Search

The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochetes in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18-depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Alcohol drinking patterns may determine the risk of hypertension and may also modify the detrimental effect of high alcohol intake. We prospectively evaluated the effect of the Mediterranean alcohol-drinking pattern and its interaction with the amount of alcohol consumed on the incidence of arterial hypertension. In the “Seguimiento Universidad de Navarra” (SUN) cohort, we followed-up 13,805 participants, all of them initially free of hypertension, during a maximum period of 16 years. Information about diet, chronic diseases, lifestyle and newly diagnosed hypertension was collected using validated questionnaires. We used a 7-item score (0 to 9 points) that jointly considered moderate alcohol consumption, distributed over the week, with meals, and a preference for red wine and avoidance of binge-drinking. During 142,404 person-years of follow-up, 1443 incident cases of hypertension were identified. Low adherence (score < 2) to the Mediterranean alcohol-drinking pattern was significantly associated with a higher incidence of hypertension (multivariable-adjusted hazard ratio 1.81, 95% confidence interval 1.09−2.99) as compared to the high-adherence (score > 7) category. Among alcohol consumers, a high adherence to the MADP is associated with a lower incidence of hypertension. Compared with abstinence, a high adherence did not seem to differ regarding its effect on hypertension risk.

Borrelia burgdorferi, the tick-transmitted spirochete agent of Lyme disease, has a highly segmented genome with a linear chromosome and various linear or circular plasmids. Here, by imaging several chromosomal loci and 16 distinct plasmids, we show that B. burgdorferi is polyploid during growth in culture and that the number of genome copies decreases during stationary phase. B. burgdorferi is also polyploid inside fed ticks and chromosome copies are regularly spaced along the spirochete's length in both growing cultures and ticks. This patterning involves the conserved DNA partitioning protein ParA whose localization is controlled by a potentially phage-derived protein, ParZ, instead of its usual partner ParB. ParZ binds its own coding region and acts as a centromere-binding protein. While ParA works with ParZ, ParB controls the localization of the condensin, SMC. Together, the ParA/ParZ and ParB/SMC pairs ensure faithful chromosome inheritance. Our findings underscore the plasticity of cellular functions, even those as fundamental as chromosome segregation., (© 2022. The Author(s).)

Introduction: Varying public views on cannabis use across countries may explain the variation in the prevalence of use, policies, and research in individual countries, and global regulation of cannabis. This paper aims to describe the current state of cannabis use, policies, and research across sixteen countries., Methods: PubMed and Google Scholar were searched for studies published from 2010 to 2020. Searches were conducted using the relevant country of interest as a search term (e.g., "Iran"), as well as relevant predefined keywords such as "cannabis," "marijuana," "hashish," "bhang "dual diagnosis," "use," "addiction," "prevalence," "co-morbidity," "substance use disorder," "legalization" or "policy" (in English and non-English languages). These keywords were used in multiple combinations to create the search string for studies' titles and abstracts. Official websites of respective governments and international organizations were also searched in English and non-English languages (using countries national languages) to identify the current state of cannabis use, policies, and research in each of those countries., Results: The main findings were inconsistent and heterogeneous reporting of cannabis use, variation in policies (e.g., legalization), and variation in intervention strategies across the countries reviewed. European countries dominate the cannabis research output indexed on PubMed, in contrast to Asian countries (Thailand, Malaysia, India, Iran, and Nepal)., Conclusions: Although global cannabis regulation is ongoing, the existing heterogeneities across countries in terms of policies and epidemiology can increase the burden of cannabis use disorders disproportionately and unpredictably. There is an urgent need to develop global strategies to address these cross-country barriers to improve early detection, prevention, and interventions for cannabis use and related disorders., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Objectives: We examined the associations of lockdown stringency and duration with Google searches for four mental health concepts (i.e., "Anxiety," "Depression," "Suicide," "Mental Health") in nine countries (i.e., Hungary, India, Iran, Italy, Paraguay, Serbia, South Africa, Spain, Turkey) during the COVID-19 pandemic., Methods: We retrieved national-level data for each country from Google Trends and the Global Panel Database of Pandemic Policies. In our primary analysis, we used data from all countries to estimate a set of multilevel regression models examining associations of overall lockdown stringency and lockdown duration with relative search volumes for each mental health term. We repeated the models after replacing overall lockdown stringency with each of the lockdown stringency components., Results: A negative association was found between overall lockdown stringency and "Depression." Lockdown duration and the most stringent stay-at-home requirements were negatively associated with "Anxiety." Policies that recommended or required the cancelation of public events evidenced negative associations with "Depression," whereas associations between policies that required some or all levels of schooling to close and "Depression" were positive. Policies that recommended or required workplaces to close and those that enforced quarantines on non-citizens arriving from high-risk regions or closed borders entirely were negatively associated with "Suicide.", Conclusions: Lockdown duration and some lockdown policies during the COVID-19 pandemic were generally associated with significantly lower, rather than higher, Google searches for selected mental health terms. These findings could be used alongside other evidence to develop future lockdown strategies that are sensitive to mental health issues during public health crises., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lysine crotonylation (Kcr) is a newly discovered post-translational modification, which is structurally and functionally different from the widely studied lysine acetylation. Kcr is found on histones and non-histone proteins, participating in many biological processes through the regulation of chromatin remodeling, metabolism, cell cycle and cellular organization. Among plants, Kcr in histones is not found in the same lysine residues but increases gene expression when it is co-localized with lysine acetylation. Kcr in non-histone proteins is mainly found in the chloroplast, which provides new insight into photosynthesis. In this review, we discuss recent findings on plant Kcr in histone and non-histone proteins, highlighting its biological implications. These findings not only point to new functions for Kcr, but also reveal the mechanisms by which crotonylation regulates cellular processes in plants and may even change the general direction of epigenome and plant regulation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Scientific literature has shown contextual factors that predict youth development, and family variables are the most important ones. In this study, we propose a model that explains the relation between family variables (relationship with parents and family activities) and Personal Positive Youth Development (assessed through Life satisfaction, Interiority, and Self-control), across different cultures. We recruited 2867 adolescents aged 12-18 years (52% female) from three countries: Spain, Mexico, and Peru. They completed an anonymous questionnaire. We run exploratory and confirmatory factor analyses, and structural equation modelling, testing for invariance across countries and sexes. In all subsamples, positive family relationships were associated with adolescents' Life Satisfaction. In addition, time invested on family activities was associated with Interiority and with Self-control. However, some differences across cultures and sex were found in the specific associations. Theoretical and practical implications are discussed regarding how to improve adolescent development through family life., (© 2021 The Authors. Journal of Community Psychology published by Wiley Periodicals LLC.)

Pseudomonas aeruginosa is an opportunistic pathogen that causes infections in a variety of settings. Many P. aeruginosa isolates are infected by filamentous Pf bacteriophage integrated into the bacterial chromosome as a prophage. Pf virions can be produced without lysing P. aeruginosa. However, cell lysis can occur during superinfection, which occurs when Pf virions successfully infect a host lysogenized by a Pf prophage. Temperate phages typically encode superinfection exclusion mechanisms to prevent host lysis by virions of the same or similar species. In this study, we sought to elucidate the superinfection exclusion mechanism of Pf phage. Initially, we observed that P. aeruginosa that survive Pf superinfection are transiently resistant to Pf-induced plaquing and are deficient in twitching motility, which is mediated by type IV pili (T4P). Pf utilize T4P as a cell surface receptor, suggesting that T4P are suppressed in bacteria that survive superinfection. We tested the hypothesis that a Pf-encoded protein suppresses T4P to mediate superinfection exclusion by expressing Pf proteins in P. aeruginosa and measuring plaquing and twitching motility. We found that the Pf protein PA0721, which we termed Pf s uperinfection e xclusion (PfsE), promoted resistance to Pf infection and suppressed twitching motility by binding the T4P protein PilC. Because T4P play key roles in biofilm formation and virulence, the ability of Pf phage to modulate T4P via PfsE has implications in the ability of P. aeruginosa to persist at sites of infection. IMPORTANCE Pf bacteriophage (phage) are filamentous viruses that infect Pseudomonas aeruginosa and enhance its virulence potential. Pf virions can lyse and kill P. aeruginosa through superinfection, which occurs when an already infected cell is infected by the same or similar phage. Here, we show that a small, highly conserved Pf phage protein (PA0721, PfsE) provides resistance to superinfection by phages that use the type IV pilus as a cell surface receptor. PfsE does this by inhibiting assembly of the type IV pilus via an interaction with PilC. As the type IV pilus plays important roles in virulence, the ability of Pf phage to modulate its assembly has implications for P. aeruginosa pathogenesis.

Concrete conceptual knowledge is supported by a distributed neural network representing different semantic features according to the neuroanatomy of sensory and motor systems. If and how this framework applies to abstract knowledge is currently debated. Here we investigated the specific brain correlates of different abstract categories. After a systematic a priori selection of brain regions involved in semantic cognition, i.e. responsible of, respectively, semantic representations and cognitive control, we used a fMRI-adaptation paradigm with a passive reading task, in order to modulate the neural response to abstract (emotions, cognitions, attitudes, human actions) and concrete (biological entities, artefacts) categories. Different portions of the left anterior temporal lobe responded selectively to abstract and concrete concepts. Emotions and attitudes adapted the left middle temporal gyrus, whereas concrete items adapted the left fusiform gyrus. Our results suggest that, similarly to concrete concepts, some categories of abstract knowledge have specific brain correlates corresponding to the prevalent semantic dimensions involved in their representation., (© 2021. The Author(s).)

Background: Several instruments have been developed to assess adolescent dating violence but only few have been validated in Spanish-speaking settings. Some instruments are too long and may not be feasible to include them in a multipurpose questionnaire. We developed an instrument to be used in the YourLife project, an international project about young people lifestyles., Objective: We aimed to analyze the psychometric properties of this instrument in three Spanish-speaking countries (Chile, Ecuador, and Spain)., Method: We included 1049 participants, aged 13-18 years. Exploratory and confirmatory factor analyses were conducted. Associations between dating violence and variables expected to covariate with it (substance use, school peer aggression, justification of dating violence, and relationship power imbalance), were tested., Results: Two different constructs (psychological and physical/sexual) for suffered and perpetrated violence were identified and confirmed in the three countries. The dating violence subscales had Cronbach's alpha scores higher than 0.85. The strongest associations between dating violence and variables related to it were found within the relationship power imbalance items, suggesting that these items may be useful to detect adolescent dating violence when a specific questionnaire cannot be implemented., Conclusion: This instrument seems to be adequate to assess suffered and perpetrated adolescent dating violence within a multipurpose questionnaire among schooled adolescents.

Background: Etiopathogenesis of preterm birth (PTB) is multifactorial, with a universe of risk factors interplaying between the mother and the environment. It is of utmost importance to identify the most informative factors in order to estimate the degree of PTB risk and trace an individualized profile. The aims of the present study were: 1) to identify all acknowledged risk factors for PTB and to select the most informative ones for defining an accurate model of risk prediction; 2) to verify predictive accuracy of the model and 3) to identify group profiles according to the degree of PTB risk based on the most informative factors., Methods: The Maternal Frailty Inventory (MaFra) was created based on a systematic review of the literature including 174 identified intrauterine (IU) and extrauterine (EU) factors. A sample of 111 pregnant women previously categorized in low or high risk for PTB below 37 weeks, according to ACOG guidelines, underwent the MaFra Inventory. First, univariate logistic regression enabled p-value ordering and the Akaike Information Criterion (AIC) selected the model including the most informative MaFra factors. Second, random forest classifier verified the overall predictive accuracy of the model. Third, fuzzy c-means clustering assigned group membership based on the most informative MaFra factors., Results: The most informative and parsimonious model selected through AIC included Placenta Previa, Pregnancy Induced Hypertension, Antibiotics, Cervix Length, Physical Exercise, Fetal Growth, Maternal Anxiety, Preeclampsia, Antihypertensives. The random forest classifier including only the most informative IU and EU factors achieved an overall accuracy of 81.08% and an AUC of 0.8122. The cluster analysis identified three groups of typical pregnant women, profiled on the basis of the most informative IU and EU risk factors from a lower to a higher degree of PTB risk, which paralleled time of birth delivery., Conclusions: This study establishes a generalized methodology for building-up an evidence-based holistic risk assessment for PTB to be used in clinical practice. Relevant and essential factors were selected and were able to provide an accurate estimation of degree of PTB risk based on the most informative constellation of IU and EU factors.

The spirochete Borrelia burgdorferi causes Lyme disease, an increasingly prevalent infection. While previous studies have provided important insight into B. burgdorferi biology, many aspects, including basic cellular processes, remain underexplored. To help speed up the discovery process, we adapted a CRISPR interference (CRISPRi) platform for use in B. burgdorferi For efficiency and flexibility of use, we generated various CRISPRi template constructs that produce different basal and induced levels of dcas9 and carry different antibiotic resistance markers. We characterized the effectiveness of our CRISPRi platform by targeting the motility and cell morphogenesis genes flaB, mreB, rodA, and ftsI, whose native expression levels span two orders of magnitude. For all four genes, we obtained gene repression efficiencies of at least 95%. We showed by darkfield microscopy and cryo-electron tomography that flagellin (FlaB) depletion reduced the length and number of periplasmic flagella, which impaired cellular motility and resulted in cell straightening. Depletion of FtsI caused cell filamentation, implicating this protein in cell division in B. burgdorferi Finally, localized cell bulging in MreB- and RodA-depleted cells matched the locations of new peptidoglycan insertion specific to spirochetes of the Borrelia genus. These results therefore implicate MreB and RodA in the particular mode of cell wall elongation of these bacteria. Collectively, our results demonstrate the efficiency and ease of use of our B. burgdorferi CRISPRi platform, which should facilitate future genetic studies of this important pathogen. IMPORTANCE Gene function studies are facilitated by the availability of rapid and easy-to-use genetic tools. Homologous recombination-based methods traditionally used to genetically investigate gene function remain cumbersome to perform in B. burgdorferi , as they often are relatively inefficient. In comparison, our CRISPRi platform offers an easy and fast method to implement as it only requires a single plasmid transformation step and IPTG addition to obtain potent (>95%) downregulation of gene expression. To facilitate studies of various genes in wild-type and genetically modified strains, we provide over 30 CRISPRi plasmids that produce distinct levels of dcas9 expression and carry different antibiotic resistance markers. Our CRISPRi platform represents a useful and efficient complement to traditional genetic and chemical methods to study gene function in B. burgdorferi ., (Copyright © 2020 Takacs et al.)

Preterm birth can affect cognitive functions, such as attention or more generally executive control mechanisms, with severity in impairments proportional to prematurity. The functional cross-talk between the Default Mode (DMN) and Executive Control (ECN) networks mirrors the integrity of cognitive processing and is directly related to brain development. In this study, a cohort of 20 preterm-born infants was investigated using rs-fMRI. First, we addressed biological maturity of the DMN per se and its interplay with the ECN in terms of patterns of increased functional connectivity. Second, we assessed the impact of the degree of prematurity on the DMN-ECN functional interplay development in relation to cognitive outcome at six months. Our results highlighted the emergence of DMN in preterm neonates, with connectivity strength and synchronization between the anterior DMN hub and frontal areas increasing as a function of biological maturity. Further, cognitive scores at 6 months were predicted by mPFC-ECN connectivity strength with degree of prematurity impacting on mPFC-ECN connectivity and triggering differential patterns of functional maturation of the ECN for very early/early and moderate/late preterm neonates. Our findings suggest that the prematurity window allows to observe precursors of functional plasticity that may underlie different developmental trajectories in preterm children., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Genetic studies in Borrelia require special consideration of the highly segmented genome, complex growth requirements and evolutionary distance of spirochetes from other genetically tractable bacteria. Despite these challenges, a robust molecular genetic toolbox has been constructed to investigate the biology and pathogenic potential of these important human pathogens. In this review we summarize the tools and techniques that are currently available for the genetic manipulation of Borrelia , including the relapsing fever spirochetes, viewing them in the context of their utility and shortcomings. Our primary objective is to help researchers discern what is feasible and what is not practical when thinking about potential genetic experiments in Borrelia . We have summarized published methods and highlighted their critical elements, but we are not providing detailed protocols. Although many advances have been made since B. burgdorferi was first transformed over 25 years ago, some standard genetic tools remain elusive for Borrelia . We mention these limitations and why they persist, if known. We hope to encourage investigators to explore what might be possible, in addition to optimizing what currently can be achieved, through genetic manipulation of Borrelia .

Recent evidence has shown that patterns of cortico-cortical functional synchronization are consistently traceable by the end of the third trimester of pregnancy. The involvement of subcortical structures in early functional and cognitive development has never been explicitly investigated, notwithstanding their pivotal role in different cognitive processes. We address this issue by exploring subcortico-cortical functional connectivity at rest in a group of normally developing fetuses between the 25th and 32nd weeks of gestation. Results show significant functional coupling between subcortical nuclei and cortical networks related to: (i) sensorimotor processing, (ii) decision making, and (iii) learning capabilities. This functional maturation framework unearths a Cognitive Development Blueprint, according to which grounding cognitive skills are planned to develop with higher ontogenetic priority. Specifically, our evidence suggests that a newborn already possesses the ability to: (i) perceive the world and interact with it, (ii) create salient representations for the selection of adaptive behaviors, and (iii) store, retrieve, and evaluate the outcomes of interactions, in order to gradually improve adaptation to the extrauterine environment., (© The Author(s) 2020. Published by Oxford University Press.)

Currently, there is a need of non-computationally-intensive bioinformatics tools to cope with the increase of large datasets produced by Next Generation Sequencing technologies. We present a simple and robust bioinformatics pipeline to search for novel enzymes in metagenomic sequences. The strategy is based on pattern searching using as reference conserved motifs coded as regular expressions. As a case study, we applied this scheme to search for novel proteases S8A in a publicly available metagenome. Briefly, (1) the metagenome was assembled and translated into amino acids; (2) patterns were matched using regular expressions; (3) retrieved sequences were annotated; and (4) diversity analyses were conducted. Following this pipeline, we were able to identify nine sequences containing an S8 catalytic triad, starting from a metagenome containing 9,921,136 Illumina reads. Identity of these nine sequences was confirmed by BLASTp against databases at NCBI and MEROPS. Identities ranged from 62 to 89% to their respective nearest ortholog, which belonged to phyla Proteobacteria, Actinobacteria, Planctomycetes, Bacterioidetes, and Cyanobacteria, consistent with the most abundant phyla reported for this metagenome. All these results support the idea that they all are novel S8 sequences and strongly suggest that our methodology is robust and suitable to detect novel enzymes., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2020.)

When the Lyme disease spirochete, Borrelia burgdorferi, transfers from a feeding tick into a human or other vertebrate host, the bacterium produces vertebrate-specific proteins and represses factors needed for arthropod colonization. Previous studies determined that the B. burgdorferi BpuR protein binds to its own mRNA and autoregulates its translation, and also serves as co-repressor of erp transcription. Here, we demonstrate that B. burgdorferi controls transcription of bpuR, expressing high levels of bpuR during tick colonization but significantly less during mammalian infection. The master regulator of chromosomal replication, DnaA, was found to bind specifically to a DNA sequence that overlaps the bpuR promoter. Cultured B. burgdorferi that were genetically manipulated to produce elevated levels of BpuR exhibited altered levels of several proteins, although BpuR did not impact mRNA levels. Among these was the SodA superoxide dismutase, which is essential for mammalian infection. BpuR bound to sodA mRNA in live B. burgdorferi, and a specific BpuR-binding site was mapped 5' of the sodA open reading frame. Recognition of posttranscriptional regulation of protein levels by BpuR adds another layer to our understanding of the B. burgdorferi regulome, and provides further evidence that bacterial protein levels do not always correlate directly with mRNA levels., (© 2019 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.)

Numerous methods exist for fluorescently labeling proteins either as direct fusion proteins (GFP, RFP, YFP, etc.-attached to the protein of interest) or utilizing accessory proteins to produce fluorescence (SNAP-tag, CLIP-tag), but the significant increase in size that these accompanying proteins add may hinder or impede proper protein folding, cellular localization, or oligomerization. Fluorescently labeling proteins with biarsenical dyes, like FlAsH, circumvents this issue by using a short 6-amino acid tetracysteine motif that binds the membrane-permeable dye and allows visualization of living cells. Here, we report the successful adaptation of FlAsH dye for live-cell imaging of two genera of spirochetes, Leptospira and Borrelia , by labeling inner or outer membrane proteins tagged with tetracysteine motifs. Visualization of labeled spirochetes was possible by fluorescence microscopy and flow cytometry. A subsequent increase in fluorescent signal intensity, including prolonged detection, was achieved by concatenating two copies of the 6-amino acid motif. Overall, we demonstrate several positive attributes of the biarsenical dye system in that the technique is broadly applicable across spirochete genera, the tetracysteine motif is stably retained and does not interfere with protein function throughout the B. burgdorferi infectious cycle, and the membrane-permeable nature of the dyes permits fluorescent detection of proteins in different cellular locations without the need for fixation or permeabilization. Using this method, new avenues of investigation into spirochete morphology and motility, previously inaccessible with large fluorescent proteins, can now be explored.

Objectives: To evaluate the influence of prophylactic anticonvulsive medication, above all levetiracetam monotherapy, in predicting the cognitive outcome of neurosurgical patients with post-traumatic brain injury, intracerebral hemorrhage, and encephalic tumors., Methods: We examined data concerning 232 of 327 adult patients admitted to the Neurorehabilitation Department of the San Raffaele Hospital (Milan, Italy) after discharge from the Neurosurgery Department. Cognitive status was evaluated by means of the "Mini-Mental State" examination and the Functional Independence Measure at baseline and at the end of a rehabilitation care with an average duration of about four weeks., Results: The vast majority of the patients were treated with levetiracetam. Our data showed a negative role of antiepileptic drugs on cognitive recovery in a cohort of neurosurgical patients., Conclusions: Knowing thoroughly the effects of antiepileptic drugs in rehabilitation outcome is of fundamental importance. This study represents the only large series analyzing these aspects in the rehabilitation of neurosurgical patients. Antiepileptic drugs should be managed to ensure patients the best possible cognitive outcome. Further evidence from good-quality trials is required to assess the clinical effectiveness of prophylactic anticonvulsive medication in predicting the cognitive outcome of neurosurgical patients who are treated with rehabilitation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Structured and unstructured leisure are known protective and risk factors, respectively, for alcohol consumption during adolescence. However, little is known about the interaction between the two leisure types and alcohol consumption., Method: A cross-sectional study was performed among high-school students in El Salvador and Peru. Schooled adolescents, aged 13-18 (N = 5640), completed a self-administered questionnaire about risk behaviors, including their leisure activities and whether they had consumed alcoholic beverages. They were classified into tertiles of the amount of time of both structured and unstructured activities. A non-conditional multivariate logistic regression was conducted to evaluate the association of both types of leisure with alcohol consumption. We also used a likelihood ratio test to assess the potential interaction of structured and unstructured leisure time in alcohol consumption., Results: Alcohol consumption was much more frequent among adolescents in the highest tertile of unstructured leisure time compared to the lowest one (Adjusted OR: 5.52; 95% CI: 4.49-6.78), and less frequent among those from the highest tertile of structured leisure time compared to the lowest one (Adjusted OR: 0.66; 95% CI: 0.55-0.80). We did not find an interaction effect between structured and unstructured leisure time with regard to initiation of alcohol consumption., Discussion: The study suggests that structured leisure is not enough to compensate for the possible harmful effect of unstructured leisure. Parents, educators and policy makers might be advised to discourage unstructured leisure among adolescents, and not simply to encourage structured leisure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To prospectively evaluate the association of the Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet and the Mediterranean diet (and their components), and depression risk., Methods: We followed-up (median 10.4 years) 15,980 adults initially free of depression at baseline or in the first 2 years of follow-up. Food consumption was measured at baseline through a validated food-frequency questionnaire, and was used to compute adherence to the MIND and the Mediterranean diets. Relationships between these two diets and incident depression were assessed through Cox regression models., Results: We identified 666 cases of incident depression. Comparing the highest versus the lowest quartiles of adherence, we found no association of the MIND diet and incident depression. This relation was statistically significant for the Mediterranean diet {hazard ratio (HR) 0.75, [95% confidence interval (95% CI) 0.61, 0.94]; p < 0.01}, although with departure from linearity. A reduced depression risk was associated with higher consumption of both fruits and nuts [HR 0.82 (95% CI 0.69, 0.96); p = 0.02], moderate nuts consumption [HR 0.77 (95% CI 0.64, 0.93); p = 0.01], and avoidance of fast/fried food [HR 0.63 (95% CI 0.41, 0.96); p = 0.03]., Conclusions: The Mediterranean diet was associated with reduced depression risk, but we found no evidence of such an association for the MIND diet.

Lyme disease is the most widely reported vector-borne disease in the United States. Its incidence is rapidly increasing, and disease symptoms can be debilitating. The need to understand the biology of the disease agent, the spirochete Borrelia burgdorferi , is thus evermore pressing. Despite important advances in B. burgdorferi genetics, the array of molecular tools available for use in this organism remains limited, especially for cell biological studies. Here, we adapt a palette of bright and mostly monomeric fluorescent proteins for versatile use and multicolor imaging in B. burgdorferi We also characterize two novel antibiotic selection markers and establish the feasibility of their use in conjunction with extant markers. Last, we describe a set of promoters of low and intermediate strengths that allow fine-tuning of gene expression levels. These molecular tools complement and expand current experimental capabilities in B. burgdorferi , which will facilitate future investigation of this important human pathogen. To showcase the usefulness of these reagents, we used them to investigate the subcellular localization of BB0323, a B. burgdorferi lipoprotein essential for survival in the host and vector environments. We show that BB0323 accumulates at the cell poles and future division sites of B. burgdorferi cells, highlighting the complex subcellular organization of this spirochete. IMPORTANCE Genetic manipulation of the Lyme disease spirochete B. burgdorferi remains cumbersome, despite significant progress in the field. The scarcity of molecular reagents available for use in this pathogen has slowed research efforts to study its unusual biology. Of interest, B. burgdorferi displays complex cellular organization features that have yet to be understood. These include an unusual morphology and a highly fragmented genome, both of which are likely to play important roles in the bacterium's transmission, infectivity, and persistence. Here, we complement and expand the array of molecular tools available for use in B. burgdorferi by generating and characterizing multiple fluorescent proteins, antibiotic selection markers, and promoters of varied strengths. These tools will facilitate investigations in this important human pathogen, as exemplified by the polar and midcell localization of the cell envelope regulator BB0323, which we uncovered using these reagents., (Copyright © 2018 Takacs et al.)

Evidence from both neuropsychology and neuroimaging suggests that different types of information are necessary for representing and processing concrete and abstract word meanings. Both abstract and concrete concepts, however, conjointly rely on perceptual, verbal and contextual knowledge, with abstract concepts characterized by low values of imageability (IMG) (low sensory-motor grounding) and low context availability (CA) (more difficult to contextualize). Imaging studies supporting differences between abstract and concrete concepts show a greater recruitment of the left inferior frontal gyrus (LIFG) for abstract concepts, which has been attributed either to the representation of abstract-specific semantic knowledge or to the request for more executive control than in the case of concrete concepts. We conducted an fMRI study on 27 participants, using a lexical decision task involving both abstract and concrete words, whose IMG and CA values were explicitly modelled in separate parametric analyses. The LIFG was significantly more activated for abstract than for concrete words, and a conjunction analysis showed a common activation for words with low IMG or low CA only in the LIFG, in the same area reported for abstract words. A regional template map of brain activations was then traced for words with low IMG or low CA, and BOLD regional time-series were extracted and correlated with the specific LIFG neural activity elicited for abstract words. The regions associated to low IMG, which were functionally correlated with LIFG, were mainly in the left hemisphere, while those associated with low CA were in the right hemisphere. Finally, in order to reveal which LIFG-related network increased its connectivity with decreases of IMG or CA, we conducted generalized psychophysiological interaction analyses. The connectivity strength values extracted from each region connected with the LIFG were correlated with specific LIFG neural activity for abstract words, and a regression analysis was conducted to highlight which areas recruited by low IMG or low CA predicted the greater activation of the IFG for abstract concepts. Only the left middle temporal gyrus/angular gyrus, known to be involved in semantic processing, was a significant predictor of LIFG activity differentiating abstract from concrete words. The results show that the abstract conceptual processing requires the interplay of multiple brain regions, necessary for both the intrinsic and extrinsic properties of abstract knowledge. The LIFG can be thus identified as the neural crossroads between different types of information equally necessary for representing processing and differentiating abstract concepts from concrete ones., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The SpoVG protein of Borrelia burgdorferi , the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism and is important for colonization in ticks. In addition, spirochetes engineered to dysregulate spoVG exhibited physiological alterations. IMPORTANCE B. burgdorferi persists in nature by cycling between ticks and vertebrates. Little is known about how the bacterium senses and adapts to each niche of the cycle. The present studies indicate that B. burgdorferi controls production of SpoVG and that this protein binds to specific sites of DNA and RNA in the genome and transcriptome, respectively. Altered expression of spoVG exerts effects on bacterial replication and other aspects of the spirochete's physiology., (Copyright © 2018 American Society for Microbiology.)

Lyme disease in humans is caused by several genospecies of the Borrelia burgdorferi sensu lato (s.l.) complex of spirochetal bacteria, including B. burgdorferi, B. afzelii and B. garinii. These bacteria exist in nature as obligate parasites in an enzootic cycle between small vertebrate hosts and Ixodid tick vectors, with humans representing incidental hosts. During the natural enzootic cycle, infected ticks in endemic areas feed not only upon naïve hosts, but also upon seropositive infected hosts. In the current study, we considered this environmental parameter and assessed the impact of the immune status of the blood-meal host on the phenotype of the Lyme disease spirochete within the tick vector. We found that blood from a seropositive host profoundly attenuates the infectivity (>104 fold) of homologous spirochetes within the tick vector without killing them. This dramatic neutralization of vector-borne spirochetes was not observed, however, when ticks and blood-meal hosts carried heterologous B. burgdorferi s.l. strains, or when mice lacking humoral immunity replaced wild-type mice as blood-meal hosts in similar experiments. Mechanistically, serum-mediated neutralization does not block induction of host-adapted OspC+ spirochetes during tick feeding, nor require tick midgut components. Significantly, this study demonstrates that strain-specific antibodies elicited by B. burgdorferi s.l. infection neutralize homologous bacteria within feeding ticks, before the Lyme disease spirochetes enter a host. The blood meal ingested from an infected host thereby prevents super-infection by homologous spirochetes, while facilitating transmission of heterologous B. burgdorferi s.l. strains. This finding suggests that Lyme disease spirochete diversity is stably maintained within endemic populations in local geographic regions through frequency-dependent selection of rare alleles of dominant polymorphic surface antigens.

Leptospires and other members of the evolutionarily ancient phylum of Spirochaetes are bacteria often characterized by long, highly motile spiral- or wave-shaped cells. Morphology and motility are critical factors in spirochete physiology, contributing to the ability of these bacteria to successfully colonize diverse environments. However, the mechanisms conferring the helical structure of Leptospira spp. have yet to be fully elucidated. We have identified five Leptospira biflexa bactofilin proteins, a recently characterized protein family with cytoskeletal properties. These five bactofilins are conserved in all species of the Leptospiraceae, indicating that these proteins arose early in the evolution of this family. One member of this protein family, LbbD, confers the optimal pitch distance in the helical structure of L. biflexa. Mutants lacking lbbD display a unique compressed helical morphology, a reduced motility and a decreased ability to tolerate cell wall stressors. The change in the helical spacing, combined with the motility and cell wall integrity defects, showcases the intimate relationship and coevolution between shape and motility in these spirochetes., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Amnestic mild cognitive impairment (aMCI) is a clinical condition characterized by memory impairment in the absence of any other cognitive impairment and is commonly associated with high conversion to Alzheimer's disease. Recent evidence shows that executive functions and selective attention mechanisms could also be impaired in aMCI. In this study, we investigated performance differences (i.e., reaction times [RTs] and accuracy) between a group of aMCI participants and a group of age-matched healthy individuals on the attentional network task (ANT) focusing on situations with increased interference. In particular, we assessed the relationship between interference and conflict effects and grey matter volumes (GMVs) of the anterior cingulate cortex (ACC)/pre-supplementary motor area in the entire sample because of its crucial role in conflict monitoring. When compared with controls, aMCI participants were less accurate on the ANT, showing increased interference and conflict effects, but no differences in RTs. In addition, aMCI participants exhibited lower GMV in the ACC than controls. While better accuracy for interference and conflict effects was associated with an increase of GMV in the ACC for both groups, RTs from the interference effect were negatively correlated with GMV of the ACC only in aMCI participants. In other words, lower GMV values of the ACC were paralleled with significantly impaired performance in terms of interference resolution. In conclusion, our study suggests the presence of a selective impairment in interference and conflict monitoring in aMCI, which in turn is associated with decreased GMVs in the ACC., (© 2016 The British Psychological Society.)

Speaking more than one language is associated with neurocognitive benefits in seniors (Alladi et al. 2013). Few studies however have tested this hypothesis directly by comparing bilingual seniors who vary in chronological age. We report a Voxel-Based Morphometry (VBM) study showing cumulative effects of age on grey matter volume (GMV) in brain structures that are involved in cognitive control in bilingual seniors and found no differences in RT or accuracy between bilingual and monolingual seniors on a behavioral test of cognitive control called the Attentional Network Task (ANT), and no differences in GMV for selected ROIs between groups. However, chronological age predicted the size of interference and conflict effects for monolingual speakers only. We also observed a more widespread pattern of bilateral aging-effcts in brain regions that are classically associated with aging in monolingual speakers compared to bilingual speakers. Notably, GMV in the dorsal anterior cingulate cortex (dACC) and the level of daily exposure to a second language (L2) independently predict performance on the ANT in bilingual speakers. We conclude that regular (daily) bilingual experience mitigates the typical effects of aging on cognitive control at the behavioral and the neural level., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Brain functional networks show high variability in short time windows but mechanisms governing these transient dynamics remain unknown. In this work, we studied the temporal evolution of functional brain networks involved in a working memory (WM) task while recording high-density electroencephalography (EEG) in human normal subjects. We found that functional brain networks showed an initial phase characterized by an increase of the functional segregation index followed by a second phase where the functional segregation faded after the prevailing the functional integration. Notably, wrong trials were associated with different or disrupted sequences of the segregation-integration profiles and measures of network centrality and modularity were able to identify crucial aspects of the oscillatory network dynamics. Additionally, computational investigations further supported the experimental results. The brain functional organization may respond to the information processing demand of a WM task following a 2-step atomic scheme wherein segregation and integration alternately dominate the functional configurations., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Borrelia burgdorferi is a symbiont of ticks of the Ixodes ricinus complex. These ticks serve as vectors to disseminate the spirochete to a variety of susceptible vertebrate hosts, which, in turn, act as reservoirs for naïve ticks to become infected, perpetuating the infectious life cycle of B. burgdorferi. The pivotal role of ticks in this life cycle and tick-spirochete interactions are the focus of this chapter. Here, we describe the challenging physiological environment that spirochetes encounter within Ixodes ticks, and the genetic factors that B. burgdorferi uses to successfully infect, persist, and be transmitted from the vector.

The role of the anterior cingulate cortex (ACC) in modulating the effect of bilingual experience on cognitive control has been reported at both functional and structural neural levels. Individual differences in the ACC sulcal patterns have been recently correlated with cognitive control efficiency in monolinguals. We aimed to investigate whether differences of ACC sulcation mediate the effect of bilingualism on cognitive control efficiency. We contrasted the performance of bilinguals and monolinguals during a cognitive control task (i.e., the Flanker Task) using a stratification based on the participants' ACC sulcal features. We found that performance of the two groups was differentially affected by ACC sulcation. Our findings provide the first evidence that early neurodevelopmental mechanisms may modulate the effect of different environmental backgrounds - here, bilingual vs monolingual experience - on cognitive efficiency., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There is an emerging use of brief dietary questionnaires to investigate diet-health relation. We prospectively assess the association between eating attitudes (yes/no) and incident cardiovascular disease (CVD) in 19,138 participants of the Seguimiento Universidad de Navarra (SUN) Cohort. We calculated a baseline healthy-eating attitudes score (in quartiles), positively weighting answers on more fruit, vegetables, fish and fiber and less meat, sweets and pastries, fat, butter, fatty meats and added sugar in drinks. We observed 139 incident cases of CVD. A higher score was associated with a lower risk of CVD [3-5 points Hazard Ratio (HR): 0.38 (95% confidence interval: 0.18-0.81); 6-8 points: 0.57 (0.29-1.12); 9-10 points: 0.31 (0.15-0.67), compared to 0-2 points]. Key contributors were the attitude to increase fruit [HR: 0.59 (0.40-0.87)], vegetables [HR: 0.57 (0.29-1.12)] and fiber intake [HR: 0.69 (0.48-0.98)]. Brief questionnaire on attitudes towards healthy-eating may be a useful tool for the primary prevention of CVD.

Background: Statistical Parametric Mapping (SPM) has been applied for single-subject evaluation of [18F]FDG uptake in Alzheimer Disease (AD). In a single-subject framework, the patient is compared to a dataset of [18F]FDG PET images from healthy subjects (HS) evaluating brain metabolic abnormalities. No studies exist that assess the effects on SPM analysis of HS [18F]FDG PET datasets acquired from different subjects and using different PET scanners including the same or different PET scanners than those used for patients. This work aims to elucidate this issue from a methodological perspective., Methods: We considered six different [18F]FDG PET datasets, from different HS populations, acquired by different PET scanners. We applied SPM5 procedures for single-subject comparison with each of the six HS datasets in 10 probable AD patients showing the typical [18F]FDG pattern. We also implemented the same comparison in 3 probable AD patients and in 7 patients with a clinical diagnosis of Mild Cognitive Impariment (MCI), showing subtle changes on visual inspection of [18F]FDG distribution., Results: Considering the 10 patients with the typical [18F]FDG pattern, the results were comparable for all the SPM maps. In the 3 probable AD patients with subtle changes in [18F]FDG distribution, no significant AD pattern emerged when a small number (<20) of HS was used, whereas a significant AD pattern appeared when a large (>50) HS image set was used. In the 7 considered MCI patients the use of a large (>50) HS image set allowed to assess significant hypometabolic patterns related to a probable neurodegenerative pathology., Conclusions: The use of large HS datasets of PET scans (>50) is recommended for single-subject SPM analysis. On condition that appropriate preprocessing steps are provided, large HS datasets can include HS images acquired with different PET systems, not including images from the same scanner of that used for patients.

During picture naming, the ease with which humans generate words is dependent upon the context in which they are named. For instances, naming previously presented items results in facilitation. Instead, naming a picture semantically related to previous items displays persistent interference effects (i.e., cumulative semantic interference, CSI). The neural correlates of CSI are still unclear and it is a matter of debate whether semantic control, or cognitive control more in general, is necessary for the resolution of CSI. We carried out an event-related fMRI experiment to assess the neural underpinnings of the CSI effect and the involvement and nature of semantic control. Both left inferior frontal gyrus (LIFG) and the left caudate nucleus (LCN) showed a linear increase of BOLD response positively associated with the consecutive number of presentations of semantically related pictures independently of task-load. The generalized psychophysiological interaction analysis showed that LIFG demonstrated a quantitative neural connectivity difference with the left supramarginal and angular gyri for increases of task-load and with the fusiform gyri for linear CSI increases. Furthermore, seed-to-voxel functional connectivity showed that LIFG activity coupled with different regions involved in cognitive control and lexicosemantic processing when semantic interference was elicited to a minimum or maximum degree. Our results are consistent with the lexical-competitive nature of the CSI effect, and we provide novel evidence that semantic control lies upon a more general cognitive control network (i.e., LIFG and LCN) responsible for resolving interference between competing semantically related items through connectivity with different brain areas in order to guarantee the correct response. Hum Brain Mapp 37:4179-4196, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background & Aims: Sorafenib (SOR) is the standard of care for patients with hepatocellular carcinoma (HCC) and portal vein invasion (PVI), based on the results of phase 3 trials. However, radioembolization (RE) using yttrium-90 microspheres has been shown to achieve higher response rates and better survival in large cohorts and phase 2 trials. This study aimed to compare survival of HCC patients with PVI treated by RE or SOR., Methods: Survival among patients with HCC and PVI treated with RE or SOR in four Spanish hospitals between 2005 and 2013 was analysed retrospectively. Kaplan-Meier survival curves were plotted and baseline variables tested for prognostic value using the log-rank test. A multivariate prognostic model including variables identified in the univariate analysis and adjusted by a propensity score based on factors that may determine the probability of exposure to RE was generated using Cox regression analyses., Results: After a median follow-up of 6 months, 60 deaths had occurred: 38 and 22 in SOR and RE groups respectively. Median survival was 6.7 months (95%CI 5.2-8.1 months) for the entire cohort, and 8.8 months (95%CI 1.8-15.8) in the RE group and 5.4 months (95%CI 2.7-8.1) in the SOR group (P = 0.047). The difference in survival was still statistically significant when 13 patients in the RE group who started SOR after a median time of 8 months were censored from the analysis., Conclusions: In a cohort of patients with HCC and PVI treatment with RE was associated with a more prolonged survival compared with SOR., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Language control refers to the cognitive mechanism that allows bilinguals to correctly speak in one language avoiding interference from the nontarget language. Bilinguals achieve this feat by engaging brain areas closely related to cognitive control. However, 2 questions still await resolution: whether this network is differently engaged when controlling nonlinguistic representations, and whether this network is differently engaged when control is exerted upon a restricted set of lexical representations that were previously used (i.e., local control) as opposed to control of the entire language system (i.e., global control). In the present event-related functional magnetic resonance imaging study, we investigated these 2 questions by employing linguistic and nonlinguistic blocked switching tasks in the same bilingual participants. We first report that the left prefrontal cortex is driven similarly for control of linguistic and nonlinguistic representations, suggesting its domain-general role in the implementation of response selection. Second, we propose that language control in bilinguals is hierarchically organized with the dorsal anterior cingulate cortex/presupplementary motor area acting as the supervisory attentional system, recruited for increased monitoring demands such as local control in the second language. On the other hand, prefrontal, inferior parietal areas and the caudate would act as the response selection system, tailored for language selection for both local and global control., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Borrelia burgdorferi, a Lyme disease agent, makes different major outer surface lipoproteins at different stages of its mouse-tick infectious cycle. Outer surface protein A (OspA) coats the spirochetes from the time they enter ticks until they are transmitted to a mammal. OspA is required for normal tick colonization and has been shown to bind a tick midgut protein, indicating that OspA may serve as a tick midgut adhesin. Tick colonization by spirochetes lacking OspA is increased when the infecting blood meal is derived from mice that do not produce antibody, indicating that OspA may protect the spirochetes from host antibody, which will not recognize tick-specific proteins such as OspA. To further study the importance of OspA during tick colonization, we constructed a form of B. burgdorferi in which the ospA open reading frame, on lp54, was replaced with the ospC gene or the ospB gene, encoding a mammal-specific or tick-specific lipoprotein, respectively. These fusions yielded a strain that produces OspC within a tick (from the fusion gene) and during early mammalian infection (from the normal ospC locus) and a strain that produces OspB in place of OspA within ticks. Here we show that the related, tick-specific protein OspB can fully substitute for OspA, whereas the unrelated, mammal-specific protein OspC cannot. These data were derived from three different methods of infecting ticks, and they confirm and extend previous studies indicating that OspA both protects spirochetes within ticks from mammalian antibody and serves an additional role during tick colonization., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Unlabelled: In many bacteria, the FtsH protease and its modulators, HflK and HflC, form a large protein complex that contributes to both membrane protein quality control and regulation of the cellular response to environmental stress. Both activities are crucial to the Lyme disease pathogen Borrelia burgdorferi, which depends on membrane functions, such as motility, protein transport, and cell signaling, to respond to rapid changes in its environment. Using an inducible system, we demonstrate that FtsH production is essential for both mouse and tick infectivity and for in vitro growth of B. burgdorferi FtsH depletion in B. burgdorferi cells resulted in membrane deformation and cell death. Overproduction of the protease did not have any detectable adverse effects on B. burgdorferi growth in vitro, suggesting that excess FtsH does not proteolytically overwhelm its substrates. In contrast, we did not observe any phenotype for cells lacking the protease modulators HflK and HflC (ΔHflK/C), although we examined morphology, growth rate, growth under stress conditions, and the complete mouse-tick infectious cycle. Our results demonstrate that FtsH provides an essential function in the life cycle of the obligate pathogen B. burgdorferi but that HflK and HflC do not detectably affect FtsH function., Importance: Lyme disease is caused by Borrelia burgdorferi, which is maintained in nature in an infectious cycle alternating between small mammals and Ixodes ticks. B. burgdorferi produces specific membrane proteins to successfully infect and persist in these diverse organisms. We hypothesized that B. burgdorferi has a specific mechanism to ensure that membrane proteins are properly folded and biologically active when needed and removed if improperly folded or dysfunctional. Our experiments demonstrate that FtsH, a protease that fulfills this role in other microorganisms, is essential to B. burgdorferi viability. Cells depleted of FtsH do not survive in laboratory culture medium and cannot colonize mice or ticks, revealing an absolute requirement for this protease. However, the loss of two potential modulators of FtsH activity, HflK and HflC, does not detectably affect B. burgdorferi physiology. Our results provide the groundwork for the identification of FtsH substrates that are critical for the bacterium's viability., (Copyright © 2016 Chu et al.)

Background: Borrelia burgdorferi, the tick-transmitted agent of Lyme disease, adapts to different environments as it cycles between an arthropod vector and vertebrate host. Signals encountered during nymphal tick feeding prior to transmission activate a regulon that is controlled by the alternative sigma factors RpoN and RpoS, which are required for mammalian infection. The ingested bloodmeal also provides nutrients that stimulate spirochete replication. Although the influence of tick feeding on spirochete growth and gene expression is well documented, a quantitative assessment of spirochete virulence before and after tick feeding has not been made., Methods: Homogenates were prepared from unfed and fed infected Ixodes scapularis nymphs that had acquired B. burgdorferi as larvae. Serially diluted tick homogenates were needle-inoculated into mice to determine the infectious dose of tick-derived spirochetes before and after the bloodmeal. Mouse infection was assessed by sero-reactivity with B. burgdorferi whole cell lysates on immunoblots and attempted isolation of spirochetes from mouse tissues. Viable spirochetes in tick-derived inocula were quantified by colony formation in solid media., Results: We found that an inoculum containing as many as 10(4) B. burgdorferi from unfed ticks is largely non-infectious, while the calculated ID50 for spirochetes from fed ticks is ~30 organisms. Engineered constitutive production of the essential virulence factor OspC by spirochetes within unfed ticks did not confer an infectious phenotype., Conclusion: Conditional priming of B. burgdorferi during tick feeding induces changes in addition to OspC that are required for infection of the mammalian host.

Recommended guidelines for the diagnosis of dementia due to Alzheimer's Disease (AD) were revised in recent years, including Positron Emission Tomography (PET) as an in-vivo diagnostic imaging technique for the diagnosis of neurodegeneration. In particular PET, using 18Ffluorodeoxiglucouse ([18F]FDG), is able to detect very early changes of glucose consumption at the synaptic level, enabling to support both early and differential diagnosis of AD. In standard clinical practice, interpretation of [18F] FDG-PET images is usually achieved through qualitative assessment. Visual inspection although only reveals information visible at human eyes resolution, while information at a higher resolution is missed. Furthermore, qualitative assessment depends on the degree of expertise of the clinician, preventing from the definition of accurate and standardized imaging biomarkers. Automated and computerized image processing methods have been proposed to support the in-vivo assessment of brain PET studies. In particular, objective statistical image analyses, enabling the comparison of one patient's images to a group of control images have been shown to carry important advantages for detecting significant metabolic changes, including the availability of more objective, cross-center reliable metrics and the detectability of brain subtle functional changes, as occurring in prodromal AD. The purpose of the current review is to provide a systematic overview encompassing the frontiers recently reached by quantitative approaches for the statistical analysis of PET brain images in the study of AD, with a particular focus on Statistical Parametric Mapping. Main achievements, e.g. in terms of standardized biomarkers of AD as well as of sensitivity and specificity, will be discussed.

The saprophyte Leptospira biflexa is an excellent model for studying the physiology of the medically important Leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. However, relatively little is known regarding the proteome of L. biflexa, limiting its utility as a model for some studies. Therefore, we have generated a proteomic map of both soluble and membrane-associated proteins of L. biflexa during exponential growth and in stationary phase. Using these data, we identified abundantly produced proteins in each cellular fraction and quantified the transcript levels from a subset of these genes using quantitative reverse transcription-PCR (RT-PCR). These proteins should prove useful as cellular markers and as controls for gene expression studies. We also observed a significant number of L. biflexa membrane-associated proteins with multiple isoforms, each having unique isoelectric focusing points. L. biflexa cell lysates were examined for several posttranslational modifications suggested by the protein patterns. Methylation and acetylation of lysine residues were predominately observed in the proteins of the membrane-associated fraction, while phosphorylation was detected mainly among soluble proteins. These three posttranslational modification systems appear to be conserved between the free-living species L. biflexa and the pathogenic species Leptospira interrogans, suggesting an important physiological advantage despite the varied life cycles of the different species., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Borrelia burgdorferi, a causative agent of Lyme borreliosis, is a zoonotic pathogen that survives in nutrient-limited environments within a tick, prior to transmission to its mammalian host. Survival under these prolonged nutrient-limited conditions is thought to be similar to survival during stationary phase, which is characterized by growth cessation and decreased protein production. Multiple ribosome-associated proteins are implicated in stationary-phase survival of Escherichia coli. These proteins include hibernation-promoting factor (HPF), which dimerizes ribosomes and prevents translation of mRNA. Bioinformatic analyses indicate that B. burgdorferi harbors an hpf homolog, the bb0449 gene. BB0449 protein secondary structure modeling also predicted HPF-like structure and function. However, BB0449 protein was not localized in the ribosome-associated protein fraction of in vitro-grown B. burgdorferi. In wild-type B. burgdorferi, bb0449 transcript and BB0449 protein levels are low during various growth phases. These results are inconsistent with patterns of synthesis of HPF-like proteins in other bacterial species. In addition, two independently derived bb0449 mutants successfully completed the mouse-tick infectious cycle, indicating that bb0449 is not required for prolonged survival in the nutrient-limited environment in the unfed tick or any other stage of infection by B. burgdorferi. We suggest either that BB0449 is associated with ribosomes under specific conditions not yet identified or that BB0449 of B. burgdorferi has a function other than ribosome conformation modulation., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

To evaluate brain development longitudinally in premature infants without abnormalities as compared to healthy full-term newborns, we assessed fMRI brain activity patterns in response to linguistic stimuli and white matter structural development focusing on language-related fibres. A total sample of 29 preterm newborns and 26 at term control newborns underwent both fMRI and DTI. Griffiths test was performed at 6 months of corrected age to assess development. Auditory fMRI data were analysed in 17 preterm newborns at three time points [34, 41 and 44 weeks of post menstrual age (wPMA)] and in 15 controls, at term. Analysis showed a distinctive pattern of cortical activation in preterm newborns up to 29 wPMA moving from early prevalent left temporal and supramarginal area activation in the preterm period, to a bilateral temporal and frontoopercular activation in the at term equivalent period and to a more fine-grained left pattern of activity at 44 wPMA. At term controls showed instead greater bilateral posterior thalamic activation. The different pattern of brain activity associated to preterm newborns mirrors their white matter maturation delay in peripheral regions of the fibres and thalamo-cortical radiations in subcortical areas of both hemispheres, pointing to different transient thalamo-cortical development due to prematurity. Evidence for functional thalamic activation and more mature subcortical tracts, including thalamic radiations, may represent the substantial gap between preterm and at term infants. The transition between bilateral temporal activations at term age and leftward activations at 44 weeks of PMA is correlated to better neuropsychological results in Griffiths test.

Naming abilities are typically preserved in amnestic Mild Cognitive Impairment (aMCI), a condition associated with increased risk of progression to Alzheimer's disease (AD). We compared the functional correlates of covert picture naming and word reading between a group of aMCI subjects and matched controls. Unimpaired picture naming performance was associated with more extensive activations, in particular involving the parietal lobes, in the aMCI group. In addition, in the condition associated with higher processing demands (blocks of categorically homogeneous items, living items), increased activity was observed in the aMCI group, in particular in the left fusiform gyrus. Graph analysis provided further evidence of increased modularity and reduced integration for the homogenous sets in the aMCI group. The functional modifications associated with preserved performance may reflect, in the case of more demanding tasks, compensatory mechanisms for the subclinical involvement of semantic processing areas by AD pathology., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The failure to name an object in Alzheimer's disease (AD) and in the semantic variant of the primary progressive aphasia (sv-PPA) has been generally attributed to semantic memory loss, with a progressive degradation of semantic features. Not all features, however, may have the same relevance in picture naming. We analyzed the relationship between picture naming performance and the loss of semantic features in patients with AD with or without naming impairment, with sv-PPA and in matched controls, assessing the role of distinctiveness, semantic relevance and feature type (sensorial versus non-sensorial) with a sentence verification task. The results showed that distinctive features with high values of semantic relevance were lost only in all patients with naming impairment. The performance on the sensorial distinctive features with high relevance was the best predictor of naming performance only in sv-PPA, while no difference between sensorial and non-sensorial features was found in AD patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Advantages and disadvantages of using intermediate layers underneath resin-composite restorations have been presented under different perspectives. Yet, few long-term clinical studies evaluated the effect of glass-ionomer bases on restoration survival. The present study investigated the influence of glass-ionomer-cement base in survival of posterior composite restorations, compared to restorations without base., Methods: Original datasets of one dental practice were used to retrieve data retrospectively. The presence or absence of an intermediate layer of glass-ionomer-cement was the main factor under analysis, considering survival, annual failure rate and types of failure as outcomes. Other investigated factors were: patient gender, jaw, tooth, number of restored surfaces and composite. Statistical analysis was performed using Fisher's exact test, Kaplan-Meier method and multivariate Cox-regression., Results: In total 632 restorations in 97 patients were investigated. Annual failure rates percentages up to 18-years were 1.9% and 2.1% for restorations with and without base, respectively. In restorations with glass-ionomer-cement base, fracture was the predominant reason for failure, corresponding to 57.8% of total failures. Failure type distribution was different (p=0.007) comparing restorations with and without base, but no effect in the overall survival of restorations was found (p=0.313)., Significance: The presence of a glass-ionomer-cement base did not affect the survival of resin-composite restorations in the investigated sample. Acceptable annual failure rates after 18-years can be achieved with both techniques, leading to the perspective that an intermediate layer, placed during an interim treatment, may be maintained without clinical detriment, but no improvement in survival should be expected based on such measure., (Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Background/aim: We present a clinical-neuroimaging study in a series of patients with a clinical diagnosis of semantic variant of primary progressive aphasia (svPPA), with the aim to provide clinical-functional correlations of the cognitive and behavioral manifestations at the single-subject level., Methods: We performed neuropsychological investigations, 18F-FDG-PET single-subject and group analysis, with an optimized SPM voxel-based approach, and correlation analyses. A measurement of white matter integrity by means of diffusion tensor imaging (DTI) was also available for a subgroup of patients., Results: Cognitive assessment confirmed the presence of typical semantic memory deficits in all patients, with a relative sparing of executive, attentional, visuo-constructional, and episodic memory domains. 18F-FDG-PET showed a consistent pattern of cerebral hypometabolism across all patients, which correlated with performance in semantic memory tasks. In addition, a majority of patients also presented with behavioral disturbances associated with metabolic dysfunction in limbic structures. In a subgroup of cases the DTI analysis showed FA abnormalities in the inferior longitudinal and uncinate fasciculi., Discussion: Each svPPA individual had functional derangement involving an extended, connected system within the left temporal lobe, a crucial part of the verbal semantic network, as well as an involvement of limbic structures. The latter was associated with behavioral manifestations and extended beyond the area of atrophy shown by CT scan., Conclusion: Single-subject 18F-FDG-PET analysis can account for both cognitive and behavioral alterations in svPPA. This provides useful support to the clinical diagnosis.

It has been postulated that bilingualism may act as a cognitive reserve and recent behavioral evidence shows that bilinguals are diagnosed with dementia about 4-5 years later compared to monolinguals. In the present study, we investigated the neural basis of these putative protective effects in a group of aging bilinguals as compared to a matched monolingual control group. For this purpose, participants completed the Erikson Flanker task and their performance was correlated to gray matter (GM) volume in order to investigate if cognitive performance predicts GM volume specifically in areas affected by aging. We performed an ex-Gaussian analysis on the resulting RTs and report that aging bilinguals performed better than aging monolinguals on the Flanker task. Bilingualism was overall associated with increased GM in the ACC. Likewise, aging induced effects upon performance correlated only for monolinguals to decreased gray matter in the DLPFC. Taken together, these neural regions might underlie the benefits of bilingualism and act as a neural reserve that protects against the cognitive decline that occurs during aging., (Copyright © 2015 Elsevier Ltd. All rights reserved.)