The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters.

L-Amino acid transporters (LATs) play a key role in a wide range of physiological processes. Defects in LATs can lead to neurological disorders and aminoacidurias, while the overexpression of these transporters is related to cancer. BasC is a bacterial LAT transporter with an APC fold.

Flexibility in PAM Recognition Expands DNA Targeting in xCas9.

xCas9 is an evolved variant of the CRISPR-Cas9 genome editing system, engineered to improve specificity and reduce undesired off-target effects. How xCas9 expands the DNA targeting capability of Cas9 by recognizing a series of alternative Protospacer Adjacent Motif (PAM) sequences while ignoring others is unknown. Here, we elucidate the molecular mechanism underlying xCas9's expanded PAM recognition and provide critical insights for expanding DNA targeting.

Diagnostic Efficacy of Bone SPECT Techniques in Differentiating Unilateral and Bilateral Condylar Hyperplasia.

This analytical cross-sectional study evaluates diagnostic approaches for active condylar hyperplasia using bone SPECT techniques. : it was compared the effectiveness of relative activity assessments between condyles and quantitative analysis using the condyle/clivus ratio. : This study's findings reveal that the condyle/clivus ratio method significantly outperforms the relative uptake method, achieving a sensitivity of 90.

A putative new species in the southern black-eared opossum .

spp. are cyst-forming coccidian parasites with a broad host range, infecting various wild and domestic animal species. Northamerican opossums () are severely affected by the infection with .

SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis.

SETD8 is a methyltransferase that is overexpressed in several cancers, which monomethylates H4K20 as well as other non-histone targets such as PCNA or p53. We here report novel SETD8 inhibitors, which were discovered while trying to identify chemicals that prevent 53BP1 foci formation, an event mediated by H4K20 methylation. Consistent with previous reports, SETD8 inhibitors induce p53 expression, although they are equally toxic for p53 proficient or deficient cells.

Quality of Life is an Independent Predictor of Mortality in Patients with Heart Failure: A Prospective Cohort Study from the Colombian Heart Failure Registry (RECOLFACA).

Aim: Patients with Heart Failure (HF) commonly have poor quality of life (QoL), secondary to the persistence and severity of HF symptoms. We aimed to evaluate the prognostic value of QoL measures on all-cause mortality in patients with HF from the Colombian registry of heart failure (RECOLFACA).

Methods And Results: We analyzed data from patients registered in RECOLFACA during 2017-2019.

An integrated machine-learning model to predict nucleosome architecture.

We demonstrate that nucleosomes placed in the gene body can be accurately located from signal decay theory assuming two emitters located at the beginning and at the end of genes. These generated wave signals can be in phase (leading to well defined nucleosome arrays) or in antiphase (leading to fuzzy nucleosome architectures). We found that the first (+1) and the last (-last) nucleosomes are contiguous to regions signaled by transcription factor binding sites and unusual DNA physical properties that hinder nucleosome wrapping.

Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange.

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.

MD-DATA: the legacy of the ABC Consortium.

The ABC Consortium has been generating nucleic-acids MD trajectories for more than 20 years. This brief comment highlights the importance of this data for the field, which triggered a number of critical studies, including force-field parameterization and development of new coarse-grained and mesoscopic models. With the world entering into a new data-driven era led by artificial intelligence, where data is becoming more essential than ever, the ABC initiative is leading the way for nucleic acid flexibility.

Special issue: Multiscale simulations of DNA from electrons to nucleosomes.

This editorial for Volume 16, Issue 3 of highlights the three-dimensional structural and dynamic information encoded in DNA sequences and introduces the topics covered in this special issue of the journal on Multiscale Simulations of DNA from Electrons to Nucleosomes. is the official journal of the International Union for Pure and Applied Biophysics (IUPAB 2024). The international scope of the articles in the issue exemplifies the goals of IUPAB to organize worldwide advancements, co-operation, communication, and education in biophysics.

Molecular Detection of Anaplasma marginale in Capybara (Hydrochoerus hydrochaeris) from Corrientes, Argentina.

Monitoring wildlife health is essential for understanding global disease patterns, particularly as vector-borne infections extend the geographic ranges and thereby hosts due to environmental shifts. Anaplasma marginale, primarily impacting cattle, has economic implications and has been found in diverse hosts, yet its presence in capybaras (Hydrochoerus hydrochaeris), influential in tick-borne pathogen spread, lacks comprehensive understanding. From 2015 to 2022, 14 capybaras were surveyed across two different areas of northeastern Argentina.

Using interactive Jupyter Notebooks and BioConda for FAIR and reproducible biomolecular simulation workflows.

Interactive Jupyter Notebooks in combination with Conda environments can be used to generate FAIR (Findable, Accessible, Interoperable and Reusable/Reproducible) biomolecular simulation workflows. The interactive programming code accompanied by documentation and the possibility to inspect intermediate results with versatile graphical charts and data visualization is very helpful, especially in iterative processes, where parameters might be adjusted to a particular system of interest. This work presents a collection of FAIR notebooks covering various areas of the biomolecular simulation field, such as molecular dynamics (MD), protein-ligand docking, molecular checking/modeling, molecular interactions, and free energy perturbations.

Formation of left-handed helices by C2'-fluorinated nucleic acids under physiological salt conditions.

Recent findings in cell biology have rekindled interest in Z-DNA, the left-handed helical form of DNA. We report here that two minimally modified nucleosides, 2'F-araC and 2'F-riboG, induce the formation of the Z-form under low ionic strength. We show that oligomers entirely made of these two nucleosides exclusively produce left-handed duplexes that bind to the Zα domain of ADAR1.

CGeNArate: a sequence-dependent coarse-grained model of DNA for accurate atomistic MD simulations of kb-long duplexes.

We present CGeNArate, a new model for molecular dynamics simulations of very long segments of B-DNA in the context of biotechnological or chromatin studies. The developed method uses a coarse-grained Hamiltonian with trajectories that are back-mapped to the atomistic resolution level with extreme accuracy by means of Machine Learning Approaches. The method is sequence-dependent and reproduces very well not only local, but also global physical properties of DNA.

Nucleic acids in modern molecular therapies: A realm of opportunities for strategic drug design.

RNA vaccines have made evident to society what was already known by the scientific community: nucleic acids will be the "drugs of the future." By modifying the genome, interfering in transcription or translation, and by introducing new catalysts into the cell or by mimicking antibody effects, nucleic acids can generate therapeutic activities that are not accessible by any other therapeutic agents. There are, however, challenges that need to be solved in the next few years to make nucleic acids usable in a wide range of therapeutic scenarios.

Reading tea leaves worldwide: Decoupled drivers of initial litter decomposition mass-loss rate and stabilization.

The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI).

Isolation of Microascus sp. and Cephalotheca sp. from Bats in Argentina.

Bats worldwide play significant roles in ecosystem functions, encompassing pollination, seed dispersal, and pest control while concurrently serving as diseases reservoirs. As part of a comprehensive wildlife health surveillance effort, bats were systematically sampled within two national protected areas in Argentina. During this study 67 bats were examined and samples were collected from eight Molossus spp.

Main role of fractal-like nature of conformational space in subdiffusion in proteins.

Protein dynamics involves a myriad of mechanical movements happening at different time and space scales, which make it highly complex. One of the less understood features of protein dynamics is subdiffusivity, defined as sublinear dependence between displacement and time. Here, we use all-atoms molecular dynamics (MD) simulations to directly interrogate an already well-established theory and demonstrate that subdiffusivity arises from the fractal nature of the network of metastable conformations over which the dynamics, thought of as a diffusion process, takes place.

New pyridine-based chalcones and pyrazolines with anticancer, antibacterial, and antiplasmodial activities.

New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI values from 0.38 to 0.

Molecular stripping underpins derepression of a toxin-antitoxin system.

Transcription factors control gene expression; among these, transcriptional repressors must liberate the promoter for derepression to occur. Toxin-antitoxin (TA) modules are bacterial elements that autoregulate their transcription by binding the promoter in a T:A ratio-dependent manner, known as conditional cooperativity. The molecular basis of how excess toxin triggers derepression has remained elusive, largely because monitoring the rearrangement of promoter-repressor complexes, which underpin derepression, is challenging.

Experiences of Aging with Opioid Use Disorder and Comorbidity in Opioid Treatment Programs: A Qualitative Analysis.

Background: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined.

Objective: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs.

The Rhodium Analogue of Coenzyme B as an Anti-Photoregulatory Ligand Inhibiting Bacterial CarH Photoreceptors.

Coenzyme B (AdoCbl; 5'-deoxy-5'-adenosylcobalamin), the quintessential biological organometallic radical catalyst, has a formerly unanticipated, yet extensive, role in photoregulation in bacteria. The light-responsive cobalt-corrin AdoCbl performs this nonenzymatic role by facilitating the assembly of CarH photoreceptors into DNA-binding tetramers in the dark, suppressing gene expression. Conversely, exposure to light triggers the decomposition of this AdoCbl-bound complex by a still elusive photochemical mechanism, activating gene expression.

Site-specific incorporation of a fluorescent nucleobase analog enhances i-motif stability and allows monitoring of i-motif folding inside cells.

The i-motif is an intriguing non-canonical DNA structure, whose role in the cell is still controversial. Development of methods to study i-motif formation under physiological conditions in living cells is necessary to study its potential biological functions. The cytosine analog 1,3-diaza-2-oxophenoxazine (tCO) is a fluorescent nucleobase able to form either hemiprotonated base pairs with cytosine residues, or neutral base pairs with guanines.