The Regulation of Axon Diameter: From Axonal Circumferential Contractility to Activity-Dependent Axon Swelling

In the adult nervous system axon caliber varies widely amongst different tracts. When considering a given axon, its diameter can further fluctuate in space and time, according to processes including the distribution of organelles and activity-dependent mechanisms. In addition, evidence is emerging supporting that in axons circumferential tension/contractility is present. Axonal diameter is generically regarded as being regulated by neurofilaments. When neurofilaments are absent or low, microtubule-dependent mechanisms can also contribute to the regulation of axon caliber. Despite this knowledge, the fine-tune mechanisms controlling diameter and circumferential tension throughout the lifetime of an axon, remain largely elusive. Recent data supports the role of the actin-spectrin-based membrane periodic skeleton and of non-muscle myosin II in the control of axon diameter. However, the cytoskeletal arrangement that underlies circumferential axonal contraction and expansion is still to be discovered. Here, we discuss in a critical viewpoint the existing knowledge on the regulation of axon diameter, with a specific focus on the possible role played by the axonal actin cytoskeleton.This work from the authors’ group was supported by Prémio Melo e Castro—Santa Casa da Misericórdia de Lisboa; by the Infrastructure for NMR, EM and X-rays for Translational Research (iNEXT); and by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the Norte Portugal Regional Operational Programme (NORTE 2020), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project NORTE-01-0145-FEDER-028623. AC and RP-C are funded by Fundação para a Ciência e Tecnologia—FCT (fellowships SFRH/BPD/114912/2016 and SFRH/BD/112112/2015, respectively)

Utilização de própolis como alternativa no controlo de mastites para garantir a qualidade do leite e proteção da saúde pública.

Os antimicrobianos e antisséticos são utilizados para o controlo das mastites. Esta prática conduz a eliminação de resíduos no leite além de induzir a pressão de seleção sobre estirpes resistentes a antimicrobianos. A própolis é uma massa, utilizada para proteger as colmeias das abelhas (Apis mellifera), formada por resinas retiradas de vários vegetais, selecionadas de forma natural pelas abelhas. Este produto altamente variável, consoante os vegetais utilizados, apresenta colorações diversas e também qualidades antimicrobianas variáveis. O objetivo deste estudo foi testar a suscetibilidade, de isolados de Staphylococccus aureus provenientes de amostras de leite de cabras e ovelhas com mastite, a 16 antimicrobianos utilizados em Portugal no controlo desta doença, e analisar “in vitro” a ação antimicrobiana de extratos etanólicos de própolis (EEP).FCT – Fundação para a Ciência e a Tecnologia no âmbito do Projecto UID/AGR/00115/2013. M. Laranjo agradece a bolsa de Pós-Doutoramento da FCT (SFRH/BPD/108802/2015)

A challenging coexistence of central diabetes insipidus and cerebral salt wasting syndrome: A case report

Background: Combined central diabetes insipidus and cerebral salt wasting syndrome is a rare clinical finding. However, when this happens, mortality is high due to delayed diagnosis and/or inadequate treatment. Case presentation: A 42-year-old white man was referred to neurosurgery due to a non-functional pituitary macroadenoma. He underwent a partial resection of the tumor on July 2, 2015. On the day following surgery he presented polyuria with sodium 149 mEq/L, plasma osmolality 301 mOsm/kg, and urine osmolality 293 mOsm/kg. He started nasal desmopressin 0.05 mg/day with good response. He was already on dexamethasone 4 mg and levothyroxine 75 mcg due to hypopituitarism after surgery. On July 9 he became confused. Cerebral computed tomography was performed with no significant changes. His natremia dropped to 128 mEq/L with development of polyuria despite maintenance of desmopressin dose. His hemoglobin and hematocrit rose from 9.1 g/L to 11.6 g/L and 27.5 to 32.5, respectively. His thyroid function was normal and he was on hydrocortisone 30 mg/day. At 12 p.m. 150 mg/hydrocortisone infusion was initiated, but sodium did not increase. Plasma and urine osmolality were 264 mOsm/kg and 679 mOsm/kg, respectively. At 4 p.m. hydrocortisone was increased and hypertonic saline replacement started. Two hours later he was dehydrated with polyuria and vomiting, and natremia of 124 mEq/L. Hyponatremia was very resistant to treatment despite hypertonic saline replacement, hence desmopressin was suspended. The following day, urine spot analysis showed that natriuresis was 63 mEq/L with serum sodium 132 mEq/L. This was interpreted as a cerebral salt wasting syndrome and control was achieved with aggressive hypertonic saline replacements and fludrocortisone 0.1 mg/three times a day. Conclusions: We present a rare case of a patient with diabetes insipidus and cerebral salt wasting syndrome, who was successfully treated. Hyponatremia in a patient with diabetes insipidus may erroneously be interpreted as inadequate diabetes insipidus control or as syndrome of inappropriate antidiuretic hormone secretion, leading to therapeutic errors. Thus, all clinical and analytical data should be evaluated together for early and correct diagnosis

Improved methods for high-precision Pb-Pb dating of extra-terrestrial materials

Dating meteoritic materials by the Pb–Pb isochron method depends on constructing linear arrays typically defined by mixtures of initial and radiogenic Pb after the removal of terrestrial contaminant Pb. The method also depends on minimizing the amount of laboratory Pb blank added to the sample during processing and analyses. With the aim to analyze smaller sample sizes and decrease processing times, we have devised a new method for the construction of isochrons using the stepwise dissolution of meteoritic materials that better defines reduced amounts of Pb blank, reduces the risk of random anomalous Pb contamination, and increases sample throughput. Samples are processed in a PFA Teflon™ pipette tip fitted with a frit inside a heated, sealed chamber that can be manually over-pressured to expel reagents directly into a PFA Teflon™ vial below. With four independent chambers, three samples can be processed simultaneously with a fourth position to assess the Pb contribution of the combined blank and spike for each step. The matched blank-spike Pb for each step provides a specific blank estimate for each step that ensures a more accurate correction for non-sample Pb and, therefore, reduces the uncertainty on each analysis. We assess the performance of this new method by reporting the results of dating a fragment of a chondrule from the well-characterized CBa chondrite Gujba and compare these results with previously published data for this meteorite. The improvements reduce the minimum sample sizes that can be successfully dated by the Pb–Pb method, an important development for size-limited materials such as small chondrules and samples returned from space missions

Big data analyses reveal patterns and drivers of the movements of southern elephant seals

The growing number of large databases of animal tracking provides an opportunity for analyses of movement patterns at the scales of populations and even species. We used analytical approaches, developed to cope with big data, that require no a priori assumptions about the behaviour of the target agents, to analyse a pooled tracking dataset of 272 elephant seals (Mirounga leonina) in the Southern Ocean, that was comprised of >500,000 location estimates collected over more than a decade. Our analyses showed that the displacements of these seals were described by a truncated power law distribution across several spatial and temporal scales, with a clear signature of directed movement. This pattern was evident when analysing the aggregated tracks despite a wide diversity of individual trajectories. We also identified marine provinces that described the migratory and foraging habitats of these seals. Our analysis provides evidence for the presence of intrinsic drivers of movement, such as memory, that cannot be detected using common models of movement behaviour. These results highlight the potential for big data techniques to provide new insights into movement behaviour when applied to large datasets of animal tracking.Comment: 18 pages, 5 figures, 6 supplementary figure

Propolis components accountable for bactericidal accomplishment and antibiofilm activity

This study aimed at evaluating antimicrobial and antibiofilm activity of phenolic compounds present in propolis ethanol extracts (PEE). Seventy per cent ethanol extracts from seven types of propolis, one Green, two Red and four Brown collected in four Brazilian States were prepared and total phenolics, flavonoids, tannins and anthocyanins were assessed by high-performance liquid chromatography (HPLC). Minimum bactericidal concentration (MBC) and inhibitor effect on Staphylococcus aureus biofilm formation and capacity to disrupt established biofilms were assessed towards eight S. aureus isolates from milk of small ruminants with mastitis, one methicillin-resistant S. aureus (MRSA) and S. aureus ATCC 25923. To evaluate different propolis components accountability for bactericidal accomplishment and antibiofilm activity, the results were analysed by the non-parametric Spearman coefficient. Results of phenolic compounds were 216,21 to 312,08 gallic acid milligram equivalent per extract gram (mg EGA/g) of total phenolics, 55,08 to 140,6 quercetin milligram equivalent per extract gram (mg EQ/g) of flavonoids, 118,51 to 3766,16 catechin milligram equivalent per extract gram (mg EC/g) of tannins and 1,03 to 8,39 milligram per extract gram (mg/g) of anthocyanins. Red1 and Red2 showed higher tannin contents, while Red2 exhibited superior amount of anthocyanins and total phenolics. Brown3 presented higher flavonoid quantity. Green, Red1 and Red2 PEE showed the lowest levels of flavonoids, but the higher antimicrobial activity. Most PEE exhibit bactericidal activity at a concentration of 1.6 mg/mL. Brown4 PEE showed the worst capacity to inhibit S. aureus. Green PEE showed to be the most efficient in both preventing and disrupting biofilm. All PEE studied exhibited a better inhibitory activity prior-to than post-biofilm formation. According to non-parametric Spearman correlation analysis, there seems to be a significant negative correlation between the ability to disrupt biofilm and both tannins and anthocyanins contents

Dysproteinemia-Associated Kidney Diseases: Clinicopathological Correlations

Introduction: Dysproteinemia-associated kidney diseases can have diverse clinical and histological presentation but not all patients with monoclonal gammopathy have Monoclonal Gammopathy of Renal Significance (MGRS) and some have other causes for kidney lesions. Therefore, kidney biopsy is essential to make this diagnosis. We made a retrospective study, which aimed to: 1. Identify dysproteinemiaassociated kidney lesions; 2. Establish clinicopathological correlations of patients with those lesions and 3. Identify kidney and patient survival predictors. Methods: A retrospective, observational chart review of kidney biopsies performed, between January 2015 and February 2020, in three Portuguese Hospitals, to a total of 39 patients, with kidney lesions associated with monoclonal gammopathy, was undertaken. Results: The three main dysproteinemic kidney diseases identified were cast nephropathy, AL amyloidosis and Monoclonal Immunoglobulin Deposition Disease (MIDD), with different features among them. Only three patients fulfilled the criteria to Monoclonal Gammopathy of Renal Significance (MGRS). In regard to treatment, we verified that most of our patients were treated with chemotherapy. Unfortunately, only four recovered, either partially or completely. The mean kidney survival since kidney biopsy was 29,23 months and the mean patient survival since diagnosis was 24,46 months. Some clinical and pathologic features correlated to lowerkidney survival: acute tubular necrosis, cast nephropathy, Thrombotic Microangiopathy (TMA), haemoglobin and estimated Glomerular Filtration Rate (eGFR). Previous Nephrology follow-up correlated with higher kidney survival. Only eGFR was associated with lowerpatient survival.info:eu-repo/semantics/publishedVersio

Association of child neurodevelopmental or behavioural problems with maternal unemployment in a population-based birth cohort

PurposeTo estimate associations between suspected or diagnosed neurodevelopmental or behavioural problems in 7-year-old children and maternal unemployment at child age 7 and 10, in a Portuguese birth cohort.MethodsWe evaluated 5754 mothers and their children of the population-based birth cohort Generation XXI in Porto, Portugal. Data on suspected and diagnosed child neurodevelopmental and behavioural problems (exposures)-learning, attention and language problems, externalising behaviours, developmental delay, autism spectrum disorders, and other neurodevelopmental problems-were retrieved at 7 years of age by interviewing caregivers. Maternal employment status (outcome) was collected at the 7- and 10-year follow-up waves. Robust Poisson regression models were used to estimate associations.ResultsAfter adjustment for maternal and household characteristics, women were more likely to be unemployed at child age 10 if the child had, up to age 7, any of the following suspected problems: an autism spectrum disorder (PR = 1.73; 95% CI 1.07, 2.79), developmental delay (PR = 1.58; 95% CI 1.20, 2.06), externalising behaviours (PR = 1.29; 95% CI 1.11, 1.50) or learning problems (PR = 1.26; 95% CI 1.07, 1.48). When the exposure was restricted to clinically diagnosed disorders, the magnitude of associations remained similar but estimates were less precise. Associations with unemployment were stronger at child age 10 (prospective analyses), than at child age 7 (cross-sectional).ConclusionHaving a child with learning, developmental or behavioural problems, or an autism spectrum disorder up to age 7 was associated with maternal unemployment three years later, even in a less affluent European economy where the dual-earner family structure is often necessary to make ends meet.This study was funded by European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization; national funding from Foundation for Science and Technology (FCT)-Portuguese Ministry of Science, Technology and Higher Education under the projects 'STEPACHE-Raizes pediatricas da resposta ampliada a dor: das influencias contextuais a estratificacao do risco' (POCI- 01- 0145FEDER-029087) [Ref. FCT PTDC/SAUEPI/29087/2017], 'HIneC: Quando se revelam as desigualdades em saude?' (POCI-01-0145FEDER-029567) [Ref. FCT PTDC/SAU-PUB/29567/2017]; Epidemiology Research Unit-Instituto de Saude Publica, Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; UID/DTP/04750/2019); Administracao Regional de Saude Norte (Regional Department of Ministry of Health) and Fundacao Calouste Gulbenkian; EEA Grants through the Work-life Balance and Gender Equality program operated by CIG (SGS3A2); ERDF, through the North Regional Operational Program in the framework of the project HEALTHUNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145FEDER-000039); PhD grant (Joana Amaro) co-funded by the FCT and the Human Capital Operating Program of the European Social Fund (POPH/ FSE Program) [PD/BD/128009/2016]; research grant from FOREUM Foundation for Research in Rheumatology (Career Research Grant). This study was based upon work from COST Action CA16216 (OMEGA-NET), supported by COST (European Cooperation in Science and Technology)