Exaptation of ancestral cell-identity networks enables C photosynthesis.

C photosynthesis is used by the most productive plants on the planet, and compared with the ancestral C pathway, it confers a 50% increase in efficiency. In more than 60 C lineages, CO fixation is compartmentalized between tissues, and bundle-sheath cells become photosynthetically activated. How the bundle sheath acquires this alternate identity that allows efficient photosynthesis is unclear.

Spontaneous intramedullary abscesses caused by Streptococcus anginosus: two case reports and review of the literature.

Background: Intramedullary abscesses are rare infections of the spinal cord. Intramedullary abscesses often have a complex presentation, making a high index of suspicion essential for prompt diagnosis and management.

Case Presentation: We present two cases of intramedullary abscesses referred to and ultimately managed at our institution.

Case Report: Overwhelming Parasitemia Successfully Treated Promptly With RBC Apheresis and Triple Therapy With Clindamycin, Azithromycin, and Atovaquone.

Babesiosis with high-grade parasitemia is life-threatening, especially in asplenic hosts. We report an asplenic patient with parasitemia >50% who was successfully treated with prompt red blood cell apheresis and triple therapy with clindamycin + azithromycin + atovaquone. This regimen may be an alternative to poorly tolerated clindamycin + quinine in severe cases.

Synonymous Mutation in DKC1 Causes Telomerase RNA Insufficiency Manifesting as Familial Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is the most common of short telomere phenotypes. Familial clustering of IPF is common, but the genetic basis remains unknown in more than one-half of cases. We identified a 65-year-old man with familial IPF, short telomere length, and low telomerase RNA levels.

, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation.

Short telomere syndromes manifest as familial idiopathic pulmonary fibrosis; they are the most common premature aging disorders. We used genome-wide linkage to identify heterozygous loss of function of , a zinc-knuckle containing protein, as a cause of autosomal dominant pulmonary fibrosis. ZCCHC8 associated with and was required for telomerase function.

Diagnostic utility of telomere length testing in a hospital-based setting.

Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries.

Ancient duons may underpin spatial patterning of gene expression in C leaves.

If the highly efficient C photosynthesis pathway could be transferred to crops with the C pathway there could be yield gains of up to 50%. It has been proposed that the multiple metabolic and developmental modifications associated with C photosynthesis are underpinned by relatively few master regulators that have allowed the evolution of C photosynthesis more than 60 times in flowering plants. Here we identify a component of one such regulator that consists of a pair of -elements located in coding sequence of multiple genes that are preferentially expressed in bundle sheath cells of C leaves.

Germline Mutations in DNA Repair Genes in Lung Adenocarcinoma.

Introduction: Although lung cancer is generally thought to be environmentally provoked, anecdotal familial clustering has been reported, suggesting that there may be genetic susceptibility factors. We systematically tested whether germline mutations in eight candidate genes may be risk factors for lung adenocarcinoma.

Methods: We studied lung adenocarcinoma cases for which germline sequence data had been generated as part of The Cancer Genome Atlas project but had not been previously analyzed.

Systematic Computational Identification of Variants That Activate Exonic and Intronic Cryptic Splice Sites.

We developed a variant-annotation method that combines sequence-based machine-learning classification with a context-dependent algorithm for selecting splice variants. Our approach is distinctive in that it compares the splice potential of a sequence bearing a variant with the splice potential of the reference sequence. After training, classification accurately identified 168 of 180 (93.

Telomerase and the Genetics of Emphysema Susceptibility. Implications for Pathogenesis Paradigms and Patient Care.

In the past five decades, alpha-1 antitrypsin deficiency has been the only known genetic cause of emphysema, yet it explains the genetics in only 1-2% of severe cases. Recently, mutations in telomerase genes were found to induce susceptibility to young-onset, severe, and familial emphysema at a frequency comparable to that of alpha-1 antitrypsin deficiency. Telomerase mutation carriers with emphysema report a family history of idiopathic pulmonary fibrosis, and both lung phenotypes show autosomal dominant inheritance within families.

Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema.

Chronic obstructive pulmonary disease and pulmonary fibrosis have been hypothesized to represent premature aging phenotypes. At times, they cluster in families, but the genetic basis is not understood. We identified rare, frameshift mutations in the gene for nuclear assembly factor 1, NAF1, a box H/ACA RNA biogenesis factor, in pulmonary fibrosis-emphysema patients.

An Untranslated cis-Element Regulates the Accumulation of Multiple C4 Enzymes in Gynandropsis gynandra Mesophyll Cells.

C4 photosynthesis is a complex phenotype that allows more efficient carbon capture than the ancestral C3 pathway. In leaves of C4 species, hundreds of transcripts increase in abundance compared with C3 relatives and become restricted to mesophyll (M) or bundle sheath (BS) cells. However, no mechanism has been reported that regulates the compartmentation of multiple enzymes in M or BS cells.

The short and long telomere syndromes: paired paradigms for molecular medicine.

Recent advances have defined a role for abnormally short telomeres in a broad spectrum of genetic disorders. They include rare conditions such as dyskeratosis congenita as well pulmonary fibrosis and emphysema. Now, there is new evidence that some familial cancers, such as melanoma, are caused by mutations that lengthen telomeres.

Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders.

Background: Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease.

Dissecting Human Gene Functions Regulating Islet Development With Targeted Gene Transduction.

During pancreas development, endocrine precursors and their progeny differentiate, migrate, and cluster to form nascent islets. The transcription factor Neurogenin 3 (Neurog3) is required for islet development in mice, but its role in these dynamic morphogenetic steps has been inferred from fixed tissues. Moreover, little is known about the molecular genetic functions of NEUROG3 in human islet development.

Telomere dysfunction causes alveolar stem cell failure.

Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the capacity of alveolar epithelial and stromal cells from mice with short telomeres to support alveolar organoid colony formation and found that type 2 alveolar epithelial cells (AEC2s), the stem cell-containing population, were limiting.

Telomerase mutations in smokers with severe emphysema.

Mutations in the essential telomerase genes TERT and TR cause familial pulmonary fibrosis; however, in telomerase-null mice, short telomeres predispose to emphysema after chronic cigarette smoke exposure. Here, we tested whether telomerase mutations are a risk factor for human emphysema by examining their frequency in smokers with chronic obstructive pulmonary disease (COPD). Across two independent cohorts, we found 3 of 292 severe COPD cases carried deleterious mutations in TERT (1%).

Unintentional dural puncture with a Tuohy needle increases risk of chronic headache.

Background: Neuraxial analgesia is chosen by almost half of women who give birth in the United States. Unintentional dural puncture is the most common complication of this pain management technique, occurring in 0.4% to 6% of parturients.

Independent and parallel recruitment of preexisting mechanisms underlying C₄ photosynthesis.

C₄ photosynthesis allows increased photosynthetic efficiency because carbon dioxide (CO₂) is concentrated around the key enzyme RuBisCO. Leaves of C₄ plants exhibit modified biochemistry, cell biology, and leaf development, but despite this complexity, C₄ photosynthesis has evolved independently in at least 45 lineages of plants. We found that two independent lineages of C₄ plant, whose last common ancestor predates the divergence of monocotyledons and dicotyledons about 180 million years ago, show conserved mechanisms controlling the expression of genes important for release of CO(2) around RuBisCO in bundle sheath (BS) cells.

C acid decarboxylases required for C photosynthesis are active in the mid-vein of the C species Arabidopsis thaliana, and are important in sugar and amino acid metabolism.

Cells associated with veins of petioles of C(3) tobacco possess high activities of the decarboxylase enzymes required in C(4) photosynthesis. It is not clear whether this is the case in other C(3) species, nor whether these enzymes provide precursors for specific biosynthetic pathways. Here, we investigate the activity of C(4) acid decarboxylases in the mid-vein of Arabidopsis, identify regulatory regions sufficient for this activity, and determine the impact of removing individual isoforms of each protein on mid-vein metabolite profiles.

Photosynthesis in cells around veins of the C(3) plant Arabidopsis thaliana is important for both the shikimate pathway and leaf senescence as well as contributing to plant fitness.

Cells associated with veins of C(3) species often contain significant amounts of chlorophyll, and radiotracer analysis shows that carbon present in the transpiration stream may be used for photosynthesis in these cells. It is not clear whether CO2 is also supplied to these cells close to veins via stomata, nor whether this veinal photosynthesis supplies carbon skeletons to particular metabolic pathways. In addition, it has not been possible to determine whether photosynthesis in cells close to veins of C(3) plants is quantitatively important for growth or fitness.