SHORT Syndrome with Partial Lipodystrophy Due to Impaired Phosphatidylinositol 3 Kinase Signaling

The phosphatidylinositol 3 kinase (PI3K) pathway regulates fundamental cellular processes such as metabolism, proliferation, and survival. A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1. Using whole-exome sequencing, we identified a heterozygous PIK3R1 mutation (c.1945C>T [p.Arg649Trp]) in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome). This mutation led to impaired interaction between p85α and IRS-1 and reduced AKT-mediated insulin signaling in fibroblasts from affected subjects and in reconstituted Pik3r1-knockout preadipocytes. Normal PI3K activity is critical for adipose differentiation and insulin signaling; the mutated PIK3R1 therefore provides a unique link among lipodystrophy, growth, and insulin signaling.     

Local temperatures inferred from plant communities suggest strong spatial buffering of climate warming across Northern Europe

Recent studies from mountainous areas of small spatial extent (<2500 km²) suggest that fine‐grained thermal variability over tens or hundreds of metres exceeds much of the climate warming expected for the coming decades. Such variability in temperature provides buffering to mitigate climate‐change impacts. Is this local spatial buffering restricted to topographically complex terrains? To answer this, we here study fine‐grained thermal variability across a 2500‐km wide latitudinal gradient in Northern Europe encompassing a large array of topographic complexities. We first combined plant community data, Ellenberg temperature indicator values, locally measured temperatures (LmT) and globally interpolated temperatures (GiT) in a modelling framework to infer biologically relevant temperature conditions from plant assemblages within <1000‐m² units (community‐inferred temperatures: CiT). We then assessed: (1) CiT range (thermal variability) within 1‐km² units; (2) the relationship between CiT range and topographically and geographically derived predictors at 1‐km resolution; and (3) whether spatial turnover in CiT is greater than spatial turnover in GiT within 100‐km² units. Ellenberg temperature indicator values in combination with plant assemblages explained 46–72% of variation in LmT and 92–96% of variation in GiT during the growing season (June, July, August). Growing‐season CiT range within 1‐km² units peaked at 60–65°N and increased with terrain roughness, averaging 1.97 °C (SD = 0.84 °C) and 2.68 °C (SD = 1.26 °C) within the flattest and roughest units respectively. Complex interactions between topography‐related variables and latitude explained 35% of variation in growing‐season CiT range when accounting for sampling effort and residual spatial autocorrelation. Spatial turnover in growing‐season CiT within 100‐km² units was, on average, 1.8 times greater (0.32 °C km^?1) than spatial turnover in growing‐season GiT (0.18 °C km^?1). We conclude that thermal variability within 1‐km² units strongly increases local spatial buffering of future climate warming across Northern Europe, even in the flattest terrains.     

Can Triticum urartu (Poaceae) be identified by pollen analysis? Implications for detecting the ancestor of the extinct two‐grained einkorn‐like wheat

The domestication of the one‐grained einkorn (Triticum monococcum) in the Near East is relatively well known. However, an independent two‐grained einkorn‐like domestication has been archaeobotanically detected and scarce information is available. Triticum urartu, a wild wheat, was not fully described until the 1970s because the phenology does not allow it to be distinguished easily from wild einkorn (Triticum boeoticum subsp. thaoudar), although a genetic separation exists. Both species are mostly two grained and could potentially be the relatives of the extinct two‐grained form. Pollen grains of several genetically well‐identified wheat species, including T. urartu and T. boeoticum subsp. thaoudar, were studied by measuring the grain diameter and examining the exine sculpturing with phase‐contrast microscopy and scanning electron microscopy to gain an insight into differences enabling taxonomic identification. This work showed that, although T. urartu pollen is smaller on average, grain diameter is not sufficient because of the size overlap between the species, but T. urartu presents a different exine sculpturing (scabrate) from other Triticum spp. (aerolate). This outcome is useful for taxonomists and archaeobotanists. First, it will allow a simple re‐classification of herbarium materials. Second, further research could establish whether T. urartu was cultivated. © 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2015, 177 , 278–289.     

The climate of the Younger Dryas as a boundary for Einkorn domestication

The domestication of the Neolithic founder crops of the Near East has recently been a topic of debate particularly with respect to how rapidly the domestication of these crops occurred. One school of thought maintains that these processes lasted several thousand years (‘protracted model’ with ‘gathering’, ‘cultivation’ and ‘domestication’ as three stages of a continuum, each taking up to several thousand years), while another favors the view that domestication occurred much more quickly, over several hundred years at most (‘rapid transition’). Our study focuses on one of these crops, 1-grained domesticated Einkorn wheat, incorporating data from geology, vegetation history, and climate. In the Karacadağ region of southeastern Turkey, where 1-grained Einkorn wheat was domesticated, the climate was severe (i.e. cold and dry) during the Younger Dryas. The climate of the Younger Dryas acted as boundary during which a) conditions were not suitable for ‘cultivation’, and b) Einkorn would have retreated to refugia exhibiting more suitable moisture-bearing soils that would have made ‘gathering’ difficult. Around 11600 cal. b.p., the Younger Dryas ended and a very rapid climatic amelioration commenced at the beginning of the Early Holocene, enabling grasses to spread throughout the region. A ritual PPNA/PPNB site (G?bekli Tepe) and associated PPNB settlements such as Nevali ?ori and ?ay?nü were established at this time. In the settlements of Nevali ?ori and Cafer H?yük, the oldest domesticated Einkorn was found in the earliest archaeological layers. This confirms that the inhabitants made use of domesticated 1-grained Einkorn from the very beginning of settlement activity, although they continued to practice a mixed lifestyle as hunter-gatherers and farmers. For ?ay?nü the issue is more complex, but here domesticated Einkorn also appears around the same time. In summary, by 10400 cal. b.p. domesticated 1-grained Einkorn was present in large quantities at a variety of sites. This would give a maximum window of time lasting approximately 1,200 years and is therefore not in agreement with the ‘protracted’ model but would be consistent with a ‘rapid transition’. It is improbable that the ‘cultivation’ of wild Einkorn was practiced in the Karacadağ region, since wild Einkorn was plentiful during the favorable growing conditions following the Younger Dryas, making it more likely that ‘gathering’ would have been practiced. Because Einkorn has not been found in early settlements in the southern Levant, this crop cannot have been ‘gathered’ and ‘cultivated’ there but instead was ‘domesticated’ independently and solely in southeastern Turkey. Therefore, the YD acts as a boundary, providing a maximum time frame for 1-grained Einkorn domestication.     

Short‐term costs related to male and female structures in alpine Parnassia palustris

The aim of this study was to investigate the potential costs related to male and female structures in a small, hermaphroditic alpine plant species, Parnassia palustris L. We studied in the field the effect of experimental manipulation of seed set (female structures) as well as anthers and staminodes (male structures) on next year's survival, flowering, seed set and growth. We found no statistically significant differences between the treatments in survival, number of flowers and fruits, fruit/flower ratio, seed number or mean mass per seed the following year. Furthermore, there was no statistically significant difference in growth response between the treatments. These observations indicate both that the manipulations of the flowers the previous year had no effect on growth and that the competition between growth and sexual reproduction was negligible. Our results may reflect small investments in reproduction, abundance of soil resources and/or that all resources saved by the plant one year are not necessarily invested in reproduction or growth next year.     

A five-year prospective study of fatigue in primary Sjögren's syndrome

Introduction  

Fatigue is prevalent in primary Sj?gren's syndrome (pSS), and contributes to the considerably reduced health related quality of life in this disease. The symptom is included in proposed disease activity and outcome measures for pSS. Several studies indicate that there is an inflammatory component of fatigue in pSS and other chronic inflammatory rheumatic diseases. The purpose of this study was to investigate fatigue change in pSS in a longitudinal study, and explore whether any clinical or laboratory variables at baseline, including serum cytokines, were associated with a change in fatigue scores over time.     

Oil removal and effects of spilled oil on active microbial communities in close to salt-saturation brines

Abiotic and biotic processes associated with the degradation of a light petroleum in brines close to the salt-saturation (~31 %) and the effect of labile organic matter (LOM) supply (casaminoacids/citrate; 0.2 and 0.1 % w/v, respectively) were followed during an incubation of 30 days. After 4-week incubation at 40 °C under light/dark cycles, a 24 % of abiotic degradation was observed in untreated brines. The stimulation of native brines community with LOM addition allowed an additional 12.8 % oil attenuation due to biodegradation processes. Successional changes in the active microbial community structure due to the oil contamination (16S rRNA DGGE approach) showed the selection of one phylotype affiliated to Salinibacter and the disappearance of Haloquadratum walsbyi in untreated brines. In LOM-amended microcosms, phylotypes related to Salinibacter, Haloarcula, Haloterrigena and Halorhabdus were selected. An effect of hydrocarbon contamination was only observed in the bacterial community with the inhibition of two dominant proteobacterial phylotypes. This study further confirms that short-term and moderate oil biodegradation is possible in LOM-stimulated brines. Biodegradation should be much more reduced under in situ conditions. Self-cleaning capacities of close to saturation hypersaline lakes appears, therefore very limited compared to non-extreme haline environments.     

Detection of anabolic steroid abuse using a yeast transactivation system

The classical analytical method for detection of anabolic steroid abuse is gas chromatography followed by mass spectrometry (GC/MS). However, even molecules with a chemical structure typical for this class of substances, are sometimes not identified in routine screening by GC/MS when their precise chemical structure is still unknown. A supplementary approach to identify anabolic steroid abuse could be a structure-independent identification of anabolic steroids based on their biological activity. To test the suitability of such a system, we have analyzed the yeast androgen receptor (AR) reporter gene system to identify anabolic steroids in human urine samples. Analysis of different anabolic steroids dissolved in buffer demonstrated that the yeast reporter gene system is able to detect a variety of different anabolic steroids and their metabolites with high specificity, including the so-called 'designer steroid' tetrahydrogestrinone. In contrast, other non-androgenic steroids, like glucocordicoids, progestins, mineralocordicoids and estrogens had a low potency to stimulate transactivation. To test whether the system would also allow the detection of androgens in urine, experiments with spiked urine samples were performed. The androgen reporter gene in yeast responds very sensitive to 5alpha-dihydrotestosterone (DHT), even at high urine concentrations. To examine whether the test system would also be able to detect anabolic steroids in the urine of anabolic steroid abusers, anonymous urine samples previously characterized by GCMS were analyzed with the reporter gene assay. Even when the concentration of the anabolic metabolites was comparatively low in some positive samples it was possible to identify the majority of positive samples by their biological activity. In conclusion, our results demonstrate that the yeast reporter gene system detects anabolic steroids and corresponding metabolites with high sensitivity even in urine of anabolic steroid abusing athletes. Therefore we believe that this system can be developed towards a powerful (pre) screening tool for the established doping tests. The system is easy to handle, robust, cost-efficient and needs no high-tech equipment. But most importantly, a biological test system does not require knowledge of the chemical structure of androgenic substances and therefore suitable to detect previously unidentified substances, especially those of the class of so-called designer steroids.     

Costs of reproduction in circumpolar <Emphasis Type="Italic">Parnassia palustris</Emphasis> L. in light of global warming

In frequently burnt savannas, saplings face the formidable challenge of both recovering from, and eventually growing tall enough to escape from, frequent fire damage. The aim of this study was to explore how saplings allocate carbon to achieve these ends through carbon partitioning, storage and remobilization. Lignotuber total non-structural carbohydrate (TNC) concentrations and δ¹³C values of Acacia karroo (Fabaceae; Mimosoideae) were determined in plants from two different juvenile stages. These were one year after a fire when the plant consisted of numerous leafy shoots or coppices (“coppicing” stage), and three years after a fire when the plant consisted of one pole-like stem (“Gulliver” stage). Gulliver lignotubers were found to have significantly larger TNC pools (150 g vs. 97 g) and larger TNC concentrations (33% vs. 24%, w/w) than coppice lignotubers showing that post-coppice Gullivers recharged TNC in the lignotuber. δ¹³C values from the stems of plants in the Gulliver stage were significantly enriched (>1‰) in ¹³C compared to both coppicing (P < 0.01) and adult (P < 0.05) plants. Changes in both the amount of stored carbon and in the δ¹³C values indicated dependence on stored carbon reserves, and partially heterotrophic growth for initial resprouting. The plants appeared to use both current photosynthate and stored carbon reserves for growth of the Gulliver stem. The use of stored carbon is hypothesized to promote fast stem growth rates to a height where saplings escape fire injury.