Adult Richardson's Ground Squirrels (Spermophilus richardsonii) Ignore Rate Changes in Juvenile Alarm Calls: Age‐Differential Response Urgency Perception?

Juvenile Richardson's ground squirrels (RGS; Spermophilus richardsonii) communicate response urgency by modulating the rate of syllable production in repetitive alarm calls, although longer call bouts do not promote more pronounced or longer‐lasting (tonic) vigilance in juvenile call recipients. We exposed free‐living adult RGS to playbacks of alarm calls differing in rate and length to determine whether adult receivers respond to the same alarm parameters as juveniles. Adult squirrels did not respond differentially to differences in call rate or length, suggesting that adult RGS do not attend to call rate as do juveniles. This difference in response may be attributable to a developmental change in the perceptual mechanisms by which individuals extract information regarding response urgency, but could also be a product of adult receivers devaluing information encoded in alarm calls emitted by relatively inexperienced juvenile signalers.     

HETEROTROPHY OF FOUR MARINE PHYTOPLANKTERS AT LOW SUBSTRATE CONCENTRATIONS1

Three pelagic marine phytoplankters, Coccolithus huxleyi, Skeletonema costatum, and Thalassiosira ro-tula, and a facultative heterotroph, Cyclotella cryp-tica, have been exposed to three organic substrates, viz, glucose, acetate, and glutamate, at low concentrations (organic carbon 0.25 mg/liter). Experiments were performed in the dark and light and the net assimilation of substrate was measured by using radiocarbon. The dark uptake of carbon dioxide was also determined, together with photosynthesis at near optimum light intensity. The expected heterotrophy was detected with Cyclotella cryptica. Thalassiosira rotula was found to assimilate glutamate at an appreciable rate. In all cases, however, the short-term uptake of carbon dioxide in the dark was the greatest assimilation rate measured. Values are discussed in relation to their ecological significance and it is concluded that heterotrophic survival of these and probably most other algae in the open ocean xuould be impossible unless they were in contact with a high concentration of substrate in the form of particulate matter.     

CYP2E1-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane in mice

1-bromopropane (1-BrP) induces dose- and time-dependent reproductive organ toxicity and reduced sperm motility in rodents. The contribution of cytochrome P4502E1 (CYP2E1) to both 1-BrP metabolism and the induction of male reproductive toxicity was investigated using wild-type (WT) and Cyp2e1-/- mice. In gas uptake inhalation studies, the elimination half-life of [1,2,3-(13)C]-1-BrP was longer in Cyp2e1-/- mice relative to WT (3.2 vs. 1.3 h). Urinary metabolites were identified by 13C nuclear magnetic resonance. The mercapturic acid of 1-bromo-2-hydroxypropane (2OHBrP) was the major urinary metabolite in WT mice, and products of conjugation of 1-BrP with glutathione (GSH) were insignificant. The ratio of GSH conjugation to 2-hydroxylation increased 5-fold in Cyp2e1-/- mice relative to WT. After 1-BrP exposure, hepatic GSH was decreased by 76% in WT mice vs. 47% in Cyp2e1-/- mice. Despite a 170% increase in 1-BrP exposure in Cyp2e1-/- vs. WT mice, sperm motility in exposed Cyp2e1-/- mice did not change relative to unexposed matched controls. This suggests that metabolites produced through CYP2E1-mediated oxidation may be responsible for 1-BrP-induced sperm toxicity. Both 1-BrP and 2OHBrP inhibited the motility of sperm obtained from WT mice in vitro. However, only 2OHBrP reduced the motility of sperm obtained from Cyp2e1-/- mice in vitro, suggesting that conversion of parent compound to 2OHBrP within the spermatozoa may contribute, at least in part, to reduced motility. Overall, these data suggest that metabolism of 1-BrP is mediated in part by CYP2E1, and activation of 1BrP via this enzyme may contribute to the male reproductive toxicity of this chemical.     

Breast cancer found at the time of breast reduction.

In a recent study involving 27,500 women who had breast reduction surgery in Ontario, Canada, 17 women who were diagnosed as having breast cancer at the time of their breast reduction surgery were identified. The aims of this study were to (1) describe a population-based series of patients who had breast cancer diagnosed at the time of breast reduction, (2) describe the treatment of these cancers, and (3) compare their survival rate with survival in patients in the general population who had breast cancer. Information about these women, their treatment, and outcome was extracted from hospital records, pathology reports, and reports from regional cancer centers. The chance of finding an invasive breast cancer at the time of breast reduction was 0.06 percent, which is lower than what has been reported previously. Sixty-seven percent of these women were treated with total mastectomy. In the remaining 33 percent, who were treated with partial mastectomy, the entire tumor was removed at the time of breast reduction. Fifty percent of the women were treated with radiation, and 25 percent were treated with chemotherapy or hormonal therapy. Compared with women in the general population of Ontario who have breast cancer, women whose breast cancer is discovered during breast reduction surgery are more likely to be treated with complete mastectomy and less likely to be treated with radiotherapy or chemotherapy. Seventy-one percent of the breast reduction group were axillary node-negative at diagnosis, compared with 58 percent in the general population of women with breast cancer. Survival from breast cancer in women diagnosed at the time of breast reduction (88 percent, 5-year survival) was better than survival from breast cancer in the general population (77 percent). These findings suggest that cancers found in women at the time of breast reduction are less advanced, possibly because they are diagnosed at an earlier stage.     

Four Decades of Forest Persistence,Clearance and Logging on Borneo

The native forests of Borneo have been impacted by selective logging, fire, and conversion to plantations at unprecedented scales since industrial-scale extractive industries began in the early 1970s. There is no island-wide documentation of forest clearance or logging since the 1970s. This creates an information gap for conservation planning, especially with regard to selectively logged forests that maintain high conservation potential. Analysing LANDSAT images, we estimate that 75.7% (558,060 km²) of Borneo''s area (737,188 km²) was forested around 1973. Based upon a forest cover map for 2010 derived using ALOS-PALSAR and visually reviewing LANDSAT images, we estimate that the 1973 forest area had declined by 168,493 km² (30.2%) in 2010. The highest losses were recorded in Sabah and Kalimantan with 39.5% and 30.7% of their total forest area in 1973 becoming non-forest in 2010, and the lowest in Brunei and Sarawak (8.4%, and 23.1%). We estimate that the combined area planted in industrial oil palm and timber plantations in 2010 was 75,480 km², representing 10% of Borneo. We mapped 271,819 km of primary logging roads that were created between 1973 and 2010. The greatest density of logging roads was found in Sarawak, at 0.89 km km⁻², and the lowest density in Brunei, at 0.18 km km⁻². Analyzing MODIS-based tree cover maps, we estimate that logging operated within 700 m of primary logging roads. Using this distance, we estimate that 266,257 km² of 1973 forest cover has been logged. With 389,566 km² (52.8%) of the island remaining forested, of which 209,649 km² remains intact. There is still hope for biodiversity conservation in Borneo. Protecting logged forests from fire and conversion to plantations is an urgent priority for reducing rates of deforestation in Borneo.     

Mucin-associated T antigens in benign and malignant epithelium of the gall bladder,extrahepatic bile ducts and ampulla of Vater

The mucin-associated antigens Tn, sialosyl-Tn (STn), T and sialosyl-T (STAg) antigens accumulate through aberrant and incomplete glycosylation in malignant epithelial cells. Their diagnostic and prognostic significance in tumours of the colon and cervix has been described, and a possible role for Tn antigen in cell-to-cell adhesion has been suggested. These antigens have been demonstrated through peanut agglutinin (PNA) lectin binding and more recently using specific monoclonal antisera. Differences between the two methods have been described, which may be due to fixation schedules and/or specificity. We have investigated the effect of fixation on the binding of biotinylated PNA lectin and compared its reactivity with the immunoreactivity of monoclonal antisera to Tn, STn, T and STAg antigens in benign and malignant epithelium of the gall bladder, extrahepatic bile ducts and ampulla of Vater. We found that short-term fixation in formol sublimate resulted in poor PNA binding. All other tested fixation schedules showed strong perinuclear binding, similar to that found on cryostat sections. When compared with monoclonal antisera, PNA binding demonstrated the lowest specificity in benign epithelium. In both benign and malignant epithelium, the two methods cannot substitute for each other. STn and STAg antigens were found to be oncodevelopmental throughout the extrahepatic biliary tract. When used in a panel, they are useful as diagnostic markers of malignancy in gall bladder epithelium.     

Histone Deacetylase Inhibitor Romidepsin Induces HIV Expression in CD4 T Cells from Patients on Suppressive Antiretroviral Therapy at Concentrations Achieved by Clinical Dosing

Persistent latent reservoir of replication-competent proviruses in memory CD4 T cells is a major obstacle to curing HIV infection. Pharmacological activation of HIV expression in latently infected cells is being explored as one of the strategies to deplete the latent HIV reservoir. In this study, we characterized the ability of romidepsin (RMD), a histone deacetylase inhibitor approved for the treatment of T-cell lymphomas, to activate the expression of latent HIV. In an in vitro T-cell model of HIV latency, RMD was the most potent inducer of HIV (EC₅₀ = 4.5 nM) compared with vorinostat (VOR; EC₅₀ = 3,950 nM) and other histone deacetylase (HDAC) inhibitors in clinical development including panobinostat (PNB; EC₅₀ = 10 nM). The HIV induction potencies of RMD, VOR, and PNB paralleled their inhibitory activities against multiple human HDAC isoenzymes. In both resting and memory CD4 T cells isolated from HIV-infected patients on suppressive combination antiretroviral therapy (cART), a 4-hour exposure to 40 nM RMD induced a mean 6-fold increase in intracellular HIV RNA levels, whereas a 24-hour treatment with 1 µM VOR resulted in 2- to 3-fold increases. RMD-induced intracellular HIV RNA expression persisted for 48 hours and correlated with sustained inhibition of cell-associated HDAC activity. By comparison, the induction of HIV RNA by VOR and PNB was transient and diminished after 24 hours. RMD also increased levels of extracellular HIV RNA and virions from both memory and resting CD4 T-cell cultures. The activation of HIV expression was observed at RMD concentrations below the drug plasma levels achieved by doses used in patients treated for T-cell lymphomas. In conclusion, RMD induces HIV expression ex vivo at concentrations that can be achieved clinically, indicating that the drug may reactivate latent HIV in patients on suppressive cART.     

Similarity of Cortical Activity Patterns Predicts generalization Behavior

Humans and animals readily generalize previously learned knowledge to new situations. Determining similarity is critical for assigning category membership to a novel stimulus. We tested the hypothesis that category membership is initially encoded by the similarity of the activity pattern evoked by a novel stimulus to the patterns from known categories. We provide behavioral and neurophysiological evidence that activity patterns in primary auditory cortex contain sufficient information to explain behavioral categorization of novel speech sounds by rats. Our results suggest that category membership might be encoded by the similarity of the activity pattern evoked by a novel speech sound to the patterns evoked by known sounds. Categorization based on featureless pattern matching may represent a general neural mechanism for ensuring accurate generalization across sensory and cognitive systems.