The connecting cilium inner scaffold provides a structural foundation that protects against retinal degeneration

Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause of human blindness. These cells possess a photosensitive outer segment linked to the cell body through the connecting cilium (CC). While structural defects of the CC have been associated with retinal degeneration, its nanoscale molecular composition, assembly, and function are barely known. Here, using expansion microscopy and electron microscopy, we reveal the molecular architecture of the CC and demonstrate that microtubules are linked together by a CC inner scaffold containing POC5, CENTRIN, and FAM161A. Dissecting CC inner scaffold assembly during photoreceptor development in mouse revealed that it acts as a structural zipper, progressively bridging microtubule doublets and straightening the CC. Furthermore, we show that Fam161a disruption in mouse leads to specific CC inner scaffold loss and triggers microtubule doublet spreading, prior to outer segment collapse and photoreceptor degeneration, suggesting a molecular mechanism for a subtype of retinitis pigmentosa.

Inherited retinal degeneration due to loss of photoreceptor cells is a leading cause of human blindness. Ultrastructure expansion microscopy on mouse retina reveals the presence of a novel structure inside the photoreceptor connecting cilium, the inner scaffold, that protects the outer segment against degeneration.     

Standardized Aronia melanocarpa extract regulates redox status in patients receiving hemodialysis with anemia

Molecular and Cellular Biochemistry - The aim of our study was to investigate the effects of one-month consumption of polyphenol-rich standardized Aronia melanocarpa extract (SAE) on redox status...     

Guaianolides from two subspecies of Amphoricarpos neumayeri from Montenegro

Quantitative (1)H NMR measurements revealed delta(11(13)) sesquiterpene gamma-lactones as the main constituents ( >or= 1% per weight of dried plant material) in the crude extracts of the aerial parts of Amphoricarpos neumayeri ssp. neumayeri and ssp. murbeckii from mountains Orjen and Visitor (Montenegro), respectively. Preparative silica gel chromatography afforded thirteen guai-11(13)-en-12,6alpha-olides, named amphoricarpolides (1-13), with the same relative (1alphaH,4betaH,5alphaH,7betaH) configuration of the basic skeleton. The common structural feature of lactones 2-13 was 3beta,15-dioxygenation pattern. The only exception was 1 (3-deoxyamphoricarpolide), containing a single oxygen substituent (15-OH). Eight of them exhibited an additional oxygen substituent, 9beta-OH (5 and 6), 2alpha-OH (8-12), or 2alpha-OAc (13). Compound 7 was epoxydated at 10alpha(14)-position, whereas the remaining lactones contained a 10(14) double bond.     

A role for interferon-gamma in the hypermetabolic response to murine toxoplasmosis

Toxoplasma gondii (Me49 strain) infection into Swiss Webster mice is followed by hypermetabolism and weight loss in the acute phase lasting 14 days. In the subsequent chronic phase of infection, mice showed either a resolution of hypermetabolism and partial weight recovery (Gainers) or persistent hypermetabolism, with stable weight loss (Non-Gainers). The hypermetabolic response was not associated with an augmentation in the thermogenic uncoupling protein 1 (UCP1) mRNA expression in interscapular brown adipose tissue (BAT), but rather UCP1 expression was reduced. Hypermetabolism is associated with high lipid oxidation as attested by a low respiratory quotient (RQ). Neither BAT nor sympathetic nervous system appear to be involved in the increased lipid utilization, since propranolol did not increase the lower RQ in infected mice. The mitochondrial lipid oxidation blocker mercaptoacetate did not reestablish the respiratory quotient RQ in acute infection (on day 4) and in chronically infected Non-Gainer mice. This suggests an important extra-mitochondrial mechanism of lipid oxidation. Increased lipid peroxidation was detected especially in serum, lung, spleen and liver, which are rich in macrophage-type cells. Following infection peritoneal macrophages exhibited an enhanced capacity to produce reactive oxygen species (ROS). Using IFN-gamma knockout mice we observed that not only the hypermetabolic response was ablated in these mice but there was not a marked increase in ROS production or preferential oxidation/peroxidation of lipids in the acute phase of infection prior to the cachectic phase. The present study described a novel hypermetabolic mechanism involving enhanced lipid peroxidation dependent on IFN-gamma, especially associated with tissues rich in macrophages.     

Micronuclei and ageing in a sample of Yugoslavian population

OBJECTIVE: Instability in the organization and expression of the genetic material has been hypothesized as the basic mechanism of ageing. Aim of this study was to quantify the effect of ageing on spontaneous micronuclei (MN) frequency in peripheral blood lymphocytes. METHOD: Analysis of Yugoslavian population sample (164 tested individuals, age 0-62 years) has performed by application of cytokinesis-block technique (CB). RESULTS: There was an increase of MN frequency with age, from newborns to 40-year-old persons. The total average of MN frequency per 1000 analyzed binuclear cells amounts to 8.03 +/- 0.42, with variation from 0 to 26 MNs. In a sample of 29 newborns the recorded average MN frequency was 6.91 +/- 0.81, while among 69 persons 25-39 years old, the MN frequency was 9.16 +/- 1.00. The lowest average MN frequency, however, was noted in the sample of 34 tested individuals 40 to 62 years of age. CONCLUSION: An increase with age in MN frequency has been observed in samples of studied individuals from newborns to 40-year-old persons. A decrease of MN frequency in older groups could be explained by a gradual decrease of proliferative cell capacities.     

The effect of experience and gender on cardiovascular and metabolic responses with dynamic Tae Kwon Do exercise

This study, conducted at the Exercise Physiology Laboratory of Auburn University, AL, addressed and compared the acute cardiovascular and metabolic effects elicited by novice and experienced men and women participants during a single bout of dynamic Tae Kwon Do exercise and investigated whether or not dynamic Tae Kwon Do practice is an exercise modality that provides sufficient cardiorespiratory demand for enhancing aerobic fitness and promoting weight and fat loss. Twenty-eight men and women (aged 19-42) were assigned to 1 of the following 4 groups: Tae Kwon Do experienced and trained men (ME), Tae Kwon Do experienced and trained women (FE), novice Tae Kwon Do men (MN), and novice Tae Kwon Do women (FN). The results of this investigation indicate that this form of exercise can be performed for an extended period of 20 minutes. All 4 groups achieved the recommended stimulus for effective initiation of cardiovascular adaptations and conditioning. The mean exercise heart rate responses (88.3-92.2% of maximal heart rate [HR max]) were similar for all groups. The observed exercise intensity ranged from 67.9 to 72.1% VO2max, and no significant difference based on the experience and gender and exercise oxygen uptake could be established. Data in this study indicate a high caloric expenditure for this mode of exercise. Total caloric cost of 20 minutes of dynamic Tae Kwon Do, 194.8 and 201.6 kcal for novice women and experienced women, respectively, was significantly lower in comparison with that of their men counterparts (316.5 and 286.5 kcal, respectively), but no significant relationship between experience and energy cost was found. The conclusion of this study indicates that dynamic Tae Kwon Do is an exercise modality that can be appropriately prescribed for cardiovascular conditioning, weight control, and fat loss.     

The effect of acute heat exposure on rat pituitary corticotroph activation: the role of vasopressin

The increased ambient temperature affects the function of hypothalamic-pituitary-adrenal (HPA) axis. Since the correlation among vasopressin (VP), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses to various stressors have been long recognized, the aim of this study was to reveal the aforementioned hormones production and morphology of the pituitary gland after exposure to acute heat. Rats were exposed to high ambient temperature (38 °C) for 20 or 60 minutes. The circulating hormones were determined by an ELISA test or chemiluminescence's method. The results obtained show the elevation in ACTH and CORT secretion depending on the duration of heat exposure. The VP concentration increased only after prolonged exposure to heat (60 min). The pituitary morphology was examined by routine and fluorescent immunohistochemistry as well as electron microscopy. Observed changes in the anterior and posterior pituitary well corresponded to circulating hormones, regarding the volume density of ACTH-immunopositive cells, percentage of ACTH immunopositive area v. total area and number of VP-immunopositive containing varicose fibers per total area. Acute heat exposure also induced changes in shapes of ACTH-immunopositive cells. Cells appeared stellate with numerous slender cytoplasmic processes and degranulated, which is the most obvious after 20 min. In addition, immunopositivity of endothelial and anterior pituitary cells for VP suggests its influence on ACTH secretion.