The Adaptive, Pain Sensitive, and Global Symptoms Clusters: Evidence from a Patient-Based Study.

OBJECTIVES: The largest epidemiologic study conducted about painful temporomandibular disorders (pTMDs) to date identified 3 clusters of individuals with similar symptoms-adaptive, pain sensitive, and global symptoms-which hold promise as a means of personalizing pain care. Our goal was to compare the clinical and psychological characteristics that are consistent with a pTMD clinical examination among patients who are seeking care and assigned to the different clusters. METHODS: This cross-sectional study used data from the medical records of patients attending Duke Innovative Pain Therapies between August 2017 and April 2021 who received a pTMD diagnosis (i.e., myalgia) and consented to have their data used for research. Data included orofacial and pain-related measures, dental features, and psychological measures. We used the Rapid OPPERA Algorithm to assign clusters to patients and multinomial regression to determine the likelihood (odds ratios [OR] and 95% confidence intervals [CI]) of being assigned to the pain sensitive or global symptoms cluster attributed to each measure. RESULTS: In total, 131 patients were included in this study and assigned a cluster: adaptive (n = 54, 41.2%), pain sensitive (n = 49, 37.4%), and global symptoms (n = 28, 21.4%). The PS cluster displayed greater numbers of temporomandibular joint sites (OR, 1.29; 95% CI, 1.01 to 1.65) and masticatory (1.48; 1.19 to 1.83) and cervical (1.23; 1.09 to 1.39) muscles with pain evoked by palpation. The GS cluster displayed greater scores of pain catastrophizing (1.04; 1.01 to 1.06) and perceived stress (1.23; 1.03 to 1.46) and was more likely to report persistent pain (16.23; 1.92 to 137.1) of higher impact (1.43; 1.14 to 1.80). CONCLUSION: Our findings support that care-seeking patients with pTMDs who are assigned to the GS cluster display a poorer psychological profile, even though those assigned to the PS cluster display more measures consistent with orofacial pain. Findings also establish the PS cluster as a group that does not display psychological comorbidities despite being hypersensitive. KNOWLEDGE TRANSFER STATEMENT: This study informs clinicians that patients seeking care for painful temporomandibular disorders, in specific cases of myalgia, can be classified into 1 of 3 groups that display unique profiles of symptoms. Most importantly, it emphasizes the importance of examining patients with painful temporomandibular disorders in a holistic manner that includes assessing symptoms of psychological distress. Patients with greater psychological distress will likely benefit from multidisciplinary treatment strategies that may include psychological treatments.

Low Intake of Choline Is Associated with Diminished Strength and Lean Mass Gains in Older Adults.

OBJECTIVES: Choline is an essential micronutrient for many physiological processes related to exercise training including biosynthesis of acetylcholine. Though dietary choline intake has been studied in relation to endurance training and performance, none have studied it during resistance exercise training (RET) in older adults. The objective of the study was to examine the relationship between choline intake and muscle responses to RET in older adults. METHODS: Forty-six, 60-69-year-old individuals (M=19, F=27) underwent 12 weeks of RET (3x/week, 3 sets, 8-12 reps, 75% of maximum strength [1RM], 8 exercises). Body composition (DEXA) and 1RM tests were performed before and after training. After analyzing 1,656 diet logs (3x/week, 46 participants, 12 weeks), participants' mean choline intakes were categorized into three groups: Low (2.9-5.5 mg/kg lean/d), Med-Low (5.6-8.0 mg/kg lean/d), or Adequate (8.1-10.6 mg/kg lean/d). These correspond to <50%, ~63%, and ~85% of Adequate Intake (AI) for choline, respectively. RESULTS: Gains in composite strength (leg press + chest press 1RM) were significantly lower in the Low group compared with the other groups (Low: 30.9 ± 15.1%, Med-Low: 70.3 ± 48.5%, Adequate: 81.9 ± 68.4%; p=0.004). ANCOVA with cholesterol, protein, or other nutrients did not alter this result. Reduced gains in lean mass were also observed in the Low group, compared with higher choline intake of 5.6-10.6 mg/kg lean/d (1.3 ± 0.6% vs. 3.2 ± 0.6%, p<0.05). CONCLUSION: These data suggest that this population of older adults does not consume adequate choline and lower choline intake is negatively and independently associated with muscle responses to RET.

Efferent unmasking of speech-in-noise encoding?

OBJECTIVE: The medial olivocochlear (MOC) reflex provides efferent feedback from the brainstem to cochlear outer hair cells. Physiologic studies have demonstrated that the MOC reflex is involved in "unmasking" of signals-in-noise at the level of the auditory nerve; however, its functional importance in human hearing remains unclear. DESIGN: This study examined relationships between pre-neural measurements of MOC reflex strength (click-evoked otoacoustic emission inhibition; CEOAE) and neural measurements of speech-in-noise encoding (speech frequency following response; sFFR) in four conditions (Quiet, Contralateral Noise, Ipsilateral Noise, and Ipsilateral + Contralateral Noise). Three measures of CEOAE inhibition (amplitude reduction, effective attenuation, and input-output slope inhibition) were used to quantify pre-neural MOC reflex strength. Correlations between pre-neural MOC reflex strength and sFFR "unmasking" (i.e. response recovery from masking effects with activation of the MOC reflex in time and frequency domains) were assessed. STUDY SAMPLE: 18 young adults with normal hearing. RESULTS: sFFR unmasking effects were insignificant, and there were no correlations between pre-neural MOC reflex strength and sFFR unmasking in the time or frequency domain. CONCLUSION: Our results do not support the hypothesis that the MOC reflex is involved in speech-in-noise neural encoding, at least for features that are represented in the sFFR at the SNR tested.

The molecular chaperone sigma 1 receptor mediates rescue of retinal cone photoreceptor cells via modulation of NRF2.

Sigma 1 receptor (Sig1R), a putative molecular chaperone, has emerged as a novel therapeutic target for retinal degenerative disease. Earlier studies showed that activation of Sig1R via the high-affinity ligand (+)-pentazocine ((+)-PTZ) induced profound rescue of cone photoreceptor cells in the rd10 mouse model of retinitis pigmentosa; however the mechanism of rescue is unknown. Improved cone function in (+)-PTZ-treated mice was accompanied by reduced oxidative stress and normalization of levels of NRF2, a transcription factor that activates antioxidant response elements (AREs) of hundreds of cytoprotective genes. Here, we tested the hypothesis that modulation of NRF2 is central to Sig1R-mediated cone rescue. Activation of Sig1R in 661W cone cells using (+)-PTZ induced dose-dependent increases in NRF2-ARE binding activity and NRF2 gene/protein expression, whereas silencing Sig1R significantly decreased NRF2 protein levels and increased oxidative stress, although (+)-PTZ did not disrupt NRF2-KEAP1 binding. In vivo studies were conducted to investigate whether, in the absence of NRF2, activation of Sig1R rescues cones. (+)-PTZ was administered systemically for several weeks to rd10/nrf2+/+ and rd10/nrf2-/- mice. Through post-natal day 42, cone function was significant in rd10/nrf2+/+, but minimal in rd10/nrf2-/- mice as indicated by electroretinographic recordings using natural noise stimuli, optical coherence tomography and retinal histological analyses. Immunodetection of cones was limited in (+)-PTZ-treated rd10/nrf2-/-, though considerable in (+)-PTZ-treated rd10/nrf2+/+mice. The data suggest that Sig1R-mediated cone rescue requires NRF2 and provide evidence for a previously-unrecognized relationship between these proteins.

Investigating peripheral sources of speech-in-noise variability in listeners with normal audiograms.

A current initiative in auditory neuroscience research is to better understand why some listeners struggle to perceive speech-in-noise (SIN) despite having normal hearing sensitivity. Various hypotheses regarding the physiologic bases of this disorder have been proposed. Notably, recent work has suggested that the site of lesion underlying SIN deficits in normal hearing listeners may be either in "sub-clinical" outer hair cell damage or synaptopathic degeneration at the inner hair cell-auditory nerve fiber synapse. In this study, we present a retrospective investigation of these peripheral sources and their relationship with SIN performance variability in one of the largest datasets of young normal-hearing listeners presented to date. 194 participants completed detailed case history questionnaires assessing noise exposure, SIN complaints, tinnitus, and hyperacusis. Standard and extended high frequency audiograms, distortion product otoacoustic emissions, click-evoked auditory brainstem responses, and SIN performance measures were also collected. We found that: 1) the prevalence of SIN deficits in normal hearing listeners was 42% when based on subjective report and 8% when based on SIN performance, 2) hearing complaints and hyperacusis were more common in listeners with self-reported noise exposure histories than controls, 3) neither extended high frequency thresholds nor compound action potential amplitudes differed between noise-exposed and control groups, 4) extended high frequency hearing thresholds and compound action potential amplitudes were not predictive of SIN performance. These results suggest an association between noise exposure and hearing complaints in young, normal hearing listeners; however, SIN performance variability is not explained by peripheral auditory function to the extent that these measures capture subtle physiologic differences between participants.

Glucose and acetate metabolism in bovine intramuscular and subcutaneous adipose tissues from steers infused with glucose, propionate, or acetate.

We hypothesized that abomasal infusion of glucose would promote de novo fatty acid biosynthesis from glucose in vitro in bovine intramuscular (i.m.) and subcutaneous (s.c.) adipose tissues to a greater extent than ruminal infusion of acetate, propionate, or glucose. Angus crossbred steers (n = 24), 22 mo of age, were fitted with ruminal cannulas, and steers were adapted to another corn/sorghum finishing diet over a 2-wk period while recovering from the placement of the cannulas. After the adaptation period, the steers were fed the second finishing diet at 130% of their voluntary intake and were infused with isocaloric amounts (3.76 Mcal/d) of glucose, propionate, or acetate for 35 d. Glucose was infused either into the rumen or into the abomasum, whereas propionate and acetate were infused into the rumen. Acetate infusion decreased DM and DE intakes (P < 0.05). The 5th to 8th longissimus muscle section was removed immediately and transported to the laboratory within 10 min post-exsanguination in 38 °C, oxygenated Krebs Henseleit buffer containing 5 mM glucose and 5 mM acetate. Intramuscular and s.c. adipose tissues were dissected from the muscle and incubated in vitro in 5 mM glucose plus 5 mM acetate (containing [U-14C]glucose or [1-14C]acetate). Lipid content was lower (P = 0.04) in i.m. adipose tissue of the acetate-infused steers than in the other treatment groups, and i.m. adipocytes from acetate-infused steers were smaller (P = 0.01) than those from propionate-infused steers. The rate of incorporation of acetate into glyceride-fatty acids (GFA) in i.m. and s.c. adipose tissues was greater (P < 0.03) in steers receiving ruminal or abomasal infusions of glucose than in adipose tissues from steers infused with acetate. The greatest rates of GFA synthesis were observed in s.c. adipose tissue from steers infused ruminally with propionate or abomasally infused with glucose (P < 0.001). In i.m. and s.c. adipose tissues, the proportion of acetyl units from acetate incorporated into GFA was greater in steers receiving glucose infusion in the rumen or abomasum than in steers receiving acetate or propionate infusion (P < 0.05). Contrary to our hypothesis, abomasal glucose infusion did not promote greater fatty acid biosynthesis from glucose in i.m. adipose tissue than ruminal glucose infusion. However, glucose infusion caused the greatest production of acetyl units from acetate in i.m. and s.c. adipose tissues.

Efferent modulation of pre-neural and neural distortion products.

Distortion product otoacoustic emissions (DPOAEs) and distortion product frequency following responses (DPFFRs) are respectively pre-neural and neural measurements associated with cochlear nonlinearity. Because cochlear nonlinearity is putatively linked to outer hair cell electromotility, DPOAEs and DPFFRs may provide complementary measurements of the human medial olivocochlear (MOC) reflex, which directly modulates outer hair cell function. In this study, we first quantified MOC reflex-induced DPOAE inhibition at spectral fine structure peaks in 22 young human adults with normal hearing. The f1 and f2 tone pairs producing the largest DPOAE fine structure peak for each subject were then used to evoke DPFFRs with and without MOC reflex activation to provide a related neural measure of efferent inhibition. We observed significant positive relationships between DPOAE fine structure peak inhibition and inhibition of DPFFR components representing neural phase locking to f2 and 2f1-f2, but not f1. These findings may support previous observations that the MOC reflex inhibits DPOAE sources differentially. That these effects are maintained and represented in the auditory brainstem suggests that the MOC reflex may exert a potent influence on subsequent subcortical neural representation of sound.

CELL BIOLOGY SYMPOSIUM: Practical application of the basic aspects of GLUT4 membrane trafficking and insulin signaling on issues related to animal agriculture.

Because of the relatively short lifespans of beef cattle, membrane trafficking in relation to inflammation is not considered important unless it overtly affects productivity. However, glucose uptake and utilization is important for adipose tissue development in beef cattle, and increasing glucose utilization in intramuscular adipose tissue can increase carcass quality. Research from the 1980s demonstrated a lack of insulin sensitivity in isolated bovine adipocytes and adipose tissue explants incubated in vitro. Insulin did not stimulate glucose or acetate incorporation into fatty acids, nor did it increase concentrations of glycolytic intermediates in bovine adipose tissue incubated with exogenous glucose. Specific binding of [I] iodoinsulin and insulin degradation in bovine isolated adipocytes was low to non-detectable. These early studies indicated that insulin-dependent receptor-mediated signaling was less important in bovine adipose tissue than in adipose tissues of humans, swine, or laboratory species. More recent research demonstrated that glucose transporter protein 4 (GLUT4) expression in muscle and adipose tissue declines markedly after birth in calves, indicating the development of insulin resistance as cattle transition from suckling to functional ruminants. Insulin resistance is important in dairy cattle, causing ketosis and fatty liver. Consistent with this, subcutaneous adipose tissue expression decreases 50% following parturition in dairy cattle, although expression of genes associated with insulin responsiveness (, , and ) is up-regulated by 21 d postpartum. Understanding the underlying mechanisms of insulin resistance in beef and dairy cattle would increase animal health and thereby improve productivity.

Dietary whole and cracked linseed increases the proportion of oleic and α-linolenic acids in adipose tissues and decreases stearoyl-coenzyme A desaturase, acetyl-coenzyme A carboxylase, and fatty acid synthase gene expression in the longissimus thoracis muscle of Yanbian Yellow cattle.

We hypothesized that supplementation of linseed in a beef cattle fattening diet would increase PUFA concentrations in intramuscular adipose tissue and depress (), (), and () gene expression by decreasing () expression. Conversely, supplemental linseed would upregulate expression of () and () in muscle of Yanbian Yellow steers. Thirty steers were assigned at random to 3 groups of 10 steers fed either the basal diet (corn grain and corn silage-based commercial concentrate [CON]), the CON diet plus 8% whole linseed (WLS; DM basis), or the CON diet plus 8% cracked linseed (CLS; DM basis) for 6 mo. The WLS and CLS supplements did not affect carcass weight, backfat thickness, or marbling scores ( > 0.10) but increased rib eye area and fat color (more yellow; < 0.05). The WLS and CLS diets decreased the proportions of 16:0 and 18:0 and increased the proportions of 18:1-9, 18:3-3, -9, -11 conjugated linoleic acid, total MUFA, and total PUFA in intramuscular, intermuscular, and subcutaneous adipose tissues. The WLS and CLS diets increased and gene expression whereas the supplements depressed , , , and gene expression in longissimus thoracis muscle, relative to CON muscle, consistent with our hypothesis. Because the WLS and CLS treatments did not affect any measure of carcass adiposity, these results indicated that linseed supplements promoted uptake of dietary lipids while concurrently depressing de novo fatty acid biosynthesis in adipose tissue.

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The most promising single-nucleotide polymorphisms (SNPs) were tested in meta-analysis of 4 independent cohorts. One replication cohort was from the United States, and the others were from Germany, Finland, and Brazil, totaling 1,911 TMD cases and 6,903 controls. A locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 × 106) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. In the discovery cohort, sex-stratified analysis identified 2 additional genome-wide significant loci in females. One lying upstream of the relaxin/insulin-like family peptide receptor 2 ( RXP2) (chromosome 13, rs60249166, odds ratio [OR] = 0.65, P = 3.6 × 10-8) was replicated among females in the meta-analysis (1-tailed P = 0.052). The other (chromosome 17, rs1531554, OR = 0.68, P = 2.9 × 10-8) was replicated among females (1-tailed P = 0.002), as well as replicated in meta-analysis of both sexes (1-tailed P = 0.021). A novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 × 10-8) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 × 10-7) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. The SGCA gene encodes SGCA, which is involved in the cellular structure of muscle fibers and, along with DMD, forms part of the dystrophin-glycoprotein complex. Functional annotation suggested that several of these variants reside in loci that regulate processes relevant to TMD pathobiologic processes.

Dietary linseed oil with or without malate increases conjugated linoleic acid and oleic acid in milk fat and and gene expression in mammary gland and milk somatic cells of lactating goats.

Supplementary dietary plant oils have the potential to alter milk fatty acid composition in ruminants as a result of changes in the amount and kind of fatty acid precursors. We hypothesized that linseed oil in combination with malate (a key propionate precursor in the rumen) would increase ∆9 unsaturated fatty acids and specific gene expression in somatic cells and mammary glands of lactating goats. Twelve lactating goats were used in a 3 × 3 Latin square design. Treatments included the basal diet (CON), the CON plus 4% linseed oil (LO), and the CON plus 4% linseed oil and 2% -malate (LOM). Relative to CON, the LO and LOM supplements increased the daily intake of palmitic (16:0), stearic (18:0), oleic (18:1-9), linoleic (18:2-6), α-linolenic (18:3-3), and γ-linolenic acids (18:2-6); α-linolenic acid intake was increased over 9-fold, from 6.77 to over 51 g/d ( < 0.02). The LO and LOM supplements increased daily milk yield, milk fat yield, and milk fat percentage ( < 0.05). The LOM supplement also increased milk lactose percentage and daily yield ( = 0.03). Both the LO and LOM supplements increased plasma glucose and total cholesterol and decreased plasma ß-hydroxbutyrate concentrations ( = 0.03). The LO and LOM supplements increased concentrations of stearic acid; -vaccenic acid (TVA; 18:1-11); -9, -11 CLA; -10 -12 CLA; and α-linolenic acid in rumen fluid and increased the concentrations of oleic acid; TVA; -9, -11 CLA; -10, -12 CLA; and α-linolenic acid in plasma lipids and milk fat ( < 0.05). Conversely, the LO and LOM supplements decreased short- and medium-chain SFA, including lauric (12:0), myristic (14:0), and palmitic acids, in plasma and milk fat ( < 0.05). Relative mRNA levels for and () gene expression were increased in somatic cells and mammary gland tissue by LO and LOM ( < 0.05). We conclude that the higher intake and ruminal production of stearic acid promoted SCD gene expression in somatic cells and mammary tissue. Furthermore, milk somatic cells are a suitable substitute for documenting treatment effects of dietary oils on gene expression in goat mammary tissue.

Oleic acid enhances G protein coupled receptor 43 expression in bovine intramuscular adipocytes but not in subcutaneous adipocytes.

We hypothesized that fatty acids would differentially affect G protein coupled receptor (GPR) 43 mRNA expression and GPR43 protein concentrations in bovine intramuscular (IM) and subcutaneous (SC) adipocytes. The GPR43 protein was detected in bovine liver, pancreas, and semimembranosus (MUS) muscle in samples taken at slaughter. Similarly, GPR43 protein levels were similar in IM adipose tissue and SM muscle but was barely detectable in SC adipose tissue. Primary cultures of IM and SC stromal vascular cells were isolated from bovine adipose tissues. Oleic acid (100 µ) stimulated PPARγ gene expression and decreased stearoyl-CoA desaturase (SCD) gene expression but had no effect on GPR43 gene expression, which was readily detectable in both IM and SC adipocytes. Differentiation cocktail (Diff; 10 µ insulin, 4 µ dexamethasone, and 10 µ ciglitizone) stimulated CCAAT/enhancer-binding protein ß (C/EBPß) and PPARγ gene expression in SC but not IM adipocytes, but Diff increased SCD gene expression in both cell types. Linoleic acid (10 µ) increased PPARγ gene expression relative to Diff cocktail in SC adipocytes, whereas linoleic acid and α-linolenic decreased SCD gene expression relative to control adipocytes and adipocytes incubated with Diff ( < 0.05). Increasing concentrations of oleic acid (1, 10, 100, and 500 µM) increased GPR43 protein and mRNA expression in IM but not SC adipocytes. These data indicated that oleic acid alters mRNA and protein concentrations of GPR43 in bovine IM adipocytes.

Adiposity, lipogenesis, and fatty acid composition of subcutaneous and intramuscular adipose tissues of Brahman and Angus crossbred cattle.

The objective of this study was to demonstrate differences in aspects of adipose tissue cellularity, lipid metabolism, and fatty and cholesterol composition in Angus and Brahman crossbred cattle. We hypothesized that in vitro measures of lipogenesis would be greater in three-fourths Angus progeny than in three-fourths Brahman progeny, especially in intramuscular (i.m.) adipose tissue. Progeny ( = 227) were fed a standard, corn-based diet for approximately 150 d before slaughter. Breed was considered to be the effect of interest and was forced into the model. There were 9 breed groups including all 4 kinds of three-fourths Angus calves: Angus bulls Angus-sired F cows ( = 32), Angus bulls Brahman-sired F cows ( = 20), Brahman-sired F bulls Angus cows ( = 24), and Angus-sired F bulls Angus cows ( = 20). There were all 4 kinds of three-fourths Brahman calves: Brahman bulls Brahman-sired F cows ( = 21), Brahman bulls Angus-sired F cows ( = 43), Brahman-sired F bulls Brahman cows ( = 26), and Angus-sired F bulls Brahman cows ( = 13). Additionally, F calves (one-half Brahman and one-half Angus) were produced only from Brahman-sired F bulls Angus-sired F cows ( = 28). Contrasts were calculated when breed was an important fixed effect, using the random effect family(breed) as the error term. Most contrasts were nonsignificant ( > 0.10). Those that were significant ( < 0.05) included cholesterol concentration of subcutaneous (s.c.) adipose tissue (three-fourths Angus > F, three-fourths Brahman > F, and three-fourths crossbred progeny combined > F), s.c. adipocyte volume (three-fourths Angus > F and three-fourths bloods combined > F), lipogenesis from acetate in s.c. adipose tissue (three-fourths Brahman calves from Brahman dams > three-fourths Brahman calves from F dams), and percentage 18:3-3 in s.c. adipose tissue (three-fourths Brahman calves from Brahman-sired F dams < three-fourths Brahman calves from Angus-sired F dams). Intramuscular adipocyte volume ( < 0.001) was less in three-fourths Brahman cattle than in three-fourths Angus cattle. Additionally, several differences were observed in i.m. adipose tissue that were consistent with this being a less-developed adipose tissue in three-fourths Brahman cattle than in three-fourths Angus cattle.

Endoplasmic reticulum stress-regulated CXCR3 pathway mediates inflammation and neuronal injury in acute glaucoma.

Acute glaucoma is a leading cause of irreversible blindness in East Asia. The mechanisms underlying retinal neuronal injury induced by a sudden rise in intraocular pressure (IOP) remain obscure. Here we demonstrate that the activation of CXCL10/CXCR3 axis, which mediates the recruitment and activation of inflammatory cells, has a critical role in a mouse model of acute glaucoma. The mRNA and protein expression levels of CXCL10 and CXCR3 were significantly increased after IOP-induced retinal ischemia. Blockade of the CXCR3 pathway by deleting CXCR3 gene significantly attenuated ischemic injury-induced upregulation of inflammatory molecules (interleukin-1ß and E-selectin), inhibited the recruitment of microglia/monocyte to the superficial retina, reduced peroxynitrite formation, and prevented the loss of neurons within the ganglion cell layer. In contrast, intravitreal delivery of CXCL10 increased leukocyte recruitment and retinal cell apoptosis. Inhibition of endoplasmic reticulum (ER) stress with chemical chaperones partially blocked ischemic injury-induced CXCL10 upregulation, whereas induction of ER stress with tunicamycin enhanced CXCL10 expression in retina and primary retinal ganglion cells. Interestingly, deleting CXCR3 attenuated ER stress-induced retinal cell death. In conclusion, these results indicate that ER stress-medicated activation of CXCL10/CXCR3 pathway has an important role in retinal inflammation and neuronal injury after high IOP-induced ischemia.

Substituting redberry juniper for oat hay in lamb feedlot diets: Carcass characteristics, adipose tissue fatty acid composition, and sensory panel traits.

We hypothesized that ground juniper and dried distillers grains with solubles (DDGS) fed to lambs would have no negative effects on end products. Lambs were individually fed diets containing mainly sorghum grain and oat hay (control) or DDGS-based diets consisting mainly of DDGS, sorghum grain, and oat hay (0JUN), or 33% (33JUN), 66% (66JUN), or 100% (100JUN) of the hay replaced by juniper. Lambs fed control had greater (P<0.03) shrunk BW and HCW vs. lambs fed 0JUN, but other carcass characteristics and sensory panel traits were similar (P>0.23). As juniper increased in the DDGS-based diets, HCW increased quadratically (P=0.01) and LM fatty acid composition was altered. Feeding juniper did not negatively affect (P>0.57) off-flavor in chops, but enhanced (linear, P<0.05) juiciness, tenderness, and flavor intensity. Lambs fed diets with a combination of oat hay and ground juniper appeared to produce the most acceptable carcasses and lamb chops.

GADD34 induces cell death through inactivation of Akt following traumatic brain injury.

Neuronal cell death contributes significantly to the pathology of traumatic brain injury (TBI) irrespective of the mode or severity of the injury. Activation of a pro-survival protein, Akt, is known to be regulated by an E3 ligase TRAF6 through a process of ubiquitination-coupled phosphorylation at its T308 residue. Here we show that upregulation of a pro-apototic protein, GADD34, attenuates TRAF6-mediated Akt activation in a controlled cortical impact model of TBI in mice. TBI induces the expression of GADD34 by stimulating binding of a stress inducible transcription factor, ATF4, to the GADD34 promoter. GADD34 then binds with TRAF6 and prevents its interaction with Akt. This event leads to retention of Akt in the cytosol and prevents phosphorylation at the T308 position. Finally, in vivo depletion of GADD34 using a lentiviral knockdown approach leads to a rescue of Akt activation and markedly attenuates TBI-induced cell death.

Effects of 35% corn wet distillers grains plus solubles in steam-flaked and dry-rolled corn-based finishing diets on animal performance, carcass characteristics, beef fatty acid composition, and sensory attributes.

Fifty-four individually-fed Hereford-Angus cross steers (initial BW = 308 ± 9 kg) were used in an unbalanced randomized block design with a 2 × 2 factorial treatment arrangement to determine effects of corn processing method and corn wet distillers grains plus solubles (WDGS) inclusion in finishing diets on animal performance, carcass and beef characteristics, and sensory attributes. Dietary treatments included steam-flaked corn- (SFC) and dry-rolled corn (DRC)-based finishing diets containing 0 or 35% WDGS (DM basis; 0SFC and 35SFC, 0DRC and 35DRC, respectively). Yellow grease was used to equilibrate fat content of diets. Steers were fed 174 d, and were harvested on a single date when the mean ultrasound fat thickness was estimated to be 1.30 cm. No interactions between corn processing and WDGS were observed for performance or carcass characteristics (P ≥ 0.11). Final BW (556 ± 14 kg) and ADG (1.43 ± 0.06 kg) were not affected (P ≥ 0.25) by dietary treatment. Steers fed SFC-based diets consumed less feed, and were 10.6% more efficient (P < 0.01) than those fed DRC-based diets. Including WDGS in finishing diets improved feed efficiency of steers consuming both SFC- and DRC-based diets (P ≤ 0.04). Dietary treatment did not affect HCW, dressing percentage, fat thickness, or yield grade (P ≥ 0.27). Including WDGS in finishing diets decreased the concentration of 16:1cis-9, 18:1cis-9, and 18:1cis-11 fatty acids, and tended (P ≤ 0.10) to increase total fat concentration of steaks compared with diets without WDGS. A corn processing method by WDGS interaction was detected for 18:1trans-11 where steaks from 0DRC diets had decreased concentrations compared with other diets. There were no dietary effects on palatability attributes (P > 0.20). Livery-organy aromatics (P = 0.03) and sweet basic tastes (P = 0.01) in steaks from the 35SFC treatment were more intense than in other treatments, but were barely detectable. Thiobarbituric acid reactive substances tended to be greater in steaks from steers fed WDGS after 5 d of storage (P = 0.10), and were greater after 7 d. (P < 0.01). Inclusion of WDGS used in this experiment improved G:F with minimal impacts on carcass characteristics. Both WDGS inclusion and corn processing method impacted fatty acid composition. However, diet had minimal impacts on palatability attributes. When compared with diets fat-equilibrated with yellow grease, the primary concern with incorporating WDGS appears to be decreased shelf-life after 5 d of storage.

Hyperhomocysteinemia is detrimental to pregnancy in mice and is associated with preterm birth.

Elevated levels of homocysteine produce detrimental effects in humans but its role in preterm birth is not known. Here we used a mouse model of hyperhomocysteinemia to examine the relevance of homocysteine to preterm birth. The mouse carries a heterozygous deletion of cystathionine ß-synthase (Cbs(+/-)). Gestational period was monitored in wild type and Cbs(+/-) female mice. Mouse uterine and placental tissues, human primary trophoblast cells, and human myometrial and placental cell lines were used to determine the influence of homocysteine on expression of specific genes in vitro. The activity of BKCa channel in the myometrial cell line was monitored using the patch-clamp technique. We found that hyperhomocysteinemia had detrimental effects on pregnancy and induced preterm birth in mice. Homocysteine increased the expression of oxytocin receptor and Cox-2 as well as PGE2 production in uterus and placenta, and initiated premature uterine contraction. A Cox-2 inhibitor reversed these effects. Gpr109a, a receptor for niacin, induced Cox-2 in uterus. Homocysteine upregulated GPR109A and suppressed BKCa channel activity in human myometrial cells. Deletion of Gpr109a in Cbs(+/-) mice reversed premature birth. We conclude that hyperhomocysteinemia causes preterm birth in mice through upregulation of the Gpr109a/Cox-2/PGE2 axis and that pharmacological blockade of Gpr109a may have potential in prevention of preterm birth.

Interactions between oil substrates and glucose on pure cultures of ruminal lipase-producing bacteria.

The hydrolysis of free fatty acids from lipids is a prerequisite for biohydrogenation, a process that effectively saturates free fatty acids. Anaerovibrio lipolyticus 5s and Butyrivibrio fibrisolvens have long been thought to be the major contributors to ruminal lipolysis; however, Propionibacterium avidum and acnes recently have been identified as contributing lipase activity in the rumen. In order to further characterize the lipase activity of these bacterial populations, each was grown with three different lipid substrates, olive oil, corn oil, and flaxseed oil (3 %). Because different finishing rations contain varying levels of glycogen (a source of free glucose) this study also documented the effects of glucose on lipolysis. P. avidum and A. lipolyticus 5s demonstrated the most rapid rates (P < 0.05) of lipolysis for cultures grown with olive oil and flaxseed oil, respectively. A. lipolyticus, B. fibrisolvens, and P. avidum more effectively hydrolyzed flaxseed oil than olive oil or corn oil, especially in the presence of 0.02 % glucose. Conversely, P. acnes hydrolyzed corn oil more readily than olive oil or flaxseed oil and glucose had no effect on lipolytic rate. Thus, these bacterial species demonstrated different specificities for oil substrates and different sensitivities to glucose.

Fatty acid biosynthesis and lipogenic enzyme activities in subcutaneous adipose tissue of feedlot steers fed supplementary palm oil or soybean oil.

We hypothesized that supplementing finishing diets with palm oil would promote adipocyte differentiation in subcutaneous adipose tissue of feedlot steers, and that soybean oil supplementation would depress adipocyte differentiation. Twenty-eight Angus steers were assigned randomly to 3 groups of 9 or 10 steers and fed a basal diet without additional fat (control), with 3% palm oil (rich in palmitic acid), or with 3% soybean oil (rich in polyunsaturated fatty acids), for 10 wk, top-dressed daily. Palm oil had no effect (P > 0.05) on ADG, food intake, or G:F, whereas soybean oil depressed ADG (P = 0.02), food intake (P = 0.04), and G:F (P = 0.05). Marbling scores tended (P = 0.09) to be greater in palm oil-fed steers (Modest(09)) than in soybean oil-fed steers (Small(55)). Subcutaneous adipocyte mean volume was greater in palm oil-fed steers (515.9 pL) than in soybean-supplemented cattle (395.6 pL; P = 0.01). Similarly, glucose and acetate incorporation into total lipids in vitro was greater in subcutaneous adipose tissue of palm oil-fed steers (119.9 and 242.8 nmol·3h(-1)·10(5) cells, respectively) than adipose tissue of soybean oil-fed steers in (48.9 and 95.8 nmol·3h(-1)·10(5) cells, respectively). Glucose-6-phosphate dehydrogenase and NADP-malate dehydrogenase activities were greater (P ≤ 0.05) in subcutaneous adipose tissue of palm oil-fed steers than in adipose tissue of control steers. Palm oil did not increase palmitic acid or decrease oleic acid in subcutaneous adipose tissue or LM, but decreased (P ≤ 0.05) myristoleic, palmitoleic, and cis-vaccenic acid in adipose tissue, indicating a depression in stearoyl-coenzyme A desaturase activity. Soybean oil increased the proportion of α-linolenic acid in adipose tissue and muscle and increased linoleic acid and 18:1trans-10 in muscle. We conclude that palm oil supplementation promoted lipid synthesis in adipose tissue without depressing feed efficiency or increasing the palmitic acid content of beef.