The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied ...extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH-BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer's disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson's patients with mild cognitive impairment.
This paper describes the effect of several inhibiting components on three potential hosts for the bio-based production of methyl propionate, namely, wild-type
Escherichia coli
and
Bacillus subtilis
, ...and evolved
Saccharomyces cerevisiae
IMS0351. The inhibition by the lignocellulose-derived products 5-hydroxymethyl-2-furaldehyde, vanillin, and syringaldehyde and the fermentation products 2-butanol, 2-butanone, methyl propionate, and ethyl acetate has been assessed for these strains in defined medium. Multiple screenings were performed using small-scale cultures in both shake flasks and microtiter plates. Technical drawbacks revealed the limited applicability of the latter in this study. The microbial growth was characterized by means of a lag-time model, and the inhibitory thresholds were determined using product-inhibition models. The lignocellulose-derived products were found to be highly inhibitory, and none of the strains could grow in the presence of 2.0 g L
−1
of product. From the fermentation products tested, methyl propionate had the most severe impact resulting in complete inhibition of all the strains when exposed to concentrations in the range of 12–18 g L
−1
. In general,
S. cerevisiae
and
B. subtilis
were comparatively more tolerant than
E. coli
to all the fermentation products, despite
E. coli
’s lower sensitivity towards vanillin. The results suggest that, overall, the strains investigated have good potential to be engineered and further established as hosts for the bio-based production of methyl esters.
Bantu languages are spoken by about 310 million Africans, yet the genetic history of Bantu-speaking populations remains largely unexplored. We generated genomic data for 1318 individuals from 35 ...populations in western central Africa, where Bantu languages originated. We found that early Bantu speakers first moved southward, through the equatorial rainforest, before spreading toward eastern and southern Africa. We also found that genetic adaptation of Bantu speakers was facilitated by admixture with local populations, particularly for the HLA and LCT loci. Finally, we identified a major contribution of western central African Bantu speakers to the ancestry of African Americans, whose genomes present no strong signals of natural selection. Together, these results highlight the contribution of Bantu-speaking peoples to the complex genetic history of Africans and African Americans.
Aberrant profiles of pre-mRNA splicing are frequently observed in cancer. At the molecular level, an altered profile results from a complex interplay between chromatin modifications, the ...transcriptional elongation rate of RNA polymerase, and effective binding of the spliceosome to the generated transcripts. Key players in this interplay are regulatory splicing factors (SFs) that bind to gene-specific splice-regulatory sequence elements. Although mutations in genes of some SFs were described, a major driver of aberrant splicing profiles is oncogenic signal transduction pathways. Signaling can affect either the transcriptional expression levels of SFs or the post-translational modification of SF proteins, and both modulate the ratio of nuclear versus cytoplasmic SFs in a given cell. Here, we will review currently known mechanisms by which cancer cell signaling, including the mitogen-activated protein kinases (MAPK), phosphatidylinositol 3 (PI3)-kinase pathway (PI3K) and wingless (Wnt) pathways but also signals from the tumor microenvironment, modulate the activity or subcellular localization of the Ser/Arg rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) families of SFs.
Cancer cells preferentially use aerobic glycolysis over mitochondria oxidative phosphorylation for energy production, and this metabolic reprogramming is currently recognized as a hallmark of cancer. ...Oncogenic signaling frequently converges with this metabolic shift, increasing cancer cells' ability to produce building blocks and energy, as well as to maintain redox homeostasis. Alterations in cell-cell and cell-extracellular matrix (ECM) adhesion promote cancer cell invasion, intravasation, anchorage-independent survival in circulation, and extravasation, as well as homing in a distant organ. Importantly, during this multi-step metastatic process, cells need to induce metabolic rewiring, in order to produce the energy needed, as well as to impair oxidative stress. Although the individual implications of adhesion molecules and metabolic reprogramming in cancer have been widely explored over the years, the crosstalk between cell adhesion molecular machinery and metabolic pathways is far from being clearly understood, in both normal and cancer contexts. This review summarizes our understanding about the influence of cell-cell and cell-matrix adhesion in the metabolic behavior of cancer cells, with a special focus concerning the role of classical cadherins, such as Epithelial (E)-cadherin and Placental (P)-cadherin.
Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Chronic or early-life stress is one of the key risk factors ...for depression. In addition, a growing body of data implicates chronic inflammation as a major player in depression pathogenesis. More recently, the gut microbiota has emerged as an important regulator of brain and behavior and also has been linked to depression. However, how this holy trinity of risk factors interact to maintain physiological homeostasis in the brain and body is not fully understood. In this review, we integrate the available data from animal and human studies on these three factors in the etiology and progression of depression. We also focus on the processes by which this microbiota-immune-stress matrix may influence centrally mediated events and on possible therapeutic interventions to correct imbalances in this triune.
Peru was one of the first developing countries to commit to a voluntary emissions reduction target and is seen as a bridge builder within the UNFCCC. It played an important role in advancing the ...multilateral climate process between 2013 and 2015. Peru is a member of the Independent Alliance of Latin America and the Caribbean (AILAC), a progressive coalition of countries that promotes ambitious positions within the climate regime. Although the country's level of activism in international negotiations has markedly declined since 2016, there have been no significant changes in its foreign position. What factors explain Peru's conciliatory and relatively progressive stance at the UNFCCC? To answer this question, I use the 'climate commitment approach' as analytical framework and trace the processes that link possible causes with outcomes, comparing two different periods in the trajectory of Peru's participation in the climate regime. The study is based on semi-structured interviews, governmental publications and data, reports and studies by independent organizations, news reports, and scientific literature. It concludes that Peru's position in the UNFCCC negotiations has been mainly determined by the dominant presence of Peru's Ministry of Environment (MINAM) in foreign climate policy decision-making as well as of individual agents who act as climate leaders. It also points to several other factors that determine its position: the low level of interest in, or understanding of, the climate issue by domestic pressure groups; the country's international profile; the governmental perception of economic, political, and diplomatic benefits associated with a more ambitious climate position; and the wish to access international climate financing.
Key policy insights
Foreign pressure and support were major pillars of the development of Peru's foreign climate policy.
Peru's diplomatic position was profoundly shaped by the vision and interests of MINAM, which filled a political vacuum and exercised leadership in international climate negotiations. Given the ministry's expertise, and international support for its activities, other ministries could hardly compete with MINAM for influence.
Recently, the diminished authority of MINAM, the inclusion of climate change into Peru's national policy agenda combined with domestic political turmoil, have translated into a marked decline in the country's level of foreign activism.
Peru has continued to align with AILAC due to the link between the country's foreign trade and climate policy agendas, and to the benefits associated with a more ambitious foreign climate position, including possibilities for attracting international climate finance.
Context
Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for numerous haematologic diseases and solid tumours. Increasing indications for HSCT and reduction in associated ...mortality have been raising the number of paediatric HSCT survivors and their long‐term toxicities.
Objective
To characterize the endocrine disorders developed after HSCT.
Design and Patients
Retrospective analysis of 152 patients submitted to HSCT in paediatric age with at least 24 months of follow‐up at our endocrine late‐effects clinics.
Results
Patients were followed up for 9.9 (interquartile range IQR: 12.2) years. The median age at HSCT was 7.5 (IQR: 9) years. At least one endocrine complication was observed in 65.1% of the patients. Primary hypogonadism was detected in 34.2%. Female gender (p < .001), HSCT > 10 years old (p = .01) and chemotherapy before HSCT (p < .001) were identified as risk factors for developing gonadal dysfunction. Growth hormone deficiency (GHD) occurred in 23.0% with a mean stature Z‐score at diagnosis of −1.8 ± 1.4. GHD was associated with cranial (p < .001) and HSCT < 10 years old (p ≤ 0.001). Patients who were exposed to total body irradiation (TBI) were at higher risk for primary hypothyroidism (22.3%) (p = .01), thyroid nodules (17.1%) (p < .001), thyroid carcinoma (5.3%) (p < .001), dyslipidaemia (19.1%) (p < .001) and disturbance of carbohydrate metabolism (19.1%) (p < .001).
Conclusion
At least one endocrine complication was diagnosed in 65.1% of patients, with gonadal dysfunction being the most prevalent. The conditioning regimen with TBI was a risk factor for the development of several endocrine disorders. This study is one of the largest series evaluating the endocrine disorders among survivors of paediatric HSCT and intends to reinforce the importance of routine follow‐up of these patients.
Despite growing interest in African civil society and the enduring legacy of colonialism, studies on this theme with a historical perspective are still few. This article analyses the evolution of ...associational life in Luanda from its origins in the mid-nineteenth century until the decolonisation in 1974. It is based on a complete census of the officially recognised bylaws, which confirmed that formal associationism was exclusive to settlers and a minority of ‘assimilated’ natives. Modern associations among the ‘detribalised’ urban populations, never recognised by the colonial authorities, were considered by analysing ethnographic research. Historical empirical evidence sustains the idea that the colonial encounter determinately shaped civil society and the public sphere, determining the inequality in access and exercise of citizenship while illustrating the strategies used by native people to overcome legal and political constraints to associationism.
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