Sciatic and femoral nerve sensory neurones occupy different regions of the L4 dorsal root ganglion in the adult rat.

The topographical distribution of sciatic and femoral nerve sensory neuronal somata in the L4 dorsal root ganglion of the adult rat was mapped after retrograde tracing with one or two of the dyes Fast Blue, Fluoro-Gold, or Diamidino Yellow. The tracers were applied to the proximal transected end of either nerve alone, or from both nerves in the same animal using separate tracers. Three-dimensional reconstructions of the distribution of labelled neurones were made from serial sections of the L4 dorsal root ganglion which is the only ganglion that these two nerves share. The results showed that with little overlap, femoral nerve neurones distribute dorsally and rostrally whereas sciatic nerve neurones distribute medially and ventrally. This finding indicates the existence of a somatotopical organisation for the representation of different peripheral nerves in dorsal root ganglia of adult animals.

Correlation of the EPR properties of perchlorotriphenylmethyl radical and their efficiency as DNP polarizers

Water soluble perchlorinated trityl (PTM) radicals were found to be effective 95 GHz DNP (dynamic nuclear polarization) polarizers in ex situ (dissolution) 13C DNP (Gabellieri et al., Angew Chem., Int. Ed. 2010, 49, 3360). The degree of the nuclear polarization obtained was reported to be dependent on the position of the chlorine substituents on the trityl skeleton. In addition, on the basis of the DNP frequency sweeps it was suggested that the 13C NMR signal enhancement is mediated by the Cl nuclei. To understand the DNP mechanism of the PTM radicals we have explored the 95 GHz EPR characteristics of these radicals that are relevant to their performance as DNP polarizers. The EPR spectra of the radicals revealed axially symmetric g-tensors. A comparison of the spectra with the 13C DNP frequency sweeps showed that although the solid effect mechanism is operational the DNP frequency sweeps reveal some extra width suggesting that contributions from EPR forbidden transitions involving 35,37Cl nuclear flips are likely. This was substantiated experimentally by ELDOR (electron-electron double resonance) detected NMR measurements, which map the EPR forbidden transitions, and ELDOR experiments that follow the depolarization of the electron spin upon irradiation of the forbidden EPR transitions. DFT (density functional theory) calculations helped to assign the observed transitions and provided the relevant spin Hamiltonian parameters. These results show that the 35,37Cl hyperfine and nuclear quadrupolar interactions cause a considerable nuclear state mixing at 95 GHz thus facilitating the polarization of the Cl nuclei upon microwave irradiation. Overlap of Cl nuclear frequencies and the 13C Larmor frequency further facilitates the polarization of the 13C nuclei by spin diffusion. Calculation of the 13C DNP frequency sweep based on the Cl nuclear polarization showed that it does lead to an increase in the width of the spectra, improving the agreement with the experimental sweeps, thus supporting the existence of a new heteronuclear assisted DNP mechanism.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Comment on reversal of hypogonadotropic hypogonadism in a Chinese cohort.

The reversal of congenital hypogonadotropic hypogonadism (CHH) is a relatively recent phenomenon that has gained increasing attention over the past 10 years. Yet to date, only one prospective study has been conducted estimating that 10% (95% confidence interval [CI]: 2%-18%) of cases undergo reversal. [1] Other retrospective studies have reported rates in the range of 5%-8% [2],[3] and a recent study showed 44/308 (14%, 95% CI: 11%-19%) CHH patients underwent reversal. [4] Moreover, a time-to-event analysis in this large cohort revealed a lifetime reversal incidence of 22%. The article by Mao and colleagues presented in this issue is a meaningful contribution to our understanding of reversal as it examines the largest retrospective cohort to date. [5] Interestingly, they report the rate of reversal as 5% (95% CI: 3%-8%) in this Chinese cohort. It is difficult to reconcile the discrepancies in rates of reversibility and direct comparisons are hampered by the variable definitions employed. Using a novel definition for reversal (i.e, either endogenous testosterone (T) >270 ng dl−1 , serum T gradually increasing above 150 ng dl−1 with increased testicular volume, or normal spontaneous sperm production/normal erectile function/ejaculation), Mao and colleagues posit that testicular size and triptorelin-stimulated LH levels are reliable predictive factors for reversal. However, these cannot be considered as hard and fast rules for predicting reversal as the groups intersect - akin to the overlap observed between CHH patients and those with delayed puberty. Indeed, the fact that approximately half (44%, 95% CI: 25%-66%) of the reversal patients in the study by Mao et al.[5] were diagnosed between 17 and 19 years of age, underscores the challenge in differentiating CHH from extreme normal variants of puberty. This study further lends credence the recently reported observations that reversals may relapse. [4],[6] The notion that reversal may not be lasting highlights the vulnerability of the reproductive axis among CHH patients. While the mechanism(s) for relapse are unclear, it seems plausible that environmental, metabolic or psychiatric stressors could contribute. The factors that Mao and colleagues identify as significantly different in cases of reversal, were not informative for identifying those cases that relapsed back to a hypogonadal state. Notably, reversal has been reported in probands harboring mutations in genes underlying CHH. [1],[3],[4],[6] Unfortunately, comprehensive genetic screening on the Chinese cohort is not available. The reversal phenomenon is fascinating for its glimpse into the plasticity of the neuroendocrine control of reproduction. Future directions will almost certainly include investigation of specific genetic signatures and novel biomarkers for predicting reversal (and relapse). Yet CHH is a rare condition and to fully elucidate the biology of reversible CHH, it will be important to harmonize definitions of what constitutes a reversal, carefully phenotype patients and chart the natural history of their CHH. In this way, this unique human disease model may offer further insights into the control of human reproduction and provide opportunities to translate discoveries into enhanced approaches to improve the care and quality of life for these patients.

What is the potential of spread in invasive bryophytes?

Although the number of invasive bryophytes is much lower than that of higher plants, they threaten habitats that are often species rich and of high conservation relevance. Their potential of spread has, however, never been determined. Here, we assess whether the three most invasive bryophyte species shifted their niche during the invasion process and whether the extent of the study area defined to calibrate the model (geographic background, GB) affects model transferability. We then determine whether ecological niche models (ENMs) developed in their native range can be projected in other areas to assess their invasive potential. The macroclimatic niches of Campylopus introflexus, Orthodontium lineare and Lophocolea semiteres were compared in their native range (Southern Hemisphere) and in their invasion range (Northern Hemisphere) using ordination techniques. ENMs from an ensemble model were calibrated in the native range and projected onto the Northern Hemisphere using different GBs. No evidence for niche expansion in the invaded range was found and the species occur in the invaded range under climate conditions that are similar to those in the native range. The performance of the models to predict occurrences in the invaded range increased with the extent of the GB. The potential range of all species included entire regions on continents where they are still absent. The expansion of the investigated species appears to be constrained by climate conditions that are similar to those currently prevailing in their native range, which is consistent with our failure to demonstrate macroclimatic niche shift in the invaded range. The use of large GBs is recommended in such vagile organisms with large, disjunct distributions. The models indicated that invasive bryophyte species might become a threat in central and eastern Europe, North America and eastern Asia if accidentally introduced or naturally dispersed.

New genes for focal epilepsies with speech and language disorders.

The last 2 years have seen exciting advances in the genetics of Landau-Kleffner syndrome and related disorders, encompassed within the epilepsy-aphasia spectrum (EAS). The striking finding of mutations in the N-methyl-D-aspartate (NMDA) receptor subunit gene GRIN2A as the first monogenic cause in up to 20 % of patients with EAS suggests that excitatory glutamate receptors play a key role in these disorders. Patients with GRIN2A mutations have a recognizable speech and language phenotype that may assist with diagnosis. Other molecules involved in RNA binding and cell adhesion have been implicated in EAS; copy number variations are also found. The emerging picture highlights the overlap between the genetic determinants of EAS with speech and language disorders, intellectual disability, autism spectrum disorders and more complex developmental phenotypes.

Urinary and plasma catecholamines and metanephrines in dogs with pheochromocytoma, hypercortisolism, nonadrenal disease and in healthy dogs.

BACKGROUND: Diagnosis of pheochromocytoma (PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine. OBJECTIVES: To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC. ANIMALS: Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs. METHODS: Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at -80°C before analysis using high-pressure liquid chromatography (HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration. RESULTS: Dogs with PC had significantly higher urinary normetanephrine and metanephrine : creatinine ratios and significantly higher plasma-total and free normetanephrine and plasma-free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma. CONCLUSION AND CLINICAL IMPORTANCE: Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma.

The Bacterium Frischella perrara Causes Scab Formation in the Gut of its Honeybee Host.

UNLABELLED: Honeybees harbor well-defined bacterial communities in their guts. The major members of these communities appear to benefit the host, but little is known about how they interact with the host and specifically how they interface with the host immune system. In the pylorus, a short region between the midgut and hindgut, honeybees frequently exhibit scab-like structures on the epithelial gut surface. These structures are reminiscent of a melanization response of the insect immune system. Despite the wide distribution of this phenotype in honeybee populations, its cause has remained elusive. Here, we show that the presence of a common member of the bee gut microbiota, the gammaproteobacterium Frischella perrara, correlates with the appearance of the scab phenotype. Bacterial colonization precedes scab formation, and F. perrara specifically localizes to the melanized regions of the host epithelium. Under controlled laboratory conditions, we demonstrate that exposure of microbiota-free bees to F. perrara but not to other bacteria results in scab formation. This shows that F. perrara can become established in a spatially restricted niche in the gut and triggers a morphological change of the epithelial surface, potentially due to a host immune response. As an intermittent colonizer, this bacterium holds promise for addressing questions of community invasion in a simple yet relevant model system. Moreover, our results show that gut symbionts of bees engage in differential host interactions that are likely to affect gut homeostasis. Future studies should focus on how these different gut bacteria impact honeybee health. IMPORTANCE: As pollinators, honeybees are key species for agricultural and natural ecosystems. Their guts harbor simple communities composed of characteristic bacterial species. Because of these features, bees are ideal systems for studying fundamental aspects of gut microbiota-host interactions. However, little is known about how these bacteria interact with their host. Here, we show that a common member of the bee gut microbiota causes the formation of a scab-like structure on the gut epithelium of its host. This phenotype was first described in 1946, but since then it has not been much further characterized, despite being found in bee populations worldwide. The scab phenotype is reminiscent of melanization, a conserved innate immune response of insects. Our results show that high abundance of one member of the bee gut microbiota triggers this specific phenotype, suggesting that the gut microbiota composition can affect the immune status of this key pollinator species.

The kiwifruit in Chile and in the world

The kiwi is a fruit that, has only been in Europe for about 60 years, which signifies a great potential for the development of its consumption and great difficulty in the educational process of the product. Currently there is a growing increase in world production, which to date is above the growth in demand. This means that the kiwi categories are not growing significantly and, on the contrary, the kiwi is at a crossroad that will be resolved in the coming years. The changing global economic scenario affects high-value products such as kiwis, making it hard to predict their commercial results. The worldwide market has clearly indicated through the demand and the prices that it is interested in the sweeter yellow varieties. Asian markets have been and are expected to continue to grow. The increase in world production has also generated overlap in stocks between the hemispheres, which makes it necessary to closely monitor commercial strategies regarding the start and end of the season. In this way, the market entry of the southern hemisphere kiwifruit is conditioned according to the presence of fruit from the Northern Hemisphere. The unique features and uses of the kiwi make it one of the most interesting fruits present in the world. For this reason it is also a fruit with high purchase value. In spite of the described variables and market trends, there is a growing demand for consuming better quality kiwis and willingness to pay a higher price.

The odd couple: contrasting phylogeographic patterns in two sympatric sibling species of woodlouse-­‐hunter spiders in the Canary Islands

Comparative phylogeography seeks for commonalities in the spatial demographic history of sympatric organisms to characterize the mechanisms that shaped such patterns. The unveiling of incongruent phylogeographic patterns in co-occurring species, on the other hand, may hint to overlooked differences in their life histories or microhabitat preferences. The woodlouse-hunter spiders of the genus Dysdera have undergone a major diversi cation on the Canary Islands. The species pair Dysdera alegranzaensis and Dysdera nesiotes are endemic to the island of Lanzarote and nearby islets, where they co-occur at most of their known localities. The two species stand in sharp contrast to other sympatric endemic Dysdera in showing no evidence of somatic (non-genitalic) differentiation. Phylogenetic and population genetic analyses of mitochondrial cox1 sequences from an exhaustive sample of D. alegranzaensis and D. nesiotes specimens, and additional mitochondrial (16S, L1, nad1) and nuclear genes (28S, H3) were analysed to reveal their phylogeographic patterns and clarify their phylogenetic relationships. Relaxed molecular clock models using ve calibration points were further used to estimate divergence times between species and populations. Striking differences in phylogeography and population structure between the two species were observed. Dysdera nesiotes displayed a metapopulation-like structure, while D. alegranzaensis was characterized by a weaker geographical structure but greater genetic divergences among its main haplotype lineages, suggesting more complex population dynamics. Our study con rms that co-distributed sibling species may exhibit contrasting phylogeographic patterns in the absence of somatic differentiation. Further ecological studies, however, will be necessary to clarify whether the contrasting phylogeographies may hint at an overlooked niche partitioning between the two species. In addition, further comparisons with available phylogeographic data of other eastern Canarian Dysdera endemics con rm the key role of lava ows in structuring local populations in oceanic islands and identify localities that acted as refugia during volcanic eruptions

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study.

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added as a covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors.

Oncogenic K-Ras segregates at spatially distinct plasma membrane signaling platforms according to its phosphorylation status

Activating mutations in the K-Ras small GTPase are extensively found in human tumors. Although these mutations induce the generation of a constitutively GTP-loaded, active form of K-Ras, phosphorylation at Ser181 within the C-terminal hypervariable region can modulate oncogenic K-Ras function without affecting the in vitro affinity for its effector Raf-1. In striking contrast, K-Ras phosphorylated at Ser181 shows increased interaction in cells with the active form of Raf-1 and with p110α, the catalytic subunit of PI 3-kinase. Because the majority of phosphorylated K-Ras is located at the plasma membrane, different localization within this membrane according to the phosphorylation status was explored. Density-gradient fractionation of the plasma membrane in the absence of detergents showed segregation of K-Ras mutants that carry a phosphomimetic or unphosphorylatable serine residue (S181D or S181A, respectively). Moreover, statistical analysis of immunoelectron microscopy showed that both phosphorylation mutants form distinct nanoclusters that do not overlap. Finally, induction of oncogenic K-Ras phosphorylation - by activation of protein kinase C (PKC) - increased its co-clustering with the phosphomimetic K-Ras mutant, whereas (when PKC is inhibited) non-phosphorylated oncogenic K-Ras clusters with the non-phosphorylatable K-Ras mutant. Most interestingly, PI 3-kinase (p110α) was found in phosphorylated K-Ras nanoclusters but not in non-phosphorylated K-Ras nanoclusters. In conclusion, our data provide - for the first time - evidence that PKC-dependent phosphorylation of oncogenic K-Ras induced its segregation in spatially distinct nanoclusters at the plasma membrane that, in turn, favor activation of Raf-1 and PI 3-kinase.

Phylogeny and biogeography of Primula sect. Armerina: implications for plant evolution under climate change and the uplift of the Qinghai-Tibet Plateau.

BACKGROUND: The historical orogenesis and associated climatic changes of mountain areas have been suggested to partly account for the occurrence of high levels of biodiversity and endemism. However, their effects on dispersal, differentiation and evolution of many groups of plants are still unknown. In this study, we examined the detailed diversification history of Primula sect. Armerina, and used biogeographic analysis and macro-evolutionary modeling to investigate a series of different questions concerning the evolution of the geographical and ecological distribution of the species in this section. RESULTS: We sequenced five chloroplast and one nuclear genes for species of Primula sect. Armerina. Neither chloroplast nor nuclear trees support the monophyly of the section. The major incongruences between the two trees occur among closely related species and may be explained by hybridization. Our dating analyses based on the chloroplast dataset suggest that this section began to diverge from its relatives around 3.55 million years ago, largely coinciding with the last major uplift of the Qinghai-Tibet Plateau (QTP). Biogeographic analysis supports the origin of the section in the Himalayan Mountains and dispersal from the Himalayas to Northeastern QTP, Western QTP and Hengduan Mountains. Furthermore, evolutionary models of ecological niches show that the two P. fasciculata clades have significantly different climatic niche optima and rates of niche evolution, indicating niche evolution under climatic changes and further providing evidence for explaining their biogeographic patterns. CONCLUSION: Our results support the hypothesis that geologic and climatic events play important roles in driving biological diversification of organisms in the QTP area. The Pliocene uplift of the QTP and following climatic changes most likely promoted both the inter- and intraspecific divergence of Primula sect. Armerina. This study also illustrates how niche evolution under climatic changes influences biogeographic patterns.

Evolutionary patchwork of an insecticidal toxin shared between plant-associated pseudomonads and the insect pathogens Photorhabdus and Xenorhabdus.

BACKGROUND: Root-colonizing fluorescent pseudomonads are known for their excellent abilities to protect plants against soil-borne fungal pathogens. Some of these bacteria produce an insecticidal toxin (Fit) suggesting that they may exploit insect hosts as a secondary niche. However, the ecological relevance of insect toxicity and the mechanisms driving the evolution of toxin production remain puzzling. RESULTS: Screening a large collection of plant-associated pseudomonads for insecticidal activity and presence of the Fit toxin revealed that Fit is highly indicative of insecticidal activity and predicts that Pseudomonas protegens and P. chlororaphis are exclusive Fit producers. A comparative evolutionary analysis of Fit toxin-producing Pseudomonas including the insect-pathogenic bacteria Photorhabdus and Xenorhadus, which produce the Fit related Mcf toxin, showed that fit genes are part of a dynamic genomic region with substantial presence/absence polymorphism and local variation in GC base composition. The patchy distribution and phylogenetic incongruence of fit genes indicate that the Fit cluster evolved via horizontal transfer, followed by functional integration of vertically transmitted genes, generating a unique Pseudomonas-specific insect toxin cluster. CONCLUSIONS: Our findings suggest that multiple independent evolutionary events led to formation of at least three versions of the Mcf/Fit toxin highlighting the dynamic nature of insect toxin evolution.

Kannattavuusraportoinnin laadun arviointi data warehouse ratkaisussa Case: Paperiteollisuuden myynnin ja asiakaspalvelun tietojärjestelmä

Tutkielman tavoitteena oli selvittää, onko tutkielman tilaajan toteuttaman kannattavuusraportoinnin laatu käyttäjien mielestä riittävä. Kannattavuusraportointi on toteutettu data warehouse tekniikalla. Tutkielman tavoitteina oli myös määrittää, mitä ohjelmiston laatu tarkoittaa ja miten sitä voidaan arvioida. Tutkimuksessa käytettiin kvalitatiivista tutkimusmenetelmää. Laadun arviointiin käytetty aineisto kerättiin haastattelemalla seitsemäätoista kannattavuusraportoinnin aktiivikäyttäjää. Tutkielmassa ohjelmiston laatu tarkoittaa sen kykyä täyttää tai ylittää käyttäjiensä kohtuulliset toiveet ja odotukset. Laatua arvioitiin standardin ISO/IEC 9126 määrittelemällä kuudella laatuominaisuudella, jotka kuvaavat minimaalisella päällekkäisyydellä ohjelmiston laadun. Lisäksi arvioinnissa hyödynnettiin varsinaiseen standardiin kuulumatonta informatiivista liitettä, joka tarkentaa ISO/IEC 9126 standardissa esitettyjä laadun ominaispiirteitä. Tutkimuksen tuloksena voidaan todeta, että käyttäjien mukaan kannattavuusraportointi on tarpeeksi laadukas, sillä se pystyy tarjoamaan helppokäyttöisiä, oikeanmuotoisia raportteja riittävän hyvällä vasteajalla käyttäjien tarpeisiin. Tehokkaasta hyödyntämisestä voidaan päätellä data warehousen rakentamisen onnistuneen. Tutkimuksessa nousi esiin myös runsaasti kehittämis- ja parannusideoita, jotka toimivat yhtenä kehitystyön apuvälineenä tulevaisuudessa.