Cues and regulatory pathways involved in natural competence and transformation in pathogenic and environmental Gram-negative bacteria

Bacterial genomics is flourishing, as whole-genome sequencing has become affordable, readily available and rapid. As a result, it has become clear how frequently horizontal gene transfer (HGT) occurs in bacteria. The potential implications are highly significant because HGT contributes to several processes, including the spread of antibiotic-resistance cassettes, the distribution of toxin-encoding phages and the transfer of pathogenicity islands. Three modes of HGT are recognized in bacteria: conjugation, transduction and natural transformation. In contrast to the first two mechanisms, natural competence for transformation does not rely on mobile genetic elements but is driven solely by a developmental programme in the acceptor bacterium. Once the bacterium becomes competent, it is able to take up DNA from the environment and to incorporate the newly acquired DNA into its own chromosome. The initiation and duration of competence differ significantly among bacteria. In this review, we outline the latest data on representative naturally transformable Gram-negative bacteria and how their competence windows differ. We also summarize how environmental cues contribute to the initiation of competence in a subset of naturally transformable Gram-negative bacteria and how the complexity of the niche might dictate the fine-tuning of the competence windo

Crop conditional Convolutional Neural Networks for massive multi-crop plant disease classification over cell phone acquired images taken on real field conditions

Convolutional Neural Networks (CNN) have demonstrated their capabilities on the agronomical field, especially for plant visual symptoms assessment. As these models grow both in the number of training images and in the number of supported crops and diseases, there exist the dichotomy of (1) generating smaller models for specific crop or, (2) to generate a unique multi-crop model in a much more complex task (especially at early disease stages) but with the benefit of the entire multiple crop image dataset variability to enrich image feature description learning. In this work we first introduce a challenging dataset of more than one hundred-thousand images taken by cell phone in real field wild conditions. This dataset contains almost equally distributed disease stages of seventeen diseases and five crops (wheat, barley, corn, rice and rape-seed) where several diseases can be present on the same picture. When applying existing state of the art deep neural network methods to validate the two hypothesised approaches, we obtained a balanced accuracy (BAC=0.92) when generating the smaller crop specific models and a balanced accuracy (BAC=0.93) when generating a single multi-crop model. In this work, we propose three different CNN architectures that incorporate contextual non-image meta-data such as crop information onto an image based Convolutional Neural Network. This combines the advantages of simultaneously learning from the entire multi-crop dataset while reducing the complexity of the disease classification tasks. The crop-conditional plant disease classification network that incorporates the contextual information by concatenation at the embedding vector level obtains a balanced accuracy of 0.98 improving all previous methods and removing 71% of the miss-classifications of the former methods

Corporate accelerators: design and startup performance

Corporate accelerators (CAs) have emerged as a key component of entrepreneurship ecosystems, offering startups corporate guidance, industry connections, and resources for accelerated venture creation. Although their proliferation is evident, we still know little about the value they produce for startups across different contexts. This study investigates the organizational setup and program design of 15 CAs in Germany using a unique and hand-collected dataset of 223 alumni startups. Our findings reveal a tradeoff: Specialized and integrated programs positively impact startups’ speed to market and growth, while specialization and rising corporate control may hinder follow-up venture capital financing. This research contributes to our understanding of CAs and the startup acceleration process and provides insights for corporate and accelerator managers and startups alike. Startups can use these findings to identify the most suitable CA for their needs. Program managers and designers gain insights into the strategic orientation and organizational setup that positively impact startup acceleration

Mechanistic aspects of DNA uptake in naturally competent Vibrio cholerae

The physiological state of competence for natural transformation allows bacteria to take up free DNA from the environment and recombine it into their genome. As one of three modes of horizontal gene transfer, natural transformation has hence contributed substantially to the enormous diversity and plasticity of bacterial genomes. With its potential to promote the spread of antibiotic resistances and virulence factors of a variety of pathogens, natural transformation also has an important impact on human health. Even though conserved components required to undergo natural transformation have been identified in many bacterial species, our knowledge on the underlying mechanism of DNA transport remains very limited. To better understand this aspect, we established a first model of DNA uptake in the naturally competent human pathogen Vibrio cholerae. We showed that at least twenty proteins are required for efficient uptake, protection and recombination of transforming DNA in a non-species-specific manner. 14 of these proteins are needed to produce a type IV pilus, which we were able to visualize for the first time. We showed that this competence pilus is not restricted to cell poles, as has been shown for other competent bacterial species (e.g. Bacillus subtilis). Furthermore, we compared the position of this pilus to the localization of other competence proteins and determined their role in the assembly of a surface exposed pilus fiber. While this type IV pilus is important for efficient DNA uptake, we also observed rare transformation events in its absence. In contrast, three pilus-unrelated proteins that are likely involved in the transport process were absolutely required for transformation. Two of them were implicated in DNA transport across the inner membrane. Deletion of the corresponding genes led to a strong accumulation of transforming DNA within the periplasm. However, one of them, ComEA, was essential for DNA uptake across the outer membrane, independently of competence pili. We further characterized the role of this protein by showing that it is localized to the periplasm of competent V. cholerae cells and that it binds to DNA in vivo. Based on our results, we proposed that ComEA directly contributes to DNA transport. Although we showed that DNA uptake across the outer membrane and translocation of DNA into the cytoplasm are functionally uncoupled, our results suggest that the two events coincide spatially. In summary, these findings allow us to present a first mechanistic model of the DNA uptake process in V. cholerae. Many aspects of this model likely apply to other naturally competent bacteria, and therefore represent an important contribution to the general understanding of this basic biological process

Cues and regulatory pathways involved in natural competence and transformation in pathogenic and environmental Gram-negative bacteria

Bacterial genomics is flourishing, as whole-genome sequencing has become affordable, readily available, and rapid. As a result, it has become clear how frequently horizontal gene transfer (HGT) occurs in bacteria. The potential implications are highly significant because HGT contributes to several processes, including the spread of antibiotic-resistance cassettes, the distribution of toxin-encoding phages, and the transfer of pathogenicity islands. Three modes of HGT are recognized in bacteria: conjugation, transduction and natural transformation. In contrast to the first two mechanisms, natural competence for transformation does not rely on mobile genetic elements but is driven solely by a developmental program in the acceptor bacterium. Once the bacterium becomes competent, it is able to take up DNA from the environment and to incorporate the newly acquired DNA into its own chromosome. The initiation and duration of competence differ significantly among bacteria. In this review, we outline the latest data on representative naturally transformable Gram-negative bacteria and how their competence windows differ. We also summarize how environmental cues contribute to the initiation of competence in a subset of naturally transformable Gram-negative bacteria and how the complexity of the niche might dictate the fine-tuning of the competence window

DNA Transport across the Outer and Inner Membranes of Naturally Transformable Vibrio cholerae Is Spatially but Not Temporally Coupled

The physiological state of natural competence for transformation allows certain bacteria to take up free DNA from the environment and to recombine such newly acquired DNA into their chromosomes. However, even though conserved components that are required to undergo natural transformation have been identified in several naturally competent bacteria, our knowledge of the underlying mechanisms of the DNA uptake process remains very limited. To better understand these mechanisms, we investigated the competence-mediated DNA transport in the naturally transformable pathogen Vibrio cholerae. Previously, we used a cell biology-based approach to experimentally address an existing hypothesis, which suggested the competence protein ComEA plays a role in the DNA uptake process across the outer membrane of Gram-negative bacteria. Here, we extended this knowledge by investigating the dynamics of DNA translocation across both membranes. More precisely, we indirectly visualized the transfer of the external DNA from outside the cell into the periplasm followed by the shuttling of the DNA into the cytoplasm. Based on these data, we conclude that for V. cholerae, the DNA translocation across the outer and inner membranes is spatially but not temporally coupled

Influence of stress on the degradation behavior of Mg LAE442 implant systems

In this paper the performance of a magnesium based implant system is analyzed. A special emphasis is placed on the impact of stress on the corrosion behavior of the magnesium alloy. An implant system containing a plate and 4 corresponding screws is machined from Mg LAE442. Its corrosion behavior is tested in-vivo in New Zealand White Rabbits for 6 and 12 weeks of implantation. The plate is monocortically fixated on the medial tibia. At the interface between screw and plate increased corrosion is observed. This phenomenon is stronger on the caudal side of the screw. Parallel to the in-vivo test the influence of stress load on the corrosion rate is analyzed for LAE442 in in-vitro tests. Compressive load is applied on cylindrical specimens in axial direction and the corrosion rate is measured in 0.9 wt% NaCl solution by eudiometry and mass loss. Additionally rectangular samples are bent to apply tensile stress on the surface. A drop of 5 wt% NaCl is deposited on the surface and the corrosion is evaluated by microscopic images. It is shown that stress essentially influences the corrosion rate. While tensile stress decreases the corrosion, compressive stress leads to higher corrosion rates

A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia

Background: The real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations. Methods: This was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up. Results: Data from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib [n = 27], nilotinib [n = 27], dasatinib [n = 8], or ponatinib [n = 1]). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1IS ≤ 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy. Conclusions: Although patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice. Keywords: Chronic myeloid leukemia; Deep molecular response; Real-world evidence; Tyrosine kinase inhibitors

Recommendations for the Transition to Open Access in Austria

Based on 16 recommendations, efforts should be made to achieve the following goal: By 2025, a large part of all scholarly publication activity in Austria should be Open Access. In other words, the final versions of most scholarly publications (in particular all refereed journal articles and conference proceedings) resulting from the support of public resources must be freely accessible on the Internet without delay (Gold Open Access). This goal should be pursued by taking into account the different disciplinary practices and under consideration of the different disciplinary priorisations of Open Access. The resources required to meet this obligation shall be provided to the authors, or the cost of the publication venues shall be borne directly by the research organisations. The necessary funding must be brought in line with the overall funding priorities for research