Epidemiological studies have reported conflicting results between folate intake and bladder cancer risk. We conducted a meta-analysis of epidemiological studies published between 1996 and June 2013 on the relationship between folate intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of risk estimates (REs) associated to the highest versus the lowest category of folate intake using random effect models. Seven cohort and six case-control studies were eligible for inclusion. A significantly decreased risk with bladder cancer was observed in overall folate intake group (RE = 0.84; 95% CI, 0.72-0.96) and subgroup of case-control studies (RE = 0.73; 95% CI, 0.57-0.89), but not in cohort studies (RE = 0.96; 95% CI, 0.81-1.10) when comparing the highest with the lowest category of folate intake. No heterogeneity and publication bias were observed across studies. Although the current evidence, mainly based on data from case-control studies, supports an inverse association between folate intake and bladder cancer, additional large and well-designed cohort studies are needed before definitive conclusions can be drawn.

Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer of gene regulation to tissue homeostasis in adult animals remains unclear. Gain and loss of function experiments have provided key insights into the specific function of individual miRNAs, but effective genetic tools to study the functional consequences of global inhibition of miRNA activity in vivo are lacking. Here we report the generation and characterization of a genetically engineered mouse strain in which miRNA-mediated gene repression can be reversibly inhibited without affecting miRNA biogenesis or abundance. We demonstrate the usefulness of this strategy by investigating the consequences of acute inhibition of miRNA function in adult animals. We find that different tissues and organs respond differently to global loss of miRNA function. While miRNA-mediated gene repression is essential for the homeostasis of the heart and the skeletal muscle, it is largely dispensable in the majority of other organs. Even in tissues where it is not required for homeostasis, such as the intestine and hematopoietic system, miRNA activity can become essential during regeneration following acute injury. These data support a model where many metazoan tissues primarily rely on miRNA function to respond to potentially pathogenic events.

Genetic manipulation is a powerful tool to establish the causal relationship between a genetic lesion and a particular pathological phenotype. The rise of CRISPR/Cas9 genome-engineering tools overcame the traditional technical bottleneck for routine site-specific genetic manipulation in cells. To create the perfect in vitro cell model, there is significant interest from the stem cell research community to adopt this fast evolving technology. This review addresses this need directly by providing both the up-to-date biochemical rationale of CRISPR-mediated genome engineering and detailed practical guidelines for the design and execution of CRISPR experiments in cell models. Ultimately, this review will serve as a timely and comprehensive guide for this fast developing technology.

Evaluating the relationship between the human gut microbiome and disease requires computing reliable statistical associations. Here, using millions of different association modeling strategies, we evaluated the consistency—or robustness—of microbiome-based disease indicators for 6 prevalent and well-studied phenotypes (across 15 public cohorts and 2,343 individuals). We were able to discriminate between analytically robust versus nonrobust results. In many cases, different models yielded contradictory associations for the same taxon–disease pairing, some showing positive correlations and others negative. When querying a subset of 581 microbe–disease associations that have been previously reported in the literature, 1 out of 3 taxa demonstrated substantial inconsistency in association sign. Notably, >90% of published findings for type 1 diabetes (T1D) and type 2 diabetes (T2D) were particularly nonrobust in this regard. We additionally quantified how potential confounders—sequencing depth, glucose levels, cholesterol, and body mass index, for example—influenced associations, analyzing how these variables affect the ostensible correlation between Faecalibacterium prausnitzii abundance and a healthy gut. Overall, we propose our approach as a method to maximize confidence when prioritizing findings that emerge from microbiome association studies.

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