SpxA1 and SpxA2 act coordinately to fine-tune stress responses and virulence in Streptococcus pyogenes

SpxA is a unique transcriptional regulator highly conserved among members of the phylum Firmicutes that binds RNA polymerase and can act as an antiactivator. Why some Firmicutes members have two highly similar SpxA paralogs is not understood. Here, we show that the SpxA paralogs of the pathogen Streptococcus pyogenes, SpxA1 and SpxA2, act coordinately to regulate virulence by fine-tuning toxin expression and stress resistance. Construction and analysis of mutants revealed that SpxA1− mutants were defective for growth under aerobic conditions, while SpxA2− mutants had severely attenuated responses to multiple stresses, including thermal and oxidative stresses. SpxA1− mutants had enhanced resistance to the cationic antimicrobial molecule polymyxin B, while SpxA2− mutants were more sensitive. In a murine model of soft tissue infection, a SpxA1− mutant was highly attenuated. In contrast, the highly stress-sensitive SpxA2− mutant was hypervirulent, exhibiting more extensive tissue damage and a greater bacterial burden than the wild-type strain. SpxA1− attenuation was associated with reduced expression of several toxins, including the SpeB cysteine protease. In contrast, SpxA2− hypervirulence correlated with toxin overexpression and could be suppressed to wild-type levels by deletion of speB. These data show that SpxA1 and SpxA2 have opposing roles in virulence and stress resistance, suggesting that they act coordinately to fine-tune toxin expression in response to stress. SpxA2− hypervirulence also shows that stress resistance is not always essential for S. pyogenes pathogenesis in soft tissue

Thesis Statement

I use illusion to expose illusion. The viewer is first sure it is a chalkboard and yet it must not be. It seems to have all the characteristics of a chalkboard but something is not right. Surely art would not be on a chalkboard that could be erased. So, things are not always what they seem to be.&nbsp; I use the idea of a chalkboard as a metaphor for the mind and the thought process. A place to work out ideas, make new associations and expose conflicting ideas.&nbsp; I use story telling to create the context of real life from which other works discuss ideas about life and the process of living. The conflicts and counterpoints are most readily exposed in a true life story. &nbsp;</p

Immunomodulation by Blastomyces dermatitidis :

We have previously shown that Merthiolate-killed Blastomyces dermatitidis yeast cells greatly enhance the cell-mediated immune response in C57BL/6J mice. Therefore, the use of this fungus as an immunopotentiator against EL4 lymphoma was investigated. Preimmunization resulted in a doubling of the mean survival time of mice at an initial tumor challenge of 10('2) to 10('4) EL4 cells. In some experiments, mice were given a range of 10('2) to 10('6) EL4 cells intraperitoneally or 10('2) to 10('6) EL4 mixed with killed B. dermatitidis. None of the animals receiving tumor cells alone survived. Mice treated with yeast cells were protected from as many as 10('4) tumor cells. Complete suppression of tumor growth was observed in treated animals at 10('2) and 10('3) tumor cells. The mice were not immune to further EL4 challenge. The lack of tumor-specific immunity indicated nonspecific suppression by macrophages. At 10 days after treatment, the peritoneal macrophages from mice showing complete suppression were tested for their ability to prevent in vitro tumor cells proliferation. These macrophages demonstrated 90% inhibition of ('3)H-thymidine incorporation by EL4 at a 100:1 effector to target ratio. Macrophages from treated animals at 10 and 15 exhibited a two-fold increase in specific lysis of EL4 as compared to resident macrophages. Spleen and lymph node cells from protected animals showed no cytotoxic activity against EL4 in a ('51)Cr-release assay. Treatment of tumor bearing mice with a single dose of B. dermatitidis was effective only if administered within 24 hours of tumor establishment.Cell-mediated immunity (CMI) plays the dominant role in the immune response of mice to Blastomyces dermatitidis infections. Since macrophages play an important role in CMI, the interactions between sensitized murine peritoneal macrophages and the yeast phase of B. dermatitidis were investigated. Scanning electron microscopy (SEM) showed that the sensitized macrophages were more efficient in phagocytizing B. dermatitidis than non-sensitized cells. In addition, there appeared to be activation of metabolic pathways within the sensitized macrophages as indicated by increased chemiluminescence activity during phagocytosis. There was a significant difference in the ability of sensitized macrophages to control intracellular proliferation of the yeast when compared to non-sensitized cells. This was determined by disruption of macrophages and plating for viable yeast. Scanning electron microscope observations offered further substantiation. Experiments with Candida albicans indicated that B. dermatitidis nonspecifically activated macrophages. At 2 hours post-phagocytosis, 30% fewer C. albicans in activated macrophages were able to form germ tubes. SEM indicated that a number of activated macrophages may interact with a single yeast aggregate in vivo. A new mechanism of macrophage activation is suggested. These studies demonstrated the multipotential of activated macrophages with regard to their functional activity

Can "Withitness Skills" Be Applied To Teaching With Laptops?

It may amaze those in education that in this age of technology and computers, how basic concepts of classroom teaching are similar or even more important than they were 40 years ago when Kounin first defined withitness elements. New challenges, related to laptop Internet instruction, require instructors to develop withitness skills and situational awareness as they compete with computers for students attention and class participation. "Withitness" skills may be needed when teaching students in classrooms with laptops connected to the Internet

Teaching More Than The Discipline: Modeling Leadership In The Classroom

The educational process in higher education is much more than just the presentation of a discipline to a group of learners. Leaders in higher education are responsible to students to conduct themselves as educational leaders. Sensible leadership depends upon a variety of factors such as flexible behavior; an ability to identify specific behaviors needed at a particular time, and the ability to incorporate such behaviors at the appropriate time (Wilcox, 1997).  A basic understanding of the supervisory behavioral continuum is important to the development of effective leadership skills. The continuum, adapted for use in the educational process, includes ten specific behaviors: listening, clarifying, encouraging, reflecting, presenting, problem-solving, negotiating, directing, standardizing, and reinforcing. Each behavior is clustered into the sub-groups of directive, directive informational, collaborative, and nondirective. To be an effective leader one must have the ability to engage in all aspects of this continuum. To be effective in the college or university classroom, the instructor must have the knowledge about knowing when, why, and with whom to engage. Although one may have a preference or supervisory philosophy which indicates a personal preference to supervision and instruction, an understanding of the supervisory continuum is fundamental to the overall success of passing the role of leadership on to the next generation of learners

Curriculum Integration: The Use Of Technology To Support Learning

Our understanding of how people learn is continually changing. Howard Gardner&rsquo;s Theory of Multiple Intelligences revolutionized the field education, because it accounts for a broader range of human potential in children and adults and suggests that individuals learn in a multitude of ways. Gardner&rsquo;s theory suggests there are a variety of possibilities to facilitate learning. People with heightened verbal, linguistic skills are often referred to as word smart. Verbal, linguistic students learn best through the comprehension of language which includes speaking, writing, reading, and listening. Students with verbal linguistic intelligences can easily access information through worldwide databases and computer networks. Any subject content can be enhanced, enriched, and updated from a variety of easily accessed sources which allow students to master the use of technology to access and share information. Students with logical mathematical intelligence are individuals who are number smart and have innate skills which involve logical, problem solving abilities, creative and manipulative skills, and are adept visual learners. Educators can enhance logical-mathematical intelligence through challenging and innovative multimedia technology. With innovative multimedia technology, students learn at all levels and effectively gain knowledge through a variety of different software programs that offer immediate feedback. Learners with visual-spatial intelligence are aesthetically oriented and may have a greater capacity for learning certain sciences like anatomy or topology. They are skillful when it comes to visualization and memory, but may be challenged with auditory memory. Learning for visual-spatial students takes place all at once, with large chunks of information grasped in intuitive leaps. Many people have an innate kinesthetic ability, as well as a natural sense of how their body should react in physical situations. Students with bodily-Kinesthetic intelligence learn best through tactile learning experiences. Bodily-kinesthetic proficiency can be enhanced for students through the use of the whole body to express ideas and feelings. Gardner proposed that musical intelligence almost parallels linguistic intelligence. The person with interpersonal is able to collaborate, understand and work effectively with others. They are aware of their interactions with others and usually take notice of and react to the feelings of others. The interpersonal learner learns best in group situations and structured class settings. Learners with intrapersonal intelligence have accurate self-understanding and are skilled in problem-solving. There is a multitude of different ways to integrate technology into our classrooms and all should focus on learning theory and educational practices. The use of technology should not occur without thinking about how people learn best. To actively engage diverse learners in higher education, the instructor should have a good understanding of the overall nature and purpose of the group, as well as the ability to interact well within the learner&rsquo;s unique world. The instructor must also be able to structure learning activities to meet their learning needs. The use of Howard Gardner&rsquo;s Theory of Multiple Intelligences, coupled with an understanding of how effective technology can enhance the learning community, can meet the diverse learning needs of all students.&nbsp;&nbsp;&nbsp

Reducing The Risk Of ACL Injury In Female Athletes

The Anterior Cruciate Ligament (ACL) is located behind the kneecap (patella) and connects the thigh bone (femur) to the shin bone (tibia). Stabilizing the knee joint is the primary responsibility of the ACL. Injuries that affect the ACL are three to five times more common in females than males. This is a result of anatomical, biomechanical, strength, and hormonal differences. The probability of potentially devastating tears to the ACL may be reduced in female athletes by an alternative warm-up program that focuses on muscle flexibility, strength, motor skill, and balance enhancement. Once the ACL has been torn, it becomes impossible to reattach or stitch the ligament back together.&nbsp; The blood supply in this area of the body is diminished and the tissue becomes nonviable. Reconstruction of the ACL involves attaching the ligament to another tendon from the hamstring, just below the knee. Although reconstruction and treatment of ACL injuries are available, much unnecessary pain, money, and time may be wasted during these procedures. It is important to be aware of the prevention methods available to reduce the possibility of potentially devastating tears to the ACL. These prevention methods include proper warm-up and avoiding activities that cause pain. Other preventive measures include incorporating balance exercises along with stretching and strengthening muscles near the ACL. Appropriate rest and recovery time are other important factors that may prevent ACL injuries. Quality footwear, strapping, or taping may provide an additional level of support to the knee joint and ACL. &nbsp

Patellar Tendinopathy: Knee Pain Relate To Jumper’s Knee

here are common symptoms that are associated with “Jumper’s Knee”, such as pain, aching, and swelling on the lower side of the Patella on the anterior surface of the knee. Addition symptoms may include weakness and cramping of the knee joint. There are common remedies to treat "Jumper’s Knee”, such as rest, ice, compression, and elevation. Anti-inflammatory medicine, such as Aleve, Advil, or Motrin, may be appropriate in the early stages of injury. If the symptoms are left untreated, the final result may be knee surgery. A patient returning to play after diagnoses and treatment for “Jumpers Knee” should apply heat to the knee for 10 or 15 minutes before starting physical activity. Following physical activity, apply ice for 10 to 15 minutes (Donohue, 2008). Conservative treatments assist the healing process and keep Patellar Tendinopathy at bay for more than 90% of cases (Vulpiani, 2007). Along with becoming knowledgeable regarding remedies to relieve symptoms of minor “Jumper’s Knee”, it is important to know the stages of Patellar Tendinopathy. Knowledge of the warning signs and stages may assist in the avoidance of advancing the condition of Patellar Tendinopathy. Knowing the cause of Patellar Tendinopathy, the five stages, warning signs, and risk factors may assist in the process of diagnosing the injury for faster and more effective treatment. Being able to utilize the correct treatment for a particular stage of “Jumpers Knee” reduces downtime and assists the athletic trainers and doctors in the process of prescribing levels of physical activity.

Curriculum For Todays Learner

For the 21st century learner, the foundational principles of information development have grown exponentially. In many fields, the life of knowledge can be measured in months or years, with learning occurring in vastly different ways than in previous decades. Education as a continual process, can last a lifetime, and can be greatly facilitated by technological advances which alter the way in which people access information and think about the world. Faculty members in colleges and universities are challenged to provide a more complete and complex picture of the culture and world in which we live. Educators must maintain a curriculum to meet the demands of an ever-changing population of learners, while striving to diversity higher education curricula to provide a more rigorous educational experience