A population shift between two heritable cell types of the pathogen is based both on switching and selective proliferation.

Differentiated cell types often retain their characteristics through many rounds of cell division. A simple example is found in , a member of the human microbiota and also the most prevalent fungal pathogen of humans; here, two distinct cell types (white and opaque) exist, and each one retains its specialized properties across many cell divisions. Switching between the two cell types is rare in standard laboratory medium (2% glucose) but can be increased by signals in the environment, for example, certain sugars.

Transcriptional rewiring over evolutionary timescales changes quantitative and qualitative properties of gene expression.

Evolutionary changes in transcription networks are an important source of diversity across species, yet the quantitative consequences of network evolution have rarely been studied. Here we consider the transcriptional 'rewiring' of the three genes that encode the enzymes needed for cells to convert galactose to glucose. In , the transcriptional regulator Gal4 binds and activates these genes.

Delayed Ras/PKA signaling augments the unfolded protein response.

During environmental, developmental, or genetic stress, the cell's folding capacity can become overwhelmed, and misfolded proteins can accumulate in all cell compartments. Eukaryotes evolved the unfolded protein response (UPR) to counteract proteotoxic stress in the endoplasmic reticulum (ER). Although the UPR is vital to restoring homeostasis to protein folding in the ER, it has become evident that the response to ER stress is not limited to the UPR.

Dynamic characterization of growth and gene expression using high-throughput automated flow cytometry.

Cells adjust to changes in environmental conditions using complex regulatory programs. These cellular programs are the result of an intricate interplay between gene expression, cellular growth and protein degradation. Technologies that enable simultaneous and time-resolved measurements of these variables are necessary to dissect cellular homeostatic strategies.

Regulatory architecture determines optimal regulation of gene expression in metabolic pathways.

In response to environmental changes, the connections ("arrows") in gene regulatory networks determine which genes modulate their expression, but the quantitative parameters of the network ("the numbers on the arrows") are equally important in determining the resulting phenotype. What are the objectives and constraints by which evolution determines these parameters? We explore these issues by analyzing gene expression changes in a number of yeast metabolic pathways in response to nutrient depletion. We find that a striking pattern emerges that couples the regulatory architecture of the pathway to the gene expression response.

Continuous time-of-flight ion imaging: application to fragmentation.

We have designed and constructed a continuous imaging reflectron time-of-flight mass spectrometer (TOFMS) that provides a mass spectrum at every pixel of a two-dimensional image with a 100% duty cycle. The technique is based on pseudorandom ion beam modulation and three-dimensional ( x, y, t) ion imaging. We use a multichannel plate detector with a delay-line anode that provides x, y positions and flight times t of every ion arrival event.

Micromachined Bradbury-Nielsen gates.

Bradbury-Nielsen gates (BNGs) are a standard way for gating or steering beams of charged particles in ion mobility spectrometry and time-of-flight mass spectrometry. They consist of a pair of interleaved electrodes that when at the same potential allow ions to pass through the electrodes undeflected and, when a voltage is applied, cause the ions to be deflected from their propagation axis. Previous efforts to construct such devices have relied on mechanical assembly by winding wires across an aperture.

Simple template-based method to produce Bradbury-Nielsen gates.

A Bradbury-Nielsen gate (BNG) consists of two interleaved and electrically isolated sets of wires and can transmit or deflect charged particles by applying a varying voltage difference across the two wire sets. We present a simple template-based method to fabricate BNGs with wire spacings as small as 50 microm with minimal use of a microscope. The small wire spacing allows modulation rates at tens of megahertz.

Duty cycle and modulation efficiency of two-channel Hadamard transform time-of-flight mass spectrometry.

Hadamard transform time-of-flight mass spectrometry (HT-TOFMS) is based on the pseudorandom gating of ion packets into a time-of-flight mass-to-charge analyzer. In its typical implementation, the technique is able to monitor continuous ion sources with a 50% duty cycle, independent of all other figures of merit. Recently, we have demonstrated that the duty cycle can be extended to 100% using patterned, two-channel detection.

A soft on-column metal coating procedure for robust sheathless electrospray emitters used in capillary electrophoresis-mass spectrometry.

An on-column metal coating procedure was developed for sheathless electrospray emitters, based on Justus von Liebig's electroless silver mirror reaction followed by electrochemical deposition of gold onto the silver layer. The coating procedure is straightforward, mild, inexpensive, and can be performed with standard laboratory equipment. A long-term (600 h) stability investigation of the conductive coating was carried out by continuous electrospray in the positive electrospray mode, and no degradation in performance was found.

Discorhabdins S, T, and U, new cytotoxic pyrroloiminoquinones from a deep-water Caribbean sponge of the genus Batzella.

Discorhabdins S, T, and U (1-3), three new discorhabdin analogues, have been isolated from a deep-water marine sponge of the genus Batzella. These discorhabdin analogues showed in vitro cytotoxicity against PANC-1, P-388, and A-549 cell lines. The isolation and structure elucidation of discorhabdins S, T, and U are described.