Changes in the milk metabolome of the Giant Panda (Ailuropoda melanoleuca) with time after birth: three phases in early lactation and progressive individual differences

Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1–6 (Phase 1), days 7–20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth

Prolonged transition time between colostrum and mature milk in a bear, the giant panda, Ailuropoda melanoleuca

Bears produce the most altricial neonates of any placental mammal. We hypothesized that the transition from colostrum to mature milk in bears reflects a temporal and biochemical adaptation for altricial development and immune protection. Comparison of bear milks with milks of other eutherians yielded distinctive protein profiles. Proteomic and metabolomic analysis of serial milk samples collected from six giant pandas showed a prolonged transition from colostrum to main-phase lactation over approximately 30 days. Particularly striking are the persistence or sequential appearance of adaptive and innate immune factors. The endurance of immunoglobulin G suggests an unusual duration of trans-intestinal absorption of maternal antibodies, and is potentially relevant to the underdeveloped lymphoid system of giant panda neonates. Levels of certain milk oligosaccharides known to exert anti-microbial activities and/or that are conducive to the development of neonatal gut microbiomes underwent an almost complete changeover around days 20–30 postpartum, coincident with the maturation of the protein profile. A potential metabolic marker of starvation was detected, the prominence of which may reflect the natural postpartum period of anorexia in giant panda mothers. Early lactation in giant pandas, and possibly in other ursids, appears to be adapted for the unique requirements of unusually altricial eutherian neonates

Contrasting alterations to synaptic and intrinsic properties in upper-cervical superficial dorsal horn neurons following acute neck muscle inflammation

Background: Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons.<p></p> Results: Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2?g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40??l of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2?hrs. Mice in each group were sacrificed at 2?hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I - II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ~20% in neurons from carrageenan-injected mice versus control and sham animals (20.63???1.05 vs. 24.64???0.91 and 25.87???1.32 pA, respectively). The amplitude (238???33 vs. 494???96 and 593???167 pA) and inactivation time constant (12.9???1.5 vs. 22.1???3.6 and 15.3???1.4?ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice.<p></p> Conclusions: Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation

Un estudio naturalista sobre el cambio de los conflictos cognitivos durante la psicoterapia

Los autores presentan una propuesta para la operativización e investigación sobre el cambio de un tipo de conflicto cognitivo, denominado dilema implicativo (DI) en la teoría de los constructos personales. En una muestra de 87 pacientes se miden los DIs y la sintomatología al comienzo y al final de la psicoterapia. Los datos sugieren que la psicoterapia los reduce. La disminución de DIs al finalizar el proceso terapéutico parece relacionada con la mejora sintomática, por lo que se estima una relación entre la presencia de DIs y la evolución de la sintomatología que debería confirmarse en estudios controlados. Asimismo, se sugiere el interés de incluir protocolos dirigidos de forma específica a trabajar con los dilemas para incrementar la eficacia de la psicoterapia para aquellos pacientes que los presenten a su inicio

Changeover from signalling to energy-provisioning lipids during transition from colostrum to mature milk in the giant panda (Ailuropoda melanoleuca)

Among the large placental mammals, ursids give birth to the most altricial neonates with the lowest neonatal:maternal body mass ratios. This is particularly exemplified by giant pandas. To examine whether there is compensation for the provision of developmentally important nutrients that other species groups may provide in utero, we examined changes in the lipids of colostrum and milk with time after birth in giant pandas. Lipids that are developmental signals or signal precursors, and those that are fundamental to nervous system construction, such as docosahexaenoic acid (DHA) and phosphatidylserines, appear early and then fall dramatically in concentration to a baseline at 20-30 days. The dynamics of lysophosphatidic acid and eicosanoids display similar patterns, but with progressive differences between mothers. Triglycerides occur at relatively low levels initially and increase in concentration until a plateau is reached at about 30 days. These patterns indicate an early provision of signalling lipids and their precursors, particularly lipids crucial to brain, retinal and central nervous system development, followed by a changeover to lipids for energy metabolism. Thus, in giant pandas, and possibly in all bears, lactation is adapted to provisioning a highly altricial neonate to a degree that suggests equivalence to an extension of gestation

Un estudio naturalista sobre el cambio de los conflictos cognitivos durante la psicoterapia

Los autores presentan una propuesta para la operativización e investigación sobre el cambio de un tipo de conflicto cognitivo, denominado dilema implicativo (DI) en la teoría de los constructos personales. En una muestra de 87 pacientes se miden los Dls y la sintomatología al comienzo y final de la psicoterapia. Los datos sugieren que la psicoterapia los reduce. La disminución de DIs al finalizar el proceso psicoterapéutico parece relacionada con la mejora sintomática, por lo que se estima una relación entre la presencia de Dls y la evolución de la sintomatología que debería confirmarse en estudios controlados, Asimismo, se sugiere el interés de incluir protocolos dirigidos de forma específica a trabajar con los dilemas para incrementar la eficacia de la psicoterapia para aquellos pacientes que los presenten a su inicio

Towards practice-based studies of HRM: an actor-network and communities of practice informed approach

HRM may have become co-terminus with the new managerialism in the rhetorical orthodoxies of the HRM textbooks and other platforms for its professional claims. However, we have detailed case-study data showing that HR practices can be much more complicated, nuanced and indeed resistive toward management within organizational settings. Our study is based on ethnographic research, informed by actor-network theory and community of practice theory conducted by one of the authors over an 18-month period. Using actor-network theory in a descriptive and critical way, we analyse practices of managerial resistance, enrolment and counter-enrolment through which an unofficial network of managers used a formal HRM practice to successfully counteract the official strategy of the firm, which was to close parts of a production site. As a consequence, this network of middle managers effectively changed top management strategy and did so through official HRM practices, coupled with other actor-network building processes, arguably for the ultimate benefit of the organization, though against the initial views of the top management. The research reported here, may be characterized as a situated study of HRM-in-practice and we draw conclusions which problematize the concept of HRM in contemporary management literature

A human embryonic kidney 293T cell line mutated at the Golgi -mannosidase II locus

Disruption of Golgi -mannosidase II activity can result in type II congenital dyserythropoietic anemia and can induce lupus-like autoimmunity in mice. Here, we isolate a mutant human embryonic kidney (HEK) 293T cell line, called Lec36, that displays sensitivity to ricin that lies between the parental HEK 293T cells, whose secreted and membrane-expressed proteins are dominated by complex-type glycosylation, and 293S Lec1 cells, which only produce oligomannose-type N-linked glycans. The stem cell marker, 19A, was transiently expressed in the HEK 293T Lec36 cells, and in parental HEK 293T cells with and without the potent Golgi -mannosidase II inhibitor, swainsonine. Negative-ion nano-electrospray ionization mass spectra of the 19A N-linked glycans from HEK 293T Lec36 and swainsonine-treated HEK 293T cells were qualitatively indistinguishable and, as shown by collision-induced dissociation spectra, dominated by hybrid-type glycosylation. Nucleotide sequencing revealed mutations in each allele of MAN2A1, the gene encoding Golgi -mannosidase II: a point mutation in one allele mapping to the active site and an in-frame deletion of twelve-nucleotides in the other. Expression of wild-type but not the mutant MAN2A1 alleles in Lec36 cells restored processing of the 19A reporter glycoprotein to complex-type glycosylation. The Lec36 cell line will be useful for expressing therapeutic glycoproteins with hybrid-type glycans and provides a sensitive host for detecting mutations in human MAN2A1 causing type II congenital dyserythropoietic anemia

Equilibrium responses of global net primary production and carbon storage to doubled atmospheric carbon dioxide: sensitivity to changes in vegetation nitrogen concentration

We ran the terrestrial ecosystem model (TEM) for the globe at 0.5° resolution for atmospheric CO2 concentrations of 340 and 680 parts per million by volume (ppmv) to evaluate global and regional responses of net primary production (NPP) and carbon storage to elevated CO2 for their sensitivity to changes in vegetation nitrogen concentration. At 340 ppmv, TEM estimated global NPP of 49.0 1015 g (Pg) C yr−1 and global total carbon storage of 1701.8 Pg C; the estimate of total carbon storage does not include the carbon content of inert soil organic matter. For the reference simulation in which doubled atmospheric CO2 was accompanied with no change in vegetation nitrogen concentration, global NPP increased 4.1 Pg C yr−1 (8.3%), and global total carbon storage increased 114.2 Pg C. To examine sensitivity in the global responses of NPP and carbon storage to decreases in the nitrogen concentration of vegetation, we compared doubled CO2 responses of the reference TEM to simulations in which the vegetation nitrogen concentration was reduced without influencing decomposition dynamics (“lower N” simulations) and to simulations in which reductions in vegetation nitrogen concentration influence decomposition dynamics (“lower N+D” simulations). We conducted three lower N simulations and three lower N+D simulations in which we reduced the nitrogen concentration of vegetation by 7.5, 15.0, and 22.5%. In the lower N simulations, the response of global NPP to doubled atmospheric CO2 increased approximately 2 Pg C yr−1 for each incremental 7.5% reduction in vegetation nitrogen concentration, and vegetation carbon increased approximately an additional 40 Pg C, and soil carbon increased an additional 30 Pg C, for a total carbon storage increase of approximately 70 Pg C. In the lower N+D simulations, the responses of NPP and vegetation carbon storage were relatively insensitive to differences in the reduction of nitrogen concentration, but soil carbon storage showed a large change. The insensitivity of NPP in the N+D simulations occurred because potential enhancements in NPP associated with reduced vegetation nitrogen concentration were approximately offset by lower nitrogen availability associated with the decomposition dynamics of reduced litter nitrogen concentration. For each 7.5% reduction in vegetation nitrogen concentration, soil carbon increased approximately an additional 60 Pg C, while vegetation carbon storage increased by only approximately 5 Pg C. As the reduction in vegetation nitrogen concentration gets greater in the lower N+D simulations, more of the additional carbon storage tends to become concentrated in the north temperate-boreal region in comparison to the tropics. Other studies with TEM show that elevated CO2 more than offsets the effects of climate change to cause increased carbon storage. The results of this study indicate that carbon storage would be enhanced by the influence of changes in plant nitrogen concentration on carbon assimilation and decomposition rates. Thus changes in vegetation nitrogen concentration may have important implications for the ability of the terrestrial biosphere to mitigate increases in the atmospheric concentration of CO2 and climate changes associated with the increases