Foxm1 regulates cardiomyocyte proliferation in adult zebrafish after cardiac injury.

The regenerative capacity of the mammalian heart is poor, with one potential reason being that adult cardiomyocytes cannot proliferate at sufficient levels to replace lost tissue. During development and neonatal stages, cardiomyocytes can successfully divide under injury conditions; however, as these cells mature their ability to proliferate is lost. Therefore, understanding the regulatory programs that can induce post-mitotic cardiomyocytes into a proliferative state is essential to enhance cardiac regeneration. Here, we report that the forkhead transcription factor Foxm1 is required for cardiomyocyte proliferation after injury through transcriptional regulation of cell cycle genes. Transcriptomic analysis of injured zebrafish hearts revealed that foxm1 expression is increased in border zone cardiomyocytes. Decreased cardiomyocyte proliferation and expression of cell cycle genes in foxm1 mutant hearts was observed, suggesting it is required for cell cycle checkpoints. Subsequent analysis of a candidate Foxm1 target gene, cenpf, revealed that this microtubule and kinetochore binding protein is also required for cardiac regeneration. Moreover, cenpf mutants show increased cardiomyocyte binucleation. Thus, foxm1 and cenpf are required for cardiomyocytes to complete mitosis during zebrafish cardiac regeneration.

"Hydridic Hydrogen-Bond Donors" Are Not Hydrogen-Bond Donors.

Herein, we dismiss a recent proposal by Civis, Hobza, and co-workers to modify the IUPAC definition of hydrogen bonds in order to expand the scope from protonic Y-Hδ+ to hydridic Y-Hδ- hydrogen-bond donor fragments [J. Am. Chem. Soc. 2023, 145, 8550]. Based on accurate Kohn-Sham molecular orbital (KS-MO) analyses, we falsify the conclusion that interactions involving protonic and hydridic hydrogens are both hydrogen bonds; they are not. Instead, our quantitative KS-MO, energy decomposition, and Voronoi deformation density analyses reveal two fundamentally different bonding mechanisms for protonic Y-Hδ+ and hydridic Y-Hδ- fragments which go with charge transfer in opposite directions. On one hand, we confirm the IUPAC definition for regular hydrogen bonds in the case of protonic Y-Hδ+ fragments. On the other hand, complexes involving Y-Hδ- fragments are, in fact, acceptors in other well-known families of Lewis-acid/base interactions, such as halogen bonds, chalcogen bonds, and pnictogen bonds. These mechanisms lead to the same spectroscopic phenomenon in both the Y-Hδ+ and Y-Hδ- fragments, that is, the redshift in the Y-H stretching frequency, which is, thus, not an exclusive indicator for hydrogen bonding.

Stabilization of Diborynes versus Destabilization of Diborenes by Coordination of Lewis Bases: Unravelling the Dichotomy.

We have quantum chemically investigated the boron-boron bonds in B2 , diborynes B2 L2 , and diborenes B2 H2 L2 (L=none, OH2 , NH3 ) using dispersion-corrected relativistic density functional theory at ZORA-BLYP-D3(BJ)/TZ2P. B2 has effectively a single B-B bond provided by two half π bonds, whereas B2 H2 has effectively a double B=B bond provided by two half π bonds and one σ 2p-2p bond. This different electronic structure causes B2 and B2 H2 to react differently to the addition of ligands. Thus, in B2 L2 , electron-donating ligands shorten and strengthen the boron-boron bond whereas, in B2 H2 L2 , they lengthen and weaken the boron-boron bond. The aforementioned variations in boron-boron bond length and strength become more pronounced as the Lewis basicity of the ligands L increases.

Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion.

We have quantum chemically investigated the origin of the atypical blueshift of the H-C bond stretching frequency in the hydrogen-bonded complex X- •••H3 C-Y (X, Y=F, Cl, Br, I), as compared to the corresponding redshift occurring in Cl- •••H3 N and Cl- •••H3 C-H, using relativistic density functional theory (DFT) at ZORA-BLYP-D3(BJ)/QZ4P. Previously, this blueshift was attributed, among others, to the contraction of the H-C bonds as the H3 C moiety becomes less pyramidal. Herein, we provide quantitative evidence that, instead, the blueshift arises from a direct and strong X- •••C interaction of the HOMO of A- with the backside lobe on carbon of the low-lying C-Y antibonding σ* LUMO of the H3 C-Y fragment. This X- •••C bond, in essence a tetrel bond, pushes the H atoms towards a shorter H-C distance and makes the H3 C moiety more planar. The blueshift may, therefore, serve as a diagnostic for tetrel bonding.

Blueshift in Trifurcated Hydrogen Bonds: A Tradeoff between Tetrel Bonding and Steric Repulsion.

The front cover artwork is provided by the TheoCheM group at the Vrije Universiteit Amsterdam. The image shows how, in X- •••H3 C-Y complexes, the Lewis base X- tetrel-binds to the central C while sterically pushing the H atoms towards C; hence, the compression and blueshift of the H-C bonds. Read the full text of the Research Article at 10.1002/cphc.202300480.

Clinical implications of additional chromosomal abnormalities in adult acute myeloid leukemia with inv (16)/t(16;16)/CBFB::MYH11.

OBJECTIVES: This study assesses the clinical significance of additional cytogenetic abnormalities (ACAs) and/or the deletion of 3'CBFB (3'CBFBdel) resulting in unbalanced CBFB::MYH11 fusion in acute myeloid leukemia (AML) with inv (16)/t(16;16)/CBFB::MYH11. METHODS: We retrospectively evaluated the clinicopathologic features of 47 adult de novo AML with inv (16)/t(16;16)/CBFB::MYH11 fusion. There were 44 balanced and 3 unbalanced CBFB::MYH11 fusions. Given the low frequency of unbalanced cases, the latter group was combined with 19 published cases (N = 22) for statistic and meta-analysis. RESULTS: Both balanced and unbalanced cases were characterized by frequent ACAs (56.5% and 72.7%, respectively), with +8, +22, and del(7q) as the most frequent abnormalities. The unbalanced group tends to be younger individuals (p = .04) and is associated with a lower remission rate (p = .02), although the median overall survival (OS) was not statistically different (p = .2868). In the balanced group, "ACA" subgroup had higher mortality (p = .013) and shorter OS (p = .011), and patients with relapsed disease had a significantly shorter OS (p = .0011). Cox multivariate regression analysis confirmed that ACAs and history of disease relapse are independent risk factors, irrespective of disease relapse status. In the combined cohort, cases with ACAs had shorter OS than those with "Sole" abnormality (p = .0109). CONCLUSIONS: ACAs are independent high-risk factors in adult AML with inv (16)/t(16;16)/CBFB::MYH11 fusion and should be integrated for risk stratification in this disease. Larger studies are needed to assess the clinical significance of the unbalanced CBFB::MYH11 fusion resulting from the 3'CBFBdel.

Multiple hydrogen-bonded dimers: are only the frontier atoms relevant?

Non-frontier atom exchanges in hydrogen-bonded aromatic dimers can induce significant interaction energy changes (up to 6.5 kcal mol-1). Our quantum-chemical analyses reveal that the relative hydrogen-bond strengths of N-edited guanine-cytosine base pair isosteres, which cannot be explained from the frontier atoms, follow from the charge accumulation in the monomers.

The nature of metallophilic interactions in closed-shell d8-d8 metal complexes.

We have quantum chemically analyzed the closed-shell d8-d8 metallophilic interaction in dimers of square planar [M(CO)2X2] complexes (M = Ni, Pd, Pt; X = Cl, Br, I) using dispersion-corrected density functional theory at ZORA-BLYP-D3(BJ)/TZ2P level of theory. Our purpose is to reveal the nature of the [X2(CO)2M]⋯[M(CO)2X2] bonding mechanism by analyzing trends upon variations in M and X. Our analyses reveal that the formation of the [M(CO)2X2]2 dimers is favored by an increasingly stabilizing electrostatic interaction when the M increases in size and by more stabilizing dispersion interactions promoted by the larger X. In addition, there is an overlooked covalent component stemming from metal-metal and ligand-ligand donor-acceptor interactions. Thus, at variance with the currently accepted picture, the d8-d8 metallophilicity is attractive, and the formation of [M(CO)2X2]2 dimers is not a purely dispersion-driven phenomenon.

Blood levels of 21 metals and metalloids in riverside villagers of the Brazilian Amazon: A human biomonitoring study with associations with sociodemographic, dietary, and lifestyle factors.

Human biomonitoring of toxic and essential trace elements is critically important for public health protection. Amazonian riverine communities exhibit distinctive dietary patterns, heavily reliant on locally sourced fish, fruits, and vegetables. These habits may result in unique exposure profiles compared to urban populations. However, comprehensive assessments of their exposure to toxic and essential metals are lacking, representing a critical gap in understanding the health risks faced by these communities. This study aimed to establish baseline levels of 21 metals and metalloids in human blood and explore the influence of sociodemographic factors, dietary habits, and lifestyle choices as potential sources of exposure to these elements. A cross-sectional biomonitoring investigation was conducted with 1,024 individuals from 13 communities in the Tapajós and Amazon Basins (Pará, Brazil). Most of the elements in study was determined for the first time in the region. Blood samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The levels of all elements were summarized by quantiles and compared with cutoff values from other Brazilian populations. Multiple linear regression was used to assess possible associations between element concentrations and sociodemographic characteristics, dietary habits, and lifestyle choices. High detection rates (64%-100%) were observed, indicating the widespread presence of these elements. Elevated blood concentrations were found for mercury (median 21.1 µg.L-1, interquartile range: 12-34 µg.L-1), selenium (median 166 µg.L-1, interquartile range: 137-208 µg.L-1), and lead (median 34 µg.L-1, interquartile range: 20.8-64 µg.L-1). Regression analysis revealed a positive association between mercury levels and fish consumption, while manioc flour intake showed no relationship to lead levels. In conclusion, our findings emphasize the need for continued monitoring and public policy development for these vulnerable populations. Further studies should assess long-term trends and investigate the health implications of prolonged exposure to diverse chemicals in Amazonian riverside communities.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients.

BACKGROUND: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight. RESULTS: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56+CD16-) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56+CD16+), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4+CD38+ cells than controls. Contrasting changes were reported in CD25+CD127low/neg regulatory T cells, with increased and decreased proportions found in CD4+ and CD8+ T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4+ and CD8+) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8+CD57+NKG2A+ cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19. CONCLUSIONS: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.

Anatomy of the posterior Fossa: a comprehensive description for pediatric brain tumors.

Posterior fossa tumors are the most common pediatric brain tumors, and present unique challenges in terms of their location and surgical management. The posterior fossa comprehends complex anatomy and represents the smallest and deepest of the three cranial base fossae. An in-depth understanding of posterior fossa anatomy is crucial when it comes to the surgical resection of pediatric brain tumors. Mastering the knowledge of posterior fossa anatomy helps the neurosurgeon in achieving a maximal and safe volumetric resection, that impacts in both overall and progression free survival. With the advancements in microsurgery, the telovelar approach has emerged as the workhorse technique for the resection of posterior fossa tumors in pediatric patients. This approach involves meticulously dissecting of the natural clefts present in the cerebellomedullary fissure, making a comprehensive understanding of the underlying anatomy key for its success.

Doing more with less: surgical results of pediatric posterior fossa tumors from a single center in Latin America.

OBJECTIVE: We aim to report the epidemiology, surgical outcomes, and survival rates of pediatric patients with posterior fossa tumors in a large single-center case series. METHODS: A retrospective analysis was conducted on pediatric patients who underwent surgical treatment for posterior fossa tumors between January 2011 and January 2019. RESULTS: A total of 135 pediatric patients, with an average age of 7.5 years at diagnosis and a mean follow-up of 35.7 months, were included in the study. Most tumors were located within the midline, with ventriculomegaly observed in 71.4% of the patients. Pilocytic astrocytomas encompassed the majority of tumors (34.1%), followed by medulloblastomas (27.4%) and ependymomas (11.8%). Gross total resection (GTR) was achieved in 71.8% of the patients, with a recurrence rate of 20%. Surgical complications were observed in 25.9% of the patients. GTR significantly impacted 5-year overall survival (OS) and 4-year progression-free survival (PFS) in patients with posterior fossa tumors. Patients who underwent GTR had a 5-year OS of 89.7%, compared to 72.7% for near-total resection and 70.8% for subtotal resection. The 4-year PFS for patients who underwent GTR was 82.5%, whereas it was 63.6% for patients who underwent near-total resection and 54.2% for patients who underwent subtotal resection. CONCLUSION: Surgical resection remains the main treatment for pediatric posterior fossa tumors, and higher resection rates are linked to better survival outcomes. Despite limited resources for molecular diagnosis, our institution has demonstrated that a specialized neurooncological center with a high surgical volume can still achieve favorable survival outcomes for these patients.

Impacts of bycatch from beach seining: a case study of a shrimp fishery in Brazil.

It is commonly assumed that beach seining (BS) is more sustainable than bottom trawling because it involves non-motorized operations and limited fishing power. However, no scientific evidence supports this assumption. To address this gap, we evaluated the impact of beach seining, taking a small-scale shrimp fishery in northeast Brazil. Data collected monthly from December 2016 to November 2017 and in literature, were assessed (BS 31,001 individuals, 119 species, 37 families, and 19 orders; BT 6,031 individuals, 58 species, 20 families, and 14 orders). Beach seining demonstrated a lower proportion of bycatch (BS 1:2.3; BT 1:3.2), higher total shrimp catch (BS 87.2 t; BT 65 t), and greater species diversity than bottom trawling catches (BS 119; BT 58). Other aspects were closer associated with bottom trawling, such as the composition of dominant families (Sciaenidae and Pristigasteridae), the proportion of rare species (BS 30%; BT 24%) juveniles (BS 11g; BT 13g), the risk of species extinction, and the composition of ecological guilds. Despite their social significance, both fishing gears showed similar ecological indicators and adverse effects. The findings establish that the ecological concerns related to the impact of bottom trawling are also applicable to beach seine.

Experimental Tests on External and Terminal Ballistics of Different Types of Projectiles Fired From .38 SPL Caliber Cartridges and Study of Permanent Cavitation in Anatomical Modeling With 10% Ballistic Gelatin.

ABSTRACT: The present study investigated the main morphological differences between the permanent cavities formed by 4 different types of projectiles fired from .38 SPL caliber cartridges in blocks of 10% ballistic gelatin with standardized formulation (Federal Bureau of Investigation Protocol), all fired from the same distance and from the same firearm, associated with its performances in external and terminal ballistics. The velocity or the mass presented by a firearm projectile will not always be solely responsible for the final configuration of the permanent cavity, in which the projectile design, for example, is an equally important element. Each type of projectile tested in the present work generated a different kind of permanent cavity, but they also varied in velocity (m/s) and energy (J). The use of 10% ballistic gelatin in scientific research that seeks to investigate the external and terminal ballistics of projectiles can contribute to the practice of professionals working either in forensic pathology or applied ballistics scenarios, as they can experimentally simulate the events that can occur in the tissues of victims inflicted by gunshot wounds, which also allows important applications in the medical, commercial, civil, and military sectors that deal with products and technologies related to the human body.

Independent Vector Analysis for Feature Extraction in Motor Imagery Classification.

Independent vector analysis (IVA) can be viewed as an extension of independent component analysis (ICA) to multiple datasets. It exploits the statistical dependency between different datasets through mutual information. In the context of motor imagery classification based on electroencephalogram (EEG) signals for the brain-computer interface (BCI), several methods have been proposed to extract features efficiently, mainly based on common spatial patterns, filter banks, and deep learning. However, most methods use only one dataset at a time, which may not be sufficient for dealing with a multi-source retrieving problem in certain scenarios. From this perspective, this paper proposes an original approach for feature extraction through multiple datasets based on IVA to improve the classification of EEG-based motor imagery movements. The IVA components were used as features to classify imagined movements using consolidated classifiers (support vector machines and K-nearest neighbors) and deep classifiers (EEGNet and EEGInception). The results show an interesting performance concerning the clustering of MI-based BCI patients, and the proposed method reached an average accuracy of 86.7%.

Unveiling the reproductive and migrative behavior of Trichiurus lepturus in a tropical environment: Insights and implications.

This study aimed to understand the reproductive biology and migrative behavior of the largehead hairtail Trichiurus lepturus in a tropical area, specifically off Pernambuco coast, northeastern Brazil. Commercial catches from fish corrals provided samples for analysis, including measurements, weight recording, and examination of gonads to determine its maturation stage. Reproductive analyses were performed, such as sex ratio, gonado-somatic index, and sizes at first maturity. There was a slightly higher proportion of females among the 141 largehead hairtail specimens analysed. No significant differences were observed in length distributions between males and females. However, during the winter, significant differences were observed in length distributions for grouped sexes. The species exhibited a seasonal migratory pattern, with a higher presence on the continental shelf during the winter. The study identified strategic allocation of energy in feeding activities and temporal spacing of reproductive cycles, as indicated by the sex ratio and abundance of individuals during different seasons. Fish corrals probably do not harm largehead hairtail population off the southwestern Atlantic tropical coast, with minimal capture of individuals below the size of first maturity. The insights of the study into reproductive and migration patterns contribute to future assessments and management strategies for this species and corral fisheries.

An equatorial mid-Atlantic Ocean archipelago as nursery area for the cookiecutter shark: Investigating foraging strategies of neonates through bite mark inferences.

This study delves into the foraging ecology of the cookiecutter shark (Isistius brasiliensis) in the Saint Peter and Saint Paul Archipelago (SPSPA), assessing bite marks on pelagic fishes collected between March and September 2018. Examination of 200 individuals from five species revealed the shark's predilection for targeting adult fish, ensuring efficient removal of energy-rich tissue layers. However, a notable exception is Thunnus albacares, preyed on predominantly during its juvenile stage, possibly due to vertical spatial segregation. Recent bites were pervasive across species, with wahoo displaying a distinctive pattern. Cookiecutter shark bites predominantly targeted the lateral body portion (>55%) except for yellowfin tuna, which exhibited a preference for the ventral region (95%). The estimated length distribution suggests the SPSPA as a potential nursery area for cookiecutter sharks. Bite mark positions and frequencies may be linked to fish behavior, swimming velocity, and fishing gear strategy, highlighting the complex interplay in pelagic ecosystems.

Experimental and Computational Analysis of Synthesis Conditions of Hybrid Nanoflowers for Lipase Immobilization.

This work presents a framework for evaluating hybrid nanoflowers using Burkholderia cepacia lipase. It was expanded on previous findings by testing lipase hybrid nanoflowers (hNF-lipase) formation over a wide range of pH values (5-9) and buffer concentrations (10-100 mM). The free enzyme activity was compared with that of hNF-lipase. The analysis, performed by molecular docking, described the effect of lipase interaction with copper ions. The morphological characterization of hNF-lipase was performed using scanning electron microscopy. Fourier Transform Infrared Spectroscopy performed the physical-chemical characterization. The results show that all hNF-lipase activity presented values higher than that of the free enzyme. Activity is higher at pH 7.4 and has the highest buffer concentration of 100 mM. Molecular docking analysis has been used to understand the effect of enzyme protonation on hNF-lipase formation and identify the main the main binding sites of the enzyme with copper ions. The hNF-lipase nanostructures show the shape of flowers in their micrographs from pH 6 to 8. The spectra of the nanoflowers present peaks typical of the amide regions I and II, current in lipase, and areas with P-O vibrations, confirming the presence of the phosphate group. Therefore, hNF-lipase is an efficient biocatalyst with increased catalytic activity, good nanostructure formation, and improved stability.

Emergence of carbapenem-resistant Klebsiella pneumoniae species complex from agrifood systems: detection of ST6326 co-producing KPC-2 and NDM-1.

BACKGROUND: Klebsiella pneumoniae species complex (KpSC) is an important disseminator of carbapenemase-encoding genes, mainly blaKPC-2 and blaNDM-1, from hospitals to the environment. Consequently, carbapenem-resistant strains can be spread through the agrifood system, raising concerns about food safety. This study therefore aimed to isolate carbapenem-resistant KpSC strains from the agricultural and environmental sectors and characterize them using phenotypic, molecular, and genomic analyses. RESULTS: Klebsiella pneumoniae and Klebsiella quasipneumoniae strains isolated from soils used for lemon, guava, and fig cultivation, and from surface waters, displayed an extensive drug-resistance profile and carried blaKPC-2, blaNDM-1, or both. In addition to carbapenemase-encoding genes, KpSC strains harbor a broad resistome (antimicrobial resistance and metal tolerance) and present putative hypervirulence. Soil-derived K. pneumoniae strains were assigned as high-risk clones (ST11 and ST307) and harbored the blaKPC-2 gene associated with Tn4401b and Tn3-like elements on IncN-pST15 and IncX5 plasmids. In surface waters, the coexistence of blaKPC-2 and blaNDM-1 genes was identified in K. pneumoniae ST6326, a new carbapenem-resistant regional Brazilian clone. In this case, blaKPC-2 with Tn4401a isoform and blaNDM-1 associated with a Tn125-like transposon were located on different plasmids. Klebsiella quasipneumoniae ST526 also presented the blaNDM-1 gene associated with a Tn3000 transposon on an IncX3 plasmid. CONCLUSION: These findings provide a warning regarding the transmission of carbapenemase-positive KpSC across the agricultural and environmental sectors, raising critical food safety and environmental issues. © 2024 Society of Chemical Industry.