Daily torpor in the Djungarian hamster (Phodopus sungorus): interactions with food intake,activity, and social behaviour

Summary In Djungarian hamsters,Phodopus sungorus, daily torpor occurs spontaneously in winter in the presence of abundant food, but individuals show different tendencies to enter torpor. The results show that in hamsters fed rodent chow ad libitum individual torpor frequencies were negatively correlated with both food consumption and the amount of nocturnal locomotor activity. Provision of cafeteria diet at ambient temperatures below thermoneutrality significantly lowered torpor frequencies and induced body weight gains. However, in hamsters fed seeds with a high fat or carbohydrate content (i.e., sunflower seeds or wheat, respectively) neither a decrease of torpor frequencies nor an increase of body weights was observed. The results suggest that in Djungarian hamsters, daily torpor is an intrinsic component of energy balance control and is functionally linked to individual physiological adjustments of food consumption and foraging activity. In addition, the employment of daily torpor can be affected by social interactions, since the long-term pattern of alternations between torpor and normothermia was found to be synchronized in breeding pairs caged together.Abbreviations T _a ambient temperature - DIT diet-induced thermogenesis     

Neural Induction of the Blood–Brain Barrier: Still an Enigma

1. The study of the blood–brain barrier and its various realms offers a myriad of opportunities for scientific exploration. This review focuses on two of these areas in particular: the induction of the blood–brain barrier and the molecular mechanisms underlying this developmental process.2. The creation of the blood–brain barrier is considered a specific step in the differentiation of cerebral capillary endothelial cells, resulting in a number of biochemical and functional alterations. Although the specific endothelial properties which maintain the homeostasis in the central nervous system necessary for neuronal function have been well described, the inductive mechanisms which trigger blood–brain barrier establishment in capillary endothelial cells are unknown.3. The timetable of blood–brain barrier formation is still a matter of debate, caused largely by the use of varying experimental systems and by the general difficulty of quantitatively measuring the degree of blood–brain barrier tightness. However, there is a general consensus that a gradual formation of the blood–brain barrier starts shortly after intraneural neovascularization and that the neural microenvironment (neurons and/or astrocytes) plays a key role in inducing blood–brain barrier function in capillary endothelial cells. This view stems from numerous in vitro experiments using mostly cocultures of capillary endothelial cells and astrocytes and assays for easily measurable blood–brain barrier markers. In vivo, there are great difficulties in proving the inductive influence of the neuronal environment. Also dealt with in this article are brain tumors, the least understood in vivo systems, and the induction or noninduction of barrier function in the newly established tumor vascularization.4. Finally, this review tries to elucidate the question concerning the nature of the inductive signal eliciting blood–brain barrier formation in the cerebral microvasculature.     

Patients with a non-dysferlin Miyoshi myopathy have a novel membrane repair defect

Two autosomal recessive muscle diseases, limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), are caused by mutations in the dysferlin gene. These mutations result in poor ability to repair cell membrane damage, which is suggested to be the cause for this disease. However, many patients who share clinical features with MM-type muscular dystrophy do not carry mutations in dysferlin gene. To understand the basis of MM that is not due to mutations in dysferlin gene, we analyzed cells from patients in one such family. In these patients, we found no defects in several potential candidates - annexin A2, caveolin-3, myoferlin and the MMD2 locus on chromosome 10p. Similar to dysferlinopathy, these cells also exhibit membrane repair defects and the severity of the defect correlated with severity of their disease. However, unlike dysferlinopathy, none of the conventional membrane repair pathways are defective in these patient cells. These results add to the existing evidence that cell membrane repair defect may be responsible for MM-type muscular dystrophy and indicate that a previously unsuspected genetic lesion that affects cell membrane repair pathway is responsible for the disease in the non-dysferlin MM patients.     

Skin mild hypoxia enhances killing of UVB-damaged keratinocytes through reactive oxygen species-mediated apoptosis requiring Noxa and Bim

The naturally occurring skin hypoxia has emerged as a crucial host factor of the epidermal microenvironment. We wanted to systematically investigate how reduced oxygen availability of the epidermis modulates the response of keratinocytes and melanocytes to noxious ultraviolet B radiation (UVB). We report that the exposure of normal human keratinocytes (NHKs) or melanocytes (NHEMs) to mild hypoxia drastically impacts cell death responses following UVB irradiation. The hypoxic microenvironment favors survival and reduces apoptosis of UVB-irradiated NHEMs and their malignant counterparts (melanoma cells). In contrast, NHKs, but not the transformed keratinocytes, under hypoxic conditions display increased levels of reactive oxygen species (ROS) and are significantly sensitized to UVB-mediated apoptosis as compared to NHKs treated under normoxic conditions. Prolonged exposure of UVB-treated NHKs to hypoxia triggers a sustained and reactive oxygen species-dependent activation of the stress kinases p38(MAPK) and JNKs, which in turn, engage the activation of Noxa and Bim proapoptotic proteins. Combined silencing of Noxa and Bim significantly inhibits UVB-mediated apoptosis under hypoxic conditions, demonstrating that hypoxia results in an amplification of the intrinsic apoptotic pathway. Physiologically occurring skin hypoxia, by facilitating the specific removal of UVB-damaged keratinocytes, may represent a decisive host factor impeding important steps of the photocarcinogenesis process.     

Genetic analysis of beta1 integrin "activation motifs" in mice

Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin beta cytoplasmic domains. Talin binding disrupts the salt bridge between the alpha/beta tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the beta1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished beta1 integrin functions and led to a beta1 integrin-null phenotype in vivo. Surprisingly, neither the substitution of the tyrosines with phenylalanine nor the aspartic acid with alanine resulted in an obvious defect. These data suggest that the NPXY motifs of the beta1 integrin tail are essential for beta1 integrin function, whereas tyrosine phosphorylation and the membrane-proximal salt bridge between alpha and beta1 tails have no apparent function under physiological conditions in vivo.     

Cytosolic COOH terminus of the peptide transporter PEPT2 is involved in apical membrane localization of the protein

The peptide transporter PEPT2 is a polytopic transmembrane protein that mediates the cellular uptake of di- and tripeptides and a variety of peptidomimetics. It is widely expressed in mammalian tissues, including kidney, lung, mammary gland, choroid plexus, and glia cells. In renal tubular cells, PEPT2 is exclusively found at the apical membrane. The molecular mechanisms underlying this polarized expression and targeting to the brush-border membrane are not known. We have explored the role of the 36 COOH-terminal amino acid residues in PEPT2 trafficking and apical expression. EGFP-tagged PEPT2 wild-type transporter and various truncated and mutant proteins were expressed in the polarized proximal tubule cell lines SKPT and OK, and the cellular distribution of the fusion proteins was assessed using confocal microscopy. Whereas deletion of the last seven amino acids (delC7) did not alter PEPT2 surface expression, deletion of the next residue (delC8) or up to 30 terminal amino acids resulted in impaired apical expression and distinct accumulation of mutant proteins in endosomal and lysosomal vesicles. Truncation of more amino acids (delC36) containing tyrosine-based motifs led to a rather diffuse intracellular distribution pattern. Mutations introduced at isoleucine-720 (I720A) and leucine-722 (I722A) also caused an impaired surface appearance. Internalization assays revealed a higher endocytotic rate of the PEPT2 mutants I720A, L722A, and delC36. Our data suggest that a three-amino acid stretch (INL) and tyrosine-based motifs within the COOH tail of PEPT2 are involved in PEPT2's apical membrane localization and membrane steady-state level. di- and tripeptide transport; polarized epithelial cells; lysosomes     

Holocene timber-line dynamics at Bachalpsee, a lake at 2265 m a.s.l. in the northern Swiss Alps

Palaeobotanical analysis and radiocarbon dating of lake sediments from Bachalpsee (2265 m a.s.l.), a small lake above the present-day timber-line in the northern Swiss Alps reveals that the region was already deglaciated during the Younger Dryas. The sediment record is dominated by long-distance transported pollen that originates from lowland vegetation but the plant macrofossils give evidence of the local vegetation development. Comparison with palaeobotanical results from three sites along an altitudinal transect permits the reconstruction of the regional timber-line history. Throughout the entire Holocene the catchment of Bachalpsee consisted of a mosaic of open meadows and dwarf shrubs (Salix, Vaccinium, Rhododendron). Chironomid and cladoceran assemblages suggest that the early to mid-Holocene was the warmest interval at Bachalpsee. Comparison of the palaeobotanical results with those from the mire “Feld” (2130 m a.s.l.) in the vicinity of Bachalpsee showed that during the mid-Holocene the timber-line was formed by Pinus cembra and Picea abies with some scattered Abies alba trees and was situated close to Bachalpsee but never reached its catchment. The maximum timber-line in the Northern Alps was reached between 6000 and 3000 cal b.p. which is several millennia later than in the Central Alps. The species composition of the tree-line (Abies alba, Pinus cembra and the absence of Larix decidua) points to less continental and moister climatic conditions compared with the central Alps during the early to mid-Holocene. From 3000 cal b.p. onwards the timber-line was lowered by human deforestation with the most intense pulses of human impact occurring since the Middle Ages. The catchment of Bachalpsee has been used as alpine pasture since the Bronze Age.     

The steroid glycoside H.g.-12 from Hoodia gordonii activates the human bitter receptor TAS2R14 and induces CCK release from HuTu-80 cells

Steroid glycosides extracted from the succulent plant Hoodia gordonii are suggested to have appetite-suppressant effects both in animals and humans. Yet, the mechanisms underlying the putative satiety action of Hoodia steroid glycosides are not fully understood. We found that H.g.-12, a steroid glycoside purified from H. gordonii extract, initiated cholecystokinin (CCK) secretion both ex vivo in rat intestine and in vitro in the human enteroendocrine (EC) cell line HuTu-80. CCK is known to exert central effects on appetite suppression via the vagus nerve which afferents terminate in the gut wall. Recent data show that G protein-coupled receptors signaling bitter taste (T2Rs) are expressed in both rodent and human gastrointestinal tract. It was further demonstrated that bitter sensing is functional in mouse STC-1 EC cells and leads to CCK secretion via increased intracellular Ca2(+) concentrations. Based on the bitter taste of H. gordonii purified extracts, we assessed whether H.g.-12 could activate human bitter receptors. The steroid glycoside activated selectively TAS2R7 and TAS2R14, both heterologously expressed in HEK 293 cells. Removing an essential structural feature from the steroid glycoside inhibited H.g.-12-induced Ca2(+) increase in TAS2R14-expressing HEK cells and abolished H.g.-12-induced CCK secretion from human EC cells. Similarly, a nonspecific bitter receptor antagonist abolished H.g.-12-induced CCK secretion in HuTu-80 cells. These results point to a potential route of action by which components of Hoodia might influence appetite control. Our data also provide additional evidence that bitter taste-sensing mechanisms are coupled to hormone release from EC cells in the intestine. Moreover, we identified a natural agonist of TAS2R7 and TAS2R14 for further studies on the role of bitter receptors in satiety control and food intake.     

Vibrational signalling in a Gondwanan relict insect (Hemiptera: Coleorrhyncha: Peloridiidae)

Ancient, long-extinct floras and faunas can be reassembled through fossils and phylogenetics, and even palaeo-environments can be reconstructed with the aid of palaeoclimatology. However, very little is known about the sound-scape of the past. Of what kind were the first biologically meaningful sounds and vibrations ever emitted and perceived? The earliest signals in the history of life were probably produced by arthropods making use of the mechanical properties of their exoskeleton. Here, we report an observation of vibrational signalling in the coleorrhynchan Hackeriella veitchi, a representative of a Gondwanan relict insect lineage which is still extant in the Queensland rainforest. Our finding suggests that vibrational signalling by tymbal organs is ancestral for the Hemiptera (exclusive of Sternorrhyncha)--the song of the Coleorrhyncha was a likely element of the acoustic environment in the Permian moss forests and had possibly changed little since.