A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment.

Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS).

Mentoring during Uncertain Times.

Scientific success is mainly supported by mentoring, which often occurs through face-to-face interactions. Changes to the research environment incurred by the Coronavirus 2019 (COVID-19) pandemic have necessitated mentorship adaptations. Here, we describe how mentors can broaden their mentorship to support trainee growth and provide reassurance about trainee development amid uncertain circumstances.

Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes.

Aberrant redox signaling underlies the pathophysiology of many chronic metabolic diseases, including type 2 diabetes (T2D). Methodologies aimed at rebalancing systemic redox homeostasis have had limited success. A noninvasive, sustained approach would enable the long-term control of redox signaling for the treatment of T2D.

Guided genetic screen to identify genes essential in the regeneration of hair cells and other tissues.

Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury.

Loss of Mgat5a-mediated -glycosylation stimulates regeneration in zebrafish.

Background: We are using genetics to identify genes specifically involved in hearing regeneration. In a large-scale genetic screening, we identified , a gene in the -glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration.

Methods: We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish.

Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases.

Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish.

Extracellular HSP60 triggers tissue regeneration and wound healing by regulating inflammation and cell proliferation.

After injury, zebrafish can restore many tissues that do not regenerate well in mammals, making it a useful vertebrate model for studying regenerative biology. We performed a systematic screen to identify genes essential for hair cell regeneration in zebrafish, and found that the heat shock protein Hspd1 (Hsp60) has a critical role in the regeneration of hair cells and amputated caudal fins. We showed HSP60-injected extracellularly promoted cell proliferation and regeneration in both hair cells and caudal fins.

High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9.

The use of CRISPR/Cas9 as a genome-editing tool in various model organisms has radically changed targeted mutagenesis. Here, we present a high-throughput targeted mutagenesis pipeline using CRISPR/Cas9 technology in zebrafish that will make possible both saturation mutagenesis of the genome and large-scale phenotyping efforts. We describe a cloning-free single-guide RNA (sgRNA) synthesis, coupled with streamlined mutant identification methods utilizing fluorescent PCR and multiplexed, high-throughput sequencing.

Dose-response relationship of cardiorespiratory fitness adaptation to controlled endurance training in sedentary older adults.

Background: The purpose of this investigation was to identify a quantitative dose-response relationship for enhancing maximal oxygen consumption (VO2max) in healthy sedentary older adults after controlled endurance training.

Methods And Results: This meta-analysis of controlled clinical trials included 1257 exercisers and 845 controls with a mean age of 67.45 ± 5.

Controlled aerobic exercise training reduces resting blood pressure in sedentary older adults.

The results of existing controlled clinical trials were synthesized to determine effects of aerobic exercise training on resting systolic (SBP) and diastolic blood pressure (DBP) among previously sedentary older adults, to quantify the magnitude of observed changes, and to examine the influence of the associated interventional variables on these changes. Studies were identified via a systematic computer database search, hand searching, and cross-referencing of previously located articles. All potentially eligible articles were carefully reviewed and examined with the established inclusion criteria.

A large-scale zebrafish gene knockout resource for the genome-wide study of gene function.

With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way. The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation. Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome.