Hydrogel-Tissue Chemistry: Principles and Applications

Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons—even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants—or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout—is stimulating innovation across biology and medicine

Hydrogel-Tissue Chemistry: Principles and Applications

Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons—even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants—or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout—is stimulating innovation across biology and medicine

Relationships among HIV infection, metabolic risk factors, and left ventricular structure and function

Our objective was to determine if the presence of metabolic complications (MC) conveyed an additional risk for left ventricular (LV) dysfunction in people with HIV. HIV(+) and HIV(−) men and women were categorized into four groups: (1) HIV(+) with MC (43±7 years, n=64), (2) HIV(+) without MC (42±7 years, n=59), (3) HIV(−) with MC (44±8 years, n=37), or (4) HIV(−) controls without MC (42±8 years, n=41). All participants underwent two-dimensional (2-D), Doppler, and tissue Doppler echocardiography. Overall, the prevalence of systolic dysfunction (15 vs. 4%, p=0.02) and LV hypertrophy (9 vs. 1%, p=0.03) was greater in HIV(+) than in HIV(−) participants. Participants with MC had a greater prevalence of LV hypertrophy (10% vs. 1%). Early mitral annular velocity during diastole was significantly (p<0.005) lower in groups with MC (HIV(+)/MC(+): 11.6±2.3, HIV(−)/MC(+): 12.0±2.3 vs. HIV(+)/MC(−): 12.4±2.3, HIV(−)/MC(−): 13.1±2.4 cm/s) and tended to be lower in groups with HIV (p=0.10). However, there was no interaction effect of HIV and MC for any systolic or diastolic variable. Regardless of HIV status, participants with MC had reduced LV diastolic function. Although both the presence of MC and HIV infection were associated with lower diastolic function, there was no additive negative effect of HIV on diastolic function beyond the effect of MC. Also, HIV was independently associated with lower systolic function. Clinical monitoring of LV function in individuals with metabolic risk factors, regardless of HIV status, is warranted

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Beyond Learning: Leveraging Undergraduate Research into Marketable Workforce Skills

Learning outcomes can structure and enhance the undergraduate research experience, building skills such as critical thinking/problem solving, communication, and team-work/collaboration. These skills often correspond to what employers desire in their recruitment of recent college graduates: students possess career competencies that result from undergraduate research and prepare them for the workforce. However, students do not necessarily recognize the value of undergraduate research for workforce preparation, recognize how their research experience has prepared them, and/or are unable to fully articulate their preparedness. The authors discuss the value of integrating learning outcomes across the college experience to enhance undergraduate research and career readiness. They detail the implementation of an integrated model within a primarily undergraduate institution and suggest strategies to best leverage undergraduate research for workforce preparation

Association and Regulation of Protein Factors of Field Effect in Prostate Tissues

Field effect or field cancerization denotes the presence of molecular aberrations in structurally intact cells residing in histologically normal tissues adjacent to solid tumors. Currently, the etiology of prostate field‑effect formation is unknown and there is a prominent lack of knowledge of the underlying cellular and molecular pathways. We have previously identified an upregulated expression of several protein factors representative of prostate field effect, i.e., early growth response‑1 (EGR‑1), platelet‑derived growth factor‑A (PDGF‑A), macrophage inhibitory cytokine‑1 (MIC‑1), and fatty acid synthase (FASN) in tissues at a distance of 1 cm from the visible margin of intracapsule prostate adenocarcinomas. We have hypothesized that the transcription factor EGR‑1 could be a key regulator of prostate field‑effect formation by controlling the expression of PDGF‑A, MIC‑1, and FASN. Taking advantage of our extensive quantitative immunofluorescence data specific for EGR‑1, PDGF‑A, MIC‑1, and FASN generated in disease‑free, tumor‑adjacent, and cancerous human prostate tissues, we chose comprehensive correlation as our major approach to test this hypothesis. Despite the static nature and sample heterogeneity of association studies, we show here that sophisticated data generation, such as by spectral image acquisition, linear unmixing, and digital quantitative imaging, can provide meaningful indications of molecular regulations in a physiologically relevant in situ environment. Our data suggest that EGR‑1 acts as a key regulator of prostate field effect through induction of pro‑proliferative (PDGF‑A and FASN), and suppression of pro‑apoptotic (MIC‑1) factors. These findings were corroborated by computational promoter analyses and cell transfection experiments in non‑cancerous prostate epithelial cells with ectopically induced and suppressed EGR‑1 expression. Among several clinical applications, a detailed knowledge of pathways of field effect may lead to the development of targeted intervention strategies preventing progression from pre‑malignancy to cancer