Regulation of autophagy as a therapeutic option in glioblastoma

Apoptosis - Around three out of one hundred thousand people are diagnosed with glioblastoma multiforme, simply called glioblastoma, which is the most common primary brain tumor in adults. With a...     

Oystershell scale: an emerging invasive threat to aspen in the southwestern US

Biological Invasions - Oystershell scale (OSS; Lepidosaphes ulmi) is an emerging invasive insect that poses a serious threat to conservation of quaking aspen (Populus tremuloides) in the...     

Apolipoprotein E isoform-dependent effects on the processing of Alzheimer's amyloid-β

Since the identification of the apolipoprotein E (apoE) *ε4 allele as a major genetic risk factor for late-onset Alzheimer's disease, significant efforts have been aimed at elucidating how apoE4 expression confers greater brain amyloid-β (Aβ) burden, earlier disease onset and worse clinical outcomes compared to apoE2 and apoE3. ApoE primarily functions as a lipid carrier to regulate cholesterol metabolism in circulation as well as in the brain. However, it has also been suggested to interact with hydrophobic Aβ peptides to influence their processing in an isoform-dependent manner. Here, we review evidence from in vitro and in vivo studies extricating the effects of the three apoE isoforms, on different stages of the Aβ processing pathway including synthesis, aggregation, deposition, clearance and degradation. ApoE4 consistently correlates with impaired Aβ clearance, however data regarding Aβ synthesis and aggregation are conflicting and likely reflect inconsistencies in experimental approaches across studies. We further discuss the physical and chemical properties of apoE that may explain the inherent differences in activity between the isoforms. The lipidation status and lipid transport function of apoE are intrinsically linked with its ability to interact with Aβ. Traditionally, apoE-oriented therapeutic strategies for Alzheimer's disease have been proposed to non-specifically enhance or inhibit apoE activity. However, given the wide-ranging physiological functions of apoE in the brain and periphery, a more viable approach may be to specifically target and neutralise the pathological apoE4 isoform.     

Metal-Enhanced Photosensitization of Singlet Oxygen (ME1O2) from Brominated Carbon Nanodots on Silver Nanoparticle Substrates

The deleterious effects of reactive oxygen species (ROS), including singlet oxygen (¹O₂), on biological systems have cultivated widespread interest in fields ranging from therapeutic techniques to sterilization materials. Researchers have, for example, sought to capitalize on the oxidative damage from singlet oxygen to treat tumors as well as to kill antibiotic resistant bacteria. To generate ¹O₂ in a controllable manner, photosensitizers are optimized to generate ¹O₂ from ground state oxygen (³O₂) when excited by light. When considering applications of photosensitization, favorable properties include high ¹O₂ yield, low synthetic complexity, and minimal cost. Previously, studies have shown that plasmonic nanoparticles are able to amplify the photosensitization of ¹O₂ from small molecule photosensitizers in a mechanism similar to metal-enhanced fluorescence (MEF), thereby improving yield. A recent study from our lab has demonstrated that brominated carbon nanodots, which are an inexpensive and simple-to-collect as a hydrocarbon combustion byproduct, generate reactive oxygen species that can be used for antimicrobial photodynamic inactivation of bacteria. Herein we investigate the combination of these advantageous properties. Using the turn-on fluorescent probe Singlet Oxygen Sensor Green™ to detect ¹O₂, we report the metal-enhanced photosensitization of ¹O₂ by brominated dots in silvered Quanta Plate™ wells. These results provide a promising direction for the potential optimization of carbon nanodot-based agents in light-activated antimicrobial materials.

     

Azole-resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam,with marked variability by land use type

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR₃₄/L98H most frequent (34/38).     

Divergent modes for cargo-mediated control of clathrin-coated pit dynamics

Clathrin-mediated endocytosis has long been viewed as a process driven by core endocytic proteins, with internalized cargo proteins being passive. In contrast, an emerging view suggests that signaling receptor cargo may actively control its fate by regulating the dynamics of clathrin-coated pits (CCPs) that mediate their internalization. Despite its physiological implications, very little is known about such “cargo-mediated regulation” of CCPs by signaling receptors. Here, using multicolor total internal reflection fluorescence microscopy imaging and quantitative analysis in live cells, we show that the μ-opioid receptor, a physiologically relevant G protein–coupled signaling receptor, delays the dynamics of CCPs in which it is localized. This delay is mediated by the interactions of two critical leucines on the receptor cytoplasmic tail. Unlike the previously known mechanism of cargo-mediated regulation, these residues regulate the lifetimes of dynamin, a key component of CCP scission. These results identify a novel means for selectively controlling the endocytosis of distinct cargo that share common trafficking components and indicate that CCP regulation by signaling receptors can operate via divergent modes.     

First Record of Cenozoic Bird Footprints from East Asia (Tibet,China)

Cenozoic bird tracks are known largely from North America, Europe, and the Middle East. There have been no reports of Cenozoic bird tracks from East Asia. This paper describes a series of two trackways produced by a galliform-like or gruiform-like bird from the Oligocene to Early Miocene of Tibet. The tracks are represented by tracings collected from a coal mine in Shigatse, Tibet, during the late 1970s. The tracks are comparable to Ornithoformipes and Pavoformipes and likely represent a medium-sized to large cursorial or flightless bird. In relation to modern bird tracks, the tracks bear a striking resemblance to those produced by the North American Wild Turkey (Meleagris gallopavo) except that M. gallopavo tracks often possess a small, elevated hallux impression. Due to the fact that these are tracings, however, a hallux may have been present and simply have been overlooked. The Shigatse trackways were, unfortunately, lost when the mine was closed and then backfilled during the 1980s, and there is little to no likelihood of recovery. Casts can be catalogued as holotype specimens but tracings cannot; however, all the original tracings have been donated to a public institution by their discoverer, Yimin Wu.