Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice

Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain‐of‐activity mouse model presents with a premature aging‐like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging, and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75‐week‐old) female C57BL/6 mice with a Cdc42 activity‐specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan. Moreover, aged CASIN‐treated animals displayed a youthful level of the aging‐associated cytokines IL‐1β, IL‐1α, and INFγ in serum and a significantly younger epigenetic clock as based on DNA methylation levels in blood cells. Overall, our data show that systemic administration of CASIN to reduce Cdc42 activity in aged mice extends murine lifespan.     

Taxonomy, phylogeny and biogeography of Kickxia and Nanorrhinum (Scrophulariaceae)

Phylogenetic studies in Kickxia sensu lato, using morphological characters, show that two groups of species appear as distinct clades, one corresponding to sect. Kickxia and the other corresponding to sect. Valvatae. The differences between the two sections are of the same magnitude as those used to separate other closely related genera in the tribe. Therefore, the treatment of sect. Valvatae as a separate genus, Nanorrhinum , is proposed. Results from a dispersal-vicariance analysis indicate that the area of origin for Nanorrhinum is Arabia, whereas for Kickxia sensu stricto it is either Macaronesia, the Mediterranean Region or both these areas combined. The taxonomy of Nanorrhinum is revised in detail, whereas for Kickxia a synoptical treatment is given, mainly based on previous literature. The results indicate that the plasticity of the species of Nanorrhinum , as well as the variation within populations in the field, is often much greater than previously thought, and that, therefore, far too many species have been described. In the present study ten species are recognized in Nanorrhinum. New combinations are N. azraqensis, N. stenanthum, N. hastatum, N. elegans, N. kuriensis, N. asparagoides, N. heterophyllum and N. woodii. Three lectotypes are selected. Keys to all taxa are given, and new information on chromosome numbers and sexual systems are provided for several species.     

Predicting Odor Pleasantness with an Electronic Nose

A primary goal for artificial nose (eNose) technology is to report perceptual qualities of novel odors. Currently, however, eNoses primarily detect and discriminate between odorants they previously “learned”. We tuned an eNose to human odor pleasantness estimates. We then used the eNose to predict the pleasantness of novel odorants, and tested these predictions in naïve subjects who had not participated in the tuning procedure. We found that our apparatus generated odorant pleasantness ratings with above 80% similarity to average human ratings, and with above 90% accuracy at discriminating between categorically pleasant or unpleasant odorants. Similar results were obtained in two cultures, native Israeli and native Ethiopian, without retuning of the apparatus. These findings suggest that unlike in vision and audition, in olfaction there is a systematic predictable link between stimulus structure and stimulus pleasantness. This goes in contrast to the popular notion that odorant pleasantness is completely subjective, and may provide a new method for odor screening and environmental monitoring, as well as a critical building block for digital transmission of smell.     

Phylogeny of the tribe Antirrhineae (Scrophulariaceae) based on morphological andndhF sequence data

Phylogenetic relationships within the tribe Antirrhineae (Scrophulariaceae) are analysed and discussed on the basis of parsimony analyses of morphological andndhF gene sequence data. The results indicate that the tribe Antirrhineae consists of four major groups of genera, theAnarrhinum clade, theGambelia clade, theMaurandya clade, and theAntirrhinum clade. TheAnarrhinum clade, consisting of the Old World bee-pollinated generaAnarrhinum andKickxia, is sister to the rest of the tribe. TheGambelia clade consists of the New World generaGambelia andGalvezia, which are very closely related and pollinated by hummingbirds. TheMaurandya clade consists of one subclade includingMaurandya and a number of related bee- or hummingbird-pollinated New World genera and another subclade with the Old World bee-pollinated generaAsarina andCymbalaria. TheAntirrhinum clade consists mainly of bee-pollinated Old World genera, such asAntirrhinum, Linaria, Chaenorhinum, and their segregates, but also includes the New World generaMohavea andHowelliella, of which the latter is known to be partly pollinated by hummingbirds. It is concluded that hummingbirdpollination has evolved independently within Antirrhineae at least three times from bee-pollinated ancestors.     

The <Emphasis Type="Italic">Trichoderma harzianum</Emphasis> demon: complex speciation history resulting in coexistence of hypothetical biological species,recent agamospecies and numerous relict lineages

Background  

The mitosporic fungus Trichoderma harzianum (Hypocrea, Ascomycota, Hypocreales, Hypocreaceae) is an ubiquitous species in the environment with some strains commercially exploited for the biological control of plant pathogenic fungi. Although T. harzianum is asexual (or anamorphic), its sexual stage (or teleomorph) has been described as Hypocrea lixii. Since recombination would be an important issue for the efficacy of an agent of the biological control in the field, we investigated the phylogenetic structure of the species.     

Successful Treatment of Human Visceral Leishmaniasis Restores Antigen-Specific IFN-γ, but not IL-10 Production

One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole blood cells have maintained the capacity to produce IFN-γ. Here we tested the hypothesis that a population of low-density granulocytes (LDG) might contribute to T cell responses hyporesponsiveness via the release of arginase. Our results show that this population is affected by the anticoagulant used to collect blood: the frequency of LDGs is significantly lower when the blood is collected with heparin as compared to EDTA; however, the anticoagulant does not impact on the levels of arginase released. Next, we assessed the capacity of whole blood cells from patients with active VL to produce IFN-γ and IL-10 in response to antigen-specific and polyclonal activation. Our results show that whole blood cells produce low or levels below detection limit of IFN-γ and IL-10, however, after successful treatment of VL patients, these cells gradually regain their capacity to produce IFN-γ, but not IL-10, in response to activation. These results suggest that in contrast to VL patients from Bihar, India, whole blood cells from VL patients from Gondar, Ethiopia, have lost their ability to produce IFN-γ during active VL and that active disease is not associated with sustained levels of IL-10 production following stimulation.     

Abdominal ultrasound in the diagnostic work-up of visceral leishmaniasis and for detection of complications of spleen aspiration

IntroductionAbdominal ultrasound (US) is increasingly used in the diagnostic work-up of infectious diseases, but studies on its diagnostic value in visceral leishmaniasis (VL) are lacking. US could help to identify complications of spleen aspiration (SA). We aimed to assess the diagnostic value of US and the evolution of findings after VL treatment; the incidence and degree of splenic injury; and the pain perceived during SA.Methodology/resultWe conducted a cross-sectional prospective study at the Leishmaniasis Research and Treatment Center, Gondar, Ethiopia between Oct 2017 and Dec 2018. We enrolled VL suspects undergoing tissue aspiration; US were conducted before and after SA, and at the end of VL treatment. Splenic injury was graded using the American association of surgery trauma injury scale (grade 1–4). The pain perceived during SA was graded using a visual analogue scale. Out of 392 VL suspects, 192 (49%) were confirmed VL cases. The median age was 25 years (IQR 21–30). Massive splenomegaly and hepatomegaly were the most common US findings. Splenic nodules were seen in 3.7% of the 190 VL cases and 1.5% of the 197 non-VL cases. Ascites was more common in VL (16.4%) than in non-VL cases (9.1%). The frequency of US abnormalities decreased with treatment. None of the US findings had sufficient sensitivity and specificity to justify its use as a diagnostic test. US detected splenic injury in four of the 318 patients who had post-SA US. All four patients remained clinically stable. Pain was perceived as moderate or severe in 51% of patients.ConclusionThe diagnostic value of abdominal US for VL was low but found useful to detect subclinical splenic injury. SA caries a risk of splenic injury and was perceived painful by most. Further research on less invasive diagnostic tools is needed.