Have invisible barriers for women been broken in 2007, or do we still have to break through medicine's glass ceiling? Data from two of the most prestigious university hospitals in Barcelona with 700-800 beds, Hospital Clínic (HC) and Hospital de la Santa Creu i Sant Pau (HSCSP) address this issue. In the HSCSP, 87% of the department chairs are men and 85% of the department unit chiefs are also men. With respect to women, only 5 (13%) are in the top position (department chair) and 4 (15%) are department unit chiefs. Similar statistics are also found at the HC: 87% of the department chairs and 89% of the department unit chiefs are men. Currently, only 6 women (13%) are in the top position and 6 (11%) are department unit chiefs. Analysis of the 2002 data of internal promotions in HC showed that for the first level (senior specialist) sex distribution was similar. Nevertheless, for the second level (consultant) only 25% were women, and for the top level (senior consultant) only 8% were women. These proportions have not changed in 2007 in spite of a 10% increase in leadership positions during this period. Similar proportions were found in HSCSP where 68% of the top promotions were held by men. The data obtained from these two different medical institutions in Barcelona are probably representative of other hospitals in Spain. It would be ethically desirable to have males and females in leadership positions in the medical profession.

Bickel J. The work that remains at the intersection of gender and career development. Building on the study by Wagner et al, this commentary opens with a discussion of the persistence of gender disparities in career development and the challenge of interpreting those disparities. Given the multifaceted challenges facing rehabilitation medicine, facilitation of the career and leadership development of women physiatrists is critical. I suggest 3 areas of targeted action to facilitate the realization of women physiatrists' intellectual capital:(1) updated approaches to faculty and leadership development and mentoring,(2) more flexible faculty structures, and (3) chair support and accountability. Each member of the rehabilitation medicine community who cares about the future of the discipline is challenged to contribute to the dialogues that are necessary to carry these recommendations forward.

We examined the publication records of a cohort of 168 life scientists in the field of ecology and evolutionary biology to assess gender differences in research performance. Clear discrepancies in publication rate between men and women appear very early in their careers and this has consequences for the subsequent citation of their work. We show that a recently proposed index designed to rank scientists fairly is in fact strongly biased against female researchers, and advocate a modified index to assess men and women on a more equitable basis.

The controlling factors that prompt mature oligodendrocytes to myelinate axons are largely undetermined. In this study, we used a forward genetics approach to identify a mutant mouse strain characterized by the absence of CNS myelin despite the presence of abundant numbers of late-stage, process-extending oligodendrocytes. Through linkage mapping and complementation testing, we identified the mutation as a single nucleotide insertion in the gene encoding zinc finger protein 191 (Zfp191), which is a widely expressed, nuclear-localized protein that belongs to a family whose members contain both DNA-binding zinc finger domains and protein-protein-interacting SCAN domains. Zfp191 mutants express an array of myelin-related genes at significantly reduced levels, and our in vitro and in vivo data indicate that mutant ZFP191 acts in a cell-autonomous fashion to disrupt oligodendrocyte function. Therefore, this study demonstrates that ZFP191 is required for the myelinating function of differentiated oligodendrocytes.

Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.

A primer on new research by Fuentes-Medel and colleagues explains the important role of non-neural cells in clearing neural debris, which is continuously produced during the normal remodeling processes that establish and maintain neural connectivity.

The transcriptional control of CNS myelin gene expression is poorly understood. Here we identify gene model 98, which we have named myelin gene regulatory factor (MRF), as a transcriptional regulator required for CNS myelination. Within the CNS, MRF is specifically expressed by postmitotic oligodendrocytes. MRF is a nuclear protein containing an evolutionarily conserved DNA binding domain homologous to a yeast transcription factor. Knockdown of MRF in oligodendrocytes by RNA interference prevents expression of most CNS myelin genes; conversely, overexpression of MRF within cultured oligodendrocyte progenitors or the chick spinal cord promotes expression of myelin genes. In mice lacking MRF within the oligodendrocyte lineage, premyelinating oligodendrocytes are generated but display severe deficits in myelin gene expression and fail to myelinate. These mice display severe neurological abnormalities and die because of seizures during the third postnatal week. These findings establish MRF as a critical transcriptional regulator essential for oligodendrocyte maturation and CNS myelination.

Motion detection is an essential component of visual processing. On-Off direction-selective retinal ganglion cells (On-Off DSGCs) detect objects moving along specific axes of the visual field due to their precise retinal circuitry. The brain circuitry of On-Off DSGCs, however, is largely unknown. We report a mouse with GFP expressed selectively by the On-Off DSGCs that detect posterior motion (On-Off pDSGCs), allowing two-photon targeted recordings of their light responses and delineation of their complete map of central connections. On-Off pDSGCs project exclusively to the dorsal lateral geniculate nucleus and superior colliculus and in both targets form synaptic lamina that are separate from a lamina corresponding to non-DSGCs. Thus, individual On-Off DSGC subtypes are molecularly distinct and establish circuits that map specific qualities of directional motion to dedicated subcortical areas. This suggests that each RGC subtype represents a unique parallel pathway whose synaptic specificity in the retina is recapitulated in central targets.

Despite the importance of CNS blood vessels, the molecular mechanisms that regulate CNS angiogenesis and blood-brain barrier (BBB) formation are largely unknown. Here we analyze the role of Wnt/beta-catenin signaling in regulating the formation of CNS blood vessels. First, through the analysis of TOP-Gal Wnt reporter mice, we identify that canonical Wnt/beta-catenin signaling is specifically activated in CNS, but not non-CNS, blood vessels during development. This activation correlates with the expression of different Wnt ligands by neural progenitor cells in distinct locations throughout the CNS, including Wnt7a and Wnt7b in ventral regions and Wnt1, Wnt3, Wnt3a, and Wnt4 in dorsal regions. Blockade of Wnt/beta-catenin signaling in vivo specifically disrupts CNS, but not non-CNS, angiogenesis. These defects include reduction in vessel number, loss of capillary beds, and the formation of hemorrhagic vascular malformations that remain adherent to the meninges. Furthermore, we demonstrate that Wnt/beta-catenin signaling regulates the expression of the BBB-specific glucose transporter glut-1. Taken together these experiments reveal an essential role for Wnt/beta-catenin signaling in driving CNS-specific angiogenesis and provide molecular evidence that angiogenesis and BBB formation are in part linked.

Mechanistic studies of CNS myelination have been hindered by the lack of a rapidly myelinating culture system. Here, we describe a versatile CNS coculture method that allows time-lapse microscopy and molecular analysis of distinct stages of myelination. Employing a culture architecture of reaggregated neurons fosters extension of dense beds of axons from purified retinal ganglion cells. Seeding of oligodendrocyte precursor cells on these axons results in differentiation and ensheathment in as few as 3 days, with generation of compact myelin within 6 days. This technique enabled (1) the demonstration that oligodendrocytes initiate new myelin segments only during a brief window early in their differentiation,(2) identification of a contribution of astrocytes to the rate of myelin wrapping, and (3) molecular dissection of the role of oligodendrocyte gamma-secretase activity in controlling the ensheathment of axons. These insights illustrate the value of this defined system for investigating multiple aspects of CNS myelination.

A major challenge to understanding how cells work together in the central nervous system (CNS) is the heterogeneous cellular composition of the brain. In this issue, Heiman et al.(2008) and Doyle et al.(2008) introduce a new strategy (TRAP) that enables the profiling of translated mRNAs in specific CNS cell populations without the need for purifying cells to homogeneity.

In this perspective, I review recent evidence that glial cells are critical participants in every major aspect of brain development, function, and disease. Far more active than once thought, glial cells powerfully control synapse formation, function, and blood flow. They secrete many substances whose roles are not understood, and they are central players in CNS injury and disease. I argue that until the roles of nonneuronal cells are more fully understood and considered, neurobiology as a whole will progress only slowly.

The heading "Gender Psychopharmacology", presiding growing quantities of papers on the speciality, lacks coherence, altogether. The authors of the present essay discuss this phenomenon, that can be characterized as a misunderstanding, at best.

Transsexualism is incorrectly thought to be a disease of sexual centers (zones) of the brain but these sexual centers in the brain operate only in response to action of sexual hormones (androgens or estrogens) which are produced in the gonads and delivered to the brain by blood. In hermaphroditism the brain receives both androgens and estrogens. Transsexualism syndrome develops in cases when all sexual organs develop under the influence of one sex while sexual psychoorientation, sexual autoidentification and sexual behavior form under the influence of hormones of the other sex. Therefore, treatment of this syndrome should not consist of surgical correction of the sex according to psychic behavior of the patient but should be directed to detection of the gonad (or gonadal tissue) causing abnormal behavior and its removal. Gonad corresponding to sexual organs of the patient should be preserved. Of 19 patients with true hermaphroditism and 199 patients with false hermaphroditism observed by the authors 4 patients with true hermaphroditism had transsexualism.

The objective of the paper is the presentation of ideas on human sexuality development, disorders concerning this area, particularly transsexualism, homosexualism and social stigmatization of homosexuals with its consequences. Symptoms reported and identified by adolescents such as sexual identity disorder, can masque a different problem, for instance lack of self-acceptance of homosexual orientation in a person from a conservative environment. The presented case study illustrates this problem.

The aim of this study was to establish gender-associated differences in dendroarchitectonics of neurons in dorsomedial nucleus of amygdala and the role of androgens in their formation during the period of sexual differentiation of the brain. Using Golgi method, it was demonstrated that the quantitative characteristics of long-axon sparsely branched neurons of all classes--neuroblastoform, short-dendrite and reticular--reflected the influence of gender. Specifically, it was detected that long-axon sparsely branched neurons had more branching primary dendrites and greater total dendrite length in adult males as compared to females. In adult females, androgenized neonatally by injection of 1250 mg of testosterone propionate on their postnatal day 5, the neuronal characteristics were different from those in normal females, and these differences were even more pronounced in comparison with males.

We analyzed sex differences in 696 patients with spontaneous cervical artery dissection. There were more men (n = 399; p < 0.0001), and men showed a higher frequency of hypertension (31% vs 15%; p < 0.0001). Women were younger (42.5 +/- 9.9 vs 47.5 +/- 9.3 years; p < 0.0001), had more often multiple dissections (18 vs 10%; p = 0.001), migraine (47 vs 20%; p < 0.0001), and tinnitus (16 vs 8%; p = 0.001). Outcome and mortality were similar in both sexes.