Author Archives: gurjot nijjar

Image

Is Sleep Loss a Problem? Not for These Blind Fish!

Not only do all species vary in ability and behaviour, but fundamental biological needs are subject to variation across the animal kingdom. This evolutionary diversity is  reflected in the difference in amount of sleep necessary for each species (1).  Although the considerable variation in sleep is recognized, little information is known about the evolutionary basis that drives the emergence of such diversity.

A prominent example of sleep variation has recently been studied (2), comparing the Mexican cavefish (3) found in the Sierra del Abra region of Northeast Mexico, to their existing surface ancestors. Multiple Pachón cavefish populations have independently evolved to sleep up to 80% less than the surface dwelling species, with no apparent adverse effects on their function or health.

Comparison of Astyanax mexicanus surface fish and Pachón cavefish

Figure 1: A comparison of Astyanax mexicanus , the blind Mexican cavefish (right) to their relatives that live on the surface (left) Credit: J. B. Jaggard et al./eLife/CC BY 4.0

Figure 1: A comparison of Astyanax mexicanus , the blind Mexican cavefish (right) to their relatives that live on the surface (left) Credit: J. B. Jaggard et al./eLife/CC BY 4.0

The Pachón  cavefish have smaller, if not absent, eyes and lack pigment as shown in Figure 1. The enlarged hypothalamus of the Pachón cavefish has been reported, attributing to many behvioural differences from the surface counterparts. It is thought that ecological differences that affect food availability have driven this evolutionary variation in not only the physical features of these species but also in their sleep behaviour (4).

Investigation into to the regulation and expression of hcrt, a highly conserved peptide known to alter sleep in other species, has offered insight in the sleep variation observed in the Mexican cavefish. Researchers found that although the genetic sequence of this regulatory peptide is identical in the adult Pachón and surface cavefish, there is significant increase in the expression of hcrt in adult Pachón (Figure 2).

Figure 2: HCRT Expression in Pachón (orange) and Surface (blue) Cavefish

Figure2: HCRT Expression in Pachón (orange) and Surface (blue) Cavefish

The adult Pachón cavefish expressed the HCRT peptide four times more than the surface species. With this finding, researchers tested how inhibiting this particular peptide would affect the sleep behaviour of the Pachón species. When HCRT expression was suppressed in the Pachón cavefish, increases in time spent sleeping were observed, confirming the dependence of their sleep behaviour on the HCRT peptide.

-Jojo Nijjar

References:
1. Campbell, S. S.; Tobler, I. Neuroscience & Biobehavioral Reviews . 1984, 8,269–300.
2. Jaggard, J.B.; Stahl, B. A.; Lloyd, E.; Prober, D.A.; Duboue, E.R.; Keene, A.C. Life Sciences Journal. 2018, e32637.
3. Keene, A.; Yoshizawa, M.; McGaugh, S. Biology and Evolution of Mexican Cavefish. San Diego, USA, 2016.
4. Menuet, A.; Alunni, A.; Joly, J.S.; Jeffery, W.R.; Rétaux, S. Development2007, 134, 5, 845-55.
5. Siegel, J.M. Nature2005, 437, 1264-71.

 

 

 

Could there be a new cure for breast cancer?

Results from a recent study provide a new hope in the fight against breast cancer. At the frontlines of this battle against mutating cells, research teams are investigating more effective and efficient treatments. Five new chemical compounds were found to be more active in destroying breast cancer cells than current leading therapeutics.

According to the World Cancer Research Fund International, breast cancer is the most prevalent cancer in women, affecting those aged 20-59 years old worldwide.  Although classes of compounds have been recognized and applied in chemotherapy, the search for more effective treatments is on-going.

Previous therapies have targeted the mitochondria of cancer cells as the disruption of this cell component releases proteins that activate a process called apoptosis. The favourable result of this process is the death of target cells and many anticancer drugs aim to induce this activation.

YouTube Preview Image
Apoptotic Pathways (Genentech)

Non-steroidal inflammatory drugs (NSAIDS) are a group of compounds causing mitochondrial dysfunction that results in apoptosis.

Formula of the NSAID’s and triphenylarsine used (European Journal of Medicinal Chemistry)

Researchers of this study modified five of these activating NSAIDs to contain silver. The five modified compounds were tested in vitro to determine their ability to target genetic material and inhibit proliferation of the cancer cells. The compounds were compared to the leading chemical therapeutic, cisplatin.

The compounds were also analyzed to characterize other chemical and physical properties, detailed in the European Journal of Medicinal Chemistry. All five compounds are more efficient than cisplatin in damaging cancer cell DNA. One compound was three times more able to inhibit the proliferation of the cancers cells than cisplatin.

Canadian Cancer Society and Statistics Canada estimated that 26,300 women and 230 men would be diagnosed with breast cancer in Canada during 2017.  The contribution from the University of Ioannina has introduced five new compounds that could direct a new area of chemotherapy research; a field that affects a significant number of people in Canada and the world.

References:

  1. Banti, C.N.; Papatriantafyllopoulou, C.; Tasiopoulos, J.T.; Hadjikakpou, S.K.; Eur. J. Med. Chem. 2018, 143 (1), 1687-1701
  2. Breast cancer statistics https://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/breast-cancer-statistics (accessed Feb 8, 2018).
  3. Elmore, S.; Toxicologic Pathway2007,  35 (4), 495-516
  4. Non-steroidal Anti-inflammatory Drugs https://www.medicinenet.com/nonsteroidal_antiinflammatory_drugs/article.htm (accessed Feb 08, 2018)
  5. Canadian Cancer Society’s Advisory Committee on Cancer
    Statistics. Canadian Cancer Statistics 2017. Toronto, ON: Canadian
    Cancer Society; 2017. Available at: cancer.ca/Canadian-CancerStatistics-2017-EN.pdf
    (accessed Feb 08, 2018)