Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Characterization of a Novel Fibroblast Growth Factor 10 (Fgf10) Knock-In Mouse Line to Target Mesenchymal Progenitors during Embryonic Development

Fibroblast growth factor 10 (Fgf10) is a key regulator of diverse organogenetic programs during mouse development, particularly branching morphogenesis. Fgf10-null mice suffer from lung and limb agenesis as well as cecal and colonic atresia and are thus not viable. To date, the Mlcv1v-nLacZ-24 transgenic mouse strain (referred to as Fgf10LacZ), which carries a LacZ insertion 114 kb upstream of exon 1 of Fgf10 gene, has been the only strain to allow transient lineage tracing of Fgf10-positive cells. Here, we describe a novel Fgf10Cre-ERT2 knock-in line (Fgf10iCre) in which a Cre-ERT2-IRES-YFP cassette has been introduced in frame with the ATG of exon 1 of Fgf10 gene. Our studies show that Cre-ERT2 insertion disrupts Fgf10 function. However, administration of tamoxifen to Fgf10iCre; Tomatoflox double transgenic embryos or adult mice results in specific labeling of Fgf10-positive cells, which can be lineage-traced temporally and spatially. Moreover, we show that the Fgf10iCre line can be used for conditional gene inactivation in an inducible fashion during early developmental stages. We also provide evidence that transcription factors located in the first intron of Fgf10 gene are critical for maintaining Fgf10 expression over time. Thus, the Fgf10iCre line should serve as a powerful tool to explore the functions of Fgf10 in a controlled and stage-specific manner

Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent rats

Item does not contain fulltextRATIONALE: Serotonin is an important modulator of social behaviour. Individual differences in serotonergic signalling are considered to be a marker of personality that is stable throughout lifetime. While a large body of evidence indicates that central serotonin levels are inversely related to aggression and sexual behaviour in adult rats, the relationship between serotonin and social behaviour during peri-adolescence has hardly been explored. OBJECTIVE: To study the effect of acute and constitutive increases in serotonin neurotransmission on social behaviour in peri-adolescent rats. MATERIALS AND METHODS: Social behaviour in peri-adolesent rats (28-35 days old) was studied after genetic ablation of the serotonin transporter, causing constitutively increased extra-neuronal serotonin levels, and after acute treatment with the serotonin reuptake inhibitor fluoxetine or the serotonin releasing agent 3,4-methylenedioxymethamphetamine (MDMA). A distinction was made between social play behaviour that mainly occurs during peri-adolescence, and non-playful social interactions that are abundant during the entire lifespan of rats. RESULTS: In serotonin transporter knockout rats, social play behaviour was markedly reduced, while non-playful aspects of social interaction were unaffected. Acute treatment with fluoxetine or MDMA dose-dependently inhibited social play behaviour. MDMA also suppressed non-playful social interaction but at higher doses than those required to reduce social play. Fluoxetine did not affect non-playful social interaction. CONCLUSIONS: These data show that both acute and constitutive increases in serotonergic neurotransmission reduce social play behaviour in peri-adolescent rats. Together with our previous findings of reduced aggressive and sexual behaviour in adult serotonin transporter knockout rats, these data support the notion that serotonin modulates social behaviour in a trait-like manner

Demonstration of Protein-Based Human Identification Using the Hair Shaft Proteome

YesHuman identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 single nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects’ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European–American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). This study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts.The Technology Commercialization Innovation Program (Contracts #121668, #132043) of the Utah Governors Office of Commercial Development, the Scholarship Activitie

Patterns of infant handling and relatedness in Barbary macaques (Macaca sylvanus) on Gibraltar

Among papionin primates, the Barbary macaque (Macaca sylvanus) shows the most extensive interactions between infants and group members other than the mother. Two different types of interactions occur: (1) long-lasting dyadic interactions between a handler and an infant, and (2) brief triadic interactions between two handlers involving an infant. Previous investigations showed that infant handling by males is best explained as use of infants to manage relationships with other males. In contrast, no adaptive explanation for infant handling by females emerged. Here, we compared the infant-handling pattern between subadult/adult males and subadult/adult females in a free-ranging group of 46 Barbary macaques on Gibraltar to test whether the relationship management hypothesis also applies to female handlers. We further investigated the infant-handling pattern of juveniles and used microsatellite markers to estimate relatedness between infant handlers and the infant’s mother. We found that males, females and juveniles all participated extensively in triadic interactions using infants of above-average related females. In contrast, only males and juveniles were highly involved in dyadic interactions with infants of related females, while females rarely handled infants otherthan their own. The pattern of infant handling was entirely compatible with the predictions of the relationship management hypothesis for males and mostly so for females. Moreover, our genetic analysis revealed that males and females differ in their partner choice: while females preferred to interact with related females, males had no significant preference to interact with related males. We further discuss the observed above-average relatedness values between infant handlers and the infant’s mother in the light of kin-selection theory

From Mendel’s discovery on pea to today’s plant genetics and breeding

In 2015, we celebrated the 150th anniversary of the presentation of the seminal work of Gregor Johann Mendel. While Darwin’s theory of evolution was based on differential survival and differential reproductive success, Mendel’s theory of heredity relies on equality and stability throughout all stages of the life cycle. Darwin’s concepts were continuous variation and “soft” heredity; Mendel espoused discontinuous variation and “hard” heredity. Thus, the combination of Mendelian genetics with Darwin’s theory of natural selection was the process that resulted in the modern synthesis of evolutionary biology. Although biology, genetics, and genomics have been revolutionized in recent years, modern genetics will forever rely on simple principles founded on pea breeding using seven single gene characters. Purposeful use of mutants to study gene function is one of the essential tools of modern genetics. Today, over 100 plant species genomes have been sequenced. Mapping populations and their use in segregation of molecular markers and marker–trait association to map and isolate genes, were developed on the basis of Mendel's work. Genome-wide or genomic selection is a recent approach for the development of improved breeding lines. The analysis of complex traits has been enhanced by high-throughput phenotyping and developments in statistical and modeling methods for the analysis of phenotypic data. Introgression of novel alleles from landraces and wild relatives widens genetic diversity and improves traits; transgenic methodologies allow for the introduction of novel genes from diverse sources, and gene editing approaches offer possibilities to manipulate gene in a precise manner