Antibody News

By Jamshed Arslan Pharm.D.

Cancers of nerve, adipose, and other soft tissues are called soft tissue sarcomas (STS). Malignant peripheral nerve sheath tumor (MPNST) is an example of a rare and hard-to-treat STS; even after the surgical removal (which is the only viable option), the tumor often relapses causing poor patient survival. The search for novel treatment targets led a team of researchers in Japan [1] to a transcription factor called hypoxia-inducible factor (HIF). Normally, HIF-1α adapts cells to hypoxic conditions by localizing to the nucleus where it regulates cell growth with the help of transcriptional co-activators...

By Jamshed Arslan Pharm.D.

Triple-negative breast cancer (TNBC) is difficult to treat because it does not express the receptors (estrogen, progesterone, and HER2) against which effective therapies are available. TNBC defeats the body’s regulation on unchecked growth, but its winning strategy remained unclear until recently. A research team, led by Dr. William Kaelin at the Dana-Farber Cancer Institute in Boston, recently discovered that TNBC cells release glutamate to disable a cancer-stunting enzyme, EglN1. This enzyme targets the...

By Yoskaly Lazo-Fernandez, PhD

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurological disease that affects the motor neuron system and thus voluntary control of muscle movement. This disease belongs to a broader group of disorders known as motor neuron diseases, characterized by progressive degeneration and death of motor neurons. There are two types of motor neurons, including upper- and lower-motor neurons, based on the position of their somas within the CNS. Upper motor neuron somas are located in the motor cortex and their axons descend to the spinal cord where they activate the lower motor neurons. Lower motor neurons have somas within the spinal cord and extend their axons peripherally to innervate skeletal muscles. In ALS patients...

By Yoskaly Lazo-Fernandez, PhD

Polyglutamine tracts (polyQ tracts) are long chains of glutamine amino acidspresent in the sequence of many proteins. The length of polyQ tracts within proteins varies significantly as normal alleles of specific genes usually contain different number of the cytosine-adenine-guanine (CAG) nucleotide repeats¹.

It has long been known that polyQ tracts play a role in the etiology of several inheritable neurodegenerative disorders, including spinocerebellar ataxia, and Huntington's disease². These 'polyglutamine diseases' result from the excessive elongation of a polyQ tract in a particular gene which causes the resultant protein to become toxic. The toxicity of mutated polyQ tracts has been extensively studied and several explanatory hypotheses have been proposed: aggregation of polyQ tract proteins, transcriptional dysregulation, mitochondrial dysfunction, and impairment of both the ubiquitin-...

By Jamshed Arslan Pharm.D.

Alzheimer’s disease (AD) robs people of their memory and identity. One characteristic feature of AD is the increased expression of the enzyme, histone deacetylase-2 (HDAC-2). This protein stops the expression of some memory-forming genes by condensing them. So, memory can be enhanced by inhibiting HDAC-2. However, this approach is dangerous since HDAC-1, a close family member of HDAC-2, would also become inhibited, resulting in neuronal death and other toxic effects. New research,[1] led by Li-Huei Tsai at the Massachusetts Institute of Technology, Cambridge, suggests a novel way to specifically repress HDAC-2 by targeting the domain of HDAC-2 that makes a complex with the transcription factor, Sp3.

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By Bethany Veo, PhD

Our muscle cells develop from myogenic stem cells or satellite cells which have the capacity to grow, self-renew, differentiate, and regenerate under the influence of changing oxygen levels sensed from the microenvironment. Hypoxia-inducible factors HIF-1 alpha and HIF-2 alpha are transcription factors that respond to low oxygen levels, activating the expression of target genes. The current understanding of the role that HIF-1 alpha and HIF-2 alpha play in muscle development is contradictory. Case in point, upregulation and downregulation of HIF-1 alpha inhibit myoblast differentiation depending on the oxygen level in vitro.

Transgenic models including mice lacking HIF-2 alpha exhibit early embryonic arrest and HIF-1 alpha knockouts are lethal. Whereas HIF-1 alpha knockouts generated with a different Cre-...

By Bethany Veo, PhD

Mitochondria are most commonly known as the power houses of the cell, facilitating major functions such as oxidative phosphorylation and cellular respiration.  Maintenance of mitochondria is essential to a cells' physiological homeostasis and requires oversight by several factors.  PINK1 is a serine/threonine protein kinase which localizes to the mitochondrion and regulates its function and turnover by sensing when mitochondria are damaged.¹  The foremost mechanisms of mitochondrial health upkeep include fusion and fission, mitophagy, and mitochondrial transport. PINK1 is critical for mitochondrial health by facilitating all of these pathways, which serve as a quality control system to remove dysfunctional or damaged mitochondrion from the cell.  In fact, mutations in PINK1 are linked with Parkinson's disease, where dysfunction in mitophagy, mitochondrial clearance and...

The neurodegenerative disorder, Alzheimer's disease, is responsible for 60 to 80% of all dementia cases.¹   Neurodegeneration occurs in response to the accumulation of amyloid-β plaques and neurofibrillary tangles composed of hyperphosphorylated tau. The proteolytic processing of AβPP (amyloid β precursor protein) by β-secretase and γ-secretase releases Aβ fragments of 40 and 42 amino acid residues which miss-fold and aggregate into the pathogenic plaques.²  Similarly, proteolytic processing of phosphorylated tau releases monomers that are targeted to the 26S proteasome for degradation. However, proteasomal efficiency is poor when it comes to degrading ubiquitinated tau as these substrates lead to more neurofibrillary tangle aggregates.² The inability to clear these accumulating plaques intracellularly results in a significant amount of oxidative and cellular stress leading to progressive neuronal loss and...

Hypoxia is a common feature of most tumors and is a product of rapid cell growth and poor vascularization¹. When oxygen availability is low in the tumor environment, the hypoxia inducing transcription factors (HIFs) regulate a variety of signaling programs that can affect the balance between tumor cell apoptosis² and autophagy³.  In normoxia, HIFs are bound by the von Hippel-Lindau protein (VHL) in the cytosol where it is degraded by the proteasome, however, under hypoxia HIFs are translocated to the nucleus where they activate survival signals. Additionally, HIF mediated signaling can increase the metastatic capabilities of tumor cells and facilitate the pro-metastatic phenotypes of epithelial to mesenchymal transition (EMT), alter tumor cell metabolism, increase vascularization and angiogenesis, as well as suppress immune reactivity¹. Together these HIF regulated pathways help cancer cells to thrive and activate pro-...

1. Know your cytometer

The configuration of flow cytometers including light sources (lasers) and optics (mirrors, filters, and detectors) vary and a few, such as the Propel ZE5 Cell Analyzer, can detect up to 30 parameters in thousands to millions of cells. Lasers excite fluorochromes at fixed wavelengths and the emitted fluorescence is captured by optical detectors called photomultiplier tubes (PMTs). Setting PMT voltages correctly is important because a low setting can compromise signal detection. Furthermore, some instruments have interchangeable/swappable filters offering more flexibility when designing flow cytometry experiments.

2. Optimize antibody selections

To prevent complications during your experiment, take time to choose your antibodies and optimize their working conditions. Best practices dictate lowly expressed proteins or those with rare epitopes should be paired with antibodies conjugated to...

Microglia are resident macrophages in the central nervous system (CNS) that play roles in immune defense, inflammatory response, neurodegenerative disease and development. Identification of microglia has confounded researchers aiming to understand their biological function in the CNS, as they are molecularly and morphologically similar to other myeloid cells. For example, morphologically, microglia are indistinguishable from infiltrating blood derived macrophages.¹ Additionally, microglia are commonly purified for study based on their expression of molecular markers, such as CD11b^High and CD45^Low; although, these may change in disease states.^2,3

To fully understand and uncover the roles of microglia in the CNS, specific markers that accurately identify these cells are needed. Recently, investigators have embarked in efforts to elucidate specific...