Collagen modifying enzyme P4HA1 is overexpressed and plays a role in lung adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths globally and is histologically defined as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), with the latter accounting for 80% of all lung cancers. The 5-year overall survival rate for lung cancer patients is low as it is often discovered at advanced stages when potential cure by surgical resection is no longer an option. To identify a biomarker and target for lung cancer, we performed analysis of multiple datasets of lung cancer gene expression data. Our analyses indicated that the collagen-modifying enzyme Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is overexpressed in NSCLC. Furthermore, our investigation found that overexpression of enzymes involved in this pathway predicts poor outcome for patients with lung adenocarcinoma. Our functional studies using knockdown strategies in lung cancer cell lines in vitro indicated that P4HA1 is critical for lung cancer growth, migration, and invasion. Additionally, diethyl pythiDC (PythiDC), a small molecule inhibitor, decreased the malignant phenotypes of lung cancer cells. Moreover, we found that miR-124 regulates and targets P4HA1 in lung cancer cells. Thus, our study suggests that collagen-modifying enzymes play an important role in lung cancer aggressiveness. Furthermore, our studies showed that P4HA1 is required for lung cancer cell growth and invasion, suggesting its potential as a valid therapeutic target in lung adenocarcinoma.     

Ventilation of the gills by the pectoral fins in the fangtooth Anoplogaster cornutum: how to breathe with a full mouth

The midwater fangtooth Anoplogaster cornutum eats large prey items whole. To eat prey the fish distends the opercula and spreads the gill arches apart. The pectoral fins are then used to fan water over the gills until ingestion is completed.     

Responses of the mussel Mytilusedulis L. to simulated subarctic tide pool conditions

Mussels in subarctic Norway commonly occur in shallow intertidal pools. By living in pools (a habitat rarely inhabited in lower latitudes) they are insulated against low air temperatures but exposed to high salinities (<70°/oo) beneath overlying ice. Mussels avoid exposing their tissues to such high salinities because a shell valve closure response to low temperature operates at about ?1.5°C before ice sheets form and bottom water salinities rise. Shell valve closure coincides with very low cardiac and ciliary activity.     

Reversible alterations in cultured pulmonary artery endothelial cell monolayer morphology and albumin permeability induced by ionizing radiation

The effects of ionizing irradiation (0, 600, 1,500, or 3,000 rads) on the permeability of pulmonary endothelial monolayers to albumin were studied. Pulmonary endothelial cells were grown to confluence on gelatin-coated polycarbonate filters, placed in serum-free medium, and exposed to a 60Co source. The monolayers were placed in modified flux chambers 24 hours after irradiation; 125I-albumin was added to the upper well, and both the upper and lower wells were serially sampled over 4 hours. The amount of albumin transferred from the upper well/hour over the period of steady-state clearance (90-240 min after addition of 125I-albumin) was 2.8 +/- 0.2% in control monolayers and was increased in monolayers exposed to 1,500 or 3,000 rads (increase of 63 +/- 10% and 61 +/- 10%, respectively, P less than 0.01). No increase was found in monolayers exposed to 600 rads. The increases in endothelial albumin transfer rates were associated with morphologic evidence of monolayer disruption and endothelial injury which paralleled the changes in albumin permeability. Dose-dependent alterations in endothelial actin filament organization were also found. Incubation of the monolayers exposed to 3,000 rads with medium supplemented with 10% fetal calf serum for 24 hours resulted in normalization of albumin permeability, improvement in morphologic appearance of the monolayers, and reorganization of the actin filament structure. These studies demonstrate that ionizing radiation is an active principle in the reversible disorganization of cultured pulmonary endothelial cell monolayers without the need of other cell types or serum components.     

Seasonal variation in the strength of interference competition among headwater stream predators

1. Vertebrate communities in headwater streams are assumed to be regulated through competitive and predatory interactions. Although documented predation is rare, studies regularly report competitive dominance by fish that, as larger competitors reliant on aquatic habitat, exclude semi-aquatic salamanders to marginal stream habitat. However, it is unclear whether fish interact with stream-breeding salamanders through indirect effects such as competition for resources (e.g. food or cover) or fear (i.e. threat of predation) nor is it known whether these interactions are consistent through time.
2. This study used a novel caging approach to determine if competitive outcomes between a headwater fish and salamanders were regulated primarily through resource depletion (exploitative competition) or behavioural avoidance (interference competition).
3. We paired banded sculpin (Cottus carolinae) and larval red salamanders (Pseudotriton ruber) of similar body size in independent flow through mesocosms with intra- and inter-specific pairs allowed to interact physically or non-physically. The experiment was repeated in the autumn and in the spring when stream salamander larvae begin to transform into terrestrial juveniles.
4. Banded sculpin negatively influenced growth of red salamanders regardless of whether they were allowed to physically interact, suggesting interference competition and behavioural avoidance. This asymmetrical effect was strongest in the spring when salamanders underwent metamorphosis at higher rates in the presence of fish. However, in the autumn, the effects were more balanced between the two species with salamanders impacting fish through exploitative competition.
5. By studying the temporal relationships between two competitors and using a caging method novel to competition studies, we established that the outcomes of competition are dependent on season and may vary in type relative to the timing of life-history events. For this community, these results suggest that outcomes of competition are highly dependent on season and could indicate a biotic mechanism maintaining headwater salamander distributions through source–sink dynamics. Our results also suggest that, in this species interaction, it may be unwarranted to assume that the outcomes of competition at one time represent the complex relationships regulating community interactions.

     

Olfactory memory: the long and short of it

It has been proposed that memory for odors does not have a short-term (or working) memory system. The distinction between short- and long- term memory in other sensory modalities has been generally supported by three main lines of evidence: capacity differences between the proposed systems, evidence of differential coding, and differential memory losses in neuropsychological patients. The present paper examines these issues in an effort to establish a similar distinction for the memory of olfactory stimuli. Each of these lines of evidence is examined in relation to the literature on olfactory memory. Based on this examination, it seems that there is at least preliminary support from each of these lines of evidence to advocate a distinction between a long- and short-term memory for olfactory stimuli. Emphasis is placed upon the qualitative similarity of olfactory memory to other memory systems. This similarity is further highlighted through an examination of the literature pertinent to serial position effects in memory for olfactory stimuli.      

Structure of an HIV-2 gp120 in Complex with CD4

HIV-2 is a nonpandemic form of the virus causing AIDS, and the majority of HIV-2-infected patients exhibit long-term nonprogression. The HIV-1 and HIV-2 envelope glycoproteins, the sole targets of neutralizing antibodies, share 30 to 40% identity. As a first step in understanding the reduced pathogenicity of HIV-2, we solved a 3.0-Å structure of an HIV-2 gp120 bound to the host receptor CD4, which reveals structural similarity to HIV-1 gp120 despite divergence in amino acid sequence.