Environmental Light Exposure Is Associated with Increased Body Mass in Children

The timing, intensity, and duration of exposure to both artificial and natural light have acute metabolic and physiological effects in mammals. Recent research in human adults suggests exposure to moderate intensity light later in the day is concurrently associated with increased body mass; however, no studies have investigated the effect of light exposure on body mass in young children. We examined objectively measured light exposure and body mass of 48 preschool-aged children at baseline, and measured their body mass again 12 months later. At baseline, moderate intensity light exposure earlier in the day was associated with increased body mass index (BMI). Increased duration of light exposure at baseline predicted increased BMI 12-months later, even after controlling for baseline sleep duration, sleep timing, BMI, and activity. The findings identify that light exposure may be a contributor to the obesogenic environment during early childhood.     

Paucity of HPV-Related Head and Neck Cancers (HNC) in Nigeria

IntroductionThe burden of HPV-related Head and Neck Cancers (HNC) has been rising in the U.S. and other developed countries but this trend has not been reported in Africa. Objective of study was to evaluate the prevalence of HPV infection in HNC cancer cases seen between 1990 and 2011 at the tertiary health care institutions in Nigeria.MethodsWe retrieved 149 head and neck cancer formalin fixed, paraffin embedded tumor specimens diagnosed between 1990 and 2011 from four teaching hospitals in Nigeria. One hundred and twenty-three blocks (83%) contained appropriate HNC for analysis while DNA extraction was successful in 60% (90/149). PCR amplification was successful in 33% (49/149) and Linear Array genotyping for HPV was successful in 11% (17/149) of these cases. These were in tumors from the larynx (6), cervical lymph nodes (3), nasal cavity (2), parotid (1), palate (1), maxillary sinus (1) and mandible (1). Two cases were non-specific and none were from the oropharynx. Histologically, 41% (7/17) of the successfully genotyped blocks were squamous cell carcinomas (larynx 6, maxillary sinus 1).

Results and Conclusion

We were unable to detect HPV in any of the HNC samples in our study. Our result may suggest that there is a low prevalence of HPV-related HNC among the adult population in Nigeria. Our results provide a benchmark to compare future incidence of HPV -related HNC in this community in future. We had significant analytical challenges from possible poor tissue processing and urge that future studies should prospectively collect samples and ensure high quality sample processing.     

The Effects of Sub-Regional Climate Velocity on the Distribution and Spatial Extent of Marine Species Assemblages

Many studies illustrate variable patterns in individual species distribution shifts in response to changing temperature. However, an assemblage, a group of species that shares a common environmental niche, will likely exhibit similar responses to climate changes, and these community-level responses may have significant implications for ecosystem function. Therefore, we examine the relationship between observed shifts of species in assemblages and regional climate velocity (i.e., the rate and direction of change of temperature isotherms). The assemblages are defined in two sub-regions of the U.S. Northeast Shelf that have heterogeneous oceanography and bathymetry using four decades of bottom trawl survey data and we explore temporal changes in distribution, spatial range extent, thermal habitat area, and biomass, within assemblages. These sub-regional analyses allow the dissection of the relative roles of regional climate velocity and local physiography in shaping observed distribution shifts. We find that assemblages of species associated with shallower, warmer waters tend to shift west-southwest and to shallower waters over time, possibly towards cooler temperatures in the semi-enclosed Gulf of Maine, while species assemblages associated with relatively cooler and deeper waters shift deeper, but with little latitudinal change. Conversely, species assemblages associated with warmer and shallower water on the broad, shallow continental shelf from the Mid-Atlantic Bight to Georges Bank shift strongly northeast along latitudinal gradients with little change in depth. Shifts in depth among the southern species associated with deeper and cooler waters are more variable, although predominantly shifts are toward deeper waters. In addition, spatial expansion and contraction of species assemblages in each region corresponds to the area of suitable thermal habitat, but is inversely related to assemblage biomass. This suggests that assemblage distribution shifts in conjunction with expansion or contraction of thermal habitat acts to compress or stretch marine species assemblages, which may respectively amplify or dilute species interactions to an extent that is rarely considered. Overall, regional differences in climate change effects on the movement and extent of species assemblages hold important implications for management, mitigation, and adaptation on the U.S. Northeast Shelf.     

Enhancement of Bioavailability and Pharmacodynamic Effects of Thymoquinone Via Nanostructured Lipid Carrier (NLC) Formulation

Thymoquinone (TQ), obtained from black cumin (Nigella sativa), is a natural product with anti-oxidant, anti-inflammatory, and hepatoprotective effects but unfortunately with poor bioavailability. Aiming to improve its poor oral bioavailability, TQ-loaded nanostructured lipid carriers (NLCs) were prepared by high-speed homogenization followed by ultrasonication and evaluated in vitro. Bioavailability and pharmacodynamic studies were also performed. The resultant NLCs showed poor physical homogeneity in Compritol 888 ATO Pluronic F127 system which consequently produced larger particle size and polydispersity index, smaller zeta potential values, and lower short-term (30 days) physical stability than other systems. Encapsulation efficiency percentage (EE%) lied between 84.6?±?5% and 96.2?±?1.6%. TQ AUC_0–t values were higher in animals treated with NLCs, with a relative bioavailability of 2.03- and 3.97-fold (for F9 and F12, respectively) higher than TQ suspension, indicating bioavailability enhancement by NLC formulation. Hepatoprotective effects of F12 showed significant (P?<?0.05) decrease in both serum alanine amino transferase and aspartate amino transferase to reach 305.0?±?24.88 and 304.7?±?23.55 U/ml, respectively, when compared with untreated toxic group. Anti-oxidant efficacy of F12 showed significant (P?<?0.05) decline of malondialdehyde and elevation of reduced glutatione. This improvement was also confirmed histopathologically.     

Interaction of the Human Papillomavirus E6 Oncoprotein with Sorting Nexin 27 Modulates Endocytic Cargo Transport Pathways

A subset of high-risk Human Papillomaviruses (HPVs) are the causative agents of a large number of human cancers, of which cervical is the most common. Two viral oncoproteins, E6 and E7, contribute directly towards the development and maintenance of malignancy. A characteristic feature of the E6 oncoproteins from cancer-causing HPV types is the presence of a PDZ binding motif (PBM) at its C-terminus, which confers interaction with cellular proteins harbouring PDZ domains. Here we show that this motif allows E6 interaction with Sorting Nexin 27 (SNX27), an essential component of endosomal recycling pathways. This interaction is highly conserved across E6 proteins from multiple high-risk HPV types and is mediated by a classical PBM-PDZ interaction but unlike many E6 targets, SNX27 is not targeted for degradation by E6. Rather, in HPV-18 positive cell lines the association of SNX27 with components of the retromer complex and the endocytic transport machinery is altered in an E6 PBM-dependent manner. Analysis of a SNX27 cargo, the glucose transporter GLUT1, reveals an E6-dependent maintenance of GLUT1 expression and alteration in its association with components of the endocytic transport machinery. Furthermore, knockdown of E6 in HPV-18 positive cervical cancer cells phenocopies the loss of SNX27, both in terms of GLUT1 expression levels and its vesicular localization, with a concomitant marked reduction in glucose uptake, whilst loss of SNX27 results in slower cell proliferation in low nutrient conditions. These results demonstrate that E6 interaction with SNX27 can alter the recycling of cargo molecules, one consequence of which is modulation of nutrient availability in HPV transformed tumour cells.     

Anthropogenic modifications to fire regimes in the wider Serengeti‐Mara ecosystem

Fire is a key driver in savannah systems and widely used as a land management tool. Intensifying human land uses are leading to rapid changes in the fire regimes, with consequences for ecosystem functioning and composition. We undertake a novel analysis describing spatial patterns in the fire regime of the Serengeti‐Mara ecosystem, document multidecadal temporal changes and investigate the factors underlying these patterns. We used MODIS active fire and burned area products from 2001 to 2014 to identify individual fires; summarizing four characteristics for each detected fire: size, ignition date, time since last fire and radiative power. Using satellite imagery, we estimated the rate of change in the density of livestock bomas as a proxy for livestock density. We used these metrics to model drivers of variation in the four fire characteristics, as well as total number of fires and total area burned. Fires in the Serengeti‐Mara show high spatial variability—with number of fires and ignition date mirroring mean annual precipitation. The short‐term effect of rainfall decreases fire size and intensity but cumulative rainfall over several years leads to increased standing grass biomass and fuel loads, and, therefore, in larger and hotter fires. Our study reveals dramatic changes over time, with a reduction in total number of fires and total area burned, to the point where some areas now experience virtually no fire. We suggest that increasing livestock numbers are driving this decline, presumably by inhibiting fire spread. These temporal patterns are part of a global decline in total area burned, especially in savannahs, and we caution that ecosystem functioning may have been compromised. Land managers and policy formulators need to factor in rapid fire regime modifications to achieve management objectives and maintain the ecological function of savannah ecosystems.     

Sustaining ignorance: the uncertainties of groundwater and its extraction in the Salar de Atacama,northern Chile

The extraction of groundwater and the regulation of its use in many parts of the world have been found to present a particular kind of problem. A contest involving mining companies, an ‘impacted’ community, and the state arising from groundwater and its extraction in the Salar de Atacama, northern Chile, provides a stark example. What marks the case are the many uncertainties about underground water and the quantities extracted. This article argues that uncertainty characterizes conditions of ‘late industrialism’ and that corporate practice that sustains ignorance is a form of powerful agency that in turn maintains the conditions for potentially harmful extractive activity. Critically engaging with the proposition that water may act in the relational process of unknowing contributes to the analysis of how corporate practice may sustain ignorance. This also suggests that alternative political responses to uncertainty are possible.     

Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment

Monoacylglycerol lipase (MGL) inhibition provides a potential treatment approach to glaucoma through the regulation of ocular 2-arachidonoylglycerol (2-AG) levels and the activation of CB1 receptors. Herein, we report the discovery of new series of carbamates as highly potent and selective MGL inhibitors. The new inhibitors showed potent nanomolar inhibitory activity against recombinant human and purified rat MGL, were selective (>1000-fold) against serine hydrolases FAAH and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Protein-based ¹H NMR experiments indicated that inhibitor 2 rapidly formed a covalent adduct with MGL with a residence time of about 6?h. This interconversion process “intrinsic reversibility” was exploited by modifications of the ligand’s size (length and bulkiness) to generate analogs with “tunable’ adduct residence time (τ). Inhibitor 2 was evaluated in a normotensive murine model for assessing intraocular pressure (IOP), which could lead to glaucoma, a major cause of blindness. Inhibitor 2 was found to decrease ocular pressure by ～4.5?mmHg in a sustained manner for at least 12?h after a single ocular application, underscoring the potential for topically-administered MGL inhibitors as a novel therapeutic target for the treatment of glaucoma.