Miracle-dz/UniFAR-FTUs huggingface dataset:
Linking adult olfactory neurogenesis to social behavior

In the adult brain, new neurons are added to two brain areas: the olfactory bulb (OB) and the hippocampus. Newly-generated neurons integrate into the preexisting circuits, bringing a set of unique properties, such as increased plasticity and responsiveness to stimuli. However, the functional implications of the constant addition of these neurons remain unclear, although they are believed to be important for learning and memory. The levels of neurogenesis are regulated by a variety of environmental factors, as well as during learning, suggesting that new neurons could be important for coping with changing environmental demands. Notably, neurogenesis has been shown to be physiologically regulated in relation to reproductive behavior: neurogenesis increases in female mice upon exposure to cues of the mating partners, during pregnancy and lactation, and in male mice upon exposure to their offspring. In this scenario, and because of the key contribution of olfaction to maternal behavior, we sought to investigate the contribution of adult-generated neurons in the olfactory system to maternal behavior and offspring recognition. To do so, we selectively disrupted neurogenesis in the olfactory pathway of female mice using focal irradiation. Disruption of adult neurogenesis in the OB did not affect maternal behavior, or the ability of female mice to discriminate familiar from unfamiliar pups. However, reduction of olfactory neurogenesis resulted in abnormal social interaction of female mice, specifically with male conspecifics. Because the olfactory system is crucial for sex recognition, we suggest that the abnormal interaction with males could result from the inability to detect or discriminate male-specific odors and could therefore have implications for the recognition of potential mating partners. Here, I review the results of our study and others, and discuss their implications for our understanding of the function of adult neurogenesis.
Aspects of eco-immunology in molluscs

There is increasing interest in the international scientific community in eco-immunology, arelatively new discipline combining the knowledge from immunology, biology, ecology, physiology and biochemistry. The integrative approach of different scientific disciplines provides a useful perspective, mostly from an evolutionary point of view, into the understanding of the basic mechanisms of the immune responses, as well as the complex host-parasite interactions. However, while knowledge concerning factors affecting the immune response is increasing, more efforts should be made to determine the physiological mechanisms that regulate these responses. This need is particularly pressing in investigations in invertebrates because they are model organisms widely used to study the basic mechanisms of innate immunity and to assess environmental health (the immunomarker approach in biomonitoring studies). In this context, this review focuses on some of the ecoimmunology aspects of molluscs.
Impact of the Conjugate Pneumococcal Vaccine in Arkansas

Background: On the basis of the success of the early trials in the prevention of invasive pneumococcal disease in infants and children using a heptavalent conjugate pneumococcal vaccine, the American Academy of Pediatrics recommended in August 2000 that the vaccine be given concurrently with other childhood immunizations. Methods: Data concerning invasive pneumococcal infections from 1998–2000 were compared with 2001–2003 to assess the impact of the heptavalent pneumococcal conjugate vaccine in Arkansas. Basic demographic data were gathered as well as history of vaccination with the pneumococcal vaccine, underlying medical conditions, site of infection and morbidity and mortality. Pneumococcal isolates were serogrouped or serotyped and penicillin susceptibilities were obtained. Results: The incidence of invasive disease decreased from a high of 5.78/100,000 population to 3.02/100,000 population (P = 0.002). Although the percentage of White patients increased from 2001–2003, the overall incidence of disease did not change. The incidence of disease among Blacks fell from 20.5/100,000 population to 4.9/100,000 population. The greatest decrease of disease occurred in children 24 months of age or younger with the incidence rate falling from 44.2/100,00 population to 8.30/100,000 population (P < 0.02). The incidence among White children 24 months of age or younger fell from 19/100,000 population to 1.8/100,000 population, whereas that of Black children 24 months of age or younger declined from 164/100,000 to 35/100,000. From 1998 to 2000, 3.7/100 cases were from nonvaccine serogroups compared with 44/100 cases from 2001 to 2003 (P < 0.001). In children 24 months of age or younger, the number of nonvaccine isolates increased from 1.3/100 cases to 30.5/100 cases (P < 0.001). Overall 56 (44%) were nonsusceptible to penicillin from 1998 to 2000; that was not significantly different from 2001–2003 when 37 (46%) of 81 isolates were nonsusceptible to penicillin. Conclusions: A significant decrease of invasive pneumococcal disease has been documented in Arkansas. Of concern, however, is the increasing number of invasive isolates not included in the current vaccine.
The Gcn2 Regulator Yih1 Interacts with the Cyclin Dependent Kinase Cdc28 and Promotes Cell Cycle Progression through G2/M in Budding Yeast

The Saccharomyces cerevisiae protein Yih1, when overexpressed, inhibits the eIF2 alpha kinase Gcn2 by competing for Gcn1 binding. However, deletion of YIH1 has no detectable effect on Gcn2 activity, suggesting that Yih1 is not a general inhibitor of Gcn2, and has no phenotypic defect identified so far. Thus, its physiological role is largely unknown. Here, we show that Yih1 is involved in the cell cycle. Yeast lacking Yih1 displays morphological patterns and DNA content indicative of a delay in the G2/M phases of the cell cycle, and this phenotype is independent of Gcn1 and Gcn2. Accordingly, the levels of phosphorylated eIF2α, which show a cell cycle-dependent fluctuation, are not altered in cells devoid of Yih1. We present several lines of evidence indicating that Yih1 is in a complex with Cdc28. Yih1 pulls down endogenous Cdc28 in vivo and this interaction is enhanced when Cdc28 is active, suggesting that Yih1 modulates the function of Cdc28 in specific stages of the cell cycle. We also demonstrate, by Bimolecular Fluorescence Complementation, that endogenous Yih1 and Cdc28 interact with each other, confirming Yih1 as a bona fide Cdc28 binding partner. Amino acid substitutions within helix H2 of the RWD domain of Yih1 enhance Yih1-Cdc28 association. Overexpression of this mutant, but not of wild type Yih1, leads to a phenotype similar to that of YIH1 deletion, supporting the view that Yih1 is involved through Cdc28 in the regulation of the cell cycle. We further show that IMPACT, the mammalian homologue of Yih1, interacts with CDK1, the mammalian counterpart of Cdc28, indicating that the involvement with the cell cycle is conserved. Together, these data provide insights into the cellular function of Yih1/IMPACT, and provide the basis for future studies on the role of this protein in the cell cycle.
Environmental control of phosphorylation pathways in a branched two‐component system

NblS, the most conserved histidine kinase in cyanobacteria, regulates photosynthesis and acclimatization to a variety of environmental conditions. We used in silico, in vivo and in vitro approaches to identify RpaB and SrrA as the cognate response regulators of NblS and to characterize relevant interactions between components of this signalling system. While genetic analysis showed the importance of the NblS to RpaB phosphorylation branch for culture viability in Synechococcus elongatus PCC 7942, in vitro assays indicated a strong preference for NblS to phosphorylate SrrA. This apparent discrepancy can be explained by environmental insulation of the RpaB pathway, achieved by RpaB‐dependent repression of srrA under standard, low light culture conditions. After a strong but transient increase in srrA expression upon high light exposure, negative regulation of srrA and other high light inducible genes takes place, suggesting cooperation between pathways under environmental conditions in which both RpaB and SrrA are present. Complex regulatory interactions between RpaB and SrrA, two response regulators with a common evolutionary origin that are controlled by a single histidine kinase, are thus emerging. Our results provide a paradigm for regulatory interactions between response regulators in a branched two‐component system.
Intelligent personal assistants: can they understand and be understood by accented L2 learners?

Abstract Second/foreign language (L2) classrooms do not always provide opportunities for input and output practice [Lightbown, P. M. (2000). Classroom SLA research and second language teaching. Applied Linguistics, 21(4), 431–462]. The use of smart speakers such as Amazon Echo and its associated voice-controlled intelligent personal assistant (IPA) Alexa can help address this limitation because of its ability to extend the reach of the classroom, motivate practice, and encourage self-learning. Our previous study on the pedagogical use of Echo revealed that its use gave L2 learners ample opportunities for stress-free input exposure and output practice [Moussalli, S. , & Cardoso, W. (2016). Are commercial ‘personal robots’ ready for language learning? Focus on second language speech. In S. Papadima-Sophocleous, L. Bradley, & S. Thouësny (Eds.), CALL communities and culture – short papers from EUROCALL 2016 (pp. 325–329). However, the results also suggested that beginner learners, depending on their levels of accentedness, experienced difficulties interacting with and being understood by Echo. Interestingly, this observation differs from findings involving human-to-human interactions, which suggest that a speaker’s foreign accent does not impede intelligibility. In this article, we report the results of a study that investigated Echo’s ability to recognize and process non-native accented speech at different levels of accentedness, based on the accuracy of its replies for a set of pre-established questions. Using a variety of analytical methods (i.e. judges’ ratings of learners’ pronunciation, learners’ ratings of Echo’s pronunciation, transcriptions of Echo’s interactions, surveys and interviews) and via a multidimensional analysis of the data collected, our results indicate that L2 learners have no problems understanding Echo and that it adapts well to their accented speech (Echo is comparable to humans in terms of comprehensibility and intelligibility). Our results also show that L2 learners use a variety of strategies to mitigate the communication breakdown they experienced with Echo.
At a Supra-Physiological Concentration, Human Sexual Hormones Act as Quorum-Sensing Inhibitors

N-Acylhomoserine lactone (AHL)-mediated quorum-sensing (QS) regulates virulence functions in plant and animal pathogens such as Agrobacterium tumefaciens and Pseudomonas aeruginosa. A chemolibrary of more than 3500 compounds was screened using two bacterial AHL-biosensors to identify QS-inhibitors (QSIs). The purity and structure of 15 QSIs selected through this screening were verified using HPLC MS/MS tools and their activity tested on the A. tumefaciens and P. aeruginosa bacterial models. The IC50 value of the identified QSIs ranged from 2.5 to 90 µg/ml, values that are in the same range as those reported for the previously identified QSI 4-nitropyridine-N-oxide (IC50 24 µg/ml). Under the tested culture conditions, most of the identified QSIs did not exhibit bacteriostatic or bactericidal activities. One third of the tested QSIs, including the plant compound hordenine and the human sexual hormone estrone, decreased the frequency of the QS-regulated horizontal transfer of the tumor-inducing (Ti) plasmid in A. tumefaciens. Hordenine, estrone as well as its structural relatives estriol and estradiol, also decreased AHL accumulation and the expression of six QS-regulated genes (lasI, lasR, lasB, rhlI, rhlR, and rhlA) in cultures of the opportunist pathogen P. aeruginosa. Moreover, the ectopic expression of the AHL-receptors RhlR and LasR of P. aeruginosa in E. coli showed that their gene-regulatory activity was affected by the QSIs. Finally, modeling of the structural interactions between the human hormones and AHL-receptors LasR of P. aeruginosa and TraR of A. tumefaciens confirmed the competitive binding capability of the human sexual hormones. This work indicates potential interferences between bacterial and eukaryotic hormonal communications.
Metastasis-associated protein 1 induces VEGF-C and facilitates lymphangiogenesis in colorectal cancer.

AIM To study the correlation between high metastasis-associated protein 1 (MTA1) expression and lymphangiogenesis in colorectal cancer (CRC) and its role in production of vascular endothelial growth factor-C(VEGF-C). METHODS Impact of high MTA1 and VEGF-C expression levels on disease progression and lymphovascular density (LVD, D2-40-immunolabeled) in 81 cases of human CRC was evaluated by immunohistochemistry. VEGF-C mRNA and protein expressions in human LoVo and HCT116 cell lines were detected by real-time polymerase chain reaction and Western blotting, respectively, with a stable expression vector or siRNA. RESULTS The elevated MTA1 and VEGF-C expression levels were correlated with lymph node metastasis and Dukes stages (P < 0.05). Additionally, high MTA1 expression level was correlated with a large tumor size (P < 0.05). A significant correlation was found between MTA1 and VEGF-C protein expressions in tumor cells (r = 0.371, P < 0.05). Similar to the VEGF-C expression level, high MTA1 expression level was correlated with high LVD in CRC (P < 0.05). Furthermore, over-expression of MTA1 significantly enhanced the VEGF-C mRNA and protein expression levels, whereas siRNAs - knocked down MTA1 decreased the VEGF-C expression level. CONCLUSION MTA1, as a regulator of tumor-associated lymphangiogenesis, promotes lymphangiogenesis in CRC by mediating the VEGF-C expression.
Zebra lines of pamidronate therapy in children.

BACKGROUND Pamidronate therapy is increasingly used in children for the treatment of low bone mineral density and increased bone fragility resulting from a spectrum of conditions. The aim of the present study was to determine and describe the radiographic features associated with cyclical bisphosphonate therapy in the growing skeleton. METHODS A retrospective review of the radiographs of thirty-five children who had been managed with cyclical pamidronate was carried out. The physeal growth rates were estimated by measuring the band intervals on radiographs and the corresponding time intervals between the administered doses of pamidronate. RESULTS Metaphyseal bands, which we call zebra lines, were observed with band intervals that were dependent on the age of the patient, the rate of growth, and the dosing regimen. Epiphyseal and apophyseal bands were also observed in some patients. A distinction was made between Harris growth arrest lines and zebra lines. There was no evidence to suggest a deceleration in bone growth in children managed with pamidronate. CONCLUSIONS The term zebra lines is proposed as a descriptive term for the characteristic pattern of metaphyseal banding seen on the radiographs of children receiving cyclical bisphosphonate therapy.
A Bidirectional Two-Axis Electrostatic MEMS Positioning System

We report on the design, fabrication, and testing of a bidirectional two-axis MEMS positioning system that is used to move a stage. Sandia National Laboratories' MEMS foundry process was utilized for the fabrication of the device; this process incorporates five layers of polysilicon and four sacrificial layers of silicon dioxide. The positioning assembly consists of a pin and slotted-arm arrangement, wherein the pin is constrained between the slotted arms and the positioning of the pin is achieved by identical electrostatic drives on both axes. The electrostatic drives consist of a comb drive interfaced with a compliant-mechanism-based distance multiplier. The stage is connected to a cantilever arm extending from the positioning pin. The crosstalk between the X- and Y-axes was less than 0.3 ¿m through displacements of ~30 ¿m in both X- and Y-directions. The displacement shows a quadratic relationship with the applied voltage.
Deletion of the Pluripotency-Associated Tex19.1 Gene Causes Activation of Endogenous Retroviruses and Defective Spermatogenesis in Mice

As genetic information is transmitted through successive generations, it passes between pluripotent cells in the early embryo and germ cells in the developing foetus and adult animal. Tex19.1 encodes a protein of unknown function, whose expression is restricted to germ cells and pluripotent cells. During male spermatogenesis, Tex19.1 expression is highest in mitotic spermatogonia and diminishes as these cells differentiate and progress through meiosis. In pluripotent stem cells, Tex19.1 expression is also downregulated upon differentiation. However, it is not clear whether Tex19.1 has an essential function in germ cells or pluripotent stem cells, or what that function might be. To analyse the potential role of Tex19.1 in pluripotency or germ cell function we have generated Tex19.1−/− knockout mice and analysed the Tex19.1−/− mutant phenotype. Adult Tex19.1−/− knockout males exhibit impaired spermatogenesis. Immunostaining and histological analysis revealed defects in meiotic chromosome synapsis, the persistence of DNA double-strand breaks during meiosis, and a loss of post-meiotic germ cells in the testis. Furthermore, expression of a class of endogenous retroviruses is upregulated during meiosis in the Tex19.1−/− testes. Increased transposition of endogenous retroviruses in the germline of Tex19.1−/− mutant mice, and the concomitant increase in DNA damage, may be sufficient to disrupt the normal processes of recombination and chromosome synapsis during meiosis and cause defects in spermatogenesis. Our results suggest that Tex19.1 is part of a specialised mechanism that operates in the germline to repress transposable genetic elements and maintain genomic stability through successive generations.
Heuristic Sensitivity in Guided Random-Walk Based Model Checking

In this work we combine the complementary worlds of model checking and simulation. Model checking is used to verify that a model of a system satisfies some property. In general it considers all input. In simulation, a model of a system is executed for particular input. Our combined approach, referred to here as formal model simulation, uses the same formal model as model checking, but abandons the notion of verification, which seeks to prove that there are no errors in the model, and instead uses a guided random-walk search algorithm to find errors. The `guide' is provided by an abstraction of the system, which for the purposes of this work, is done by hand. Normally it would be automatically generated by analysing the model. We implement the approach in a tool called GRANSPIN, and in a series of experiments, compare the performance of GRANSPIN against the conventional model checker SPIN. Novel here is the use of a heuristic to guide the random walk towards states of the model that possibly violate user-defined properties. We also confirm in this work an earlier proposed characterisation called the Process Error Participation factor. This is a more thorough and extensive report of work that was briefly reported earlier.
A Stochastic Model to Study Rift Valley Fever Persistence with Different Seasonal Patterns of Vector Abundance: New Insights on the Endemicity in the Tropical Island of Mayotte

Rift Valley fever (RVF) is a zoonotic vector-borne disease causing abortion storms in cattle and human epidemics in Africa. Our aim was to evaluate RVF persistence in a seasonal and isolated population and to apply it to Mayotte Island (Indian Ocean), where the virus was still silently circulating four years after its last known introduction in 2007. We proposed a stochastic model to estimate RVF persistence over several years and under four seasonal patterns of vector abundance. Firstly, the model predicted a wide range of virus spread patterns, from obligate persistence in a constant or tropical environment (without needing vertical transmission or reintroduction) to frequent extinctions in a drier climate. We then identified for each scenario of seasonality the parameters that most influenced prediction variations. Persistence was sensitive to vector lifespan and biting rate in a tropical climate, and to host viraemia duration and vector lifespan in a drier climate. The first epizootic peak was primarily sensitive to viraemia duration and thus likely to be controlled by vaccination, whereas subsequent peaks were sensitive to vector lifespan and biting rate in a tropical climate, and to host birth rate and viraemia duration in arid climates. Finally, we parameterized the model according to Mayotte known environment. Mosquito captures estimated the abundance of eight potential RVF vectors. Review of RVF competence studies on these species allowed adjusting transmission probabilities per bite. Ruminant serological data since 2004 and three new cross-sectional seroprevalence studies are presented. Transmission rates had to be divided by more than five to best fit observed data. Five years after introduction, RVF persisted in more than 10% of the simulations, even under this scenario of low transmission. Hence, active surveillance must be maintained to better understand the risk related to RVF persistence and to prevent new introductions.
Regulation of B cell homeostasis and activation by the tumor suppressor gene CYLD

B cell homeostasis is regulated by multiple signaling processes, including nuclear factor-κB (NF-κB), BAFF-, and B cell receptor signaling. Conditional disruption of genes involved in these pathways has shed light on the mechanisms governing signaling from the cell surface to the nucleus. We describe a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLDex7/8 mice), which is a deubiquitinating enzyme that is integral to NF-κB signaling. This shorter CYLD protein lacks the TRAF2 and NEMO binding sites present in full-length CYLD. A dramatic expansion of mature B lymphocyte populations in all peripheral lymphoid organs occurs in this strain. The B lymphocytes themselves exhibit prolonged survival and manifest a variety of signaling disarrangements that do not occur in mice with a complete deletion of CYLD. Although both the full-length and the mutant CYLD are able to interact with Bcl-3, a predominant nuclear accumulation of Bcl-3 occurs in the CYLD mutant B cells. More dramatic, however, is the accumulation of the NF-κB proteins p100 and RelB in CYLDex7/8 B cells, which, presumably in combination with nuclear Bcl-3, results in increased levels of Bcl-2 expression. These findings suggest that CYLD can both positively and negatively regulate signal transduction and homeostasis of B cells in vivo, depending on the expression of CYLD splice variants.