The history of settlement and agrarian land use in a boreal forest in Värmland,Sweden, new evidence from pollen analysis

Vegetation History and Archaeobotany - Shielings are the historically known form of transhumance in Scandinavia, where livestock were moved from the farmstead to sites in the outlands for summer...     

Pituitary Stalk Interruption Syndrome in 53 Postpubertal Patients: Factors Influencing the Heterogeneity of Its Presentation

Background

Pituitary stalk interruption syndrome (PSIS) may induce an isolated growth hormone (GH) deficiency or multiple hypothalamic-pituitary (HP) deficiencies. Patients with multiple HP deficiencies, primarily those with adrenocorticotropin (ACTH) deficiency, are at increased risk of morbidity and mortality. Our objective was to identify the factors influencing each symptom and the MRI features of the syndrome to enhance its diagnosis and genetic analysis.

Methods

This study was a retrospective, single-center, case-cohort study of 53 patients with PSIS who had reached pubertal age.

Results

Patients were classified as having an isolated GH deficiency (n = 24, Group 1) or HP deficiencies (n = 29, Group 2); of these, 19 had complete HP deficiency, and 10 had GH deficiency associated with TSH (n = 4), TSH and ACTH (n = 3), TSH and gonadotropin (n = 1) deficiencies or amenorrhea (n = 2). The following features were less frequent in Group 1 than in Group 2: breech presentation (4% vs 35%, P = 0.008), hypoglycemia (0% vs 59%, P<0.00001), micropenis (13% vs 69%, P<0.003), hypothalamic origin (0% vs 52%, P<0.000001), ophthalmic malformation (8% vs 38%, P<0.02) and psychomotor delay (0% vs 31%, P<0.004). The frequencies of all other malformations were similar in both groups (37% vs 59%). A visible pituitary stalk was characteristic of patients belonging to Group 1 (P<0.0002). The GH peak was greater in Group 1 than in Group 2 (P<0.0003), as was the anterior pituitary height (P = 0.01).

Conclusion

The factors that best discriminate patients with multiple HP deficiencies from those with an isolated GH deficiency are breech presentation, hypoglycemia, and micropenis. No patient with an isolated GH deficiency had psychomotor delay, but associated malformations and/or syndromes, with the exception of ophthalmic disorders, occurred with similar frequencies in both groups. We have also shown that each of the above characteristics is associated with a given HP deficiency and/or malformation/syndrome in the majority of cases.     

Matrix Metalloproteinase (MMP)-1 Induces Lung Alveolar Epithelial Cell Migration and Proliferation,Protects from Apoptosis,and Represses Mitochondrial Oxygen Consumption

Idiopathic pulmonary fibrosis is a devastating lung disorder of unknown etiology. Although its pathogenesis is unclear, considerable evidence supports an important role of aberrantly activated alveolar epithelial cells (AECs), which produce a large variety of mediators, including several matrix metalloproteases (MMPs), which participate in fibroblast activation and lung remodeling. MMP-1 has been shown to be highly expressed in AECs from idiopathic pulmonary fibrosis lungs although its role is unknown. In this study, we explored the role of MMP-1 in several AECs functions. Mouse lung epithelial cells (MLE12) transfected with human Mmp-1 showed significantly increased cell growth and proliferation at 36 and 48 h of culture (p < 0.01). Also, MMP-1 promoted MLE12 cell migration through collagen I, accelerated wound closing, and protected cells from staurosporine- and bleomycin-induced apoptosis compared with mock cells (p < 0.01). MLE12 cells expressing human MMP-1 showed a significant repression of oxygen consumption ratio compared with the cells with the empty vector. As under hypoxic conditions hypoxia-inducible factor-1α (HIF-1α) mediates a transition from oxidative to glycolytic metabolism, we analyzed activation of HIF-1α. Ηigher activation of this factor was detected in MMP-1-transfected cells under normoxia and hypoxia. Likewise, a significant decrease of both total and mitochondrial reactive oxygen species was observed in MMP-1-transfected cells. Paralleling these findings, attenuation of MMP-1 expression by shRNA in A549 (human) AECs markedly reduced proliferation and migration (p < 0.01) and increased the oxygen consumption ratio. These findings indicate that epithelial expression of MMP-1 inhibits mitochondrial function, increases HIF-1α expression, decreases reactive oxygen species production, and contributes to a proliferative, migratory, and anti-apoptotic AEC phenotype.     

Structural Basis for the Association of MAP6 Protein with Microtubules and Its Regulation by Calmodulin

Microtubules are highly dynamic αβ-tubulin polymers. In vitro and in living cells, microtubules are most often cold- and nocodazole-sensitive. When present, the MAP6/STOP family of proteins protects microtubules from cold- and nocodazole-induced depolymerization but the molecular and structure determinants by which these proteins stabilize microtubules remain under debate. We show here that a short protein fragment from MAP6-N, which encompasses its Mn1 and Mn2 modules (MAP6(90–177)), recapitulates the function of the full-length MAP6-N protein toward microtubules, i.e. its ability to stabilize microtubules in vitro and in cultured cells in ice-cold conditions or in the presence of nocodazole. We further show for the first time, using biochemical assays and NMR spectroscopy, that these effects result from the binding of MAP6(90–177) to microtubules with a 1:1 MAP6(90–177):tubulin heterodimer stoichiometry. NMR data demonstrate that the binding of MAP6(90–177) to microtubules involve its two Mn modules but that a single one is also able to interact with microtubules in a closely similar manner. This suggests that the Mn modules represent each a full microtubule binding domain and that MAP6 proteins may stabilize microtubules by bridging tubulin heterodimers from adjacent protofilaments or within a protofilament. Finally, we demonstrate that Ca²⁺-calmodulin competes with microtubules for MAP6(90–177) binding and that the binding mode of MAP6(90–177) to microtubules and Ca²⁺-calmodulin involves a common stretch of amino acid residues on the MAP6(90–177) side. This result accounts for the regulation of microtubule stability in cold condition by Ca²⁺-calmodulin.     

The Bracovirus Genome of the Parasitoid Wasp Cotesia congregata Is Amplified within 13 Replication Units,Including Sequences Not Packaged in the Particles

The relationship between parasitoid wasps and polydnaviruses constitutes one of the few known mutualisms between viruses and eukaryotes. Viral particles are injected with the wasp eggs into parasitized larvae, and the viral genes thus introduced are used to manipulate lepidopteran host physiology. The genome packaged in the particles is composed of 35 double-stranded DNA (dsDNA) circles produced in wasp ovaries by amplification of viral sequences from proviral segments integrated in tandem arrays in the wasp genome. These segments and their flanking regions within the genome of the wasp Cotesia congregata were recently isolated, allowing extensive mapping of amplified sequences. The bracovirus DNAs packaged in the particles were found to be amplified within more than 12 replication units. Strikingly, the nudiviral cluster, the genes of which encode particle structural components, was also amplified, although not encapsidated. Amplification of bracoviral sequences was shown to involve successive head-to-head and tail-to-tail concatemers, which was not expected given the nudiviral origin of bracoviruses.     

Hydrolysis of milk-derived bioactive peptides by cell-associated extracellular peptidases of Streptococcus thermophilus

The trend to confer new functional properties to fermented dairy products by supplementation with bioactive peptides is growing in order to encounter the challenge of health-promoting foods. But these functional ingredients have not to be hydrolysed by proteases of bacteria used in the manufacture of these products. One of the two yoghurt bacteria, Streptococcus thermophilus, has long been considered as weakly proteolytic since its only cell wall-associated subtilisin-like protease, called PrtS, is not always present. Nevertheless, a recent study pointed out a possible peptidase activity in certain strains. In this present study, the stability of milk-derived bioactive peptides, e.g. the anxiolytic peptide, α_s1-CN-(f91-97), in the presence of two different S. thermophilus strains with PrtS⁺ or PrtS^? phenotype was studied. Both strains appeared to be capable of hydrolysing the α_s1-CN-(f91-97) and other bioactive peptides by recurrent removal of N-terminal residues. The hydrolysis was neither due to intracellular peptidases nor to HtrA protease. Results obtained showed that the observed activity originates from the presence at the surface of both strains of an extracellular aminopeptidase activity. Moreover, a cell wall-associated X-prolyl dipeptidyl peptidase activity was also highlighted when β-casomorphin-7 was used as substrate. All of these findings suggest that, in order to use fermented milks as vector of bioactive peptides, the stability of these bioactive peptides in this kind of products implies to carefully characterize the potential action of the surface proteolytic enzymes of S. thermophilus.