Barrier crossings and winds shape daily travel schedules and speeds of a flight generalist.

External factors such as geography and weather strongly affect bird migration influencing daily travel schedules and flight speeds. For strictly thermal-soaring migrants, weather explains most seasonal and regional differences in speed. Flight generalists, which alternate between soaring and flapping flight, are expected to be less dependent on weather, and daily travel schedules are likely to be strongly influenced by geography and internal factors such as sex. We GPS-tracked the migration of 70 lesser kestrels (Falco naumanni) to estimate the relative importance of external factors (wind, geography), internal factors (sex) and season, and the extent to which they explain variation in travel speed, distance, and duration. Our results show that geography and tailwind are important factors in explaining variation in daily travel schedules and speeds. We found that wind explained most of the seasonal differences in travel speed. In both seasons, lesser kestrels sprinted across ecological barriers and frequently migrated during the day and night. Conversely, they travelled at a slower pace and mainly during the day over non-barriers. Our results highlighted that external factors far outweighed internal factors and season in explaining variation in migratory behaviour of a flight generalist, despite its ability to switch between flight modes.

DARK Classics in Chemical Neuroscience: Salvinorin A.

Salvinorin A is the main bioactive compound in Salvia divinorum, an endemic plant with ancestral use by the inhabitants of the Mazateca mountain range (Sierra Mazateca) in Oaxaca, México. The main use of la pastora, as locally known, is in spiritual rites due to its extraordinary hallucinogenic effects. Being the first known nonalkaloidal opioid-mediated psychotropic molecule, salvinorin A set new research areas in neuroscience. The absence of a protonated amine group, common to all previously known opioids, results in a fast metabolism with the concomitant fast elimination and swift loss of activity. The worldwide spread and psychotropic effects of salvinorin A account for its misuse and classification as a drug of abuse. Consequently, salvinorin A and Salvia divinorum are now banned in many countries. Several synthetic efforts have been focused on the improvement of physicochemical and biological properties of salvinorin A: from total synthesis to hundreds of analogues. In this Review, we discuss the impact of salvinorin A in chemistry and neuroscience covering the historical relevance, isolation from natural sources, synthetic efforts, and pharmacological and safety profiles. Altogether, the chemistry behind and the taboo that encloses salvinorin A makes it one of the most exquisite naturally occurring drugs.

Glaucacetalin E and galphimidin B from Galphimia glauca and their anxiolytic activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Galphimia glauca is a Mexican medicinal plant used to treat anxiety, fear, phobia and stress as it possesses sedative properties which produce a calming effect. Although some chemical and pharmacological studies have already been carried out on G. glauca, there are still new chemical entities from this plant whose anxiolytic activity should be established. AIM OF THE STUDY: To validate the use of G. glauca growing in Cuernavaca, Morelos, as an anti-stress agent, through the purification and structural identification of its extracts' chemical constituents; the analysis of the biogenetic relationship of its chemical compounds, and its biological evaluation to demonstrate its traditional use as anxiolytic agents. MATERIALS AND METHODS: The structures of all isolated compounds were established based on their spectroscopic and spectrometric data. The structure of compound 2 was corroborated through X-Ray. The anxiolytic and sedative-like activities were assessed by the open-field, hole-board and exploration cylinder test. RESULTS: The nor-triterpenes glaucacetalin E (1) and galphimidin B (2) were isolated for the first time along with seven other known compounds, one of them galphimidin (3), from the CHCl3 fraction of the aerial parts of Galphimia glauca. The biogenesis of the natural nor-triterpenes isolated from Galphimia glauca is delineated for the first time starting from the taraxasteryl cation. Oral administration of CHCl3 fraction and 1-3 compounds produced significant attenuation in the anxiety-response in cylinder activity, decrease in the ambulatory activity and in head dipping when compared to the vehicle. However, only the extract enhanced the pentobarbital-induced hypnosis. Diazepam was used as a positive control. CONCLUSION: Our results suggest that G. glauca growing in Cuernavaca, Morelos, exerts anxiolytic-like activity due to the presence of the nor-triterpenes 1-3. These results reinforce the potential use of this species in the treatment of anxiety.

Further galphimines from a new population of Galphimia glauca.

Both DNA barcoding and phylogenetic data of the studied botanical material suggested the existence a new population of Galphimia glauca. Their leaves afforded three new nor-3,4-seco-friedelanes named galphimines M-O, together with known galphimines D, E, G, and I. Galphimines M and N possess bicyclic orthoacetates which are the first examples of orthoesters found in the Malpighiaceae family, while galphimine O has a 27,20-δ-lactone moiety. The structures elucidation followed from spectroscopic means and the absolute configuration followed from single crystal X-ray diffraction analyses. Tests for antibacterial and antifungal activities of galphimines N and M showed no promising effects.

A pair of peptides inhibits seeding of the hormone transporter transthyretin into amyloid fibrils.

The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloid-driving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach.

Amarisolide F, an Acylated Diterpenoid Glucoside and Related Terpenoids from Salvia amarissima.

Nine terpenoids were isolated from the leaves and flowers of Salvia amarissima, including a new acylated diterpenoid glucoside, amarisolide F (1), a new neo-clerodane diterpenoid, amarissinin D (2), which was isolated as an acetyl derivative (2a), and four known diterpenoids. The structure of amarisolide F (1) was elucidated by NMR and MS data analyses, as well as its methanolysis products 7 and 8, which also constituted new diterpenoids, named amarissinin E and 8- epi-amarissinin E, respectively. The absolute configuration of compound 7 was established by single-crystal X-ray diffraction. The cytotoxicity and anti-MDR effect of 1 in three phenotypes of the MCF-7 cell lines were assayed. Compound 1 was 2-3.6-fold more active than amarissinins A (3) and B (4), but several orders of magnitude less active than teotihuacanin (6) and reserpine.

neo-Clerodane Diterpenoids from Salvia polystachya Stimulate the Expression of Extracellular Matrix Components in Human Dermal Fibroblasts.

Eleven neo-clerodane diterpenoids (1-11) including the new analogues 1, 2, and 10, and 3',5,6,7-tetrahydroxy-4'-methoxyflavone (12) were isolated from the aerial parts of Salvia polystachya. Polystachyne G (1) and 15-epi-polystachyne G (2) were isolated as an epimeric mixture, containing a 5-hydroxyfuran-2(5H)-one unit in the side chain at C-12 of the neo-clerodane framework. Polystachyne H (10) contains a 1(10),2-diene moiety and a tertiary C-4 hydroxy group. The structures of these compounds were established by analysis of their NMR spectroscopic and MS spectrometric data. The absolute configurations of compounds 3, 4, and 10 were determined through single-crystal X-ray diffraction analysis. The antibacterial, antifungal, and phytotoxic activities of the diterpenoids were determined. In addition, the stimulatory effect of the expression of extracellular matrix components of nine of the isolates (1-8 and 11) was assayed. Compounds 1-4, 8, and 11 increased the expression of the genes codifying for type I, type III, and type V collagens and for elastin.

Structure and absolute configuration of hydroxy-bis-dihydrofarinosin from Encelia farinosa.

The structure of the dimeric eudesmanolide hydroxy-bis-dihydrofarinosin (1) from Encelia farinosa followed after contrasting their 1 H and 13 C NMR spectra with those of encelin (6), hydroxy-bis-dihydroencelin (3), and farinosin (4). Structure 1 was verified by single-crystal X-ray diffraction analysis, which further provided the stereochemistry of the hydroxy group at C-4. Comparison of the experimental vibrational circular dichroism spectrum of its derived diacetate 2 with that calculated by density functional theory provided the absolute configuration, which resulted the same as that of its biogenetic precursor 4. Evaluation of several chemical shift differences between the two eudesmanolide fragments of 1 and 3 allows also ascertaining the yet not reported absolute configuration of the C-4 stereogenic center of 3. Copyright © 2016 John Wiley & Sons, Ltd.

Factores de riesgo de la morbilidad materna critica en embarazadas de Las Tunas / Risk factors for critical maternal morbidity in pregnant women from Las Tunas

Fundamento: la morbilidad materna extremadamente grave (MMEG), complicación grave que ocurre durante el embarazo, parto y puerperio, pone en riesgo la vida de la mujer.Objetivo: determinar los factores de riesgo de morbilidad materna extremadamente grave, en embarazadas atendidas en el servicio de Ginecobstetricia del Hospital General Docente “Dr. Ernesto Guevara de la Serna”, en Las Tunas, durante los años 2012 a 2014.Métodos: se realizó un estudio analítico de tipo casos y control, en el declarado lugar y período de tiempo. El universo de estudio quedó constituido por todas las puérperas ingresadas. Se seleccionó una muestra de 80 pacientes que ingresaron en estado crítico, grupo estudio, y 160 pacientes con evolución satisfactoria en sala, grupo control. Se revisaron las historias clínicas y tarjetones de seguimiento prenatal.Resultados: la preeclampsia, el hematoma retroplacentario, la placenta previa, la sepsis ovular, la rotura uterina, la sepsis puerperal y la operación cesárea, mostraron asociación causal como factores de riesgo de la morbilidad crítica en la gestante. La atención prenatal adecuada y el parto fisiológico constituyeron factores protectores. No se obtuvo asociación causal estadísticamente significativa en las pacientes que presentaban enfermedades crónicas como cardiopatía, anemia, asma bronquial, así como las enfermedades propias del embarazo, rotura prematura de membranas y diabetes gestacional.Conclusiones: se identificaron los factores de riesgo de morbilidad materna extremadamente grave en embarazadas de Las Tunas (AU)

Background: severe maternal morbidity is a serious complication that occurs during pregnancy, labor and puerperium and is a risk for womens life.Objective: to determine the risk factors for extremely serious maternal morbidity in pregnant w omen seen at the obstetric and gynecology service of “Ernesto Guevara de la Serna” General Teaching Hospital of Las Tunas, from 2012 through 2014.Methods: a retrospective analytic study of the type cases and control was carried out at the place and during the time herein mentioned. The sample was made up of 80 patients that were admitted in a critical condition, as the study group, and 160 patients that progressed satisfactorily in the ward, as the control group. The clinical histories and prenatal follow-up charts were checked.Results: preeclampsia, retroplacental hematoma, placenta previa, ovular sepsis, uterine rupture, puerperal sepsis and cesarean section showed causal association as risk factors for critical morbidity in pregnant women. Adequate prenatal care and physiological labor were protecting factors. Statistically there was no significant causal association in those patients who presented chronic diseases as cardiopathies, anemia, bronchial asthma, as well as pregnancy conditions, premature rupture of membranes and gestational diabetes (AU)

Structural elucidation and evaluation of multidrug-resistance modulatory capability of amarissinins A-C, diterpenes derived from Salvia amarissima.

Three new diterpenes (amarissinins A-C, 1-3) containing several oxygenated functionalities were isolated from the leaves and flowers of Salvia amarissima. The structures of these compounds were established through the analysis of their NMR spectroscopy and mass spectrometry data. The structures of compounds 1 and 2 were confirmed by single crystal X-ray diffraction. Compound 2 was identified as a C-10 epimer of dugesin F (5). The cytotoxic activity of these compounds against five human cancer cell lines was determined. Additionally, the capability to modulate the multidrug resistance (MDR) in the MCF-7 cancer cell line resistant to vinblastine was tested.

Factores de riesgo de desnutrición en menores de cinco años del municipio de Manatí / Risk factors of malnutrition in children younger than five years old in Manatí municipality

Fundamento: el estado nutricional de los niños está intrínsecamente relacionado con el crecimiento y desarrollo en las distintas etapas de la vida y debe evaluarse integralmente considerando el crecimiento armónico en relación con la nutrición.Objetivo: identificar factores de riesgo, asociados a la desnutrición en niños menores de cinco años, pertenecientes al área de salud del policlínico universitario Mártires de Manatí, municipio de Manatí, Las Tunas, desde enero de 2013 hasta febrero de 2016.Métodos: se realizó un estudio observacional analítico retrospectivo, tipo caso control, en el lugar y período señalados, sobre factores de riesgo asociados a la malnutrición en niños. La muestra estuvo constituida por 460 niños, 230 desnutridos del grupo de estudio, que se encontraban por debajo del tercer percentil, según las tablas cubanas del peso para la talla, y 230 niños normo peso del grupo control, seleccionados por el método aleatorio simple.Resultados: las malas condiciones higiénico-sanitarias aumentaron en 6,2 el riesgo de malnutrición en los infantes. Los niños con ablactación inadecuada incrementaron este riesgo en 5,8 veces y la lactancia artificial en 1,8. La baja per cápita familiar, la baja escolaridad de la madre, y las enfermedades asociadas fueron otros factores de riesgo de malnutrición. No se demostró asociación causal entre el bajo peso al nacer y la desnutrición al quinto año de vida.Conclusiones: se identificaron los factores de riesgo asociados a la malnutrición. Las malas condiciones higiénico-sanitarias, la ablactación inadecuada y la lactancia artificial resultaron los de mayor incidencia (AU)

Background: the children's nutritional state is intrinsically related to their growth and development in the different stages of life and it should be assessed considering their harmonic growth in relation to nutrition. Objective: To identify the risk factors associated to malnutrition in children younger than five years old who belong to the health area of Mártires de Manatí polyclinic, Manatí municipality in Las Tunas, from January, 2013 to February, 2016.Methods: a retrospective, analytic and observational study, type case control, was carried out in the place and time period mentioned before, about risk factors associated to malnutrition in children. The sample was made up of 460 children, 230 undernourished children from the study group that were below the third percentile, according to the Cuban charts of weight for the size, and 230 children normal weight of the control group selected at random.Results: the bad hygienic-sanitary conditions increased 6, 2 times the malnutrition risk in the infants. Children with inadequate ablactation increased the risk in 5,8 times and the artificial nursing incremented it in 1,8 times. The low per capita family income, low mother schooling, and the associated dis eases were other risk factors of malnutrition. Causal association between low birth weight and malnutrition at fifth year of life was not demonstrated.Conclusions: the risk factors associated to malnutrition were identified. The bad hygienic-sanitary conditions, inadequate ablactation and the artificial breastfeeding showed the highest incidence (AU)

Relative Stereochemistry and Absolute Configuration of Farinosin, a Eudesmanolide From Encelia farinosa.

The naturally occurring eudesmanolide farinosin () is now fully characterized for the first time despite its original isolation almost half a century ago. The early assumed relative stereochemistry and absolute configuration were confirmed by vibrational circular dichroism together with evaluation of the Hooft X-ray parameters. The molecular conformation is very similar in the gas stage and in the solid state. Chirality 28:415-419, 2016. © 2016 Wiley Periodicals, Inc.

Structure elucidation of a new isoflavone by exclusive use of ¹H NMR measurements.

The leaves of Piscidia carthagenensis provided new 7,2',5'-trimethoxy-3',4'-methylenedioxyisoflavone (1), admixed with known 6,7-dimethoxy-3',4'-methylenedioxyisoflavone (2), and 5,4'-dihydroxy-7,2',5'-trimethoxyisoflavone (3), which were separated by extensive fractional solubillization. Selective irradiation of the H-5 "singlet" of 2 allowed distinction of the two methoxy group signals, whose chemical shift difference is only 0.004 ppm (1.2 Hz at 300 MHz). The (1)H and (13)C NMR data of 3 were assigned with the aid of HETCOR and gHMBC measurements. Although 1 looked inhomogeneous in the solid state, its solution structure followed from (1)H NMR measurements, where it looked homogeneous. To clarify the solid state aspect and confirm the structure of 1, two types of crystals were mechanically separated and subjected to single crystal X-ray diffraction measurements. This study revealed polymorphism because of the concomitant presence of orthorhombic and triclinic crystals, but showed no atropisomerism. The structure of 3 was also verified by X-ray diffraction crystallography.

Antiamoebic and Antigiardial Activity of Clerodane Diterpenes from Mexican Salvia Species Used for the Treatment of Diarrhea.

Terpenoids from Salvia species have been identified to possess biological properties as antiprotozoal agents. Here, we evaluated the antiamoebic and antigiardial activities of 14 known clerodane and modified clerodane-type diterpenes isolated from five Mexican Salvia species against Entamoeba histolytica and Giardia lamblia, and analyzed the effects of the functionalities in decalin ring or in the whole clerodane framework to visualize the structural requirements necessary to produce an antiprotozoal activity. Among these, linearolactone was the most active clerodane diterpene against both protozoa with IC50 values of 22.9 µM for E. histolytica and of 28.2 µM in the case of G. lamblia. In this context it may be a lead compound for the development of novel therapeutic agent for the treatment of diarrhea and dysentery. The remaining diterpenes assayed showed moderate to weak activity against both protozoa. These findings give support to the use of Salvia species in the traditional medicine from México for the treatment of diarrhea.

Teotihuacanin, a Diterpene with an Unusual Spiro-10/6 System from Salvia amarissima with Potent Modulatory Activity of Multidrug Resistance in Cancer Cells.

Teotihuacanin (1), an unusual rearranged clerodane diterpene with a new carbon skeleton containing a spiro-10/6 bicyclic system, was isolated from the leaves and flowers of Salvia amarissima. Its structure was determined through spectroscopic analyses. Its absolute configuration was established by single-crystal X-ray diffraction. Compound 1 showed potent modulatory activity of multidrug resistance in vinblastine-resistant MCF-7 cancer cell line (reversal fold, RFMCF-7/Vin+ > 10703) at 25 µg/mL.

Antiprotozoal activity of 8-acyl and 8-alkyl incomptine A analogs.

The activities of 11 C-8-O-acyl and alkyl analogs of the antiprotozoal sesquiterpene lactone, incomptine A (1) against Entamoeba histolytica and Giardia lamblia, were determined. Here, the effects of different lengths and amounts of branching of the acyl and alkyl groups on the antiprotozoal activity of the synthesized incomptine A-analogs are reported.

5,10-seco-neo-clerodanes and neo-clerodanes from Salvia microphylla.

Two new 5,10-seco-neo-clerodanes, salvimicrophyllins A and B (1 and 2), and two new neo-clerodanes, salvimicrophyllins C and D (3 and 4), were isolated from the leaves and flowers of Salvia microphylla. The structures of these compounds were elucidated mainly by analysis of their NMR spectroscopic and mass spectrometric data. The relative configurations of the salvimicrophyllins were determined by analysis of NOESY spectra and ECD curves, and the relative configuration of compound 2 was confirmed by single-crystal X-ray diffraction crystallography.

Hydroxyclerodanes from Salvia shannoni.

Six new hydroxyclerodanes (1-6), named sepulturins A-F, and four known diterpenes were isolated from the leaves of Salvia shannoni. The structures of these compounds were established by extensive analysis of their NMR and MS spectroscopic data. The relative configurations of compounds 1 and 2 were determined by NOESY experiments and were confirmed by single-crystal X-ray diffraction studies. All of the isolated diterpenes possess tertiary OH groups. The structure of infuscatin (7), a clerodane previously isolated from S. infuscata, was revised. Cytotoxic, antiprotozoal, and anti-inflammatory activities of these compounds were evaluated.

Microphyllandiolide, a new diterpene with an unprecedented skeleton from Salvia microphylla.

Microphyllandiolide (1), an unprecedented rearranged clerodane-type diterpene with a 9/3 bicyclic ring system, was isolated from the aerial parts of Salvia microphylla Kunth. Its structure was elucidated by analysis of its spectroscopic data and confirmed by single crystal X-ray diffraction analysis. A possible biogenesis for microphyllandiolide (1) is proposed.