Early fate of exogenous promoters in E. coli

Gene gain by horizontal gene transfer is a major pathway of genome innovation in bacteria. The current view posits that acquired genes initially need to be silenced and that a bacterial chromatin protein, H-NS, plays a role in this silencing. However, we lack direct observation of the early fate of a horizontally transferred gene to prove this theory. We combine sequencing, flow cytometry and sorting, followed by microscopy to monitor gene expression and its variability after large-scale random insertions of a reporter gene in a population of Escherichia coli bacteria. We find that inserted promoters have a wide range of gene-expression variability related to their location. We find that high-expression clones carry insertions that are not correlated with H-NS binding. Conversely, binding of H-NS correlates with silencing. Finally, while most promoters show a common level of extrinsic noise, some insertions show higher noise levels. Analysis of these high-noise clones supports a scenario of switching due to transcriptional interference from divergent ribosomal promoters. Altogether, our findings point to evolutionary pathways where newly-acquired genes are not necessarily silenced, but may immediately explore a wide range of expression levels to probe the optimal ones

Threshold accumulation of a constitutive protein explains E. coli cell-division behavior in nutrient upshifts

Despite a boost of recent progress in dynamic single-cell measurements and analyses in Escherichia coli, we still lack a mechanistic understanding of the determinants of the decision to divide. Specifically, the debate is open regarding the processes linking growth and chromosome replication to division and on the molecular origin of the observed “adder correlations,” whereby cells divide, adding roughly a constant volume independent of their initial volume. In order to gain insight into these questions, we interrogate dynamic size-growth behavior of single cells across nutrient upshifts with a high-precision microfluidic device. We find that the division rate changes quickly after nutrients change, much before growth rate goes to a steady state, and in a way that adder correlations are robustly conserved. Comparison of these data to simple mathematical models falsifies proposed mechanisms, where replication-segregation or septum completions are the limiting step for cell division. Instead, we show that the accumulation of a putative constitutively expressed “P-sector divisor” protein explains the behavior during the shift

Timp3 deficiency affects the progression of DEN-related hepatocellular carcinoma during diet-induced obesity in mice

Obesity and low-grade inflammation are associated with an increased risk of hepatocellular carcinoma (HCC), a leading cause of cancer-related death worldwide. The tissue inhibitor of metalloproteinase (TIMP) 3, an endogenous inhibitor of protease activity that represents a key mediator of inflammation, is reduced in inflammatory metabolic disorders and cancer. In contrast, Timp3-deficient mice (Timp3-/-) are highly resistant to developing HCC in response to a diethylnitrosamine (DEN); therefore, we aimed to elucidate the biological role of genetic loss of Timp3 in obesity-related hepatocarcinogenesis

Minimally invasive approach to incisional hernia in elective and emergency surgery: a SICE (Italian Society of Endoscopic Surgery and new technologies) and ISHAWS (Italian Society of Hernia and Abdominal Wall Surgery) online survey

Minimally invasive abdominal wall surgery is growing worldwide, with a constant and fast improvement of surgical techniques and surgeons’ confidence in treating both primary and incisional hernias (IH). The Italian Society of Endoscopic Surgery and new technologies (SICE) and the ISHAWS (Italian Society of Hernia and Abdominal Wall Surgery) worked together to investigate state of the art in IH treatment in elective and emergency settings in Italy. An online open survey was designed, and Italian surgeons interested in abdominal wall surgery were invited to fill out a 20-point questionnaire on IH surgical procedures performed in their departments. Surgeons were asked to express their points of view on specific questions about technical and clinical variables in IH treatment. Preferred approach in elective IH surgery was minimally invasive (59.7%). Open surgery was the preferred approach in 40.3% of the responses. In emergency settings, open surgery was the preferred approach (65.4%); however, 34.5% of the involved surgeons declare to prefer the laparoscopic/endoscopic approach. Most respondents opted for conversion to open surgery in case of relevant surgical field contamination, with a non-mesh repair of abdominal wall defects. Among those that used the laparoscopic approach in the emergent setting, the majority (74%) used the size of the defect of 5 cm as a decisional cut-off. The spread of minimally invasive approaches to IH repair in emergency surgery in Italy is gaining relevance. Code-sharing through scientific societies can improve clinical practice in different departments and promote a tailored approach to IH surgery