R-parity as a residual gauge symmetry : probing a theory of cosmological dark matter

We present a non-supersymmetric scenario in which the R-parity symmetry $R_P = (-1)^{3(B-L)+2s}$ arises as a result of spontaneous gauge symmetry breaking, leading to a viable Dirac fermion WIMP dark matter candidate. Direct detection in nuclear recoil experiments probes dark matter masses around $2-5$ TeV for $M_{Z^{\prime}} \sim 3-4$ TeV consistent with searches at the LHC, while lepton flavor violation rates and flavor changing neutral currents in neutral meson systems lie within reach of upcoming experiments.Comment: 7 pages, 3 figure

RAB3A Regulates Melanin Exocytosis and Transfer Induced by Keratinocyte-Conditioned Medium

Funding: We would like to thank our group for the critical reading of the manuscript and the NMS microscopy and cell culture facilities, as well as José Belo’s group, for the kind gift of mouse embryonic fibroblasts. This study was supported by Fundação para a Ciência e a Tecnologia (Portugal) through grant PTDC/BIA-CEL/29765/2017 and PhD fellowships to LCC, MVN, LBL and AF (2020.08812.BD, PD/BD/137442/2018, SFRH/BD/131938/2017 and PD/BD/ 135506/2018, respectively). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, cofinanced by Fundação para a Cieˆncia e a Tecnologia (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund). This article was supported by the LYSOCIL project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 811087. This work was also supported by iNOVA4Health e UIDB/04462/2020 and UIDP/04462/2020 and by the Associated Laboratory LS4FUTURE (LA/P/0087/2020), two programs financially supported by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (Portugal).Skin pigmentation is imparted by melanin and is crucial for photoprotection against UVR. Melanin is synthesized and packaged into melanosomes within melanocytes and is then transferred to keratinocytes (KCs). Although the molecular players involved in melanogenesis have been extensively studied, those underlying melanin transfer remain unclear. Previously, our group proposed that coupled exocytosis/phagocytosis is the predominant mechanism of melanin transfer in human skin and showed an essential role for RAB11B and the exocyst tethering complex in this process. In this study, we show that soluble factors present in KC-conditioned medium stimulate melanin exocytosis from melanocytes and transfer to KCs. Moreover, we found that these factors are released by differentiated KCs but not by basal layer KCs. Furthermore, we found that RAB3A regulates melanin exocytosis and transfer stimulated by KC-conditioned medium. Indeed, KC-conditioned medium enhances the recruitment of RAB3A to melanosomes in melanocyte dendrites. Therefore, our results suggest the existence of two distinct routes of melanin exocytosis: a basal route controlled by RAB11B and a RAB3A-dependent route, stimulated by KC-conditioned medium. Thus, this study provides evidence that soluble factors released by differentiated KCs control skin pigmentation by promoting the accumulation of RAB3A-positive melanosomes in melanocyte dendrites and their release and subsequent transfer to KCs.publishersversionpublishe

Melanin transferred to keratinocytes resides in non-degradative endocytic compartments

Funding: We thank the staff from the Unit of Imaging and Cytometry of the Instituto Gulbenkian de Ciência for assistance in microscopy and flow cytometry protocol adjustments, the CEDOC Microscopy Facility for assistance in image acquisition and analysis, Dot Bennett for the kind gift of cell lines, and Alistair Hume for the kind gift of anti-Rab5 antibody. This project was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal (PTDC/BIA-BCM/ 111735/2009, EXPL/BEX-BCM/0379/2013), MSC and HM were supported by FCT PhD studentships (SFRH/BD/65381/2009 and PD/BD/114118/2015, respectively), FJCP was supported by an FCT postdoctoral fellowship (SFRH/ BPD/70337/2010), and DCB was supported by the FCT Investigator Program (IF/00501/2014/CP1252/CT0001).Melanin transfer from melanocytes to keratinocytes and subsequent accumulation in the supra-nuclear region is a critical process in skin pigmentation and protection against ultraviolet radiation. We have previously proposed that the main mode of transfer between melanocytes and keratinocytes is through exo/endocytosis of the melanosome core, termed melanocore. In this study, we developed an in vitro uptake assay using melanocores secreted by melanocytes. We show that the uptake of melanocores, but not melanosomes, by keratinocytes is Protease-activated receptor (PAR)-2-dependent. Furthermore, we found that the silencing of the early endocytic regulator Rab5b, but not the late endocytic regulators Rab7a or Rab9a, significantly impairs melanocore uptake by keratinocytes. Following uptake, we observed that melanin accumulates in compartments that are positive for both early and late endocytic markers. We found that melanin does not localize to either highly degradative or acidic organelles, as assessed by LysoTracker and DQ-BSA staining, despite the abundance of these types of organelles within keratinocytes. Therefore, we propose that melanocore uptake leads to storage of melanin within keratinocytes in hybrid endocytic compartments that are not highly acidic or degradative. By avoiding lysosomal degradation, these specialized endosomes may allow melanin to persist within keratinocytes for long periods.publishersversionpublishe

Effect of stocking density and use of environmental enrichment materials on the welfare and the performance of pigs in the growth and finishing phases

Aim of study: To evaluate the effects of stocking density and the use of environmental enrichment (EE) objects on the welfare and the performance of pigs in the growing and finishing phases.Area of study: The southern region of Brazil.Material and methods: A total of 240 pigs, 120 immunocastrated males and 120 females, with an initial weight of 22.38 ± 2.38 kg and mean age of 65 days, were submitted to two stocking densities conditions (0.85 and 1.28 m²pig) with and without EE for 117 days. The experimental design was a 2×2×2 factorial (two categories, two densities, and two EE conditions), with six replicates. Performance variables and behavior were evaluated.Main results: For stocking density, there was a significant difference in the finishing phase from 148 to 161 days of age for the final weight (FW), average daily weight gain (ADWG), and feed conversion rate (FCR). For the EE factor, there was no difference in any of the phases or in the overall period. In the overall period, the higher availability of space improved the results of FW (140.56 kg vs 136.63 kg), ADWG (1.005 kg vs 0.974 kg), and FCR (2.05 vs 2.10). There was no effect of EE, stocking densities, or their interaction on the frequency of different behaviors of the pigs in the growth and finishing phases.Research highlights: There was no effect of interactions between enriched environments, stocking densities, and sex for animal performance and behavioral frequencies; however, differences between the factors were observed separately. The higher availability of space improved the results of FW, ADWG, and FCR

Structural and Luminescence Properties of Silica-Based Hybrids Containing New Silylated-Diketonato Europium(III) Complex

A new betadiketonate ligand displaying a trimethoxysilyl group as grafting function and a diketone moiety as complexing site (TTA-Si = 4,4,4-trifluoro-2-(3-trimethoxysilyl)propyl)-1-3-butanedione (C4H3S)COCH[(CH2)3Si(OCH3)3]COCF3) and its highly luminescent europium(III) complex [Eu(TTA-Si)3] have been synthesized and fully characterized. Luminescent silica-based hybrids have been prepared as well with this new complex grafted on the surface of dense silica nanoparticles (28 (+/-3 nm) or on mesoporous silica particles. The covalent bonding of Eu(TTA-Si)3 inside the core of uniform silica nanoparticles (40 (+/- 5 nm) was also achieved. Luminescence properties are discussed in relation to the europium chemical environment involved in each of the three hybrids. The general methodology proposed allowed high grafting ratios and overcame chelate release and tendency to agglomeration, and it could be applied to any silica matrix (in the core or at the surface, nanosized or not, dense or mesoporous) and therefore numerous applications such as luminescent markers and luminophors could be foreseen

The karst site of Las Palomas (Guadalteba County, Málaga, Spain): A preliminary study of its MiddleeLate Pleistocene archaeopaleontological record

Cleaning works in the cave of Las Palomas in Teba (Málaga, Spain), developed by the Guadalteba Consortium, have provided a number of lithic tools and knapping products that may be ascribed to the Mode III technotypological tradition as well as remains of a number of large mammal species typical of MiddleeLate Pleistocene times. Topographic measurements help to place this ancient cave within a karst landform. This discovery opens up new perspectives in the research on the Neanderthal groups that inhabited the valleys of Guadalteba and Turón rivers in the middle basin of the Guadalhorce River, and thus in the southern region of the Iberian Peninsula

Combined Raman spectroscopic and Rietveld analyses as a useful and nondestructive approach to studying flint raw materials at prehistoric archaeological sites

Artículo sobre análisis de espectroscopía

Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment

Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-β, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-β, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.publishersversionpublishe

Search for heavy stable charged particles in pp collisions at ?s = 7 TeV

The result of a search at the LHC for heavy stable charged particles produced in pp collisions at s?=7TeV is described. The data sample was collected with the CMS detector and corresponds to an integrated luminosity of 3.1 pb?1. Momentum and ionization-energy-loss measurements in the inner tracker detector are used to identify tracks compatible with heavy slow-moving particles. Additionally, tracks passing muon identification requirements are also analyzed for the same signature. In each case, no candidate passes the selection, with an expected background of less than 0.1 events. A lower limit at the 95% confidence level on the mass of a stable gluino is set at 398GeV/c 2, using a conventional model of nuclear interactions that allows charged hadrons containing this particle to reach the muon detectors. A lower limit of 311 GeV/c 2 is also set for a stable gluino in a conservative scenario of complete charge suppression, where any hadron containing this particle becomes neutral before reaching the muon detectors.We are grateful to Anna Kulesza and Michael Krämer for providing the theoretical production cross sections and associated uncertainties at next-to-leading order for pair production of eg and ˜t1. We wish to congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC machine. We thank the technical and administrative staff at CERN and other CMS institutes, and acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Search for a heavy bottom-like quark in pp collisions at √s=7 TeV.

A search for pair-produced bottom-like quarks in pp collisions at √s = 7 TeV is conducted with the CMS experiment at the LHC. The decay b’→tW is considered in this search. The b’b ̅→tW−.t ̅W+ process can be identified by the distinctive signature of trileptons and same-sign dileptons. With a data sample corresponding to an integrated luminosity of 34 pb−1, no excess above the standard model background predictions is observed and a b_ quark with a mass between 255 and 361 GeV/c2 is excluded at the 95% confidence level.We wish to congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC machine. We thank the technical and administrative staff at CERN and other CMS institutes, and acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLPFAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)