Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward.

Drugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the gene) as a marker of cocaine-activated neuronal ensembles within the rat NAc.

Observing Annual Trends in Vehicular CO Emissions.

Transportation emissions are the largest individual sector of greenhouse gas (GHG) emissions. As such, reducing transportation-related emissions is a primary element of every policy plan to reduce GHG emissions. The Berkeley Environmental Air-quality and CO Observation Network (BEACON) was designed and deployed with the goal of tracking changes in urban CO emissions with high spatial (∼1 km) and temporal (∼1 hr) resolutions while allowing the identification of trends in individual emission sectors.

Evolution of Dupilumab-Associated Cutaneous Atypical Lymphoid Infiltrates.

Background: Observations highlighting the "unmasking" of cutaneous T-cell lymphoma after treatment with dupilumab for atopic dermatitis (AD) have been recently reported. However, there remains a paucity of literature describing the evolution of clinical and histopathological features that characterizes this phenomenon.

Objective: To define the clinical and histopathologic evolution of atypical lymphoid infiltrates after the administration of dupilumab for AD.

Targeting a helix-in-groove interaction between E1 and E2 blocks ubiquitin transfer.

The ubiquitin-proteasome system (UPS) is a highly regulated protein disposal process critical to cell survival. Inhibiting the pathway induces proteotoxic stress and can be an effective cancer treatment. The therapeutic window observed upon proteasomal blockade has motivated multiple UPS-targeting strategies, including preventing ubiquitination altogether.

Homogeneous Oligomers of Pro-apoptotic BAX Reveal Structural Determinants of Mitochondrial Membrane Permeabilization.

BAX is a pro-apoptotic protein that transforms from a cytosolic monomer into a toxic oligomer that permeabilizes the mitochondrial outer membrane. How BAX monomers assemble into a higher-order conformation, and the structural determinants essential to membrane permeabilization, remain a mechanistic mystery. A key hurdle has been the inability to generate a homogeneous BAX oligomer (BAX) for analysis.

Identification of a Covalent Molecular Inhibitor of Anti-apoptotic BFL-1 by Disulfide Tethering.

The BCL-2 family is composed of anti- and pro-apoptotic members that respectively protect or disrupt mitochondrial integrity. Anti-apoptotic overexpression can promote oncogenesis by trapping the BCL-2 homology 3 (BH3) "killer domains" of pro-apoptotic proteins in a surface groove, blocking apoptosis. Groove inhibitors, such as the relatively large BCL-2 drug venetoclax (868 Da), have emerged as cancer therapies.

Identification of a Structural Determinant for Selective Targeting of HDMX.

p53 is a critical tumor-suppressor protein that guards the human genome against mutations by inducing cell-cycle arrest or apoptosis. Cancer cells subvert p53 by deletion, mutation, or overexpression of the negative regulators HDM2 and HDMX. For tumors that retain wild-type p53, its reactivation by pharmacologic targeting of HDM2 and/or HDMX represents a promising strategy, with a series of selective small-molecule HDM2 inhibitors and a dual HDM2/HDMX stapled-peptide inhibitor being evaluated in clinical trials.

Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment.

The small protein AcrZ in Escherichia coli interacts with the transmembrane portion of the multidrug efflux pump AcrB and increases resistance of the bacterium to a subset of the antibiotic substrates of that transporter. It is not clear how the physical association of the two proteins selectively changes activity of the pump for defined substrates. Here, we report cryo-EM structures of AcrB and the AcrBZ complex in lipid environments, and comparisons suggest that conformational changes occur in the drug-binding pocket as a result of AcrZ binding.

The why, when, and how of computing in biology classrooms.

Many biologists are interested in teaching computing skills or using computing in the classroom, despite not being formally trained in these skills themselves. Thus biologists may find themselves researching how to teach these skills, and therefore many individuals are individually attempting to discover resources and methods to do so. Recent years have seen an expansion of new technologies to assist in delivering course content interactively.

Pediatric tinea capitis caused by Trichophyton violaceum and Trichophyton soudanense in Rochester, Minnesota, United States.

Background: Tinea capitis is a common pediatric dermatophyte infection. Its main pathogen in the United States is Trichophyton tonsurans accounting for greater than 95% of the infections. Other pathogens including Trichophyton violaceum and Trichophyton soudanense are common in Africa.

Phylogenetics of Kingsnakes, Lampropeltis getula Complex (Serpentes: Colubridae), in Eastern North America.

Kingsnakes of the Lampropeltis getula complex range throughout much of temperate and subtropical North America. Studies over the last century have used morphology and color pattern to describe numerous subspecies. More recently, DNA analyses have made invaluable contributions to our understanding of their evolution and taxonomy.

Sequence capture and next-generation sequencing of ultraconserved elements in a large-genome salamander.

Amidst the rapid advancement in next-generation sequencing (NGS) technology over the last few years, salamanders have been left behind. Salamanders have enormous genomes-up to 40 times the size of the human genome-and this poses challenges to generating NGS data sets of quality and quantity similar to those of other vertebrates. However, optimization of laboratory protocols is time-consuming and often cost prohibitive, and continued omission of salamanders from novel phylogeographic research is detrimental to species facing decline.

Acquired lymphangiectasia (lymphangioma circumscriptum) of the vulva: Clinicopathologic study of 11 patients from a single institution and 67 from the literature.

Background: Acquired lymphangiectasia of the vulva (ALV) is a rare condition thought to be secondary to pelvic lymphatic obstruction. Although benign, this entity often occurs after previous malignancy and can be confused with conditions such as genital warts. We sought to clarify the clinicopathologic features of ALV by studying affected patients from our institution and from the existing literature.

High School Athletes' Parents' Perceptions and Knowledge of the Skills and Job Requirements of the Certified Athletic Trainer.

Context: Parents play a crucial role in determining medical services for their children, and it is important they understand the scope of practice and skills of the athletic trainer (AT).

Objective: To understand parents' perceptions and knowledge of the skills and job requirements of the secondary school AT.

Design: Cross-sectional study.

Use of Candida antigen injections for the treatment of verruca vulgaris: A two-year mayo clinic experience.

Common warts (verruca vulgaris) are one of the most common problems encountered in dermatology and may present a difficult treatment dilemma, as no particular therapy has demonstrated complete efficacy. Intralesional injection of purified Candida antigen has produced impressive treatment results in small prospective and retrospective studies and is thought to produce its effect through stimulation of a cell-mediated immune response. We report a retrospective study of adult and pediatric patients treated with Candida antigen therapy in clinical practice.

Thriving in the Cold: Glacial Expansion and Post-Glacial Contraction of a Temperate Terrestrial Salamander (Plethodon serratus).

The dynamic geologic history of the southeastern United States has played a major role in shaping the geographic distributions of amphibians in the region. In the phylogeographic literature, the predominant pattern of distribution shifts through time of temperate species is one of contraction during glacial maxima and persistence in refugia. However, the diverse biology and ecology of amphibian species suggest that a "one-size-fits-all" model may be inappropriate.

Listener estimations of talker age: A meta-analysis of the literature.

Numerous studies, most of them cross-sectional studies using one sample per talker, have demonstrated that listeners make relatively accurate age judgments from hearing talkers' voices. The current study analyzed the results of several such direct age estimation studies to characterize better the perception of talker age over a larger number of individuals. A review of the direct age estimation literature was performed.

Cryptic diversity in metropolis: confirmation of a new leopard frog species (Anura: Ranidae) from New York City and surrounding Atlantic coast regions.

We describe a new cryptic species of leopard frog from the New York City metropolitan area and surrounding coastal regions. This species is morphologically similar to two largely parapatric eastern congeners, Rana sphenocephala and R. pipiens.

Model selection as a tool for phylogeographic inference: an example from the willow Salix melanopsis.

Phylogeographic inference has typically relied on analyses of data from one or a few genes to provide estimates of demography and population histories. While much has been learned from these studies, all phylogeographic analysis is conditioned on the data, and thus, inferences derived from data that represent a small sample of the genome are unavoidably tenuous. Here, we demonstrate one approach for moving beyond classic phylogeographic research.