Intercellular interactions play a central role at the tissue and whole organism level modulating key cellular functions in normal and disease states. Studies of cell-cell communications are challenging due to ensemble averaging effects brought about by intrinsic heterogeneity in cellular function which requires such studies to be conducted with small populations of cells. Most of the current methods for producing and studying such small cell populations are complex to implement and require skilled personnel limiting their widespread utility in biomedical research labs. We present a simple and rapid method to produce small populations with varying size of epithelial cells (10–50 cells/population) with high-throughput (~1 population/second) on flat surfaces via patterning of extracellular matrix (ECM) proteins and random seeding of cells. We demonstrate that despite inherent limitations of non-contact, drop-on-demand piezoelectric inkjet printing for protein patterning, varying mixtures of ECM proteins can be deposited with high reproducibility and level of control on glass substrates using a set of dynamically adjustable optimized deposition parameters. We demonstrate high consistency for the number of cells per population (~1 cell standard error of mean), the population’s size (~0.2 coefficient of variation) and shape, as well as accurate spatial placement of and distance between colonies of a panel of metaplastic and dysplastic esophageal epithelial cells with differing adhesion and motility characteristics. The number of cells per colony, colony size and shape can be varied by dynamically varying the amount of ECM proteins deposited per spatial location and the number of spatial locations on the substrate. The method is applicable to a broad range of biological and biomedical studies including cell-cell communications, cellular microenvironment, migration, and stimulus response.

Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method (mTBM). This method allows to precisely measure local surface deformation of brain structures in infants. Here, we investigated ventricular abnormalities and their spatial relationships with surrounding subcortical structures in preterm neonates. We performed regional group comparisons on the surface morphometry and relative position of the lateral ventricles between 19 full-term and 17 preterm born neonates at term-equivalent age. Furthermore, a relative pose analysis was used to detect individual differences in translation, rotation, and scale of a given brain structure with respect to an average. Our mTBM results revealed broad areas of alterations on the frontal horn and body of the left ventricle, and narrower areas of differences on the temporal horn of the right ventricle. A significant shift in the rotation of the left ventricle was also found in preterm neonates. Furthermore, we located significant correlations between morphology and pose parameters of the lateral ventricles and that of the putamen and thalamus. These results show that regional abnormalities on the surface and pose of the ventricles are also associated with alterations on the putamen and thalamus. The complementarity of the information provided by the surface and pose analysis may help to identify abnormal white and grey matter growth, hinting toward a pattern of neural and cellular dysmaturation.

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection.

The Mars rover Spirit encountered outcrops and regolith composed of opaline silica (amorphous SiO₂·nH₂O) in an ancient volcanic hydrothermal setting in Gusev crater. An origin via either fumarole-related acid-sulfate leaching or precipitation from hot spring fluids was suggested previously. However, the potential significance of the characteristic nodular and mm-scale digitate opaline silica structures was not recognized. Here we report remarkably similar features within active hot spring/geyser discharge channels at El Tatio in northern Chile, where halite-encrusted silica yields infrared spectra that are the best match yet to spectra from Spirit. Furthermore, we show that the nodular and digitate silica structures at El Tatio that most closely resemble those on Mars include complex sedimentary structures produced by a combination of biotic and abiotic processes. Although fully abiotic processes are not ruled out for the Martian silica structures, they satisfy an a priori definition of potential biosignatures.

In several group-living species, individuals' social preferences are thought to be influenced by cooperation. For some societies with fission–fusion dynamics, sex-specific association patterns reflect sex differences in cooperation in within- and between-group contexts. In our study, we investigated this hypothesis further by comparing sex-specific association patterns in two closely related species, chimpanzees and bonobos, which differ in the level of between-group competition and in the degree to which sex and kinship influence dyadic cooperation. Here, we used long-term party composition data collected on five chimpanzee and two bonobo communities and assessed, for each individual of 10 years and older, the sex of its top associate and of all conspecifics with whom it associated more frequently than expected by chance. We found clear species differences in association patterns. While in all chimpanzee communities males and females associated more with same-sex partners, in bonobos males and females tended to associate preferentially with females, but the female association preference for other females is lower than in chimpanzees. Our results also show that, for bonobos (but not for chimpanzees), association patterns were predominantly driven by mother–offspring relationships. These species differences in association patterns reflect the high levels of male–male cooperation in chimpanzees and of mother–son cooperation in bonobos. Finally, female chimpanzees showed intense association with a few other females, and male chimpanzees showed more uniform association across males. In bonobos, the most differentiated associations were from males towards females. Chimpanzee male association patterns mirror fundamental human male social traits and, as in humans, may have evolved as a response to strong between-group competition. The lack of such a pattern in a closely related species with a lower degree of between-group competition further supports this notion.

With the advent of metagenomics approaches, a large diversity of known and unknown viruses has been identified in various types of environmental, plant, and animal samples. One such widespread virus group is the recently established family Genomoviridae which includes viruses with small (∼2–2.4 kb), circular ssDNA genomes encoding rolling-circle replication initiation proteins (Rep) and unique capsid proteins. Here, we propose a sequence-based taxonomic framework for classification of 121 new virus genomes within this family. Genomoviruses display ∼47% sequence diversity, which is very similar to that within the well-established and extensively studied family Geminiviridae (46% diversity). Based on our analysis, we establish a 78% genome-wide pairwise identity as a species demarcation threshold. Furthermore, using a Rep sequence phylogeny-based analysis coupled with the current knowledge on the classification of geminiviruses, we establish nine genera within the Genomoviridae family. These are Gemycircularvirus (n = 73), Gemyduguivirus (n = 1), Gemygorvirus (n = 9), Gemykibivirus (n = 29), Gemykolovirus (n = 3), Gemykrogvirus (n = 3), Gemykroznavirus (n = 1), Gemytondvirus (n = 1), Gemyvongvirus (n = 1). The presented taxonomic framework offers rational classification of genomoviruses based on the sequence information alone and sets an example for future classification of other groups of uncultured viruses discovered using metagenomics approaches.

Whole genome sequencing (WGS) is a promising strategy to unravel variants or genes responsible for human diseases and traits. However, there is a lack of robust platforms for a comprehensive downstream analysis. In the present study, we first proposed three novel algorithms, sequence gap-filled gene feature annotation, bit-block encoded genotypes and sectional fast access to text lines to address three fundamental problems. The three algorithms then formed the infrastructure of a robust parallel computing framework, KGGSeq, for integrating downstream analysis functions for whole genome sequencing data. KGGSeq has been equipped with a comprehensive set of analysis functions for quality control, filtration, annotation, pathogenic prediction and statistical tests. In the tests with whole genome sequencing data from 1000 Genomes Project, KGGSeq annotated several thousand more reliable non-synonymous variants than other widely used tools (e.g. ANNOVAR and SNPEff). It took only around half an hour on a small server with 10 CPUs to access genotypes of ∼60 million variants of 2504 subjects, while a popular alternative tool required around one day. KGGSeq's bit-block genotype format used 1.5% or less space to flexibly represent phased or unphased genotypes with multiple alleles and achieved a speed of over 1000 times faster to calculate genotypic correlation.

Rubisco enzymes play central roles in carbon fixation, with potential importance in biotechnology, but have eluded a full description of their multistep assembly and function. A new article describes the fascinating discovery that some archaeal Rubiscos contain a built-in assembly domain inserted into an otherwise canonical Rubisco fold, providing a tremendous expansion of our understanding of the diversity of naturally occurring Rubiscos.

Locating sources of diffusion and spreading from minimum data is a significant problem in network science with great applied values to the society. However, a general theoretical framework dealing with optimal source localization is lacking. Combining the controllability theory for complex networks and compressive sensing, we develop a framework with high efficiency and robustness for optimal source localization in arbitrary weighted networks with arbitrary distribution of sources. We offer a minimum output analysis to quantify the source locatability through a minimal number of messenger nodes that produce sufficient measurement for fully locating the sources. When the minimum messenger nodes are discerned, the problem of optimal source localization becomes one of sparse signal reconstruction, which can be solved using compressive sensing. Application of our framework to model and empirical networks demonstrates that sources in homogeneous and denser networks are more readily to be located. A surprising finding is that, for a connected undirected network with random link weights and weak noise, a single messenger node is sufficient for locating any number of sources. The framework deepens our understanding of the network source localization problem and offers efficient tools with broad applications.

Serotonin (also known as 5-hydroxytryptamine [5-HT]) is a small-molecule neurotransmitter that was identified in a series of studies conducted between 1935 and 1953 because of its capacity to induce contractions in the intestine and blood vessels. A plethora of functions for the serotonin system have been described, including regulation of mood, blood clotting, gut motility, systemic energy homeostasis, and tissue repair. Serotonin is synthesized from the essential amino acid tryptophan via tryptophan hydroxylase (TPH) in the brain and enterochromaffin cells of the gastrointestinal tract.