<Emphasis Type="Italic">CER1</Emphasis>gene variations associated with bone mineral density,bone markers,and early menopause in postmenopausal women

Background

Osteoporosis has a multifactorial pathogenesis characterized by a combination of low bone mass and increased fragility. In our study, we focused on the effects of polymorphisms in CER1 and DKK1 genes, recently reported as important susceptibility genes for osteoporosis, on bone mineral density (BMD) and bone markers in osteoporotic women. Our objective was to evaluate the effect of CER1 and DKK1 variations in 607 postmenopausal women. The entire DKK1 gene sequence and five selected CER1 SNPs were amplified and resequenced to assess whether there is a correlation between these genes and BMD, early menopause, and bone turnover markers in osteoporotic patients.

Results

Osteoporotic women seem to suffer menopause 2 years earlier than the control group. The entire DKK1 gene sequence analysis revealed six variations. There was no correlation between the six DKK1 variations and osteoporosis, in contrast to the five common CER1 variations that were significantly associated with BMD. Additionally, osteoporotic patients with rs3747532 and rs7022304 CER1 variations had significantly higher serum levels of parathyroid hormone and calcitonin and lower serum levels of osteocalcin and IGF-1.

Conclusions

No significant association between the studied DKK1 variations and osteoporosis was found, while CER1 variations seem to play a significant role in the determination of osteoporosis and a potential predictive role, combined with bone markers, in postmenopausal osteoporotic women.

     

Field studies of seahorse population density,structure and habitat use in a semi-closed north-eastern Mediterranean marine area (Stratoni,North Aegean Sea)

The present study was carried out in the marine area of Stratoni, Greece, where two seahorse species are present (Hippocampus hippocampus and Hippocampus guttulatus). Two surveys were conducted (September 2016 and May 2019) to gather information regarding seahorse species' abundance, distribution and habitat characteristics. Four different seahorse natural and artificial habitat types were identified. The results revealed that the presence of H. hippocampus was relatively high, especially at sites with artificial structures, whereas the presence of H. guttulatus was rare. Data collected can provide baseline information for future population assessments.     

Bone morphogenetic proteins (BMPs) expression in the femoral heads of patients with avascular necrosis

Avascular necrosis (AVN) is a disorder of the bone repair process which usually results in femoral head (FH) destruction. Bone morphogenetic proteins (BMPs) are the key proteins regulating bone remodelling and healing. BMPs gene expression levels were analyzed in the normal and necrotic sites of osteonecrotic FHs. Quantitative RT-PCR for BMP-2, -4, -6, -7 genes was performed in bone tissue samples from 47 osteonecrotic FHs. Protein levels of BMP-2, -4, -6 were estimated by Western Blot. Statistical analysis was performed using the Wilcoxon signed rank test. BMP-2 and BMP-6 mRNA levels were higher in the normal than the necrotic site (normal/necrotic: 16.8/6.8 and 1.75/1.64, respectively). On the contrary, BMP-4 mRNA levels were higher in the necrotic (0.75) than the normal (0.62), while BMP-7 mRNA levels were extremely low. At the protein level, BMP-2 continued to have a higher expression in the normal region (normal/necrotic: 0.67/0.64). BMP-4 and -6 were detected at higher levels in the necrotic site (normal/necrotic: 0.51/0.61 for BMP-4, 0.51/0.56 for BMP-6), while BMP-7 was not detectable. Different BMP levels between the normal and necrotic site, as well as discrepancies between the gene and protein expression pattern suggest a different regulation mechanism for BMPs between the two regions of FHs. The understanding of the expression pattern and the correlation of BMPs could lead to a more successful use in the prevention and treatment of AVN.     

Horticultural mineral oil influences Plum pox virus transmission by Myzus persicae

The residual activity of horticultural mineral oil (HMO) on the ability of green peach aphids, Myzus persicae (Sulzer), (GPA) to transmit Plum pox virus (PPV) to peach was measured by infection rates of detached leaves from plants sprayed with either HMO or water as a control that were inoculated using transfer of 25 viruliferous aphids per leaf at 0, 2, 4, 7, 9, 11 and 14 days after treatment (DAT). Persistent effects of HMO residue on the probing and feeding behaviours of GPA were also monitored with the electrical penetration graph (EPG) system. For glasshouse‐grown peach seedlings, the residual activity of HMO reduced PPV infection rates by more than 58% for up to 4 DAT following an initial reduction of approximately 81%. EPG recordings of GPA feeding behaviour showed that HMO significantly delayed first feeding probes and first intracellular punctures by more than 50 min without changing the ensuing stylet penetration behaviour. Applying HMO reduced virus infection rates for up to a week depending on the environmental conditions. EPG monitoring of aphid probing showed that HMO reduced the mean duration and mean number of potential drop (PD) phase feeding occurrences, compared with the water control. A reduction in the PD that has been shown to be related to the transmission of non‐persistently transmitted viruses may partly explain the reduction in PPV infection rates.     

The structure of shallow water fish assemblages in sandy beaches of a tropical bay in the southwestern Atlantic

Ichthyological Research - The spatial and seasonal dynamics of shallow water fish assemblages and their relationship with physical-chemical variables were investigated on Guanabara Bay, one of the...     

Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes

In mammals, sleep is regulated by circadian and homeostatic mechanisms. The circadian component, residing in the suprachiasmatic nucleus (SCN), regulates the timing of sleep, whereas homeostatic factors determine the amount of sleep. It is believed that these two processes regulating sleep are independent because sleep amount is unchanged after SCN lesions. However, because such lesions necessarily damage neuronal connectivity, it is preferable to investigate this question in a genetic model that overcomes the confounding influence of circadian rhythmicity. Mice with disruption of both mouse Period genes (mPer)1 and mPer2 have a robust diurnal sleep-wake rhythm in an entrained light-dark cycle but lose rhythmicity in a free-run condition. Here, we examine the role of the mPer genes on the rhythmic and homeostatic regulation of sleep. In entrained conditions, when averaged over the 24-h period, there were no significant differences in waking, slow-wave sleep (SWS), or rapid eye movement (REM) sleep between mPer1, mPer2, mPer3, mPer1-mPer2 double-mutant, and wild-type mice. The mice were then kept awake for 6 h (light period 6-12), and the mPer mutants exhibited increased sleep drive, indicating an intact sleep homeostatic response in the absence of the mPer genes. In free-run conditions (constant darkness), the mPer1-mPer2 double mutants became arrhythmic, but they continued to maintain their sleep levels even after 36 days in free-running conditions. Although mPer1 and mPer2 represent key elements of the molecular clock in the SCN, they are not required for homeostatic regulation of the daily amounts of waking, SWS, or REM sleep.     

Force-induced bidirectional stepping of cytoplasmic dynein

Cytoplasmic dynein is a minus-end-directed microtubule motor whose mechanism of movement remains poorly understood. Here, we use optical tweezers to examine the force-dependent stepping behavior of yeast cytoplasmic dynein. We find that dynein primarily advances in 8 nm increments but takes other sized steps (4-24 nm) as well. An opposing force induces more frequent backward stepping by dynein, and the motor walks backward toward the microtubule plus end at loads above its stall force of 7 pN. Remarkably, in the absence of ATP, dynein steps processively along microtubules under an external load, with less force required for minus-end- than for plus-end-directed movement. This nucleotide-independent walking reveals that force alone can drive repetitive microtubule detachment-attachment cycles of dynein's motor domains. These results suggest a model for how dynein's two motor domains coordinate their activities during normal processive motility and provide new clues for understanding dynein-based motility in living cells.     

Mechanisms underlying the dual-mode regulation of microtubule dynamics by Kip3/kinesin-8

The kinesin-8 family of microtubule motors plays?a critical role in microtubule length control in cells. These motors have complex effects on microtubule dynamics: they destabilize growing microtubules yet stabilize shrinking microtubules. The budding yeast kinesin-8, Kip3, accumulates on plus ends of growing but not shrinking microtubules. Here we identify an essential role of the tail domain of Kip3 in mediating both its destabilizing and its stabilizing activities. The Kip3 tail promotes Kip3's accumulation at the plus ends and facilitates the destabilizing effect of Kip3. However, the Kip3 tail also inhibits microtubule shrinkage and is required for promoting microtubule rescue by Kip3. These effects of the tail domain are likely to be mediated by the tubulin- and microtubule-binding activities that we describe. We propose a concentration-dependent model for the coordination of the destabilizing and stabilizing activities of Kip3 and discuss its relevance to cellular microtubule organization.     

A crucial requirement for Hedgehog signaling in small cell lung cancer

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer for which there is no effective treatment. Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is activated in SCLC cells independently of the lung microenvironment. Constitutive activation of the Hedgehog signaling molecule Smoothened (Smo) promoted the clonogenicity of human SCLC in vitro and the initiation and progression of mouse SCLC in vivo. Reciprocally, deletion of Smo in Rb1 and Trp53-mutant lung epithelial cells strongly suppressed SCLC initiation and progression in mice. Furthermore, pharmacological blockade of Hedgehog signaling inhibited the growth of mouse and human SCLC, most notably following chemotherapy. These findings show a crucial cell-intrinsic role for Hedgehog signaling in the development and maintenance of SCLC and identify Hedgehog pathway inhibition as a therapeutic strategy to slow the progression of disease and delay cancer recurrence in individuals with SCLC.