A comparison of humans and baboons suggests germline mutation rates do not track cell divisions.

In humans, most germline mutations are inherited from the father. This observation has been widely interpreted as reflecting the replication errors that accrue during spermatogenesis. If so, the male bias in mutation should be substantially lower in a closely related species with similar rates of spermatogonial stem cell divisions but a shorter mean age of reproduction. To test this hypothesis, we resequenced two 3-4 generation nuclear families (totaling 29 individuals) of olive baboons (Papio anubis), who reproduce at approximately 10 years of age on average, and analyzed the data in parallel with three 3-generation human pedigrees (26 individuals). We estimated a mutation rate per generation in baboons of 0.57×10-8 per base pair, approximately half that of humans. Strikingly, however, the degree of male bias in germline mutations is approximately 4:1, similar to that of humans-indeed, a similar male bias is seen across mammals that reproduce months, years, or decades after birth. These results mirror the finding in humans that the male mutation bias is stable with parental ages and cast further doubt on the assumption that germline mutations track cell divisions. Our mutation rate estimates for baboons raise a further puzzle, suggesting a divergence time between apes and Old World monkeys of 65 million years, too old to be consistent with the fossil record; reconciling them now requires not only a slowdown of the mutation rate per generation in humans but also in baboons.

Ultrasonography-guided arthrocentesis versus conventional arthrocentesis in treating internal derangement of temporomandibular joint: a systematic review.

OBJECTIVES: This systematic review assessed the clinical question: 'Does ultrasonography (USG)-guided arthrocentesis provide better outcomes than conventional arthrocentesis in patients with temporomandibular disorder (TMD)?' MATERIALS AND METHODS: The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An initial search was performed on electronic databases-including Medline, PubMed, and Cochrane Library-followed by manual and reference searches until the date September 27, 2019. The articles selected were evaluated for study and patient characteristics, arthrocentesis procedure details, and treatment outcomes (post-operative pain, maximum mouth opening (MMO), procedure time, and attempts of needle positioning). Risk of bias was assessed with the Cochrane Consumers and Communication Review Group's data extraction template and Critical Appraisal Skills Programme (CASP). RESULTS: Out of the 325 initially identified articles, four studies with 144 patients were included in the final qualitative analysis. No significant differences were found in pain reduction and improved MMO between sample groups receiving conventional arthrocentesis and USG-guided arthrocentesis. Needle positioning attempts and procedural times were conflicting between the two groups. CONCLUSIONS: This systematic review found that the outcomes of USG-guided arthrocentesis were not superior to conventional arthrocentesis. Conflicting data was found in the attempts of needle positioning and procedural time. Standardized treatment protocols and data from well-designed USG-guided arthrocentesis randomized clinical trials were lacking. CLINICAL RELEVANCE: Arthrocentesis with or without USG guidance are both effective for treating patients with TMD to reduce pain and to improve MMO. USG-guided arthrocentesis was not found to be superior to conventional arthrocentesis.

Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace.

Complex biomedical analyses require the use of multiple software tools in concert and remain challenging for much of the biomedical research community. We introduce GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative community resource that currently supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate integrative analysis by non-programmers, it offers a growing set of 'recipes', short workflows to guide investigators through high-utility analysis tasks.

Neuronavigation-guided Percutaneous Rhizotomies to Trigeminal Neuralgia: A Systematic Review.

OBJECTIVE: Neuronavigation improves intraoperative visualization of the cranial structures, which is valuable in percutaneous surgical treatments for patients with trigeminal neuralgia (TN) who are refractory to pharmacotherapy or reluctant to receive open surgery. The objective of this review was to evaluate the available neuronavigation-guided percutaneous surgical treatment modalities with cannulation of foramen ovale to TN, and their relative benefits and limitations. METHODS: This review was conducted based on the PRISMA statement. An initial search was performed on electronic databases, followed by manual and reference searches. Study and patient characteristics, rhizotomy procedure and neuronavigation details, and treatment outcomes (initial pain relief and pain recurrence within 2 y, success rate of forman ovale cannulation, and complications) were evaluated. The risk of bias was assessed with a quality assessment based on the ROBINS-I tools. RESULTS: Ten studies (491 operations, 403 participants) were analyzed. Three percutaneous trigeminal rhizotomy modalities identified were radiofrequency thermocoagulation rhizotomy (RFTR), percutaneous balloon compression, and glycerol rhizotomy. Intraoperative computed tomography and magnetic resonance imaging fusion-based RFTR had the highest initial pain relief rate of 97.0%. The success rate of foramen ovale cannulation ranged from 92.3% to 100% under neuronavigation. Facial hypoesthesia and masticatory muscle weakness were the most reported complications. DISCUSSION: Neuronavigation-guided percutaneous trigeminal rhizotomies showed possible superior pain relief outcomes to that of conventional rhizotomies in TN, with the benefits of radiation reduction and lower complication development rates. The limitations of neuronavigation remain its high cost and limited availability. Higher-quality prospective studies and randomized clinical trials of neuronavigation-guided percutaneous trigeminal rhizotomy were lacking.

3D Printing and processing of miniaturized transducers with near-pristine piezoelectric ceramics for localized cavitation.

The performance of ultrasonic transducers is largely determined by the piezoelectric properties and geometries of their active elements. Due to the brittle nature of piezoceramics, existing processing tools for piezoelectric elements only achieve simple geometries, including flat disks, cylinders, cubes and rings. While advances in additive manufacturing give rise to free-form fabrication of piezoceramics, the resultant transducers suffer from high porosity, weak piezoelectric responses, and limited geometrical flexibility. We introduce optimized piezoceramic printing and processing strategies to produce highly responsive piezoelectric microtransducers that operate at ultrasonic frequencies. The 3D printed dense piezoelectric elements achieve high piezoelectric coefficients and complex architectures. The resulting piezoelectric charge constant, d33, and coupling factor, kt, of the 3D printed piezoceramic reach 583 pC/N and 0.57, approaching the properties of pristine ceramics. The integrated printing of transducer packaging materials and 3D printed piezoceramics with microarchitectures create opportunities for miniaturized piezoelectric ultrasound transducers capable of acoustic focusing and localized cavitation within millimeter-sized channels, leading to miniaturized ultrasonic devices that enable a wide range of biomedical applications.

A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell division numbers.

In humans and other mammals, germline mutations are more likely to arise in fathers than in mothers. Although this sex bias has long been attributed to DNA replication errors in spermatogenesis, recent evidence from humans points to the importance of mutagenic processes that do not depend on cell division, calling into question our understanding of this basic phenomenon. Here, we infer the ratio of paternal-to-maternal mutations, α, in 42 species of amniotes, from putatively neutral substitution rates of sex chromosomes and autosomes. Despite marked differences in gametogenesis, physiologies and environments across species, fathers consistently contribute more mutations than mothers in all the species examined, including mammals, birds, and reptiles. In mammals, α is as high as 4 and correlates with generation times; in birds and snakes, α appears more stable around 2. These observations are consistent with a simple model, in which mutations accrue at equal rates in both sexes during early development and at a higher rate in the male germline after sexual differentiation, with a conserved paternal-to-maternal ratio across species. Thus, α may reflect the relative contributions of two or more developmental phases to total germline mutations, and is expected to depend on generation time even if mutations do not track cell divisions.

Multiplex recording of cellular events over time on CRISPR biological tape.

Although dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here we describe a framework for storing temporal biological information directly in the genomes of a cell population. We developed a "biological tape recorder" in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording over multiple days and accurate reconstruction of temporal and lineage information by sequencing CRISPR arrays. We further demonstrate a multiplexing strategy to simultaneously record the temporal availability of three metabolites (copper, trehalose, and fucose) in the environment of a cell population over time. This work enables the temporal measurement of dynamic cellular states and environmental changes and suggests new applications for chronicling biological events on a large scale.

Reduced generation of lung tissue-resident memory T cells during infancy.

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant-T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet-regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage.

Constellation Map: Downstream visualization and interpretation of gene set enrichment results.

UNLABELLED: Gene set enrichment analysis (GSEA) approaches are widely used to identify coordinately regulated genes associated with phenotypes of interest. Here, we present Constellation Map, a tool to visualize and interpret the results when enrichment analyses yield a long list of significantly enriched gene sets. Constellation Map identifies commonalities that explain the enrichment of multiple top-scoring gene sets and maps the relationships between them. Constellation Map can help investigators take full advantage of GSEA and facilitates the biological interpretation of enrichment results. AVAILABILITY: Constellation Map is freely available as a GenePattern module at http://www.genepattern.org.