As an injury heals, an embryo develops, or a carcinoma spreads, epithelial cells systematically change their shape. In each of these processes cell shape is studied extensively whereas variability of shape from cell-to-cell is regarded most often as biological noise. But where do cell shape and its variability come from? Here we report that cell shape and shape variability are mutually constrained through a relationship that is purely geometrical. That relationship is shown to govern processes as diverse as maturation of the pseudostratified bronchial epithelial layer cultured from non-asthmatic or asthmatic donors, and formation of the ventral furrow in the Drosophila embryo. Across these and other epithelial systems, shape variability collapses to a family of distributions that is common to all. That distribution, in turn, is accounted for by a mechanistic theory of cell-cell interaction showing that cell shape becomes progressively less elongated and less variable as the layer becomes progressively more jammed. These findings suggest a connection between jamming and geometry that spans living organisms and inert jammed systems, and thus transcends system details. Although molecular events are needed for any complete theory of cell shape and cell packing, observations point to the hypothesis that jamming behavior at larger scales of organization sets overriding geometrical constraints.

Despite increasing knowledge on phylogenetic composition of the human microbiome, our understanding of the in situ activities of the organisms in the community and their interactions with each other and with the environment remains limited. Characterizing gene expression profiles of the human microbiome is essential for linking the role of different members of the bacterial communities in health and disease. The oral microbiome is one of the most complex microbial communities in the human body and under certain circumstances, not completely understood, the healthy microbial community undergoes a transformation toward a pathogenic state that gives rise to periodontitis, a polymicrobial inflammatory disease. We report here the in situ genome-wide transcriptome of the subgingival microbiome in six periodontally healthy individuals and seven individuals with periodontitis. The overall picture of metabolic activities showed that iron acquisition, lipopolysaccharide synthesis and flagellar synthesis were major activities defining disease. Unexpectedly, the vast majority of virulence factors upregulated in subjects with periodontitis came from organisms that are not considered major periodontal pathogens. One of the organisms whose gene expression profile was characterized was the uncultured candidate division TM7, showing an upregulation of putative virulence factors in the diseased community. These data enhance understanding of the core activities that are characteristic of periodontal disease as well as the role that individual organisms in the subgingival community play in periodontitis.

Introductory paragraph Evidence suggests that testicular germ cell tumors (TGCT) have a strong underlying genetic component. We performed a genome-wide scan among 277 TGCT cases and 919 controls. Seven markers at 12p22 within c-KIT ligand (KITLG) reached genome-wide significance (P < 5.0 × 10−8). In independent replication, TGCT risk was increased 3-fold per copy of the major allele at rs3782179 and rs4474514 (OR=3.08, 95% CI 2.29, 4.13; OR=3.07, 95% CI 2.29, 4.13, respectively). We also replicated associations with rs4324715 and rs6897876 at 5q31.3 near sprouty 4 (SPRY4; P < 5.0 × 10−6 in discovery). Risk of TGCT was increased nearly 40% per copy of the major allele (OR=1.37, 95% CI 1.14, 1.64; OR=1.39, 95% CI 1.16, 1.66, respectively). All of the genotypes were associated with both seminoma and non-seminoma TGCT subtypes. These results demonstrate that common genetic variants affect TGCT risk and implicate KITLG and SPRY4 as TGCT susceptibility genes.