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Preprints have arrived. In increasing numbers, researchers across the life sciences are embracing the once-niche practice, shaking off decades of reluctance and posting hundreds of papers per week to preprint servers, sharing their findings with the community before embarking on the weary march through peer review. However, there are limited methods for individuals sifting through this avalanche of research to identify the preprints that are most relevant to their interests. Here, we describe , a website that indexes all preprints posted to , the largest preprint server in the life sciences, and allows users to filter and sort papers based on download metrics and Twitter activity over a variety of categories and time periods. In this work, we hope to make it easier for readers to find relevant research on bioRxiv and to improve the visibility of preprints currently being read and discussed online. [ABSTRACT FROM AUTHOR]

The thesis presented here is that biomedical research is based on the trusted exchange of services. That exchange would be conducted more efficiently if the trusted software platforms to exchange those services, if they exist, were more integrated. While simpler and narrower in scope than the services governing biomedical research, comparison to existing internet-based platforms, like Airbnb, can be informative. We illustrate how the analogy to internet-based platforms works and does not work and introduce The Commons, under active development at the National Institutes of Health (NIH) and elsewhere, as an example of the move towards platforms for research. [ABSTRACT FROM AUTHOR]

Infections with human herpesviruses are ubiquitous and a public health concern worldwide. Current treatments reduce the severity of some symptoms associated to herpetic infections but neither remove the viral reservoir from the infected host nor protect from the recurrent symptom outbreaks that characterise herpetic infections. The difficulty in therapeutically tackling these viral systems stems in part from their remarkably large proteomes and the complex networks of physical and functional associations that they tailor. This study presents our efforts to unravel the complexity of the interactome of herpes simplex virus type 1 (HSV1), the prototypical herpesvirus species. Inspired by our previous work, we present an improved and more integrative computational pipeline for the protein–protein interaction (PPI) network reconstruction in HSV1, together with a newly developed consensus clustering framework, which allowed us to extend the analysis beyond binary physical interactions and revealed a system-level layout of higher-order functional associations in the virion proteome. Additionally, the analysis provided new functional annotation for the currently undercharacterised protein in unique short region 10 (pUS10). In-depth bioinformatics sequence analysis unravelled structural features in pUS10 reminiscent of those observed in some capsid-associated proteins in tailed bacteriophages, with which herpesviruses are believed to share a common ancestry. Using immunoaffinity purification (IP)–mass spectrometry (MS), we obtained additional support for our bioinformatically predicted interaction between pUS10 and the inner tegument protein in unique long region 37 (pUL37), which binds cytosolic capsids, contributing to initial tegumentation and eventually virion maturation. In summary, this study unveils new, to our knowledge, insights at both the system and molecular levels that can help us better understand the complexity behind herpesvirus infections. [ABSTRACT FROM AUTHOR]

Biological processes in living cells are often carried out by gene networks in which signals and reactions are integrated through network hubs. Despite their functional importance, it remains unclear to what extent network hubs are evolvable and how alterations impact long-term evolution. We investigated these issues using heat shock protein 90 (Hsp90), a central hub of proteostasis networks. When native Hsp90 in Saccharomyces cerevisiae cells was replaced by the ortholog from hypersaline-tolerant Yarrowia lipolytica that diverged from S. cerevisiae about 270 million years ago, the cells exhibited improved growth in hypersaline environments but compromised growth in others, indicating functional divergence in Hsp90 between the two yeasts. Laboratory evolution shows that evolved Y. lipolytica-HSP90–carrying S. cerevisiae cells exhibit a wider range of phenotypic variation than cells carrying native Hsp90. Identified beneficial mutations are involved in multiple pathways and are often pleiotropic. Our results show that cells adapt to a heterologous Hsp90 by modifying different subnetworks, facilitating the evolution of phenotypic diversity inaccessible to wild-type cells. [ABSTRACT FROM AUTHOR]

A developing plant organ exhibits complex spatiotemporal patterns of growth, cell division, cell size, cell shape, and organ shape. Explaining these patterns presents a challenge because of their dynamics and cross-correlations, which can make it difficult to disentangle causes from effects. To address these problems, we used live imaging to determine the spatiotemporal patterns of leaf growth and division in different genetic and tissue contexts. In the simplifying background of the speechless (spch) mutant, which lacks stomatal lineages, the epidermal cell layer exhibits defined patterns of division, cell size, cell shape, and growth along the proximodistal and mediolateral axes. The patterns and correlations are distinctive from those observed in the connected subepidermal layer and also different from the epidermal layer of wild type. Through computational modelling we show that the results can be accounted for by a dual control model in which spatiotemporal control operates on both growth and cell division, with cross-connections between them. The interactions between resulting growth and division patterns lead to a dynamic distributions of cell sizes and shapes within a deforming leaf. By modulating parameters of the model, we illustrate how phenotypes with correlated changes in cell size, cell number, and organ size may be generated. The model thus provides an integrated view of growth and division that can act as a framework for further experimental study. [ABSTRACT FROM AUTHOR]

That a scientist might shape and cultivate a personal brand is a relatively new concept but one that is finding increasing acceptance in this new age of rapid communications and social media. A key driver is the abrupt rise in well-funded and organized antiscience movements, especially in North America and Europe, such that society now benefits from scientists with strong personal brands and public personas who are willing to engage general audiences. In this sense, branding itself can advance science, the sharing of information, and the promotion of science as a public good. Still another dimension to branding is that it affords an opportunity to mentor younger scientists and helps you to become an important role model for the next generation. There is also a practical side, as today, fewer scientists spend their entire career at a single institution, so owning a strong brand can sometimes create easier paths for transitions and mobility. However, brand cultivation ideally begins in collaboration with your institutional office of communications and is done in a way that is seen as a win for both you and your university or research institution. Described here are some steps to consider when embarking on brand cultivation and how to avoid some of the potential pitfalls. [ABSTRACT FROM AUTHOR]

The mammalian pancreas is a branched organ that does not exhibit stereotypic branching patterns, similarly to most other glands. Inside branches, it contains a network of ducts that undergo a transition from unconnected microlumen to a mesh of interconnected ducts and finally to a treelike structure. This ductal remodeling is poorly understood, both on a microscopic and macroscopic level. In this article, we quantify the network properties at different developmental stages. We find that the pancreatic network exhibits stereotypic traits at each stage and that the network properties change with time toward the most economical and optimized delivery of exocrine products into the duodenum. Using in silico modeling, we show how steps of pancreatic network development can be deconstructed into two simple rules likely to be conserved for many other glands. The early stage of the network is explained by noisy, redundant duct connection as new microlumens form. The later transition is attributed to pruning of the network based on the flux of fluid running through the pancreatic network into the duodenum. [ABSTRACT FROM AUTHOR]

Drosophila segmentation is a well-established paradigm for developmental pattern formation. However, the later stages of segment patterning, regulated by the “pair-rule” genes, are still not well understood at the system level. Building on established genetic interactions, I construct a logical model of the Drosophila pair-rule system that takes into account the demonstrated stage-specific architecture of the pair-rule gene network. Simulation of this model can accurately recapitulate the observed spatiotemporal expression of the pair-rule genes, but only when the system is provided with dynamic “gap” inputs. This result suggests that dynamic shifts of pair-rule stripes are essential for segment patterning in the trunk and provides a functional role for observed posterior-to-anterior gap domain shifts that occur during cellularisation. The model also suggests revised patterning mechanisms for the parasegment boundaries and explains the aetiology of the even-skipped null mutant phenotype. Strikingly, a slightly modified version of the model is able to pattern segments in either simultaneous or sequential modes, depending only on initial conditions. This suggests that fundamentally similar mechanisms may underlie segmentation in short-germ and long-germ arthropods. [ABSTRACT FROM AUTHOR]

Understanding the rat neurochemical connectome is fundamental for exploring neuronal information processing. By using advanced data mining, supervised machine learning, and network analysis, this study integrates over 5 decades of neuroanatomical investigations into a multiscale, multilayer neurochemical connectome of the rat brain. This neurochemical connectivity database (ChemNetDB) is supported by comprehensive systematically-determined receptor distribution maps. The rat connectome has an onion-type structural organization and shares a number of structural features with mesoscale connectomes of mouse and macaque. Furthermore, we demonstrate that extremal values of graph theoretical measures (e.g., degree and betweenness) are associated with evolutionary-conserved deep brain structures such as amygdala, bed nucleus of the stria terminalis, dorsal raphe, and lateral hypothalamus, which regulate primitive, yet fundamental functions, such as circadian rhythms, reward, aggression, anxiety, and fear. The ChemNetDB is a freely available resource for systems analysis of motor, sensory, emotional, and cognitive information processing. [ABSTRACT FROM AUTHOR]

Lymph nodes are meeting points for circulating immune cells. A network of reticular cells that ensheathe a mesh of collagen fibers crisscrosses the tissue in each lymph node. This reticular cell network distributes key molecules and provides a structure for immune cells to move around on. During infections, the network can suffer damage. A new study has now investigated the network’s structure in detail, using methods from graph theory. The study showed that the network is remarkably robust to damage: it can still support immune responses even when half of the reticular cells are destroyed. This is a further important example of how network connectivity achieves tolerance to failure, a property shared with other important biological and nonbiological networks. [ABSTRACT FROM AUTHOR]

The phosphotransferase system (PTS) plays a pivotal role in the uptake of multiple sugars in Escherichia coli and many other bacteria. In the cell, individual sugar-specific PTS branches are interconnected through a series of phosphotransfer reactions, thus creating a global network that not only phosphorylates incoming sugars but also regulates a number of cellular processes. Despite the apparent importance of the PTS network in bacterial physiology, the holistic function of the network in the cell remains unclear. Here we used Förster resonance energy transfer (FRET) to investigate the PTS network in E. coli, including the dynamics of protein interactions and the processing of different stimuli and their transmission to the chemotaxis pathway. Our results demonstrate that despite the seeming complexity of the cellular PTS network, its core part operates in a strikingly simple way, sensing the overall influx of PTS sugars irrespective of the sugar identity and distributing this information equally through all studied branches of the network. Moreover, it also integrates several other specific metabolic inputs. The integrated output of the PTS network is then transmitted linearly to the chemotaxis pathway, in stark contrast to the amplification of conventional chemotactic stimuli. Finally, we observe that default uptake through the uninduced PTS network correlates well with the quality of the carbon source, apparently representing an optimal regulatory strategy. [ABSTRACT FROM AUTHOR]

Mammals show a wide range of brain sizes, reflecting adaptation to diverse habitats. Comparing interareal cortical networks across brains of different sizes and mammalian orders provides robust information on evolutionarily preserved features and species-specific processing modalities. However, these networks are spatially embedded, directed, and weighted, making comparisons challenging. Using tract tracing data from macaque and mouse, we show the existence of a general organizational principle based on an exponential distance rule (EDR) and cortical geometry, enabling network comparisons within the same model framework. These comparisons reveal the existence of network invariants between mouse and macaque, exemplified in graph motif profiles and connection similarity indices, but also significant differences, such as fractionally smaller and much weaker long-distance connections in the macaque than in mouse. The latter lends credence to the prediction that long-distance cortico-cortical connections could be very weak in the much-expanded human cortex, implying an increased susceptibility to disconnection syndromes such as Alzheimer disease and schizophrenia. Finally, our data from tracer experiments involving only gray matter connections in the primary visual areas of both species show that an EDR holds at local scales as well (within 1.5 mm), supporting the hypothesis that it is a universally valid property across all scales and, possibly, across the mammalian class. [ABSTRACT FROM AUTHOR]

Fibroblastic reticular cells (FRCs) form the cellular scaffold of lymph nodes (LNs) and establish distinct microenvironmental niches to provide key molecules that drive innate and adaptive immune responses and control immune regulatory processes. Here, we have used a graph theory-based systems biology approach to determine topological properties and robustness of the LN FRC network in mice. We found that the FRC network exhibits an imprinted small-world topology that is fully regenerated within 4 wk after complete FRC ablation. Moreover, in silico perturbation analysis and in vivo validation revealed that LNs can tolerate a loss of approximately 50% of their FRCs without substantial impairment of immune cell recruitment, intranodal T cell migration, and dendritic cell-mediated activation of antiviral CD8+ T cells. Overall, our study reveals the high topological robustness of the FRC network and the critical role of the network integrity for the activation of adaptive immune responses. [ABSTRACT FROM AUTHOR]

One of the most fundamental features of the human brain is its ability to detect and attend to salient goal-relevant events in a flexible manner. The salience network (SN), anchored in the anterior insula and the dorsal anterior cingulate cortex, plays a crucial role in this process through rapid detection of goal-relevant events and facilitation of access to appropriate cognitive resources. Here, we leverage the subsecond resolution of large multisession fMRI datasets from the Human Connectome Project and apply novel graph-theoretical techniques to investigate the dynamic spatiotemporal organization of the SN. We show that the large-scale brain dynamics of the SN are characterized by several distinctive and robust properties. First, the SN demonstrated the highest levels of flexibility in time-varying connectivity with other brain networks, including the frontoparietal network (FPN), the cingulate–opercular network (CON), and the ventral and dorsal attention networks (VAN and DAN). Second, dynamic functional interactions of the SN were among the most spatially varied in the brain. Third, SN nodes maintained a consistently high level of network centrality over time, indicating that this network is a hub for facilitating flexible cross-network interactions. Fourth, time-varying connectivity profiles of the SN were distinct from all other prefrontal control systems. Fifth, temporal flexibility of the SN uniquely predicted individual differences in cognitive flexibility. Importantly, each of these results was also observed in a second retest dataset, demonstrating the robustness of our findings. Our study provides fundamental new insights into the distinct dynamic functional architecture of the SN and demonstrates how this network is uniquely positioned to facilitate interactions with multiple functional systems and thereby support a wide range of cognitive processes in the human brain. [ABSTRACT FROM AUTHOR]

Crowdfunding represents an attractive new option for funding research projects, especially for students and early-career scientists or in the absence of governmental aid in some countries. The number of successful science-related crowdfunding campaigns is growing, which demonstrates the public’s willingness to support and participate in scientific projects. Putting together a crowdfunding campaign is not trivial, however, so here is a guide to help you make yours a success. [ABSTRACT FROM AUTHOR]

: This transcranial stimulation study shows that selective modulation of synchronized neuronal activity between the hemispheres of the brain can affect conscious perception. [ABSTRACT FROM AUTHOR]

: Accelerated evolution of the human brain and muscle metabolomes reflects our unique cognitive and physical capacities. [ABSTRACT FROM AUTHOR]

: Network modeling of interactions between proteases and their inhibitors reveals a network of new protein connections and cascades in the protease web. [ABSTRACT FROM AUTHOR]