Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.     

Evidence for Inbreeding and Genetic Differentiation among Geographic Populations of the Saprophytic Mushroom Trogia venenata from Southwestern China

During the past 40 years, more than 400 Sudden Unexplained Deaths (SUDs) have occurred in Yunnan, southwestern China. Epidemiological and toxicological analyses suggested that a newly discovered mushroom called Trogia venenata was the leading culprit for SUDs. At present, relatively little is known about the genetics and natural history of this mushroom. In this study, we analyzed the sequence variation at four DNA fragments among 232 fruiting bodies of T. venenata collected from seven locations. Our ITS sequence analyses confirmed that all the isolates belonged to the same species. The widespread presence of sequence heterozygosity within many strains at each of three protein-coding genes suggested that the fruiting bodies were diploid, dikaryotic or heterokaryotic. Within individual geographic populations, we found significant deviations of genotype frequencies from Hardy-Weinberg expectations, with the overall observed heterozygosity lower than that expected under random mating, consistent with prevalent inbreeding within local populations. The geographic populations were overall genetically differentiated. Interestingly, while a positive correlation was found between population genetic distance and geographic distance, there was little correlation between genetic distance and barium concentration difference for the geographic populations. Our results suggest frequent inbreeding, geographic structuring, and limited gene flow among geographic populations of T. venenata from southwestern China.     

RNA‐seq analysis reveals new candidate genes for drip loss in a Pietrain × Duroc × Landrace × Yorkshire population

Drip loss, one of the most important meat quality traits, is characterized by low heritability. To date, the genetic factors affecting the drip loss trait have not been clearly elucidated. The objective of this study was to identify critical candidate genes affecting drip loss. First, we generated a Pietrain × Duroc × Landrace × Yorkshire commercial pig population and obtained phenotypic values for the drip loss trait. Furthermore, we constructed two RNA libraries from pooled samples of longissimus dorsi muscles with the highest (H group) and lowest (L group) drip loss and identified the differentially expressed genes (DEGs) between these extreme phenotypes using RNA‐seq technology. In total, 25 883 genes were detected in the H and L group libraries, and none was specifically expressed in only one library. Comparative analysis of gene expression levels found that 150 genes were differentially expressed, of which 127 were upregulated and 23 were downregulated in the H group relative to the L group. In addition, 68 drip loss quantitative trait loci (QTL) overlapping with 63 DEGs were identified, and these QTL were distributed mainly on chromosomes 1, 2, 5 and 6. Interestingly, the triadin (TRDN) gene, which is involved in muscle contraction and fat deposition, and the myostatin (MSTN) gene, which has a role in muscle growth, were localized to more than two drip loss QTL, suggesting that both are critical candidate genes responsible for drip loss.     

Structural Insight of a Trimodular Halophilic Cellulase with a Family 46 Carbohydrate-Binding Module

Cellulases are the key enzymes used in the biofuel industry. A typical cellulase contains a catalytic domain connected to a carbohydrate-binding module (CBM) through a flexible linker. Here we report the structure of an atypical trimodular cellulase which harbors a catalytic domain, a CBM46 domain and a rigid CBM_X domain between them. The catalytic domain shows the features of GH5 family, while the CBM46 domain has a sandwich-like structure. The catalytic domain and the CBM46 domain form an extended substrate binding cleft, within which several tryptophan residues are well exposed. Mutagenesis assays indicate that these residues are essential for the enzymatic activities. Gel affinity electrophoresis shows that these tryptophan residues are involved in the polysaccharide substrate binding. Also, electrostatic potential analysis indicates that almost the entire solvent accessible surface of CelB is negatively charged, which is consistent with the halophilic nature of this enzyme.     

Yield Responses of Wheat to Mulching Practices in Dryland Farming on the Loess Plateau

Improving farming practices of soil and water conservation has profound effects on the yield of wheat (Triticum aestivum L.) in dryland farming regions of the Loess Plateau in China. Mulching has proven to be an effective practice to increase crop yield, and possibly contribute to replenishing groundwater. This evaluation study collected and analyzed the data of 1849 observations published in 38 papers using meta-analysis to investigate effects of the mulching practices on wheat yield in terms of different rainfall and regions in comparison with conventional tillage. The main results of the study follow. The effects of the mulching practices were ranked in the order of RFM (ridge–furrow mulching) > MTMC (mulching with two materials combined) > MOM (mulching with other materials) > WSM (wheat straw mulching) > FM (flat mulching). The effects of the mulching practices at the different levels of rainfall during the wheat growing season were in the order: (< 150 mm) > (> 250 mm) > (150–250 mm). The effects of the mulching practices in the different regions were in the order of Henan > Shanxi > Shaanxi > Gansu. WSM, MTMC and FM performed better in improving wheat yield for rainfall of < 150, 150–250 and > 250 mm during the growing season, respectively. The wheat yield with FM, MTMC, MOM and MOM was higher than those with the other mulching practices in Shaanxi, Gansu, Henan and Shanxi. The wheat yield with RFM was 27.4% higher than that with FM, indicating that RFM was the most effective practice to improve wheat yield among all the practices. These findings have important implications for choosing appropriate crop field management to improve wheat yield.     

A Microarray-Based Analysis Reveals that a Short Photoperiod Promotes Hair Growth in the Arbas Cashmere Goat

Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding.