Corticotropin-releasing hormone (CRH) is centrally involved in coordinating responses to a variety of stress-associated stimuli. Recent clinical data implicate CRH in the pathophysiology of human affective disorders. To differentiate the CNS pathways involving CRH and CRH receptor 1 (Crhr1) that modulate behavior from those that regulate neuroendocrine function, we generated a conditional knockout mouse line (Crhr1(loxP/loxP)Camk2a-cre) in which Crhr1 function is inactivated postnatally in anterior forebrain and limbic brain structures, but not in the pituitary. This leaves the hypothalamic-pituitary-adrenocortical (HPA) system intact. Crhr1(loxP/loxP)Camk2a-cre mutants showed reduced anxiety, and the basal activity of their HPA system was normal. In contrast to Crhr1 null mutants, conditional mutants were hypersensitive to stress corticotropin and corticosterone levels remained significantly elevated after stress. Our data clearly show that limbic Crhr1 modulates anxiety-related behavior and that this effect is independent of HPA system function. Furthermore, we provide evidence for a new role of limbic Crhr1 in neuroendocrine adaptation to stress.

Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type 1 (TH1) responses, or IL-4, which induces TH2 cells and susceptibility. Paradoxically, we show here that when present during the initial activation of dendritic cells (DCs) by infectious agents, IL-4 instructed DCs to produce IL-12 and promote TH1 development. This TH1 response established resistance to Leishmania major in susceptible BALB/c mice. When present later, during the period of T cell priming, IL-4 induced TH2 differentiation and progressive leishmaniasis in resistant mice. Because immune responses developed via the consecutive activation of DCs and then T cells, the contrasting effects of IL-4 on DC development and T cell differentiation led to immune responses that had opposing functional phenotypes.

The sexual dimorphic position of the gonads in mammals is dependent on differential development of two ligaments, the cranial suspensory ligament (CSL) and the gubernaculum. During male embryogenesis, outgrowth of the gubernaculum and regression of the CSL result in transabdominal descent of the testes, whereas in the female, development of the CSL in conjunction with failure of the gubernaculum development holds the ovaries in a position lateral to the kidneys. Several lines of evidence suggest that regression of the CSL and induction of gubernaculum development are mediated by testosterone and a yet unidentified testicular factor, respectively. The Insl3 gene (originally designated Ley I-L), a member of the insulin-like superfamily, is specifically expressed in Leydig cells of the fetal and postnatal testis and in theca cells of the postnatal ovary. Here we show that male mice homozygous for a targeted deletion of the Insl3 locus exhibit bilateral cryptorchidism with free moving testes and genital ducts. These malformations are due to failure of gubernaculum development during embryogenesis. In double-mutant male mice for Insl3 and androgen receptor genes, testes are positioned adjacent to the kidneys and steadied in the abdomen by the CSL. These findings demonstrate, that the Insl3 induces gubernaculum development in an androgen-independent way, while androgen-mediated regression of the CSL occurs independently from Insl3.

Soil compaction is a major disturbance associated with logging, but we lack a fundamental understanding of how this affects the soil microbiome. We assessed the structural resistance and resilience of the microbiome using a high-throughput pyrosequencing approach in differently compacted soils at two forest sites and correlated these findings with changes in soil physical properties and functions. Alterations in soil porosity after compaction strongly limited the air and water conductivity. Compaction significantly reduced abundance, increased diversity, and persistently altered the structure of the microbiota. Fungi were less resistant and resilient than bacteria; clayey soils were less resistant and resilient than sandy soils. The strongest effects were observed in soils with unfavorable moisture conditions, where air and water conductivities dropped well below 10% of their initial value. Maximum impact was observed around 6-12 months after compaction, and microbial communities showed resilience in lightly but not in severely compacted soils 4 years post disturbance. Bacteria capable of anaerobic respiration, including sulfate, sulfur, and metal reducers of the Proteobacteria and Firmicutes, were significantly associated with compacted soils. Compaction detrimentally affected ectomycorrhizal species, whereas saprobic and parasitic fungi proportionally increased in compacted soils. Structural shifts in the microbiota were accompanied by significant changes in soil processes, resulting in reduced carbon dioxide, and increased methane and nitrous oxide emissions from compacted soils. This study demonstrates that physical soil disturbance during logging induces profound and long-lasting changes in the soil microbiome and associated soil functions, raising awareness regarding sustainable management of economically driven logging operations.