Efficient DNA-free co-targeting of nuclear genes in Chlamydomonas reinhardtii.

Chlamydomonas reinhardtii, a model organism for unicellular green microalgae, is widely used in basic and applied research. Nonetheless, proceeding towards synthetic biology requires a full set of manipulation techniques for inserting, removing, or editing genes. Despite recent advancements in CRISPR/Cas9, still significant limitations in producing gene knock-outs are standing, including (i) unsatisfactory genome editing (GE) efficiency and (ii) uncontrolled DNA random insertion of antibiotic resistance markers.

Gritty Parenting: The Development and Validation of the Parental Grit Scale.

In this study, we aimed to expand the domain specificity of grit by exploring it in the realm of parenting. Parental grit was defined as parents' inclination to demonstrate perseverance, sustained passion, and adaptability in pursuing long-term parenting goals. With longitudinal data from 1,373 U.

Tracking individual animals can reveal the mechanisms of species loss.

As biodiversity loss continues, targeted conservation interventions are increasingly necessary. Stemming species loss requires mechanistic understanding of the processes governing population dynamics. However, this information is unavailable for most animals because it requires data that are difficult to collect using traditional methods.

Dedicated developmental programing for group-supporting behaviors in eusocial honeybees.

The evolutionary changes from solitary to eusocial living in vertebrates and invertebrates are associated with the diversification of social interactions and the development of queen and worker castes. Despite strong innate patterns, our understanding of the mechanisms manifesting these sophisticated behaviors is still rudimentary. Here, we show that () manifests group-supporting behaviors in the honeybee () worker caste.

Mortality rates in radical cystectomy patients with bladder cancer after radiation therapy for prostate cancer.

Objective: To conduct a population-based study examining cancer-specific mortality (CSM) and other-cause mortality (OCM) differences in patients with radiation-induced secondary bladder cancer (RT-BCa) vs those with primary bladder cancer (pBCa) undergoing radical cystectomy (RC).

Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with TNM bladder cancer treated with RC, who had previously been treated with external beam radiation therapy (EBRT) or brachytherapy for prostate cancer, as well as patients with TNM pBCa treated with RC. Cumulative incidence plots and multivariable competing risks regression (CRR) models were used to assess CSM after additional adjustment for OCM.

Idiosyncratic Hepatocellular Drug-Induced Liver Injury by Flucloxacillin with Evidence Based on Roussel Uclaf Causality Assessment Method and HLA B*57:01 Genotype: From Metabolic CYP 3A4/3A7 to Immune Mechanisms.

Idiosyncratic drug-induced liver injury (iDILI) by flucloxacillin presents as both cholestatic and hepatocellular injury. Its mechanistic steps are explored in the present analysis as limited data exist on the cascade of events leading to iDILI in patients with an established diagnosis assessed for causality by the Roussel Uclaf Causality Assessment Method (RUCAM). Studies with human liver microsomes showed that flucloxacillin is a substrate of cytochrome P450 (CYP) with ist preferred isoforms CYP 3A4/3A7 that toxified flucloxacillin toward 5'-hydroxymethylflucloxacillin, which was cytotoxic to human biliary epithelial cell cultures, simulating human cholestatic injury.

Assessment of Different Castration Resistance Definitions and Staging Modalities in Metastatic Castration-Resistant Prostate Cancer.

: Progression to metastatic castration-resistant prostate cancer (mCRPC) is defined either biochemically, radiographically or both. Moreover, staging for mCRPC can be performed either conventionally or with molecular imaging such as prostate-specific membrane antigen computer tomography (PSMA-PET/CT). : We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to compare progression-free (PFS) and overall survival (OS) outcomes regarding the cause of castration resistance and the staging modality used.

Dissecting the Conformational Heterogeneity of Stem-Loop Substructures of the Fifth Element in the 5'-Untranslated Region of SARS-CoV-2.

Throughout the family of coronaviruses, structured RNA elements within the 5' region of the genome are highly conserved. The fifth stem-loop element from SARS-CoV-2 (5_SL5) represents an example of an RNA structural element, repeatedly occurring in coronaviruses. It contains a conserved, repetitive fold within its substructures SL5a and SL5b.

Neoadjuvant chemotherapy before radical cystectomy in patients with organ-confined and non-organ-confined urothelial carcinoma.

Introduction: Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is guideline-recommended in patients with cT2-T4N0M0 urothelial carcinoma of urinary bladder (UCUB). However, no population-based study validated the survival benefit of NAC recorded in clinical trials in a stage-specific fashion. We addressed this knowledge gap.

Demographic and Clinical Characteristics of Malignant Solitary Fibrous Tumors: A SEER Database Analysis.

Background/objectives: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes.

Methods: Within the SEER database (2000-2019), we identified 1134 patients diagnosed with malignant SFTs.

Homonuclear Super-Resolution NMR Spectroscopy.

In homonuclear H NMR (nuclear magnetic resonance) spectra such as [H,H]-NOESY (Nuclear Overhauser Enhancement spectroscopy), which is a historic cornerstone spectrum for biomolecular NMR structural biology, hundreds to thousands of cross peaks are present within a square of approximately 100 ppm leading to a lot of signal overlap. Spectral resolution is thus a limiting factor for unambiguous chemical shift assignment and data interpretation for dynamics and structure elucidation. Acquiring the spectra at higher magnetic fields such as at a 1.

Single Center Characterization of a Cohort of Salivary Gland Carcinomas.

Salivary gland cancer (SGC) is a rare cancer that can present a diagnostic challenge to pathologists, with emerging, but still limited options for the treatment of recurrent/metastatic disease. We aimed to characterize the cohort of salivary gland cancers in our institute and generate a tissue microarray (TMA) with clinical data available for immunohistochemical analysis. We extracted the cases of salivary gland cancers in our institute and generated a TMA with 72 patients between 2002 and 2017 with sufficient paraffin block material.

Chem-CRISPR/dCas9FCPF: a platform for chemically induced epigenome editing.

Epigenetic aberration is one of the major driving factors in human cancer, often leading to acquired resistance to chemotherapies. Various small molecule epigenetic modulators have been reported. Nonetheless, outcomes from animal models and clinical trials have underscored the substantial setbacks attributed to pronounced on- and off-target toxicities.

Enhanced photodynamic therapy of curcumin using biodegradable PLGA coated mesoporous silica nanoparticles.

Since the available treatments are not highly effective to combat cancer, therefore, the alternative strategies are unavoidable. Photodynamic therapy (PDT) is one of the emerging approaches which is target specific and minimally invasive. This study explores the successful development of Poly (D,L-lactide-co-glycolide) (PLGA) coated mesoporous silica nanoparticles (MSNs) and their augmented effects achieved by integrating curcumin (Cur) and cetyltrimethylammonium bromide (CTAB) in the polymeric layer and silica's pores, respectively.

Covalent Probes To Capture Dup Effector Enzymes.

Upon infection of host cells, releases a multitude of effector enzymes into the cell's cytoplasm that hijack a plethora of cellular activities, including the host ubiquitination pathways. Effectors belonging to the SidE-family are involved in noncanonical serine phosphoribosyl ubiquitination of host substrate proteins contributing to the formation of a Legionella-containing vacuole that is crucial in the onset of Legionnaires' disease. This dynamic process is reversed by effectors called Dups that hydrolyze the phosphodiester in the phosphoribosyl ubiquitinated protein.

Perovskite-Like Carbodiimides (NCN): Synthesis and Characterization of MnHf(NCN) and FeHf(NCN).

Two novel ternary air-stable transition-metal carbodiimides, MnHf(NCN) and FeHf(NCN), were synthesized via solid-state metathesis using either ZnNCN or NaNCN as the carbodiimide source and the corresponding binary metal chlorides. These two phases are the first examples of transition-metal carbodiimides with an (NCN) composition, akin to ubiquitous O perovskite oxides. The crystal structure of MnHf(NCN) was determined and refined from powder X-ray diffraction (XRD) data in the non-centrosymmetric space group 622 allowing for chirality, the assignment of which is supported by second-harmonic generation (SHG) measurements.

Learning Enhancer-Gene associations from Bulk Transcriptomic and Epigenetic Sequencing Data with STITCHIT.

To reveal gene regulation mechanisms, it is essential to understand the role of regulatory elements, which are possibly distant from gene promoters. Integrative analysis of epigenetic and transcriptomic data can be used to gain insights into gene-expression regulation in specific phenotypes. Here, we discuss STITCHIT, an approach to dissect epigenetic variation in a gene-specific manner across many samples for the identification of regulatory elements without relying on peak calling algorithms.

Prediction of Enhancer-Gene Interactions Using Chromatin-Conformation Capture and Epigenome Data Using STARE.

Disentangling the relationship of enhancers and genes is an ongoing challenge in epigenomics. We present STARE, our software to quantify the strength of enhancer-gene interactions based on enhancer activity and chromatin contact data. It implements the generalized Activity-by-Contact (gABC) score, which allows predicting putative target genes of candidate enhancers over any desired genomic distance.

Strategic Fluorination to Achieve a Potent, Selective, Metabolically Stable, and Orally Bioavailable Inhibitor of CSNK2.

The host kinase casein kinase 2 (CSNK2) has been proposed to be an antiviral target against β-coronaviral infection. To pharmacologically validate CSNK2 as a drug target in vivo, potent and selective CSNK2 inhibitors with good pharmacokinetic properties are required. Inhibitors based on the pyrazolo[1,5-]pyrimidine scaffold possess outstanding potency and selectivity for CSNK2, but bioavailability and metabolic stability are often challenging.

Auditory objects in working memory include task-irrelevant features.

Object-based attention operates both in perception and visual working memory. While the efficient perception of auditory stimuli also requires the formation of auditory objects, little is known about their role in auditory working memory (AWM). To investigate whether attention to one object feature in AWM leads to the involuntary maintenance of another, task-irrelevant feature, we conducted four experiments.