Length-sensitive partitioning of Caenorhabditis elegans meiotic chromosomes responds to proximity and number of crossover sites.

Sensing and control of size are critical for cellular function and survival. A striking example of size sensing occurs during meiosis in the nematode Caenorhabditis elegans. C.

Phosphoregulation of DSB-1 mediates control of meiotic double-strand break activity.

In the first meiotic cell division, proper segregation of chromosomes in most organisms depends on chiasmata, exchanges of continuity between homologous chromosomes that originate from the repair of programmed double-strand breaks (DSBs) catalyzed by the Spo11 endonuclease. Since DSBs can lead to irreparable damage in germ cells, while chromosomes lacking DSBs also lack chiasmata, the number of DSBs must be carefully regulated to be neither too high nor too low. Here, we show that in , meiotic DSB levels are controlled by the phosphoregulation of DSB-1, a homolog of the yeast Spo11 cofactor Rec114, by the opposing activities of PP4 phosphatase and ATR kinase.

Nematode chromosomes.

The nematode Caenorhabditis elegans has shed light on many aspects of eukaryotic biology, including genetics, development, cell biology, and genomics. A major factor in the success of C. elegans as a model organism has been the availability, since the late 1990s, of an essentially gap-free and well-annotated nuclear genome sequence, divided among 6 chromosomes.

Sequential peripheral enrichment of H2A.Zac and H3K9me2 during trophoblast differentiation in human embryonic stem cells.

During the transition from pluripotency to a lineage-committed state, chromatin undergoes large-scale changes in structure, involving covalent modification of histone tails, use of histone variants and gene position changes with respect to the nuclear periphery. Here, using high-resolution microscopy and quantitative image analysis, we surveyed a panel of histone modifications for changes in nuclear peripheral enrichment during differentiation of human embryonic stem cells to a trophoblast-like lineage. We found two dynamic modifications at the nuclear periphery, acetylation of histone H2A.

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans.

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms.

Intestine-to-Germline Transmission of Epigenetic Information Intergenerationally Ensures Systemic Stress Resistance in C. elegans.

Changes in epigenetic states affect organismal homeostasis, including stress resistance. However, the mechanisms coordinating epigenetic states and systemic stress resistance remain largely unknown. Here, we identify the intestine-to-germline communication of epigenetic states, which intergenerationally enhances stress resistance in C.

Sycp2 is essential for synaptonemal complex assembly, early meiotic recombination and homologous pairing in zebrafish spermatocytes.

Meiotic recombination is essential for faithful segregation of homologous chromosomes during gametogenesis. The progression of recombination is associated with dynamic changes in meiotic chromatin structures. However, whether Sycp2, a key structural component of meiotic chromatin, is required for the initiation of meiotic recombination is still unclear in vertebrates.

The meiotic phosphatase GSP-2/PP1 promotes germline immortality and small RNA-mediated genome silencing.

Germ cell immortality, or transgenerational maintenance of the germ line, could be promoted by mechanisms that could occur in either mitotic or meiotic germ cells. Here we report for the first time that the GSP-2 PP1/Glc7 phosphatase promotes germ cell immortality. Small RNA-induced genome silencing is known to promote germ cell immortality, and we identified a separation-of-function allele of C.

Phosphorylation of the synaptonemal complex protein SYP-1 promotes meiotic chromosome segregation.

Chromosomes that have undergone crossing over in meiotic prophase must maintain sister chromatid cohesion somewhere along their length between the first and second meiotic divisions. Although many eukaryotes use the centromere as a site to maintain cohesion, the holocentric organism instead creates two chromosome domains of unequal length termed the short arm and long arm, which become the first and second site of cohesion loss at meiosis I and II. The mechanisms that confer distinct functions to the short and long arm domains remain poorly understood.

5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability.

5-hydroxymethylcytosine (5hmC) is a DNA base created during active DNA demethylation by the recently discovered TET enzymes. 5hmC has essential roles in gene expression and differentiation. Here, we demonstrate that 5hmC also localizes to sites of DNA damage and repair.

The histone variant H2A.Z is dynamically expressed in the developing mouse placenta and in differentiating trophoblast stem cells.

The histone variant H2A.Z is important in establishing new chromatin environments necessary for permitting changes in gene expression and thus differentiation in mouse embryonic stem (mES) cells. In this study we show that H2A.

Nucleosome compaction facilitates HP1γ binding to methylated H3K9.

The α, β and γ isoforms of mammalian heterochromatin protein 1 (HP1) selectively bind to methylated lysine 9 of histone H3 via their chromodomains. Although the phenotypes of HP1-knockout mice are distinct for each isoform, the molecular mechanisms underlying HP1 isoform-specific function remain elusive. In the present study, we found that in contrast to HP1α, HP1γ could not bind tri-methylated H3 lysine 9 in a reconstituted tetra-nucleosomes when the nucleosomes were in an uncompacted state.

Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-β signaling and astrocyte functions.

Astrocytes modulate neuronal activity and inhibit regeneration. We show that cleaved p75 neurotrophin receptor (p75(NTR)) is a component of the nuclear pore complex (NPC) required for glial scar formation and reduced gamma oscillations in mice via regulation of transforming growth factor (TGF)-β signaling. Cleaved p75(NTR) interacts with nucleoporins to promote Smad2 nucleocytoplasmic shuttling.

ECHO-liveFISH: in vivo RNA labeling reveals dynamic regulation of nuclear RNA foci in living tissues.

Elucidating the dynamic organization of nuclear RNA foci is important for understanding and manipulating these functional sites of gene expression in both physiological and pathological states. However, such studies have been difficult to establish in vivo as a result of the absence of suitable RNA imaging methods. Here, we describe a high-resolution fluorescence RNA imaging method, ECHO-liveFISH, to label endogenous nuclear RNA in living mice and chicks.

Protein phosphatase 4 promotes chromosome pairing and synapsis, and contributes to maintaining crossover competence with increasing age.

Prior to the meiotic divisions, dynamic chromosome reorganizations including pairing, synapsis, and recombination of maternal and paternal chromosome pairs must occur in a highly regulated fashion during meiotic prophase. How chromosomes identify each other's homology and exclusively pair and synapse with their homologous partners, while rejecting illegitimate synapsis with non-homologous chromosomes, remains obscure. In addition, how the levels of recombination initiation and crossover formation are regulated so that sufficient, but not deleterious, levels of DNA breaks are made and processed into crossovers is not understood well.

NanoScript: a nanoparticle-based artificial transcription factor for effective gene regulation.

Transcription factor (TF) proteins are master regulators of transcriptional activity and gene expression. TF-based gene regulation is a promising approach for many biological applications; however, several limitations hinder the full potential of TFs. Herein, we developed an artificial, nanoparticle-based transcription factor, termed NanoScript, which is designed to mimic the structure and function of TFs.

A review of the first 10 years of critical care aeromedical transport during operation iraqi freedom and operation enduring freedom: the importance of evacuation timing.

Importance: Advances in the care of the injured patient are perhaps the only benefit of military conflict. One of the unique aspects of the military medical care system that emerged during Operation Iraqi Freedom and Operation Enduring Freedom has been the opportunity to apply existing civilian trauma system standards to the provision of combat casualty care across an evolving theater of operations.

Objectives: To identify differences in mortality for soldiers undergoing early and rapid evacuation from the combat theater and to evaluate the capabilities of the Critical Care Air Transport Team (CCATT) and Joint Theater Trauma Registry databases to provide adequate data to support future initiatives for improvement of performance.

Application of advanced fluorescence microscopy to the structure of meiotic chromosomes.

Chromosomes undergoing meiosis are defined by a macromolecular protein assembly called the synaptonemal complex which holds homologs together and carries out important meiotic functions. By retaining the molecular specificity, multiplexing ability, and in situ imaging capabilities of fluorescence microscopy, but with vastly increased resolution, 3D-SIM and other superresolution techniques are poised to make significant discoveries about the structure and function of the synaptonemal complex. This review discusses recent developments in this field and poses questions approachable with current and future technology.

Business continuity after catastrophic medical events: the Joplin medical business continuity report.

On May 22, 2011, The St Johns Mercy Medical Center in Joplin, MO, was destroyed by an F-5 tornado. There were 183 patients in the building at that time in this 367-bed Medical Center. The preparation and response were superbly done and resulted in many lives saved.

HAL-2 promotes homologous pairing during Caenorhabditis elegans meiosis by antagonizing inhibitory effects of synaptonemal complex precursors.

During meiosis, chromosomes align with their homologous pairing partners and stabilize this alignment through assembly of the synaptonemal complex (SC). Since the SC assembles cooperatively yet is indifferent to homology, pairing and SC assembly must be tightly coordinated. We identify HAL-2 as a key mediator in this coordination, showing that HAL-2 promotes pairing largely by preventing detrimental effects of SC precursors (SYP proteins).

Dynein-dependent processive chromosome motions promote homologous pairing in C. elegans meiosis.

Meiotic chromosome segregation requires homologue pairing, synapsis, and crossover recombination, which occur during meiotic prophase. Telomere-led chromosome motion has been observed or inferred to occur during this stage in diverse species, but its mechanism and function remain enigmatic. In Caenorhabditis elegans, special chromosome regions known as pairing centers (PCs), rather than telomeres, associate with the nuclear envelope (NE) and the microtubule cytoskeleton.

OMX: a new platform for multimodal, multichannel wide-field imaging.

Bioimaging is currently undergoing an exciting revolution. This includes all aspects of imaging from probe development, specimen preparation, and instrumentation to image analysis and quantitation. Perhaps the most exciting developments are new platforms for imaging that radically advance the capabilities for collecting high spatial and temporal resolution data.

Quantitative immunofluorescence mapping reveals little functional coclustering of proteins within platelet α-granules.

Platelets are small anucleate blood cells that aggregate to seal leaks at sites of vascular injury and are important in the pathology of atherosclerosis, acute coronary syndromes, rheumatoid arthritis, cancer, and the regulation of angiogenesis. In all cases, platelet aggregation requires release of stored proteins from α-granules. However, how proteins with potentially antagonistic functions are packaged within α-granules is controversial.

Sequence-dependent sorting of recycling proteins by actin-stabilized endosomal microdomains.

The functional consequences of signaling receptor endocytosis are determined by the endosomal sorting of receptors between degradation and recycling pathways. How receptors recycle efficiently, in a sequence-dependent manner that is distinct from bulk membrane recycling, is not known. Here, in live cells, we visualize the sorting of a prototypical sequence-dependent recycling receptor, the beta-2 adrenergic receptor, from bulk recycling proteins and the degrading delta-opioid receptor.