Alzheimer’s disease (AD) is a major healthcare problem, with
over five million patients in the United States, and an annual economic impact
of approximately $200 billion. With recent therapeutic trial failures and a
rapidly increasing number of cases, improved approaches for high-throughput
screening of large compound numbers are needed. To this end, simple models of
AD, such as cellular models, invertebrate models, and transgenic mouse models,
have been created. However, the invertebrate models described to date displaynumerous dissimilarities to human AD, such as expression of the relevant gene
in muscle or eye rather than brain, and the hyper-expression of the gene,
leading to generalized motor reflex deficits. In an effort to create a more
relevant Drosophila AD model, we utilized the gene switch approach, inducibly
expressing low levels of human amyloid-β precursor protein (hAβPP) and human
β-site AβPP cleaving enzyme 1 (hBACE1). Surprisingly, this expression led to a
phenotype highly reminiscent of attention deficit hyperactivity disorder
(ADHD), with hyperactivity, male predominance, marked exacerbation by simple
carbohydrates, reversible response to dextroamphetamine, and a “paradoxical
response” to stimulants, all characteristics of human ADHD. This represents the
first invertebrate model of ADHD faithfully reproducing these key features of
ADHD.
We sought to create an invertebrate model of AD that more
closely mimics the human disease in target tissue, mnemonic effects, and
response to candidate therapeutics. To create such a Drosophila AD model, we
used the RU-486-induced Elav-GeneSwitch driver to express low levels of hAβPPand hBACE1 in Drosophila. Previous studies have shown that over-expression of
hAβPP and hBACE1 leads to severe motor reflex deficits. We therefore employed
the Drosophila population activity monitors to measure spontaneous activity.
Surprisingly, these flies were not found to be hypoactive compared to the
uninduced controls, but rather were hyperactive, typically 50-100% more active
than the control, uninduced Drosophila.
Cerebral Toxoplasmosis is
a very common cause of focal neurologic disorder in Acquired Immune Deficiency
Syndrome (AIDS) patients with cerebral lesions, but it seems to be a rare cause of spinal cord disease. If not treated and detected immediately,
Toxoplasmosis may cause considerable mortality and morbidity.
Toxoplasma
gondii is an intracellular pathogen that contracts a major proportion of the
world population. Also, it is a well-known cause of sickness among persons with
Acquired Immune Deficiency Syndrome(AIDS). Although brain has been the major site for Toxoplasma
infection in Acquired Immune Deficiency Syndrome (AIDS) patients, spinal cord involvement by Toxoplasma has
been seldom reported. Spinal cord Toxoplasmosis may present as severe outset
weakness in both lower limbs correlating with both sensory and bladder
dysfunction. On the other hand, progression of cerebral infection may produce
seizures, ataxia, confusion, aphasia, hemianopsia, hemiparesis, drowsiness, and
cranial nerve palsies. Congenital Toxoplasmosis is an illness caused by
intrauterine transmission of the parasite Toxoplasma gondii to the fetus. A
pregnant woman may acquire this parasite during gestation. Toxoplasma gondii
can be found in up to 50% of the world population. Approximately 10% of
patients with Acquired Immune Deficiency Syndrome (AIDS) show some kind of
neurological deficit as their primary complaint, and around 80% will have Central Nervous System (CNS) involvement
during the course of their illness. The retina and the lungs are the major sites of extracerebral
manifestation of Toxoplasmosis, and such manifestations may happen with/without
concomitant Encephalitis. Here we present a case report and review of the
literature on Toxoplasmosis in Acquired Immune Deficiency Syndrome (AIDS)
patients.
It is often explicitly, or
implicitly, considered that an enzyme reaction occurring under steady state
conditions is a system that collects connected states of the enzyme that
appear during the reaction. Moreover,
there is little doubt that many enzymes in vivo are aggregated as multienzyme
complexes in such a way that one can wonder whether the corresponding enzyme
reactions are not aggregated to form a functional structure that connects and
associates the elementary reactions as to form a coherent whole.
The rate equation of the
global system of becomes more complex than the individual equations of
the enzymes E1 and E2 in isolation. However, one can notice that the global
system is dependent upon antagonistic effects exerted by system 1. A first
effect is a tendency to drift towards thermodynamic equilibrium. This tendency
is exerted through the rate constants of substrate binding and release. A
second effect is a tendency of the system to drift from the equilibrium and
is exerted through a subtle combination of catalytic and substrate binding
constants . The situation is thus of the same type, but more complex, than the
one already described. A global steady state of the system its organization, is
the result of these interactions.
Leeches (Clitellata: Hirudinida) are hermaphrodite worms and abundant predators or ecto-parasites in various freshwater habitats. Many leeches have a significant adverse impact on freshwater culture and animal health. Erpobdella octoculata Linnaeus, 1758 (Hirudinea: Arhynchobdellida: Erpobdelliformes) is one of the most common leech species in freshwaters. Its assemblage typically dominates the lowlands in lake, streams and rivers as well as in urban park ponds. Despite widely distributed, the current genomic knowledge of leeches is scant and taxon diversity is poorly constructed.
Animal mitochondrial DNA (mtDNA) is a single circular duplex molecule typically coding for 13 protein-coding genes, 2 rRNA genes and 22 tRNA genes. The mitochondrial genome has been extensively used to study the phylogenetic relationships at several taxonomic levels. Compared to other metazoan animals, only five complete mt genome sequences of leech species for the suborder Hirudiniformes have been sequenced and deposited in GenBank to date, and no mt genome for the suborder Erpobdelliformes has been reported. In this study, we sequenced the complete mitochondrial (mt) genomes of E. octoculata, analysized its mitochondrial gene arrangements, gene compositions, translation and initiation codons and codon usage as well as the structure of rRNA and tRNA genes. In addition, we used the currently available nucleotide sequences to reconstruct the phylogenetic relationship among the included annelids. The new mt genome sequence may provide novel and useful mtDNA markers for investigating genetic composition of suborder Erpobdelliformes, as it is the first reported complete mtDNA sequence in this suborder.
There are viable minimally invasive technologies and minimally invasive surgical procedures that make it feasible to move away from fusion as an early surgical option for treating chronic low back pain if non-surgical methods fail. Surgeons who are familiar with and who have training in endoscopic spine surgery are able to utilize the transforaminal endoscopic approach to the lumbar spine and use these endoscopic techniques to identify and treat the pain generators with the least invasive, most effective methods available. Sub-acute and chronic causes of debilitating back pain are effectively treated in trained hands. The “surgeon factor” is a critical step for each endoscopic surgeon who needs to possess a wide range of surgical experience and skill to pick the procedures and techniques that works best, limited only by their own surgical experience and ability.
