Project description:High genetic and phenotypic variability between Leishmania species and strains within species make the development of broad-spectrum antileishmanial drugs challenging. Thus, screening panels consisting of several diverse Leishmania species can be useful in enabling compound prioritization based on their spectrum of activity. In this study, a robust and reproducible high content assay was developed, and 1280 small molecules were simultaneously screened against clinically relevant cutaneous and visceral species: L. amazonensis, L. braziliensis, and L. donovani. The assay is based on THP-1 macrophages infected with stationary phase promastigotes and posterior evaluation of both compound antileishmanial activity and host cell toxicity. The profile of compound activity was species-specific, and out of 51 active compounds, only 14 presented broad-spectrum activity against the three species, with activities ranging from 52% to 100%. Notably, the compounds CB1954, Clomipramine, Maprotiline, Protriptyline, and ML-9 presented pan-leishmanial activity, with efficacy greater than 70%. The results highlight the reduced number of compound classes with pan-leishmanial activity that might be available from diversity libraries, emphasizing the need to screen active compounds against a panel of species and strains. The assay reported here can be adapted to virtually any Leishmania species without the need for genetic modification of parasites, providing the basis for the discovery of broad spectrum anti-leishmanial agents.
Project description:IntroductionSensory-processing sensitivity (SPS) refers to interindividual differences in sensitivity to positive and negative environmental stimuli and reflects the concept of differential susceptibility. The Highly Sensitive Person Scale (HSPS) has been utilized to capture the multifaceted experiences of highly sensitive individuals. The scale's total score (i.e., the sum of the subfactors) is an indicator of high sensitivity. However, it cannot differentiate between the contributions of the specific subfactors. Consequently, interpreting the total score cannot help resolve the current theoretical debate about how individuals integrate the positive and negative aspects of sensitivity, whereas a multidimensional profile should be able to offer a more comprehensive understanding. Intriguingly, in variable-centered research, the subfactors' differential associations with external constructs in negative or positive trait spaces have suggested heterogeneity (i.e., interindividual differences) among highly sensitive individuals. Thus, person-centered approaches should be better suited to address this heterogeneity.MethodsTo explore heterogeneity within the highly sensitive population, we conducted a three-step Latent Profile Analysis in two independent German-speaking samples (N = 1,102; N = 526). Subsequently, we employed the Five-Factor Model of personality to provide a detailed description of the latent sensitivity groups.ResultsBeyond the frequently identified quantitative three-class differentiation of sensitivity groups, we obtained a four-class model that included two qualitatively different high-sensitivity groups, each displaying distinct HSPS subfactor and personality patterns that corresponded to prototypical personality profiles. Within these high sensitivity groups, (i) the Confident Sensitivity Group exhibited average Neuroticism, significantly above-average Openness, and slightly above-average Extraversion. By contrast, (ii) the Vulnerable Sensitivity Group displayed the typical personality pattern of significantly above-average Neuroticism, below-average Extraversion, and slightly above-average Openness. Personality analyses revealed that features such as passiveness, internalizing tendencies, giftedness, and aesthetics, often commonly ascribed to all highly sensitive individuals, are features that differ across distinct sensitivity groups.DiscussionTo avoid over- or underestimating sensitivity effects, future research should consider these interindividual differences in highly sensitive individuals. For instance, studies could focus on the different associations of sensitivity groups with abilities, health aspects, emotion regulation and intervention outcomes, taking into account the different environmental factors that shape the type of sensitivity.
Project description:Collective decision-making processes emerge from social feedback networks within a group. Many studies on collective behaviour underestimate the role of individual personality and, as a result, personality is rarely analysed in the context of collective dynamics. Here, we show evidence of sheltering behaviour personality in a gregarious insect (Periplaneta americana), which is characterized by a collective personality at the group level. We also highlight that the individuals within groups exhibited consistent personality traits in their probability of sheltering and total time sheltered during the three trials over one week. Moreover, the group personality, which arises from the synergy between the distribution of behaviour profiles in the group and social amplifications, affected the sheltering dynamics. However, owing to its robustness, personality did not affect the group probability of reaching a consensus. Finally, to prove social interactions, we developed a new statistical method that will be helpful for future research on personality traits and group behaviour. This approach will help to identify the circumstances under which particular group compositions may improve the fitness of individuals in gregarious species.
Project description:Multi-stability refers to the phenomenon of perception stochastically switching between possible interpretations of an unchanging stimulus. Despite considerable variability, individuals show stable idiosyncratic patterns of switching between alternative perceptions in the auditory streaming paradigm. We explored correlates of the individual switching patterns with executive functions, personality traits, and creativity. The main dimensions on which individual switching patterns differed from each other were identified using multidimensional scaling. Individuals with high scores on the dimension explaining the largest portion of the inter-individual variance switched more often between the alternative perceptions than those with low scores. They also perceived the most unusual interpretation more often, and experienced all perceptual alternatives with a shorter delay from stimulus onset. The ego-resiliency personality trait, which reflects a tendency for adaptive flexibility and experience seeking, was significantly positively related to this dimension. Taking these results together we suggest that this dimension may reflect the individual's tendency for exploring the auditory environment. Executive functions were significantly related to some of the variables describing global properties of the switching patterns, such as the average number of switches. Thus individual patterns of perceptual switching in the auditory streaming paradigm are related to some personality traits and executive functions.
Project description:In temperate forests, climate seasonality restricts the photosynthetic activity of primary producers to the warm season from spring to autumn, while the cold season with temperatures below the freezing point represents a period of strongly reduced plant activity. Although soil microorganisms are active all-year-round, their expressions show seasonal patterns. This is especially visible on the ectomycorrhizal fungi, the most abundant guild of fungi in coniferous forests. We quantified the production of fungal mycelia using ingrowth sandbags in the organic layer of soil in temperate coniferous forest and analysed the composition of fungal communities in four consecutive seasons. We show that fungal biomass production is as low as 0.029 µg g-1 of sand in December-March, while it reaches 0.122 µg g-1 in June-September. The majority of fungi show distinct patterns of seasonal mycelial production, with most ectomycorrhizal fungi colonising ingrowth bags in the spring or summer, while the autumn and winter colonisation was mostly due to moulds. Our results indicate that fungal taxa differ in their seasonal patterns of mycelial production. Although fungal biomass turnover appears all-year-round, its rates are much faster in the period of plant activity than in the cold season.
Project description:During malaria infection, Plasmodium sporozoites, the fast-moving stage of the parasite, are injected by a mosquito into the skin of the mammalian host. In the skin, sporozoites need to migrate through the dermal tissue to enter the blood vessel. Sporozoite motility is critical for infection but not well understood. Here, we used collagen hydrogels with tunable fiber structures, as an in vitro model for the skin. After injecting sporozoites into the hydrogel, we analyzed their motility in three-dimension (3D). We found that sporozoites demonstrated chiral motility, in that they mostly follow right-handed helical trajectories. In high-concentration collagen gel, sporozoites have lower instantaneous speed, but exhibit straighter tracks compared to low-concentration collagen gel, which leads to longer net displacement and faster dissemination. Taken together, our study indicates an inner mechanism for sporozoites to adapt to the environment, which could help with their successful exit from the skin tissue.
Project description:BackgroundOne of the major challenges in evolutionary biology is identifying rare species and devising management plans to protect them while also sustaining their genetic diversity. However, in attempting a broad understanding of rarity, single-species studies provide limited insights because they do not reveal whether the factors that affect rare species differ from those that affect more common species. To illustrate this important concept and to arrive at a better understanding of the form of rarity characterizing the rare Gerbillus henleyi, we explored its population genetic structure alongside that of the locally common Gerbillus andersoni allenbyi. We trapped gerbils in several locations in Israel's western and inner Negev sand dunes. We then extracted DNA from ear samples, and amplified two mitochondrial sequences: the control region (CR) and the cytochrome oxidase 2 gene (CO2).ResultsNucleotide diversity was low for all sequences, especially for the CR of G. a. allenbyi, which showed no diversity. We could not detect any significant population genetic structure in G. henleyi. In contrast, G. a. allenbyi's CO2 sequence showed significant population genetic structure. Pairwise PhiPT comparisons showed low values for G. henleyi but high values for G. a. allenbyi. Analysis of the species' demographic history indicated that G. henleyi's population size has not changed recently, and is under the influence of an ongoing bottleneck. The same analysis for G. a. allenbyi showed that this species has undergone a recent population expansion.ConclusionsComparing the two species, the populations of G. a. allenbyi are more isolated from each other, likely due to the high habitat specificity characterizing this species. The bottleneck pattern found in G. henleyi may be the result of competition with larger gerbil species. This result, together with the broad habitat use and high turnover rate characterizing G. henleyi, may explain the low level of differentiation among its populations. The evidence for a recent population expansion of G. a. allenbyi fits well with known geomorphological data about the formation of the Negev sand dunes and paleontological data about this species' expansion throughout the Levant. In conclusion, we suggest that adopting a comparative approach as presented here can markedly improve our understanding of the causes and effects of rarity, which in turn can allow us to better protect biodiversity patterns.
Project description:Diverse interactions among species within bacterial colonies lead to intricate spatiotemporal dynamics, which can affect their growth and survival. Here, we describe the emergence of complex structures in a colony grown from mixtures of motile and non-motile bacterial species on a soft agar surface. Time-lapse imaging shows that non-motile bacteria 'hitchhike' on the motile bacteria as the latter migrate outward. The non-motile bacteria accumulate at the boundary of the colony and trigger an instability that leaves behind striking flower-like patterns. The mechanism of the front instability governing this pattern formation is elucidated by a mathematical model for the frictional motion of the colony interface, with friction depending on the local concentration of the non-motile species. A more elaborate two-dimensional phase-field model that explicitly accounts for the interplay between growth, mechanical stress from the motile species, and friction provided by the non-motile species, fully reproduces the observed flower-like patterns.
Project description:Animals can learn about sources of danger while minimizing their own risk by observing how others respond to threats. However, the distinct neural mechanisms by which threats are learned through social observation (known as observational fear learning1-4 (OFL)) to generate behavioural responses specific to such threats remain poorly understood. The dorsomedial prefrontal cortex (dmPFC) performs several key functions that may underlie OFL, including processing of social information and disambiguation of threat cues5-11. Here we show that dmPFC is recruited and required for OFL in mice. Using cellular-resolution microendoscopic calcium imaging, we demonstrate that dmPFC neurons code for observational fear and do so in a manner that is distinct from direct experience. We find that dmPFC neuronal activity predicts upcoming switches between freezing and moving state elicited by threat. By combining neuronal circuit mapping, calcium imaging, electrophysiological recordings and optogenetics, we show that dmPFC projections to the midbrain periaqueductal grey (PAG) constrain observer freezing, and that amygdalar and hippocampal inputs to dmPFC opposingly modulate observer freezing. Together our findings reveal that dmPFC neurons compute a distinct code for observational fear and coordinate long-range neural circuits to select behavioural responses.
Project description:Nuclear integrations of mitochondrial DNA (numts) are widespread among eukaryotes, although their prevalence differs greatly among taxa. Most knowledge of numt evolution comes from analyses of whole-genome sequences of single species or, more recently, from genomic comparisons across vast phylogenetic distances. Here we employ a comparative approach using human and chimpanzee genome sequence data to infer differences in the patterns and processes underlying numt integrations. We identified 66 numts that have integrated into the chimpanzee nuclear genome since the human-chimp divergence, which is significantly greater than the 37 numts observed in humans. By comparing these closely related species, we accurately reconstructed the preintegration target site sequence and deduced nucleotide changes associated with numt integration. From >100 species-specific numts, we quantified the frequency of small insertions, deletions, duplications, and instances of microhomology. Most human and chimpanzee numt integrations were accompanied by microhomology and short indels of the kind typically observed in the nonhomologous end-joining pathway of DNA double-strand break repair. Human-specific numts have integrated into regions with a significant deficit of transposable elements; however, the same was not seen in chimpanzees. From a separate data set, we also found evidence for an apparent increase in the rate of numt insertions in the last common ancestor of humans and the great apes using a polymerase chain reaction-based screen. Last, phylogenetic analyses indicate that mitochondrial-numt alignments must be at least 500 bp, and preferably >1 kb in length, to accurately reconstruct hominoid phylogeny and recover the correct point of numt insertion.