Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3&beta;/4E-BP1, and muscle atrophy, including TNF&alpha;/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 &plusmn; 0.2 years) and 16 older (70 &plusmn; 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40&ndash;45% in the type II muscle fibers. TNF&alpha; and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3&beta; were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNF&alpha;, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.<br /

Living with severe allergy: an Anaphylaxis Campaign national survey of young people

<p>Abstract</p> <p>Background</p> <p>The transition to adulthood can be particularly challenging for young people with severe allergies, who must learn to balance personal safety with independent living. Information and support for young people and their families are crucial to successfully managing this transition. We sought to: gather insights into the impact of severe allergies on the lives of young people; explore where young people go for information about anaphylaxis and what information they want and need; identify areas where further support is needed.</p> <p>Methods</p> <p>An online questionnaire survey of young people aged 15–25 years with severe allergies in the United Kingdom (UK) was conducted on behalf of the Anaphylaxis Campaign, the main patient support organisation. Participants were recruited mainly from the Anaphylaxis Campaign membership database and also via allergy clinics and social media. The study was funded by the Anaphylaxis Campaign’s In Memoriam Fund.</p> <p>Results</p> <p>A total of 520 young people responded to the survey. The majority had lived with severe allergies since they were young children; 59% reported having attended Accident and Emergency units as a consequence of their allergies. Only 66% of respondents reported always carrying their epinephrine auto-injectors; only 23% had ever used these. Few were currently receiving specialist allergy care; younger respondents were more likely to be under specialist care (34%) than those 18 years and above (23%). Respondents wanted more information about eating out (56%), travelling (54%) and food labelling (43%). Almost a quarter of respondents (23%) reported needing more information on managing their allergies independently without parental help. Managing allergies in the context of social relationships was a concern for 22% of respondents.</p> <p>Conclusions</p> <p>This survey has identified the information and support needs and gaps in service provision for young people with severe allergies. Healthcare professionals and patient support organisations, with the support of the food industry, can help to meet these needs.</p

Steps toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. XII. Ground-Based Monitoring of 3C 390.3

Results of a ground-based optical monitoring campaign on 3C 390.3 in 1994-95 are presented. The broad-band fluxes (B, V, R, and I), the spectrophotometric optical continuum flux F(5177) and the integrated emission-line fluxes of Ha, Hb, Hg, HeI, and HeII all show a nearly monotonic increase with episodes of milder short-term variations superposed. The amplitude of the continuum variations increases with decreasing wavelength (4400-9000 A). The optical continuum variations follow the variations in the ultraviolet and X-ray with time delays, measured from the centroids of the cross- correlation functions, typically around 5 days, but with uncertainties also typically around 5 days; zero time delay between the high-energy and low-energy continuum variations cannot be ruled out. The strong optical emission lines Ha, Hb, Hg, and HeI respond to the high-energy continuum variations with time delays typically about 20 days, with uncertainties of about 8 days. There is some evidence that HeII responds somewhat more rapidly, with a time delay of around 10 days, but again, the uncertainties are quite large (~8 days). The mean and rms spectra of the Ha and Hb line profiles provide indications for the existence of at least three distinct components located at +-4000 and 0 km/s relative to the line peak. The emission-line profile variations are largest near line center.Comment: 42 pages (Latex), 13 figures, 14 table

Optimized two-dimensional thin layer chromatography to monitor the intracellular concentration of acetyl phosphate and other small phosphorylated molecules

Acetyl phosphate (acetyl-P) serves critical roles in coenzyme A recycling and ATP synthesis. It is the intermediate of the Pta-AckA pathway that inter-converts acetyl-coenzyme A and acetate. Acetyl-P also can act as a global signal by donating its phosphoryl group to specific two-component response regulators. This ability derives from its capacity to store energy in the form of a high-energy phosphate bond. This bond, while critical to its function, also destabilizes acetyl-P in cell extracts. This lability has greatly complicated biochemical analysis, leading in part to widely varying acetyl-P measurements. We therefore developed an optimized protocol based on two-dimensional thin layer chromatography that includes metabolic labeling under aerated conditions and careful examination of the integrity of acetyl-P within extracts. This protocol results in greatly improved reproducibility, and thus permits precise measurements of the intracellular concentration of acetyl-P, as well as that of other small phosphorylated molecules

The rapid assembly of an elliptical galaxy of 400 billion solar masses at a redshift of 2.3

Stellar archeology shows that massive elliptical galaxies today formed rapidly about ten billion years ago with star formation rates above several hundreds solar masses per year (M_sun/yr). Their progenitors are likely the sub-millimeter-bright galaxies (SMGs) at redshifts (z) greater than 2. While SMGs' mean molecular gas mass of 5x10^10 M_sun can explain the formation of typical elliptical galaxies, it is inadequate to form ellipticals that already have stellar masses above 2x10^11 M_sun at z ~ 2. Here we report multi-wavelength high-resolution observations of a rare merger of two massive SMGs at z = 2.3. The system is currently forming stars at a tremendous rate of 2,000 M_sun/yr. With a star formation efficiency an order-of-magnitude greater than that of normal galaxies, it will quench the star formation by exhausting the gas reservoir in only ~200 million years. At a projected separation of 19 kiloparsecs, the two massive starbursts are about to merge and form a passive elliptical galaxy with a stellar mass of ~4x10^11 M_sun. Our observations show that gas-rich major galaxy mergers, concurrent with intense star formation, can form the most massive elliptical galaxies by z ~ 1.5.Comment: Appearing in Nature online on May 22 and in print on May 30. Submitted here is the accepted version (including the Supplementary Information), see nature.com for the final versio

Intravital Two-Photon Microscopy of Immune Cell Dynamics in Corneal Lymphatic Vessels

BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM). Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible physiological conditions

Dressed for Sex: Red as a Female Sexual Signal in Humans

Background: In many non-human primate species, a display of red by a female serves as a sexual signal to attract male conspecifics. Red is associated with sex and romance in humans, and women convey their sexual interest to men through a variety of verbal, postural, and behavioral means. In the present research, we investigate whether female red ornamentation in non-human primates has a human analog, whereby women use a behavioral display of red to signal their sexual interest to men. Methodology/Principal Findings: Three studies tested the hypothesis that women use red clothing to communicate sexual interest to men in profile pictures on dating websites. In Study 1, women who imagined being interested in casual sex were more likely to display red (but not other colors) on their anticipated web profile picture. In Study 2, women who indicated interest in casual sex were more likely to prominently display red (but not other colors) on their actual web profile picture. In Study 3, women on a website dedicated to facilitating casual sexual relationships were more likely to prominently exhibit red (but not other colors) than women on a website dedicated to facilitating marital relationships. Conclusions/Significance: These results establish a provocative parallel between women and non-human female primates in red signal coloration in the mating game. This research shows, for the first time, a functional use of color in women’s sexual self-presentation, and highlights the need to extend research on color beyond physics, physiology, and preference to psychological functioning

An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.

Progressive hearing loss is common in the human population, but little is known about the molecular basis. We report a new N-ethyl-N-nitrosurea (ENU)-induced mouse mutant, diminuendo, with a single base change in the seed region of Mirn96. Heterozygotes show progressive loss of hearing and hair cell anomalies, whereas homozygotes have no cochlear responses. Most microRNAs are believed to downregulate target genes by binding to specific sites on their mRNAs, so mutation of the seed should lead to target gene upregulation. Microarray analysis revealed 96 transcripts with significantly altered expression in homozygotes; notably, Slc26a5, Ocm, Gfi1, Ptprq and Pitpnm1 were downregulated. Hypergeometric P-value analysis showed that hundreds of genes were upregulated in mutants. Different genes, with target sites complementary to the mutant seed, were downregulated. This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally

Female Fertility Affects Men's Linguistic Choices

We examined the influence of female fertility on the likelihood of male participants aligning their choice of syntactic construction with those of female confederates. Men interacted with women throughout their menstrual cycle. On critical trials during the interaction, the confederate described a picture to the participant using particular syntactic constructions. Immediately thereafter, the participant described to the confederate a picture that could be described using either the same construction that was used by the confederate or an alternative form of the construction. Our data show that the likelihood of men choosing the same syntactic structure as the women was inversely related to the women's level of fertility: higher levels of fertility were associated with lower levels of linguistic matching. A follow-up study revealed that female participants do not show this same change in linguistic behavior as a function of changes in their conversation partner's fertility. We interpret these findings in the context of recent data suggesting that non-conforming behavior may be a means of men displaying their fitness as a mate to women

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods