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Abstract Connexins (Cxs) are fundamental in cell–cell communication, functioning as gap junction channels (GJCs) that facilitate solute exchange between adjacent cells and as hemichannels (HCs) that mediate solute exchange between the cytoplasm and the extracellular environment. Mutations in the GJB1 gene, which encodes Cx32, lead to X-linked Charcot-Marie-Tooth type 1 (CMTX1), a rare hereditary demyelinating disorder of the peripheral nervous system (PNS) without an effective cure or treatment. In Schwann cells, Cx32 HCs are thought to play a role in myelination by enhancing intracellular and intercellular Ca2+ signaling, which is crucial for proper PNS myelination. Single-point mutations (p.S85C, p.D178Y, p.F235C) generate pathological Cx32 HCs characterized by increased permeability (“leaky”) or excessive activity (“hyperactive”). We investigated the effects of abEC1.1-hIgG1, a fully human immunoglobulin G1 (hIgG1) monoclonal antibody, on wild-type (WT) and mutant Cx32D178Y HCs. Using HeLa DH cells conditionally co-expressing Cx and a genetically encoded Ca2+ biosensor (GCaMP6s), we demonstrated that mutant HCs facilitated 58% greater Ca2+ uptake in response to elevated extracellular Ca2+ concentrations ([Ca2+]ex) compared to WT HCs. abEC1.1-hIgG1 dose-dependently inhibited Ca2+ uptake, achieving a 50% inhibitory concentration (EC50) of ~ 10 nM for WT HCs and ~ 80 nM for mutant HCs. Additionally, the antibody suppressed DAPI uptake and ATP release. An atomistic computational model revealed that serine 56 (S56) of the antibody interacts with aspartate 178 (D178) of WT Cx32 HCs, contributing to binding affinity. Despite the p.D178Y mutation weakening this interaction, the antibody maintained binding to the mutant HC epitope at sub-micromolar concentrations. In conclusion, our study shows that abEC1.1-hIgG1 effectively inhibits both WT and mutant Cx32 HCs, highlighting its potential as a therapeutic approach for CMTX1. These findings expand the antibody’s applicability for treating diseases associated with Cx HCs and inform the rational design of next-generation antibodies with enhanced affinity and efficacy against mutant HCs.

Abstract Background The present paper focuses on socio-demographics, clinical variables, and the distance from the infection in predicting the long-term psycho-social consequences of COVID-19. Methods Patients were screened with a cross-sectional design at the Psychological Service of the University Hospital of Verona (Italy) at 3, 6, 12, and 18 months after their SARS-CoV-2 infection. The assessment was part of the Horizon 2020-funded ORCHESTRA Project and included the Hospital Anxiety and Depression Scale (HADS), the Short Form Health Survey 36 (SF-36), the Impact of Event Scale-Revised (IES-R), and ad-hoc questions measuring pre-post COVID-19 changes on psycho-social dimensions (sleep quality, nutrition, level of autonomy, work, social relationships, emotional wellbeing). Results Between June 2021 and June 2023, we evaluated 1317 patients (mean age 56.6 ± 14.8 years; 48% male): 35% at three months, 40% at 6, 20% at 12, and 5% at 18 months after the infection. Thirty-five percent were hospitalized due to COVID-19. Overall, 16% reported some form of clinically significant mental distress following the infection (HADS-TOT), with 13% and 6%, respectively, experiencing anxiety (HADS-Anxiety) and depressive symptoms (HADS-Depression). Four percent testified post-traumatic symptoms. The SF-36 scale revealed that 16% and 17% of subjects had physical or psychological deterioration in quality of life, respectively. The regression analyses showed that females experienced higher levels of anxiety and depression compared to males, along with worse mental and physical quality of life and pre-post infection changes in nearly all the investigated psycho-social dimensions. Younger people felt more anxiety and had a reduced mental quality of life than their older counterparts, who, in turn, had poorer scores in terms of autonomy and physical functioning. Hospitalized patients had lower levels of self-sufficiency, social relationships, and work than non-hospitalized people. The latter were more anxious and reported a lower physical quality of life. Finally, patients evaluated for the first time at 12- and 18 months showed a more significant impairment in mental and physical quality of life than those assessed at three months. Conclusions Our data show that COVID-19 psychological sequelae tend to persist over time, still needing clinical attention and intervention planning, especially for females.

IntroductionThe effect of co-inoculation with plant growth-promoting bacteria on the microbiome of soybean roots was investigated in a field experiment. Soybean plants were inoculated with Bacillus subtilis, Bacillus aryabhattai, Streptomyces sp., and Saccharopolyspora spinosa and compared to a control treatment that received mineral fertilization.MethodsThe yield parameters and endophytic microbiome of soybean roots were evaluated.ResultsNo significant differences in yield were observed among the treatments, suggesting that microbial inoculation can serve as an alternative to mineral fertilization without compromising productivity. Among the most abundant genera, there was a high prevalence of members of the phylum Proteobacteria (21 of the top 25 genera). Overall, the genera of these phyla represented 88.61% of the samples on average. There were also genera in the phyla Bacteroidetes (2/25), Actinobacteria (1/25), and Firmicutes (1/25). The massive presence of Bradyrhizobium, which represented 71.22% of the sequences at the genus level, was remarkable. Bradyrhizobium was the most abundant genus in all samples, except for Saccharopolyspora spinosa (ST treatment), whose abundance was only 12.66%. Co-occurrence network analysis revealed changes in the microbial community structure and genera considered as hubs.DiscussionThese findings demonstrate the potential of co-inoculation with plant growth-promoting bacteria to modulate the root microbiome and enhance the colonization of B. japonicum, which may contribute to improving the efficiency of this symbiont in promoting plant growth. Further research is required to elucidate the mechanisms underlying these interactions and their implications for soybean productivity.

ABSTRACT Objectives: The aim of this study was to assess the perception of quality of life of patients with spinal muscular atrophy (SMA) and investigate whether there is a correlation between patients’ perception and that of their carers. Methods: Cross-sectional analytical observational study. In the first part, socioeconomic, demographic, clinical, and treatment information were collected from patients diagnosed with SMA, regardless of type, sex, or age. SMA type 1 does not sit; SMA type 2 sits; SMA type 3 walks; and SMA type 4 begins in adulthood. In the second part of the study, patients aged between 2 and 25 years and their caregivers responded to the Pediatric Quality of Life Inventory 4.0 questionnaire. Results: Of the 235 families recruited, 167 were eligible to respond to the questionnaire, 115 caregivers and 49 patients were included. The results point to a different perception of quality of life between patients and caregivers. Patients with SMA type 2 perceive more impaired physical and emotional capacity compared to SMA type 3 and 1, respectively. As for caregivers, the perception of quality of life in relation to physical and social capacity and the total score are worse for patients with SMA type 1 compared to other types. Perceptions correlate with emotional capacity in SMA type 2 and the total aspect in SMA type 3. Conclusions: Patients with SMA type 2 had a worse perception of their quality of life than other patients. Perception differed between patients and their caregivers, with the former having a better perception than the latter.

Light-textured soils are widely distributed globally and, despite their limitations, have been integrated into agricultural production systems. This study aimed to assess how management systems—conventional tillage (CT) and no-till (NT)—affect aggregate formation pathways (physicogenic and biogenic) and bacterial communities. Two management systems (NT and CT) and three cover crops were evaluated: CJ: Crotalária (Crotalaria juncea (40 ​kg ​ha−1); M: Millet (Pennisetum glaucum - 60 ​kg ​ha−1); and C: Cocktail (Crotalária - Crotalaria juncea - 10 ​kg ​ha−1, Jack bean - Canavalia ensiformis - 75 ​kg ​ha−1, and Millet - Pennisetum glaucum - 30 ​kg ​ha−1). Undisturbed soil samples were collected from the crop row at a depth of 0.00–0.10 ​m. Aggregates with diameters between 9.7 and 8.0 ​mm were classified as biogenic or physicogenic. In addition to the chemical attributes of the aggregates, total organic carbon (TOC) and its fractions (mineral-associated organic carbon, MAOC; particulate organic carbon, POC; and free light fraction carbon, FLFC) were quantified. The structure and bacterial composition of the aggregates were also characterized. A higher proportion of biogenic aggregates (53–64%) was observed compared to physicogenic aggregates (36–47%). Cover crops exhibited significant differences in pH, calcium (Ca2+), base saturation, phosphorous (P), and percentage of base saturation. The management systems differed significantly for Ca2+ and P, with CT showing higher values than NT. The management system influenced organic matter accumulation and stabilization in the aggregates, with MAOC content being significantly lower in CT. POC and TOC were also significantly lower in physicogenic aggregates under CT. Bacterial community richness, diversity, and structure were significantly influenced by the management system, with greater richness and diversity in NT compared to CT. Network analysis revealed NT had more nodes and edges (65 and 406, respectively) than CT (52 and 357, respectively. Phyla abundance differed between the systems, with Firmicutes and Entotheonellaeota more abundant in CT, while WPS_2, GAL15, Bdellovibrionota, and Myxococcota were more abundant in NT. Despite the relatively short period of NT implementation (5 years), it had a positive effect on the bacterial community, which may subsequently influence nutrient and carbon content and their fractions in the aggregates.

Abstract Advancing research and practice that recognize diverse worldviews, knowledge systems, and value orientations is essential to enable transformative change towards sustainability. Biocultural approaches recognize the diverse ways in which people relate to nature, offering a potential pathway for sustainability transformations. However, recent scholarship on biocultural approaches to sustainability has highlighted that social aspects such as equity and justice have not been substantively addressed, whereby gender issues have been overlooked to a great extent. Through qualitative content analysis, this review synthesizes the conceptualizations of gender and social difference within the literature on biocultural approaches to sustainability published in English and Spanish. The biocultural literature predominantly focuses on describing knowledge and management practices, neglecting power and gender relations that affect access and control over resources, and how different axes of social difference matter across different social‐ecological contexts. Overall, we found that gender considerations within the literature reviewed do not build upon feminist and gender theories. Based on these findings, we provide insights into how more nuanced engagements, especially in relation to feminist theories and tools as intersectionality and decolonial perspectives, can allow for more just scholarly efforts to address biocultural relations. Finally, we draw attention to responsible and engaged praxis towards promoting biocultural approaches that include the diverse perspectives of those who can contribute to transformative change, and which prevent the reinforcement of gender‐based power relations. Read the free Plain Language Summary for this article on the Journal blog.

O presente artigo visa revisar a trajetória e as contribuições de Maria Montessori para a educação, enfatizando como seu ambiente natal, experiências profissionais e ideias inovadoras impactaram o desenvolvimento do Método Montessori. A pesquisa realiza uma análise qualitativa da vida de Montessori, destacando eventos marcantes desde seu nascimento em Chiaravalle até sua formação médica, atuação em psiquiatria e desenvolvimento de práticas pedagógicas inspiradas em Édouard Séguin e Jean Marc Gaspard Itard. Montessori criou um sistema educacional baseado em educação sensorial, autonomia e liberdade, influenciado pelas condições culturais e profissionais que enfrentou. Sua abordagem promoveu avanços significativos na pedagogia, evidenciados pela eficácia do Método Montessori aplicado na Casa dei Bambini e amplamente adotado internacionalmente. O estudo conclui que o Método Montessori transformou a educação ao priorizar o desenvolvimento individual da criança, proporcionando-lhe um ambiente preparado e materiais que estimulam a autoaprendizagem. A duradoura influência de Montessori na educação reflete sua visão progressista e sua contribuição para o respeito à autonomia infantil.

ABSTRACT More information is needed on the potential of using drill cuttings (crushed rocks) from the oil industry in agriculture and forestry. An experiment in forest nursery was carried out to evaluate the influence of substrates formulated from onshore gravel on characteristics of Ipê-branco (Tabebuia roseoalba) seedlings (i.e., growth, quality, and nutrition). We used five gravimetric proportions of gravel from drill cuttings mixed with Pinus-bark - commercial substrate (Mecplant® Florestal 3): control with only commercial substrate and zero gravel (G0), 2.5 % gravel (G2.5), 5 % gravel (G5), 7.5 % gravel (G7.5), and 10 % gravel (G10). In general, high proportion of drill cuttings increases density and decrease current moisture and total porosity of the formulated substrates. The drill cuttings proportions G2.5, G5 and G7.5 significantly contributed to the available water and readily available water in these substrates, with percentage values ranging 23 – 30 % higher than the G10 substrate. Increasing the gravel proportion generally resulted in increased pH levels, P, Na, K and metals (Cu, Fe, Ni, Mn, Cd, Zn, Cr and Pb), except for Ca and Mg nutrients that decreased. Heavy metal contents in all substrates did not exceed the permissible values in legal standards. The G2.5 and G5 substrates increased by 20 % approximately the stem diameter and height of seedlings, and G2.5 proportion also affected the root dry mass and Dickson quality index, with values two times higher than G0 substrate. Multivariate analysis proved suitable as a complementary approach to evaluate the seedling quality. Drilling cuttings addition, in general, increased the accumulation of nutrients and heavy metals of the Ipê-branco seedlings, and G2.5 and G5 substrates provided the greatest accumulation of the nutrients P, Ca, Pb and Zn in the shoot, while G2.5 proportion contributed with higher accumulation of N, Ca, Fe, Cr, Mn and Pb in the root. Adding drill cuttings as a conditioning component of the substrate at 2.5 and 5 % proportions is a viable alternative for using this residue to produce high-quality Tabebuia roseoalba seedling.

Colorectal cancer represents 10% of all the annual tumors diagnosed worldwide, being often not timely diagnosed, because its symptoms are typically lacking or very mild. Therefore, it is crucial to develop and validate innovative low-invasive techniques to detect it before becoming intractable. To this aim, a device equipped with nanostructured gas sensors has been employed to detect the airborne molecules of blood samples collected from healthy subjects, and from colorectal cancer affected patients at different stages of their pre- and post-surgery therapeutic path. Data was scrutinized by using statistical standard techniques to highlight their statistical differences, and through principal component analysis and support vector machine to classify them. The device was able to readily distinguish between the pre-surgery blood samples (i.e., taken when the patient had cancer), and the ones up to three years post-surgery (i.e., following the tumor removal) or the ones from healthy subjects. Finally, the correlation of the sensor responses with the patient/healthy subject’s gender was investigated, resulting negligible. These results pave the path toward a clinical validation of this device to monitor the patient’s health status by detecting possible relapses, to parallel to clinical follow-up protocols.

Interactions between macromolecules orchestrate many mechanobiology processes. However, progress in the field has often been hindered by the monetary and time costs of obtaining reliable experimental structures. In recent years, deep-learning methods, such as AlphaFold, have democratized access to high-quality predictions of the structural properties of proteins and other macromolecules. The newest implementation, AlphaFold 3, significantly expands the applications of its predecessor, AlphaFold 2, by incorporating reliable models for small molecules and nucleic acids and enhancing the prediction of macromolecular complexes. While several limitations still exist, the continuous improvement of machine learning methods like AlphaFold is producing a significant revolution in the field. The possibility of easily accessing structural predictions of biomolecular complexes may create substantial impacts in mechanobiology. Indeed, structural studies are at the basis of several applications in the field, such as drug discovery for mechanosensing proteins, development of mechanotherapy, understanding the mechanotransduction mechanisms and the mechanistic basis of diseases, or designing biomaterials for tissue engineering.

No-tillage (NT) has been adopted in organic agriculture as an alternative to conventional tillage (CT) for improving soil conservation. Cover crops (CC) play a vital role in this process by providing straw and releasing nutrients into the soil. Therefore, in this study, we aimed to evaluate the effects of NT and CT management on the chemical properties and bacterial diversity of soil following the cultivation of diverse CC in an organic system. The experiment was conducted using a randomized block design with subdivided plots, wherein the plots represented CT and NT, and the subplots represented the diverse CC tested, including pearl millet, sunn hemp, jack bean, seed mixes 1 and 2 (containing 100 % and 50 % of the recommended seeding rates for each crop), and spontaneous plants. The evaluations were conducted one year after the experiment was conducted. The results demonstrated that NT promoted increases in soil magnesium, phosphorus, and organic carbon contents, including increased bacterial richness. Moreover, NT resulted in a higher abundance of Bacteroidetes, GAL15, and Myxococcota. Conversely, CT favored a greater relative abundance of Actinobacteria, in addition to the members of Bacteroidetes. Regarding the influence of CC, no significant differences were observed in the diversity and structure of the bacterial communities, except for subgroup 17, which was more abundant in spontaneously grown plants. NT proved to be more effective than CT in improving soil chemical properties and bacterial diversity, implying its potential to contribute to sustainable agricultural systems.

IntroductionSexually transmitted infections (STIs) cause considerable morbidity worldwide and, depending on the specific pathogen, may lead to serious complications in the female reproductive tract. Incarcerated women are particularly vulnerable to health problems with a disproportionate high rate of STIs, including infections with human papillomavirus (HPV).MethodsHere, cervical swab samples collected from 299 women (18 to 64 years) living in one of the women’s prisons of São Paulo, Brazil were submitted for liquid-based cytology to determine the prevalence of precancerous lesions. Furthermore, direct detection of 30 genital HPV genotypes (18 high-risk and 12 low-risk types) and 11 additional STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus 1 and 2, Haemophilus ducreyi, Mycoplasma genitalium and hominis, Treponema pallidum, Trichomonas vaginalis, Ureaplasma parvum and urealyticum) were performed by molecular typing using two PCR-based DNA microarray systems, i.e., EUROArray HPV and EUROArray STI (EUROIMMUN), respectively.ResultsThe overall prevalence of cytological abnormalities was 5.8%, including five women with low-grade and five women with high-grade squamous intraepithelial lesions. The overall prevalence of HPV was 62.2, and 87.1% of the HPV-positive women were infected with oncogenic high-risk (HR) HPV types. HPV types 16 (24.1%), 33 and 52 (both 10.4%) were the most frequently detected. The prevalence of the other STIs was 72.8%. Up to four different pathogens were found in the infected women, the most frequent being Ureaplasma parvum (45.3%), Mycoplasma hominis (36.2%) and Trichomonas vaginalis (24.8%).ConclusionThe high number of HR-HPV infections and other STIs described here highlights the fact that the Brazilian female prison population requires more attention in the country’s health policies. The implementation of screening programs and treatment measures might contribute to a decrease in the incidence of STIs and cervical cancer in this vulnerable population. However, for such measures to be effective, further studies are needed to investigate the best practice to get more women to engage in in-prison prevention programs, e.g., through offering further sexual health education and self-sampling.

Background Children with cerebral palsy have a higher prevalence of sleep disorders, with numerous factors associated with a negative impact on the quality of life of caregivers.