Feed aggregator

Modeling of photomorphogenic UV-B signaling [Plant Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Long-wavelength and low-fluence UV-B light is an informational signal known to induce photomorphogenic development in plants. Using the model plant Arabidopsis thaliana, a variety of factors involved in UV-B–specific signaling have been experimentally characterized over the past decade, including the UV-B light receptor UV resistance locus 8; the positive regulators...

Method for identifying kinase substrates [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
In eukaryotes, cell cycle progression is controlled by cyclin/cyclin-dependent kinase (CDK) pairs. To better understand the details of this process, it is necessary to dissect the CDK’s substrate pool in a cyclin- and cell cycle stage-specific way. Here, we report a mass spectrometry-based method that couples rapid isolation of native...

CAMTA controls Purkinje cell function and survival [Neuroscience]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Members of the calmodulin-binding transcription activator (CAMTA) family of proteins function as calcium-sensitive regulators of gene expression in multicellular organisms ranging from plants to humans. Here, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling...

Critical role of TRPC7 in initiation of seizures [Physiology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early...

Glutamate rotamers in the AChR selectivity filter [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
On the basis of single-channel currents recorded from the muscle nicotinic acetylcholine receptor (AChR), we have recently hypothesized that the conformation adopted by the glutamate side chains at the first turn of the pore-lining α-helices is a key determinant of the rate of ion permeation. In this paper, we set...

NGS identifies novel variants for Noonan syndrome [Medical Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Noonan syndrome (NS) is a relatively common genetic disorder, characterized by typical facies, short stature, developmental delay, and cardiac abnormalities. Known causative genes account for 70–80% of clinically diagnosed NS patients, but the genetic basis for the remaining 20–30% of cases is unknown. We performed next-generation sequencing on germ-line DNA...

Genome sequence of a spheroid body [Evolution]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The evolution of mitochondria and plastids from bacterial endosymbionts were key events in the origin and diversification of eukaryotic cells. Although the ancient nature of these organelles makes it difficult to understand the earliest events that led to their establishment, the study of eukaryotic cells with recently evolved obligate endosymbiotic...

Molecular genetic framework for phloem formation [Plant Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
The phloem performs essential systemic functions in tracheophytes, yet little is known about its molecular genetic specification. Here we show that application of the peptide ligand CLAVATA3/EMBRYO SURROUNDING REGION 45 (CLE45) specifically inhibits specification of protophloem in Arabidopsis roots by locking the sieve element precursor cell in its preceding developmental...

Prolactin deters liver cancer [Medical Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Women are more resistant to hepatocellular carcinoma (HCC) than men despite equal exposure to major risk factors, such as hepatitis B or C virus infection. Female resistance is hormone-dependent, as evidenced by the sharp increase in HCC incidence in postmenopausal women who do not take hormone replacement therapy. In rodent...

Protection from arthritis by denervation [Immunology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Two-way communication between the mammalian nervous and immune systems is increasingly recognized and appreciated. An intriguing example of such crosstalk comes from clinical observations dating from the 1930s: Patients who suffer a stroke and then develop rheumatoid arthritis atypically present with arthritis on only one side, the one not afflicted...

Impact of DNA3'pp5'G capping on repair reactions [Biochemistry]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Many biological scenarios generate “dirty” DNA 3′-PO4 ends that cannot be sealed by classic DNA ligases or extended by DNA polymerases. The noncanonical ligase RtcB can “cap” these ends via a unique chemical mechanism entailing transfer of GMP from a covalent RtcB–GMP intermediate to a DNA 3′-PO4 to form DNA3′pp5′G....

Correlating animal and human data with CALAA-01 [Medical Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01 is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA interference (RNAi)–based, experimental therapeutic to be administered to cancer patients. Here, we report the results from the initial phase...

Sequence-resolved free energy profiles of vimentin [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Intermediate filaments (IFs) are key to the mechanical strength of metazoan cells. Their basic building blocks are dimeric coiled coils mediating hierarchical assembly of the full-length filaments. Here we use single-molecule force spectroscopy by optical tweezers to assess the folding and stability of coil 2B of the model IF protein...

Sensory neurons mediate asthmatic bronchospasms [Neuroscience]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Asthma is a common debilitating inflammatory lung disease affecting over 200 million people worldwide. Here, we investigated neurogenic components involved in asthmatic-like attacks using the ovalbumin-sensitized murine model of the disease, and identified a specific population of neurons that are required for airway hyperreactivity. We show that ablating or genetically...

Combinatorial biosynthesis of fungal polyketides [Applied Biological Sciences]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases...

Interferon-{beta} is required for necroptosis [Immunology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Myeloid cells play a critical role in perpetuating inflammation during various chronic diseases. Recently the death of macrophages through programmed necrosis (necroptosis) has emerged as an important mechanism in inflammation and pathology. We evaluated the mechanisms that lead to the induction of necrotic cell death in macrophages. Our results indicate...

Harmonization of shale gas LCAs [Sustainability Science]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Recent technological advances in the recovery of unconventional natural gas, particularly shale gas, have served to dramatically increase domestic production and reserve estimates for the United States and internationally. This trend has led to lowered prices and increased scrutiny on production practices. Questions have been raised as to how greenhouse...

Blockade of I{kappa}B kinase activity by BET inhibitors [Cell Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
In the activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), NF-κB activity is essential for viability of the malignant cells and is sustained by constitutive activity of IκB kinase (IKK) in the cytoplasm. Here, we report an unexpected role for the bromodomain and extraterminal domain (BET) proteins BRD2...

Fruit fly's sensing rate from flight simulations [Biophysics and Computational Biology]

PNAS Early Edition Articles - Mon, 07/21/2014 - 13:05
Without sensory feedback, flies cannot fly. Exactly how various feedback controls work in insects is a complex puzzle to solve. What do insects measure to stabilize their flight? How often and how fast must insects adjust their wings to remain stable? To gain insights into algorithms used by insects to...
Syndicate content