Pig acute-phase protein levels after stress induced by changes in the pattern of food administration

A total of 240 pigs, 74 days old, half boars and half females, were included in a trial designed to assess the effect of the stress caused by changes in the pattern of food administration on the concentration of acute phase proteins (APP) and productive performance parameters. Half of the animals (pigs fed ad libitum, AL group) had free access to feed, while the rest were fed following a disorderly pattern (DIS group), in which animals had alternating periods of free access to feed and periods of no feeding, when food was removed from the feeder. The periods of free access to feed (two daily periods of 2-h duration) were randomly assigned, and varied from day to day. Total feed supplied per day was identical in both groups, and exceeded the minimal amount required for animals of these ages. Pen feed intake, individual body weights and the main positive pig APP pig major acute phase protein (Pig-MAP), haptoglobin, serum amyloid A (SAA), C-reactive protein (CRP), and the negative APP apolipoprotein A-I (ApoA-I) and transtherytin were determined every 2 weeks during the period 76 to 116 days of age. Animals fed ad libitum had better average daily gain (ADG) than DIS animals in the whole experimental period (P < 0.01) but the differences in ADG were only produced in the two first experimental sub-periods (60 to 74 and 74 to 116 days of age), suggesting that the stress diminished when the animals get used to the DIS feeding. Interestingly differences in ADG between DIS and AL pigs were due to males, whereas no differences were observed between females. The same differences observed for ADG were found for APP. DIS males had higher Pig-MAP concentration than AL males at 74 and 116 days of age, lower ApoA-I concentration at 74 days of age and higher haptoglobin and CRP concentration at 116 days of age (P < 0.05). The results obtained in this trial show an inverse relationship between weight gain and APP levels, and suggest that APP may be biomarkers for the evaluation of distress and welfare in pigs.     

Met-204 and Tyr-205 are together important for binding GLP-1 receptor agonists but not their N-terminally truncated analogues

A mutagenesis study to systematically analyse residues spanning the first extracellular loop of the GLP-1 receptor identified a double mutant, Met-204/Tyr-205-Ala/Ala, which displayed: markedly reduced affinity for the natural agonist GLP-1; slightly reduced affinity for its analogue exendin-4; and unaltered affinity for several N-terminally truncated analogues of GLP-1 and exendin-4. This suggests that the locus is important for the formation of the binding site for the N-terminal residues of peptide agonists.     

The isolated N-terminal domain of the glucagon-like peptide-1 (GLP-1) receptor binds exendin peptides with much higher affinity than GLP-1

Two fragments of the receptor for glucagon-like peptide-1 (GLP-1), each containing the N-terminal domain, were expressed and characterized in either bacterial or mammalian cells. The first fragment, rNT-TM1, included the N-terminal domain and first transmembrane helix and was stably expressed in the membrane of human embryonic kidney 293 cells. The second, 6H-rNT, consisted of only the N-terminal domain of the receptor fused with a polyhistidine tag at its N terminus. The latter fragment was expressed in Escherichia coli in the form of inclusion bodies from which the protein was subsequently purified and refolded in vitro. Although both receptor fragments displayed negligible (125)I-labeled GLP-1(7-36)amide-specific binding, they both displayed high affinity for the radiolabeled peptide antagonist (125)I-exendin-4(9-39). Competition binding studies demonstrated that the N-terminal domain of the GLP-1 receptor maintains high affinity for the agonist exendin-4 as well as the antagonists exendin-4(3-39) and exendin-4(9-39) whereas, in contrast, GLP-1 affinity was greatly reduced. This study shows that although the exendin antagonists are not dependent upon the extracellular loops and transmembrane helices for maintaining their normal high affinity binding, the endogenous agonist GLP-1 requires regions outside of the N-terminal domain. Hence, distinct structural features in exendin-4, between residues 9 and 39, provide additional affinity for the N-terminal domain of the receptor. These data are consistent with a model for the binding of peptide ligands to the GLP-1 receptor in which the central and C-terminal regions of the peptides bind to the N terminus of the receptor, whereas the N-terminal residues of peptide agonists interact with the extracellular loops and transmembrane helices.     

Diffusional properties of methanogenic granular sludge: 1H NMR characterization

The diffusive properties of anaerobic methanogenic and sulfidogenic aggregates present in wastewater treatment bioreactors were studied using diffusion analysis by relaxation time-separated pulsed-field gradient nuclear magnetic resonance (NMR) spectroscopy and NMR imaging. NMR spectroscopy measurements were performed at 22 degrees C with 10 ml of granular sludge at a magnetic field strength of 0.5 T (20 MHz resonance frequency for protons). Self-diffusion coefficients of H(2)O in the investigated series of mesophilic aggregates were found to be 51 to 78% lower than the self-diffusion coefficient of free water. Interestingly, self-diffusion coefficients of H(2)O were independent of the aggregate size for the size fractions investigated. Diffusional transport occurred faster in aggregates growing under nutrient-rich conditions (e.g., the bottom of a reactor) or at high (55 degrees C) temperatures than in aggregates cultivated in nutrient-poor conditions or at low (10 degrees C) temperatures. Exposure of aggregates to 2.5% glutaraldehyde or heat (70 or 90 degrees C for 30 min) modified the diffusional transport up to 20%. In contrast, deactivation of aggregates by HgCl(2) did not affect the H(2)O self-diffusion coefficient in aggregates. Analysis of NMR images of a single aggregate shows that methanogenic aggregates possess a spin-spin relaxation time and self-diffusion coefficient distribution, which are due to both physical (porosity) and chemical (metal sulfide precipitates) factors.     

Cytokine Profiles at Admission Can Be Related to Outcome in AIDS Patients with Cryptococcal Meningitis

Cryptococcal meningitis (CM) remains as common life-threatening AIDS-defining illness mainly in resource-limited settings. Previous reports suggested that baseline cytokine profiles can be associated to fungal burden and clinical outcome. This study aimed to evaluate the baseline cytokine profiles in AIDS patients with CM and its relation with the outcome at weeks 2 and 10. Thirty AIDS patients with CM diagnosed by cerebrospinal fluid (CSF) Cryptococcus neoformans positive culture, India ink stain and cryptococcal antigen test were prospectively evaluated. As controls, 56 HIV-infected patients without CM and 48 non-HIV individuals were included. Baseline CSF and sera levels of IL-2, IL-4, IL-8, IL-10, IL-12p40, IL-17A, INF-γ and TNF-α were measured by ELISA. Of 30 CM patients, 24 (80%) were male, median age of 38.1. The baseline CSF high fungal burden and positive blood culture were associated with a positive CSF culture at week 2 (p = 0.043 and 0.029). Most CSF and sera cytokines presented higher levels in CM patients than control subjects (p < 0.05). CSF levels of IL-8, IL-12p40, IL-17A, TNF-α, INF-γ and sera TNF-α were significantly higher among survivors at weeks 2 and 10 (p < 0.05). Patients with increased intracranial pression exhibited CSF IL-10 high levels and poor outcome at week 10 (p = 0.032). Otherwise, baseline CSF log10 IFN-γ and IL-17A were negatively correlated with fungal burden (r = -0.47 and -0.50; p = 0.0175 and 0.0094, respectively). The mortality rate was 33% (10/30) at week 2 and 57% (17/30) at week 10. The severity of CM and the advanced immunodeficiency at admission were related to a poor outcome in these patients. Otherwise, the predominant Th1 cytokines profile among survivors confirms its pivotal role to infection control and would be a prognostic marker in cryptococcal meningitis.     

Exploitative strategies of the invasive Argentine ant (Linepithema humile) and native ant species in a southern Spanish pine forest

The Argentine ant, Linepithema humile (Mayr, 1868), is displacing native ant species in Do?ana National Park (Spain). This paper discusses the results of experiments aimed at analyzing exploitation competition between the invading species and other ant species in a park community. The Argentine ant was found to implement several strategies favoring its success in exploitation competition: mass recruitment, use of various microhabitats (on the ground and in trees), and activity over a wide range of temperatures. Although these strategies were not exclusive to L. humile, their joint use, together with the large number of workers forming each "unicolony," conferred a clear advantage for resource exploitation. Some native species were more severely affected than others by the presence of L. humile in terms of both abundance and behavior. The worst affected species were those whose ecological characteristics were similar to those of the Argentine ant, e.g., Pheidole pallidula (Nylander, 1849); the species least affected was Cataglyphis floricola Tinaut, 1993, possibly because of its subordinate and thermophilous nature (little overlap of daily activity rhythms with the exotic species).     

Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement

Background

Osteoarthritis of the knee is a major clinical problem affecting a greater proportion of women than men. Women generally report higher pain intensity at rest and greater perceived functional deficits than men. Women also perform worse than men on function measures such as the 6-minute walk and timed up and go tests. Differences in pain sensitivity, pain during function, psychosocial variables, and physical activity levels are unclear. Further the ability of various biopsychosocial variables to explain physical activity, function and pain is unknown.

Methods

This study examined differences in pain, pain sensitivity, function, psychosocial variables, and physical activity between women and men with knee osteoarthritis (N = 208) immediately prior to total knee arthroplasty. We assessed: (1) pain using self-report measures and a numerical rating scale at rest and during functional tasks, (2) pain sensitivity using quantitative sensory measures, (3) function with self-report measures and specific function tasks (timed walk, maximal active flexion and extension), (4) psychosocial measures (depression, anxiety, catastrophizing, and social support), and (5) physical activity using accelerometry. The ability of these mixed variables to explain physical activity, function and pain was assessed using regression analysis.

Results

Our findings showed significant differences on pain intensity, pain sensitivity, and function tasks, but not on psychosocial measures or physical activity. Women had significantly worse pain and more impaired function than men. Their levels of depression, anxiety, pain catastrophizing, social support, and physical activity, however, did not differ significantly. Factors explaining differences in (1) pain during movement (during gait speed test) were pain at rest, knee extension, state anxiety, and pressure pain threshold; (2) function (gait speed test) were sex, age, knee extension, knee flexion opioid medications, pain duration, pain catastrophizing, body mass index (BMI), and heat pain threshold; and (3) physical activity (average metabolic equivalent tasks (METS)/day) were BMI, age, Short-Form 36 (SF-36) Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale.

Conclusions

Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks.     

Changes in the root-associated fungal communities along a primary succession gradient analysed by 454 pyrosequencing

We investigated changes in the root-associated fungal communities associated with the ectomycorrhizal herb Bistorta vivipara along a primary succession gradient using 454 amplicon sequencing. Our main objective was to assess the degree of variation in fungal richness and community composition as vegetation cover increases along the chronosequence. Sixty root systems of B. vivipara were sampled in vegetation zones delimited by dated moraines in front of a retreating glacier in Norway. We extracted DNA from rinsed root systems, amplified the ITS1 region using fungal-specific primers and analysed the amplicons using 454 sequencing. Between 437 and 5063 sequences were obtained from each root system. Clustering analyses using a 98.5% sequence similarity cut-off yielded a total of 470 operational taxonomic units (OTUs), excluding singletons. Between eight and 41 fungal OTUs were detected within each root system. Already in the first stage of succession, a high fungal diversity was present in the B. vivipara root systems. Total number of OTUs increased significantly along the gradient towards climax vegetation, but the average number of OTUs per root system stayed unchanged. There was a high patchiness in distribution of fungal OTUs across root systems, indicating that stochastic processes to a large extent structure the fungal communities. However, time since deglaciation had impact on the fungal community structure, as a systematic shift in the community composition was observed along the chronosequence. Ectomycorrhizal basidiomycetes were the dominant fungi in the roots of B. vivipara, when it comes to both number of OTUs and number of sequences.     

Cross-Species Functional Genomic Analysis Identifies Resistance Genes of the Histone Deacetylase Inhibitor Valproic Acid

The mechanisms of successful epigenetic reprogramming in cancer are not well characterized as they involve coordinated removal of repressive marks and deposition of activating marks by a large number of histone and DNA modification enzymes. Here, we have used a cross-species functional genomic approach to identify conserved genetic interactions to improve therapeutic effect of the histone deacetylase inhibitor (HDACi) valproic acid, which increases survival in more than 20% of patients with advanced acute myeloid leukemia (AML). Using a bidirectional synthetic lethality screen revealing genes that increased or decreased VPA sensitivity in C. elegans, we identified novel conserved sensitizers and synthetic lethal interactors of VPA. One sensitizer identified as a conserved determinant of therapeutic success of HDACi was UTX (KDM6A), which demonstrates a functional relationship between protein acetylation and lysine-specific methylation. The synthetic lethal screen identified resistance programs that compensated for the HDACi-induced global hyper-acetylation, and confirmed MAPKAPK2, HSP90AA1, HSP90AB1 and ACTB as conserved hubs in a resistance program for HDACi that are drugable in human AML cell lines. Hence, these resistance hubs represent promising novel targets for refinement of combinatorial epigenetic anti-cancer therapy.     

Social is Emotional

This is a biological approach to the philosophy of mind that feeds an investigation of the phenomena of “social” and “emotional”, both of which are widespread in nature. I scrutinize the non-dualistic Darwinian concept of the continuity of mind. For practical reasons, I address mind at different levels of organization: The systemic mind are the properties of which a common, coherent evolution works upon. Separated from this is “language-mind”: the crystallization of thought in words, which is a strictly human phenomenon. As the phenomenology of the body is a theory of philosophy that lie beyond language it can—to a certain extent—be extrapolated across a species boundary. In the process the phenomenology of the body comes to resemble biosemiotics and with this tool, I investigate a field study of social play behavior in canids. This leads to a possibility to study the non-human experience of emotion as “locally meaningful phenomena”.