Search for the standard model Higgs boson in ℓν\bm{\ellν}+jets final states in 9.7~fb−1\bm{^{-1}} of ppˉ\bm{p\bar{p}} collisions with the D0 detector

We present, in detail, a search for the standard model Higgs boson, $H$, in final states with a charged lepton (electron or muon), missing energy, and two or more jets in data corresponding to 9.7 fb$^{-1}$ of integrated luminosity collected at a center of mass energy of $\sqrt{s}$ = 1.96 TeV with the D0 detector at the Fermilab Tevatron $p\bar{p}$ Collider. The search uses $b$-jet identification to categorize events for improved signal versus background separation and is sensitive to associated production of the $H$ with a $W$ boson, $WH\to\ell\nu b\bar{b}$; gluon fusion with the Higgs decaying to $W$ boson pairs, $H\to WW\to\ell\nu jj$; and associated production with a vector boson where the Higgs decays to $W$ boson pairs, $VH\to VWW \to \ell\nu jjjj$ production (where $V = W$ or $Z$). We observe good agreement between data and expected background. We test our method by measuring $WZ$ and $ZZ$ production with $Z\to b\bar{b}$ and find production rates consistent with the standard model prediction. For a Higgs boson mass of 125 GeV, we set a 95%\ C.L. upper limit on the production of a standard model Higgs boson of \obslimA$\times\sigma_{\rm SM}$, where $\sigma_{\rm SM}$ is the standard model Higgs boson production cross section, while the expected limit is \explimA$\times\sigma_{\rm SM}$. We also interpret the data considering models with fourth generation fermions, or a fermiophobic Higgs boson

Bmp7 Functions via a Polarity Mechanism to Promote Cloacal Septation

During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood.We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse.Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations

In vitro and in vivo neuroprotective effects of cJun N-terminal kinase inhibitors on retinal ganglion cells

BACKGROUND: The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in neuronal pathophysiology. Using JNK inhibitors, we examined involvement of the JNK pathway in cultured rat retinal ganglion cell (RGC) death and in mouse retinal ischemia/reperfusion (I/R) injury of the visual axis. The in vitro effects of JNK inhibitors were evaluated in cultured adult rat retinal cells enriched in RGCs. Retinal I/R was induced in C57BL/6J mice through elevation of intraocular pressure to 120 mmHg for 60 min followed by reperfusion. SP600125 was administered intraperitoneally once daily for 28 days. Phosphorylation of JNK and c-Jun in the retina was examined by immunoblotting and immunohistochemistry. The thickness of retinal layers and cell numbers in the ganglion cell layer (GCL) were examined using H&E stained retinal cross sections and spectral domain optical coherence tomography (SD-OCT). Retinal function was measured by scotopic flash electroretinography (ERG). Volumetric measurement of the superior colliculus (SC) as well as VGLUT2 and PSD95 expression were studied. RESULTS: JNK inhibitors SP600125 and TAT-JNK-III, dose-dependently and significantly (p < 0.05) protected against glutamate excitotoxicity and trophic factor withdrawal induced RGC death in culture. In the I/R model, phosphorylation of JNK (pJNK) in the retina was significantly (p < 0.05) increased after injury. I/R injury significantly (p < 0.05) decreased the thickness of retinal layers, including the whole retina, inner plexiform layer, and inner nuclear layer and cell numbers in the GCL. Administration of SP600125 for 28 days protected against all these degenerative morphological changes (p < 0.05). In addition, SP600125 significantly (p < 0.05) protected against I/R-induced reduction in scotopic ERG b-wave amplitude at 3, 7, 14, 21 and 28 days after injury. SP600125 also protected against the I/R-induced losses in volume and levels of synaptic markers in the SC. Moreover, the protective effects of SP600125 in the retina and SC were also detected even with only 7 days (Days 1–7 after I/R) of SP600125 treatment. CONCLUSIONS: Our results demonstrate the important role the JNK pathway plays in retinal degeneration in both in vitro and in vivo models and suggest that JNK inhibitors may be a useful therapeutic strategy for neuroprotection of RGCs in the retina. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13024-016-0093-4) contains supplementary material, which is available to authorized users

Sperm structure in Parasitidae mites (Parasitiformes : Mesostigmata : Gamasina)

This contribution reviews the ultrastructure of ribbon-type sperm in 14 genera of both subfamilies (7 in Pergamasinae and 7 in Parasitinae) of the Parasitidae family (Parasitiformes: Mesostigmata: Gamasina); in total 27 species were considered, of which sperm ultrastructure was studied for the first time in 17 species and 9 genera. We found a wide range of sperm dimensions and nucleus lengths, but basic external and internal structures were substantially constant across genera. Spermatozoa are rod- or club-shaped cells with an elongated nucleus. The chromatin granules are focused in the middle zone of the nucleus. The cytoplasm around the nucleus and in the adjoining postnuclear region is filled with inclusion bodies with striated content (striated inclusion bodies, sIBs), whereas in the distant postnuclear region they are replaced by larger granular inclusion bodies (gIBs) usually containing a striated core surrounded by granular material. Mitochondria are distributed mostly subplasmalemmally in the nuclear region and between gIBs in the postnuclear region of the sperm cell. The most variable feature of the spermatozoa is the number of compound longitudinal ribbons of plasmalemmal origin alternating with subplasmalemmal cisterns: 9 (Leptogamasus anoxygenellus) to 21 (Pergamasus barbarus) in Pergamasinae and 5 (Parasitus berlesei and Paracarpais loricatus) to 30 (Paracarpais lunulata) in Parasitinae. In general, ribbons are electron-dense in the nuclear region but more lucent in the postnuclear region. The variation in sperm structure was not reflected in the taxonomic arrangement of genera and subfamilies within Parasitidae, but it must be emphasized that the taxonomy of Parasitidae is still awaiting a comprehensive modern revision

Sperm structure in Parasitidae mites (Parasitiformes: Mesostigmata: Gamasina)

Witalinski, W., Podkowa, D. (2016): Sperm structure in Parasitidae mites (Parasitiformes: Mesostigmata: Gamasina). Acarologia 56 (1): 3-32, DOI: 10.1051/acarologia/20162190, URL: http://dx.doi.org/10.1051/acarologia/2016219

Expression of primary cilia-related genes in developing mouse gonads

International audienceMechanisms governing differentiation of the bipotential gonad into the testes or ovaries are complex and still vague. The primary cilium is an organelle involved in cell signaling, which controls the development of many organs, but the role of primary cilium in the sex determination and sexual differentiation of gonads is completely unknown. Here we studied the expression of genes involved in primary cilium formation and functioning in fetal mouse gonads, before, during and after sexual differentiation. We studied the expression of 175 primary cilia-related genes using microarray technique. 144 of these genes were ubiquitously expressed in all studied cell types with no significant differences in expression level. Such a high level of expression of primary cilia-related genes in developing mouse gonads suggests that the primary cilia and/or primary cilia-related genes are important for the development of both somatic and germline component of the gonads. Only 31 genes showed a difference in expression between different cell types, which suggests that they have different functions in the somatic and germ cells. These results justify further studies on the role of primary cilia and the primary cilia-related genes in gonad development

Brush cells in the human duodenojejunal junction: an ultrastructural study

Brush cells have been identified in the respiratory and gastrointestinal tract mucosa of many mammalian species. In humans they are found in the respiratory tract and the gastrointestinal apparatus, in both the stomach and the gallbladder. The function of brush cells is unknown, and most morphological data have been obtained in rodents. To extend our knowledge of human brush cells, we performed an ultrastructural investigation of human small intestine brush cells. Six brush cells identified in five out of more than 300 small intestine biopsies performed for gastrointestinal tract disorders were examined by transmission electron microscopy. Five brush cells were located on the surface epithelium and one in a crypt. The five surface brush cells were characterized by a narrow apical pole from which emerged microvilli that were longer and thicker than those of enterocytes. The filamentous core extended far into the cell body without forming the terminal web. Caveolae were abundant. Filaments were in the form of microfilaments and intermediate filaments. Cytoplasmic projections containing filaments were found on the basolateral surface of brush cells. In a single cell, axons containing vesicles and dense core granules were in close contact both with the basal and the lateral surface of the cell. The crypt brush cell appeared less mature. We concluded that human small intestine brush cells share a similar ultrastructural biology with those of other mammals. They are polarized and well-differentiated cells endowed with a distinctive cytoskeleton. The observation of nerve fibres closely associated with brush cells, never previously described in humans, lends support to the hypothesis of a receptor role for these cells