Cas12f1 gene drives propagate efficiently in herpesviruses and induce minimal resistance.

Background: Synthetic CRISPR-Cas9 gene drive has been developed to control harmful species. However, resistance to Cas9 gene drive can be acquired easily when DNA repair mechanisms patch up the genetic insults introduced by Cas9 and incorporate mutations to the sgRNA target. Although many strategies to reduce the occurrence of resistance have been developed so far, they are difficult to implement and not always effective.

Language in job advertisements and the reproduction of labor force gender and racial segregation.

Job advertisements (ads) represent the first point of contact between employers and job seekers. By signaling characteristics expected of an ideal candidate, job ads "gatekeep" the labor force and configure its composition. Meanwhile, labor force composition can also shape the wording of job ads.

The Impact and Mechanism of Action of Peptostreptococcus anaerobius on Chemotherapy Resistance in Human Colorectal Cancer.

Peptostreptococcus anaerobius plays an important role in the development of colorectal cancer, and previous studies by our group have demonstrated that Peptostreptococcus anaerobius promotes resistance to 5-Fu chemotherapy in animal models of colorectal cancer. In this study, the effects of Peptostreptococcus anaerobius on chemotherapy resistance in colorectal cancer and its possible mechanism of action were investigated from the clinical point of view. Patients were selected according to exclusion and inclusion criteria and divided into sensitive and chemotherapy groups (n = 20/group).

Successful treatment of refractory ascites in a patient with liver cirrhosis combined with hepatic artery-portal vein malformation: A case report.

Introduction: Hepatic artery-portal vein malformation is rarely encountered in clinical practice. Here, we reported a case of liver cirrhosis combined with hepatic artery-portal vein malformation with refractory ascites as the main symptom. And it was successfully treated by us.

Ball divergence for the equality test of crossing survival curves.

It is a very common problem to test survival equality using the right-censored time-to-event data in clinical research. Although the log-rank test is popularly used in various studies, it may become insensitive when the proportional hazards assumption is violated. As follows, there have a variety of statistical methods being proposed to identify the discrepancy between crossing survival curves or hazard functions.

ZipHiC: a novel Bayesian framework to identify enriched interactions and experimental biases in Hi-C data.

Motivation: Several computational and statistical methods have been developed to analyze data generated through the 3C-based methods, especially the Hi-C. Most of the existing methods do not account for dependency in Hi-C data.

Results: Here, we present ZipHiC, a novel statistical method to explore Hi-C data focusing on the detection of enriched contacts.

Efficient empirical likelihood inference for recovery rate of COVID19 under double-censoring.

Doubly censored data are very common in epidemiology studies. Ignoring censorship in the analysis may lead to biased parameter estimation. In this paper, we highlight that the publicly available COVID19 data may involve high percentage of double-censoring and point out the importance of dealing with such missing information in order to achieve better forecasting results.

The role of insulators and transcription in 3D chromatin organization of flies.

The DNA in many organisms, including humans, is shown to be organized in topologically associating domains (TADs). In , several architectural proteins are enriched at TAD borders, but it is still unclear whether these proteins play a functional role in the formation and maintenance of TADs. Here, we show that depletion of BEAF-32, Cp190, Chro, and Dref leads to changes in TAD organization and chromatin loops.

Balancing Gender Bias in Job Advertisements With Text-Level Bias Mitigation.

Despite progress toward gender equality in the labor market over the past few decades, gender segregation in labor force composition and labor market outcomes persists. Evidence has shown that job advertisements may express gender preferences, which may selectively attract potential job candidates to apply for a given post and thus reinforce gendered labor force composition and outcomes. Removing gender-explicit words from job advertisements does not fully solve the problem as certain implicit traits are more closely associated with men, such as , while others are more closely associated with women, such as .

Single-molecule imaging reveals the concerted release of myosin from regulated thin filaments.

Regulated thin filaments (RTFs) tightly control striated muscle contraction through calcium binding to troponin, which enables tropomyosin to expose myosin-binding sites on actin. Myosin binding holds tropomyosin in an open position, exposing more myosin-binding sites on actin, leading to cooperative activation. At lower calcium levels, troponin and tropomyosin turn off the thin filament; however, this is antagonised by the high local concentration of myosin, questioning how the thin filament relaxes.

BSC2 induces multidrug resistance via contributing to the formation of biofilm in Saccharomyces cerevisiae.

Biofilm plays an important role in fungal multidrug resistance (MDR). Our previous studies showed that BSC2 is involved in resistance to amphotericin B (AMB) through antioxidation in Saccharomyces cerevisiae. In this study, the overexpression of BSC2 and IRC23 induced strong MDR in S.

Oncolytic HSV-Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition.

Purpose: To examine the effect of oncolytic herpes simplex virus (oHSV) on NOTCH signaling in central nervous system tumors.

Experimental Design: Bioluminescence imaging, reverse phase protein array proteomics, fluorescence microscopy, reporter assays, and molecular biology approaches were used to evaluate NOTCH signaling. Orthotopic glioma-mouse models were utilized to evaluate effects .

An oncolytic herpesvirus expressing E-cadherin improves survival in mouse models of glioblastoma.

The efficacy of oncolytic herpes simplex virus (oHSV) is limited by rapid viral clearance by innate immune effector cells and poor intratumoral viral spread. We combine two approaches to overcome these barriers: inhibition of natural killer (NK) cells and enhancement of intratumoral viral spread. We engineered an oHSV to express CDH1, encoding E-cadherin, an adherent molecule and a ligand for KLRG1, an inhibitory receptor expressed on NK cells.

Refining value-at-risk estimates using a Bayesian Markov-switching GJR-GARCH copula-EVT model.

In this paper, we propose a model for forecasting Value-at-Risk (VaR) using a Bayesian Markov-switching GJR-GARCH(1,1) model with skewed Student's-t innovation, copula functions and extreme value theory. A Bayesian Markov-switching GJR-GARCH(1,1) model that identifies non-constant volatility over time and allows the GARCH parameters to vary over time following a Markov process, is combined with copula functions and EVT to formulate the Bayesian Markov-switching GJR-GARCH(1,1) copula-EVT VaR model, which is then used to forecast the level of risk on financial asset returns. We further propose a new method for threshold selection in EVT analysis, which we term the hybrid method.

Molecular Basis for the Recognition of Herpes Simplex Virus Type 1 Infection by Human Natural Killer Cells.

Primary infection with Herpes simplex virus type 1 (HSV1) is subclinical or only mildly symptomatic in normal individuals, yet the reason for the body's effective immune defense against this pathogen in the absence of antigen-specific immunity has not been well understood. It is clear that human natural killer (NK) cells recognize and kill HSV1-infected cells, and those individuals who either lack or have functionally impaired NK cells can suffer severe, recurrent, and sometimes fatal HSV1 infection. In this article, we review what is known about the recognition of HSV1 by NK cells, and describe a novel mechanism of innate immune surveillance against certain viral pathogens by NK cells called Fc-bridged cell-mediated cytotoxicity.

The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells.

Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a.

Bortezomib Treatment Sensitizes Oncolytic HSV-1-Treated Tumors to NK Cell Immunotherapy.

Purpose: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy.

Joint longitudinal and survival-cure models in tumour xenograft experiments.

In tumour xenograft experiments, treatment regimens are administered, and the tumour volume of each individual is measured repeatedly over time. Survival data are recorded because of the death of some individuals during the observation period. Also, cure data are observed because of a portion of individuals who are completely cured in the experiments.

Directed evolution of a virus exclusively utilizing human epidermal growth factor receptor as the entry receptor.

Rational design and directed evolution are powerful tools to generate and improve protein function; however, their uses are mostly limited to enzyme and antibody engineering. Here we describe a directed-evolution strategy, named the tandem selection and enrichment system (TSES), and its use in generating virus with exclusive specificity for a particular cellular receptor. In TSES, evolving viruses are sequentially and iteratively transferred between two different host cells, one for selection of receptor specificity and the other for enrichment of the fittest virus.

Accelerated failure time models for censored survival data under referral bias.

The estimation of progression to liver cirrhosis and identifying its risk factors are often of epidemiological interest in hepatitis C natural history study. In most hepatitis C cohort studies, patients were usually recruited to the cohort with a referral bias because clinically the patients with more rapid disease progression were preferentially referred to liver clinics. A pair of correlated event times may be observed for each patient, time to development of cirrhosis and time to referral to a cohort.

[Study on the mechanism of enhancing homing efficiency of human hematopoietic stem/progenitor cells into bone marrow after manipulation with tumor necrosis factor alpha in xenotransplanted BALB/c mouse model].

Objective: To investigate the role of tumor necrosis factor (TNF) alpha on the homing efficiency of hematopoietic stem/progenitor cells (HS/PC) into bone marrow and its mechanism.

Methods: CFSE-labeled umbilical cord blood (UCB) CD34+ cells were transplanted into irradiated (control group) or combined with TNF alpha prepared (experimental group) BALB/c recipient mice. The distribution in peripheral blood, liver, lung and homing characteristics in bone marrow and spleen of UCB CD34+ cells, in BALB/c recipient mice were determined 20 hours after xenotransplantation by flow cytometry (FACS) and their homing efficiency was calculated.