Vitamin D Intake,Month the Mammogram Was Taken and Mammographic Density in Norwegian Women Aged 50–69

BackgroundThe role of vitamin D in breast cancer etiology is unclear. There is some, but inconsistent, evidence that vitamin D is associated with both breast cancer risk and mammographic density (MD). We evaluated the associations of MD with month the mammogram was taken, and with vitamin D intake, in a population of women from Norway—a country with limited sunlight exposure for a large part of the year.Methods3114 women aged 50–69, who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004 or 2006/07, completed risk factor and food frequency (FFQ) questionnaires. Dietary and total (dietary plus supplements) vitamin D, calcium and energy intakes were estimated by the FFQ. Month when the mammogram was taken was recorded on the mammogram. Percent MD was assessed using a computer assisted method (Madena, University of Southern California) after digitization of the films. Linear regression models were used to investigate percent MD associations with month the mammogram was taken, and vitamin D and calcium intakes, adjusting for age, body mass index (BMI), study year, estrogen and progestin therapy (EPT), education, parity, calcium intakes and energy intakes.ResultsThere was no statistical significant association between the month the mammogram was taken and percent MD. Overall, there was no association between percent MD and quartiles of total or dietary vitamin D intakes, or of calcium intake. However, analysis restricted to women aged <55 years revealed a suggestive inverse association between total vitamin D intake and percent MD (p for trend = 0.03).ConclusionOverall, we found no strong evidence that month the mammogram was taken was associated with percent MD. We found no inverse association between vitamin D intake and percent MD overall, but observed a suggestive inverse association between dietary vitamin D and MD for women less than 55 years old.     

Association between Levels of Serum Ferritin and Bone Mineral Density in Korean Premenopausal and Postmenopausal Women: KNHANES 2008–2010

Background

As women go through menopause, serum estrogen decreases and ferritin increases. Decreased serum estrogen is well known to cause detrimental effects on bone health; however, data on the associations of serum ferritin with BMD before and after menopause are still lacking. Therefore, this study aimed to investigate the association between serum ferritin levels and BMD in premenopausal and postmenopausal Korean women.

Methods

This study was performed using data from the 2008–2010 Korean National Health and Nutrition Examination Survey, including 7300 women (4229 premenopausal and 3071 postmenopausal). BMD was measured using dual X-ray absorptiometry at the femur and the lumbar spine, and serum ferritin levels were measured by chemiluminescent immunoassay.

Results

Median serum ferritin levels in postmenopausal women were higher than those in premenopausal women despite the same age ranges. Serum ferritin levels were only significantly correlated with BMD on the lumbar spine (β = −0.189, p-value = 0.005) in premenopausal women after adjusting confounding factors. Additionally, BMD on the lumbar spine had tended to decrease as serum ferritin quartiles increase (P for trend = 0.035) in premenopausal women after adjusting confounding factors. On the other hand, there were no significant associations between serum ferritin levels and BMD on the total femur and, femur neck in premenopausal women, and BMD on the total femur, femur neck, and lumbar spine in postmenopausal women.

Conclusion

Increased serum ferritin levels were significantly associated with BMD in premenopausal women, particularly on the lumbar spine, but not in postmenopausal women.     

Differences in Sensitivity to Cold in Japanese Men and Postmenopausal Women Aged ≥50 Years

Background: Sensitivity to cold is associated with several factors, such as aging, sex, and body composition. However, no previous studies have examined the differences in sensitivity to cold in men and women or the association of hormonal levels with sensitivity to cold.Objective: The aim of the present study was to clarify both the change in sensitivity to cold with aging and the difference in sensitivity to cold between men and women. Associations were also examined between circulating hormonal concentrations and the changes with aging and differences in sensitivity.Methods: This population-based cohort study enrolled healthy Japanese men and women aged ≥ 50 years. A standardized 210-item health questionnaire was used to obtain information on symp- toms of sensitivity to cold. Serum concentrations of luteinizing hormone, follicle-stimulating hor- mone (FSH), estradiol, testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globu- lin (SHBG) were measured.Results: Of the 154 men and 180 women enrolled in this study, more women than men had sensitivity to cold. Whereas the percentage of men who had sensitivity to cold significantly increased with aging (P < 0.05), the percentage of women who had sensitivity to cold was already high (23.7%) at 50 to 60 years of age and did not change with aging. In men, advancing age and low body mass index (BMI) were significantly associated with sensitivity to cold (P < 0.05); however, age and BMI in women were not similarly associated. In addition, the effect of sex after adjustment for age was significant (P < 0.05), and there was also a numeric but nonsignificant effect of sex after adjustment for BMI. In men, low serum levels of the gonadal hormone FSH were significantly associated with sensitivity to cold in logistic analysis, but this association was nonsignificant after multivariate analysis. Serum concentrations of gonadal hormones and SHBG in women were not associated with sensitivity to col.Conclusions: The association of age with sensitivity to cold was different in men and women; the association of BMI with sensitivity to cold might be different in men and women. In addition, these changes in sensitivity to cold were not associated with circulating hormonal concentrations.     

Prevalence and Burden of Gait Disorders in Elderly Men and Women Aged 60–97 Years: A Population-Based Study

Background

Although gait disorders are common in the elderly, the prevalence and overall burden of these disorders in the general community is not well defined.

Methods

In a cross-sectional investigation of the population-based Bruneck Study cohort, 488 community-residing elderly aged 60–97 years underwent a thorough neurological assessment including a standardized gait evaluation. Gait disorders were classified according to an accepted scheme and their associations to falls, neuropsychological measures, and quality of life were explored.

Results

Overall, 32.2% (95% confidence interval [CI] 28.2%–36.4%) of participants presented with impaired gait. Prevalence increased with age (p<0.001), but 38.3% (95%CI 30.1%–47.3%) of the subjects aged 80 years or older still had a normally preserved gait. A total of 24.0% (95%CI 20.4%–28.0%) manifested neurological gait disorders, 17.4% (14.3%–21.0%) non-neurological gait problems, and 9.2% (6.9%–12.1%) a combination of both. While there was no association of neurological gait disorders with gender, non-neurological gait disorders were more frequent in women (p = 0.012). Within the group of neurological gait disorders 69.2% (95%CI 60.3%–76.9%) had a single distinct entity and 30.8% (23.1%–39.7%) had multiple neurological causes for gait impairment. Gait disorders had a significant negative impact on quantitative gait measures, but only neurological gait disorders were associated with recurrent falls (odds ratio 3.3; 95%CI 1.4–7.5; p = 0.005 for single and 7.1; 2.7–18.7; p<0.001 for multiple neurological gait disorders). Finally, we detected a significant association of gait disorders, in particular neurological gait disorders, with depressed mood, cognitive dysfunction, and compromised quality of life.

Conclusions

Gait disorders are common in the general elderly population and are associated with reduced mobility. Neurological gait disorders in particular are associated with recurrent falls, lower cognitive function, depressed mood, and diminished quality of life.     

Clinal Variation at Phenology-Related Genes in Spruce: Parallel Evolution in FTL2 and Gigantea?

Parallel clines in different species, or in different geographical regions of the same species, are an important source of information on the genetic basis of local adaptation. We recently detected latitudinal clines in SNPs frequencies and gene expression of candidate genes for growth cessation in Scandinavian populations of Norway spruce (Picea abies). Here we test whether the same clines are also present in Siberian spruce (P. obovata), a close relative of Norway spruce with a different Quaternary history. We sequenced nine candidate genes and 27 control loci and genotyped 14 SSR loci in six populations of P. obovata located along the Yenisei river from latitude 56°N to latitude 67°N. In contrast to Scandinavian Norway spruce that both departs from the standard neutral model (SNM) and shows a clear population structure, Siberian spruce populations along the Yenisei do not depart from the SNM and are genetically unstructured. Nonetheless, as in Norway spruce, growth cessation is significantly clinal. Polymorphisms in photoperiodic (FTL2) and circadian clock (Gigantea, GI, PRR3) genes also show significant clinal variation and/or evidence of local selection. In GI, one of the variants is the same as in Norway spruce. Finally, a strong cline in gene expression is observed for FTL2, but not for GI. These results, together with recent physiological studies, confirm the key role played by FTL2 and circadian clock genes in the control of growth cessation in spruce species and suggest the presence of parallel adaptation in these two species.     

Neurotropin Suppresses Inflammatory Cytokine Expression and Cell Death through Suppression of NF-κB and JNK in Hepatocytes

Inflammatory response and cell death in hepatocytes are hallmarks of chronic liver disease, and, therefore, can be effective therapeutic targets. Neurotropin® (NTP) is a drug widely used in Japan and China to treat chronic pain. Although NTP has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the action mechanism of NTP remains elusive. We hypothesize that NTP functions to suppress inflammatory pathways, thereby attenuating disease progression. In the present study, we investigated whether NTP suppresses inflammatory signaling and cell death pathways induced by interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) in hepatocytes. NTP suppressed nuclear factor-κB (NF-κB) activation induced by IL-1β and TNFα assessed by using hepatocytes isolated from NF-κB-green fluorescent protein (GFP) reporter mice and an NF-κB-luciferase reporter system. The expression of NF-κB target genes, Il6, Nos2, Cxcl1, ccl5 and Cxcl2 induced by IL-1β and TNFα was suppressed after NTP treatment. We also found that NTP suppressed the JNK phosphorylation induced by IL-1β and TNFα. Because JNK activation contributes to hepatocyte death, we determined that NTP treatment suppressed hepatocyte death induced by IL-1β and TNFα in combination with actinomycin D. Taken together, our data demonstrate that NTP attenuates IL-1β and TNFα-mediated inflammatory cytokine expression and cell death in hepatocytes through the suppression of NF-κB and JNK. The results from the present study suggest that NTP may become a preventive or therapeutic strategy for alcoholic and non-alcoholic fatty liver disease in which NF-κB and JNK are thought to take part.     

Variation in Ambrosia pollen concentration in Southern and Central Poland in 1982–1999

The aim of the study was to investigate theAmbrosia pollen concentrations inselected Polish cities and for Kraków torelate it to some meteorological factors.Sampling was carried out in Kraków in1982–1997 and in Rabka in 1992–1996 with theuse of the gravimetric method. In Zakopane,Kraków, Ostrowiec witokrzyski,Warszawa and Pozna in 1995–1996 both thegravimetric and volumetric methods (Burkardtrap) were employed. In Kraków themonitoring has been performed since 1994 usingthe volumetric method. The results show theragweed pollen presence in August and Septemberwith the tendency to appear more frequently inAugust in some years. In Kraków (1994–1999)Ambrosia pollen was found either in thelast two weeks of August or in the first twoweeks of September which seems to be a regularand repeatable pattern every two years.Seasonal fluctuations of Ambrosia pollenconcentration do not show a clear increasingtendency except at Warszawa and Ostrowiecwitokrzyski in 1996 and at Krakówin 1999. Percentage of Ambrosia pollen inannual sums of total pollen is very low anddoes not exceed 1% except at Ostrowiecwitokrzyski in 1996 (1.2%) and atKraków in 1999 (2%). For Kraków theanalysis of some meteorological factors (Tmax,Tmin, precipitation, wind direction) wasperformed. High temperature and lack of rain orlow precipitation correlate well with ragweedpollen concentrations. During the Ambrosia pollen seasons ESE, E, S, SE, WSW, SWwind directions prevailed which could suggest along-distance transport from Ukraine, the CzechRepublic, Slovakia and also from Hungary, one ofthe most ragweed-polluted countries.     

Prevalence and Incidence of Memory Complaints in Employed Compared to Non-Employed Aged 55–64 Years and the Role of Employment Characteristics

Objectives

To examine the association of employment status and characteristics with prevalent and incident memory complaints (MC) in 55–64-year-olds.

Methods

Subjects were participants of the Longitudinal Aging Study Amsterdam (LASA). Respondents with baseline data were selected to examine the association of employment status (n = 1525) and employment characteristics (n = 1071) with prevalent MC (i.e., MC at baseline). Respondents without MC at baseline were selected to examine the association of employment (n = 526) and employment characteristics (n = 379; working hours, job prestige, job level, psychological job demands, iso-strain) with incident MC (i.e., no MC at baseline and MC at three-year follow-up). Associations were adjusted for relevant covariates (demographics, memory performance, physical health, mental health, personality traits). Logistic regression was applied. Data were weighed according to gender and age of the Dutch population.

Results

At baseline 20.5% reported MC. At three-year follow-up, 15.4% had incident MC. No associations were found between employment status and MC. Adjusted analysis revealed that individuals with high occupational cognitive demands were more likely to have prevalent MC.

Conclusions

Middle-aged workers are equally as likely to experience MC as non-working age-peers. Among workers, those with cognitively demanding work were more likely to experience MC, independent of memory performance. Memory decline due to ageing may be noticed sooner in 55–64-year-olds performing cognitively demanding work.     

Comparison of Neuronal Death,Blood–Brain Barrier Leakage and Inflammatory Cytokine Expression in the Hippocampal CA1 Region Following Mild and Severe Transient Forebrain Ischemia in Gerbils

Neurochemical Research - Transient ischemia in the brain causes blood–brain barrier (BBB) breakdown and dysfunction, which is related to ischemia-induced neuronal damage. Leakage of plasma...     

Use of Smokeless Tobacco by Indian Women Aged 18–40 Years during Pregnancy and Reproductive Years

Objectives

This paper discusses patterns of daily smokeless tobacco (SLT) use and correlates of poly SLT use among married women aged 18–40 years in a Mumbai slum community with implications for tobacco control.

Methods

Using a mixed methods approach, the study included a structured survey with 409 daily SLT users and in-depth interviews with 42 women. Participants for the survey were selected using a systematic sampling procedure (one woman in every fourth eligible household). Univariate and bivariate analysis, and multiple logistic regressions were conducted to identify demographic and social factors associated with women’s use of poly SLT products. To illustrate survey results, in-depth interviews were analyzed using Atlas ti software.

Results

Sixty-four percent of the women surveyed used only one type of SLT; of these, 30% used mishri, 32% used pan with tobacco and the rest used chewed tobacco (11%), gul (17%) or gutkha (10%). Thirty-six percent used more than one type of SLT. Poly SLT users chewed or rubbed 50% more tobacco as compared to single users (mean consumption of tobacco per day: 9.54 vs. 6.49 grams; p<0.001). Women were more likely to be poly SLT users if they were illiterate as compared to literate (adjusted odds ratio [AOR]=1.67; 95% confidence interval [CI]=1.07-2.71), if they had lived in Mumbai for 10 years or more, versus less than ten years (AOR=1.67, 95% CI=1.03-2.71); and if their husband was a poly SLT user as compared to a non SLT user (AOR=2.78, 95% CI=1.63-4.76). No differences were noted between pregnant and non-pregnant women in SLT consumption patterns.

Conclusions

Tobacco control policies and programs must focus specifically on both social context and use patterns to address SLT use among women of reproductive age with special attention to poly SLT users, an understudied and vulnerable population.     

Mortality and Life Expectancy in Homeless Men and Women in Rotterdam: 2001–2010

Background

Data on mortality among homeless people are limited. Therefore, this study aimed to describe mortality patterns within a cohort of homeless adults in Rotterdam (the Netherlands) and to assess excess mortality as compared to the general population in that city.

Methods

Based on 10-year follow-up of homeless adults aged ≥ 20 years who visited services for homeless people in Rotterdam in 2001, and on vital statistics, we assessed the association of mortality with age, sex and type of service used (e.g. only day care, convalescence care, other) within the homeless cohort, and also compared mortality between the homeless and general population using Poisson regression. Life tables and decomposition methods were used to examine differences in life expectancy.

Results

During follow-up, of the 2096 adult homeless 265 died. Among the homeless, at age 30 years no significant sex differences were found in overall mortality rates and life expectancy. Compared with the general Rotterdam population, mortality rates were 3.5 times higher in the homeless cohort. Excess mortality was larger in women (rate ratio [RR] RR 5.56, 95% CI 3.95–7.82) as compared to men (RR 3.31, 95% CI 2.91–3.77), and decreased with age (RR 7.67, 95% CI 6.87–8.56 for the age group 20–44 and RR 1.63, 95% CI 1.41–1.88 for the age group 60+ years). Life expectancy at age 30 years was 11.0 (95% CI 9.1–12.9) and 15.9 (95% CI 10.3–21.5) years lower for homeless men and women compared to men and women in the general population respectively.

Conclusion

Homeless adults face excessive losses in life expectancy, with greatest disadvantages among homeless women and the younger age groups.     

Variation and covariation in infectivity,virulence and immunodepression in the host–parasite association Gammarus pulex–Pomphorhynchus laevis

Parasites often manipulate host immunity for their own benefit, either by exacerbating or suppressing the immune response and this may directly affect the expression of parasite virulence. However, genetic variation in immunodepression, which is a prerequisite to its evolution, and the relationship between immunodepression and virulence, have rarely been studied. Here, we investigated the variation among sibships of the acanthocephalan parasite, Pomphorhynchus laevis, in infecting and in immunodepressing its amphipod host, Gammarus pulex. We also assessed the covariation between infectivity, parasite-induced immune depression and host mortality (parasite virulence). We found that infectivity, the intensity of immunodepression and virulence were variable among parasite sibships. Infectivity and the level of immunodepression were not correlated across parasite sibships. Whereas infectivity was unrelated to host mortality, we found that gammarids that were exposed to the parasite sibships that immunodepressed their hosts the most survived better. This positive covariation between host survival and immunodepression suggests that gammarids exposed to the less immunodepressive parasites could suffer from damage imposed by a higher activity of the phenoloxidase.     

Association Study of Polymorphisms in Selenoprotein Genes and Kashin–Beck Disease and Serum Selenium/Iodine Concentration in a Tibetan Population

Background

Kashin-Beck disease is a kind of degenerative osteoarthropathy. Genetic factors may play an important role in the pathogenesis of KBD.

Objective

To investigate the association of the selenoprotein genes GPX1 (rs1050450, rs1800668, and rs3811699), TrxR2 (rs5748469), and DIO2 (rs225014) with Kashin-Beck disease (KBD) in a Tibetan population and to investigate the association of these SNPs with the serum iodine/selenium concentration in the Tibetan population.

Design

Five SNPs including rs1050450, rs1800668, and rs3811699 in the GPX1 gene, rs5748469 in the TrxR2 gene, and rs225014 in the DIO2 gene were analyzed in Tibetan KBD patients and controls using the SNaPshot method. P trend values of the SNPs were calculated using an additive model.

Results

None of the five SNPs in the three genes showed a significant association with KBD. Haplotypes TCC, TTC and TTT of rs1050450, rs1800668 and rs3811699 in GPX1 showed a significant association with KBD and controls with P value of 0.0421, 5.0E-4 and 0.0066, respectively. The GPX1 gene (rs1050450) showed a potential significant association with the iodine concentration in the Tibetan study population (P = 0.02726). However, no such association was detected with the selenium concentration (P = 0.2849).

Conclusion(s)

In this study, we showed that single SNPs in the genes GPX1 (rs1050450, rs1800668 and rs3811699), TrxR2 (rs5748469), and DIO2 (rs225014) may not be significantly associated with KBD in a Tibetan population. However, haplotype analysis of SNPs rs1050450, rs1800668 and rs3811699 in GPX1 gene showed a significant association with KBD. The results suggested that GPX1 gene play a protective role in the susceptivity of KBD in Tibetans. Furthermore, the GPX1 gene (rs1050450) may be significantly associated with the serum iodine concentration in Tibetans.     

Vinpocetine Reduces Carrageenan-Induced Inflammatory Hyperalgesia in Mice by Inhibiting Oxidative Stress,Cytokine Production and NF-κB Activation in the Paw and Spinal Cord

Vinpocetine is a safe nootropic agent used for neurological and cerebrovascular diseases. The anti-inflammatory activity of vinpocetine has been shown in cell based assays and animal models, leading to suggestions as to its utility in analgesia. However, the mechanisms regarding its efficacy in inflammatory pain treatment are still not completely understood. Herein, the analgesic effect of vinpocetine and its anti-inflammatory and antioxidant mechanisms were addressed in murine inflammatory pain models. Firstly, we investigated the protective effects of vinpocetine in overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone (PBQ) and formalin. The intraplantar injection of carrageenan was then used to induce inflammatory hyperalgesia. Mechanical and thermal hyperalgesia were evaluated using the electronic von Frey and the hot plate tests, respectively, with neutrophil recruitment to the paw assessed by a myeloperoxidase activity assay. A number of factors were assessed, both peripherally and in the spinal cord, including: antioxidant capacity, reduced glutathione (GSH) levels, superoxide anion, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels, as well as nuclear factor kappa B (NF-κB) activation. Vinpocetine inhibited the overt pain-like behavior induced by acetic acid, PBQ and formalin (at both phases), as well as the carrageenan-induced mechanical and thermal hyperalgesia and associated neutrophil recruitment. Both peripherally and in the spinal cord, vinpocetine also inhibited: antioxidant capacity and GSH depletion; increased superoxide anion; IL-1β and TNF-α levels; and NF-κB activation. As such, vinpocetine significantly reduces inflammatory pain by targeting oxidative stress, cytokine production and NF-κB activation at both peripheral and spinal cord levels.     

Variation in style length and anther–stigma distance in Ixiolirion songaricum (Amaryllidaceae)

Variation in style length and anther–stigma distance (ASD) was investigated in 18 populations of Ixiolirion songaricum, an early-spring ephemeral perennial herb in northern Xinjiang. The effect of ASD on autonomous self-pollen deposition and seed set was assessed using bagging experiments. Seed production under autonomous self-pollination, cross-pollination and natural pollination was determined by manual pollination experiments. Stigmas of multiple flowers within an individual were sandwiched between two separate anther levels, and no individuals possessed approach or reverse herkogamy. Style length varied continuously among flowers, resulting in a wide range of variation in ASD. There were fewer flowers with a small ASD than with a large ASD in populations. ASD was negatively correlated with autonomous self-pollen deposition and seed set, but it was positively correlated with natural pollination seed set. Seed production under natural pollination was higher than that under autonomous self-pollination, but it was smaller than that under cross-pollination. Variation in style length and ASD among flowers was not caused by style or stamen elongation in I. songaricum, which differ from other species reported in literature that have continuous variation in style length and ASD.     

Who Cares About Marrying a Rich Man? Intelligence and Variation in Women’s Mate Preferences

Although robust sex differences are abundant in men and women’s mating psychology, there is a considerable degree of overlap between the two as well. In an effort to understand where and when this overlap exists, the current study provides an exploration of within-sex variation in women’s mate preferences. We hypothesized that women’s intelligence, given an environment where women can use that intelligence to attain educational and career opportunities, would be: (1) positively related to their willingness to engage in short-term sexual relationships, (2) negatively related to their desire for qualities in a partner that indicated wealth and status, and (3) negatively related to their endorsement of traditional gender roles in romantic relationships. These predictions were supported. Results suggest that intelligence may be one important individual difference influencing women’s mate preferences.     

Carbon–Nitrogen Interaction Modulates Plant Growth and Expression of Metabolic Genes in Rice

Carbon (C) and nitrogen (N) interact to coordinate their metabolism in achieving C:N homeostasis in all cellular organisms. Plant shoots and roots take up C and N, respectively, and the coordinated C and N assimilation is essential for normal plant growth and development. In this study, rice was used as a model system for the investigation of molecular mechanisms underlying C–N interactions and coordination in cereal species. We investigated the growth response of rice seedlings to a wide range of exogenous C:N availabilities and established balanced exogenous C:N that was optimal for rice seedling growth. To assess correlations between the modulation of plant growth and the regulation of metabolic gene expression by C:N availabilities, we examined the expression of PEPC, PK, NR, GS, and GOGAT in rice seedlings treated with four C:N availabilities: low C/low N, low C/high N, high C/low N, and high C/high N. It was found that their expression was subjected to complex regulation by C:N availabilities. Our results demonstrate that growth of shoot and root rice seedlings is regulated by C–N interaction and growth modulations are associated with changes in metabolic gene expression. Our findings suggest that rice is a useful model system for the investigation of regulation mechanisms responsible for C–N interaction and coordination in plants.     

Modeled Changes in Potential Grassland Productivity and in Grass-Fed Ruminant Livestock Density in Europe over 1961–2010

About 25% of European livestock intake is based on permanent and sown grasslands. To fulfill rising demand for animal products, an intensification of livestock production may lead to an increased consumption of crop and compound feeds. In order to preserve an economically and environmentally sustainable agriculture, a more forage based livestock alimentation may be an advantage. However, besides management, grassland productivity is highly vulnerable to climate (i.e., temperature, precipitation, CO₂ concentration), and spatial information about European grassland productivity in response to climate change is scarce. The process-based vegetation model ORCHIDEE-GM, containing an explicit representation of grassland management (i.e., herbage mowing and grazing), is used here to estimate changes in potential productivity and potential grass-fed ruminant livestock density across European grasslands over the period 1961–2010. Here “potential grass-fed ruminant livestock density” denotes the maximum density of livestock that can be supported by grassland productivity in each 25 km × 25 km grid cell. In reality, livestock density could be higher than potential (e.g., if additional feed is supplied to animals) or lower (e.g., in response to economic factors, pedo-climatic and biotic conditions ignored by the model, or policy decisions that can for instance reduce livestock numbers). When compared to agricultural statistics (Eurostat and FAOstat), ORCHIDEE-GM gave a good reproduction of the regional gradients of annual grassland productivity and ruminant livestock density. The model however tends to systematically overestimate the absolute values of productivity in most regions, suggesting that most grid cells remain below their potential grassland productivity due to possible nutrient and biotic limitations on plant growth. When ORCHIDEE-GM was run for the period 1961–2010 with variable climate and rising CO₂, an increase of potential annual production (over 3%) per decade was found: 97% of this increase was attributed to the rise in CO₂, -3% to climate trends and 15% to trends in nitrogen fertilization and deposition. When compared with statistical data, ORCHIDEE-GM captures well the observed phase of climate-driven interannual variability in grassland production well, whereas the magnitude of the interannual variability in modeled productivity is larger than the statistical data. Regional grass-fed livestock numbers can be reproduced by ORCHIDEE-GM based on its simple assumptions and parameterization about productivity being the only limiting factor to define the sustainable number of animals per unit area. Causes for regional model-data misfits are discussed, including uncertainties in farming practices (e.g., nitrogen fertilizer application, and mowing and grazing intensity) and in ruminant diet composition, as well as uncertainties in the statistical data and in model parameter values.     

Variation of protein binding cavity volume and ligand volume in protein–ligand complexes

We have systematically analyzed the variation of protein binding cavity volume of 200 protein–ligand complexes belonging to eight protein families. Wide variation in protein binding cavity volume for the same protein is observed on binding different ligands. Analysis of individual protein families shows high correlation between atom–atom interactions in binding site and ligand volume. This study implies the significance of protein flexibility in docking small molecule inhibitors on the basis of protein binding cavity volume with respect to ligand volume.