y. , Stornetta Ruth L. , Foley C. Michael , Potts Jeffrey T. 
Published: October 2005

AbstractThe role of γ‐aminobutyric acid (GABA) in homeostatic control in the brainstem, in particular, in the nucleus tractus solitarius (NTS), is well established. However, to date, there is no detailed description of the distribution of GABAergic neurons within the NTS. The goal of the current study was to reexamine the efficacy of immunohistochemical localization of glutamic acid decarboxylase (GAD) protein, specifically the 67‐kDa isoform (GAD67), as a marker for GABAergic neurons in the medulla and to provide a detailed map of GAD67‐immunoreactive (‐ir) cells within rat NTS by using a recently developed mouse monoclonal antibody. We describe a distribution of GAD67‐ir cells in the medulla similar to that reported previously from in situ hybridization study. GAD67‐ir cells were localized in regions known to contain high GABA content, including the ventrolateral medulla, raphe nuclei, and area postrema, but were absent from all motor nuclei, although dense terminal labeling was discerned in these regions. In the NTS, GAD67‐ir was localized in all subregions. Semiquantitative analysis of the GAD67‐ir distribution in the NTS revealed greater numbers of GAD67‐ir cells medial to the solitary tract. Finally, dense GAD67 terminal labeling was found in the medial, central, intermediate, commissural, and subpostremal subregions, whereas sparse labeling was observed in the ventral subregion. Our findings support the use of immunohistochemistry for GAD67 as a marker for the localization of GABAergic cells and terminal processes in the rat brainstem. Furthermore, the reported heterogeneous distribution of GAD67‐ir in the NTS suggests differential inhibitory modulation of sensory processing. J. Comp. Neurol. 493:274–290, 2005. © 2005 Wiley‐Liss, Inc.
Expression and function of the neuronal gap junction protein connexin 36 in developing mammalian retina
Authors: Hansen Kristi A. , Torborg Christine L. , Elstrott Justin , Feller Marla B. 
Published: October 2005

AbstractWith the advent of transgenic mice, much has been learned about the expression and function of gap junctions. Previously, we reported that retinal ganglion cells in mice lacking the neuronal gap junction protein connexin 36 (Cx36) have nearly normal firing patterns at postnatal day 4 (P4) but many more asynchronous action potentials than wild‐type mice at P10 (Torborg et al. [2005] Nat. Neurosci. 8:72–78). With the goal of understanding the origin of this increased activity in Cx36–/– mice, we used a transgenic mouse (Deans et al. [2001] Neuron 31:477–485) to characterize the developmental expression of a Cx36 reporter in the retina. We found that Cx36 was first detected weakly at P2 and gradually increased in expression until it reached an adult pattern at P14. Although the onset of expression varied by cell type, we identified Cx36 in the glycinergic AII amacrine cell, glutamatergic cone bipolar cell, and retinal ganglion cells (RGCs). In addition, we used calcium imaging and multielectrode array recording to characterize further the firing patterns in Cx36–/– mice. Both correlated and asynchronous action potentials in P10 Cx36–/– RGCs were significantly inhibited by bath application of an ionotropic glutamate receptor antagonist, indicating that the increase in activity was synaptically mediated. Hence, both the expression patterns and the physiology suggest an increasing role for Cx36‐containing gap junctions in suppressing RGC firing between waves during postnatal retinal development. J. Comp. Neurol. 493:309–320, 2005. © 2005 Wiley‐Liss, Inc.
Frontotemporal and dopaminergic control of idea generation and creative drive
Authors: Flaherty Alice W. 
Published: October 2005

AbstractThis article presents a three‐factor anatomical model of human idea generation and creative drive, focusing on interactions between the temporal lobes, frontal lobes, and limbic system. Evidence is drawn from functional imaging, drug studies, and lesion analysis. Temporal lobe changes, as in hypergraphia, often increase idea generation, sometimes at the expense of quality. Frontal lobe deficits may decrease idea generation, in part because of rigid judgments about an idea's worth. These phenomena are clearest in verbal creativity, and roughly parallel the pressured communication of temporal lobe epilepsy, mania, and Wernicke's aphasia—compared to the sparse speech and cognitive inflexibility of depression, Broca's aphasia, and other frontal lobe lesions. The phenomena also shape non‐linguistic creativity, as in that of frontotemporal dementia. The appropriate balance between frontal and temporal activity is mediated by mutually inhibitory corticocortical interactions. Mesolimbic dopamine influences novelty seeking and creative drive. Dopamine agonists and antagonists have opposite effects on goal‐directed behavior and hallucinations. Creative drive is not identical to skill—the latter depends more on neocortical association areas. However, drive correlates better with successful creative output than skill does. Traditional neuroscientific models of creativity, such as the left brain – right brain hemispheric model, emphasize skills primarily, and stress art and musical skill at the expense of language and mathematics. The three‐factor model proposed here predicts findings in a broad range of normal and pathological states and can be tested in many experimental paradigms. J. Comp. Neurol. 493:147–153, 2005. © 2005 Wiley‐Liss, Inc.
Neural control of ejaculation
Authors: Coolen Lique M. 
Published: October 2005

AbstractEjaculation is the most reinforcing component of sexual behavior. However, the neural substrates mediating ejaculation and processing ejaculation‐related signals remain poorly understood. We review the current understanding of central control of ejaculation. Specifically, the recent identification of a candidate spinothalamic pathway involved in relay of ejaculation‐specific signals is discussed. In addition, the discovery of a neural population of lumbar interneurons playing an pivotal role in expression of ejaculation is reviewed. J. Comp. Neurol. 493:39–45, 2005. © 2005 Wiley‐Liss, Inc.
Development and evolution of hidden regulators: Selective breeding for an infantile phenotype
Authors: Brunelli Susan A. 
Published: October 2005

AbstractMother‐infant separation in the rat has been used as an analytical tool to reveal biosocial processes underlying infant physiology and behavior. The same strategy has guided a project in which selective breeding for an infantile behavior has provided insights into how biological systems become recruited and integrated as expressions of temperamental affective responses. Two lines of rats (High and Low USV lines) were selectively bred based on rates of USV emission to maternal separation and isolation at postnatal day (P) 10. After many generations of breeding, the High and Low lines show widespread and distinctly different profiles of physiology and behavior in the first 3 weeks of life. Insights gained from longitudinal studies suggest that selection may work by reorganizing developmental processes, not just a given trait, over the postnatal period. As animal models, the lines have the potential to provide valuable tools for understanding developmental mechanisms underlying genetic and developmental risk for depression/anxiety syndromes in children and adults. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 47: 243–252, 2005.