Resistance to the Bacteriocin Lcn972 Deciphered by Genome Sequencing.

In view of the current threat of antibiotic resistance, new antimicrobials with low risk of resistance development are demanded. Lcn972 is a lactococcal bacteriocin that inhibits septum formation by binding to the cell wall precursor lipid II in Lactococcus. It has a species-specific spectrum of activity, making Lcn972 an attractive template to develop or improve existing antibiotics. The aim of this work was to identify mutations present in the Lcn972-resistant clone Lactococcus cremoris D1-20, previously evolved from the sensitive strain L. cremoris MG1614. Whole-genome sequencing and comparison over the reference genome L. cremoris MG1363 identified several unexpected mutations in the parental strain MG1614, likely selected during in-house propagation. In the Lcn972R clone, two previously identified mutations were mapped and confirmed. Additionally, another transposition event deregulating cellobiose uptake was identified along with three point mutations of unknown consequences for Lcn972 resistance. Two new independent evolution experiments exposing L. cremoris MG1614 to Lcn972 revealed transposition of IS981 into the LLMG_RS12285 locus as the predominant mutation selected by Lcn972. This event occurs early during evolution and was found in 100% of the evolved clones, while other mutations were not selected. Therefore, activation of LLMG_RS12285 coding for a putative anti-ECF (extra-cytoplasmic function) sigma factor is regarded as the main Lcn972 resistance factor in L. cremoris MG1614.

Estenosis gastroduodenal: una complicación infrecuente del carcinoma gástrico de células en anillo de sello / Upper gastrointestinal stenosis: a rare complication of gastric-signet ring cell carcinoma / Estenose gastroduodenal: uma complicação rara do carcinoma gástrico de células em anel de sinete

El carcinoma de células en anillo de sello es una variante histopatológica de cáncer gástrico que se encuentra en aumento, se caracteriza por un mal pronóstico. Se presenta el caso de un hombre joven al que se le hizo este diagnóstico en el contexto de una complicación rara como es el síndrome de estenosis gastroduodenal.

Signet ring cell carcinoma is a histopathological variant of gastric cancer that is increasing and is characterized by a poor prognosis. We present the case of a young man who underwent this diagnosis in the context of a rare complication such as upper gastrointestinal stenosis syndrome.

O carcinoma de células em anel de sinete é uma variante histopatológica do câncer gástrico que está aumentando e é caracterizado por um mau prognóstico. É apresentado o caso de um jovem que recebeu este diagnóstico no contexto de uma complicação rara como a síndrome de estenose gastroduodenal.

Colored Surfaces Made of Synthetic Eumelanin.

The polymerization of 3,4-dihydroxy-L-phenylalanine leads to a carboxylic acid-rich synthetic melanin-like material (poly-L-DOPA). Synthetic melanin most resembles natural eumelanin in chemical structure. However, its deposition on surfaces leading to colored surfaces by interference is not as easy to accomplish as in the case of the preparation of colored surfaces by dopamine hydrochloride polymerization. This study deals with the preparation of new colored surfaces made from poly-L-DOPA displaying vivid colors by interference. These surfaces were obtained by depositing thin films of poly-L-DOPA on a reflective silicon nitride substrate. A high ionic strength in the polymerization medium was essential to accomplish the coating. The effect of ionic strength on the resulting surfaces was studied via reflectance, Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). The refractive index was determined by ellipsometry, and was nearly constant to 1.8 when λ > 650 nm. In the visible spectral region, the imaginary part of the refractive index becomes relevant. The refractive index in the visible wavelength range (400-600 nm) was in the range 1.7-1.80.

Evaluación del tratamiento con infiltraciones intraarticulares en la patología osteoarticular del hombro en atención primaria / Evaluation of treatment with intra-articular injections in osteoarticular pathology of the shoulder in primary care

Objetivo principal: Evaluar la respuesta clínica a las 24semanas de la infiltración, medida como alivio del dolor y recuperación funcional, en el síndrome de hombro doloroso (SHD) en atención primaria (AP). Diseño: Serie de casos longitudinal con tratamiento de inyección en la articulación escapulohumeral; se describen la funcionalidad y la evolución del dolor previa y a las 24semanas postinfiltración. Emplazamiento: Atención Primaria. Centro de salud no urbano. Participantes: Pacientes con patología osteoarticular de hombro susceptible de infiltración, fracaso de tratamiento farmacológico y calificación en la escala analógica visual (EVA) ≥4 o Constant Score (CS) ≤70. Intervenciones: Inyección intraarticular corticosteroide y anestésico local en la articulación escapulohumeral, describiendo su evolución a 1, 4, 12 y 24semanas postinfiltración. Mediciones principales: Respuesta de la infiltración según EVA antes-después, CS antes-después, número de infiltraciones, efectos secundarios, incapacidad laboral transitoria (ILT). Resultados: Se infiltraron 66 pacientes, edad media 51,1años (DE: 14,7), 57,6% mujeres, 63,3% infiltración hombro derecho. El 22,7% precisaron ILT y cursaron alta con una mediana de 14días (rango de 7-56días). Precisaron una infiltración (80,3%) y la patología infiltrada más frecuente fue la tendinitis de los rotadores (90,9%). Sufrieron efectos secundarios leves un 9,4%. Encontramos disminución de dolor de severo a leve y una mejoría funcional de pobre a buena. Las variables: ser jubilado (OR: 37,82, p=0,001) y tener un puntaje EVA previo a la infiltración >8 (OR; 15,67, p=0,055, cuasi significativo) se asociaron a mala respuesta. Conclusiones: La administración intraarticular de corticosteroides en el SHD disminuye el dolor y aporta una mejoría funcional tras la primera semana postinfiltración, manteniéndose a largo plazo.(AU)

Main objective: To evaluate the clinical response at 24weeks after injection, measured as pain relief and functional recovery, in painful shoulder syndrome (PSS) in primary care (PC). Design: Longitudinal case series with injection treatment in the scapulohumeral joint, describing functionality and pain evolution before and at 24weeks post injection. Location: Non-urban primary care centres. Participants: Patients with osteoarticular shoulder pathology susceptible to injection, failure of pharmacological treatment and rating on the visual analogue scale (VAS) ≥4 or constant score (CS) ≤70. Interventions: Intra-articular injection of corticosteroid and local anaesthetic into the scapulohumeral joint, describing its evolution at 1, 4, 12 and 24weeks post injection. Main measurements: Infiltration response according to EVA before and after, CS before and after, number of infiltrations, side effects, temporary inability to work (TIL). Results: Sixty-six patients receiving injection, mean age 51.1years (SD 14.7), 57.6% were women and 63.3% were injection in the right shoulder. A 22.7% required TIL and were discharged with a median of 14days (range 7-56days). They required an injection (80.3%) and the most frequent injection pathology was rotator cuff tendinitis (90.9%). They suffered mild side effects (9.4%). We found a decrease in pain from severe to mild and a functional improvement from poor to good. The variables: being retired (OR: 37.82, P=.001) and having an EVA score prior to injection >8 (OR: 15.67, P=.055, almost significant) were associated with poor response. Conclusions: Intra-articular administration of corticosteroids in PSS reduces pain and provides functional improvement after the first week after injection, and is maintained in the long term. This allows a quick recovery to work after an injection at two weeks reducing recovery time by 50%, with few side effects.

[Evaluation of treatment with intra-articular injections in osteoarticular pathology of the shoulder in primary care]. / Evaluación del tratamiento con infiltraciones intraarticulares en la patología osteoarticular del hombro en atención primaria.

MAIN OBJECTIVE: To evaluate the clinical response at 24weeks after injection, measured as pain relief and functional recovery, in painful shoulder syndrome (PSS) in primary care (PC). DESIGN: Longitudinal case series with injection treatment in the scapulohumeral joint, describing functionality and pain evolution before and at 24weeks post injection. LOCATION: Non-urban primary care centres. PARTICIPANTS: Patients with osteoarticular shoulder pathology susceptible to injection, failure of pharmacological treatment and rating on the visual analogue scale (VAS) ≥4 or constant score (CS) ≤70. INTERVENTIONS: Intra-articular injection of corticosteroid and local anaesthetic into the scapulohumeral joint, describing its evolution at 1, 4, 12 and 24weeks post injection. MAIN MEASUREMENTS: Infiltration response according to EVA before and after, CS before and after, number of infiltrations, side effects, temporary inability to work (TIL). RESULTS: Sixty-six patients receiving injection, mean age 51.1years (SD 14.7), 57.6% were women and 63.3% were injection in the right shoulder. A 22.7% required TIL and were discharged with a median of 14days (range 7-56days). They required an injection (80.3%) and the most frequent injection pathology was rotator cuff tendinitis (90.9%). They suffered mild side effects (9.4%). We found a decrease in pain from severe to mild and a functional improvement from poor to good. The variables: being retired (OR: 37.82, P=.001) and having an EVA score prior to injection >8 (OR: 15.67, P=.055, almost significant) were associated with poor response. CONCLUSIONS: Intra-articular administration of corticosteroids in PSS reduces pain and provides functional improvement after the first week after injection, and is maintained in the long term. This allows a quick recovery to work after an injection at two weeks reducing recovery time by 50%, with few side effects.

Mutations Selected After Exposure to Bacteriocin Lcn972 Activate a Bce-Like Bacitracin Resistance Module in Lactococcus lactis.

Resistance against antimicrobial peptides (AMPs) is often mediated by detoxification modules that rely on sensing the AMP through a BceAB-like ATP-binding cassette (ABC) transporter that subsequently activates a cognate two-component system (TCS) to mount the cell response. Here, the Lactococcus lactis ABC transporter YsaDCB is shown to constitute, together with TCS-G, a detoxification module that protects L. lactis against bacitracin and the bacteriocin Lcn972, both AMPs that inhibit cell wall biosynthesis. Initially, increased expression of ysaDCB was detected by RT-qPCR in three L. lactis resistant to Lcn972, two of which were also resistant to bacitracin. These mutants shared, among others, single-point mutations in ysaB coding for the putative Bce-like permease. These results led us to investigate the function of YsaDCB ABC-transporter and study the impact of these mutations. Expression in trans of ysaDCB in L. lactis NZ9000, a strain that lacks a functional detoxification module, enhanced resistance to both AMPs, demonstrating its role as a resistance factor in L. lactis. When the three different ysaB alleles from the mutants were expressed, all of them outperformed the wild-type transporter in resistance against Lcn972 but not against bacitracin, suggesting a distinct mode of protection against each AMP. Moreover, P ysaD promoter fusions, designed to measure the activation of the detoxification module, revealed that the ysaB mutations unlock transcriptional control by TCS-G, resulting in constitutive expression of the ysaDCB operon. Finally, deletion of ysaD was also performed to get an insight into the function of this gene. ysaD encodes a secreted peptide and is part of the ysaDCB operon. YsaD appears to modulate signal relay between the ABC transporter and TCS-G, based on the different response of the P ysaD promoter fusions when it is not present. Altogether, the results underscore the unique features of this lactococcal detoxification module that warrant further research to advance in our overall understanding of these important resistance factors in bacteria.

Trastornos musculoesqueléticos en los técnicos de laboratorio / Musculoskeletal Problems in Laboratory Technicians

OBJETIVO: analizar la prevalencia de síntomas musculoesqueléticos de origen laboral en los técnicos de laboratorio y su relación con los factores personales y organizacionales, así como con la falta de formación específica en riesgos ergonómicos. METODOLOGÍA: se aplica a una muestra de 460 técnicos de laboratorio, el Cuestionario Nórdico Estandarizado de Kuorinka validado en población española y una encuesta de caracterización de la muestra que contempla tanto variables personales como aspectos organizativo. Para realizar el análisis estadístico se aplicó el programa R. RESULTADOS: el 84.5% de la muestra estudiada presenta dolencias musculares, con mayor porcentaje en mujeres, siendo el cuello la parte más afectada. La probabilidad de sufrir molestias se multiplica por ocho en personas mayores de 46 años y las variables que se asociaron significativamente fueron: el sexo, el nivel de educación, la formación específica en riesgos ergonómicos y la antigüedad en el puesto de trabajo. Las principales causas asociadas fueron: posturas forzadas y movimientos repetitivos debido a tareas realizadas en campana, al deficiente diseño de alturas de planos de trabajo, al uso de micropipeta, microscopio, microtomo y ordenador. CONCLUSIONES: existe un elevado riesgo de padecer problemas músculoesqueléticos relacionados con la actividad de técnico de laboratorio. Se requieren medidas de intervención en el entorno de trabajo bajo criterios ergonómicos y se hace imprescindible implementar planes de formación de riesgos específicos, acordes a las actividades desarrolladas por estos profesionales

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A low-mass planet candidate orbiting Proxima Centauri at a distance of 1.5 AU.

Our nearest neighbor, Proxima Centauri, hosts a temperate terrestrial planet. We detected in radial velocities evidence of a possible second planet with minimum mass m c sin i c = 5.8 ± 1.9M ⊕ and orbital period P c = 5.21 - 0.22 + 0.26 years. The analysis of photometric data and spectro-scopic activity diagnostics does not explain the signal in terms of a stellar activity cycle, but follow-up is required in the coming years for confirming its planetary origin. We show that the existence of the planet can be ascertained, and its true mass can be determined with high accuracy, by combining Gaia astrometry and radial velocities. Proxima c could become a prime target for follow-up and characterization with next-generation direct imaging instrumentation due to the large maximum angular separation of ~1 arc second from the parent star. The candidate planet represents a challenge for the models of super-Earth formation and evolution.

Intervención grupal desde un enfoque sensoriomotriz para reducir la intensidad del dolor crónico / Group intervention from a sensorimotor approach to reduce the intensity of chronic pain

Objetivo: Determinar la eficacia de una intervención (Time In) para reducir el dolor y mejorar los síntomas psicológicos en personas con dolor crónico. Diseño: Ensayo clínico aleatorizado con grupo control y con 3 mediciones realizadas a lo largo de 3 meses. Emplazamiento: Granada. Participantes: Un total de 40 mujeres mayores de 18 años con una historia de dolor crónico (más de 6 meses de duración). La captación fue en la Asociación de Fibromialgia de Granada (AGRAFIM). Intervenciones: Time In es un trabajo sensoriomotriz que combina procedimientos biomecánicos fisioterapéuticos y estrategias psicológicas. Se planificó una sesión semanal de 3h de duración y el total del programa se desarrolló durante 5 semanas seguidas. Mediciones principals: Variables dependientes: puntuaciones de las escalas Brief Pain Inventory (BPI-S), Short-Form Health Survey (SF-12), Symptom Check List-90-R (SCL-90-R) y Clinical Outcome in Routine Evaluation (CORE-OM). Variables independientes: información sociodemográfica, historial clínico y grupo de intervención o control. Resultados: Se observaron diferencias significativas entre grupo control y grupo intervención de gran parte de las escalas utilizadas en las mediciones postintervención y seguimiento. Así pues, se obtuvieron puntuaciones medias significativamente inferiores en la intensidad, interferencia y zonas de dolor, calidad de vida, síntomas psicológicos y cambio de comportamiento. Se observaron resultados similares en las puntuaciones de d Cohen "muy importantes" en la intensidad del dolor (d = -1,01, d = -0,97) y la interferencia del dolor (d = -0,85, d = 0,74), con un porcentaje de mejoría del 21 al 30%. Conclusiones. La intervención Time In reduce el dolor y mejora los síntomas psicológicos en pacientes con fibromialgia, lo que redunda en una mejor calidad de vida

Objective: To assess the effectiveness, on people with chronic pain, of an intervention (Time In) designed to reduce pain and to improve psychological symptoms. Design: A randomized clinical trial with a control group, taking three measurements over three months. Setting: Granada, Spain. Participants: A sample of 40 women aged 18 or older with a history (over 6 months) of chronic pain. The recruitment was in the Fibromyalgia Association of Granada, Spain (AGRAFIM). Interventions: Time In is a sensorimotor intervention that combines biomechanical physiotherapeutic procedures and psychological strategies. A weekly session of 3h was planned and the total of the program was developed during five weeks. Main measurements: Independent variables: sociodemographic information, clinical history and Time In intervention. Dependent variables: Brief Pain Inventory (BPI-S), Short-Form Health Survey (SF-12), Symptom Check List-90-R (SCL-90-R) and Clinical Outcome in Routine Evaluation (CORE-OM). Results: Significant differences were observed between control group and intervention group of most of the scales used in postintervention and follow up measurements. Thus, significantly lower mean scores were obtained in intensity, interference and areas of pain, quality of life, psychological symptoms and behavioural change. Similar results were observed on d Cohen scores. They were 'very important' on intensity of pain (d = -1.01, d = -0.97) and interference of pain (d = -0.85, d = -0.74), with an improvement percentage from 21% to 30%. Conclusions: Time In intervention reduces pain and improves psychological symptoms in patients with fibromyalgia; this results in a better quality of life

[Group intervention from a sensorimotor approach to reduce the intensity of chronic pain]. / Intervención grupal desde un enfoque sensoriomotriz para reducir la intensidad del dolor crónico.

OBJECTIVE: To assess the effectiveness, on people with chronic pain, of an intervention (Time In) designed to reduce pain and to improve psychological symptoms. DESIGN: A randomized clinical trial with a control group, taking three measurements over three months. SETTING: Granada, Spain. PARTICIPANTS: A sample of 40 women aged 18 or older with a history (over 6 months) of chronic pain. The recruitment was in the Fibromyalgia Association of Granada, Spain (AGRAFIM). INTERVENTIONS: Time In is a sensorimotor intervention that combines biomechanical physiotherapeutic procedures and psychological strategies. A weekly session of 3h was planned and the total of the program was developed during five weeks. MAIN MEASUREMENTS: Independent variables: sociodemographic information, clinical history and Time In intervention. Dependent variables: Brief Pain Inventory (BPI-S), Short-Form Health Survey (SF-12), Symptom Check List-90-R (SCL-90-R) and Clinical Outcome in Routine Evaluation (CORE-OM). RESULTS: Significant differences were observed between control group and intervention group of most of the scales used in postintervention and follow up measurements. Thus, significantly lower mean scores were obtained in intensity, interference and areas of pain, quality of life, psychological symptoms and behavioural change. Similar results were observed on d Cohen scores. They were 'very important' on intensity of pain (d=-1.01, d=-0.97) and interference of pain (d=-0.85, d=-0.74), with an improvement percentage from 21% to 30%. CONCLUSIONS: Time In intervention reduces pain and improves psychological symptoms in patients with fibromyalgia; this results in a better quality of life.

Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school-aged children with obesity/overweight and with normal weight.

OBJECTIVES: Genetic variation of the fat mass and obesity associated gene (FTO) has been identified as a risk factor for obesity and obesity traits. Distribution of FTO single nutleotide polymorphisms (SNPs) rs1421085T>C, rs9939609T>A, rs8057044G>A and copy number variation (CNV) was evaluated in association with childhood obesity or overweight status in children with Mayan ethnicity. METHODS: We included 318 school-aged children with obesity or overweight status (body mass index [BMI]: >85th percentile) and 303 children with normal weight (BMI: 15th-85th percentile). Genotyping was performed using real-time polymerase chain reaction (RT-PCR) with TaqMan probes. The cross-sectional study was carried out using univariate and multivariate logistic regression models adjusted for gender. RESULTS: FTO-SNP rs1421085 showed significant differences between children with obesity and children with normal weight for the heterozygous genotype (P = 0.003) and for allele frequencies (P = 0.023). Adjusting by gender, significant differences were found in frequencies of the hetezygous genotype of SNPs rs9939609 (P = 0.023) and rs1421085 (P = 0.003) as well as in allele frequencies (P = 0.042 and P = 0.013, respectively) between girls with obesity and girls without obesity. In contrast, SNP rs8057044 was significantly different only between heterozygous overweight versus normal weight boys (P = 0.035) and for the allele frequency of rs8057044 (P = 0.021). The mean relative CNV was significantly higher in male overweight children than in boys with normal weight (P = 0.000). CONCLUSIONS: The FTO SNP rs1421085 is a genetic factor associated with obesity in Mayan school-aged children. FTO SNPs rs1421085 and rs9939609 affect genetic susceptibility for obesity only in girls, whereas, SNP rs8057044 and CNV are associated with overweight status only in boys.

Acquisition of analgesic properties by the cholecystokinin (CCK)/CCK2 receptor system within the amygdala in a persistent inflammatory pain condition.

Pain is associated with negative emotions such as anxiety, but the underlying neurocircuitry and modulators of the association of pain and anxiety remain unclear. The neuropeptide cholecystokinin (CCK) has both pronociceptive and anxiogenic properties, so we explored the role of CCK in anxiety and nociception in the central amygdala (CeA), a key area in control of emotions and descending pain pathways. Local infusion of CCK into the CeA of control rats increased anxiety, as measured in the light-dark box test, but had no effect on mechanical sensitivity. By contrast, intra-CeA CCK infusion 4 days after Complete Freund's Adjuvant (CFA) injection into the hindpaw resulted in analgesia, but also in loss of its anxiogenic capacity. Inflammatory conditions induced changes in the CeA CCK signaling system with an increase of CCK immunoreactivity and a decrease in CCK1, but not CCK2, receptor mRNA. In CFA rats, patch-clamp experiments revealed that CCK infusion increased CeA neuron excitability. It also partially blocked the discharge of wide dynamic range neurons in the dorsal spinal cord. These effects of CCK on CeA and spinal neurons in CFA rats were mimicked by the specific CCK2 receptor agonist, gastrin. This analgesic effect was likely mediated by identified CeA neurons projecting to the periaqueductal gray matter that express CCK receptors. Together, our data demonstrate that intra-CeA CCK infusion activated a descending CCK2 receptor-dependent pathway that inhibited spinal neuron discharge. Thus, persistent pain induces a functional switch to a newly identified analgesic capacity of CCK in the amygdala, indicating central emotion-related circuit controls pain transmission in spinal cord.

Adaptive Evolution of Industrial Lactococcus lactis Under Cell Envelope Stress Provides Phenotypic Diversity.

Lactococcus lactis is widely used as a starter in the manufacture of cheese and fermented milk. Its main role is the production of lactic acid, but also contributes to the sensory attributes of cheese. Unfortunately, the diversity of suitable strains to be commercialized as dairy starters is limited. In this work, we have applied adaptive evolution under cell envelope stress (AE-CES) as means to provide evolved L. lactis strains with distinct physiological and metabolic traits. A total of seven strains, three of industrial origin and four wild nisin Z-producing L. lactis, were exposed to subinhibitory concentrations of Lcn972, a bacteriocin that triggers the cell envelope stress response in L. lactis. Stable Lcn972 resistant (Lcn972R) mutants were obtained from all of them and two mutants per strain were further characterized. Minimal inhibitory Lcn972 concentrations increased from 4- to 32-fold compared to their parental strains and the Lcn972R mutants retained similar growth parameters in broth. All the mutants acidified milk to a pH below 5.3 with the exception of one that lost the lactose plasmid during adaptation and was unable to grow in milk, and two others with slower acidification rates in milk. While in general phage susceptibility was unaltered, six mutants derived from three nisin Z producers became more sensitive to phage attack. Loss of a putative plasmid-encoded anti-phage mechanism appeared to be the reason for phage susceptibility. Otherwise, nisin production in milk was not compromised. Different inter- and intra-strain-dependent phenotypes were observed encompassing changes in cell surface hydrophobicity and in their autolytic profile with Lcn972R mutants being, generally, less autolytic. Resistance to other antimicrobials revealed cross-protection mainly to cell wall-active antimicrobials such as lysozyme, bacitracin, and vancomycin. Finally, distinct and shared non-synonymous mutations were detected in the draft genome of the Lcn972R mutants. Depending on the parental strain, mutations were found in genes involved in stress response, detoxification modules, cell envelope biogenesis and/or nucleotide metabolism. As a whole, the results emphasize the different strategies by which each strain becomes resistant to Lcn972 and supports the feasibility of AE-CES as a novel platform to introduce diversity within industrial L. lactis dairy starters.

Small RNA-Seq reveals novel miRNAs shaping the transcriptomic identity of rat brain structures.

In the central nervous system (CNS), miRNAs are involved in key functions, such as neurogenesis and synaptic plasticity. Moreover, they are essential to define specific transcriptomes in tissues and cells. However, few studies were performed to determine the miRNome of the different structures of the rat CNS, although a major model in neuroscience. Here, we determined by small RNA-Seq, the miRNome of the olfactory bulb, the hippocampus, the cortex, the striatum, and the spinal cord and showed the expression of 365 known miRNAs and 90 novel miRNAs. Differential expression analysis showed that several miRNAs were specifically enriched/depleted in these CNS structures. Transcriptome analysis by mRNA-Seq and correlation based on miRNA target predictions suggest that the specifically enriched/depleted miRNAs have a strong impact on the transcriptomic identity of the CNS structures. Altogether, these results suggest the critical role played by these enriched/depleted miRNAs, in particular the novel miRNAs, in the functional identities of CNS structures.

Resistance to bacteriocin Lcn972 improves oxygen tolerance of Lactococcus lactis IPLA947 without compromising its performance as a dairy starter.

BACKGROUND: Lactococcus lactis is the main component of the mesophilic starters used in cheese manufacture. The success of milk fermentation relies on the viability and metabolic activity of the starter bacteria. Therefore, robust strains able to withstand the harsh conditions encountered during cheese manufacture and starter production are demanded. In this work, we have applied adaptive evolution under cell envelope stress imposed by the cell wall active bacteriocin Lcn972 to evolve strains with more robust phenotypes. RESULTS: Consecutive exposure of the starter strain L. lactis IPLA947 to Lcn972 yielded a stable mutant, L. lactis R5, with enhanced survival when challenged with hydrogen peroxide. L. lactis R5 exhibited faster growth rates in aerobic fermentations in broth and was able to acidify milk to a lower pH in aerated milk cultures. The improved behavior of L. lactis R5 in the presence of oxygen did not translate into a better performance in the presence of heme (i.e. respiration metabolism) or into higher survival during storage at cold temperatures or after freeze-drying compared to the wild type L. lactis IPLA947. L. lactis R5 retained the same milk acidification rate and no changes in the consumption of lactose and production of organic acids were noticed. However, the profile of volatile compounds revealed a significant increase in 3-hydroxy-2-butanone (acetoin) in curds manufactured with L. lactis R5. CONCLUSIONS: Based on our results, L. lactis R5 can be proposed as a suitable dairy starter with improved survival under oxidative stress and enhanced metabolic traits. The results support the notion that adaptive evolution under cell envelope stress might be useful to generate strain diversity within industrial L. lactis strains.

Oxaliplatin treatment impairs extension of sensory neuron neurites in vitro through miR-204 overexpression.

Oxaliplatin is a platinum-based drug used in the treatment of gastric cancers. Oxaliplatin treatment induces sensory neuropathy characterized by cold hypersensibility in the acute phase and sensory impairment when the neuropathy becomes chronic. In order to determine the effect of oxaliplatin on sensory neurons, we used an in vitro model in which oxaliplatin treatment reduced arborization of dorsal root ganglia neurons in a dose-dependent manner. Moreover, we characterized the role of microRNAs in oxaliplatin induced-neuropathy. In particular, we focused on microRNAs that control the expression of axon guidance molecules, and therefore, regulate neurite arborization. As a result, we highlighted the upregulation of miR-204, a microRNA that controls the expression of PlexinA2, a semaphorin receptor involved in neurite guidance. Interaction of miR-204 and Plexin A2 was confirmed by luciferase assay. In addition, overexpression of miR-204 in dorsal root ganglia neuron cultures reduced length and extension of neurites and also reduced Plexin A2 labelling without increasing apoptosis rate. On the other hand, sequestration of miR-204 by a specific microRNA sponge increases neurite length and PlexinA2 expression. Taken together, our data indicate that oxaliplatin impairs sensory neurons arborization through up-regulation of miR-204 that decreases PlexinA2 expression and neurite length.

Immunomodulation of mesenchymal stem cells in discogenic pain.

BACKGROUND CONTEXT: Back pain is a highly prevalent health problem in the world today and has a great economic impact on health-care budgets. Intervertebral disc (IVD) degeneration has been identified as a main cause of back pain. Inflammatory cytokines produced by macrophages or disc cells in an inflammatory environment play an important role in painful progressive degeneration of IVD. Mesenchymal stem cells (MSCs) have shown to have immunosuppressive and anti-inflammatory properties. Mesenchymal stem cells express a variety of chemokines and cytokines receptors having tropism to inflammation sites. PURPOSE: This study aimed to develop an in vitro controlled and standardized model of inflammation and degeneration of IVD with rat cells and to evaluate the protective and immunomodulatory effect of conditioned medium (CM) from the culture of MSCs to improve the conditions presented in herniated disc and discogenic pain processes. STUDY DESIGN: This is an experimental study. METHODS: In this study, an in vitro model of inflammation and degeneration of IVD has been developed, as well as the effectiveness of CM from the culture of MSCs. RESULTS: Conditioned medium from MSCs downregulated the expression of various proinflammatory cytokines produced in the pathogenesis of discogenic pain such as interleukin (IL)-1ß, IL-6, IL-17, and tumor necrosis factor (TNF). CONCLUSION: Mesenchymal stem cells represent a promising alternative strategy in the treatment of IVD degeneration inasmuch as there is currently no treatment which leads to a complete remission of long-term pain in the absence of drugs.