Habitat preferences and distribution characteristics are indicative of species long-term persistence in the Estonian flora

Large-scale changes in regional floras provide direct information about changes in biodiversity through time and enable the evaluation of conservation targets. We compared the distribution ranges in 2004 of Estonian native terrestrial flora with the distribution ranges before 1970, using the Atlas of Estonian Flora. Relative persistence was related to species endemism, commonness, occurrence at its border of the global distribution range, main habitat type, sensitivity to human impact, life-form, conservation category, and Red List category. A literature-based database of the flora of Estonian habitat types was used to evaluate relative persistence of the flora of different habitats. Changes in the flora are largely dependent on human activities. The decrease in mire and grassland habitats and the increase in forests are reflected in the persistences of related species. Flora of mire habitats decreased the most. The fact that an almost ten-fold decrease of grasslands has not resulted in as large a decrease in the ranges of grassland species could serve as evidence of the extinction debt of these habitats. We also found a greater decrease among habitat specialists than habitat generalists and lower average persistence of the species of species-rich habitats. Our data show that current prioritization of species for conservation is in concordance with needs, as reflected in the changes in the range of species. However, conservation has not been entirely successful: the decrease of protected species continues. Our simple method for summarizing large databases was effective for the evaluation of large scale effects of conservation actions.     

Conception date affects litter type and foetal sex ratio in female moose in Estonia

1.  The Trivers–Willard model of optimal sex ratios predicts that in polygynous species mothers in better condition should produce more male than female offspring. However, empirical support for this hypothesis in mammals and especially ungulates has been equivocal. This may be because the fitness of mothers has been defined in different ways, reflecting morphological, physiological or behavioural measures of condition. In addition, factors other than maternal condition can influence a mother's fitness. Given that recent studies of wild ungulates have demonstrated the importance of the timing of conception and birth on offspring fitness, litters conceived at different stages of the rut might be expected to exhibit differences in types and embryonic sex ratio.
2.  Based on a 6-year survey of the reproductive tracts of female moose harvested in Estonia, we investigated the effect of conception date on the types of litters produced and on the foetal sex ratio.
3.  There was a clear relationship between conception date and litter characteristics. Overall, earlier conceived litters were more likely than those conceived late to contain multiple embryos and a high proportion of males. However, while foetal sex ratio varied nonlinearly with conception date in yearlings and subadults, no relationship was found in adults.
4.  We conclude that female moose adjust foetal sex ratio and litter type/size depending on their age and the date of conception, and that these adjustments are in accordance with the Trivers–Willard hypothesis if females that conceive earlier are in better condition.     

Amyotrophic lateral sclerosis: an emerging era of collaborative gene discovery

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS.     

Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly

The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi. ADP-ribosylation factor-related protein 1 (ARFRP1) is a small trans-Golgi-associated guanosine triphosphatase (GTPase) that regulates protein sorting and is required for chylomicron lipidation and assembly in the intestine. Here we show that the hepatocyte-specific deletion of Arfrp1 (Arfrp1^liv−/−) results in impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state as well as after inhibition of lipoprotein lipase activity by Triton WR-1339. In addition, the concentration of ApoC3 that comprises 40% of protein mass of secreted VLDLs is markedly reduced in the plasma of Arfrp1^liv−/− mice but accumulates in the liver accompanied by elevated triglycerides. Fractionation of Arfrp1^liv−/− liver homogenates reveals more ApoB48 and a lower concentration of triglycerides in the Golgi compartments than in the corresponding fractions from control livers. In conclusion, ARFRP1 and the Golgi apparatus play an important role in lipoprotein maturation in the liver by influencing lipidation and assembly of proteins to the lipid particles.     

Association of Pericardial Fat With Liver Fat and Insulin Sensitivity After Diet‐Induced Weight Loss in Overweight Women

Pericardial adipose tissue (PAT) is positively associated with fatty liver and obesity‐related insulin resistance. Because PAT is a well‐known marker of visceral adiposity, we investigated the impact of weight loss on PAT and its relationship with liver fat and insulin sensitivity independently of body fat distribution. Thirty overweight nondiabetic women (BMI 28.2–46.8 kg/m², 22–41 years) followed a 14.2 ± 4‐weeks low‐calorie diet. PAT, abdominal subcutaneous (SAT), and visceral fat volumes (VAT) were measured by magnetic resonance imaging (MRI), total fat mass, trunk, and leg fat by dual‐energy X‐ray absorptiometry and intrahepatocellular lipids (IHCL) by (¹)H‐magnetic resonance spectroscopy. Euglycemic hyperinsulinemic clamp (M) and homeostasis model assessment of insulin resistance (HOMA_IR) were used to assess insulin sensitivity or insulin resistance. At baseline, PAT correlated with VAT (r = 0.82; P < 0.001), IHCL (r = 0.46), HOMA_IR (r = 0.46), and M value (r = ?0.40; all P < 0.05). During intervention, body weight decreased by ?8.5%, accompanied by decreases of ?12% PAT, ?13% VAT, ?44% IHCL, ?10% HOMA2‐%B, and +24% as well as +15% increases in HOMA2‐%S and M, respectively. Decreases in PAT were only correlated with baseline PAT and the loss in VAT (r = ?0.56; P < 0.01; r = 0.42; P < 0.05) but no associations with liver fat or indexes of insulin sensitivity were observed. Improvements in HOMA_IR and HOMA2‐%B were only related to the decrease in IHCL (r = 0.62, P < 0.01; r = 0.65, P = 0.002) and decreases in IHCL only correlated with the decrease in VAT (r = 0.61, P = 0.004). In conclusion, cross‐sectionally PAT is correlated with VAT, liver fat, and insulin resistance. Longitudinally, the association between PAT and insulin resistance was lost suggesting no causal relationship between the two.     

Clonal ability,height and growth form explain species’ response to habitat deterioration in Fennoscandian wooded meadows

Fennoscandian calcareous wooded meadows have high conservation value due to very high diversity which has been maintained by consistent mowing, but undergo species loss when this management is abandoned. We compared species richness and composition of regularly mown and abandoned wooded meadows in Estonia and established species groups with respect to their response to abandonment. These meadows were very species rich with a maximum of 43 species per 0.25 m². Species whose populations are maintained by mowing constituted >60 % of the floristic diversity of the mown wooded meadows. Abandonment suppressed species with a preference for dry infertile open habitats. Response to abandonment was related to clonality, height and growth form. The greatest negative response was associated with low graminoids, short-lived and non-clonal species, rosette and semi-rosette growth form. Weak competitors with low height and light seeds exhibited a slow decline; perennial life span and clonality enable a delay in local extinction of these species. Response groups had similar persistence at a national level, revealing that earlier assessment of species dynamics at larger spatial scales could underestimate the number of threatened species. Application of restoration measures could avoid local extinctions of many mowing-supported species, whereas some of the mowing-dependent species likely need reintroduction.     

1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines as TRPV1 antagonists with improved properties

Based upon a previously reported lead compound 1, a series of 1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines were synthesized and evaluated for improved physiochemical and pharmacokinetic properties while maintaining TRPV1 antagonist activity. Structure-activity relationship studies directed toward improving the aqueous solubility (pH 2 and fasted-state simulated intestinal fluid (SIF)) and rat pharmacokinetics led to the discovery of compound 13. Aqueous solubility of compound 13 (pH 2 ≥237 μg/mL and SIF=11 μg/mL) was significantly improved over compound 1 (pH 2=5 μg/mL and SIF=0.5 μg/mL). In addition, compound 13 afforded improved rat pharmacokinetics (CL=0.7 L/kg/h) compared to compound 1 (CL=3.1 L/kg/h). Compound 13 was orally bioavailable and afforded a significant reversal of carrageenan-induced thermal hyperalgesia at 5 and 30 mg/kg in rats.     

Serum Nogo-A levels are not elevated in amyotrophic lateral sclerosis patients

Improved biomarkers would facilitate the diagnosis and treatment of amyotrophic lateral sclerosis (ALS). Muscle content of the neuritic outgrowth inhibitor Nogo-A is increased in patients with ALS and other denervating conditions. Seeking a less invasive diagnostic method, we sought to determine whether or not Nogo increases in the serum of ALS patients. We developed a dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) protocol to screen serum samples from 172 ALS patients and 172 healthy controls for Nogo-A immunoreactivity. Unexpectedly, there was a trend toward decreased levels of serum Nogo-A in ALS. Mean serum Nogo-A level in ALS patients was 0.71?nM (95% confidence interval (CI) 0.42–1.00), as opposed to 1.15?nM (95% CI 0.72–1.59) in healthy controls. A significantly larger percentage of healthy control sera (11.0% vs 4.7%) displayed markedly elevated levels of Nogo-A. Additional study is required to determine the factors that lead to elevated Nogo-A levels in a subset of both ALS patients and healthy controls.     

Alternative transient states and slow plant community responses after changed flooding regimes

Climate change will have large consequences for flooding frequencies in freshwater systems. In interaction with anthropogenic activities (flow regulation, channel restoration and catchment land‐use) this will both increase flooding and drought across the world. Like in many other ecosystems facing changed environmental conditions, it remains difficult to predict the rate and trajectory of vegetation responses to changed conditions. Given that critical ecosystem services (e.g. bank stabilization, carbon subsidies to aquatic communities or water purification) depend on riparian vegetation composition, it is important to understand how and how fast riparian vegetation responds to changing flooding regimes. We studied vegetation changes over 19 growing seasons in turfs that were transplanted in a full‐factorial design between three riparian elevations with different flooding frequencies. We found that (a) some transplanted communities may have developed into an alternative stable state and were still different from the target community, and (b) pathways of vegetation change were highly directional but alternative trajectories did occur, (c) changes were rather linear but faster when flooding frequencies increased than when they decreased, and (d) we observed fastest changes in turfs when proxies for mortality and colonization were highest. These results provide rare examples of alternative transient trajectories and stable states under field conditions, which is an important step towards understanding their drivers and their frequency in a changing world.     

Epidemiology of Pediatric Functional Abdominal Pain Disorders: A Meta-Analysis

ObjectiveWe aimed to review the literature regarding epidemiology of functional abdominal pain disorders in children and to assess its geographic, gender and age distribution including associated risk factors of developing functional abdominal pain.MethodsThe Cochrane Library, MEDLINE, EMBASE, CINAHL and PsychInfo databases were systematically searched up to February 2014. Study selection criteria included: (1) studies of birth cohort, school based or general population samples (2) containing data concerning epidemiology, prevalence or incidence (3) of children aged 4-18 years (4) suffering from functional abdominal pain. Quality of studies was rated by a self-made assessment tool. A random-effect meta-analysis model was used to estimate the prevalence of functional abdominal pain in childhood.ResultsA total of 58 articles, including 196,472 children were included. Worldwide pooled prevalence for functional abdominal pain disorders was 13.5% (95% CI 11.8-15.3), of which irritable bowel syndrome was reported most frequently (8.8%, 95% CI 6.2-11.9). The prevalence across studies ranged widely from 1.6% to 41.2%. Higher pooled prevalence rates were reported in South America (16.8%) and Asia (16.5%) compared to Europe (10.5%). And a higher pooled prevalence was reported when using the Rome III criteria (16.4%, 95% CI 13.5-19.4). Functional abdominal pain disorders are shown to occur significantly more in girls (15.9% vs. 11.5%, pooled OR 1.5) and is associated with the presence of anxiety and depressive disorders, stress and traumatic life events.ConclusionFunctional abdominal pain disorders are a common problem worldwide with irritable bowel syndrome as most encountered abdominal pain-related functional gastrointestinal disorder. Female gender, psychological disorders, stress and traumatic life events affect prevalence.