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Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders caused by various genetic and environmental factors that result in synaptic abnormalities. ASD development is suggested to involve microglia, which have a role in synaptic refinement during development. Autophagy and related pathways are also suggested to be involved in ASDs. However, the precise roles of microglial autophagy in synapses and ASDs are unknown. Here, we show that microglial autophagy is involved in synaptic refinement and neurobehavior regulation. We found that deletion of atg7, which is vital for autophagy, from myeloid cell-specific lysozyme M-Cre mice resulted in social behavioral defects and repetitive behaviors, characteristic features of ASDs. These mice also had increases in dendritic spines and synaptic markers and altered connectivity between brain regions, indicating defects in synaptic refinement. Synaptosome degradation was impaired in atg7-deficient microglia and immature dendritic filopodia were increased in neurons co-cultured with atg7-deficient microglia. To our knowledge, our results are the first to show the role of microglial autophagy in the regulation of the synapse and neurobehaviors. We anticipate our results to be a starting point for more comprehensive studies of microglial autophagy in ASDs and the development of putative therapeutics.

Study design:Retrospective study.Objectives:The objective of this study was to find out whether ossification of posterior longitudinal ligament (OPLL) characteristics, including size, shape and subtype, can be used to diagnose myelopathy using somatosensory evoked potential (SEP) in cervical OPLL patients.Setting:Yonsei University College of Medicine, Seoul, Korea.Methods:We retrospectively reviewed the medical records of 153 cervical OPLL patients who underwent SEP study. OPLL anterior–posterior (AP) diameter, area and involved longitudinal vertebral level were measured. OPLL was classified into subtypes according to longitudinal continuity and shape. Correlation analysis and receiver operating curve were used.Results:Tibial SEP latency was significantly correlated with OPLL AP diameter (P=0.001), diameter occupying ratio (P=0.019), area (P=0.007), area occupying ratio (P=0.008), involved longitudinal vertebral level (P=0.028) and space available for the spinal cord (P=0.019). The cutoff values that were diagnostic for SEP prolongation suggesting myelopathy were 4.91 mm for OPLL AP diameter, 6.02 mm for space available for the spinal cord, 44.5% for diameter occupying ratio, 63.4 mm2for area, 36.1% for area occupying ratio and level 2 for the involved longitudinal vertebral level.Conclusions:Our results revealed that tibial SEP latency was significantly correlated with OPLL size and suggested cutoff values of OPLL diameter (4.91 mm, 44.5%) and area (63.4 mm2, 36.1%) for early diagnosis of myelopathy. These results can help to establish treatment plans.

A freeze–gel casting method has been proposed to fabricate porous mullite–alumina composite with controlled ‘designer’ pore structure and improved compressive strength. In this work, a tertiary butyl alcohol–coal fly ash slurry system with appropriate addition of Al2O3was used. Unidirectional aligned macropore channels were developed by controlling the solidification direction of the tertiary butyl alcohol solvent. Simultaneously, microsized pores formed in the walls of the pore channels; consequently, the inner section of the walls of the pore channels exhibited a more porous structure than the outer walls. The compressive strength of the sintered porous composite increased as the porosity decreased, i.e. the low porosity gave a high compressive strength. After sintering at 1500°C with 40 wt-% solid loading, the mullite–alumina composite with a porosity of 61·2% exhibited a compressive strength of ∼64·3 MPa.

Four experiments were conducted to determine the effects of dietary supplementation of corn distillers dried grain with solubles (DDGS) diets with mannanase on performance, apparent total tract digestibility (ATTD) of energy and nutrients, blood metabolites, and carcass characteristics of grower-finisher pigs. In Exp. 1, 96 grower pigs (initial BW, 57.6 kg), 6 pigs per pen and 4 pens per treatment, were fed corn-soybean meal-based diets containing 10% DDGS and 0, 200, 400, or 600 units (U) of mannanase/kg. The ADG and blood glucose increased (linear, P< 0.05) with increasing concentrations of dietary mannanase. Pigs fed diets containing increasing levels of mannanase had improved ATTD of DM and CP (quadratic, P< 0.05). In Exp. 2, 64 finisher pigs (initial BW, 92.7 kg) were allotted to 4 treatment groups with 4 pigs per pen and 4 pens per treatment. Pigs were fed corn-soybean meal-based diets containing 15% DDGS and 0, 200, 400, or 600 U of mannanase/kg. Linear increases (P< 0.05) in ADG, blood glucose, and ATTD of DM, GE, and CP were observed with increasing levels of dietary mannanase supplementation. In Exp. 3, 208 grower pigs (initial BW, 60.5 kg) were allotted to 4 treatment groups with 13 pigs per pen and 4 pens per treatment. Pigs were fed diets containing 0 or 10% DDGS and 0 or 400 U of mannanase/kg in a 2 × 2 factorial arrangement. An increase (P< 0.05) in ADG and blood glucose for pigs fed diets containing mannanase was observed. The ATTD of DM and CP (P< 0.05) was decreased with the inclusion of DDGS, whereas pigs fed the mannanase-supplemented diets had an increased (P< 0.05) ATTD of CP. In Exp. 4, 208 finisher pigs (initial BW, 86.5 kg), with 13 pigs per pen and 4 pens per treatment, were fed diets containing 0 or 15% DDGS and 0 or 400 U of mannanase/kg in a 2 × 2 factorial arrangement. The ADG and blood glucose increased (P< 0.05) when mannanase was included in the diets. The ATTD of DM (P< 0.05), GE (P< 0.10), and CP (P< 0.05) increased by the supplementation with mannanase in the diets of finisher pigs. The carcass characteristics and meat quality were not affected by the DDGS or mannanase inclusion. These results indicated that including 10 and 15% DDGS in conventional swine grower and finisher diets had no detrimental effects on growth performance or carcass characteristics. In addition, supplementation with 400 U of mannanase/kg to diets containing 10 and 15% DDGS fed to grower and finisher pigs may improve growth performance and the ATTD of CP.

The cost of genetic testing and the limited knowledge about the BRCA1and BRCA2genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1or BRCA2genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia. A total of 187 breast cancer patients with either early-onset breast cancer (at age ≤ 40 years) or a personal and/or family history of breast or ovarian cancer were comprehensively tested by full sequencing of both BRCA1and BRCA2. Two algorithms to predict the presence of mutations, the Manchester Scoring System and BOADICEA, were evaluated. Twenty-seven deleterious mutations were detected (14 in BRCA1and 13 in BRCA2), only one of which was found in two unrelated individuals (BRCA2490 delCT). In addition, 47 variants of uncertain clinical significance were identified (16 in BRCA1and 31 in BRCA2). Notably, many mutations are novel (13 of the 30 BRCA1mutations and 24 of the 44 BRCA2). We report that while there were an equal proportion of BRCA1and BRCA2mutations in the Chinese population in our study, there were significantly more BRCA2mutations among the Malays. In addition, we show that the predictive power of the BOADICEA risk-prediction model and the Manchester Scoring System was significantly better for BRCA1than BRCA2, but that the overall sensitivity, specificity and positive-predictive value was lower in this population than has been previously reported in Caucasian populations. Our study underscores the need for larger collaborative studies among non-Caucasian populations to validate the role of genetic testing and the use of risk-prediction models in ensuring that the other populations in the world may also benefit from the genomics and genetics era.

A total of 280 weaned pigs (Landrace × Yorkshire × Duroc) were used in a 28-d growth study to investigate the effect of feeding different levels of potato proteins on growth performance, nutrient digestibility, immune response, small intestinal morphology, and bacterial populations in feces and large intestine. Pigs (initially 6.42 ± 0.74 kg of BW and 23 ± 3 d of age) were randomly allotted to 5 treatments on the basis of BW, each treatment composed of 4 pens, each pen having 14 pigs. Dietary treatments included positive control (PC; basal diet + 150 mg/kg apramycin and 10 mg/ kg colistin sulfate); and potato protein (PP), consisting of the basal diet with 0, 0.25, 0.50, or 0.75% of potato protein. Diets were fed in 2 phases: phase I (d 0 to 14 postweaning) and phase 2 (d 14 to 28 postweaning). Potato protein was extracted from a value-added type of the new potato variety, Solanum tuberosumL. cv. Gogu valley, and was shown to have a minimum inhibitory concentration of 300 to 500 μg/mL. Performance of PC was compared with 0.25 to 0.75% PP, whereas linear and quadratic trends of increasing PP (0 to 0.75% PP) were tested. Over the 28-d trial, pigs fed the PC diets showed improved overall ADG (P< 0.05) and G:F (P= 0.090) compared with pigs fed PP, whereas increasing levels of PP linearly improved ADG (P< 0.05), ADFI (P= 0.052), and G:F (P= 0.098). The digestibility of DM and CP in both the phases was greater in PC than PP, and feeding of PP linearly improved the DM digestibility (P< 0.05) in phase II. The bacterial populations in the feces of pigs fed PC and PP were comparable, except for total bacteria and coliform bacteria in the feces at d 14 and 28, which were decreased in PC; and feeding of PP was effective in linearly reducing the populations of microbes in feces and contents of cecum, colon, and rectum. There was linear increase (P< 0.10) in skin-fold thickness in response to phytohemagglutinin with an increase in PP levels. Haemagglutinin titers on d 21 were greater (P= 0.054) in PC, and at d 28 the haemagglutinin titers were quadratically affected in pigs fed PP (P= 0.070). There was a trend toward a decrease in crypt depth (P= 0.068) and a greater villus height:crypt depth ratio (P= 0.082) of ileum in PC compared with PP. These results suggest that PP may be an alternative to medicated feed with antibiotics because it showed antimicrobial activity by effectively reducing the population of coliform bacteria and also improved the performance of weanling pigs.

We have identified a UDP-glucose-binding site within human UDP-glucose dehydrogenase (hUGDH) by photoaffinity labeling with a specific probe, [³²P]5N3UDP-glucose, and cassette mutagenesis using a synthetic hUGDH gene. Photolabel-containing peptides were generated by photolysis followed by tryptic digestion and isolated using the phosphopeptide isolation kit. Photolabeling of these peptides was effectively prevented by the presence of UDP-glucose during photolysis, demonstrating a selectivity of the photoprobe for the UDP-glucose-binding site. Amino acid sequencing and compositional analysis identified the UDP-glucose-binding site of hUGDH as the region containing the sequence, ASVGFGGSXFQK, corresponding to A268−K279 of the amino acid sequence of hUGDH. The unidentified residue, X, can be designated as a photolabeled C276 because the sequences including the cysteine residue in question have a complete identity with those of other UGDH species known. The importance of the C276 residue in the binding of UDP-glucose was further examined with mutant proteins at the C276 site. The mutagenesis at C276 has no effect on the expression of the mutants (C276G, C276K, C276E, C276L, and C276Y). Enzyme activities of the C276 mutants were not measurable under normal assay conditions, suggesting an important role for the C276 residue. No incorporation of [³²P]5N3UDP-glucose was also observed for the mutants. These results indicate that C276 plays an important role for efficient binding of UDP-glucose to hUGDH.

Si/SiO2/Ta/NiFe/Mn–Ir/CoFe/NOL/CoFe/Al–O/CoFe/NiFe/Ta bottom conventional (without nano-oxide layer, NOL) and specular (with NOL) MTJs were prepared by DC magnetron sputtering methods. In the case of a conventional MTJ, the TMR ratio increased up to 300 °C but the TMR ratio of a specular MTJ increased up to 400 °C. The highest TMR ratios of two samples after annealing at each optimal temperature were 21.6% (conventional MTJ) and 22.7% (specular MTJ), respectively, This improved thermal property of the specular MTJ is due to the NOL, which could act as a diffusion barrier for Mn. The bias-voltage dependence of both samples was vastly improved after annealing at each optimal temperature. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

A new decorrelating arrangement for asynchronous up-link direct sequence code division multiple access communication, which employs coherent detection with pilot symbol aided channel estimation, is proposed. The proposed coherent scheme improves the bit error rate (BER) and exhibits no error floor compared to the previous noncoherent schemes. The BER performance for BPSK is obtained by simulations over a frequency-nonselective Rayleigh fading channel.