Miracle-dz/UniFAR-FTUs huggingface dataset:
Within-Farm Changes in Dairy Farm-Associated Salmonella Subtypes and Comparison to Human Clinical Isolates in Michigan, 2000-2001 and 2009

ABSTRACT Temporal changes in the distribution of Salmonella subtypes in livestock populations may have important impacts on human health. The first objective of this research was to determine the within-farm changes in the population of subtypes of Salmonella on Michigan dairy farms that were sampled longitudinally in 2000-2001 and again in 2009. The second objective was to determine the yearly frequency (2001 through 2012) of reported human illnesses in Michigan associated with the same subtypes. Comparable sampling techniques were used to collect fecal and environmental samples from the same 18 Michigan dairy farms in 2000-2001 and 2009. Serotypes, multilocus sequence types (STs), and pulsed-field gel electrophoresis (PFGE) banding patterns were identified for isolates from 6 farms where >1 Salmonella isolate was recovered in both 2000-2001 and 2009. The distribution of STs was significantly different between time frames (P < 0.05); only two of 31 PFGE patterns were identified in both time frames, and each was recovered from the same farm in each time frame. Previously reported within-farm decreases in the frequency of multidrug-resistant (MDR) Salmonella were due to recovery of MDR subtypes of S. enterica serotypes Senftenberg and Typhimurium in 2000-2001 and genetically distinct, pansusceptible subtypes of the same serotypes in 2009. The annual frequency of human illnesses between 2001 and 2012 with a PFGE pattern matching a bovine strain decreased for patterns recovered from dairy farms in 2000-2001 and increased for patterns recovered in 2009. These data suggest important changes in the population of Salmonella on dairy farms and in the frequency of human illnesses associated with cattle-derived subtypes.
Precursors to Schizophrenia: Do Biological Markers Have Specificity?

This review addresses childhood antecedents and biological markers of schizophrenia within a neurodevelopmental framework. General-population birth-cohort studies illustrate delays in developmental milestones, abnormalities in social functioning, and cognitive deficits throughout childhood, adolescence, and early adulthood. Abnormal neurology and motor dysfunction have been measured in children prior to the onset of schizophrenia, at first onset of disease, and in those with chronic schizophrenia Minor physical anomalies, a static marker of developmental disturbance, are also increased in schizophrenia. None of these factors has high specificity for this disorder. This review examines the associations between these precursors and some etiological factors for schizophrenia, comments on their lack of complete specificity to this psychotic syndrome, and considers their usefulness as predictors of risk.
Associations Between Employment and Financial and Parental Stress in Low-Income Single Black Mothers

SUMMARY Using a sample of 188 low-income single black mothers (93 employed and 95 nonemployed), this study investigated financial strain, maternal depressive affect, and parenting stress among former welfare recipients who are now working, and current welfare recipients who are not employed. The findings suggested that being employed did not reduce financial strain, as the two groups reported similar levels of strain. However, regression analyses indicated that not being employed was associated with reporting higher levels of stress. Parenting stresswas also associated with attaining less education, having boys, reporting more financial strain and depressive affect. Correlates of maternal depressive affect were mother's education and financial strain. Interaction effects were found for employment by financial strain, indicating that higher levels of depressive affect were related to more financial strain among nonemployed mothers. The findings suggest that although employment is associated with better mental health for poor mothers, entry into the workforce is associated with stronger links between financial strain, parenting stress and depressive affect for mothers leaving welfare.
Three-dimensional information exchange over the semantic web for the domain of architecture, engineering, and construction

Abstract Three-dimensional (3-D) geometry can be described in many ways, with both a varying syntax and a varying semantics. As a result, several very diverse schemas and file formats can be deployed to describe geometry, depending on the application domain in question. In a multidisciplinary domain such as the domain of architecture, engineering, and construction, this range of specialized schemas makes file format conversions inevitable. The approach adopted by current conversion tools, however, often results in a loss of information, most often due to a “mistranslation” between different syntaxes and/or semantics, leading to errors and limitations in the design conception stage and to inefficiency due to the required remodeling efforts. An approach based on semantic web technology may reduce the loss of information significantly, leading to an improved processing of 3-D information and hence to an improved design practice in the architecture, engineering, and construction domain. This paper documents our investigation of the nature of this 3-D information conversion problem and how it may be encompassed using semantic web technology. In an exploratory double test case, we show how the specific deployment of semantic rule languages and an appropriate inference engine are to be adopted to improve this 3-D information exchange. It shows how semantic web technology allows the coexistence of diverse descriptions of the same 3-D information, interlinked through explicit conversion rules. Although only a simple example is used to document the process, and a more in-depth investigation is needed, the initial results indicate the suggested approach to be a useful alternative approach to obtain an improved 3-D information exchange.
A new perspective on the relationships among race, social class, and psychological distress.

Over the past decade, a body of research has developed which purports to show that the well-established relationship between race and psychological distress is due entirely to social class. In our paper we demonstrate that this view is incorrect: Most prior research has assumed that the effects of race and social class are additive; our analysis shows that they are actually interactive. The form of interaction is such that the true effect of race is suppressed and the true effect of social class is magnified in a model that fails to take the interaction into consideration. An analysis of eight different epidemiologic surveys documents this result and shows that race differences in psychological distress are particularly pronounced among people with low incomes. On the basis of this result we callfor renewed interest in the effect of race on mental health.
The Empathy Quotient: A cross-cultural comparison of the Italian version

Introduction. The Empathy Quotient (EQ) is a self-report questionnaire that was developed to measure the cognitive, affective, and behavioural aspects of empathy. We evaluated its cross-cultural validity in an Italian sample. Methods. A sample of 18- to 30-year-old undergraduate students of both sexes (N=256, males=118) were invited to fill in the Italian version of the EQ, as well as other measures of emotional competence and psychological distress. Results. The EQ had an excellent reliability (Cronbach's alpha=.79; test–retest at 1 month: Pearson's r=.85), and was normally distributed. Females scored higher than males, and more males (n=14, 11.9%) than females (n=4, 2.9%) scored lower than 30, the cutoff score that best differentiates autism spectrum conditions from controls. EQ was negatively related to the Toronto Alexithymia Scale (TAS) and positively related to the Marlowe-Crowne Social Desirability Scale (SDS). Principal component analysis retrieved the three-factor structure of the EQ. Lower emotional reactivity correlated with higher scores in measures of risk in both the schizophrenia-like (Peters et al. Delusions Inventory) and the bipolar (Hypomanic Personality Scale) spectra. Conclusions. The Italian version of the EQ has good validity, with an acceptable replication of the original three-factor solution, yielding three subscales with high internal and test–retest reliability.
A functional genetic link between distinct developmental language disorders.

BACKGROUND Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. We hypothesized that neural pathways downstream of FOXP2 influence more common phenotypes, such as specific language impairment. METHODS We performed genomic screening for regions bound by FOXP2 using chromatin immunoprecipitation, which led us to focus on one particular gene that was a strong candidate for involvement in language impairments. We then tested for associations between single-nucleotide polymorphisms (SNPs) in this gene and language deficits in a well-characterized set of 184 families affected with specific language impairment. RESULTS We found that FOXP2 binds to and dramatically down-regulates CNTNAP2, a gene that encodes a neurexin and is expressed in the developing human cortex. On analyzing CNTNAP2 polymorphisms in children with typical specific language impairment, we detected significant quantitative associations with nonsense-word repetition, a heritable behavioral marker of this disorder (peak association, P=5.0x10(-5) at SNP rs17236239). Intriguingly, this region coincides with one associated with language delays in children with autism. CONCLUSIONS The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language.
The C-Terminal Region Mesd Peptide Mimics Full-Length Mesd and Acts as an Inhibitor of Wnt/β-Catenin Signaling in Cancer Cells

While Mesd was discovered as a specialized molecular endoplasmic reticulum chaperone for the Wnt co-receptors LRP5 and LRP6, recombinant Mesd protein is able to bind to mature LRP5 and LRP6 on the cell surface and acts as a universal antagonist of LRP5/6 modulators. In our previous study, we found that the C-terminal region of Mesd, which is absent in sequences from invertebrates, is necessary and sufficient for binding to mature LRP6 on the cell surface. In the present studies, we further characterized the interaction between the C-terminal region Mesd peptide and LRP5/6. We found that Mesd C-terminal region-derived peptides block Mesd binding to LRP5 at the cell surface too. We also showed that there are two LRP5/6 binding sites within Mesd C-terminal region which contain several positively charged residues. Moreover, we demonstrated that the Mesd C-terminal region peptide, like the full-length Mesd protein, blocked Wnt 3A- and Rspodin1-induced Wnt/β-catenin signaling in LRP5- and LRP6- expressing cells, suppressed Wnt/β-catenin signaling in human breast HS578T cells and prostate cancer PC-3 cells, and inhibited cancer cell proliferation, although the full-length Mesd protein is more potent than its peptide. Finally, we found that treatment of the full-length Mesd protein and its C-terminal region peptide significantly increased chemotherapy agent Adriamycin-induced cytotoxicity in HS578T and PC-3 cells. Together, our results suggest that Mesd C-terminal region constitutes the major LRP5/6-binding domain, and that Mesd protein and its C-terminal region peptide have a potential therapeutic value in cancer.
Combined β-adrenergic and corticosteroid receptor activation regulates AMPA receptor function in hippocampal neurons

Shortly after stress, limbic neurons are exposed to high levels of noradrenaline and corticosterone. These hormones are necessary for optimal behavioural adaptation. Behavioural effects critically depend on noradrenaline acting via β-adrenergic receptors, but these effects are strongly modulated by corticosterone, indicating putative interactions between the two hormones. Since both noradrenaline and corticosterone are known to quickly affect properties of AMPA-type glutamate receptors (AMPAR), we here examined – in hippocampal neurons – three parameters which give insight in the functionality of AMPARs: phosphorylation, surface expression and spontaneous synaptic transmission. In homogenates of adult hippocampal slices, application of corticosterone (30 nM for 15 min) by itself did not affect phosphorylation of the AMPAR GluA1 subunit at S845 or S831. Co-application of the β-adrenergic receptor agonist isoproterenol (10 µM) largely increased S845 (but not S831) phosphorylation. Corticosterone also did not change GluA1 and GluA2 surface expression in hippocampal primary cultures. However, combined administration of corticosterone and 1 µM isoproterenol – which by itself was ineffective – enhanced surface expression. Interestingly, 10 µM isoproterenol alone enhanced GluA1 surface expression, but this was decreased by corticosterone. Finally, in hippocampal primary cultures, the inter-event interval of miniature excitatory postsynaptic currents (mEPSCs) was decreased by the combination of 1 µM isoproterenol and corticosterone (which were ineffective by themselves) while the same combination did not affect the amplitude. We conclude that AMPAR phosphorylation, surface expression and mEPSC inter-event interval respond most strongly to a combination of corticosterone and β-adrenergic receptors. These combined hormonal effects on glutamate transmission might contribute to their memory-enhancing effects.
Stability and Generalization

We deﬁne notions of stability for learning algorithms and show how to use these notions to derive generalization error bounds based on the empirical error and the leave-one-out error. The methods we use can be applied in the regression framework as well as in the classiﬁcation one when the classiﬁer is obtained by thresholding a real-valued function. We study the stability properties of large classes of learning algorithms such as regularization based algorithms. In particular we focus on Hilbert space regularization and Kullback-Leibler regularization. We demonstrate how to apply the results to SVM for regression and classiﬁcation.
Synthetic Lethal Approaches Exploiting DNA Damage in Aggressive Myeloma.

UNLABELLED Ongoing DNA damage is a common feature of epithelial cancers. Here, we show that tumor cells derived from multiple myeloma, a disease of clonal plasma cells, demonstrate DNA-replicative stress, leading to DNA damage. We identified a poor-prognosis subset of multiple myeloma with extensive chromosomal instability and replicative stress, which rely on ATR to compensate for DNA-replicative stress; conversely, silencing of ATR or treatment with a specific ATR inhibitor triggers multiple myeloma cell apoptosis. We show that oncogenes, such as MYC, induce DNA damage in multiple myeloma cells not only by increased replicative stress, but also via increased oxidative stress, and that reactive oxygen species-inducer piperlongumine triggers further DNA damage and apoptosis. Importantly, ATR inhibition combined with piperlongumine triggers synergistic multiple myeloma cytotoxicity. This synthetic lethal approach, enhancing oxidative stress while concomitantly blocking replicative stress response, provides a novel combination targeted therapy to address an unmet medical need in this subset of multiple myeloma. SIGNIFICANCE Multiple myeloma remains an incurable disease. We have identified a subset of multiple myeloma patients with poor prognosis, whose tumors present chromosomal instability, replicative and oxidative stress, and DNA damage. We define a synthetic lethal approach enhancing oxidative stress while targeting replicative stress response, inducing tumor cell apoptosis in this patient subset. Cancer Discov; 5(9); 972-87. ©2015 AACR.This article is highlighted in the In This Issue feature, p. 893.
Development of binocular vision in the kitten's striate cortex

Studies of the development and plasticity of the visual pathway are well documented, but a basic question remains open: what is the physiological status of the system prior to extensive visual experience? Somewhat conflicting answers have been put forward, and in a major area, binocular vision, reports have ranged from severe immaturity to well-developed maturity. This is an important question to resolve since binocular cells in the visual cortex are thought to be the neural substrate for stereoscopic depth perception. We have addressed this question by recording from single cells in the striate cortex of kittens at postnatal ages 2, 3, and 4 weeks and from adults for comparison. Gratings with sinusoidal luminance distribution are presented to left, right, or both eyes. For each cell, we determine optimal values for orientation and spatial frequency. Relative phase (retinal disparity) is then varied in a dichoptic sequence so that binocular interaction may be studied. Results are as follows. In the normal adult, we have shown in previous work that most binocular interaction in the visual cortex can be accounted for on the basis of linear summation. Results from 3 and 4 week postnatal kittens are closely similar to those from adults. All types of binocular interaction found in adults are present in kittens. This includes phase- specific and non-phase-specific suppression or facilitation. Furthermore, monocular and binocular tuning characteristics are comparable in kittens and adults. The clear changes that occur with age are optimal spatial frequencies and peak responses. In addition, at 2 weeks, there is a substantially higher proportion of monocular cells compared to other ages and correspondingly, lower relative numbers of cells that exhibit phase-specific or suppressive binocular interactions. From increases in optimal spatial frequency and interpupillary distance with age, we calculated predicted changes in binocular disparity thresholds (stereo acuity) with age. Although there are methodological limits with respect to the behavioral testing of young kittens, the predicted results are comparable to some of the values obtained. Considered together, our results show that the physiological apparatus for binocular vision is functional at an early stage in postnatal development. It is possible that the connections that underlie this function are developed rapidly during early postnatal experience. An alternative possibility is that there is an elaborate genetic organization of binocular vision, but our study does not address this issue directly. A combination of these factors may be applicable. (ABSTRACT TRUNCATED AT 400 WORDS)
Bridging the depleted MORB mantle and the continental crust using titanium isotopes

The mechanisms driving the chemical complementarity between depleted MORB mantle (DMM) and continental crust (with an average 'andesitic' composition) remain unclear. By investigating Archean komatiites, and modern enriched (E) and normal (N) MORB samples, we demonstrate that partial melting of the mantle does not fractionate Ti isotopes, whereas intracrustal differentiation causes significant Ti isotopic fractionation between melts and minerals, specifically Fe-Ti oxides. Thus, Ti isotope ratios are tracers of these two magmatic regimes. N-MORB and late Archean (2.9-2.7 Ga) komatiites are depleted in the heavier Ti isotopes compared to E-MORB and middle Archean (3.5-3.3 Ga) komatiites. We show that the depletion in the heavier Ti isotopes of the DMM is due to mantle recycling of the isotopically light residues from the generation of felsic continental crust over 3.5-2.7 Ga. This process must have reached a steady state by ≈ 2.5 Ga, based on the uniform Ti isotopic composition of contemporary N-MORBs and late Archean komatiites. This change is likely due to a decrease in the mantle potential temperature related to the emergence of plate tectonics.
SMA-Causing Missense Mutations in Survival motor neuron (Smn) Display a Wide Range of Phenotypes When Modeled in Drosophila

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of phenotypic severities, similar to the human disease. Furthermore, specific interactions with other proteins known to be important for SMN's role in RNP assembly are conserved. Intragenic complementation analyses revealed that the three most severe mutations, all of which map to the YG box self-oligomerization domain of SMN, display a stronger phenotype than the null allele and behave in a dominant fashion. In support of this finding, the severe YG box mutants are defective in self-interaction assays, yet maintain their ability to heterodimerize with wild-type SMN. When expressed at high levels, wild-type SMN is able to suppress the activity of the mutant protein. These results suggest that certain SMN mutants can sequester the wild-type protein into inactive complexes. Molecular modeling of the SMN YG box dimer provides a structural basis for this dominant phenotype. These data demonstrate that important structural and functional features of the SMN YG box are conserved between vertebrates and invertebrates, emphasizing the importance of self-interaction to the proper functioning of SMN.