Leaky Gut’s Contribution to Inefficient Nutrient Utilization

There are a variety of situations in an animal’s life when nutrient utilization is reprioritized from productive towards agriculturally unproductive purposes. Two well-known examples that markedly reduce production are heat stress and ketosis. Decreased feed intake, experienced during both disorders, is unable to fully explain production losses. Additionally, both disorders are characterized by negative energy balance, body weight loss, inflammation, and liver fat accumulation. While the metabolism of ketosis and heat stress has been thoroughly studied for the last 40 years, the initial insult in the cascade of events ultimately reducing productivity in both heat-stressed and ketotic cows has not been identified. To that end, we have generated preliminary data strongly implicating a metabolic disruptor, endotoxin, as the underlying cause in each case

Correlations of RMT Characteristic Polynomials and Integrability: Hermitean Matrices

Integrable theory is formulated for correlation functions of characteristic polynomials associated with invariant non-Gaussian ensembles of Hermitean random matrices. By embedding the correlation functions of interest into a more general theory of tau-functions, we (i) identify a zoo of hierarchical relations satisfied by tau-functions in an abstract infinite-dimensional space, and (ii) present a technology to translate these relations into hierarchically structured nonlinear differential equations describing the correlation functions of characteristic polynomials in the physical, spectral space. Implications of this formalism for fermionic, bosonic, and supersymmetric variations of zero-dimensional replica field theories are discussed at length. A particular emphasis is placed on the phenomenon of fermionic-bosonic factorisation of random-matrix-theory correlation functions.Comment: 62 pages, 1 table, published version (typos corrected

Humane Orientation as a New Cultural Dimension of the GLOBE Project: A Validation Study of the GLOBE Scale and Out-Group Humane Orientation in 25 Countries

We validate, extend, and empirically and theoretically criticize the cultural dimension of humane orientation of the project GLOBE (Global Leadership and Organizational Behavior Effectiveness Research Program). Theoretically, humane orientation is not just a one-dimensionally positive concept about being caring, altruistic, and kind to others as discussed by Kabasakal and Bodur (2004), but there is also a certain ambivalence to this concept. We suggest differentiating humane orientation toward in-group members from humane orientation toward out-group members. A multicountry construct validation study used student samples from 25 countries that were either high or low in humane orientation (N = 876) and studied their relation to the traditional GLOBE scale and other cultural-level measures (agreeableness, religiosity, authoritarianism, and welfare state score). Findings revealed a strong correlation between humane orientation and agreeableness, welfare state score, and religiosity. Out-group humane orientation proved to be the more relevant subfacet of the original humane orientation construct, suggesting that future research on humane orientation should make use of this measure instead of the vague original scale. The ambivalent character of out-group humane orientation is displayed in its positive correlation to high authoritarianism. Patriotism was used as a control variable for noncritical acceptance of one’s society but did not change the correlations. Our findings are discussed as an example of how rigid expectations and a lack of tolerance for diversity may help explain the ambivalent nature of humane orientatio

Cytokines Elevated in HIV Elite Controllers Reduce HIV Replication In Vitro and Modulate HIV Restriction Factor Expression

A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4+ T cells, and individually SDF-1β, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1β, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4+ T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies.IMPORTANCE Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the exact mechanisms of how their immune responses control infection are not known. In this study, we identified five soluble immune signaling molecules (cytokines) in the blood that were higher in ECs than in subjects with typical chronic HIV infection. We demonstrated that these cytokines can activate CD4+ T cells, the target cells for HIV infection. Furthermore, these five EC-associated cytokines could change expression levels of intrinsic resistance factors, or molecules inside the target cell that fight HIV infection. This study is significant in that it identified cytokines elevated in subjects with a good immune response against HIV and defined potential mechanisms as to how these cytokines could induce resistance to the virus in target cells

The UfM and the Middle East 'Peace Process': An Unhappy Symbiosis

This contribution explores differing theories on how the failure of the ‘peace process’ featured in the design and goals of the UfM, drawing on lessons from the period when the EMP was pursued in parallel with the peace process. In each case, institutional overlaps are identified, as well as commonalities in the approaches of the actors to both pursuits. Crucially, however, the persistence and intensification of the Arab–Israeli conflict, in combination with the shift from multilateralism to bilateralism embodied in the UfM, has politicized the latter at the expense of the functionalist aspirations of its architects

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

<p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

A global picture of the S-1/S-0 conical intersection seam of benzene

A global picture of the S1/S0intersection seam of benzene is presented. Eleven new conical intersection critical points were located at the CASSCF level, the connectivity was mapped and the energies refined with CASPT 2. There are two seam branches related with pairs of degenerate A1g/B2uand Egstates at D6hsymmetry, respectively, and the two branches are connected by a seam segment of Cssymmetry. The global energy minimum of the seam is the half-boat shaped intersection that leads to a pre-fulvenic intermediate [I.J. Palmer, I.N. Ragazos, F. Bernardi, M. Olivucci, M.A. Robb, J. Am. Chem. Soc. 115 (1993) 673]. Several other intersections that can lead to the same intermediate or vibrationally hot benzene lie in a range of 3.7 eV above the global seam minimum. There is a recurrent connectivity pattern where permutationally isomeric seam segments are connected by intersections of a higher symmetry point groupThis work has been supported by Grant CTQ2008-06696 from the Spanish Ministerio de Ciencia e Innovación (MICINN

Minimal clinically important differences for patient-reported outcome measures of fatigue in patients with COPD after pulmonary rehabilitation

Fatigue is a burdensome and prevailing symptom in patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves fatigue however, interpreting when such improvement is clinically relevant is challenging. Minimal clinically important differences (MCIDs) for instruments assessing fatigue are warranted to better tailor PR and guide clinical decisions. We estimated MCIDs for the functional assessment of chronic illness therapy-fatigue subscale (FACIT-FS), the modified-FACIT-FS and the checklist of individual strength-fatigue subscale (CIS-FS), in patients with COPD after PR.publishe