Entanglement‐scar acquisition rates and scar frequency for Bering‐Chukchi‐Beaufort Seas bowhead whales using aerial photography

The Bering‐Chukchi‐Beaufort Seas (BCBS) bowhead whale (Balaena mysticetus) has been considered at low‐risk for entanglement injuries and ship strikes because their range is mainly north of commercial fisheries; nevertheless, changes to their arctic habitat, including a longer open water period and declining sea ice, have resulted in increasing commercial activity and concern about fisheries interactions. We examined interyear matches (between 1985 and 2011) from a photo identification project and identified whales that had acquired entanglement injuries. We estimated the probability of a bowhead acquiring an entanglement injury using two statistical methods: interval censored survival analysis and a simple binomial model. Both methods give similar results, suggesting a 2.2% (95% CI: 1.1%–3.3%) annual probability of acquiring a scar. We also include an entanglement scar frequency analysis of aerial photographs from the 2011 spring and fall surveys near Point Barrow, Alaska, which suggest 12.4% of live bowheads show evidence of entanglement scarring. Entanglement rates for the BCBS bowhead stock are lower than many other large whale stocks, and abundance has increased over the past 35 yr; however, our findings indicate that fishing gear entanglement is a more serious concern for the BCBS bowhead whale population than previously thought.     

Cationic liposome codelivering PI3K pathway regulator improves the response of BRCA1-deficient breast cancer cells to PARP1 inhibition

Although some progresses have been made in breast cancer therapy, effective treatment for BRCA1-deficient breast cancer remains to be a great challenge. It has been demonstrated that the PI3K pathway is inappropriately activated in BRCA1-deficient breast cancers which can be downregulated by microRNA 451 (miR-451). In addition, although PARP1 inhibitors showed relatively positive results in both preclinical and clinical studies, additional efforts to decrease drug resistance as well as reduce systematic toxicity need to be addressed. To this end, by encapsulating the miR-451 mimic and PARP1 inhibitor in the same cationic liposome, we examined the potential of enhancing the response of PARP1 inhibition on BRCA1-deficient breast cancer by regulating the PI3K pathway. Our results revealed that in BRCA1-deficient human breast cancer cell line, PARP1 inhibition resulted in DNA damage with viability decrease, G2/M arrest as well as apoptosis. In contrast, single PI3K inhibition induced G1 arrest along with retarded cell proliferation. However, it was noted that combination of PARP inhibitor and PI3K regulator could exert synergetic function to evidently decrease cell proliferation compared with PARP inhibition alone, which was also confirmed by in vivo antitumor assay using xenograft tumor models. Collectively, our results offer an alternative but superior strategy for the therapy of BRCA1-deficient human breast cancers which may benefit the clinical applications.     

Inhibition of miR146b-5p suppresses CT-guided renal cell carcinoma by targeting TRAF6

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. Due to the lack of early symptoms, diagnosis of RCC usually occurs at late stages or after cancer metastasis leading to poor prognosis. Therefore, it is crucial to study early molecular mechanisms and biomarkers. Previous studies have suggested that microRNAs are involved in RCC initiation and development, making them a good candidate for early diagnosis and therapy. MiR146b-5P plays important roles in the progression of multiple cancers including thyroid cancer, pancreatic cancer, cervical cancer. However, it is not clear whether and how miR146b-5P is involved in RCC. In this study, we aimed to investigate the function of miR146b-5P in RCC. We examined the expression levels of miR146b-5p in renal cancer tissue and cell lines. We also explored the effects of blocking miR146b-5p in renal tumor growth and inflammatory signaling. Finally, we determined if miR146b-5p regulates tumorigenesis through TRAF6. We found that miR146b-5p levels were significantly increased in renal cancer tissue and renal cancer cells. Blocking miR146b-5p suppressed renal tumor growth and enhanced inflammatory response through increased TRAF6 expression. These effects were eliminated in TRAF6 knockout mice. Our results suggest that enhanced miR146b-5p expression may be a biomarker for RCC and modulating miR146b-5p and TRAF6 levels represent a potential therapeutic strategy for RCC.     

Hsa-miRNA-29a protects against high glucose-induced damage in human umbilical vein endothelial cells

Sustained exposure to high glucose (HG) results in dysfunction of vascular endothelial cells. Hence, diabetic patients often suffer from secondary vascular damages, such as vascular sclerosis and thrombogenesis, which may eventually cause cardiovascular problems. Thus, elucidating how HG results in vascular endothelial cell damage and finding an approach for prevention are important to prevent and treat vascular damages in diabetic patients. In the current study, we first showed that 72-hour exposure to HG-decreased hsa-miRNA-29a and increased the expression of Bcl-2 associated X protein (Bax), which subsequently inhibited Bcl-2 and promoted the expression of apoptotic protease activating factor-1 and activation of caspase-3, thus directly triggering the mitochondrial apoptotic pathway in human umbilical vein endothelial cells (HUVECs). Study of the underlying mechanism showed that hsa-miRNA-29a/Bax plays an essential role in the decreased proliferation and increased apoptosis of HUVECs induced by HG, and overexpression of hsa-miRNA-29a effectively inhibits HG-induced apoptosis and restores the proliferation and tube formation of HUVECs exposed to HG by inhibiting its target gene Bax. In short, our study demonstrates that hsa-miRNA-29a is a promising target for the prevention and treatment of vascular injury in diabetic patients.     

Optimization of α-ketoamide based p38 inhibitors through modifications to the region that binds to the allosteric site

We have optimized a novel series of potent p38 MAP kinase inhibitors based on an α-ketoamide scaffold through structure based design that due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME, in vivo PK and efficacy studies show these compounds to have drug-like characteristics and have resulted in the nomination of a development candidate which is currently in phase II clinical trials for the oral treatment of inflammatory conditions.     

Characterization of the lipid and protein contents of myelin bodies isolated from the renal cortex of gentamicin-treated rats.

Myelin bodies were isolated from the renal cortex of gentamicin-treated rats (100 mg/kg body weight, twice daily for 3 days, i.p.) employing an initial pelleting by differential centrifugation and subsequent flotation on a discontinuous sucrose gradient. These structures were found to contain almost twice as much protein as phospholipid and SDS-polyacrylamide gel electrophoresis revealed the presence of many different polypeptides. All the major phospholipids are present, although myelin bodies contain a considerably higher proportion of phosphatidylinositol, somewhat more phosphatidylcholine and considerably lower percentages of phosphatidylserine and sphingomyelin than do normal renal phospholipids. The fatty acids of myelin body phospholipids are highly saturated (67.3-87.9%) and a striking feature is the occurrence of relatively large amounts of 22:1, presumably erucic acid, especially in sphingomyelin. Myelin bodies contain small amounts of unesterified cholesterol, unesterified dolichol and coenzymes Q9 and Q10.     

Landscape effects on birds in urban woodlands: an analysis of 34 Swedish cities

Aim To compare bird abundances in woodlands along gradients from the city centre to the peri‐urban area. To evaluate the importance of the proportion of woodland within the city and in the peri‐urban landscape to forest bird communities breeding in urban woodlands. To test whether fragmentation effects on birds were linked to the type of peri‐urban matrix. Location A total of 34 Swedish cities with > 10,000 inhabitants in south‐central Sweden. The study area covered 105,000 km², in which 84% of the Swedish population of 9.1 million lives. Methods Repeated point count surveys were conducted in 2004 in a total of 474 woodlands. General linear models were used to test for possible differences in abundance along urban to peri‐urban gradients, and to regress bird abundances in local urban woodlands on: (1) total woodland cover in the city, (2) total woodland cover in the peri‐urban landscape, (3) the interaction between woodland cover in the city and in the peri‐urban area, (4) region, and (5) human density. Results More than 12,000 individuals of 100 forest bird species were recorded. Of the 34 most common species detected, 13 bird species had higher abundances in urban than in peri‐urban woodlands, and seven species showed the opposite trend. The bird community of urban woodlands was characterized by species associated with deciduous forests and tree nesters, whereas the bird community of peri‐urban woodlands was characterized by species associated with coniferous woodland and ground nesters. Twelve species were significantly linearly associated with the proportion of urban woodland and/or the proportion of peri‐urban woodland, and a further eight species were associated with the interaction between these two factors. Local breeding bird abundances of four species were significantly positively associated with the proportion of urban woodland only in farmland‐dominated landscapes. Main conclusions Fragmentation effects on some urban birds are linked to the type of peri‐urban matrix. In farmland landscapes, peri‐urban woodlands may have been too scarce to act as a source of bird immigrants to fragmented urban woodlands. To maintain populations of specialized forest birds within cities in landscapes dominated by agriculture, it is of paramount importance to conserve any remaining urban woodlands.