Neuroscience: Seq-ing maps in the olfactory cortex.

Many cortical brain regions are spatially organized to optimize sensory representation. Such topographic maps have so far been elusive in the olfactory cortex. A high-throughput tracing study reveals that the neural circuits connecting olfactory regions are indeed topographically organized.

Spinal Inhibitory Interneuron Diversity Delineates Variant Motor Microcircuits.

Animals generate movement by engaging spinal circuits that direct precise sequences of muscle contraction, but the identity and organizational logic of local interneurons that lie at the core of these circuits remain unresolved. Here, we show that V1 interneurons, a major inhibitory population that controls motor output, fractionate into highly diverse subsets on the basis of the expression of 19 transcription factors. Transcriptionally defined V1 subsets exhibit distinct physiological signatures and highly structured spatial distributions with mediolateral and dorsoventral positional biases. These positional distinctions constrain patterns of input from sensory and motor neurons and, as such, suggest that interneuron position is a determinant of microcircuit organization. Moreover, V1 diversity indicates that different inhibitory microcircuits exist for motor pools controlling hip, ankle, and foot muscles, revealing a variable circuit architecture for interneurons that control limb movement.

Diet-induced obesity attenuates cytokine production following an immune challenge.

Obesity increases susceptibility for numerous diseases and neurological disorders including cardiovascular disease, metabolic syndrome, and dementia. One factor that may contribute to the increased risk for these conditions is the development of chronic inflammation. The current study evaluated whether diet-induced obesity (DIO) affects cognitive performance by increasing neuroinflammation and prolonging the behavioral and inflammatory response to an immune challenge. Adult male C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for 2 or 5 months. After consuming their respective diets for two months, sickness associated behaviors were assessed 4 and 24h after a lipopolysaccharide (LPS) or saline injection. In a separate experiment, DIO and control mice were tested for spatial learning in the water maze and challenged with LPS one month later. Peripheral cytokine production was assessed in adipose and spleen samples and the neuroinflammatory response was assessed in hippocampal, cortical, and brain samples. DIO impaired acquisition of a spatial learning task relative to control mice. However, these deficits are unlikely to be related to inflammation as DIO showed no changes in basal cytokine levels within the periphery or brain. Further, in response to LPS DIO mice showed comparable or attenuated levels of the proinflammatory cytokines interleukin-1ß and interleukin-6 relative to control mice. DIO also reduced hippocampal expression of brain-derived neurotrophic factor and the pre-synaptic marker synaptophysin. Presently, the data indicate that DIO suppresses aspects of the immune response and that cognitive deficits associated with DIO may be related to reduced neurotrophic support rather than inflammation.

The role of the neuropeptide somatostatin on methamphetamine and glutamate-induced neurotoxicity in the striatum of mice.

A large body of evidence shows that methamphetamine (METH) causes sustained damage to the brain in animal models and human METH users. In chronic users there are indications of cognitive and motor deficits. Striatal neuropeptides are in a position to modulate the neurochemical effects of METH and consequently striatal neural damage. Somatostatin (SST) is an intrinsic striatal neuropeptide that has been shown to inhibit glutamate transmission; glutamate is integral to METH toxicity and contributes to nitric oxide (NO) synthesis. We hypothesize that SST will protect from METH by inhibition of NO synthesis and thus reducing oxidative stress. To this end, the SST analogue octreotide (OCT) was microinjected into the striatum prior to a systemic injection of METH (30mg/kg). We then assessed 3-nitrotyrosine (3-NT), an indirect index of NO production, tyrosine hydroxylase (TH) protein levels (dopamine terminal marker) and Fluoro-Jade C positive cells (degenerating cells). The SST agonist OCT dose dependently attenuated the METH-induced accumulation of striatal 3-NT. Moreover, pretreatment with OCT effectively mitigated cell death but failed to protect dopamine terminals. Next we co-infused OCT and NMDA and measured 3-NT and Fluoro-Jade C staining. Treatment with OCT had no effect on these parameters. The data demonstrate that SST attenuates the METH-induced production of NO protecting the striatum from the METH-induced cell loss. However, SST failed to prevent the toxicity of the dopamine terminals suggesting that pre- and post-synaptic striatal damage occur via independent mechanisms.

Physiological and proteomic analysis of salinity tolerance in Puccinellia tenuiflora.

Soil salinity poses a serious threat to agriculture productivity throughout the world. Studying mechanisms of salinity tolerance in halophytic plants will provide valuable information for engineering plants for enhanced salt tolerance. Monocotyledonous Puccinellia tenuiflora is a halophytic species that widely distributed in the saline-alkali soil of the Songnen plain in northeastern China. Here we investigate the molecular mechanisms underlying moderate salt tolerance of P. tenuiflora using a combined physiological and proteomic approach. The changes in biomass, inorganic ion content, osmolytes, photosynthesis, defense-related enzyme activities, and metabolites in the course of salt treatment were analyzed in the leaves. Comparative proteomic analysis revealed 107 identities (representing 93 unique proteins) differentially expressed in P. tenuiflora leaves under saline conditions. These proteins were mainly involved in photosynthesis, stress and defense, carbohydrate and energy metabolism, protein metabolism, signaling, membrane, and transport. Our results showed that reduction of photosynthesis under salt treatment was attributed to the down-regulation of the light-harvesting complex (LHC) and Calvin cycle enzymes. Selective uptake of inorganic ions, high K(+)/Na(+) ratio, Ca(2+) concentration changes, and an accumulation of osmolytes contributed to ion balance and osmotic adjustment in leaf cells. Importantly, P. tenuiflora plants developed diverse reactive oxygen species (ROS) scavenging mechanisms in their leaves to cope with moderate salinity, including enhancement of the photorespiration pathway and thermal dissipation, synthesis of the low-molecular-weight antioxidant α-tocopherol, and an accumulation of compatible solutes. This study provides important information toward improving salt tolerance of cereals.

Exoproteome of Staphylococcus aureus reveals putative determinants of nasal carriage.

Due to the increasing prevalence of nosocomial and community-acquired antibiotic resistant Staphylococcus aureus (SA), understanding the determinants of SA nasal carriage has become a major imperative. Previous research has revealed many host and bacterial factors that contribute to SA nasal carriage. To assess bacterial factors that facilitate nasal carriage, we compared the exoproteome of a nasal carrier strain of SA to a genetically similar noncarrier strain. Additionally, the carrier strain biofilm exoproteome was also compared against its planktonic counterpart. Using high throughput proteomics, it was observed that the carrier strain of SA secretes a greater number of proteins that may promote successful colonization of the human nose, including cell attachment and immunoevasive proteins, than the noncarrier strain. Similarly, SA carrier strain biofilm exoproteome contains a greater number of immunoevasive proteins than its planktonic counterpart. Analysis of the most abundant immunoevasive proteins revealed that Staphylococcal protein A was present at significantly higher levels in carrier than in noncarrier strains of SA, suggesting an association with nasal carriage. While further analyses of specific differences between carrier and noncarrier strains of SA are required, many of the differentially expressed proteins identified can be considered to be putative determinants of nasal carriage.

Determination of steroidal estrogens in flushed dairy manure wastewater by gas chromatography-mass spectrometry.

There is a critical need to accurately measure the concentrations of natural steroidal estrogens in flushed dairy manure wastewater (FDMW) to assess any potential risk of waterway contamination resulting from land application. Estrogens are a concern because low concentrations (10-100 ng L-1) in water can adversely affect aquatic vertebrate species such as fish, turtles, and frogs by disrupting the normal function of their endocrine systems. The objective of this study was to develop a sample preparation method that permits the quantification of four natural steroidal estrogens (17alpha-estradiol, 17beta-estradiol, estrone, and estriol) in FDMW by gas chromatography-mass spectrometry (GC-MS). Solid-phase extraction with graphitized carbon black was used for the bulk extraction of estrogens from FDMW and additional sample purification was accomplished with C-18. The sample preparation method allowed estrogens to be detected accurately by GC-MS in FDMW. Spiked recovery experiments indicated that the method is satisfactory for measuring the estrogens of interest in FDMW with average recovery of >90%. As expected in FDMW, characterization of the estrogen profile revealed a large abundance of 17alpha-estradiol relative to 17beta-estradiol and estrone. Estriol was not detected in FDMW. The methodology developed in this research helps provide an analytical foundation for the quantification of steroidal estrogens in FDMW by GC-MS.