Is There a Role for a Traditional Herbal Formula in the Treatment of Hepatitis C?

Perspectives on the role of traditional and alternative treatments for hepatitis C, and the challenges facing practicing physicians on its relationship to established guidelines

Sitting Down with Dr. John Weg: Pulmonary Medicine Pioneer

Recently, the Quill & Scope’s Jenny Lam and Edward Hurley spoke with pulmonary medicine pioneer Dr. John Weg, Class of 1959, about his career, medicine in general and his time at New York Medical College

The Subset Assignment Problem for Data Placement in Caches

We introduce the subset assignment problem in which items of varying sizes are placed in a set of bins with limited capacity. Items can be replicated and placed in any subset of the bins. Each (item, subset) pair has an associated cost. Not assigning an item to any of the bins is not free in general and can potentially be the most expensive option. The goal is to minimize the total cost of assigning items to subsets without exceeding the bin capacities. This problem is motivated by the design of caching systems composed of banks of memory with varying cost/performance specifications. The ability to replicate a data item in more than one memory bank can benefit the overall performance of the system with a faster recovery time in the event of a memory failure. For this setting, the number n of data objects (items) is very large and the number d of memory banks (bins) is a small constant (on the order of 3 or 4). Therefore, the goal is to determine an optimal assignment in time that minimizes dependence on n. The integral version of this problem is NP-hard since it is a generalization of the knapsack problem. We focus on an efficient solution to the LP relaxation as the number of fractionally assigned items will be at most d. If the data objects are small with respect to the size of the memory banks, the effect of excluding the fractionally assigned data items from the cache will be small. We give an algorithm that solves the LP relaxation and runs in time O(binom{3^d}{d+1} poly(d) n log(n) log(nC) log(Z)), where Z is the maximum item size and C the maximum storage cost

A Positive Feedback Loop Between Myc and Aerobic Glycolysis Sustains Tumor Growth in a Drosophila Tumor Model

Cancer cells usually exhibit aberrant cell signaling and metabolic reprogramming. However, mechanisms of crosstalk between these processes remain elusive. Here, we show that in an in vivo tumor model expressing oncogenic Drosophila Homeodomain-interacting protein kinase (Hipk), tumor cells display elevated aerobic glycolysis. Mechanistically, elevated Hipk drives transcriptional upregulation of Drosophila Myc (dMyc; MYC in vertebrates) likely through convergence of multiple perturbed signaling cascades. dMyc induces robust expression of pfk2 (encoding 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase; PFKFB in vertebrates) among other glycolytic genes. Pfk2 catalyzes the synthesis of fructose-2,6-bisphosphate, which acts as a potent allosteric activator of Phosphofructokinase (Pfk) and thus stimulates glycolysis. Pfk2 and Pfk in turn are required to sustain dMyc protein accumulation post-transcriptionally, establishing a positive feedback loop. Disruption of the loop abrogates tumorous growth. Together, our study demonstrates a reciprocal stimulation of Myc and aerobic glycolysis and identifies the Pfk2-Pfk governed committed step of glycolysis as a metabolic vulnerability during tumorigenesis

Evaluating snow microbial assemblages

Psychrophiles are organisms that grow optimally below 20C (1). The US Great Basin is home to many mountain peaks with an abundance of alpine snow environments perfect for psychrophilic habitation. We analyzed samples from three different locations, Wheeler Peak, Pacific Crest Trail, and Mount Conness, characterizing and comparing the psychrophilic communities at varying depth intervals in the snow. Polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) showed no notable difference in community structure with depth, but there was a distinct difference when comparing different snow environments (i.e. shaded vs. full sun exposure). The chlorophyll concentration decreased as the depth of the snow increased. By creating a clone library and utilizing DNA sequencing technology we were able to obtain 16S and 18S rRNA gene sequences from samples collected from Mount Conness, which allowed us to identify microbes living in the ecosystem. This information enabled us to produce bacterial and eukaryl phylogenetic trees, giving us a clear look into the diversity of this psychrophilic community. Out of seventy bacterial results there were fifty‐three ‐Proteobacteria, thirteen Sphingobacteria, and only three Actinobacteria, with one unclassified bacteria as well. These results will guide us in our future plans for experimentation

MASP-1 of the complement system enhances clot formation in a microvascular whole blood flow model.

The complement and coagulation systems closely interact with each other. These interactions are believed to contribute to the proinflammatory and prothrombotic environment involved in the development of thrombotic complications in many diseases. Complement MASP-1 (mannan-binding lectin-associated serine protease-1) activates coagulation factors and promotes clot formation. However, this was mainly shown in purified or plasma-based static systems. Here we describe the role of MASP-1 and complement activation in fibrin clot formation in a microvascular, whole blood flow model. This microfluidic system simulates blood flow through microvessels at physiological flow and shear rates and represents the closest model system to human physiology so far. It features parallel microchannels cultured with endothelial cells in a transparent microfluidic chip allowing real-time evaluation of clot formation by confocal microscopy. To test their effects on clot formation, we added the following activators or inhibitors (individually or in combination) to whole blood and performed perfusion experiments: rMASP-1cf (recombinant active form of MASP-1), complement activator zymosan, selective MASP-1 inhibitor SGMI-1 (based on the Schistocerca gregaria protease inhibitor scaffold), classical pathway inhibitor rSALO (recombinant salivary anti-complement from Lutzomyia longipalpis). Addition of rMASP-1cf resulted in accelerated fibrin clot formation while addition of SGMI-1 delayed it. Complement activation by zymosan led to increased clot formation and this effect was partially reversed by addition of rSALO and almost abolished in combination with SGMI-1. We show for the first time a strong influence of MASP-1, complement activation and pathway-specific inhibition on coagulation in a microvascular flow system that is closest to human physiology, further underpinning the in vivo relevance of coagulation and complement interactions

Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections

Monoclonal antibodies represent an exciting class of therapeutics against respiratory viral infections. Notwithstanding their specificity and affinity, the conventional parenteral administration is suboptimal in delivering antibodies for neutralizing activity in the airways due to the poor distribution of macromolecules to the respiratory tract. Inhaled therapy is a promising approach to overcome this hurdle in a noninvasive manner, while advances in antibody engineering have led to the development of unique antibody formats which exhibit properties desirable for inhalation. In this Opinion, we examine the major challenges surrounding the development of inhaled antibodies, identify knowledge gaps that need to be addressed and provide strategies from a drug delivery perspective to enhance the efficacy and safety of neutralizing antibodies against respiratory viral infections