Do MCF7 cells cope with metformin treatment under energetic stress in low glucose conditions?

There is a growing body of evidence about metformin being effective in cancer therapy. Despite controversies about the ways of its effectiveness, several ongoing clinical trials are evaluating the drug when used as an adjuvant or a neo-adjuvant agent. We aimed to investigate metformin’s effects on proliferation, metastasis, and hormone receptor expressions in breast cancer cell line MCF-7 incubated in two different glucose conditions. MCF-7 cells were incubated in high or low glucose media and treated with various doses of metformin. The cell viability was studied using MTT test. The Ki-67, estrogen and progesterone receptor expression were evaluated by ICC and galectin-3 expression was evaluated by ELISA or spectrophotometrically. The cell viability following consecutive metformin doses in either glucose condition for 24 and 48 h represented a significant decrease when compared to control. The proliferation detected in low glucose medium following metformin at doses < 20 mM was found significantly decreased when compared to high glucose medium at 48 h. In terms of galectin-3 levels, the increase in high glucose medium treated with metformin and the decrease in low glucose medium were found statistically significant when compared to control. Progesterone receptor staining demonstrated a significant increase in low glucose medium. Our findings represent better outcomes for cancer lines incubated in low glucose medium treated with metformin in terms of viability, receptor expression and metastatic activity, and highlight the potential benefit of metformin especially in restraining the cancer cell’s ability to cope energetic stress in low glucose conditions.     

Social and spatial relationships in captive southern white rhinoceros (Ceratotherium simum simum)

Although critical to the conservation of white rhinoceros, captive breeding has proven challenging because of the poor and irregular reproductive health of many captive rhinos, and social interactions may play a significant role. This research investigated the social and spatial relationships of two captive groups of southern white rhinoceros (Ceratotherium simum simum) by examining the frequency of companion changes, the number of space maintenance vocalizations made per hour by each reproductively mature female, and dominant/subordinate interactions. The observed captive rhinos did not change their companionships during the study. They exhibited space maintenance vocalizations and display greater than once per hour, particularly when feeding. Females housed with four calves on 0.033 km² exhibited space maintenance vocalizations more frequently (X±SE = 6.19±0.199/hr) than females housed with one calf and more space (0.06 km², X±SE = 0.55±0.182/hr) and females housed without calves and more space (0.65 km², X±SE = 1.90±0.086/hr). Wider separation of food piles and of females with young calves is suggested to reduce the interpreted spatial stress. The presence of a large number of rhinos in restricted captive space resulted in the formation of herds with dominance hierarchies that were enforced during competition for food and shade. The most subordinate rhino in each of the herds exhibited unusual behaviors such as dung‐kicking and nonestrus urine squirting, and neither has ever reproduced. Suppression of subordinate rhinos might lead to social stress that could negatively impact reproductive success. Zoo Biol 26:487–502, 2007. © 2007 Wiley‐Liss, Inc.     

Ubiquitination Increases Parkin Activity to Promote Autophagic α-Synuclein Clearance

Parkinson’s disease (PD) is a movement disorder associated with genetic and age related causes. Although autosomal recessive early onset PD linked to parkin mutations does not exhibit α-Synuclein accumulation, while autosomal dominant and sporadic PD manifest with α-Synuclein inclusions, loss of dopaminergic substantia nigra neurons is a common denominator in PD. Here we show that decreased parkin ubiquitination and loss of parkin stability impair interaction with Beclin-1 and alter α-Synuclein degradation, leading to death of dopaminergic neurons. Tyrosine kinase inhibition increases parkin ubiquitination and interaction with Beclin-1, promoting autophagic α-Synuclein clearance and nigral neuron survival. However, loss of parkin via deletion increases α-Synuclein in the blood compared to the brain, suggesting that functional parkin prevents α-Synuclein release into the blood. These studies demonstrate that parkin ubiquitination affects its protein stability and E3 ligase activity, possibly leading to α-Synuclein sequestration and subsequent clearance.     

Drought mildly reduces plant dominance in a temperate prairie ecosystem across years

1. Shifts in dominance and species reordering can occur in response to global change. However, it is not clear how altered precipitation and disturbance regimes interact to affect species composition and dominance.
2. We explored community‐level diversity and compositional similarity responses, both across and within years, to a manipulated precipitation gradient and annual clipping in a mixed‐grass prairie in Oklahoma, USA. We imposed seven precipitation treatments (five water exclusion levels [?20%, ?40%, ?60%, ?80%, and ?100%], water addition [+50%], and control [0% change in precipitation]) year‐round from 2016 to 2018 using fixed interception shelters. These treatments were crossed with annual clipping to mimic hay harvest.
3. We found that community‐level responses were influenced by precipitation across time. For instance, plant evenness was enhanced by extreme drought treatments, while plant richness was marginally promoted under increased precipitation.
4. Clipping promoted species gain resulting in greater richness within each experimental year. Across years, clipping effects further reduced the precipitation effects on community‐level responses (richness and evenness) at both extreme drought and added precipitation treatments.
5. Synthesis: Our results highlight the importance of studying interactive drivers of change both within versus across time. For instance, clipping attenuated community‐level responses to a gradient in precipitation, suggesting that management could buffer community‐level responses to drought. However, precipitation effects were mild and likely to accentuate over time to produce further community change.

     

Histone synthesis in Rhynchosciara salivary glands. I. Site and timing of synthesis.

The site of histone synthesis was studied in polytene cells of the salivary glands of the Rhynchosciara americana (Diptera). It was found that, as is the case in non-polytene systems, these proteins are synthesized in the cytoplasm in a class of light polysomes which contain 3-4 ribosomes. This class of polyribosomes is most active at about 5 days before pupation when the nuclei are most active in DNA synthesis and the chromosomes of the gland show many open 'DNA puffs'.