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Alx1 Gene Related to Evolution of Larval Skeleton

Submitted by jgirgis on Fri, 04/28/2017 - 11:09

In the study titled “Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton” by Hiroyuki Koga, the alx1 gene was proven to be necessary for the acquisition of the larval skeleton. It also was proven to play a vital role in the evolution of the larval skeleton (Koga, 2016). Echinoderm larvae were the model organisms used to see if alx1 is a necessary gene for the attainment of larval skeleton. Scientists pinpointed Alx1 to see if this gene was necessary for the evolution of the larval skeleton by inducing the expression of alx1 in starfish that do not have a skeleton. To induce the expression of alx1 in starfish, Koga and his team inserted mRNA that coded for Alx1 into the eggs of the starfish through microinjection (Koga, 2016). The goal was to increase the cell numbers of skeletogenic cells. In addition, green fluorescent protein was inserted into starfish embryos, specifically the nuclei to mark the skeletogenic cells.

References:

1. Koga, Hiroyuki, Haruka Fujitani, Yoshiaki Morino, Norio Miyamoto, Jun Tsuchimoto, Tomoko F. Shibata, Masafumi Nozawa, Shuji Shigenobu, Atsushi Ogura, Kazunori Tachibana, Masato Kiyomoto, Shonan Amemiya, and Hiroshi Wada. "Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton." PLoS ONE. Public Library of Science, 11 Feb. 2016. Web. 24 Apr. 2017.

SOX9 Gene

Submitted by jgirgis on Fri, 04/28/2017 - 09:53

The malformations and syndromes associated with the SOX9 gene include acampomelic campomelic dysplasia, campomelic dysplasia with autosomal sex reversal, and campomelic dysplasia. Campomelic dysplasia and acampomelic campomelic dysplasia with or without sex reversal are caused by a heterozygous on chromosome 17q24.1 Campomelic dysplasia is an autosomal dominant skeletal dysplasia. The malformations include congenital shortness and bowing of long tubular bones, especially in lower extremities.1 Other malformations include narrow iliac wings and nonmineralized thoracis pedicles.1 Patients that have campomelic dysplasia often die within the first year of being diagnosed due to a small chest size and tracheobronchial hypoplasia. Furthermore, SOX9 mutations causing campomelic dysplasia have been related with 46, XY, sex reversal, with some variability in the degree of gonadal dysgenesis.

The malformations and syndromes associated with the BMP pathway include malformations in BMP4, which lead to microphthalmia syndromic 6 and orofacial cleft 11.2 BMP4 is a regulatory molecule that is involved with development in mesoderm induction, tooth development, limb formation, bone induction, and fracture repair. BMP4 is part of the BMP family and TGF-beta-1. When BMP4 is overactive, it causes microphthalmia syndromic 6 and orofacial cleft 11. 2 Microphthalmia syndromic 6 leads to hypoplastic kidneys, asbsence of optic nerves, underdeveloped genitalia, and brain anomalies such as a small cerebellum. Orofacial cleft is an opening or split in the roof of the mouth. Additionally, when BMPR2, which is bone morphogenetic protein receptor II, is mutated, it leads to pulmonary hypertension and pulmonary venoocclusive disease 1. The primary pulmonary hypertension is due to a heterozygous mutation that results in termination, frameshift, and nonconservative missense changes in amino acid sequence. 2 The pulmonary venoocclusive disease is to due a heterozygous transversion in exon 2 of the bmpr2 gene, which leads to a tyr40-to-ter substitution. 2 Venoocclusive disease is when blood flow is blocked in very small blood vessels in the liver, and hypertension is high blood pressure.

References:

1. http://omim.org/entry/608160?search=sox9%20&highlight=sox9

2. https://www.omim.org/entry/607932

Treating Pancreatic Cancer

Submitted by jgirgis on Fri, 04/28/2017 - 09:51

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States.  In fact, only 8% of patients diagnosed with PDAC survive for more than five years from the point of their diagnosis (Indolfi, 2016). Though significant advances have been made in treating PDAC, patients diagnosed still generally have one of the lowest survival rates. This is due to its asymptomatic nature in early stages, meaning that it often goes undetected until the solid tumor has metastasized. Even when pancreatic cancer is detected in its early stages and has the potential to be resected via pancreaticoduodenectomy, most patients will develop metastatic disease. Knowing this, it is important that research surrounding the treatment of PDAC properly accounts for the nuances associated with a metastatic cancer and how it may differ from common therapies associated with a solid tumor.

Role of Alx and Evolution

Submitted by jgirgis on Thu, 04/27/2017 - 23:44

            In the study titled, “Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton” by Hiroyuki Koga, the alx1 gene was proven to be necessary for the acquisition of the larval skeleton and played a necessary role in the evolution of the larval skeleton (Koga, 2016).

            In the study, echinoderm larvae were the model organisms used to see if alx1 is the gene that is necessary for the attainment of the larval skeleton. There are five classes of echinoderm, which include sea urchins, sea cucumbers, brittle stars, starfish, and sea lilies (Koga, 2016). The transcription factors, Ets1/2, Alx1, and Tbr, control the differentiation of primary mesenchyme cells that form the larval skeleton. Scientists pinpointed Alx1 to see if this gene was important with the evolution of the larval skeleton by inducing the expression of alx1 in starfish that do not have a skeleton.

            To induce the expression of alx1 in starfish, Koga and his team inserted mRNA that coded for Alx1 into the eggs of the starfish (Koga, 2016). This was done by utilizing microinjection. The goal was to increase the cell numbers of skeletogenic cells, and green fluorescent protein was inserted into starfish embryos, specifically the nuclei. Researchers measured the effects of inserting different types of mRNA. When the researchers inserted high levels of mRNA resulted in prevention of gastrulation (Koga, 2016). This then led to a halt in the process of development. Low levels of mRNA led to a high production of skeletogenic cells in sea urchin. But in starfish embryos, this did not occur (Koga, 2016).

            Koga’s team demonstrated that alx1 was necessary for the larval skeletons of sea urchins and sea cucumbers (Koga, 2016). However, alx1 was not expressed in starfish embryos, but was rather highly expressed in adult skeletogenesis. Koga and his team concluded that their data did not support the previous claimed statement that there is high expression of alx1 in embryonic and early larval stage of the starfish. There team also found that alx is replicated in the echinoderm lineage (Koga, 2016). Specifically, this study proved that in echinoderms, the expression of alx1 occurs more frequently in skeletogenic cells of adult and larvae. Starfish do not have tube foot spicules and in starfish, alx1 is expressed in the tube foot. Therefore, Koga and his team concluded that alx organically was necessary for coelomic development (Koga, 2016). One repeated paralog was involved with skletogenesis and researchers therefore concluded that alx is involved with the creation of the larval skeleton and the calcareous skeleton (Koga, 2016).

References:

1. Koga, Hiroyuki, Haruka Fujitani, Yoshiaki Morino, Norio Miyamoto, Jun Tsuchimoto, Tomoko F. Shibata, Masafumi Nozawa, Shuji Shigenobu, Atsushi Ogura, Kazunori Tachibana, Masato Kiyomoto, Shonan Amemiya, and Hiroshi Wada. "Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton." PLoS ONE. Public Library of Science, 11 Feb. 2016. Web. 24 Apr. 2017.

Treating PDAC Metastasis

Submitted by jgirgis on Sun, 04/23/2017 - 14:49

Pancreatic Ductal Adenocarcinoma (PDAC) is the third of the leading cause of cancer-related death in the United States and only 8% of patients diagnosed with PDAC survive past 5 years from point of diagnosis (Indolfi, 2016). Though significant advances have been made in the treatment of other forms of cancer, patients diagnosed with PDAC generally have one of the lowest survival rates, not only because PDAC is a particularly aggressive cancer, but also because its asymptomatic nature in early stages means that it often goes undetected until the solid tumor has metastasized. Even when pancreatic cancer is detected in its early stages and has the potential to be resected via pancreaticoduodenectomy, most patients will go on to develop recurrent or metastatic disease. This is likely due to the development of undetected micrometastases that could not have been identified initially. Knowing this, it is important that research surrounding the treatment of PDAC properly accounts for the nuances associated with a metastatic cancer and how it may differ from common therapies associated with a solid tumor.

            This novel treatment will combine preventative measures to halt any future metastases in patients with Pancreatic Ductal Adenocarcinoma with therapies, which address the changes associated with metastases and already observed in the patient population. Metastasis occurs when the epithelial primary tumor cells break through the basement membrane due to a loss of cell-cell adhesion. As a result, epithelial cells transition to mesenchymal cells, which allows tumor cells to leave the pancreas and enter the bloodstream. At this point of extravasation, tumor cells have the freedom to nest in other areas of the body and become metastatic sites of the primary solid tumor.

Reward and Uncertainty in the Prefrontal Cortex

Submitted by jgirgis on Sun, 04/23/2017 - 13:59

In Daeyol Lee's lecture about reward and uncertaing in the prefrontal cortex in Morrill II, he discussed persistence versus perseveration and how they both depend on uncertainty. Neurons and cortical signals are involved in choice and reward history. In the brain, the medial area of the brain is the most active when it comes to reinforcement signals in the brain. Past, but not future, choice signals are amplified by reward. The main neurons involved in this amplification are SEF, DLPFC, LIP, and ACC. Reward signals are ubiquotilsy represented in the braing. Reward also moduluates other signals in the prefrontal cortex related to previous choices and outcomes, but largely only when they are important for learning.

One experiment Lee discussed was about reinforcement learning during matching pennies. The task involved using a monkey to fixate on a yellow square. Then the monkey had a decision to choose either a green circle on the left or the right of the screen. After the monkey chooses, the computers places a ring on one of the green circles. If the monkey chose the green circle that the computer placed a ring around, then the monkey received juice. If not, then the monkey did not receive juice. The computer is detecting the choices the monkey is making and then switches up which green circle gets a ring around it. Therefore, the monkey realized that there is no point in choosing the same green circle each time. Therefore, the way to maximize the monkey’s reward would be by choosing a green circle randomly, like when playing “rock, papers, scissors, shoot”. The conclusion was therefore monkeys utilized reinforcement to be successful.

As a follow up experiment, they marked single neurons on the monkey’s brain that was performing the task mentioned above to see which ones were most active while the monkey performed the task.

Classical Music Reduces Stress in Dogs (PP)

Submitted by jgirgis on Fri, 04/07/2017 - 11:50

 Scientists are interested in the effect of long-term auditory stimulation of classical music on kenneled dogs. In the paper Classical Music Reduces Environmental Stress in Kenneled Dogs, researchers decided to test this. To do so, there was a control group, which did not listen to any music and the experimental group, which listened to classical music. Classical music was played from 10:00 am till 6:30 pm for 7 days straight. The researchers assessed the dogs’ heart rates and behavior to see if classical music positively or negatively affected the dogs in the experimental group. If the dogs’ heart rates decreased, then that would signify a positive reaction to the classical music. The findings were that classical music decreased the heart rates and reduced stress levels of the dogs compared to the control group. In conclusion, this study displayed that classical music positively impacted the kenneled dogs.

 

Source:

Bowman, A., Scottish Spca, F.j. Dowell, and N.p. Evans. "Four Seasons™ in an Animal Rescue Centre; Classical Music Reduces Environmental Stress in Kenneled Dogs." Physiology & Behavior 143 (2015): 70-82. Web.

Classical Music Reduces Stress

Submitted by jgirgis on Fri, 04/07/2017 - 11:32

Source: Bowman, A., Scottish Spca, F.j. Dowell, and N.p. Evans. "Four Seasons™ in an Animal Rescue Centre; Classical Music Reduces Environmental Stress in Kenneled Dogs." Physiology & Behavior 143 (2015): 70-82. Web.

            The aim of this study was to observe the effect of long-term auditory stimulation of classical music on kenneled dogs. In this study, there was a control group, which did not listen to any music and the experimental group, which listened to classical music. Classical music was played from 10:00 am till 6:30 pm for 7 days straight. The researchers assessed the dogs’ heart rates and behavior to see if classical music positively or negatively affected the dogs in the experimental group. If the dogs’ heart rates decreased, then that would signify a positive reaction to the music. The results displayed that auditory stimulation for the experimental group decreased the heart rates of the dogs, and they had reduced stress levels compared to the control group. In conclusion, this study displayed that classical music positively impacted the kenneled dogs because it reduced their stress.

Genre of Music Cats Prefer

Submitted by jgirgis on Wed, 04/05/2017 - 22:02

Source: Mira, Filipa. Influence of Music and Its Genres on Respiratory Rate and Pupil Diameter Variations in Cats under General Anaesthesia: Contribution to Promoting Patient Safety - Mar 30, 2015. N.p., n.d. Web. 03 Apr. 2017.

            The goal of this study was to detect if certain genres (classical music, pop music, and heavy metal) of music had a negative or a positive impact on cats that were under anesthesia.  To decipher if a positive or negative impact was made, researchers observed the cats’ respiration rates. If the respiration rate was lower than it began with, that was perceived as a positive reaction; if the respiration rate increased throughout the study, then that was perceived as a negative reaction. In the study, 12 cats were tested and the music was transmitted through headphones that were placed around the heads of each cat.  The results were that classical music lowered all of the cats’ respiration rates, while pop music and heavy metal increased the cats’ respiration rates. In conclusion, classical music had the most positive effect on the cats. In addition, this paper relates to my study because it tests how different genres of music affect cats.

Classical Music Affects Dogs Positively

Submitted by jgirgis on Wed, 04/05/2017 - 10:46

Soure: Wells, D. L. "The Influence of Auditory Stimulation on the Behaviour of Dogs Housed in a Rescue Shelter." (2002): n. pag. 1 Nov. 2002. Web. 3 Apr. 2017.

This paper is about how certain genres of music affect dogs. The researchers tested five different types of music: human conservation, control, pop music, classical music, and heavy metal music. They tested 50 dogs that were located in a rescue shelter. To test them, they allowed each of the dogs to hear each type of music for 4 hours in one day, and they allowed one day in between each genre of music. The researchers were observing for negative (standing, barking, restless) or positive (sitting, no barking, calm) reactions to the music. The results were that dogs reacted the most positively to classical music, as they were sitting when classical music played, and they reacted the most negatively to heavy metal music because the dogs would not stop barking when listening to this type of music.

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