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Abstract The human papillomavirus minor capsid protein L2 is being extensively explored in pre-clinical studies as an attractive vaccine antigen capable of inducing broad-spectrum prophylactic antibody responses. Recently, we have developed two HPV vaccine antigens – PANHPVAX and CUT-PANHPVAX- both based on heptameric nanoparticle antigens displaying polytopes of the L2 major cross-neutralizing epitopes of eight mucosal and twelve cutaneous HPV types, respectively. Prompted by the variable neutralizing antibody responses against some of the HPV types targeted by the antigens observed in previous studies, here we investigated the influence on immunogenicity of six distinct glycine-proline spacers inserted upstream to a specific L2 epitope. We show that spacer variants differentially influence antigen immunogenicity in a mouse model, with the antigen constructs M8merV6 and C12merV6 displaying a superior ability in the induction of neutralizing antibodies as determined by pseudovirus-based neutralization assays (PBNAs). L2-peptide enzyme-linked immunosorbent assay (ELISA) assessments determined the total anti-L2 antibody level for each antigen variant, showing for the majority of sera a correlation with their repective neutralizing antibody level. Surface Plasmon Resonance revealed that L2 epitope-specific, neutralizing monoclonal antibodies (mAbs) display distinct avidities to different antigen spacer variants. Furthermore, mAb affinity toward individual spacer variants was well correlated with their neutralizing antibody induction capacity, indicating that the mAb affinity assay predicts L2-based antigen immunogenicity. These observations provide insights on the development and optimization of L2-based HPV vaccines.

Inflammatory Bowel Disease (IBD) is a chronic condition that affects approximately 1.6 million Americans. While current polyphenols for treating IBD can be expensive and cause unwanted side effects, there is an opportunity regarding a new drug/polymer formulation using silymarin and an electrospray procedure. Silymarin is a naturally occurring polyphenolic flavonoid antioxidant that has shown promising results as a pharmacological agent due to its antioxidant and hepatoprotective characteristics. This study aims to produce a drug–polymer complex named the SILS100-Electrofiber complex, using an electrospray system. The vertical set-up of the electrospray system was optimized at a 1:10 of silymarin and Eudragit® S100 polymer to enhance surface area and microfiber encapsulation. The SILS100-Electrofiber complex was evaluated using drug release kinetics via UV Spectrophotometry, Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC). Drug loading, apparent solubility, and antioxidant activity were also evaluated. The study was successful in creating fiber-like encapsulation of the silymarin drug with strand diameters ranging from 5–7 μm, with results showing greater silymarin release in Simulated Intestinal Fluid (SIF) compared to Simulated Gastric Fluid (SGF). Moving forward, this study aims to provide future insight into the formulation of drug–polymer complexes for IBD treatment and targeted drug release using electrospray and microencapsulation.

Resumo As duas décadas seguintes ao pós-abolição configuram-se como um momento chave para se observarem elementos que indicam a continuidade ou a ressignificação da subalternidade socioeconômica da população negra. Após discutir os conceitos de raça, racismo, racismo estrutural e processos de racialização que irão produzir a subcidadania negra, o presente artigo busca ressaltar, a partir de um escopo variado de fontes, dimensões empíricas da subalternidade negra com base no estudo aprofundado de um município característico da economia cafeeira do oeste paulista.

Abstract How species interact with human‐disturbed environments is a central focus of conservation biology. Within disturbed landscapes, regenerating forests have potential to provide habitat for forest species, especially as increasing amounts of primary forest are lost. As secondary forest regenerates beside primary forest, it increases habitat heterogeneity. However, relatively little is known about the influence of habitat heterogeneity on space use. In this study, we analyzed the topography and vertical vegetation structure of regenerating forest, small forest fragments, and undisturbed rainforest in the central Amazon to determine (1) how these structural characteristics influence understory mixed‐species flock space use and (2) how the vegetative preferences of flocks varied across a disturbance gradient. We first used behavioral observations to quantify the vertical foraging niche of flocks and then associated variation in horizontal space use with the three‐dimensional features of forest structure. Surprisingly, we found that flock space use was not consistently associated with any variable, even though available habitat differed both within and across forest types. Overall, the best predictors were elevation and leaf area density within the subcanopy (16–25 m), yet most flock foraging occurred in the midstory (6–15 m). Together, these results indicate that while flocks may have certain habitat preferences, these preferences are flexible or idiosyncratic and do not correspond to a specific vertical profile. For example, flocks spent a disproportionate amount of time in low elevations when available, but not all flocks had access to low‐lying areas within their home ranges. Although other studies show flock size and diversity can be highly sensitive to habitat disturbance, mixed‐species flocks demonstrate remarkable plasticity as a unit, virtually saturating undisturbed and disturbed forest at our site, as long as regeneration has passed a certain threshold.

Abstract Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post‐viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post‐viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID‐related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro‐clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.

Introduction The prevalence of intra-articular knee injuries and reparative surgeries is increasing in many countries. Alarmingly, there is a risk of developing post-traumatic osteoarthritis (PTOA) after sustaining a serious intra-articular knee injury. Although physical inactivity is suggested as a risk factor contributing to the high prevalence of the condition, there is a paucity of research characterising the association between physical activity and joint health. Consequently, the primary aim of this review will be to identify and present available empirical evidence regarding the association between physical activity and joint degeneration after intra-articular knee injury and summarise the evidence using an adapted Grading of Recommendations Assessment, Development and Evaluations. The secondary aim will be to identify potential mechanistic pathways through which physical activity could influence PTOA pathogenesis. The tertiary aim will be to highlight gaps in current understanding of the association between physical activity and joint degeneration following joint injury.Methods A scoping review will be conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist and best-practice recommendations. The review will be guided by the following research question: what is the role of physical activity in the trajectory from intra-articular knee injury to PTOA in young men and women? We will identify primary research studies and grey literature by searching the electronic databases Scopus, Embase: Elsevier, PubMed, Web of Science: all databases, and Google Scholar. Reviewing pairs will screen abstracts, full texts and will extract data. Data will be presented descriptively using charts, graphs, plots and tables.Ethics and dissemination This research does not require ethical approval due to the data being published and publicly available. This review will be submitted for publication in a peer-reviewed sports medicine journal irrespective of discoveries and disseminated through scientific conference presentations and social media.Trial registration number https://osf.io/84pnh/.

Background Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO‐based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2‐hit” murine model. Methods and Results Nine‐week‐old male C57BL/6 N mice (n=15 per group) were treated concurrently with high‐fat diet and N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME) (0.5 g/L per day) via drinking water for 10 weeks. At week 5, mice were randomized into either vehicle (normal saline) or combination treatment with sodium nitrite (75 mg/L in the drinking water) and hydralazine (2.0 mg/kg IP, BID). Cardiac structure and function were monitored with echocardiography and invasive hemodynamic measurements. Cardiac mitochondrial respiration, aortic vascular function, and exercise performance were also evaluated. Circulating and myocardial nitrite were measured to determine the bioavailability of NO. Circulating markers of oxidative or nitrosative stress as well as systemic inflammation were also determined. Severe HFpEF was evident by significantly elevated E/E', LVEDP, and Tau in mice treated with L‐NAME and HFD, which was associated with impaired NO bioavailability, mitochondrial respiration, aortic vascular function, and exercise capacity. Treatment with sodium nitrite and hydralazine restored NO bioavailability, reduced oxidative and nitrosative stress, preserved endothelial function and mitochondrial respiration, limited the fibrotic response, and improved exercise capacity, ultimately attenuating the severity of “two‐hit” HFpEF. Conclusions Our data demonstrate that nitrite, a well‐established biomarker of NO bioavailability and a physiological source of NO, is significantly reduced in the heart and circulation in the “2‐hit” mouse HFpEF model. Furthermore, sodium nitrite+hydralazine combined therapy significantly attenuated the severity of HFpEF in the “2‐hit” cardiometabolic HFpEF. These data suggest that supplementing NO‐based therapeutics with a potent antioxidant and vasodilator agent may result in synergistic benefits for the treatment of HFpEF.

Honey is the oldest and nowadays widely used natural sweetener for food worldwide. Its composition is associated with its botanical and geographical origin and honey is often mislabeled and has a high potential for food fraud. Thus, quick easy and sensitive analyses are required. For the first time, we developed and applied an automated, fast, sensitive and robust, in-tube extraction dynamic headspace in-tube extraction-dynamic headspace (ITEX-DHS) method for a variety of Honey containing VOCs in connection with GC–MS. Another advantage of ITEX is, that it is a green analytical solventless method. The method provides very low method detection limits (MDL) from 0.8 to 47 ng g−1 for VOCs in honey samples as well as very good repeatabilities with averages below 9 % RSD. Recoveries are between 83 and 100 %. Only octanal possess a repeatability 13 % and a recovery of 62 % due to its high polarity. 38 honey samples were measured after method validation. Four acacia honeys (A), six forest honeys (F) and 22 blossom honeys (B). The type of six honeys was not known (U) but could be predicted with the help of a linear discriminant analysis (LDA). The LDA was carried out with the three groups (A, B, F) leading to a proportion of correct predictions of 90.6 %. With the help of a scatterplot, two of the unknown samples were classified as forest honeys and four of them as blossom honeys.

Abstract Background Sacrospinous ligament fixation (SSLF) is a widely used vaginal procedure for correction of apical vaginal prolapse. The objective of this study was to evaluate subjective and objective outcomes of SSLF performed in a fast-track setting. Methods This was a prospective cohort study of sacrospinous ligament fixation performed using local anesthesia and light sedation in a fast-track setting at Aarhus University Hospital between April 2016 and December 2017. Objective signs of prolapse were assessed by gynecological examination preoperatively and at 6 months after the operation. Subjective symptoms were evaluated by questionnaires (the Pelvic Floor Distress Inventory (PFDI 20), and the Patient Global Impression of Improvement (PGI-I) supplemented with individual questions from the ICIQ-vaginal Symptoms (ICIQ-VS) and Sexual Questionnaire-IR (PISQ-12) questionnaires). Results One hundred and three women with a median age of 65 (36–84) years were included. Previous hysterectomy had been performed in 40% of the women, and 43% had a history of previous prolapse operations. At follow-up, 75% of the women had apical descent less than stage 2. However, 18% had anterior vaginal wall prolapse beyond the hymen, and 25% had recurrence of the apical prolapse stage 2 or more and were offered reoperation. Bladder and anal symptoms improved in most women after the operation, and the number of women reporting dyspareunia was halved. In the overall assessment by Patient Global Impression of Improvement (PGI-I) questionnaire, 76% reported improvement. No serious operative complications were reported, and 81% of the patients were discharged on the day of the surgery. Conclusion In this cohort with a high rate of previous prolapse surgery, sacrospinous ligament fixation performed in a fast-track setting showed subjective and objective results comparable to the results of apical native tissue repair reported in the literature. Furthermore, the complication rate was low. Trial registration This study was notified to The Central Denmark Region Committees on Health Research Ethics on July 7, 2015, and was approved by The Danish Data Protection Agency (1-16-02-442-15). All methods were performed in accordance with the relevant guidelines and regulations. An informed consent for participation in the study and acceptance of using data for scientific purposes and publication was signed by all patients.

To analyze the volatile organic compounds of olive oils, an automated, robust and sensitive and solventless in-tube extraction dynamic headspace (ITEX-DHS) GC–MS method was developed, optimized and validated. 21 VOCs, typically appearing in olive oils and extra virgin olive oils, were used to develop the method. The extraction procedure was optimized for incubation time, incubation temperature, number of extraction cycles and desorption volume. Repeatability was between 1 and 9% for all analytes, except octanal (11%), and a good recovery (84–118%) was found. The ITEX-DHS method allowed VOC analysis in olive oils at much smaller concentration than in previous studies using solid phase microextraction, with limits of detections from 0.1 to 68.6 µg kg−1. In terms of an application, a linear discriminant analysis (LDA) was conducted including 31 olive oil samples from five different geographical origins, which led to 90.3% correct predictions.

The Oja median is one of several extensions of the univariate median to the multivariate case. It has many desirable properties, but is computationally demanding. In this paper, we first review the properties of the Oja median and compare it to other multivariate medians. Then, we discuss four algorithms to compute the Oja median, which are implemented in our R package OjaNP. Besides these algorithms, the package contains also functions to compute Oja signs, Oja signed ranks, Oja ranks, and the related scatter concepts. To illustrate their use, the corresponding multivariate one- and C-sample location tests are implemented.

Abstract Background The apical prolapse is probably the most complex form of pelvic organ prolapse (POP). Adequate apical support is essential in the treatment of POP, as it contributes to the support in all vaginal compartments. This study aimed to evaluate the rate of symptomatic recurrent apical prolapse after high uterosacral ligament suspension (HUSLS), in a cohort of women characterised by a high prevalence of previous pelvic operations and a significant degree of prolapse. Methods This is a retrospective chart review of 95 women who underwent HUSLS for symptomatic apical prolapse from 2002 to 2009 at Aarhus University Hospital, Denmark. Of these women, 97% attended a six-month clinical control. Recurrence was defined as symptomatic vaginal vault prolapse stage 2 or more (according to the International Continence Society (ICS) quantification system). Medical charts were reviewed for a mean period of 7.2 years. Any new contacts due to prolapse were noted. Results Before the operation, 73% of the women were hysterectomised, and 52% had previous prolapse surgery. Stage 2 apical prolapse was reported in 71% of the women, whereas 26% had stage 3 or 4. At six-month follow-up, 19% of the women had recurrent symptomatic apical prolapse, and 9% of the women had symptomatic recurrent prolapse in other compartments 6 months after operation. In all, 35% of the women had a renewed prolapse operation during the long-term follow-up period. Perioperative adverse events were seen in 7%. Two women were re-operated due to postoperative complications. Conclusions This retrospective study of 95 women with a significant degree of prolapse and a high prevalence of previous pelvic operations demonstrates that the rate of recurrent prolapse associated with HUSLS might be higher than originally described. In conclusion, HUSLS may not be the optimal first choice of operation in this group of patients.

Within a pilot study, after pedological and mineralogical characterization, various kinetic models were tested to fit lead (Pb)-mobilization kinetics from soils at historic mining and smelting sites. Pb mobilization was obtained by modified electro-ultrafiltration (EUF) after addition of diethylenetriaminepentaacetic acid (DTPA) at variable conditions of extraction. 10 fractions were sequentially produced, under mild conditions at 20°C/200 V (to simulate an initial release) for fractions 1-5, and subsequently harder conditions at 80°C/400 V (to simulate a long-term release) for fractions 6-10. The special samples treated within this work yielded higher extraction rates within the first runs. Closest fits in terms of the coefficient of determination (R2) were obtained from the 2nd order polynomial model y = a + bt + ct2, and in terms of re-calculated results by the parabolic equation y = a + b √t. The fitted constants obtained by the modified EUF method correlated better with soil pH than with organic carbon and clay contents. From this, it remains open, whether the dissolution of the Pb-minerals in the electric field or concentration resp. diffusion of the DTPA is rate-determining.

Information on land cover is vital to numerous United Nations (UN) missions, including achieving the Sustainable Development Goals (SDGs). Because land cover data are developed by a variety of organizations for a range of objectives, they are based on different classification schemes and have discrepancies. In addition, the sustainability for land cover is hampered by limited access to information and documentation. Accordingly, international standards for land cover are developed to improve interoperability between different land cover datasets. However, the use and development of land cover datasets are limited by various factors including availability of properly documented land cover legends in support of different applications including change assessment, comparison, and international reporting. The purpose of this article is to highlight the importance of land cover in achieving several goals and to introduce the first international platform for land cover legend, named Land Cover Legend Registry (LCLR). This registry is a contribution to the international land cover community and the UN in effort to promote and support data harmonization processes and interoperability from local to global level, and vice versa. Users can not only use the registry for preparing consistent datasets, but also contribute to it by providing the latest data to ensure the long-term availability of both updated and existing datasets around the world. Moreover, building on the experience developing land cover legends with different nations, a brief explanation on the preparation of legends is also provided. Additionally, it is more important than ever to develop land cover registers to support the use, expansion, integration, and use uptake of land cover data, particularly for innovative remote sensing, machine learning, and information and communication technologies and techniques that build on existing and national contexts.

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Purpose: The density of the neuronal dopamine transporter (DAT) is directly correlated with the presynaptic dopaminergic system injury. In a first study, we evaluated the brain distribution and kinetics of [18F]LBT-999, a DAT PET radioligand, in a group of eight healthy subjects. Taking into account the results obtained in healthy volunteers, we wanted to evaluate whether the loss of presynaptic striatal dopaminergic fibers could be estimated, under routine clinical conditions, using [18F]LBT-999 and a short PET acquisition.Materials and methods: Six patients with Parkinson's disease (PD) were compared with eight controls. Eighty-nine minutes of dynamic PET following an intravenous injection of [18F]LBT-999 were acquired. Using regions of interest for striatal nuclei, substantia nigra (SN), cerebellum, and occipital cortex, defined over each T1 3D MRI, time–activity curves (TACs) were obtained. From TACs, binding potential (BPND) using the simplified reference tissue model and distribution volume ratios (DVRs) using Logan graphical analysis were calculated. Ratios obtained for a 10-min image, acquired between 30 and 40 min post-injection, were also calculated. Cerebellum activity was used as non-specific reference region.Results: In PD patients and as expected, striatal uptake was lower than in controls which is confirmed by BPND, DVR, and ratios calculated for both striatal nuclei and SN, significantly inferior in PD patients compared with controls (p < 0.001).Conclusions: PET with [18F]LBT-999 could be an alternative to assess dopaminergic presynaptic injury in a clinical environment using a single 10 min acquisition.

Background and objectives: Current studies show an important role of affective temperament in sport performance. The aim of this study was to assess the feasibility of the use of the TEMPS-A scale, by using it to examine five dimensions of affective temperament in three groups of athletes. We hypothesized that temperament may be a predisposing factor to the level of commitment and type of training. Materials and methods: The study group (N:71, 33 female) consisted of professional canoeists (N:25, aged 18–30), sports pilots (N:21, aged 19–57) and non-professionals regularly performing aerobic exercises (N:25, aged 23–33). The Affective Temperament of Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) was used to evaluate affective temperament dimensions. Statistical analysis was performed using non-parametric tests. Results: The TEMPS_A scale shows good internal consistency; a hyperthymic temperament was associated with different factors compared to other temperament traits. The most prevalent trait in the study group was hyperthymic temperament. The study group scored higher on hyperthymic and lower on depressive and anxious temperaments when compared with the general population. Canoeists scored higher on cyclothymic temperament compared with non-professional athletes and on cyclothymic and irritable dimensions in comparison with pilots. Pilots obtained significantly lower scores on irritable and anxious temperaments than non-professional athletes. Females scored higher on both hyperthymic and irritable dimensions. No significant differences were found in respect of depressive, cyclothymic and anxious traits. Age was negatively correlated with cyclothymic and irritable temperament scores. Conclusions: TEMPS-A scale is a useful tool for assessing affective temperament in athletes. The results suggest that affective temperament may be a factor influencing physical activity engagement. Different types of activities may be connected with different temperament dimensions. Younger athletes present a higher tendency to mood lability and sensitivity to environmental factors. However, further research is needed, involving larger numbers of subjects.

In recent years, Brazil has experienced a large wave of immigration, especially of Haitians, Bolivians and Colombians. In general these are poor immigrants with little knowledge of local language, laws and customs, who spend their savings paying intermediaries to help them get established in the country, to which they are attracted by promises of employment. The reality of this process, however, is different from the promises. This kind of relationship already existed in the 19th and early 20thcenturies, when immigration entrepreneurs participated in the colonization process, attracting immigrants and regularizing settlements. This article discusses the intermediary role of such agents in historical perspective, focusing on the activities of a 19th century immigration entrepreneur in Rio Grande do Sul and his relations with settlers in the colony he established

Light Detection And Ranging sensors (lidar) are key to autonomous driving, but their data is severely impacted by weather events (rain, fog, snow). To increase the safety and availability of self-driving vehicles, the analysis of the phenomena consequences at stake is necessary. This paper presents experiments performed in a climatic chamber with lidars of different technologies (spinning, Risley prisms, micro-motion and MEMS) that are compared in various artificial rain and fog conditions. A specific target with calibrated reflectance is used to make a first quantitative analysis. We observe different results depending on the sensors, valuable multi-echo information, and unexpected behaviors in the analysis with artificial rain are seen where higher rain rates do not necessarily mean higher degradations on lidar data.

O artigo avalia as consequências da presença de migrantes de outros estados brasileiros para a renda de negros e brancos paulistas. A literatura sociológica internacional inclui amplo debate sobre as consequências da imigração para os trabalhadores nativos, mas pouca discussão das consequências das migrações internas para os trabalhadores do local de destino dos migrantes. Usando os microdados do censo de 2010, estimamos modelos estatísticos hierárquicos para examinar o efeito contextual da proporção de migrantes em cada município do interior paulista sobre os salários de negros e brancos nativos. Os resultados mostram primeiro, que negros nativos do interior de São Paulo sofrem forte discriminação no mercado de trabalho relativo aos brancos nativos, que diminui seus salários em mais de dez per cento, em comparação com brancos com os mesmos níveis de escolarização e experiência nas mesmas categorias ocupacionais. A migração interestadual também se associa com aumentos salariais significativos para a população nativa, efeito que continua forte e altamente significante mesmo quando controlamos o PIB dos municípios. Este resultado é coerente com a literatura sobre as migrações internacionais, e mostra que a migração interna pode beneficiar trabalhadores nativos da mesma maneira que a imigração internacional. Os resultados também mostram que os benefícios da migração podem estar um pouco maiores para os brancos nativos que para os negros nativos, mas esse efeito é fraco e não significante. Estes resultados se referem às tendências gerais e podem esconder efeitos maiores nos salários dos negros nativos em ocupações ou indústrias específicas. É importante complementar esta pesquisa com o exame das mesmas tendências separadamente dentro das categorias ocupacionais e ao longo do tempo.

Background: Autosomal dominant optic atrophy (ADOA) is usually caused by mutations in the essential gene, OPA1. This encodes a ubiquitous protein involved in mitochondrial dynamics, hence tissue specificity is not understood. Dysregulated mitophagy (mitochondria recycling) is implicated in ADOA, being increased in OPA1 patient fibroblasts. Furthermore, autophagy may be increased in retinal ganglion cells (RGCs) of the OPA1Q285STOP mouse model.Aims: We developed a mouse model for studying mitochondrial dynamics in order to investigate mitophagy in ADOA.Methods: We crossed the OPA1Q285STOP mouse with our RedMIT/GFP-LC3 mouse, harboring red fluorescent mitochondria and green fluorescent autophagosomes. Colocalization between mitochondria and autophagosomes, the hallmark of mitophagy, was quantified in fluorescently labeled organelles in primary cell cultures, using two high throughput imaging methods Imagestream (Amnis) and IN Cell Analyzer 1000 (GE Healthcare Life Sciences). We studied colocalization between mitochondria and autophagosomes in fixed sections using confocal microscopy.Results: We validated our imaging methods for RedMIT/GFP-LC3 mouse cells, showing that colocalization of red fluorescent mitochondria and green fluorescent autophagosomes is a useful indicator of mitophagy. We showed that colocalization increases when lysosomal processing is impaired. Further, colocalization of mitochondrial fragments and autophagosomes is increased in cultures from the OPA1Q285STOP/RedMIT/GFP-LC3 mice compared to RedMIT/GFP-LC3 control mouse cells that were wild type for OPA1. This was apparent in both mouse embryonic fibroblasts (MEFs) using IN Cell 1000 and in splenocytes using ImageStream imaging flow cytometer (Amnis). We confirmed that this represents increased mitophagic flux using lysosomal inhibitors. We also used microscopy to investigate the level of mitophagy in the retina from the OPA1Q285STOP/RedMIT/GFP-LC3 mice and the RedMIT/GFP-LC3 control mice. However, the expression levels of fluorescent proteins and the image signal-to-background ratios precluded the detection of colocalization so we were unable to show any difference in colocalization between these mice.Conclusions: We show that colocalization of fluorescent mitochondria and autophagosomes in cell cultures, but not fixed tissues from the RedMIT/GFP-LC3, can be used to detect mitophagy. We used this model to confirm that mitophagy is increased in a mouse model of ADOA. It will be useful for cell based studies of diseases caused by impaired mitochondrial dynamics.

Nos últimos anos, o Brasil experimentou uma grande onde migratória, especialmente com a entrada de haitianos, bolivianos e colombianos. Em geral, são imigrantes pobres com pouco conhecimento da língua, das leis e dos costumes locais, que gastam suas economias contratando agenciadores para aqui se estabelecerem, atraídos por promessas de emprego. A realidade desse processo, entretanto, não condiz com as promessas. Esse tipo de relação já existia no século XIX e início do XX, quando empresários da imigração participavam no processo de colonização do país, agenciando imigrantes e regularizando assentamentos. Esse artigo busca discutir em perspectiva histórica o papel de intermediação desses agentes, a partir da análise de um empresário da imigração em Rio Grande do Sul e as relações por ele estabelecidas em sua colônia no século XIX.

Background/Aims: Hemorrhagic transformation (HT) is usually taken into account when symptomatic, but the role of asymptomatic HT is not well known. The aim of our study was to evaluate the link between HT after thrombolysis for ischemic stroke and functional outcome at 3 months, with particular emphasis on asymptomatic HT. Methods: Our study was performed prospectively between June 2012 and June 2013 in the Stroke Unit of the University Hospital Center of Tours (France). All patients treated with intravenous thrombolysis were consecutively included. HT was classified on susceptibility-weighted imaging (SWI) with 3-tesla MRI at 7 ± 3 days after treatment. We evaluated functional outcome at 3 months using the modified Rankin Scale (mRS). Dependency was defined as an mRS score of ≥3. Results: After 1 year, 128 patients had received thrombolytic therapy for ischemic stroke, of whom 90 patients underwent both 3-tesla MRI and SWI at day 7. Fifty-two had HT, including 8 symptomatic cases. At 3 months, 68% of those patients were dependent compared to 31% of patients without HT [OR 4.6 (1.9-11.4), p = 0.001]. In asymptomatic HT, the rate was 62% [OR 3.5 (1.4-8.9), p = 0.007], but did not reach significance after adjustment for stroke severity. Discussion: Our study found no statistically significant effect of HT on outcome after adjustment for initial stroke severity. However, the innocuousness of HT is not certain, and only few studies have already highlighted the increased risk of dependency. Using 3-tesla MRI with SWI allows us to increase the detection rate of small hemorrhage. Conclusion: HT after thrombolysis is very frequent on SWI, but the initial stroke severity is an important predictor to assess the role of HT for patient outcome.

Abstract Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal–habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities.

Background: Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimer's disease (AD). The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET) between PCA and AD subjects. Methods: We performed 18F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results: The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion: This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution.

[This corrects the article DOI: 10.1371/journal.pone.0130631.].

The Axelrod library is an open source Python package that allows for reproducible game theoretic research into the Iterated Prisoner’s Dilemma. This area of research began in the 1980s but suffers from a lack of documentation and test code. The goal of the library is to provide such a resource, with facilities for the design of new strategies and interactions between them, as well as conducting tournaments and ecological simulations for populations of strategies. With a growing collection of 139 strategies, the library is a also a platform for an original tournament that, in itself, is of interest to the game theoretic community. This paper describes the Iterated Prisoner’s Dilemma, the Axelrod library and its development, and insights gained from some novel research.

One essential prerequisite to ANOVA is homogeneity of variances in underlying populations. Violating this assumption may lead to an increased type I error rate. The reason for this undesirable effect is due to the calculation of the corresponding F-value. A slightly different test statistic keeps the level ®. The underlying distribution of this alternative method is Hotelling’s T2. As Hotelling’s T2 can be approximated by a Fisher’s F-distribution, this alternative test is very similar to an ordinary analysis of variance.

À partir d'un recensement municipal, on compare les situations de Noirs, de Brésiliens blancs et de divers groupes d'immigrants dans l'ouest de l'État de São Paulo en 1907. Contrairement à ce que dit la littérature, de nombreuses familles noires travaillaient comme colons du café et les Noirs disputaient avec les Européens certaines occupations manuelles. Par ailleurs, on vérifie l'absence presque totale de Noirs parmi les élites ainsi que des taux d'alphabétisation très bas chez eux, y compris dans la nouvelle génération née après l'abolition de l'esclavage. En montrant les avantages et désavantages vécus par les groupes répertoriés, cette recherche aide à l'élaboration de nouvelles hypothèses sur les conséquences de la grande immigration sur la population noire.

Recent concerns expressed by various national and international organisations about global livestock sector development and its consequences on the environment and on human and animal health suggest the need to reinforce efforts to monitor and collect more accurate and detailed statistics on livestock. Modern technologies for the organisation, analysis, dissemination and presentation of data and results enhance the contribution that these statistics can make towards the planning of efficient and sustainable animal production and health interventions. To this end, the Food and Agriculture Organization Animal Production and Health Division (FAO-AGA) has developed the Global Livestock Impact Mapping System (GLIMS). GLIMS provides a repository for sub-national data pertaining to the livestock sector and produces and distributes, through various channels and formats, a number of global public products, namely: the Gridded Livestock of the World (GLW), mapping the spatial distribution of the main livestock species, the Global Livestock Production and Health Atlas (GLiPHA), disseminating sub-national geo-referenced statistics, and the AGA Livestock Sector Briefs, which are concise national reports on the livestock sector. These products have a variety of applications. The authors focus attention on applications in the field of animal health, both to increase knowledge of the occurrence of livestock diseases and to assess their impact.

Species identification—of importance for most biological disciplines—is not always straightforward as cryptic species hamper traditional identification. Fibre-optic near-infrared spectroscopy (NIRS) is a rapid and inexpensive method of use in various applications, including the identification of species. Despite its efficiency, NIRS has never been tested on a group of more than two cryptic species, and a working routine is still missing. Hence, we tested if the four morphologically highly similar, but genetically distinct ant species Tetramorium alpestre, T. caespitum, T. impurum, and T. sp. B, all four co-occurring above 1,300 m above sea level in the Alps, can be identified unambiguously using NIRS. Furthermore, we evaluated which of our implementations of the three analysis approaches, partial least squares regression (PLS), artificial neural networks (ANN), and random forests (RF), is most efficient in species identification with our data set. We opted for a 100% classification certainty, i.e., a residual risk of misidentification of zero within the available data, at the cost of excluding specimens from identification. Additionally, we examined which strategy among our implementations, one-vs-all, i.e., one species compared with the pooled set of the remaining species, or binary-decision strategies, worked best with our data to reduce a multi-class system to a two-class system, as is necessary for PLS. Our NIRS identification routine, based on a 100% identification certainty, was successful with up to 66.7% of unambiguously identified specimens of a species. In detail, PLS scored best over all species (36.7% of specimens), while RF was much less effective (10.0%) and ANN failed completely (0.0%) with our data and our implementations of the analyses. Moreover, we showed that the one-vs-all strategy is the only acceptable option to reduce multi-class systems because of a minimum expenditure of time. We emphasise our classification routine using fibre-optic NIRS in combination with PLS and the one-vs-all strategy as a highly efficient pre-screening identification method for cryptic ant species and possibly beyond.

BACKGROUND:Effective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth. METHOD:We assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA) content in mice at embryonic (E) day 18 (E18). Females maintained on either low- (LPD) or normal- (NPD) protein diets were mated with NPD males. RESULTS:Fetal dry weight and placental efficiency (embryo/placental fresh weight) were positively correlated (r = 0.53, P = 0.0001). Individual placental dry weight was reduced by LPD (P = 0.003), as was the expression of amino acid transporter Slc38a2 and of growth factor Igf2. Placental water content, which is regulated by active transport of solutes, was increased by LPD (P = 0.0001). However, placental ATP content was also increased (P = 0.03). To investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos). High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta. CONCLUSIONS:These findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post-implantation trophoblast responses to nutrition.

Perennial grasslands play an important role as an extensive CO2 sink. Fodder and biofuels can be produced in an ecologically acceptable manner on such sites. Projected future climate-change scenarios suggest that Central Europe’s grasslands will be increasingly affected by drought. In order to determine whether there is potential for some alternative drought-adapted grass species to contribute to herbage production for either forage or biomass, we tested the agronomic performance of ten grass species (Agropyron elongatum, Agropyron intermedium, Agropyron desertorum, Agropyron trachycaulum, Elymus hoffmannii, Elymus junceus, Bromus inermis, Bromus marginatus, Festuca arundinacea and Panicum virgatum) in comparison to four reference grasses (Dactylis glomerata, Arrhenatherum elatius, Agrostis gigantea and Agropyron repens). Experiments were conducted in small-plot cutting trials at two sites across two growing seasons with either one or multiple cuts per season. In the one-cut system, P. virgatum provided the highest average annual dry matter (DM) yield (14 258 kg ha–1), followed by A. elongatum (13 086 kg ha–1). The multi-annual persistence of these two species under the experimental conditions was given only when P. virgatum was not harvested before freezing off and A. elongatum was harvested only once per year. Moreover, both species are susceptible to lodging. In the multiple-cut system, F. arundinacea showed a high yield (12 533 kg DM ha–1 average annual yield) and a low presence of associated weeds (only 0.1% surface area). Cultivating this grass species requires considering its only moderate competitiveness during the establishment phase. Based on the rapid establishment of A. trachycaulum, this species is expected to be best suited as a cover crop in seed mixtures. The yields of A. desertorum, A. trachycaulum, A. repens, E. junceus and B. marginatus were below the experimental average (9255 kg DM ha–1 at multiple cuttings). DOI: 10.5073/JfK.2014.06.01, https://doi.org/10.5073/JfK.2014.06.01

Trimmed regions are a powerful tool of multivariate data analysis. They describe a probability distribution in Euclidean d-space regarding location, dispersion, and shape, and they order multivariate data with respect to their centrality. Dyckerhoff and Mosler (2011) have introduced the class of weighted-mean trimmed regions, which possess attrac- tive properties regarding continuity, subadditivity, and monotonicity.We present an exact algorithm to compute the weighted-mean trimmed regions of a given data cloud in arbitrary dimension d. These trimmed regions are convex polytopes in Rd. To calculate them, the algorithm builds on methods from computational geometry. A characterization of a region’s facets is used, and information about the adjacency of the facets is extracted from the data. A key problem consists in ordering the facets. It is solved by the introduction of a tree-based order, by which the whole surface can be traversed efficiently with the minimal number of computations. The algorithm has been programmed in C++ and is available as the R package WMTregions.

Wolbachia are wide-spread, endogenous α-Proteobacteria of arthropods and filarial nematodes. 15-75% of all insect species are infected with these endosymbionts that alter their host's reproduction to facilitate their spread. In recent years, many insect species infected with multiple Wolbachia strains have been identified. As the endosymbionts are not cultivable outside living cells, strain typing relies on molecular methods. A Multi Locus Sequence Typing (MLST) system was established for standardizing Wolbachia strain identification. However, MLST requires hosts to harbour individual and not multiple strains of supergroups without recombination. This study revisits the applicability of the current MLST protocols and introduces Allele Intersection Analysis (AIA) as a novel approach. AIA utilizes natural variations in infection patterns and allows correct strain assignment of MLST alleles in multiply infected host species without the need of artificial strain segregation. AIA identifies pairs of multiply infected individuals that share Wolbachia and differ in only one strain. In such pairs, the shared MLST sequences can be used to assign alleles to distinct strains. Furthermore, AIA is a powerful tool to detect recombination events. The underlying principle of AIA may easily be adopted for MLST approaches in other uncultivable bacterial genera that occur as multiple strain infections and the concept may find application in metagenomic high-throughput parallel sequencing projects.

BackgroundRepetitive behaviours (RB) in patients with Gilles de la Tourette syndrome (GTS) are frequent. However, a controversy persists whether they are manifestations of obsessive-compulsive disorder (OCD) or correspond to complex tics.Methods166 consecutive patients with GTS aged 15-68 years were recruited and submitted to extensive neurological, psychiatric and psychological evaluations. RB were evaluated by the YBOCS symptom checklist and Mini International Neuropsychiatric Interview (M.I.N.I), and classified on the basis of a semi-directive psychiatric interview as compulsions or tics.ResultsRB were present in 64.4% of patients with GTS (107/166) and categorised into 3 major groups: a 'tic-like' group (24.3%-40/166) characterised by RB such as touching, counting, 'just right' and symmetry searching; an 'OCD-like' group (20.5%-34/166) with washing and checking rituals; and a 'mixed' group (13.2%-22/166) with both 'tics-like' and 'OCD-like' types of RB present in the same patient. In 6.3% of patients, RB could not be classified into any of these groups and were thus considered 'undetermined'.ConclusionsThe results confirm the phenomenological heterogeneity of RB in GTS patients and allows to distinguish two types: tic-like behaviours which are very likely an integral part of GTS; and OCD-like behaviours, which can be considered as a comorbid condition of GTS and were correlated with higher score of complex tics, neuroleptic and SSRIs treatment frequency and less successful socio-professional adaptation. We suggest that a meticulous semiological analysis of RB in GTS patients will help to tailor treatment and allow to better classify patients for future pathophysiologic studies.Trial registrationClinicalTrials.gov NCT00169351.

Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD): tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2) die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau) in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576) with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Ass load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD.

O artigo examina relações entre fazendeiros de café e trabalhadores negros após a abolição no município de São Carlos, no Oeste paulista, focalizando sobretudo conflitos violentos registrados em autos penais. Os negros reivindicavam respeito e dignidade, e lutavam para defender seu direito à privacidade; os fazendeiros, ainda ressentidos pela rebeldia dos escravos nos últimos anos antes da abolição, se irritavam com qualquer sinal de desacato dos negros, recorrendo rapidamente à violência para os rebaixar e humilhar, tendência que manifestavam menos nos conflitos com trabalhadores imigrantes. Os imigrantes que compraram fazendas de café ou assumiram posições de autoridade nas fazendas rapidamente internalizaram as mesmas disposições raciais exibidas por seus congêneres brasileiros.

Based on data from a municipal census in 1907, this study compared the situations of Blacks, White Brazilians, and various immigrant groups in early 20th century Western São Paulo. Contrary to assertions in the literature, many Black families were small coffee farmers, and Blacks competed with Europeans in various other manual occupations. Meanwhile, Blacks were almost completely absent from the elites, and literacy rates were extremely low among Blacks, including in the new generation, born after Abolition. The study analyzes the advantages and disadvantages of these various groups, thereby contributing to new hypotheses on the consequences of large-scale European immigration for the Black population.

Resumo Em vários países de imigração hoje, especialmente na Europa e na América do Norte, os “novos” imigrantes não europeus são vistos como mais problemáticos do que os imigrantes “históricos” da Europa. Geralmente, os movimentos e políticos anti-imigrantistas negam que sejam racistas, alegando que os novos imigrantes não aceitam os valores ocidentais, e que suas características culturais impedem a integração e produzem atitudes antidemocráticas, machistas e até terroristas. O artigo apresenta evidências históricas de que tal caracterização dos novos imigrantes, como se fossem portadores de uma alteridade insuperável, sem nenhuma relação com os países de imigração, só é possibilitada por duas formas de amnésia social: o esquecimento do tratamento sofrido por muitos imigrantes da periferia europeia no passado, e o esquecimento do passado colonial e neocolonial dos países de imigração. No passado, vários grupos imigrantes da periferia da Europa sofreram bastante hostilidade e estigmatização nos principais países de imigração. Também precisamos levar em conta o passado colonial para compreender as mudanças nos fluxos migratórios e as representações dos novos imigrantes, muitos dos quais não chegaram em grandes números antes, porque eram excluídos por políticas racistas de imigração. Distinguimos entre impérios de ultramar e impérios continentais, que muitas vezes incorporam povos conquistados como minorias nacionais e arbitrariamente dividem nações, redefinindo como “imigrantes” ou “ilegais” povos que migram dentro de seus próprios territórios. Argumentamos que a amnésia histórica e colonial não corresponde somente à vontade psicológica de deslegitimar os novos imigrantes; também é institucionalizada nos lugares e nas instituições da memória, que excluem da memória pública a integração dolorosa dos imigrantes da periferia europeia e as relações coloniais e neocoloniais entre os países de imigração e os territórios de origem dos novos imigrantes.

Resumo Este texto tem por objetivo problematizar a temática das migrações e sua importância no campo sociológico, tendo em vista o incremento global recente dos fluxos migratórios, que não se faz acompanhar de políticas adequadas à sua gestão, configurando um quadro social dramático e complexo cuja compreensão constitui um grande desafio para as ciências sociais e para a sociologia em particular. Buscando trazer elementos que contribuam para a compreensão da questão e para estimular o debate produtivo em torno dela, o texto introduz um conjunto de trabalhos que compõem o dossiê Sociologia das migrações: entre a compreensão do passado e os desafios do presente. Os artigos apresentam diferentes dimensões da problemática: em termos de abrangência (internacional ou focada no Brasil), em termos de passado e presente, em termos de abordagens macro e micro.