Computationally guided AAV engineering for enhanced gene delivery.

Gene delivery vehicles based on adeno-associated viruses (AAVs) are enabling increasing success in human clinical trials, and they offer the promise of treating a broad spectrum of both genetic and non-genetic disorders. However, delivery efficiency and targeting must be improved to enable safe and effective therapies. In recent years, considerable effort has been invested in creating AAV variants with improved delivery, and computational approaches have been increasingly harnessed for AAV engineering.

Optimal trade-off control in machine learning-based library design, with application to adeno-associated virus (AAV) for gene therapy.

Adeno-associated viruses (AAVs) hold tremendous promise as delivery vectors for gene therapies. AAVs have been successfully engineered-for instance, for more efficient and/or cell-specific delivery to numerous tissues-by creating large, diverse starting libraries and selecting for desired properties. However, these starting libraries often contain a high proportion of variants unable to assemble or package their genomes, a prerequisite for any gene delivery goal.

Anxiety-related behavior and associated brain transcriptome and epigenome alterations in adult female zebrafish exposed to atrazine during embryogenesis.

Atrazine often contaminates drinking water sources, exceeding the maximum contaminant level established by the US Environmental Protection Agency at 3 parts per billion (ppb; μg/L). Atrazine is linked to endocrine disruption, neurotoxicity, and cancer, with delayed health effects observed after developmental exposure in line with the developmental origins of health and disease (DOHaD) hypothesis. To test the hypothesis that embryonic atrazine exposure induces delayed neurotoxicity in adult female zebrafish (Danio rerio), embryos were exposed to 0, 0.

Atrazine exposure in zebrafish induces aberrant genome-wide methylation.

Atrazine (ATZ) is the second most common agricultural herbicide used in the United States and is an endocrine disrupting chemical (EDC). Developmental exposure to ATZ can lead to significant behavioral and morphological alterations in exposed animals and their progeny suggesting the involvement of an epigenetic mechanism. Specific epigenetic mechanisms responsible for these alterations, however, are yet to be elucidated.

Acylated homoserine lactones regulate the response of methane metabolism and nitrogen metabolism to florfenicol in anaerobic fermentation.

Antimicrobial agents enter the ecological environment through animal excreta and disrupt metabolism in environmental microorganisms. Quorum sensing (QS) can help bacteria adapt to their surroundings. To explore how acyl-homoserine lactone (AHL) can adjust the influence of florfenicol on nitrogen cycling and methane metabolism in anaerobic fermentation, a small indoor thermostatic anaerobic fermentation model was established by adding exogenous acylated homoserine lactone (AHL) signal molecules with florfenicol as the stress factor.

Single-Cell Image-Based Analysis Reveals Chromatin Changes during the Acquisition of Tamoxifen Drug Resistance.

Cancer drug resistance is the leading cause of cancer related deaths. The development of drug resistance can be partially contributed to tumor heterogeneity and epigenetic plasticity. However, the detailed molecular mechanism underlying epigenetic modulated drug resistance remains elusive.

Lead exposure induces dysregulation of constitutive heterochromatin hallmarks in live cells.

Lead (Pb) is a heavy metal contaminant commonly found in air, soil, and drinking water due to legacy uses. Excretion of ingested Pb can result in extensive kidney damages due to elevated oxidative stress. Epigenetic alterations induced by exposure to Pb have also been implied but remain poorly understood.

Low dose lead exposure induces alterations on heterochromatin hallmarks persisting through SH-SY5Y cell differentiation.

Lead (Pb) is a commonly found heavy metal due to its historical applications. Recent studies have associated early-life Pb exposure with the onset of various neurodegenerative disease. The molecular mechanisms of Pb conferring long-term neurotoxicity, however, is yet to be elucidated.

Embryonic atrazine exposure and later in life behavioral and brain transcriptomic, epigenetic, and pathological alterations in adult male zebrafish.

Atrazine (ATZ), a commonly used pesticide linked to endocrine disruption, cancer, and altered neurochemistry, frequently contaminates water sources at levels above the US Environmental Protection Agency's 3 parts per billion (ppb; μg/L) maximum contaminant level. Adult male zebrafish behavior, brain transcriptome, brain methylation status, and neuropathology were examined to test the hypothesis that embryonic ATZ exposure causes delayed neurotoxicity, according to the developmental origins of health and disease paradigm. Zebrafish (Danio rerio) embryos were exposed to 0 ppb, 0.

Feasibility of using the International Classification of Functioning, Disability and Health Core Set for evaluation of fall-related risk factors in acute rehabilitation settings.

Background: Previously, we reported the use of an International Classification of Functioning (ICF) core set that can provide a holistic framework for evaluating the risk factors of falls; however, data on the feasibility of applying this core set are lacking.

Aim: To investigate the feasibility of applying the fall-related ICF risk-factor core set in the case of patients in an acute-rehabilitation setting.

Design: A cross-sectional and descriptive correlational design.

Evaluation of the mass measles vaccination campaign in Guangdong Province, China.

Objective: To evaluate the mass measles vaccination campaign of 2009 in Guangdong Province, China.

Methods: Data on the campaign implementation, measles surveillance, and serological surveillance were reviewed and analyzed by statistical methods.

Results: Rapid coverage surveys showed that 98.

Higher nigrostriatal dopamine neuron loss in early than late onset Parkinson's disease?--a [99mTc]-TRODAT-1 SPECT study.

Early-onset Parkinson's disease (EOPD) is distinct from the classic late-onset PD (LOPD) because of its slower disease progression. The aim of this study was to compare dopamine neuronal loss in EOPD with that of LOPD with the same disease duration, through dopamine transporter (DAT) estimation. Fourteen patients, seven EOPD (<50 years) and seven LOPD, matched for disease duration were scanned with [(99m)Tc]-TRODAT-1-SPECT (INER-Taiwan), and were assessed with standard PD scales.

[Neuroimaging of the dopamine transporter in Parkinsons disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil].

Background: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in Parkinsons disease (PD).

Objective: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD.

Method: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT.