Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus.

AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4-/- mice (KO) due to stenosis of Silvio's aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4-/- mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.

Characterization of medium and small-scale gold processing operations, wastewaters, and tailings in the Arequipa region of Peru.

Gold cyanidation facilities in the Arequipa Region of Peru are challenged by the availability and quality of water for processing in an arid environment. The facilities reuse decant water which recycles residual cyanide but also undesirable constituents. To understand the impact of intensive water recycling on cyanide and metals concentrations, we collected barren water, decant water, and tailings samples from six gold cyanidation facilities with ore capacities of 10-430 tons per day. Processing facilities in Arequipa recycle all effluents, with decant waters making up 58 ± 11 % of process waters. Decant water contained non-target metals: copper (394 ± 161 mg/L), iron (59 ± 34 mg/L), and zinc (74 ± 42 mg/L). In addition, decant water mean free and complexed cyanide concentrations were 534 ± 129 mg/L and 805 ± 297 mg/L, respectively. Complexed cyanide concentrations remained more constant than free cyanide concentrations with 786 ± 299 mg/L for barren water and 805 ± 297 mg/L for decant water. Cyanide mass balances showed between 21 % and 42 % of unaccounted free cyanide from the start of gold cyanidation and discharge to the tailings storage facility (TSF). Free cyanide estimated losses due to volatilization were 0.8 kg and 2.5 kg of hydrogen cyanide per ton of ore processed at barren water pH of 10.1 and 9.7. Together these results indicate two acute hazards: 1) volatilization of free cyanide during processing and 2) loading and retention of cyanides and metals into TSFs. This study elucidates the extent of uncontrolled vapor phase cyanide release during gold processing operation and contaminant concentrations in the tailings storage facilities. The data highlights the need for improvement oversight, accountability, and regulation of gold processing facilities practicing intensive recycling and zero discharge.

Seasonal changes in body composition in children from Maya agriculturalists in central Yucatán, Mexico.

INTRODUCTION: Development policies have aimed to substitute subsistence agriculture for cash crops or other cash generating activities to encourage local farmers to depend on store-bought groceries available year-round instead of seasonal subsistence crops. In this paper, we test the hypothesis that increased dependence on store bought foods has decreased seasonal changes in nutritional status and fat mass in Maya Children from Yucatan, Mexico. METHODS: Weight for age (W/A), body mass index (BMI), and tricipital Skinfold z scores in children under the age of 10 years from 14 Maya rural towns with different degrees of development were compared longitudinally between scarcity and abundance seasons using a repeated measures analysis of variance. Height for age (H/A) z scores were also estimated. RESULTS: Origin of food consumed corresponded to the town's degree of development. Nutritional status (W/Az) and adiposity, BMI, and tricipital z scores were significantly lower during the scarcity season in every community. W/Az, tricipital skinfold z, and H/Az scores were significantly higher in developed than in traditional towns, yet in both types of town W/Az and H/Az scores were below the WHO standard mean. Tricipital skinfold z score was only below the WHO standard amongst traditional towns during the scarcity season. CONCLUSIONS: Increased dependence on store foods failed to eliminate significant losses in body fat during the scarcity season. This failure may be affecting linear growth and promoting a thrifty phenotype that is seen in short and stocky individuals with a tendency to accumulate fat during abundance seasons.

Synergistic Activity of DNA Damage Response Inhibitors in Combination with Radium-223 in Prostate Cancer.

Radium-223 (223Ra) and Lutetium-177-labelled-PSMA-617 (177Lu-PSMA) are currently the only radiopharmaceutical treatments to prolong survival for patients with metastatic-castration-resistant prostate cancer (mCRPC); however, mCRPC remains an aggressive disease. Recent clinical evidence suggests patients with mutations in DNA repair genes associated with homologous recombination have a greater clinical benefit from 223Ra. In this study, we aimed to determine the utility of combining DNA damage response (DDR) inhibitors to increase the therapeutic efficacy of X-rays, or 223Ra. Radiobiological responses were characterised by in vitro assessment of clonogenic survival, repair of double strand breaks, cell cycle distribution, and apoptosis via PARP-1 cleavage. Here, we show that DDR inhibitors increase the therapeutic efficacy of both radiation qualities examined, which is associated with greater levels of residual DNA damage. Co-treatment of ATM or PARP inhibition with 223Ra increased cell cycle arrest in the G2/M phase. In comparison, combined ATR inhibition and radiation qualities caused G2/M checkpoint abrogation. Additionally, greater levels of apoptosis were observed after the combination of DDR inhibitors with 223Ra. This study identified the ATR inhibitor as the most synergistic inhibitor for both radiation qualities, supporting further pre-clinical evaluation of DDR inhibitors in combination with 223Ra for the treatment of prostate cancer.

Interactions with humans reduce the success of foraging for anthropogenic food by capuchin monkeys (Sapajus libidinosus) in Brasília National Park, Brazil.

The progressive growth of urban environments has increasingly forced populations of nonhuman primates to coexist with humans in many cities, which has resulted in problems such as behavioral alterations, conflicts with humans, and threats to the health of the monkeys, due to their consumption of anthropogenic foodstuffs. These anthropogenic foods, which are rich in calories, are the principal driver of the proximity between humans and primates, even though the acquisition of these foods tends to be risky for the monkeys and involve a variety of challenges derived from specific features of the urban environment. The present study evaluated the success/risk relationship of foraging for anthropogenic food by tufted capuchins (Sapajus libidinosus) in Brasília National Park. The data were analyzed using a binary logistic regression, with the backward-stepwise Wald method, to investigate the factors related to the foraging success of the capuchins, considering variables such as their sex and age, the type of approach and its context, and interactions with humans. The capuchins were influenced by the anthropogenic context, which affected their foraging strategies and diet. Interactions with humans reduced the success of foraging for anthropogenic foods. Conflicts between humans and the capuchins were common, especially in the context of access to food. The capuchins thus preferred to access feeding resources directly, probably due to the reduced human interference, which resulted in greater foraging success for unattended food brought by park visitors and the raiding of trash cans. Based on the observed behavior patterns, a number of measures can be proposed to mitigate these conflicts. These recommendations include not bringing food into areas frequented by the capuchins, not reacting to approaching animals, and removing all trash generated during a visit. A cleaning team dedicated to the maintenance of the visitation area free of anthropogenic waste is also be recommended.

Trust in leadership and perceptions of justice in fostering employee commitment.

In a period of uncertainty, trust in leadership and perceptions of fairness have emerged as pivotal factors for fostering employee identification and affective commitment. Drawing from authentic leadership theory, this leadership style is identified as a crucial antecedent of affective commitment, examining the mediating role of distributive justice and the moderating role of interactional justice. A quantitative approach was employed, utilizing data from 302 questionnaires completed by Spanish retail workers. For data analysis, SPSS v.25 was used to generate descriptive statistics, while partial least squares structural equation modeling was applied to test the proposed hypotheses. Our findings revealed that authentic leadership is positively associated with the development of affective commitment, with distributive justice acting as a mediating factor between the two. Furthermore, interactional justice negatively moderates the relationship between distributive justice and affective commitment. Contrary to initial expectations, the second moderation, between authentic leadership and affective commitment, was not found to be significant. The research concludes by discussing the practical implications of the results.

Semi-continuous hydrothermal processing of pine sawdust for integrated production of fuels precursors and platform chemicals.

This research reports data for the integrated obtaining of fermentable sugars (FSs), bio-oil (BO), and hydro-char (HC) - all fuel precursors - as well as platform chemicals (PCs - acetic, formic, and levulinic acid, besides furfural, and hydroxymethylfurfural) through semi-continuous hydrothermal processing of sawdust from pine wood. The influence of temperature (260, 300, and 340 °C) and the water-to-biomass ratio (25 and 50 g H2O (g biomass)-1) were the parameters considered to evaluate the mass yields, kinetic profiles, and BO properties. For FSs (and PCs), a detailed analysis considering the kinetic profiles of obtaining cellobiose, glucose, xylose, and arabinose is presented. For the conditions evaluated, a distinct behavior concerning the process parameters was observed, where 7.11 and 9.28 g (100 g biomass)-1 of FSs and PCs were synergistically obtained, respectively, after 30 min, 20 MPa, 260 °C, and 50 g H2O (g biomass)-1. Contextually, 17.59 g (100 g biomass)-1 of BO was obtained at 340 °C and the same water/biomass ratio. FTIR analysis of the BO samples suggested the presence of aldehydes, carboxylic acids, ketones, hydrocarbons, ethers as well as aromatic, alcohols, and nitrogenous compounds. Similar HC yields were achieved among the conditions analyzed, where 24.68 g (100 g biomass)-1 were obtained at 340 °C and 50 g H2O (g biomass)-1 for a higher heating value of 29.14 MJ kg-1 (1.5 times higher than the in natura biomass).

Disputes over provisioned resources are no more intense between groups than within groups in free-ranging Sapajus libidinosus.

Socioecological models predict that disputes between primate groups will be more intense than those within groups, given that the systematic loss of contests over a given resource will restrict the access of all of the members of that group to that resource. Higher levels of aggression are also expected for provisioned resources that have a more lucrative cost:benefit ratio. The levels of aggression in and between two free-ranging tufted capuchin monkey (Sapajus libidinosus) groups in the context of daily provisioning with bananas were evaluated. The aim of a complementary analysis was to identify possible predictors of the frequency of disputes at the site of the provisioned resource. The disputes were recorded using all-events sampling, while the social behaviour of the study groups was recorded by instantaneous scan sampling. The data were analysed using t-test, Mann-Whitney's U, and generalised linear modelling. Between-group disputes were no more intense than within-group events, and did not involve more individuals, or more adult females. The frequency of disputes increased as the number of individuals eating bananas increased. No evidence was found that disputes between groups were any more intense than those within groups. Dominance patterns may have affected these findings, by mediating intergroup disputes. An increase in the number of competitors affected the frequency of disputes at the site of the provisioned resource.

Most DNA repair defects do not modify the relationship between relative biological effectiveness and linear energy transfer in CRISPR-edited cells.

BACKGROUND: Cancer is a highly heterogeneous disease, driven by frequent genetic alterations which have significant effects on radiosensitivity. However, radiotherapy for a given cancer type is typically given with a standard dose determined from population-level trials. As a result, a proportion of patients are under- or over-dosed, reducing the clinical benefit of radiotherapy. Biological optimization would not only allow individual dose prescription but also a more efficient allocation of limited resources, such as proton and carbon ion therapy. Proton and ion radiotherapy offer an advantage over photons due to their elevated Relative Biological Effectiveness (RBE) resulting from their elevated Linear Energy Transfer (LET). Despite significant interest in optimizing LET by tailoring radiotherapy plans, RBE's genetic dependence remains unclear. PURPOSE: The aim of this study is to better define the RBE/LET relationship in a panel of cell lines with different defects in DSB repair pathways, but otherwise identical biological features and genetic background to isolate these effects. METHODS: Normal human cells (RPE1), genetically modified to introduce defects in DNA double-strand break (DSB) repair genes, ATM, BRCA1, DCLRE1C, LIG4, PRKDC and TP53, were used to map the RBE-LET relationship. Cell survival was measured with clonogenic assays after exposure to photons, protons (LET 1 and 12 keV/µm) and alpha particles (129 keV/µm). Gene knockout sensitizer enhancement ratio (SER) values were calculated as the ratio of the mean inactivation dose (MID) of wild-type cells to repair-deficient cells, and RBE values were calculated as the ratio of the MID of X-ray and particle irradiated cells. 53BP1 foci were used to quantify radiation-induced DSBs and their repair following irradiation. RESULTS: Deletion of NHEJ genes had the greatest impact on photon sensitivity (ATM-/- SER = 2.0 and Lig4-/- SER = 1.8), with genes associated with HR having smaller effects (BRCA1-/- SER = 1.2). Wild-type cells showed RBEs of 1.1, 1.3, 5.0 for low- and high-LET protons and alpha particles respectively. SERs for different genes were independent of LET, apart from NHEJ knockouts which proved to be markedly hypersensitive across all tested LETs. Due to this hypersensitivity, the impact of high LET was reduced in cell models lacking the NHEJ repair pathway. HR-defective cells had moderately increased sensitivity across all tested LETs, but, notably, the contribution of HR pathway to survival appeared independent of LET. Analysis of 53BP1 foci shows that NHEJ-defective cells had the least DSB repair capacity after low LET exposure, and no visible repair after high LET exposure. HR-defective cells also had slower repair kinetics, but the impact of HR defects is not as severe as NHEJ defects. CONCLUSIONS: DSB repair defects, particularly in NHEJ, conferred significant radiosensitivity across all LETs. This sensitization appeared independent of LET, suggesting that the contribution of different DNA repair pathways to survival does not depend on radiation quality.

Identification of intergenerational epigenetic inheritance by whole genome DNA methylation analysis in trios.

Genome-wide association studies have identified thousands of loci associated with common diseases and traits. However, a large fraction of heritability remains unexplained. Epigenetic modifications, such as the observed in DNA methylation have been proposed as a mechanism of intergenerational inheritance. To investigate the potential contribution of DNA methylation to the missing heritability, we analysed the methylomes of four healthy trios (two parents and one offspring) using whole genome bisulphite sequencing. Of the 1.5 million CpGs (19%) with over 20% variability between parents in at least one family and compatible with a Mendelian inheritance pattern, only 3488 CpGs (0.2%) lacked correlation with any SNP in the genome, marking them as potential sites for intergenerational epigenetic inheritance. These markers were distributed genome-wide, with some preference to be located in promoters. They displayed a bimodal distribution, being either fully methylated or unmethylated, and were often found at the boundaries of genomic regions with high/low GC content. This analysis provides a starting point for future investigations into the missing heritability of simple and complex traits.

Monkeypox Virus Immune Evasion and Eye Manifestation: Beyond Eyelid Implications.

Monkeypox virus (MPXV), belonging to the Poxviridae family and Orthopoxvirus genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFNγ, CC and CXC chemokines, IL-1ß, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFNα and IFNß. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.

The Repurposing of Non-Peptide Neurokinin-1 Receptor Antagonists as Antitumor Drugs: An Urgent Challenge for Aprepitant.

The substance P (SP)/neurokinin-1 receptor (NK-1R) system is involved in cancer progression. NK-1R, activated by SP, promotes tumor cell proliferation and migration, angiogenesis, the Warburg effect, and the prevention of apoptosis. Tumor cells overexpress NK-1R, which influences their viability. A typical specific anticancer strategy using NK-1R antagonists, irrespective of the tumor type, is possible because these antagonists block all the effects mentioned above mediated by SP on cancer cells. This review will update the information regarding using NK-1R antagonists, particularly Aprepitant, as an anticancer drug. Aprepitant shows a broad-spectrum anticancer effect against many tumor types. Aprepitant alone or in combination therapy with radiotherapy or chemotherapy could reduce the sequelae and increase the cure rate and quality of life of patients with cancer. Current data open the door to new cancer research aimed at antitumor therapeutic strategies using Aprepitant. To achieve this goal, reprofiling the antiemetic Aprepitant as an anticancer drug is urgently needed.

Peptidergic Systems as Antitumor Targets: A Right Direction to Fight Cancer?

Undoubtedly, much progress has been made in treating cancer over the past few years, but unfortunately, 28 [...].

Adiabatic Shortcuts Completion in Quantum Field Theory: Annihilation of Created Particles.

Shortcuts to adiabaticity (STA) are relevant in the context of quantum systems, particularly regarding their control when they are subjected to time-dependent external conditions. In this paper, we investigate the completion of a nonadiabatic evolution into a shortcut to adiabaticity for a quantum field confined within a one-dimensional cavity containing two movable mirrors. Expanding upon our prior research, we characterize the field's state using two Moore functions that enables us to apply reverse engineering techniques in constructing the STA. Regardless of the initial evolution, we achieve a smooth extension of the Moore functions that implements the STA. This extension facilitates the computation of the mirrors' trajectories based on the aforementioned functions. Additionally, we draw attention to the existence of a comparable problem within nonrelativistic quantum mechanics.

Classification system for nanotechnology-enabled health products with both scientific and regulatory application.

The lack of specific regulatory guidelines for nanotechnology-enabled health products (NHPs) is hampering development and patient access to these innovative technologies. Namely, there is an urgent need for harmonized regulatory definitions and classification systems that allow establishing a standardized framework for NHPs regulatory assessment. In this work, a novel classification system for NHPs is proposed. This classification can be applied for sorting nano-based innovations and regulatory guidelines according to the type of NHPs they address. Said methodology combines scientific and regulatory principles and it is based on the following criteria: principal mode of action, chemical composition, medical purpose and nanomanufacturing approach. This classification system could serve as a useful tool to sensor the state of the art of NHPs which is particularly useful for regulators to support strategy development of regulatory guidelines. Additionally, this tool would also allow manufacturers of NHPs to align their development plans with their applicable guidelines and standards and thus fulfill regulators expectations.

Involvement of the Opioid Peptide Family in Cancer Progression.

Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins) in cancer development. Anticancer therapeutic strategies targeting the opioid peptidergic system and the main research lines to be developed regarding the topic reviewed are suggested. There is much to investigate about opioid peptides and cancer: basic information is scarce, incomplete, or absent in many tumors. This knowledge is crucial since promising anticancer strategies could be developed alone or in combination therapies with chemotherapy/radiotherapy.

High-LET radiation induces large amounts of rapidly-repaired sublethal damage.

There is agreement that high-LET radiation has a high Relative Biological Effectiveness (RBE) when delivered as a single treatment, but how it interacts with radiations of different qualities, such as X-rays, is less clear. We sought to clarify these effects by quantifying and modelling responses to X-ray and alpha particle combinations. Cells were exposed to X-rays, alpha particles, or combinations, with different doses and temporal separations. DNA damage was assessed by 53BP1 immunofluorescence, and radiosensitivity assessed using the clonogenic assay. Mechanistic models were then applied to understand trends in repair and survival. 53BP1 foci yields were significantly reduced in alpha particle exposures compared to X-rays, but these foci were slow to repair. Although alpha particles alone showed no inter-track interactions, substantial interactions were seen between X-rays and alpha particles. Mechanistic modelling suggested that sublethal damage (SLD) repair was independent of radiation quality, but that alpha particles generated substantially more sublethal damage than a similar dose of X-rays, [Formula: see text]. This high RBE may lead to unexpected synergies for combinations of different radiation qualities which must be taken into account in treatment design, and the rapid repair of this damage may impact on mechanistic modelling of radiation responses to high LETs.

Transitional dynamics from mercury to cyanide-based processing in artisanal and small-scale gold mining: Social, economic, geochemical, and environmental considerations.

Artisanal and small-scale gold mining (ASGM) is the leading global source of anthropogenic mercury (Hg) release to the environment. Top-down mercury reduction efforts have had limited results, but a bottom-up embrace of cyanide (CN) processing could eventually displace mercury amalgamation for gold recovery. However, ASGM transitions to cyanidation nearly always include an overlap phase, with mercury amalgamation then cyanidation being used sequentially. This paper uses a transdisciplinary approach that combines natural and social sciences to develop a holistic picture of why mercury and cyanide converge in gold processing and potential impacts that may be worse than either practice in isolation. We show that socio-economic factors drive the comingling of mercury and cyanide practices in ASGM as much or more so than technical factors. The resultant Hg-CN complexes have been implicated in increasing the mobility of mercury, compared to elemental mercury used in Hg-only processing. To support future inquiry, we identify key knowledge gaps including the role of Hg-CN complexes in mercury oxidation, transport, and fate, and possible links to mercury methylation. The global extent and increase of mercury and cyanide processing in ASGM underscores the importance of further research. The immediacy of the problem also demands interim policy responses while research advances, though ultimately, the well-documented struggles of mercury reduction efforts in ASGM temper optimism about policy responses to the mercury-cyanide transition.

Seasonal differences in trace metal concentrations in the major rivers of the hyper-arid southwestern Andes basins of Peru.

The southern rivers of Peru originate in the Andes Mountains and flow in a southwestern direction to the Pacific Ocean through one of the most hyper-arid regions of the world. During each sub-equatorial summer from December to February, rains and snow melt in the Andes increase the streamflow in these rivers, even as they pass through the 100 km arid zone to the ocean. This study quantified seasonal dynamics of 34 trace metal elements (TM) and other constituent concentrations in four southern river basins of Peru (Chili-Quilca, Tambo, Camana-Majes-Colca, and Ocoña) during 2019-2020. Consistent with previous studies, we observed that: (1) the river water in the southern basins had relatively high concentrations of B, As, Fe, Al, Mn, P, Pb and Ni, with As the most ubiquitous toxic TM in all the basins, often detected at concentrations surpassing Peruvian and USEPA regulated concentrations; and (2) basins with the most to least toxic TM contamination were the Tambo > Chili-Quilca > Camana-Majes-Colca > Ocoña. Seasonal streamflow strongly influenced the concentrations of twenty TM, with 15 TM (Al, Au, Ba, Cd, Co, Cu, Fe, Gd, Mn, Ni, P, Pb, Ti, Yb and Zr) consistently higher in the wet season, and with As, B, Ge, Li, and Pd higher in the dry season. Our results improve the understanding of seasonal variability and vulnerability in western Andes superficial water sources, which are highly influenced by both local geogenic and anthropogenic conditions. A Spanish translation of this paper is available in the online Supplementary Material.