Neurons in the lateral part of the lumbar spinal cord show distinct novel axon trajectories and are excited by short propriospinal ascending inputs

The role of spinal dorsal horn propriospinal connections in nociceptive processing is not yet established. Recently described, rostrocaudally oriented axon collaterals of lamina I projection and local-circuit neurons (PNs and LCNs) running in the dorsolateral funiculus (DLF) may serve as the anatomical substrate for intersegmental processing. Putative targets of these axons include lateral dendrites of superficial dorsal horn neurons, including PNs, and also neurons in the lateral spinal nucleus (LSN) that are thought to be important integrator units receiving, among others, visceral sensory information. Here we used an intact spinal cord preparation to study intersegmental connections within the lateral part of the superficial dorsal horn. We detected brief monosynaptic and prolonged polysynaptic excitation of lamina I and LSN neurons when stimulating individual dorsal horn neurons located caudally, even in neighboring spinal cord segments. These connections, however, were infrequent. We also revealed that some projection neurons outside the dorsal grey matter and in the LSN have distinct, previously undescribed course of their projection axon. Our findings indicate that axon collaterals of lamina I PNs and LCNs in the DLF rarely form functional connections with other lamina I and LSN neurons and that the majority of their targets are on other elements of the dorsal horn. The unique axon trajectories of neurons in the dorsolateral aspect of the spinal cord, including the LSN do not fit our present understanding of midline axon guidance and suggest that their function and development differ from the neurons inside lamina I. These findings emphasize the importance of understanding the connectivity matrix of the superficial dorsal horn in order to decipher spinal sensory information processing.This work was supported by FEDER funds through the Operational Competitiveness Programme-COMPETE and by national funds through FCT-Fundacao para a Ciencia e a Tecnologia under the project FCOMP-01-0124-FEDER-029632 (PTDC/NEU-SCC/0347/2012 to BS), the Hungarian Academy of Sciences (MTA-TKI 242 to MA), the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (PSz), the Hungarian Brain Research Program (KTIA_NAP_13-2-2014-0005 to PSz and KTIA_NAP_13-1-2013-0001 to MA) and TAMOP-4.2.4.A/2-11/1-2012-0001 'National Excellence Program' supported by the Sate of Hungary and the European Union, co-financed by the European Social Fund (ZsA). The authors are grateful to Raquel Pinho for her excellent help with the histological processing and reconstruction

Living with chronic migraine: a qualitative study on female patients' perspectives from a specialised headache clinic in Spain

OBJECTIVES: The aim of this study was to explore the views and experiences of a group of Spanish women suffering from chronic migraine (CM). SETTING: Headache clinic at a university hospital in Madrid (Spain). PARTICIPANTS: Purposeful sampling of patients that attended a specialised headache clinic for the first time between June 2016 and February 2017 was performed. The patients included were females aged 18–65 and with positive diagnoses of CM according to the International Classification of Headache disorders (third edition, beta version), with or without medication overuse. Accordingly, 20 patients participated in the study with a mean age of 38.65 years (SD 13.85). DESIGN: Qualitative phenomenological study. METHODS: Data were collected through in-depth interviews, researchers’ field notes and patients’ drawings. A thematic analysis was performed following appropriate guidelines for qualitative research. RESULTS: Five main themes describing the significance of suffering emerged: (a) the shame of suffering from an invisible condition; (b) treatment: between need, scepticism and fear; (c) looking for physicians’ support and sincerity and fighting misconceptions; (d) limiting the impact on daily life through self-control; and (e) family and work: between understanding and disbelief. The disease is experienced as an invisible process, and the journey to diagnosis can be a long and tortuous one. Drug prescription by the physician is greeted with distrust and scepticism. Patients expect sincerity, support and the involvement of their doctors in relation to their disease. Pain becomes the main focus of the patient’s life, and it requires considerable self-control. The disease has a strong impact in the work and family environment, where the patient may feel misunderstood. CONCLUSIONS: Qualitative research offers insight into the way patients with CM experience their disease and it may be helpful in establishing a more fruitful relationship with these patients

Unusual and potential distribution of the common cattle tick, <em>Rhipicephalus (Boophilus) microplus<em>, in high mountain tropical zones of the Colombian Andes

Potential areas of distribution of the common cattle tick Rhipicephalus (Boophilus) microplus in the Altiplano Cundiboyacense are presented, using two algorithms of ecological niche modeling (Maxent and Classification Trees). The algorithms were complementary, with excellent and significant returns, registering AUC (0.70 and 0.90 Maxent Classification Trees), and low values of omission errors (0.00% and 4.6% Maxent Classification Trees). The landscape along with the presence of the host, altitude, precipitation, temperature and humidity of the first wet quarter, were the most important variables in modeling. The north-eastern region of the Altiplano has the best potential for the establishment of this species

Unusual and potential distribution of the common cattle tick, Rhipicephalus (Boophilus) microplus, in high mountain tropical zones of the Colombian Andes

Potential areas of distribution of the common cattle tick Rhipicephalus (Boophilus) microplus in the Altiplano Cundiboyacense are presented, using two algorithms of ecological niche modeling (Maxent and Classification Trees). The algorithms were complementary, with excellent and significant returns, registering AUC (0.70 and 0.90 Maxent Classification Trees), and low values of omission errors (0.00% and 4.6% Maxent Classification Trees). The landscape along with the presence of the host, altitude, precipitation, temperature and humidity of the first wet quarter, were the most important variables in modeling. The north-eastern region of the Altiplano has the best potential for the establishment of this species.Se presentan las áreas potenciales de distribución de la garrapata común del ganado Rhipicephalus (Boophilus) microplus en el altiplano cundiboyacense, Colombia, mediante el uso de dos algoritmos de modelamiento de nicho ecológico (Maxent y árboles de clasificación). Los algoritmos fueron complementarios, con rendimientos óptimos y significativos, registrando valores de AUC (0.70 Maxent y 0.90 árboles de clasificación, y bajos valores de errores omisión (0,04 % Maxent y 4,6 % árboles de clasificación). El paisaje, junto con la presencia del hospedero, la altitud, la precipitación, la temperatura y la humedad del primer trimestre húmedo, fueron las variables más relevantes en el modelamiento. La región nororiental del altiplano presenta las áreas potencialmente óptimas para el establecimiento de esta especie

Distribución inusual y potencial de la garrapata común del ganado, Rhipicephalus (Boophilus) microplus, en zonas tropicales de alta montaña de los Andes colombianos

Potential areas of distribution of the common cattle tick Rhipicephalus (Boophilus) microplus in the Altiplano Cundiboyacense are presented, using two algorithms of ecological niche modeling (Maxent and Classification Trees). The algorithms were complementary, with excellent and significant returns, registering AUC (0.70 and 0.90 Maxent Classification Trees), and low values of omission errors (0.00% and 4.6% Maxent Classification Trees). The landscape along with the presence of the host, altitude, precipitation, temperature and humidity of the first wet quarter, were the most important variables in modeling. The north-eastern region of the Altiplano has the best potential for the establishment of this species.Se presentan las áreas potenciales de distribución de la garrapata común del ganado Rhipicephalus (Boophilus) microplus en el altiplano cundiboyacense, Colombia, mediante el uso de dos algoritmos de modelamiento de nicho ecológico (Maxent y árboles de clasificación). Los algoritmos fueron complementarios, con rendimientos óptimos y significativos, registrando valores de AUC (0.70 Maxent y 0.90 árboles de clasificación, y bajos valores de errores omisión (0,04 % Maxent y 4,6 % árboles de clasificación). El paisaje, junto con la presencia del hospedero, la altitud, la precipitación, la temperatura y la humedad del primer trimestre húmedo, fueron las variables más relevantes en el modelamiento. La región nororiental del altiplano presenta las áreas potencialmente óptimas para el establecimiento de esta especie

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain

Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms. The 5-HT3-receptor antagonist MDL-72222 or 5-HT1B/D-receptor antagonist GR127935 largely reduced, but their combination completely prevented the excitatory pro-nociceptive action of 5-HT. The 5-HT3 agonist mCPBG activated spikes in MDL-72222-dependent manner but the 5HT-1 receptor agonist sumatriptan did not affect the nociceptive firing. 5-HT also triggered peripheral CGRP release in meninges, which was blocked by MDL-72222.5-HT evoked fast membrane currents and Ca2+ transients in a fraction of trigeminal neurons. Immunohistochemistry showed expression of 5-HT3A receptors in fibers innervating meninges. Endogenous release of 5-HT from degranulated mast cells increased nociceptive firing. Low pH but not histamine strongly activated firing. 5-HT reduced monosynaptic inputs from trigeminal Aδ- and C-afferents to the upper cervical lamina I neurons and this effect was blocked by MDL-72222. Consistent with central inhibitory effect, 5-HT reduced CGRP release in the brainstem slices. In conclusion, 5-HT evokes powerful pro-nociceptive peripheral and anti-nociceptive central effects in trigeminal system transmitting migraine pain.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The study was supported by the Finnish Academy (grant 277442). AZ was supported by the subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities and the Government of the Russian Federation (grant No.11.G34.31.0075). The work of IS was supported by RFBR grant 14-04-00885. BVS was supported by the grant from the Fundacao para a Ciencia e a Tecnologia (PTDC/NEU-NMC/1259/2014) and from the programme NORTE 2020

Genetic variation in the Solanaceae fruit bearing species lulo and tree tomato revealed by Conserved Ortholog (COSII) markers

The Lulo or naranjilla (Solanum quitoense Lam.) and the tree tomato or tamarillo (Solanum betaceum Cav. Sendt.) are both Andean tropical fruit species with high nutritional value and the potential for becoming premium products in local and export markets. Herein, we present a report on the genetic characterization of 62 accessions of lulos (n = 32) and tree tomatoes (n = 30) through the use of PCR-based markers developed from single-copy conserved orthologous genes (COSII) in other Solanaceae (Asterid) species. We successfully PCR amplified a set of these markers for lulos (34 out of 46 initially tested) and tree tomatoes (26 out of 41) for molecular studies. Six polymorphic COSII markers were found in lulo with a total of 47 alleles and five polymorphic markers in tree tomato with a total of 39 alleles in the two populations. Further genetic analyses indicated a high population structure (with FST > 0.90), which may be a result of low migration between populations, adaptation to various niches and the number of markers evaluated. We propose COSII markers as sound tools for molecular studies, conservation and the breeding of these two fruit species