tele-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials

We have discovered and studied a tele-substitution reaction in a biologically important heterocyclic ring system. Conditions that favor the tele-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base or the use of softer nucleophiles, less polar solvents, and larger halogens on the electrophile. Using results from X-ray crystallographic and isotope labeling experiments, a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the in vivo active antiplasmodium compounds of Series 4 of the Open Source Malaria consortium

DYSMENORRHEA AMONG FEMALE MEDICAL SCIENCES STUDENTS IN MACHS: PREVALENCE, PREDICTORS AND OUTCOME

Objective: This study intended to determine the prevalence, predictors, and outcome of dysmenorrhea among female medical sciences students at Mohammed Al-Mana College for Medical Sciences (MACHS), Dammam, Saudi Arabia. Methods: A cross-sectional study was adopted, and 292 female medical sciences students of MACHS were selected using stratified random sampling. A semi-structured and self- administrated questionnaire was used to collect personal and socio-demographic information from the selected female medical sciences students. The information about the menstrual history, stress, and smoking were also gathered. The data analysis was carried out using the descriptive statistics and Chi-square test. Results: The prevalence of dysmenorrhea was 73.28% among female medical sciences students. Concerning the signs and symptoms of dysmenorrhea, the abdominal pain was predominant symptoms among 73.28% of the respondents, and it was found to be statistically significant (p≤0.05). Sleep disturbance was observed as the prominent outcome of dysmenorrhea, as reported by 64% of the respondents

Recent Basal Melting of a Mid-Latitude Glacier on Mars

Evidence for past basal melting of young (late Amazonian), debris-covered glaciers in Mars’ mid-latitudes is extremely rare. Thus, it is widely thought that these viscous flow features (VFFs) have been perennially frozen to their beds. We identify an instance of recent, localized wet-based mid-latitude glaciation, evidenced by a candidate esker emerging from a VFF in a tectonic rift in Tempe Terra. Eskers are sedimentary ridges deposited in ice-walled meltwater conduits and are indicative of glacial melting. We compare the candidate esker to terrestrial analogues, present a geomorphic map of landforms in the rift, and develop a landsystem model to explain their formation. We propose that the candidate esker formed during a transient phase of wet-based glaciation. We then consider the similarity between the geologic setting of the new candidate esker and that of the only other candidate esker to be identified in association with an existing mid-latitude VFF; both are within tectonic graben/rifts proximal to volcanic provinces. Finally, we calculate potential basal temperatures for a range of VFF thicknesses, driving stresses, mean annual surface temperatures, and geothermal heat fluxes, which unlike previous studies, include the possible role of internal strain heating. Strain heating can form an important additional heat source, especially in flow convergence zones, or where ice is warmer due to elevated surface temperatures or geothermal heat flux. Elevated geothermal heat flux within rifts, perhaps combined with locally-elevated strain heating, may have permitted wet-based glaciation during the late Amazonian, when cold climates precluded more extensive wet-based glaciation on Mars

Effect of maturity and harvest season on antioxidant activity, phenolic compounds and ascorbic acid of Morinda citrifolia L. (noni) grown in Mexico (with track change)

Antioxidant activity diphenylpicrylhydrazyl (DPPH), the ferric-reducing antioxidant power assay (FRAP), nitric oxide (NO)], total polyphenols, phenolic compounds and ascorbic acid of Morinda citrifolia L. fruits were investigated as a function of maturity and three seasons patterns in Mexico. Maturity was evaluated in early, middle, sub-mature and mature stages (1 to 4) according to color and firmness. Significant differences were observed in the antioxidant activities and chemical composition of the fruits at different maturity and seasons. During February-March and May- June, fruits from middle and mature stages exhibited the highest antioxidant activities and total polyphenol content compared to other stages, while in November, ripe fruits reached the greatest antioxidant efficacy, total phenolic and ascorbic acid contents. Total polyphenols and ascorbic acid reached the highest amounts during May-June, although antioxidant activities were moderate compared to greater values in February-March or November depending upon maturity. The ability of M. citrifolia fruits to inhibit NO production by LPSactivated RAW 264.7 cells was quite comparable to or higher than N-nitro-L-arginine methyl ester (LNAME). This work shows that season and maturity stages have a profound effect on the antioxidant capacity, phenols and ascorbic acid of M. Citrifolia fruits.Keywords: Morinda citrifolia, diphenylpicrylhydrazyl (DPPH) radical scavenging, maturity, seasons, total polyphenol and phenolics compounds, reducing power, ascorbic acid, scavenging nitric oxide.African Journal of Biotechnology Vol. 12(29), pp. 4630-463

Reconstructions of deltaic environments from Holocene palynological records in the Volga delta, northern Caspian Sea

This article was made available through open access by the Brunel Open Access Publishing Fund.New palynological and ostracod data are presented from the Holocene Volga delta, obtained from short cores and surface samples collected in the Damchik region, near Astrakhan, Russian Federation in the northern Caspian Sea. Four phases of delta deposition are recognized and constrained by accelerated mass spectrometry (AMS) radiocarbon ages. Palynological records show that erosive channels, dunes (Baer hills) and inter-dune lakes were present during the period 11,500–8900 cal. BP at the time of the Mangyshlak Caspian lowstand. The period 8900–3770 cal. BP was characterized regionally by extensive steppe vegetation, with forest present at times with warmer, more humid climates, and with halophytic and xerophytic vegetation present at times of drought. The period 3770–2080 cal. BP was a time of active delta deposition, with forest or woodland close to the delta, indicating relatively warm and humid climates and variable Caspian Sea levels. From 2080 cal. BP to the present-day, aquatic pollen is frequent in highstand intervals and herbaceous pollen and fungal hyphae frequent in lowstand intervals. Soils and incised valley sediments are associated with the regional Derbent regression and may be time-equivalent with the ‘Medieval Warm Period’. Fungal spores are an indicator of erosional or aeolian processes, whereas fungal hyphae are associated with soil formation. Freshwater algae, ostracods and dinocysts indicate mainly freshwater conditions during the Holocene with minor brackish influences. Dinocysts present include Spiniferites cruciformis, Caspidinium rugosum, Impagidinium caspienense and Pterocysta cruciformis, the latter a new record for the Caspian Sea. The Holocene Volga delta is a partial analogue for the much larger oil and gas bearing Mio-Pliocene palaeo-Volga delta.Funding for the data collection and field work was provided from the following sources: 1 – IGCP-UNESCO 2003–2008 (Project 481 CASPAGE, Dating Caspian Sea Level Change); 2 – NWO, Netherlands Science Foundation and RFFI, Russian Science Foundation 2005–2008 (Programme: ‘VHR Seismic Stratigraphy and Paleoecology of the Holocene Volga Delta’); and 3 – BP Exploration (Caspian Sea) Sea Ltd. (Azeri-Chirag-Gunashli) 2005–2008 (‘Unravelling the Small-Scale Stratigraphy and Sediment Dynamics of the Modern Volga Delta Using VHR Marine Geophysics’). The palynological work was funded jointly by BP Exploration (Caspian Sea) Ltd., Delft University of Technology and KrA Stratigraphic Ltd. Ostracod analyses were funded by StrataData Ltd. and funding for two additional radiocarbon dates provided by Deltares

Gene diversity in grevillea populations introduced in Brazil and its implication on management of genetic resources.

A variabilidade isoenzimática para seis populações de Grevillea robusta, oriundas de um teste de procedências/progenies, implantado no delineamento em blocos casualizados com 5 plantas por parcela, no Sul do Brasil, é descrita. A estrutura genética da população foi analisada utilizando-se marcadores bioquímicos, aos 5 anos de idade, especificamente para os locos MDH-3, PGM-2, DIA-2, PO-1, PO-2, SOD-1, e SKDH-1. As procedências do norte de ocorrência natural (Rathdowney e Woodenbong) apresentaram divergência genética superior, em relação à média das progênies, considerando o número de alelos por locus, (Ap), a riqueza alélica (Rs), a diversidade genética de Nei (H), e o coeficiente de endogamia (f). A endogamia foi detectada em diversos graus. A testemunha comercial apresentou o maior coeficiente de endogamia, (f = 0,4448), comparativamente à média das procedências (f = 0,2306), possivelmente devido à insuficiente amostragem populacional na região de origem (Austrália). Apesar de sua ocorrência natural restrita, observou-se correlação positiva entre divergência genética e distância geográfica entre as populações originais. A distância genética e análise de cluster, baseada no modelo bayesiano, mostrou três grupos de procedências distintos: 1) Rathdowney- QLD e Woodenbong-QLD; 2) Paddy?s Flat-NSW; e 3) Mann River-NSW, Boyd River-NSW e a testemunha comercial (material utilizado no Brasil). O agrupamento da testemunha com as procedências Mann River-NSW e Boyd River-NSW sugere um maior potencial das procedências do norte para o melhoramento genético visando à produção de madeira no Brasil, devido a sua elevada diversidade genética e baixo coeficiente de endogamia

Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism

Narcissism and prosocial behavior

There are many motivations for prosocial behavior, some more altruistic and some more egoistic. We posit that more narcissistic people may perform prosocial acts strategically, for example, to improve their reputations or to receive something in return

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus

Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases