Transcription factor SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating the neurogenic gene Hes5.

SOX2 and SOX15 are Sox family transcription factors enriched in embryonic stem cells (ESCs). The role of SOX2 in activating gene expression programs essential for stem cell self-renewal and acquisition of pluripotency during somatic cell reprogramming is well-documented. However, the contribution of SOX15 to these processes is unclear and often presumed redundant with SOX2 largely because overexpression of SOX15 can partially restore self-renewal in SOX2-deficient ESCs.

ATP-binding cassette protein ABCF1 couples transcription and genome surveillance in embryonic stem cells through low-complexity domain.

OCT4 and SOX2 confer pluripotency by recruiting coactivators to activate stem cell–specific transcription. However, the composition of coactivator complexes and their roles in maintaining stem cell fidelity remain unclear. Here, we report the ATP-binding cassette subfamily F member 1 (ABCF1) as a coactivator for OCT4/SOX2 critical for stem cell self-renewal.

Structure of the human Mediator-bound transcription preinitiation complex.

Eukaryotic transcription requires the assembly of a multisubunit preinitiation complex (PIC) composed of RNA polymerase II (Pol II) and the general transcription factors. The coactivator Mediator is recruited by transcription factors, facilitates the assembly of the PIC, and stimulates phosphorylation of the Pol II C-terminal domain (CTD) by the TFIIH subunit CDK7. Here, we present the cryo-electron microscopy structure of the human Mediator-bound PIC at a resolution below 4 angstroms.

Reliability and Validity of the Sit-to-Stand as a Muscular Power Measure in Older Adults.

The study aims were to analyze the reliability and validity of the GymAware™ linear position transducer's velocity and power measures during the sit-to-stand, compared with the Dartfish 2D videography analysis, and to assess the relationship of age and handgrip strength with velocity and power in 48 older men and women (77.6 ± 11.1 years).

Determining cellular CTCF and cohesin abundances to constrain 3D genome models.

Achieving a quantitative and predictive understanding of 3D genome architecture remains a major challenge, as it requires quantitative measurements of the key proteins involved. Here, we report the quantification of CTCF and cohesin, two causal regulators of topologically associating domains (TADs) in mammalian cells. Extending our previous imaging studies (Hansen et al.

Relationship between physical and cognitive performance in community dwelling, ethnically diverse older adults: a cross-sectional study.

Background: Regular exercise training stimulates physiological adaptations to improve physical performance, reduce chronic disease risk, and slow age-related cognitive decline. Since the physiological mechanisms responsible for aging-associated cognitive decline are not yet fully understood, and training-induced physiological adaptations responsible for performance measure improvements are specific to the type (aerobic vs. strength) and intensity of training, studies are needed to assess the relationships between physical performance measures and cognitive performance in older adults.

Reinterpretation of the localization of the ATP binding cassette transporter ABCG1 in insulin-secreting cells and insights regarding its trafficking and function.

The ABC transporter ABCG1 contributes to the regulation of cholesterol efflux from cells and to the distribution of cholesterol within cells. We showed previously that ABCG1 deficiency inhibits insulin secretion by pancreatic beta cells and, based on its immunolocalization to insulin granules, proposed its essential role in forming granule membranes that are enriched in cholesterol. While we confirm elsewhere that ABCG1, alongside ABCA1 and oxysterol binding protein OSBP, supports insulin granule formation, the aim here is to clarify the localization of ABCG1 within insulin-secreting cells and to provide added insight regarding ABCG1's trafficking and sites of function.

Estimating and valuing the carbon release in scenarios of land-use and climate changes in a Brazilian coastal area.

Deforestation is a significant source of man-made carbon in the atmosphere, contributing to the greenhouse gas (GHG) effect. Although carbon releases are associated to the ecosystem functions of climate regulation and are essential ecological processes that sustain life, their incremental economic impact is difficult to estimate. Using the InVEST model, this work quantifies and assesses the value of the carbon balance generated by predictive land-use change (LUC) scenarios for the Northern Coast of São Paulo State, Brazil.

Control of insulin granule formation and function by the ABC transporters ABCG1 and ABCA1 and by oxysterol binding protein OSBP.

In pancreatic β-cells, insulin granule membranes are enriched in cholesterol and are both recycled and newly generated. Cholesterol's role in supporting granule membrane formation and function is poorly understood. ATP binding cassette transporters ABCG1 and ABCA1 regulate intracellular cholesterol and are important for insulin secretion.

dCas9-targeted locus-specific protein isolation method identifies histone gene regulators.

Eukaryotic gene regulation is a complex process, often coordinated by the action of tens to hundreds of proteins. Although previous biochemical studies have identified many components of the basal machinery and various ancillary factors involved in gene regulation, numerous gene-specific regulators remain undiscovered. To comprehensively survey the proteome directing gene expression at a specific genomic locus of interest, we developed an in vitro nuclease-deficient Cas9 (dCas9)-targeted chromatin-based purification strategy, called "CLASP" (Cas9 locus-associated proteome), to identify and functionally test associated gene-regulatory factors.

Primary parotid adenocarcinoma metastasis to the spleen with mutation: cytological findings and review of the literature.

Background: Primary solid tumor metastasis to the spleen is a rare event, and often presents as an incidental finding without clinical symptoms of the patient. The most common primary tumors that metastasize to the spleen are colorectal, ovarian, and lung carcinomas. Parotid tumor metastasis to the spleen is extremely rare.

Muscle Power Predicts Bone Strength in Division II Athletes.

Yingling, VR, Webb, SL, Inouye, C, O, J, and Sherwood, JJ. Muscle power predicts bone strength in Division II athletes. J Strength Cond Res 34(6): 1657-1665, 2020-The relationship between muscle fitness measures and tibial bone strength in collegiate level athletes was investigated.

Using whiteboards to support college students' learning of complex physiological concepts.

Research underscores the importance of retrieval-based practice and application of knowledge for meaningful learning. However, the didactic lecture format continues to persist in traditional university physiology courses. A strategy called whiteboarding, where students use handheld dry erase boards and work in small groups to actively retrieve, discuss, and apply concepts presented in the lecture, has the potential to address challenges associated with actively engaging students in science courses for greater learning.

Fine-needle aspiration of metastatic melanoma presenting as bilateral breast cysts.

Melanoma is the second most common non-hematopoietic malignancy after carcinomas to metastasize to the breast and often appears as a well-circumscribed, dense nodule on imaging. Although metastatic lesions presenting as bilateral cysts have been reported, this presentation is not common and may mimic benign breast cysts. We present a challenging case of metastatic melanoma presenting as bilateral breast cysts with spindled cytomorphology in a patient with a history of mammary carcinoma.

Rapid dynamics of general transcription factor TFIIB binding during preinitiation complex assembly revealed by single-molecule analysis.

Transcription of protein-encoding genes in eukaryotic cells requires the coordinated action of multiple general transcription factors (GTFs) and RNA polymerase II (Pol II). A "step-wise" preinitiation complex (PIC) assembly model has been suggested based on conventional ensemble biochemical measurements, in which protein factors bind stably to the promoter DNA sequentially to build a functional PIC. However, recent dynamic measurements in live cells suggest that transcription factors mostly interact with chromatin DNA rather transiently.

Near-atomic resolution visualization of human transcription promoter opening.

In eukaryotic transcription initiation, a large multi-subunit pre-initiation complex (PIC) that assembles at the core promoter is required for the opening of the duplex DNA and identification of the start site for transcription by RNA polymerase II. Here we use cryo-electron microscropy (cryo-EM) to determine near-atomic resolution structures of the human PIC in a closed state (engaged with duplex DNA), an open state (engaged with a transcription bubble), and an initially transcribing complex (containing six base pairs of DNA-RNA hybrid). Our studies provide structures for previously uncharacterized components of the PIC, such as TFIIE and TFIIH, and segments of TFIIA, TFIIB and TFIIF.

Monitoring C-Peptide Storage and Secretion in Islet β-Cells In Vitro and In Vivo.

Human proinsulin with C-peptide-bearing Superfolder Green Fluorescent Protein (CpepSfGFP) has been expressed in transgenic mice, driven by the Ins1 promoter. The protein, expressed exclusively in β-cells, is processed and stored as CpepSfGFP and human insulin comprising only ∼0.04% of total islet proinsulin plus insulin, exerting no metabolic impact.

Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation.

Intrinsically disordered proteins/regions (IDPs/IDRs) are proteins or peptide segments that fail to form stable 3-dimensional structures in the absence of partner proteins. They are abundant in eukaryotic proteomes and are often associated with human diseases, but their biological functions have been elusive to study. In this study, we report the identification of a tin(IV) oxochloride-derived cluster that binds an evolutionarily conserved IDR within the metazoan TFIID transcription complex.

The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells.

Acquisition of pluripotency is driven largely at the transcriptional level by activators OCT4, SOX2, and NANOG that must in turn cooperate with diverse coactivators to execute stem cell-specific gene expression programs. Using a biochemically defined in vitro transcription system that mediates OCT4/SOX2 and coactivator-dependent transcription of the gene, we report the purification and identification of the dyskerin (DKC1) ribonucleoprotein complex as an OCT4/SOX2 coactivator whose activity appears to be modulated by a subset of associated small nucleolar RNAs (snoRNAs). The DKC1 complex occupies enhancers and regulates the expression of key pluripotency genes critical for self-renewal in embryonic stem (ES) cells.

p53 expression is a strong marker of inferior survival in de novo diffuse large B-cell lymphoma and may have enhanced negative effect with MYC coexpression: a single institutional clinicopathologic study.

Objectives: To examine interactions among clinical factors and pathologic biomarkers in predicting the outcome of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-based immunochemotherapy.

Methods: In 85 patients treated at a single institution, clinicopathologic variables were analyzed, including the International Prognostic Index (IPI); germinal/nongerminal center phenotype; MYC, p53, BCL2, Ki-67, and Epstein-Barr virus (EBV) expression; and MYC translocation status.

Results: In univariate analysis, overall survival (OS) was worse for patients with high IPI scores, nongerminal center phenotype, high MYC and p53 expression by immunohistochemistry, and EBV positivity.

Transcription initiation by human RNA polymerase II visualized at single-molecule resolution.

Forty years of classical biochemical analysis have identified the molecular players involved in initiation of transcription by eukaryotic RNA polymerase II (Pol II) and largely assigned their functions. However, a dynamic picture of Pol II transcription initiation and an understanding of the mechanisms of its regulation have remained elusive due in part to inherent limitations of conventional ensemble biochemistry. Here we have begun to dissect promoter-specific transcription initiation directed by a reconstituted human Pol II system at single-molecule resolution using fluorescence video-microscopy.

Propofol effects on the morphology of rat testes subjected to testicular ischemia-reperfusion.

Purpose: To evaluate the effects of propofol as an inhibitor of tissue injury in testicular ischemia-reperfusion in rats.

Methods: 30 Wistar rats were assigned to one of three groups of 10 animals: G1, testicular exposure alone; G2 and G3: testicular ischemia caused by left spermatic cord torsion of 720º. In G3, propofol was administered intraperitoneally at 20 mg/kg/h 45 minutes after spermatic cord torsion.