Role of the Fractalkine Receptor in CNS Autoimmune Inflammation: New Approach Utilizing a Mouse Model Expressing the Human CX3CR1

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During experimental autoimmune encephalomyelitis (EAE), CX3CR1 deficiency confers exacerbated disease defined by severe inflammation and neuronal loss. The CX3CR1 human polymorphism I249/M280 present in ∼20% of the population exhibits reduced adhesion for FKN conferring defective signaling whose role in microglia function and influence on neurons during MS remains unsolved. The aim of this study is to assess the effect of weaker signaling through hCX3CR1I249/M280 during EAE. We hypothesize that dysregulated microglial responses due to impaired CX3CR1 signaling enhance neuronal/axonal damage. We generated an animal model replacing the mouse CX3CR1 locus for the hCX3CR1I249/M280 variant. Upon EAE induction, these mice exhibited exacerbated EAE correlating with severe inflammation and neuronal loss. We also observed that mice with aberrant CX3CR1 signaling are unable to produce FKN and ciliary neurotrophic factor during EAE in contrast to wild type mice. Our results provide validation of defective function of the hCX3CR1I249/M280 variant and the foundation to broaden the understanding of microglia dysfunction during neuroinflammation. © 2018 Cardona et al

The SCUBA-2 Cosmology Legacy Survey: The EGS deep field -- III. The evolution of faint submillimeter galaxies at z<4z<4

We present a demographic analysis of the physical and morphological properties of $450/850~\mu\rm m$-selected galaxies from the deep observations of the SCUBA-2 Cosmology Legacy Survey in the Extended Groth Strip that are detected below the classical submillimeter-galaxy regime ($S_{850 \mu\rm m}\lesssim 6~\rm mJy$/beam) and compare them with a sample of optically-selected star-forming galaxies detected in the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey in the same field. We derive the evolution of the main sequence of star-forming galaxies, finding a steeper specific star formation rate versus stellar mass at $z>2.5$ than previous studies. Most faint submillimeter-galaxies fall within $3\sigma$ of the main sequence, but 40~per cent are classified as starbursts. Faint submillimeter galaxies have 50~per cent larger sizes at $2<z<3$ than optically-selected star-forming galaxies of the same mass range. This is also the redshift bin where we find the largest fraction of starbursts, and hence we could be witnessing merging processes, as confirmed by the preference for visual-morphology classifications of these systems as irregular disk galaxies and mergers. Both populations show an increment towards lower redshifts ($z<2$) of their concentration in $H$-band morphology, but faint submillimeter galaxies on average show larger concentration values at later times. These findings support the claim that faint submillimeter galaxies are mostly a population of massive dust-obscured disk-like galaxies that develop larger bulge components at later epochs. While the similarities are great, the median sizes, starburst numbers and $H$-band concentration of faint submillimeter galaxies differ from those of optically-selected star-forming galaxies of the same stellar mass.Comment: Accepted for publication in MNRA

A Facile High-Throughput Model of Surface-Independent Staphylococcus aureus Biofilms by Spontaneous Aggregation

Many microbes in their natural habitats are found in biofilm ecosystems attached to surfaces and not as free-floating (planktonic) organisms. Furthermore, it is estimated that nearly 80% of human infections are associated with biofilms. Biofilms are traditionally defined as three-dimensional, structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material. While this view of biofilm largely arises from in vitro studies under static or flow conditions, in vivo observations have indicated that this view of biofilms is essentially true only for foreign-body infections on catheters or implants where biofilms are attached to the biomaterial. In mucosal infections such as chronic wounds or cystic fibrosis or joint infections, biofilms can be found unattached to a surface and as three-dimensional aggregates. In this work, we describe a high-throughput model of aggregate biofilms of methicillin-resistant Staphylococcus aureus (MRSA) using 96-well plate hanging-drop technology. We show that MRSA forms surface-independent biofilms, distinct from surface-attached biofilms, that are rich in exopolymeric proteins, polysaccharides, and extracellular DNA (eDNA), express biofilm-related genes, and exhibit heightened antibiotic resistance. We also show that the surface-independent biofilms of clinical isolates of MRSA from cystic fibrosis and central catheter-related infections demonstrate morphological differences. Overall, our results show that biofilms can form by spontaneous aggregation without attachment to a surface, and this new in vitro system can model surface-independent biofilms that may more closely mimic the corresponding physiological niche during infection. IMPORTANCE The canonical model of biofilm formation begins with the attachment and growth of microbial cells on a surface. While these in vitro models reasonably mimic biofilms formed on foreign bodies such as catheters and implants, this is not the case for biofilms formed in cystic fibrosis and chronic wound infections, which appear to present as aggregates not attached to a surface. The hanging-drop model of biofilms of methicillin-resistant Staphylococcus aureus (MRSA), the major causative organism of skin and soft tissue infections, shows that these biofilms display morphological and antibiotic response patterns that are distinct from those of their surface-attached counterparts, and biofilm growth is consistent with their in vivo location. The simplicity and throughput of this model enable adoption to investigate other single or polymicrobial biofilms in a physiologically relevant setting

Role of the Fractalkine Receptor in CNS Autoimmune Inflammation: New Approach Utilizing a Mouse Model Expressing the Human CX3CR1I249/M280 Variant

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During experimental autoimmune encephalomyelitis (EAE), CX3CR1 deficiency confers exacerbated disease defined by severe inflammation and neuronal loss. The CX3CR1 human polymorphism I249/M280 present in ∼20% of the population exhibits reduced adhesion for FKN conferring defective signaling whose role in microglia function and influence on neurons during MS remains unsolved. The aim of this study is to assess the effect of weaker signaling through hCX3CR1I249/M280 during EAE. We hypothesize that dysregulated microglial responses due to impaired CX3CR1 signaling enhance neuronal/axonal damage. We generated an animal model replacing the mouse CX3CR1 locus for the hCX3CR1I249/M280 variant. Upon EAE induction, these mice exhibited exacerbated EAE correlating with severe inflammation and neuronal loss. We also observed that mice with aberrant CX3CR1 signaling are unable to produce FKN and ciliary neurotrophic factor during EAE in contrast to wild type mice. Our results provide validation of defective function of the hCX3CR1I249/M280 variant and the foundation to broaden the understanding of microglia dysfunction during neuroinflammation

Physically active men show better semen parameters than their sedentary counterparts

CITATION: Lalinde-Acevedo, P. C., et al. 2017. Physically active men show better semen parameters than their sedentary counterparts. International Journal of Fertility and Sterility, 11(3):156-165, doi:10.22074/ijfs.2017.4881.The original publication is available at http://ijfs.irBackground: The quality of semen depends upon several factors such as environment, life style, physical activity, age, and occupation. The aim of this study was to analyze and compare the conventional and functional semen parameters in men practicing vigorous physical activity to those of sedentary men. Materials and Methods: In this descriptive cross-sectional study, semen samples of 17 physically active men and 15 sedentary men were collected for analysis. Semen analysis was performed according to the World Health Organization (WHO) guidelines, while functional parameters were evaluated by flow cytometry. Results: Results showed that several semen parameters (semen volume, viability, progressive motility, total motility, normal morphology, and moribund cells) were superior in the physically active group in comparison with the sedentary group. Semen parameters such as viability, progressive motility and total motility, as well as the percentage of moribund spermatozoa were significantly different between both groups. However, sperm DNA damage, lipid peroxidation and mitochondrial potential were not significantly different among the groups. Conclusion: Nevertheless, the physical activity shows better semen parameters than sedentary group. Taken together, our results demonstrate that regular physical activity has beneficial impact in sperm fertility parameters and such a life style can enhance the fertility status of men.http://ijfs.ir/journal/article/abstract/4881Publisher's versio

Selección de tipos de tiempo en Canarias. Un ejemplo: las invasiones de aire sahariano

Ponencia presentada en: 1er Encuentro sobre Meteorología y Atmósfera de Canarias, celebrado en el Puerto de la Cruz, los días 12,13 y 14 de noviembre de 2003. El encuentro estuvo organizado por el Centro Meteorológico Territorial en Canarias Occidental, con la colaboración del Observatorio Atmosférico de Izaña y del Grupo de Física de la Atmósfera de la Facultad de Física (Universidad de La Laguna)Se presenta una propuesta de clasificación de tipos de tiempo por medio de técnicas de estadística inferencia/ combinadas con los análisis sinópticos tradicionales, con el fin de agrupar y seleccionar fechas de rasgos similares. Se muestra un ejemplo con uno de los tipos de tiempo más representativos del clima de Canarias: las invasiones de aire sahariano. Su aplicación permitirá estudiar, de manera relativamente simple, las tendencias en series temporales largas de estas situaciones desde que se cuenta con datos en las estaciones meteorológicas de las islas. Se contribuye así al estudio del clima del archipiélago y del cambio climático en esta región del planeta

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

STUDY OBJECTIVE: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. METHODS: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score >/=4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2x3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. RESULTS: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. CONCLUSION: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain

Algunas consideraciones sobre la importancia del polvo de origen sahariano en el clima del archipiélago canario y su aporte a las aguas superficiales oceánicas: el episodio de abril de 2002

Ponencia presentada en: III Congreso de la Asociación Española de Climatología “El agua y el clima”, celebrado en Palma de Mallorca del 16 al 19 de junio de 2002.[ES]El clima del archipiélago canario, por su cercanía al mayor desierto del planeta, sufre periódicamente advecciones de aire sahariano. El desplazamiento de estas masas de aire tropical continental da lugar al transporte de grandes cantidades de material particulado de origen litogénico, conocido como calima, que se deposita sobre la superficie insular y oceánica. En este trabajo tratamos de establecer las bases para su estudio, mostrando técnicas de selección y aparatos de medida a la vez que se expone un ejemplo de estas situaciones atmosféricas tan singulares del clima de esta región del planeta.[EN]The Canary Islands, being so close to the biggest desert on earth, stand periodical invasions of saharian winds. The sliding of these masses of continental-tropical air usually carries great quantities of particled material of a sandy structure, known as dust, which falls on the islands an their surrounding sea. On this work we try to fix the bases to study some selection techniques and measurement devices, showing at the sametime an example of these atmospheric situations, so singular on the climate of this region of the planet

Observation of two new Ξb−\Xi_b^- baryon resonances

Two structures are observed close to the kinematic threshold in the $\Xi_b^0 \pi^-$ mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb$^{-1}$ recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content $bds$ are expected in this mass region: the spin-parity $J^P = \frac{1}{2}^+$ and $J^P=\frac{3}{2}^+$ states, denoted $\Xi_b^{\prime -}$ and $\Xi_b^{*-}$. Interpreting the structures as these resonances, we measure the mass differences and the width of the heavier state to be $m(\Xi_b^{\prime -}) - m(\Xi_b^0) - m(\pi^{-}) = 3.653 \pm 0.018 \pm 0.006$ MeV$/c^2$, $m(\Xi_b^{*-}) - m(\Xi_b^0) - m(\pi^{-}) = 23.96 \pm 0.12 \pm 0.06$ MeV$/c^2$, $\Gamma(\Xi_b^{*-}) = 1.65 \pm 0.31 \pm 0.10$ MeV, where the first and second uncertainties are statistical and systematic, respectively. The width of the lighter state is consistent with zero, and we place an upper limit of $\Gamma(\Xi_b^{\prime -}) < 0.08$ MeV at 95% confidence level. Relative production rates of these states are also reported.Comment: 17 pages, 2 figure