Neurogenic hypothesis and psychiatric disorders

Psychiatric illness, such as affective disorders, anxiety disorders and schizophrenia, exerts exceptional personal burden on affected individuals. Although not physically noticeable, these disorders cost enormously on ones’ family and society. Currently pharma-ceutical and psychological treatments are generally accepted as effective for psychiatric disorders, while the exact mechanisms underlying the treatment efficacy, etiology and neurobiology of the disorders remain elusive. In the past decade, "neurogenic hy-pothesis" emerged as an attempt to explain the nature of psychiatric illness. The origination of the hypothesis is based on several pre-clinical and clinical observations. First, stress, which is a common risk factor of the disorders, was found to suppress neurogenesis; second, treatment for the illnesses like antidepressants and antipsychotics were shown to improve neurogenesis and behavioral deficits simultaneously; and third, the therapeutic effect of antidepressants was abolished in animal models when neuro-genesis was blocked. Increasing efforts were invested to determine whether neurogenesis is a key to the understanding and treatment of psychiatric disorders, although contrasting results are also found and thus the importance of neurogenesis remains a matter of debate. The present chapter will discuss the recent findings about the involvement of neurogenesis in major depression, anxiety disorders and schizophrenia, and whether neurogenesis would be a potential target for development of the treatment in the future.     

Winter survival of Northern Pintails in the Middle Rio Grande Valley, New Mexico

In response to continued low population numbers of Northern Pintail ( Anas acuta ) in North America and to increase knowledge of the geographic variation in pintail survival rates, we estimated 126-day (27 October–2 March) survival for male and female pintails wintering in the Middle Rio Grande Valley, New Mexico, during 2001–2002 (SY1) and 2002–2003 (SY2). Sixty-nine adult male and female pintails were marked with radio-transmitters and tracked throughout the study period. Weekly relocation data in relation to study year, sex, time (week), body condition at capture, and hunting seasons were modeled using the known-fate procedure in Program MARK. Year, sex, time, and body condition covariates did not improve model performance in estimating survival, so we used the most parsimonious model to produce an overall winter survival estimate of 0.597 ± 0.077 (95% C.I. = 0.442–0.735). Weekly survival estimates did not differ between hunting and nonhunting seasons. Male and female point estimates did not differ (χ 1 2 = 0.209, P = 0.65). Our adult female survival estimate of 0.639 ± 0.117 (95% C.I. = 0.396–0.827) was 5.5%–28.6% lower than published estimates for adult female pintails in 5 other geographic regions. No winter survival estimates for males in other geographic regions were available for direct comparison with our study. Although relatively small sample sizes may have contributed to the lack of statistical differences in weekly survival between years, sexes, and hunting seasons, as well as to the lack of influence of body condition, relatively abundant water and food resources and absence of hunting in a refuge setting contributed to consistent survival probabilities. Because our low survival estimates, relative to other geographic regions, cannot be attributed to hunting, we postulate that natural causes of mortality play a larger role in pintail survival in our study region than in other wintering regions.     

Differential use of an in-frame translation initiation codon regulates human mu opioid receptor (OPRM1)

The pharmacological effects of morphine and morphine-like drugs are mediated primarily through the μ opioid receptor. Here we show that differential use of an in-frame translational start codon in the 5′-untranslated region of the OPRM1 generates different translational products in vivo and in vitro. The 5′-end of the OPRM1 gene is necessary for initiating the alternate form and for subsequent degradation of the protein. Initiation of OPRM1 at the upstream site decreases the initiation at the main AUG site. However, alternative initiation of the long form of OPRM1 produces a protein with a short half-life, resulting from degradation mediated by the ubiquitin–proteasome pathway. Reporter and degradation assays showed that mutations of this long form at the second and third lysines reduce ubiquitin-dependent proteasome degradation, stabilizing the protein. The data suggest that MOP expression is controlled in part by initiation of the long form of MOP at the alternate site.     

Smad4 signalling in T cells is required for suppression of gastrointestinal cancer

SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling. Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer. Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis. This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours.     

Interplay of electron-lattice interactions and superconductivity in superconductivity in Bi2Sr2CaCu2O8+delta

Formation of electron pairs is essential to superconductivity. For conventional superconductors, tunnelling spectroscopy has established that pairing is mediated by bosonic modes (phonons); a peak in the second derivative of tunnel current d2I/dV2 corresponds to each phonon mode. For high-transition-temperature (high-T(c)) superconductivity, however, no boson mediating electron pairing has been identified. One explanation could be that electron pair formation and related electron-boson interactions are heterogeneous at the atomic scale and therefore challenging to characterize. However, with the latest advances in d2I/dV2 spectroscopy using scanning tunnelling microscopy, it has become possible to study bosonic modes directly at the atomic scale. Here we report d2I/dV2 imaging studies of the high-T(c) superconductor Bi2Sr2CaCu2O8+delta. We find intense disorder of electron-boson interaction energies at the nanometre scale, along with the expected modulations in d2I/dV2 (refs 9, 10). Changing the density of holes has minimal effects on both the average mode energies and the modulations, indicating that the bosonic modes are unrelated to electronic or magnetic structure. Instead, the modes appear to be local lattice vibrations, as substitution of 18O for 16O throughout the material reduces the average mode energy by approximately 6 per cent--the expected effect of this isotope substitution on lattice vibration frequencies. Significantly, the mode energies are always spatially anticorrelated with the superconducting pairing-gap energies, suggesting an interplay between these lattice vibration modes and the superconductivity.     

Space geodesy: subsidence and flooding in New Orleans

It has long been recognized that New Orleans is subsiding and is therefore susceptible to catastrophic flooding. Here we present a new subsidence map for the city, generated from space-based synthetic-aperture radar measurements, which reveals that parts of New Orleans underwent rapid subsidence in the three years before Hurricane Katrina struck in August 2005. One such area is next to the Mississippi River-Gulf Outlet (MRGO) canal, where levees failed during the peak storm surge: the map indicates that this weakness could be explained by subsidence of a metre or more since their construction.     

Long-term eruptive activity at a submarine arc volcano

Three-quarters of the Earth's volcanic activity is submarine, located mostly along the mid-ocean ridges, with the remainder along intraoceanic arcs and hotspots at depths varying from greater than 4,000 m to near the sea surface. Most observations and sampling of submarine eruptions have been indirect, made from surface vessels or made after the fact. We describe here direct observations and sampling of an eruption at a submarine arc volcano named NW Rota-1, located 60 km northwest of the island of Rota (Commonwealth of the Northern Mariana Islands). We observed a pulsating plume permeated with droplets of molten sulphur disgorging volcanic ash and lapilli from a 15-m diameter pit in March 2004 and again in October 2005 near the summit of the volcano at a water depth of 555 m (depth in 2004). A turbid layer found on the flanks of the volcano (in 2004) at depths from 700 m to more than 1,400 m was probably formed by mass-wasting events related to the eruption. Long-term eruptive activity has produced an unusual chemical environment and a very unstable benthic habitat exploited by only a few mobile decapod species. Such conditions are perhaps distinctive of active arc and hotspot volcanoes.