ALBERT

Description: Genes, Vol. 9, Pages 407: Seasonal and Sexual Differences in the Microbiota of the Hoopoe Uropygial Secretion Genes doi: 10.3390/genes9080407 Authors: Sonia M. Rodríguez-Ruano Manuel Martín-Vivaldi Juan M. Peralta-Sánchez Ana B. García-Martín Ángela Martínez-García Juan J. Soler Eva Valdivia Manuel Martínez-Bueno The uropygial gland of hoopoe nestlings and nesting females hosts bacterial symbionts that cause changes in the characteristics of its secretion, including an increase of its antimicrobial activity. These changes occur only in nesting individuals during the breeding season, possibly associated with the high infection risk experienced during the stay in the hole-nests. However, the knowledge on hoopoes uropygial gland microbial community dynamics is quite limited and based so far on culture-dependent and molecular fingerprinting studies. In this work, we sampled wild and captive hoopoes of different sex, age, and reproductive status, and studied their microbiota using quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH) and pyrosequencing. Surprisingly, we found a complex bacterial community in all individuals (including non-nesting ones) during the breeding season. Nevertheless, dark secretions from nesting hoopoes harbored significantly higher bacterial density than white secretions from breeding males and both sexes in winter. We hypothesize that bacterial proliferation may be host-regulated in phases of high infection risk (i.e., nesting). We also highlight the importance of specific antimicrobial-producing bacteria present only in dark secretions that may be key in this defensive symbiosis. Finally, we discuss the possible role of environmental conditions in shaping the uropygial microbiota, based on differences found between wild and captive hoopoes.

Description: Genes, Vol. 8, Pages 217: Alternative Splicing in Breast Cancer and the Potential Development of Therapeutic Tools Genes doi: 10.3390/genes8100217 Authors: Nancy Martínez-Montiel Maricruz Anaya-Ruiz Martín Pérez-Santos Rebeca Martínez-Contreras Alternative splicing is a key molecular mechanism now considered as a hallmark of cancer that has been associated with the expression of distinct isoforms during the onset and progression of the disease. The leading cause of cancer-related deaths in women worldwide is breast cancer, and even when the role of alternative splicing in this type of cancer has been established, the function of this mechanism in breast cancer biology is not completely decoded. In order to gain a comprehensive view of the role of alternative splicing in breast cancer biology and development, we summarize here recent findings regarding alternative splicing events that have been well documented for breast cancer evolution, considering its prognostic and therapeutic value. Moreover, we analyze how the response to endocrine and chemical therapies could be affected due to alternative splicing and differential expression of variant isoforms. With all this knowledge, it becomes clear that targeting alternative splicing represents an innovative approach for breast cancer therapeutics and the information derived from current studies could guide clinical decisions with a direct impact in the clinical advances for breast cancer patients nowadays.

Description: Genes, Vol. 8, Pages 307: The MXL-3/SBP-1 Axis Is Responsible for Glucose-Dependent Fat Accumulation in C. elegans Genes doi: 10.3390/genes8110307 Authors: Fanny Mejia-Martinez Berenice Franco-Juarez Elizabeth Moreno-Arriola Alain Hernández-Vázquez Marco Martinez-Avila Saul Gómez-Manzo Jaime Marcial-Quino Karla Carvajal Antonio Velazquez-Arellano Daniel Ortega-Cuellar Chronic exposure to elevated glucose levels leads to fatty acid accumulation, which promotes the development of metabolic diseases such as obesity and type 2 diabetes. MXL-3 is a conserved transcriptional factor that modulates the inhibition of lipolysis in Caenorhabditis elegans. However, the role of MXL-3 in lipid metabolism during nutrient excess remains unknown. We hypothesized that inhibition of MXL-3 prevents glucose-dependent fat accumulation. Nematodes from wild-type N2, MXL-3::GFP and sbp-1 or mxl-3 null strains were grown on standard, high glucose or high glucose plus metformin plates for 24 h. Using laser-scanning confocal microscopy, we monitored the glucose-induced activation of MXL-3 labeled with GFP (MXL-3::GFP). Lipid levels were determined by Oil Red O (ORO) staining and gas chromatography/mass spectrometry, and gene expression was assessed by qRT-PCR. We found that high glucose activated MXL-3 by increasing its rate of nuclear entry, which in turn increased lipid levels via sterol regulatory element-binding protein (SBP-1). This activated critical genes that synthesize long chain unsaturated fatty acids (MUFAs and PUFAs) and repress lipolytic genes. Interestingly, the anti-diabetic drug metformin inhibited MXL-3 activation and subsequently prevented glucose-dependent fat accumulation. These findings highlight the importance of the MXL-3/SBP-1 axis in the regulation of lipid metabolism during nutritional excess and provide new insight into the mechanism by which metformin prevents lipid accumulation. This study also suggests that inhibition of MXL-3 may serve as a potential target for the treatment of chronic metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disease.

Description: Studies on the experimental evolution of microorganisms, on their in vivo evolution (mainly in the case of bacteria producing chronic infections), as well as the availability of multiple full genomic sequences, are placing bacteria in the playground of evolutionary studies. In the present article we review the differential contribution to the evolution of bacterial genomes that processes such as gene modification, gene acquisition and gene loss may have when bacteria colonize different habitats that present characteristic ecological features. In particular, we review how the different processes contribute to evolution in microbial communities, in free-living bacteria or in bacteria living in isolation. In addition, we discuss the temporal constraints in the evolution of bacterial genomes, considering bacterial evolution from the perspective of processes of short-sighted evolution and punctual acquisition of evolutionary novelties followed by long stasis periods.

Description: Genes, Vol. 9, Pages 347: Possible Role of Envelope Components in the Extreme Copper Resistance of the Biomining Acidithiobacillus ferrooxidans Genes doi: 10.3390/genes9070347 Authors: Nia Oetiker Rodrigo Norambuena Cristóbal Martínez-Bussenius Claudio A. Navarro Fernando Amaya Sergio A. Álvarez Alberto Paradela Carlos A. Jerez Acidithiobacillus ferrooxidans resists extremely high concentrations of copper. Strain ATCC 53993 is much more resistant to the metal compared with strain ATCC 23270, possibly due to the presence of a genomic island in the former one. The global response of strain ATCC 53993 to copper was analyzed using iTRAQ (isobaric tag for relative and absolute quantitation) quantitative proteomics. Sixty-seven proteins changed their levels of synthesis in the presence of the metal. On addition of CusCBA efflux system proteins, increased levels of other envelope proteins, such as a putative periplasmic glucan biosynthesis protein (MdoG) involved in the osmoregulated synthesis of glucans and a putative antigen O polymerase (Wzy), were seen in the presence of copper. The expression of A. ferrooxidansmdoG or wzy genes in a copper sensitive Escherichia coli conferred it a higher metal resistance, suggesting the possible role of these components in copper resistance of A. ferrooxidans. Transcriptional levels of genes wzy, rfaE and wzz also increased in strain ATCC 23270 grown in the presence of copper, but not in strain ATCC 53993. Additionally, in the absence of this metal, lipopolysaccharide (LPS) amounts were 3-fold higher in A. ferrooxidans ATCC 53993 compared with strain 23270. Nevertheless, both strains grown in the presence of copper contained similar LPS quantities, suggesting that strain 23270 synthesizes higher amounts of LPS to resist the metal. On the other hand, several porins diminished their levels in the presence of copper. The data presented here point to an essential role for several envelope components in the extreme copper resistance by this industrially important acidophilic bacterium.

Description: Genes, Vol. 9, Pages 357: Genetic Targeting of GRP78 in the VMH Improves Obesity Independently of Food Intake Genes doi: 10.3390/genes9070357 Authors: Laura Liñares-Pose Eva Rial-Pensado Ánxela Estévez-Salguero Edward Milbank Ismael González-García Claudia Rodríguez Patricia Seoane-Collazo Noelia Martinez-Sánchez Rubén Nogueiras Dolores Prieto Carlos Diéguez Cristina Contreras Miguel López Recent data have demonstrated that the hypothalamic GRP78/BiP (glucose regulated protein 78 kDa/binding immunoglobulin protein) modulates brown adipose tissue (BAT) thermogenesis by acting downstream on AMP-activated protein kinase (AMPK). Herein, we aimed to investigate whether genetic over-expression of GRP78 in the ventromedial nucleus of the hypothalamus (VMH: a key site regulating thermogenesis) could ameliorate very high fat diet (vHFD)-induced obesity. Our data showed that stereotaxic treatment with adenoviruses harboring GRP78 in the VMH reduced hypothalamic endoplasmic reticulum ER stress and reversed vHFD-induced obesity. Herein, we also demonstrated that this body weight decrease was more likely associated with an increased BAT thermogenesis and browning of white adipose tissue (WAT) than to anorexia. Overall, these results indicate that the modulation of GRP78 in the VMH may be a target against obesity.

Description: Genes, Vol. 9, Pages 277: Size and Content of the Sex-Determining Region of the Y Chromosome in Dioecious Mercurialis annua, a Plant with Homomorphic Sex Chromosomes Genes doi: 10.3390/genes9060277 Authors: Paris Veltsos Guillaume Cossard Emmanuel Beaudoing Genséric Beydon Dessislava Savova Bianchi Camille Roux Santiago C. González-Martínez John R. Pannell Dioecious plants vary in whether their sex chromosomes are heteromorphic or homomorphic, but even homomorphic sex chromosomes may show divergence between homologues in the non-recombining, sex-determining region (SDR). Very little is known about the SDR of these species, which might represent particularly early stages of sex-chromosome evolution. Here, we assess the size and content of the SDR of the diploid dioecious herb Mercurialis annua, a species with homomorphic sex chromosomes and mild Y-chromosome degeneration. We used RNA sequencing (RNAseq) to identify new Y-linked markers for M. annua. Twelve of 24 transcripts showing male-specific expression in a previous experiment could be amplified by polymerase chain reaction (PCR) only from males, and are thus likely to be Y-linked. Analysis of genome-capture data from multiple populations of M. annua pointed to an additional six male-limited (and thus Y-linked) sequences. We used these markers to identify and sequence 17 sex-linked bacterial artificial chromosomes (BACs), which form 11 groups of non-overlapping sequences, covering a total sequence length of about 1.5 Mb. Content analysis of this region suggests that it is enriched for repeats, has low gene density, and contains few candidate sex-determining genes. The BACs map to a subset of the sex-linked region of the genetic map, which we estimate to be at least 14.5 Mb. This is substantially larger than estimates for other dioecious plants with homomorphic sex chromosomes, both in absolute terms and relative to their genome sizes. Our data provide a rare, high-resolution view of the homomorphic Y chromosome of a dioecious plant.

Description: Genes, Vol. 9, Pages 362: Dual RNA-Seq Analysis of Trichophyton rubrum and HaCat Keratinocyte Co-Culture Highlights Important Genes for Fungal-Host Interaction Genes doi: 10.3390/genes9070362 Authors: Monise Fazolin Petrucelli Kamila Peronni Pablo Rodrigo Sanches Tatiana Takahasi Komoto Josie Budag Matsuda Wilson Araújo da Silva Junior Rene Oliveira Beleboni Nilce Maria Martinez-Rossi Mozart Marins Ana Lúcia Fachin The dermatophyte Trichophyton rubrum is the major fungal pathogen of skin, hair, and nails that uses keratinized substrates as the primary nutrients during infection. Few strategies are available that permit a better understanding of the molecular mechanisms involved in the interaction of T. rubrum with the host because of the limitations of models mimicking this interaction. Dual RNA-seq is a powerful tool to unravel this complex interaction since it enables simultaneous evaluation of the transcriptome of two organisms. Using this technology in an in vitro model of co-culture, this study evaluated the transcriptional profile of genes involved in fungus-host interactions in 24 h. Our data demonstrated the induction of glyoxylate cycle genes, ERG6 and TERG_00916, which encodes a carboxylic acid transporter that may improve the assimilation of nutrients and fungal survival in the host. Furthermore, genes encoding keratinolytic proteases were also induced. In human keratinocytes (HaCat) cells, the SLC11A1, RNASE7, and CSF2 genes were induced and the products of these genes are known to have antimicrobial activity. In addition, the FLG and KRT1 genes involved in the epithelial barrier integrity were inhibited. This analysis showed the modulation of important genes involved in T. rubrum–host interaction, which could represent potential antifungal targets for the treatment of dermatophytoses.

Description: Genes, Vol. 9, Pages 381: Gut Microbiota of Great Spotted Cuckoo Nestlings is a Mixture of Those of Their Foster Magpie Siblings and of Cuckoo Adults Genes doi: 10.3390/genes9080381 Authors: Magdalena Ruiz-Rodríguez Manuel Martín-Vivaldi Manuel Martínez-Bueno Juan José Soler Diet and host genetic or evolutionary history are considered the two main factors determining gut microbiota of animals, although studies are scarce in natural populations. The system of great spotted cuckoos (Clamator glandarius) parasitizing magpies (Pica pica) is ideal to study both effects since magpie adults feed cuckoo and magpie nestlings with the same diet and, consequently, differences in gut microbiota of nestlings of these two species will mainly reflect the importance of genetic components. Moreover, the diet of adults and of nestling cuckoos drastically differ from each other and, thus, differences and similarities in their microbiotas would respectively reflect the effect of environmental and genetic factors. We used next-generation sequencing technologies to analyze the gut microbiota of cuckoo adults and nestlings and of magpie nestlings. The highest α-diversity estimates appeared in nestling cuckoos and the lowest in nestling magpies. Moreover, despite the greatest differences in the microbiome composition of magpies and cuckoos of both ages, cuckoo nestlings harbored a mixture of the Operational Taxonomic Units (OTUs) present in adult cuckoos and nestling magpies. We identified the bacterial taxa responsible for such results. These results suggest important phylogenetic components determining gut microbiome of nestlings, and that diet might be responsible for similarities between gut microbiome of cuckoo and magpie nestlings that allow cuckoos to digest food provided by magpie adults.

Description: The etiology and pathophysiology of type 1 diabetes remain largely elusive with no established concepts for a causal therapy. Efforts to clarify genetic susceptibility and screening for environmental factors have identified the vitamin D system as a contributory pathway that is potentially correctable. This review aims at compiling all genetic studies addressing the vitamin D system in type 1 diabetes. Herein, association studies with case control cohorts are presented as well as family investigations with transmission tests, meta-analyses and intervention trials. Additionally, rare examples of inborn errors of vitamin D metabolism manifesting with type 1 diabetes and their immune status are discussed. We find a majority of association studies confirming a predisposing role for vitamin D receptor (VDR) polymorphisms and those of the vitamin D metabolism, particularly the CYP27B1 gene encoding the main enzyme for vitamin D activation. Associations, however, are tenuous in relation to the ethnic background of the studied populations. Intervention trials identify the specific requirements of adequate vitamin D doses to achieve vitamin D sufficiency. Preliminary evidence suggests that doses may need to be individualized in order to achieve target effects due to pharmacogenomic variation.