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1. Pollination services of cacao are crucial for global chocolate production, yet remain critically understudied, particularly in regions of origin of the species. Notably, uncertainties remain concerning the identity of cacao pollinators, the influence of landscape (forest distance) and management (shade cover) on flower visitation and the role of pollen deposition in limiting fruit set.
2. Here, we aimed to improve understanding of cacao pollination by studying limiting factors of fruit set in Peru, part of the centre of origin of cacao. Flower visitors were sampled with sticky insect glue in 20 cacao agroforests in two biogeographically distinct regions of Peru, across gradients of shade cover and forest distance. Further, we assessed pollen quantities and compared fruit set between naturally and manually pollinated flowers.
3. The most abundant flower visitors were aphids, ants and thrips in the north and thrips, midges and parasitoid wasps in the south of Peru. We present some evidence of increasing visitation rates from medium to high shade (40%–95% canopy closure) in the dry north, and opposite patterns in the semi-humid south, during the wet season.
4. Natural pollination resulted in remarkably low fruit set rates (2%), and very low pollen deposition. After hand pollination, fruit set more than tripled (7%), but was still low.
5. The diversity and high relative abundances of herbivore flower visitors limit our ability to draw conclusions on the functional role of different flower visitors. The remarkably low fruit set of naturally and even hand pollinated flowers indicates that other unaddressed factors limit cacao fruit production. Such factors could be, amongst others, a lack of effective pollinators, genetic incompatibility or resource limitation. Revealing efficient pollinator species and other causes of low fruit set rates is therefore key to establish location-specific management strategies and develop high yielding native cacao agroforestry systems in regions of origin of cacao
Cancer is one of the leading causes of death worldwide, with currently assessed chances to develop at least one cancer in a lifetime for about 20%. High cases rates and mortality require the development of new anticancer therapies and treatment strategies. Another important concern is toxicity normally associated with conventional therapy methods, such as chemo- and radiotherapy. Among many proposed antitumoral agents, oncolytic viruses are still one of the promising and fast-developing fields of research with almost a hundred studies published data on over 3000 patients since the beginning of the new millennia.
Among all oncolytic viruses, the Vaccinia virus is arguably one of the safest, with an extremely long and prominent history of use, since it was the one and only vaccine used in the Smallpox Eradication Program in the 1970s. Interestingly enough, it was the first oncolytic virus proven to have tumor tropism in vitro and in vivo in laboratory settings, and this year we can celebrate an unofficial 100th anniversary since the publication of the fact. While being highly immunogenic, Vaccinia virus DNA replication takes place in the cytoplasm of the infected cell, and virus genes never integrate into the host genome. Another advantage of using Vaccinia as an oncolytic agent is its high genome capacity, which allows inserting up to 25 kbps of exogenous genes, thus allowing to additionally arm the virus against the tumor.
Oncolytic virus action consists of two major parts: direct oncolysis and immune activation against the tumor, with the latter being the key to successful treatment. To this moment, preclinical research data are mostly generated in immunocompromised xenograft models, which have hurdles to be properly translated for clinical use. In the first part of the current study, fourteen different recombinant Vaccinia virus strains were tested in two different murine tumor cell lines and corresponding immunocompetent animal models. We found, that Copenhagen backbone Vaccinia viruses while being extremely effective in cell culture, do not show significant oncolytic efficacy in animals. In contrast, several of the LIVP backbone viruses tested (specifically, IL-2 expressing ones) have little replication ability when compared to the Copenhagen strain, but are able to significantly delay tumor growth and prolong survival of the treated animals. We have also noted cytokine related toxicity of the animals to be mouse strain specific.
We have also tested the virus with the highest therapeutic benefit in combination with romidepsin and cyclophosphamide. While the combination with histone deacetylase inhibitor romidepsin did not result in therapeutic benefit in our settings, the addition of cyclophosphamide significantly improved the efficacy of the treatment, at the same time reducing cytokine-associated toxicity of the IL-2 expressing virus.
In the second part of the work, we analyzed the ability of adipose-derived mesenchymal stem cells to serve as a carrier for the oncolytic Vaccinia virus. We showed for the first time that the cells can be infected with the virus and can generate virus progeny. They are also able to survive for a substantially long time and, when injected into the bloodstream of tumor-bearing animals, produce the virus that is colonizing the tumor. Analysis of the systemic distribution of the cells after injection revealed that infected and uninfected cells are not distributed in the same manner, possibly suggesting that infected cells are getting recognized and cleared by an impaired immune system of athymic mice faster than non-infected cells. Despite this, injection of virus-loaded adipose-derived mesenchymal stem cells to human A549 tumor-bearing xenograft mice resulted in rapid tumor regression and reduced virus-related side effects of the treatment when compared to injection of the naked virus.
In conclusion, we have tested two different approaches to augmenting oncolytic Vaccinia virus therapy. First, the combination of recombinant Vaccinia virus expressing IL-2 and cyclophosphamide showed promising results in a syngeneic mouse model, despite the low permissivity of murine cells to the virus. Second, we loaded the oncolytic Vaccinia virus into mesenchymal stem cells and have proven that they can potentially serve as a vehicle for the virus.
Biodiversity loss, as often found in intensively managed agricultural landscapes, correlates with reduced ecosystem functioning, for example, pollination by insects, and with altered plant composition, diversity, and abundance. But how does this change in floral resource diversity and composition relate to occurrence and resource use patterns of trap-nesting solitary bees? To better understand the impact of land-use intensification on communities of trap-nesting solitary bees in managed grasslands, we investigated their pollen foraging, reproductive fitness, and the nutritional quality of larval food along a land-use intensity gradient in Germany. We found bee species diversity to decrease with increasing land-use intensity irrespective of region-specific community compositions and interaction networks. Land use also strongly affected the diversity and composition of pollen collected by bees. Lack of suitable pollen sources likely explains the absence of several bee species at sites of high land-use intensity. The only species present throughout, Osmia bicornis (red mason bee), foraged on largely different pollen sources across sites. In doing so, it maintained a relatively stable, albeit variable nutritional quality of larval diets (i.e., protein to lipid (P:L) ratio). The observed changes in bee–plant pollen interaction patterns indicate that only the flexible generalists, such as O. bicornis, may be able to compensate the strong alterations in floral resource landscapes and to obtain food of sufficient quality through readily shifting to alternative plant sources. In contrast, other, less flexible, bee species disappear.
Contact to nature and greenspace is important for emotional well-being and can promote human health. Forest landscapes provide such access to greenspace, especially in protected areas. However, forested protected areas are impacted by natural disturbances such as bark beetle infestations. On the one hand, such disturbances have positive impacts on ecological processes and biodiversity. On the other hand, they have allegedly negative impacts on the recreational value of a landscape. Limited knowledge about the public’s perception of forests subject to natural disturbances still hampers forest management to balance ecological functions and visitors’ recreational experience. Thus, our aim was to determine how attitudes towards nature influence the personal well-being in a naturally disturbed landscape. We investigated self-reported well-being and attitudes towards nature in a standardized questionnaire-based survey of 1008 German inhabitants in an experimentally adapted landscape visualization. Self-reported well-being was generally highest in landscapes with relatively few bark-beetle-killed trees. This was especially the case for people who felt included with nature and preferred an appreciative use or preservation of nature. Conversely, people who had previously visited a national park with visible bark beetle infestations rated their personal well-being highest in landscapes with larger proportions of beetle-killed trees. Our results indicate that it is necessary to analyze people’s knowledge about and relations to forest landscapes as well as concepts of nature conservation, natural landscapes, and biodiversity to gain a better understanding of people’s perceptions of natural disturbances.
Honeybees (Apis mellifera) need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses. In vivo experiments have demonstrated collective responses of the whole Gr-set. We here disentangle the contributions of all three honeybee sugar receptors (AmGr1-3), combining CRISPR/Cas9 mediated genetic knock-out, electrophysiology and behaviour. We show an expanded sugar spectrum of the AmGr1 receptor. Mutants lacking AmGr1 have a reduced response to sucrose and glucose but not to fructose. AmGr2 solely acts as co-receptor of AmGr1 but not of AmGr3, as we show by electrophysiology and using bimolecular fluorescence complementation. Our results show for the first time that AmGr2 is indeed a functional receptor on its own. Intriguingly, AmGr2 mutants still display a wildtype-like sugar taste. AmGr3 is a specific fructose receptor and is not modulated by a co-receptor. Eliminating AmGr3 while preserving AmGr1 and AmGr2 abolishes the perception of fructose but not of sucrose. Our comprehensive study on the functions of AmGr1, AmGr2 and AmGr3 in honeybees is the first to combine investigations on sugar perception at the receptor level and simultaneously in vivo. We show that honeybees rely on two gustatory receptors to sense all relevant sugars.
Introduction
Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release.
Methods
We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system.
Results and discussion
Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13\(^{GFSTF}\) 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13\(^{GFSTF}\), Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13\(^{GFSTF}\) subclusters that move toward the AZ center during PHP with unaltered Unc-13\(^{GFSTF}\) protein levels.
An epidemic of avian type H7N9 influenza virus, which took place in China in 2013, was enhanced by a naturally occurring R294K mutation resistant against Oseltamivir at the catalytic site of the neuraminidase. To cope with such drug-resistant neuraminidase mutations, we applied the molecular docking technique to evaluate the fitness of the available drugs such as Oseltamivir, Zanamivir, Peramivir, Laninamivir, L-Arginine and Benserazide hydrochloride concerning the N9 enzyme with single (R294K, R119K, R372K), double (R119_294K, R119_372K, R294_372K) and triple (R119_294_372K) mutations in the pocket. We found that the drugs Peramivir and Zanamivir score best amongst the studied compounds, demonstrating their high binding potential towards the pockets with the considered mutations. Despite the fact that mutations changed the shape of the pocket and reduced the binding strength for all drugs, Peramivir was the only drug that formed interactions with the key residues at positions 119, 294 and 372 in the pocket of the triple N9 mutant, while Zanamivir demonstrated the lowest RMSD value (0.7 Å) with respect to the reference structure.
Robotic-assisted colon surgery may contain advantages over the laparoscopic approach, but clear evidence is sparse. This study aimed to analyze postoperative inflammation status, short-term outcome and cost-effectiveness of robotic-assisted versus laparoscopic left hemicolectomy. All consecutive patients who received minimal-invasive left hemicolectomy at the Department of Surgery I at the University Hospital of Wuerzburg in 2021 were prospectively included. Importantly, no patient selection for either procedure was carried out. The robotic-assisted versus laparoscopic approaches were compared head to head for postoperative short-term outcomes as well as cost-effectiveness. A total of 61 patients were included, with 26 patients having received a robotic-assisted approach. Baseline characteristics did not differ among the groups. Patients receiving a robotic-assisted approach had a significantly decreased length of hospital stay as well as lower rates of complications in comparison to patients who received laparoscopic surgery (n = 35). In addition, C-reactive protein as a marker of systemic stress response was significantly reduced postoperatively in patients who were operated on in a robotic-assisted manner. Consequently, robotic-assisted surgery could be performed in a cost-effective manner. Thus, robotic-assisted left hemicolectomy represents a safe and cost-effective procedure and might improve patient outcomes in comparison to laparoscopic surgery.
Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design.
In recent decades, our planet has undergone dramatic environmental changes resulting in the loss of numerous species. This contrasts with species that can adapt quickly to rapidly changing ambient conditions, which require physiological plasticity and must occur rapidly. The Western honeybee (Apis mellifera) apparently meets this challenge with remarkable success, as this species is adapted to numerous climates, resulting in an almost worldwide distribution. Here, coordinated individual thermoregulatory activities ensure survival at the colony level and thus the transmission of genetic material. Recently, we showed that shivering thermogenesis, which is critical for honeybee thermoregulation, depends on octopamine signaling. In this study, we tested the hypothesis that the thoracic neuro-muscular octopaminergic system strives for a steady-state equilibrium under cold stress to maintain endogenous thermogenesis. We can show that this applies for both, octopamine provision by flight muscle innervating neurons and octopamine receptor expression in the flight muscles. Additionally, we discovered alternative splicing for AmOARβ2. At least the expression of one isoform is needed to survive cold stress conditions. We assume that the thoracic neuro-muscular octopaminergic system is finely tuned in order to contribute decisively to survival in a changing environment.