Temperature-related behavior of some migrant birds in the desert

Behavior of migrant birds in relation to temperature was studied and compared to that of resident species in the northern Mojave Desert. Migrants reduced foraging intensity above 30 C, but resident species showed no striking decrease in intensity of foraging at temperatures up to 35 C. Migrant species shifted activities to shaded microhabitats at temperatures between 20 and 30 C; the resident Verdin showed a similar shift at 35 C. Most migrants decreased the amount of time spent foraging at temperatures above 30; Verdins showed a similar but stronger response to temperatures about 30 C. Significant reductions in the use of hovering and hawking maneuvers were found among migrants at temperatures above 30 C. Migrants showed similar types of behavioral adjustments to temperatures as did resident desert species, but they responded earlier in the daily temperature cycle. Desert birds appear to correlate their daily activity strongly with temperature, but nondesert species may respond either to temperature or time of day.     

Colony isolation and isozyme variability of the western seep fritillary, Speyeria nokomis apacheana (Nymphalidae), in the western Great Basin

Thirteen Speyeria nokomis apacheana (Edwards) (Nymphalidae) populations from the western Great Basin were assayed for isozyme variability using starch-gel electrophoresis. Eight of the 25 presumptive isozyme loci analyzed were found to be polymorphic. Collections made in 1991and 1992 allowed for between-year comparisons of heterozygosity and the estimation of effective population size for five of the sampled populations. Speyeria nokomis apacheana populations exhibit lower mean heterozygosity levels than other nymphalids. This may be attributed to genetic drift in apparently isolated populations with small effective sizes.     

Dynamic personalities of proteins

Because proteins are central to cellular function, researchers have sought to uncover the secrets of how these complex macromolecules execute such a fascinating variety of functions. Although static structures are known for many proteins, the functions of proteins are governed ultimately by their dynamic character (or 'personality'). The dream is to 'watch' proteins in action in real time at atomic resolution. This requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.     

A black hole in a globular cluster

Globular star clusters contain thousands to millions of old stars packed within a region only tens of light years across. Their high stellar densities make it very probable that their member stars will interact or collide. There has accordingly been considerable debate about whether black holes should exist in these star clusters. Some theoretical work suggests that dynamical processes in the densest inner regions of globular clusters may lead to the formation of black holes of approximately 1,000 solar masses. Other numerical simulations instead predict that stellar interactions will eject most or all of the black holes that form in globular clusters. Here we report the X-ray signature of an accreting black hole in a globular cluster associated with the giant elliptical galaxy NGC 4472 (in the Virgo cluster). This object has an X-ray luminosity of about 4 x 10(39) erg s(-1), which rules out any object other than a black hole in such an old stellar population. The X-ray luminosity varies by a factor of seven in a few hours, which excludes the possibility that the object is several neutron stars superposed.     

Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis

Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the development and regulation of immunity to infection is unknown. Here we show that IEC-intrinsic IkappaB kinase (IKK)-beta-dependent gene expression is a critical regulator of responses of dendritic cells and CD4+ T cells in the GI tract. Mice with an IEC-specific deletion of IKK-beta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (T(H)2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40 and tumour necrosis factor-alpha, increased levels of CD4+ T-cell-derived interferon-gamma and interleukin-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKK-beta in IECs to promote CD4+ T(H)2 cell-dependent immunity, identifying an essential function for IECs in tissue-specific conditioning of dendritic cells and limiting type 1 cytokine production in the GI tract. These results indicate that the balance of IKK-beta-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation.     

In vivo genome editing restores haemostasis in a mouse model of haemophilia

Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. Genome editing improves on simple gene-replacement strategies by effecting in situ correction of a mutant gene, thus restoring normal gene function under the control of endogenous regulatory elements and reducing risks associated with random insertion into the genome. Gene-specific targeting has historically been limited to mouse embryonic stem cells. The development of zinc finger nucleases (ZFNs) has permitted efficient genome editing in transformed and primary cells that were previously thought to be intractable to such genetic manipulation. In vitro, ZFNs have been shown to promote efficient genome editing via homology-directed repair by inducing a site-specific double-strand break (DSB) at a target locus, but it is unclear whether ZFNs can induce DSBs and stimulate genome editing at a clinically meaningful level in vivo. Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease.     

Functional specificity of local synaptic connections in neocortical networks

Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.     

Cryptic and non-cryptic diversity in New Guinea ground snakes of the genus Stegonotus Duméril,Bibron and Duméril, 1854: a description of four new species (Squamata: Colubridae)

ABSTRACT

The island of New Guinea has been identified as biologically megadiverse but many taxa are still poorly known. This is especially the case for many of the island’s snakes, which by their very nature can be difficult to collect and study. Here we examine the phylogenetic and phylogeographic structure of a poorly studied snake genus, Stegonotus, focusing on the species of New Guinea; until now, Stegonotus has never been examined using modern phylogenetic methods. Using molecular data from 49 individuals representing eight of the ten described species, and including all New Guinea taxa, we estimate a multilocus phylogeny and examine population structure to help identify undescribed taxa. We use morphological data from the corresponding museum vouchered specimens (where available) and also examine additional specimens for taxa not included in the molecular data set to determine morphological differences among putative taxa. We find molecular evidence for four new species of Stegonotus, both morphologically obvious and cryptic, and describe them herein. The recognition of these four species indicates that Stegonotus diversity has been previously underestimated and also suggests that there are likely additional undescribed taxa within the genus. These four taxa increase the number of described species by 40% and further confirm New Guinea as the centre of diversity for the genus.

www.zoobank.org/urn:lsid:zoobank.org:pub:9E21390E-3FD4-40EB-9442-31BC92A76B4F     

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.