Specific features of ex‐obese patients significantly influence the functional cell properties of adipose‐derived stromal cells

Adipose‐derived stromal cells (ADSC) are increasingly used in clinical applications due to their regenerative capabilities. However, ADSC therapies show variable results. This study analysed the effects of specific factors of ex‐obese patients on ADSC functions. ADSC were harvested from abdominal tissues (N = 20) after massive weight loss. Patients were grouped according to age, sex, current and maximum body mass index (BMI), BMI difference, weight loss method, smoking and infection at the surgical site. ADSC surface markers, viability, migration, transmigration, sprouting, differentiation potential, cytokine secretion, telomere length and mtDNA copy number were analysed. All ADSC expressed CD73, CD90, CD105, while functional properties differed significantly among patients. A high BMI difference due to massive weight loss was negatively correlated with ADSC proliferation, migration and transmigration, while age, sex or weight loss method had a smaller effect. ADSC from female and younger donors and individuals after weight loss by increase of exercise and diet change had a higher activity. Telomere length, mtDNA copy number, differentiation potential and the secretome did not correlate with patient factors or cell function. Therefore, we suggest that factors such as age, sex, increase of exercise and especially weight loss should be considered for patient selection and planning of regenerative therapies.     

Olfactory discrimination in the western lowland gorilla, Gorilla gorilla gorilla

The olfactory abilities of great apes have been subject to little empirical investigation, save for a few observational reports. This study, using an habituation/dishabituation task, provides experimental evidence for a core olfactory ability, namely, olfactory discrimination, in the gorilla. In Experiment 1, six zoo-housed western lowland gorillas were individually presented with the same odour on four trials, and with a novel odour on the fifth trial. Odours (almond and vanilla) were presented on plastic balls, and behavioural responses of sniffing and chewing/licking the balls were recorded. A second experiment presented the same odour on four trials and no odour on the fifth to examine whether any dishabituation was due to the presence of a new odour or the absence of the familiar odour. Gorillas habituated their behaviour with repeated presentation of the same odour, but dishabituated, i.e. increased sniffing and chewing/licking, when presented with the novel odour. No dishabituation was noted when using water as the stimulus across all trials or when used as the novel odour. Overall, results show that gorillas are able to discriminate between odours.     

The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins

Rab5 and Rab4 are small monomeric GTPases localized on early endosomes and function in vesicle fusion events. These Rab proteins regulate the endocytosis and recycling or degradation of activated receptor tyrosine kinases such as the platelet-derived growth factor receptor (PDGFR). The p85alpha subunit of phosphatidylinositol 3'-kinase contains a BH domain with sequence homology to GTPase activating proteins (GAPs), but has not previously been shown to possess GAP activity. In this report, we demonstrate that p85alpha has GAP activity toward Rab5, Rab4, Cdc42, Rac1 and to a lesser extent Rab6, with little GAP activity toward Rab11. Purified recombinant Rab5 and p85alpha can bind directly to each other and not surprisingly, the p85alpha-encoded GAP activity is present in the BH domain. Because p85alpha stays bound to the PDGFR during receptor endocytosis, p85alpha will also be localized to the same early endosomal compartment as Rab5 and Rab4. Taken together, the physical co-localization and the ability of p85alpha to preferentially stimulate the down-regulation of Rab5 and Rab4 GTPases suggests that p85alpha regulates how long Rab5 and Rab4 remain in their GTP-bound active state. Cells expressing BH domain mutants of p85 show a reduced rate of PDGFR degradation as compared with wild type p85 expressing cells. These cells also show sustained activation of the mitogen-activated protein kinase and Akt pathways. Thus, the p85alpha protein may play a role in the down-regulation of activated receptors through its temporal control of the GTPase cycles of Rab5 and Rab4.     

Respiratory Phenomics across Multiple Models of Protein Hyperacylation in Cardiac Mitochondria Reveals a Marginal Impact on Bioenergetics

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The Use of a Respiratory Rate Biofeedback Device to Reduce Dental Anxiety: An Exploratory Investigation

Anxiety experienced by individuals visiting the dental office to receive treatment is common. Evidence has shown biofeedback to be a useful modality of treatment for numerous maladies associated with anxiety. The purpose of the current pilot study was to investigate the use of a novel biofeedback device (RESPeRATE™) to reduce patients’ pre-operative general anxiety levels and consequently reduce the pain associated with dental injections. Eighty-one subjects participated in this study, forty in the experimental group and forty-one in the control group. Subjects in the experimental group used the biofeedback technique, while those in the control group were not exposed to any biofeedback. All subjects filled out a pre-injection anxiety survey, then received an inferior alveolar injection of local anesthetic. Post-injection, both groups were given an anxiety survey and asked to respond to four questions regarding the injection experience using a Visual Analog Scale (VAS). With the use of the respiratory rate biofeedback device, there was a significant reduction of negative feelings regarding the overall injection experience, as measured by a VAS. Our findings demonstrate that this novel biofeedback technique may be helpful in the amelioration of dental anxiety, and may help produce a more pleasant overall experience for the patient.     

α-Synuclein Delays Endoplasmic Reticulum (ER)-to-Golgi Transport in Mammalian Cells by Antagonizing ER/Golgi SNAREs

Toxicity of human α-synuclein when expressed in simple organisms can be suppressed by overexpression of endoplasmic reticulum (ER)-to-Golgi transport machinery, suggesting that inhibition of constitutive secretion represents a fundamental cause of the toxicity. Whether similar inhibition in mammals represents a cause of familial Parkinson''s disease has not been established. We tested elements of this hypothesis by expressing human α-synuclein in mammalian kidney and neuroendocrine cells and assessing ER-to-Golgi transport. Overexpression of wild type or the familial disease-associated A53T mutant α-synuclein delayed transport by up to 50%; however, A53T inhibited more potently. The secretory delay occurred at low expression levels and was not accompanied by insoluble α-synuclein aggregates or mistargeting of transport machinery, suggesting a direct action of soluble α-synuclein on trafficking proteins. Co-overexpression of ER/Golgi arginine soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) specifically rescued transport, indicating that α-synuclein antagonizes SNARE function. Ykt6 reversed α-synuclein inhibition much more effectively than sec22b, suggesting a possible neuroprotective role for the enigmatic high expression of ykt6 in neurons. In in vitro reconstitutions, purified α-synuclein A53T protein specifically inhibited COPII vesicle docking and fusion at a pre-Golgi step. Finally, soluble α-synuclein A53T directly bound ER/Golgi SNAREs and inhibited SNARE complex assembly, providing a potential mechanism for toxic effects in the early secretory pathway.     

Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain

Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer''s disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer''s, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk.