Gleevec and competitive inhibition

Submitted by bthoole on Mon, 10/22/2018 - 18:41

Bcr-Abl presented a new challenge to treating cancer because of its newly conformed shaped. After some time, Gleevec was invented that acted as a superior treatment compared to previous attempts, earning it the moniker of “wonder drug”. Gleevec was able to competitively bind to the kinase domain on Bcr-Abl that normally bound with a different substrate that allowed it to be phosphorylated and thereby activated. Once Gleevec was introduced, the substrate was no longer able to bind and could no longer be phosphorylated. This rendered the tumor cell unable to proliferate. Because Gleevec acts as an inhibitor does not mean that Bcr-Abl is incapable of binding to the substrate that causes proliferation. It just means that this occurs less frequently. That leads to the possibility of a mutation in Bcr-Abl that increase the activity and allows for an increase in binding to the non-Gleevec substrate. This is one of the potential factors that could lead to resistance of the drug.

Evolution Genetic Drift Simulation Discussion Draft Part 2

Submitted by sbrownstein on Mon, 10/22/2018 - 18:16

Although the data from both reserves were very similar, I have concluded that Reserve 2 is better for reducing the risk of genetic drift in a population. This is because I believe that maintaining heterozygosity is more important than the loss of alleles when trying to decrease the risk of genetic drift. Preserving genetic variation will ensure that the genes within the population do not drift. On the other hand, losing alleles may influence genetic drift but will be contradicted if genetic diversity is still present within the population.

 

Lac Operon

Submitted by fmillanaj on Mon, 10/22/2018 - 10:18

The lac operon is important in maintaining the breakdown of lactose. When there is no lactose to be metabolized, the Lac genes are "turned off". This is to conserve energy for other vital tasks. Genes are turned off when a lac repressor binds to the promoter region of the lac operon, disabling any ability to metabolize lactose. This inhibitory gene is the default for genes. When there is lactose, however, it must be metabolized. This is accomplished when lactose binds to the repressor, enabling the operon to work. 

Parasites and Monarch Butterfly Migration - Conclusion

Submitted by jmalloldiaz on Mon, 10/22/2018 - 09:59

I chose this paper because I am interested in evolution and long-distance migratory species like monarch butterflies are an interesting subject of study for their host-pathogen interactions. The selective pressure that the parasite imposes over the butterflies is added to the physiological cost of migration, thus setting the scenario for adaptations to overcome or tolerate the infection in order to successfully reach their wintering grounds. Although this paper focused mostly on the actual capacity of different monarch populations to reach their wintering grounds during fall migration, it did not investigate the evolutionary aspect of this phenomenon. A follow-up study could look at the genomes of populations in northern and southern latitudes, in order to see if there are genetic differences involved with overcoming the cost of parasite infection. This research could be useful for the conservation of monarch butterflies, which have been consistently declining over the past 20 years, in order to plan the introduction of resistant monarchs in declining populations.

Summary Discussion Draft

Submitted by jmalloldiaz on Mon, 10/22/2018 - 09:11

The results support the hypothesis that infected monarchs would travel shorter distances, and that among infected individuals shorter distances are correlated with higher parasite loads. The researchers suggest that infected butterflies from more northern locations were not able to reach their wintering grounds in Mexico, thus backing the "migratory culling" idea of reducing parasites among a population by removing infected individuals. Since there was no significant effect of latitude on the odds of infection, the researchers propose that the flight performance of monarch butteflies has a greater effect on the chances of reaching their wintering grounds than the incidence of parasite transmission among populations.

S. dulcamara research 2

Submitted by cdkelly on Mon, 10/22/2018 - 04:19

Once the protein was produced, the team began a series of analyses to elucidate some of the features of the newly cloned Solanum dulcamara THP. They did a western blot, a gel shift assay, RNA blot analysis, and analysed the hysteresis activity. Following the completion of these analyses, they identified STHP-64 as the hydrophilic THP protein present in the November sample of Solanum dulcamara. It differed in weight slightly (3 kDa) compared to the original THP used as a template, but they attributed this to the loss of exons from the N-terminus. Functionally and structurally, the protein was extremely similar to the original and they believed that it was derived from the same gene within the plant. They observed thermal hysteresis activity for STHP-64, albeit not much. Citrate was found to increase the thermal hysteresis activity, which confirmed for them that STHP was in fact THP. The low activity was attributed to potential protein-folding issues among other things. Amino acid repeats were identified in the clone and thought to facilitate thermal hysteresis by hydrogen bonding with the ice on the plant, effectively inhibiting the further crystallization of ice. STHP-64 also demonstrated DNA-binding ability and they believed that it could act as a transcription factor for the upregulation of proteins related to pathogenesis. In conclusion, although the THP activity was low in the isolated sample from Solanum dulcamara, the THP protein was only present in the November sample. This suggests that STHP-64 is at least partially responsible for the overwintering capabilities demonstrated by Solanum dulcamara.

 

S. dulcamara research 1

Submitted by cdkelly on Mon, 10/22/2018 - 04:15

Overwintering plants have the ability to survive throughout the winter, and many of them contain thermal hysteresis proteins (THPs), which lower the freezing point and melting point of water. These proteins are present in fish and insects as well, but the mechanism is likely to be different. Unlike insects and fish, plant THPs allow them to survive the freezing of their extracellular water, rather than preventing freezing altogether. Solanum dulcamara is an example of an overwintering plant, and is at the center of this article. The objective of the research was to isolate and characterize a specific THP within Solanum dulcamara that allows it to survive through the winter’s harsh temperature decline.

    Researchers collected and purified samples of Solanum dulcamara RNA from leaves at two separate points in time; one sample in September and the other in November. This was done to compare the RNA present during warmer weather and colder weather; they assumed that the THP would be present in the RNA extracted from the November leaves. The extracted RNA was then used to generate a cDNA expression libraries for both samples. An antibody generated from a previously purified S. dulcamara THP was used to screen the two libraries for the presence of matching THPs. A total of 20,000 recombinants from both the September and November samples were put through the antibody screening. The November sample was found to have eight matches and like the expected, the September sample had zero. Two of these matches were then isolated and prepared for cloning. Using PCR, a clone was generated, duplicated, and integrated into E. coli as a plasmid. Finally, the protein was grown in culture and extracted.

  

 

Plant ID; anyone like plants?

Submitted by cdkelly on Mon, 10/22/2018 - 02:26

Solanum dulcamara (Solanaceae) An invasive, perennial, semi-woody climber that can grow in a wide array of environments. It can be upwards of 13 feet tall, but generally is found to be around 3-6 feet in height. Both the leaf blades and the stems are unarmed. The shape of most of the leaves is ovate with a cordate base, arranged in a alternate pattern. These leaves are simple, with a margin that can be entire, subentire, or toothed. But, the larger leaves can have a small pair of basal lobes resulting in a hastate base, or leaflets at their base; toothed or toothed and lobed margins are associated with these larger leaves. This feature of Solanum dulcamara differentiates it from similar plants, such as Solanum nigrum or Solanum ptycanthum, because it uniquely has the aforementioned leaflets. Pubescent simple hairs or glabrous surface textures are present on all its leaves. Blueish-Purple, radially symmetrical flowers comprise the inflorescence. Solanum dulcamara can contain anywhere from 10-25 flowers, each with 5 petals and 5 tepals. Flowers contain both gynoecium and androecium. Ellipsoid to ovoid berries are present on the plant and are known to be poisonous to humans, but in fact, the entire plant is actually considered to be toxic.

Summary Results Draft

Submitted by jmalloldiaz on Sun, 10/21/2018 - 19:24

In order to ascertain the origin of the monarchs, hydrogen isotope (δ2H ) data was collected, knowing that it decreases northwards. Infected monarchs had higher average δ2H values, showing that such individuals originated in southern latitudes, while those born further north had lower δ2H values. As well, monarchs originated from northern areas had larger forewings, but the correlation between δ2H values and wing area was not significant in infected individuals. Regarding parasite loads, butterflies from southern populations closer to their wintering grounds were more heavily infected. Finally, citizen science data indicates that there is no significant effect of latitude on the odds of infection.

Summary Objective Draft

Submitted by jmalloldiaz on Sun, 10/21/2018 - 19:12

•In your summary reflect on one aspect that you find important to your interests (eg a new model for fat metabolism, or a unique system for conservation biology etc):

My interest in this paper: parasite infection setting conditions for a possible speciation event

Long distance migratory species like monarch butterflies (Danaus plexippus) are an interesting subject of study, because if they are exposed to selective pressures like parasitic protozoans such as Ophryocystis elektroscirrha during their migratory journeys, there are chances of fragmenting the population and setting the conditions for an speciation event to occur.

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Overview:

Migration is triggered by cues of habitat deterioration such as the photoperiod that instill an animal to travel to another location where resources and living conditions will be more favorable. It can also have indirect benefits, like reducing the predominance of parasites among a population by removing the infected individuals, a phenomenon known as "migratory culling". Such is the case for long-distance migratory monarch butterflies (Danaus plexippus) and parasitic protozoans like Ophryocystis elektroscirrha in North America.

Objective:

It is known that parasitic infection rates are higher southwards in eastern North America, supporting the evidence that infected monarchs are slower and have less endurance, thus performing poorly in migration. The objective of this study was to determine the effect of parasite infection in the flight performance of monarchs migrating towards their wintering grounds in Mexico. The researchers hypothesized that infected individuals would travel shorter distances, and that among infected individuals shorter distances are correlated with higher parasite loads.

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