BMAL1-HIF2α heterodimers contribute to ccRCC.

Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). Furthermore, the clock gene is higher in ccRCC than in healthy kidneys, unlike in other tumor types.

BMAL1-HIF2α heterodimers contribute to ccRCC.

Circadian disruption enhances cancer risk, and many tumors exhibit disordered circadian gene expression. We show rhythmic gene expression is unexpectedly robust in clear cell renal cell carcinoma (ccRCC). Furthermore, the clock gene is higher in ccRCC than in healthy kidneys, unlike in other tumor types.

A prospective longitudinal approach to examine the association between social position in childhood, adolescence, and adulthood with the control of hypertension during adulthood.

Introduction: Hypertension is one of the main concerns in public health, since it is related with increased morbidity, and potential years of life lost in addition to loss of quality of life. This study aimed to assess: (1) the distribution of indicators of life course SEP in a cohort of Colombian patients with hypertension and (2) to assess the association of life course SEP and control of hypertension among this cohort of patients.

Methods: Data were obtained using the baseline survey of 258 patients from the Social Determinants and Inequities in the Control of Blood Hypertension Program (ProDSICHA).

Effects and mechanisms of mindfulness training and physical exercise on cognition, emotional wellbeing, and brain outcomes in chronic stroke patients: Study protocol of the MindFit project randomized controlled trial.

Background: Post-stroke cognitive and emotional complications are frequent in the chronic stages of stroke and have important implications for the functionality and quality of life of those affected and their caregivers. Strategies such as mindfulness meditation, physical exercise (PE), or computerized cognitive training (CCT) may benefit stroke patients by impacting neuroplasticity and brain health.

Materials And Methods: One hundred and forty-one chronic stroke patients are randomly allocated to receive mindfulness-based stress reduction + CCT ( = 47), multicomponent PE program + CCT ( = 47), or CCT alone ( = 47).

Marker-free co-selection for successive rounds of prime editing in human cells.

Prime editing enables the introduction of precise point mutations, small insertions, or short deletions without requiring donor DNA templates. However, efficiency remains a key challenge in a broad range of human cell types. In this work, we design a robust co-selection strategy through coediting of the ubiquitous and essential sodium/potassium pump (Na/K ATPase).

Socioeconomic position and quality of life among Colombian hypertensive patients: The mediating effect of perceived stress.

This study aimed to assess the relationships between socioeconomic position, perceived stress and Health Related Quality of Life (HRQoL) of patients with hypertension. Data were obtained using the baseline survey of 258 patients from the Social Determinants and Inequities in the Control of Blood Hypertension Program (ProDSICHA). HRQoL was measured with SF-8 Health Survey.

Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study.

Background And Objective: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers.

Methods: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals.

The role of stressful life events appraisal in major depressive disorder.

Introduction: Major depressive disorder (MDD) is a multifactorial disease in which, due to the interaction of several variables, the vulnerability of suffering from it increases. Several models, such as the diathesis-stress model, have explained these interactions. However, experiencing stressful events does not always lead to the development of MDD, and the attribution and appraisal of stressful events contributing to further development of depression symptoms has been considered as a possible explanation.

Rewired Cas9s with Minimal Sequence Constraints.

The genome editing toolkit is ever expanding. Although CRISPR-Cas systems can target virtually any gene, single-nucleotide resolution is yet to be achieved. Walton and colleagues engineered nucleases and base editors compatible with every protospacer adjacent motif (PAM) to achieve high-precision targeting.

Versatile and robust genome editing with CRISPR1-Cas9.

Targeting definite genomic locations using CRISPR-Cas systems requires a set of enzymes with unique protospacer adjacent motif (PAM) compatibilities. To expand this repertoire, we engineered nucleases, cytosine base editors, and adenine base editors from the archetypal CRISPR1-Cas9 (St1Cas9) system. We found that St1Cas9 strain variants enable targeting to five distinct A-rich PAMs and provide a structural basis for their specificities.

Cas9 Allosteric Inhibition by the Anti-CRISPR Protein AcrIIA6.

In the arms race against bacteria, bacteriophages have evolved diverse anti-CRISPR proteins (Acrs) that block CRISPR-Cas immunity. Acrs play key roles in the molecular coevolution of bacteria with their predators, use a variety of mechanisms of action, and provide tools to regulate Cas-based genome manipulation. Here, we present structural and functional analyses of AcrIIA6, an Acr from virulent phages, exploring its unique anti-CRISPR action.

Genotoxicity and cytotoxicity of three microcystin-LR containing cyanobacterial samples from Antioquia, Colombia.

The presence of cyanobacterial blooms and cyanotoxins in water presents a global problem due to the deterioration of ecosystems and the possibility of poisoning in human and animals. Microcystin LR is the most widely distributed cyanotoxin and liver cells are its main target. In the present study, HepG2 cells were used to determine DNA damage of three crude extracts of cyanobacterial blooms containing MC-LR, through comet assay.

Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins.

CRISPR-Cas systems are bacterial anti-viral systems, and bacterial viruses (bacteriophages, phages) can carry anti-CRISPR (Acr) proteins to evade that immunity. Acrs can also fine-tune the activity of CRISPR-based genome-editing tools. While Acrs are prevalent in phages capable of lying dormant in a CRISPR-carrying host, their orthologs have been observed only infrequently in virulent phages.

Loading efficacy and binding analysis of retinoids with milk proteins: a short review.

In this review, the loading efficacies of retinoids with milk proteins are investigated. It has been shown that milk proteins β-lactoglobulin, α-, and β-caseins bind retinol and retinoic acid via hydrophobic, hydrophilic, and H-bonding contacts causing minor alterations of protein secondary structure. Hydrophobic contact is predominant in retinoid-protein conjugation and several amino acids are involved in complex formation, stabilized by H-bonding network.

Marker-free coselection for CRISPR-driven genome editing in human cells.

Targeted genome editing enables the creation of bona fide cellular models for biological research and may be applied to human cell-based therapies. Therefore, broadly applicable and versatile methods for increasing its efficacy in cell populations are highly desirable. We designed a simple and robust coselection strategy for enrichment of cells with either nuclease-driven nonhomologous end joining (NHEJ) or homology-directed repair (HDR) events by harnessing the multiplexing capabilities of CRISPR-Cas9 and Cpf1 systems.

Testosterone and its dimers alter tRNA morphology.

The morphology of tRNA was studied upon conjugation with testosterone and its aliphatic and aromatic dimers, using multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling. Structural analysis showed that testosterone binds tRNA through A62, A64, C60, C61, C63, G51, U50 and U59 bases. The binding affinity was testosterone dimer-aromatic>testosterone dimer-aliphatic>testosterone.

Effect of testosterone and its aliphatic and aromatic dimers on DNA morphology.

Conjugation of DNA with testosterone and it aliphatic dimer (alip) and aromatic dimer (arom) was investigated in aqueous solution at pH 7.4. Multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were used to characterize steroid-DNA binding and DNA morphology.

Review on the targeted conjugation of anticancer drugs doxorubicin and tamoxifen with synthetic polymers for drug delivery.

In this review, the binding and loading efficacy (LE) of anticancer drugs doxorubicin (DOX), tamoxifen (Tam) and its metabolites 4-hydroxytamoxifen (4-Hydroxytam) and endoxifen (Endox) with several synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3), and polyamidoamine (PAMAM-G4) dendrimers were compared in aqueous solution at pH 7.4. The results of multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling of conjugated drug-polymer were examined.

PEG and mPEG-anthracene conjugate with trypsin and trypsin inhibitor: hydrophobic and hydrophilic contacts.

The conjugation of trypsin (try) and trypsin inhibitor (tryi) with poly(ethylene glycol) (PEG) and methoxypoly(ethylene glycol) anthracene (mPEG-anthracene) was investigated in aqueous solution, using multiple spectroscopic methods, thermodynamic analysis, and molecular modeling. Thermodynamic parameters ΔS, ΔH, and ΔG showed protein-PEG bindings occur via H-bonding and van der Waals contacts with trypsin inhibitor forming more stable conjugate than trypsin. As polymer size increased more stable PEG-protein conjugate formed, while hydrophobic mPEG-anthracene forms less stable protein complexes.

Targeted conjugation of breast anticancer drug tamoxifen and its metabolites with synthetic polymers.

Conjugation of antitumor drug tamoxifen and its metabolites, 4-hydroxytamxifen and ednoxifen with synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3) and polyamidoamine (PAMAM-G4) dendrimers was studied in aqueous solution at pH 7.4. Multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were used to characterize the drug binding process to synthetic polymers.

An overview on the delivery of antitumor drug doxorubicin by carrier proteins.

Serum proteins play an increasing role as drug carriers in the clinical settings. In this review, we have compared the binding modalities of anticancer drug doxorubicin (DOX) to three model carrier proteins, human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (β-LG) in order to determine the potential application of these model proteins in DOX delivery. Molecular modeling studies showed stronger binding of DOX with HSA than BSA and β-LG with the free binding energies of -10.

Review on the binding of anticancer drug doxorubicin with DNA and tRNA: Structural models and antitumor activity.

In this review, we have compared the results of multiple spectroscopic studies and molecular modeling of anticancer drug doxorubicin (DOX) bindings to DNA and tRNA. DOX was intercalated into DNA duplex, while tRNA binding is via major and minor grooves. DOX-DNA intercalation is close to A-7, C-5, *C-19 (H-bonding with DOX NH2 group), G-6, T-8 and T-18 with the free binding energy of -4.

tRNA conjugation with chitosan nanoparticles: An AFM imaging study.

The conjugation of tRNA with chitosan nanoparticles of different sizes 15,100 and 200 kDa was investigated in aqueous solution using multiple spectroscopic methods and atomic force microscopy (AFM). Structural analysis showed that chitosan binds tRNA via G-C and A-U base pairs as well as backbone PO2 group, through electrostatic, hydrophilic and H-bonding contacts with overall binding constants of KCh-15-tRNA=4.1 (±0.

Microscopic and spectroscopic analysis of chitosan-DNA conjugates.

Conjugations of DNA with chitosans 15 kD (ch-15), 100 kD (ch-100) and 200 kD (ch-200) were investigated in aqueous solution at pH 5.5-6.5.