Effect of nutrient intake on intramuscular glucose metabolism during the early growth stage in cross-bred steers (Japanese Black male × Holstein female).

The objective was to investigate the impact of nutrient intake during the early growth period on the expression of glucose metabolism-related genes in skeletal muscle of cross-bred cattle. From 1.5 to 5 months of age, group H (n=7) animals were intensively fed a high-protein and low-fat milk replacer [crude protein (CP) 28%; ether extracts (EE) 18%; max: 2.0 kg, 12 l/day], and group R (n=7) animals were fed a restricted amount of normal milk replacer (CP 25%; EE 23%; max 0.5 kg, 4 l/day). From 6 to 10 months of age, group H cattle were fed a high-nutrition total mixed ration mainly prepared from grain feed, and group R cattle were fed only roughage. Blood samples were taken from each animal at three biopsy times (1.5, 5 and 10 months of age), and the blood plasma concentration of glucose and insulin was analysed. In glucose concentration, there were no significant differences; however, the concentrations of insulin were higher in group H than in group R at 5 and 10 months of age. Muscle samples were taken by biopsy from longissimus thoracis muscle (LT) at 1.5, 5 and 10 months of age. We analysed mRNA expression levels using the quantitative real-time polymerase chain reaction (PCR) assay for glucose transporters (GLUT1 and GLUT4), insulin receptor, phosphatidylinositol 3-kinase (PI-3K), protein kinase B (PKB, also known as Akt), hexokinase 1 (HK1) and tumour necrosis factor alpha (TNFα). Although no differences were detected at 1.5 and 5 months of age, at 10 months of age, GLUT1, HK1 and TNFα mRNA expression levels were significantly higher in group H than in group R. These results suggested Glut1 that affects insulin-independently mediated glucose uptake was more responsive to improved nutrition during early growth stage than GLUT4 that insulin-dependently mediated glucose uptake in LT of cattle.

Deconvolution of 1D NMR spectra: A deep learning-based approach.

The analysis of nuclear magnetic resonance (NMR) spectra to detect peaks and characterize their parameters, often referred to as deconvolution, is a crucial step in the quantification, elucidation, and verification of the structure of molecular systems. However, deconvolution of 1D NMR spectra is a challenge for both experts and machines. We propose a robust, expert-level quality deep learning-based deconvolution algorithm for 1D experimental NMR spectra. The algorithm is based on a neural network trained on synthetic spectra. Our customized pre-processing and labeling of the synthetic spectra enable the estimation of critical peak parameters. Furthermore, the neural network model transfers well to the experimental spectra and demonstrates low fitting errors and sparse peak lists in challenging scenarios such as crowded, high dynamic range, shoulder peak regions as well as broad peaks. We demonstrate in challenging spectra that the proposed algorithm is superior to expert results.

Self-management-competency as a new target in Hidradenitis suppurativa care.

Background: Hidradenitis suppurativa affects approximately 1% of the population.Objective: Highlighting the relevance of self-management-competency as a new therapeutic target.Method: 258 patients from the 'Epidemiology and Care in Acne inversa (EpiCAi)' project were included in the study. Disease burden was measured by patient-rated questionnaires in terms of disease activity, pain, quality of life, depression and insomnia and correlated with the domains of the health education impact questionnaire (heiQ) measuring self-management-competency.Results: 66 male (25.6%) and 192 female (74.4%) patients, with a mean age of 40.3 ± 10.24 years were included. Mean scores of pain on the numeric rating scale (NRS), Dermatology Life Quality Index (DLQI) and Hospital Anxiety and Depression Scale (HADS) were 5.11 ± 2.68, 11.35 ± 7.79 and 13.71 ± 7.57, respectively. The Insomnia severity index (ISI) showed a mean of 9.58 ± 5.76. The HADS has the highest increased total risk across all heiQ domains. With respect to the heiQ domains, the highest exposure can be attributed to improving constructive attitudes and approaches as well as decreasing emotional distress.Conclusion: There is a clear association of self-management-competency with overall disease burden, which underlines the need for psychoeducational support. This study provides ideas to develop new possible strategies of care.

A low-frequency torsion pendulum with interferometric readout.

We describe a torsion pendulum with a large mass-quadrupole moment and a resonant frequency of 2.8 mHz, whose angle is measured using a Michelson interferometer. The system achieved noise levels of ∼200prad/Hz between 0.2 and 30 Hz and ∼10prad/Hz above 100 Hz. Such a system can be applied to a broad range of fields from the study of rotational seismic motion and elastogravity signals to gravitational wave observation and tests of gravity.

Differences in muscle and fat accretion in Japanese Black and European cattle.

The development of different muscles and adipose tissues during growth was investigated in commercial Japanese Black (JB) cattle and compared with breeds of the largest variation to be found in Europe. Animals, reared under typical conditions for Japanese and European beef production systems, gained similar body weights but different carcass composition at 24months of age. The carcass of JB contained more adipose tissue and the least proportion of muscle. The longissimus muscle of JB developed extraordinary amounts of 23.3% intramuscular fat (IMF) at 24months of age, compared from 0.6% to 4.7% in European breeds. The relationships between IMF content in the longissimus muscle and different adipose tissue weights indicate that a large amount of "waste fat" is accreted with every percent of IMF. However in JB, the good ability of IMF deposition is associated with relatively least development of "waste fat", as a result of unique breed characteristics combined with special feeding system.

Perilipin, C/EBPα, and C/EBPß mRNA abundance in longissimus muscle and different adipose tissues of Holstein and Charolais cattle.

Possible regulators of intramuscular fat deposition were investigated in longissimus muscle (LM) and adipose tissues of 18months old Holstein and Charolais bulls. The mRNA abundance of perilipin and transcription factors C/EBPα and C/EBPß was analyzed by real-time RT-PCR. Carcass traits and marbling traits were recorded and relationships among adipogenic genes and tissue traits were determined. Charolais cattle were heavier (P<0.001) and had less body fat (P<0.001). Holstein bulls accumulated more fat in the LM (P=0.02), but the number and size of marbling flecks did not differ (P>0.7) between breeds. Perilipin, C/EBPα, and C/EBPß mRNA abundance was influenced by tissue but not by breed. Relationships between mRNA abundance and marbling traits could not be confirmed, however relationships among adipogenic genes. The transcriptional activity of adipogenic genes in LM suggests that intramuscular adipose tissue is still developing and differentiation still occurs.

Meat quality is associated with muscle metabolic status but not contractile myofiber type composition in premature pigs.

Longissimus muscles were sampled from Erhualian (EHL) and Pietrain (PIE) pigs at 20kg of body weight. No breed differences were detected in either the proportions or the mRNA/protein expression of respective MyHC isoforms, or the mRNA expression of PGC-1α (all P>0.10). However, meat quality traits were already divergent between breeds, and were associated with distinct energy metabolic status, as reflected by dramatically lower AMPK activity yet higher CK and LDH activities (all P<0.01) in longissimus muscle of EHL pigs. Moreover, mRNA expression of glucocorticoid receptor (GR) was found to be higher (P<0.05) in longissimus muscle of EHL pigs. These results indicate that the differences in meat quality traits occur early in premature pigs, and these are attributed to skeletal muscle energy metabolism and not contractile myofiber type composition. Breed-specific GR expression in muscle may be related to the pattern of energy metabolism and meat quality, yet the mechanism awaits further investigation.

An altered intron inhibits synthesis of the acetylcholine receptor alpha-subunit in the paralyzed zebrafish mutant nic1.

The acetylcholine receptor (AChR), an oligomeric protein composed of five subunits, is a component of the postsynaptic membrane at the vertebrate neuromuscular junction that plays a central role in synaptic transmission. The zebrafish mutation nic1 blocks the expression of functional and clustered nicotinic muscle AChRs. To understand the mechanisms underlying this lack of AChRs, we characterized the molecular defect in nic1 mutants. Our results suggest that the mutation affects the gene coding for the alpha-subunit of the AChR. Southern blot hybridization and DNA sequence analyses showed that the nic1 AChR alpha-subunit gene lacks part of intron 6 where the splicing branchpoint normally forms. Several lines of evidence suggest that this deletion blocks normal splicing; most nic1 alpha-subunit mRNAs retain intron 6 and are larger and less abundant than wild-type, some nic1 alpha-subunit mRNAs are internally deleted, and wild-type alpha-subunit mRNA rescues nic1 mutant cells. The nic1 mutation reduces the size of an intron, which prevents efficient splicing of the pre-mRNA, thus blocking synthesis of the alpha-subunit and assembly of AChRs. By this route, the nic1 mutation leads to paralysis.

Schizophrenics with tardive dyskinesia. Neuropsychological deficit and family psychopathology.

We investigated the role neurologic soft signs, premorbid asociality, psychometric tests, and family history of psychiatric illness may play in the identification of patients at risk for tardive dyskinesia (TD) development. Thirty-two TD and 32 non-TD schizophrenics served as subjects. The results indicated that patients with TD have more soft signs, are more frequently rated as poor premorbid asocials, perform more poorly on psychometric testing, and have a familial loading for affective disorders in first-degree relatives higher than control patients. A discriminant function analysis correctly classified 84.4% of the patients into their respective groups. Subtle yet quantifiable differences exist between TD and non-TD patients and these deficits may render the individual more vulnerable to TD development.

Attitudinal changes of involuntarily committed patients following treatment.

Thirty-five involuntarily hospitalized psychiatric patients were interviewed immediately following admission and again prior to discharge to assess attitudinal changes and their relationship to patient characteristics and treatment outcome. The results indicate significant changes toward recognition of the original need for involuntary treatment. Those patients achieving remission of symptoms were most likely to have positive attitudes. Follow-up data indicate that the majority continued to receive outpatient treatment after the index episode, and among those readmissions that occurred, 92% were voluntary.

Relationship between the B-mitten EEG pattern and tardive dyskinesia. A pilot control study.

The identification of patients at high risk for the development of tardive dyskinesia (TD) is a major problem in psychopharmacology. We found a possible relationship between the subcortical B-mitten EEG pattern and TD. Twenty-one TD pateints were matched on a number of relevant variables with 21 patients without TD. Ninety-five percent of the TD patients had mittens, compared to 33.3% of controls. The results suggest that the mitten dysrhythmia may be a risk factor for the development of TD. Additional findings suggest that among TD patients, mittens are differentially more frequent in younger (93.1%) as opposed to older (0.0%) subjects.

Synergistic cytotoxic effects in myeloid leukemia cells upon cotreatment with farnesyltransferase and geranylgeranyl transferase-I inhibitors.

As deregulation of RAS signaling is important in the pathogenesis of myeloid leukemias, molecular targeting of RAS signaling may be a promising therapeutic strategy. Farnesyl transferase inhibitors (FTIs) are the most promising class of these new cancer therapeutics. Several FTIs have entered phase II clinical trials in acute myeloid leukemia (AML). Since geranylgeranylation of K-RAS and N-RAS in the presence of FTIs may represent an important mechanism of FTI resistance, 6 geranylgeranyl transferase-I inhibitors (GGTIs) were screened alone and in combination with FTI for growth inhibition of myeloid leukemia cells. Significant growth inhibition (>70%) in myeloid cell lines was observed for GGTI-286 (9/19), GGTI-298 (14/19), GGTI-2147 (16/19) and FTI L-744,832 (17/17). GGTI treatment of NB-4 cells resulted in an accumulation of cells in G(0)/G(1), whereas FTI L-744,832 primarily caused an increase in G(2)/M. FTI and GGTIs both induced apoptosis. In all cases, FTI/GGTI cotreatment led to synergistic cytotoxic effects in both myeloid cell lines (5/5) and primary AML cells (6/6). This synergy coincided with increased apoptosis. FTI/GGTI cotreatment caused an accumulation of unprocessed N-RAS and inactive N-RAS-RAF complexes. Our results suggest that alternative geranylgeranylation of N-RAS may represent an important mechanism of resistance to FTI monotherapy in myeloid leukemia cells.

Application of computer image analysis to measure pork marbling characteristics.

Sixty longissimus (L) muscle chops were selected according to marbling score in order to develop a technique for the quantitative description of marbling fat by means of computer image analysis (CIA) and study its relationship with intramuscular fat content and shear force variation in pork. L muscle samples were taken from gilts belonging to three genetic lines differing in carcass leanness, namely Large White (LW), Meishan-derived dam line (M) and Synthetic Genex 3000 (SG). SG gilts had leaner loins (P<0.001) than LW and M. However, the SG loins were more marbled (P<0.001) and had higher IMF content. In addition, CIA analysis showed that marbling fat was finer and better distributed in the SG line. CIA marbling characteristics were significantly correlated with both IMF content (P<0.001) and shear force values (P<0.05) demonstrating the reliability of this technique to assess the contribution of marbling characteristics to variations in pork eating quality.

Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: II. Modulation of the transient and resting cytosolic free calcium alters progesterone secretion.

A previous study demonstrated that prostaglandin F2 alpha (PGF2 alpha) stimulates a transient increase in cytosolic free Ca2+ levels [( Ca2+]i) in ovine large luteal cells. In the present study, the magnitude of the PGF2 alpha (0.5 microM)-induced calcium transient in Hanks' medium (87 +/- 2 nM increase above resting levels) was reduced (P less than 0.05) but not completely eliminated in fura-2 loaded large luteal cells incubated in Ca2(+)-free or phosphate- and carbonate-free medium (10 +/- 1 nM, 32 +/- 6 nM, above resting levels; respectively). Preincubation for 2 min with 1 mM LaCl3 (calcium antagonist) eliminated the PGF2 alpha-induced calcium transient. The inhibitory effect of PGF2 alpha on secretion of progesterone was reduced in Ca2(+)-free medium or medium plus LaCl3. Resting [Ca2+]i levels and basal secretion of progesterone were both reduced (P less than 0.05) in large cells incubated in Ca2(+)-free medium (27 +/- 4 nM; 70 +/- 6% control, respectively) or with 5 microM 5,5'-dimethyl bis-(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (40 +/- 2 nM; 49 +/- 1% control; respectively). In addition, secretion of progesterone was inhibited (P less than 0.05) by conditions that increased (P less than 0.05) [Ca2+]i; that is LaCl3 ([Ca2+]i, 120 +/- 17 nM; progesterone, 82 +/- 8% control) and PGF2 alpha ([Ca2+]i, 102 +/- 10 nM; progesterone, 82 +/- 3% control). In small luteal cells, resting [Ca2+]i levels and secretion of progesterone were reduced by incubation in Ca2(+)-free Hanks ([Ca2+]i, 28 +/- 2 nM; progesterone, 71 +/- 6% control), however, neither LaCl3 nor PGF2 alpha increased [Ca2+]i levels or inhibited secretion of progesterone. The findings presented here provide evidence that extracellular as well as intracellular calcium contribute to the PGF2 alpha-induced [Ca2+]i transient in large cells. Furthermore, whereas an adequate level of [Ca2+]i is required to support progesterone production in both small and large cells, optimal progesterone production in large cells depends upon an appropriate window of [Ca2+]i.

Differential regulation of Ca2+ homeostasis in ovine large and small luteal cells.

This study was undertaken to characterize differences in Ca2+ homeostasis between small and large ovine luteal cells. Although increasing extracellular pH (pHex) resulted in increases in intracellular calcium ([Ca2+]in) in both cell types, the large cells exhibited a greater sensitivity, suggesting that distinct [Ca2+]in regulatory mechanisms with distinct pH optima are operating in the two cell types. The sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase inhibitors thapsigargin (TG) and cyclopiazonic acid (CPA) increased [Ca2+]in in both cell types. Treatment of small cells with CPA resulted in transient increases in [Ca2+]in, whereas CPA produced sustained increases in [Ca2+]in in large cells. In small cells, pretreatment with CPA prevented further increases in [Ca2+]in in response to TG and vice versa. In large cells, TG pretreatment precluded further increases in [Ca2+]in with either prostaglandin F2 alpha (PGF2 alpha) or CPA. In contrast, after CPA pretreatment, PGF2 alpha or TG induced further increases in [Ca2+]in in large cells. This suggests that a TG-sensitive, CPA-insensitive Ca2+ pool is present in large cells but not in small cells. Neither Na+ removal nor KCl addition affected [Ca2+]in in either cell type, indicating that neither the Na+/Ca2+ exchanger nor voltage-dependent Ca2+ channels are involved in Ca2+ homeostasis in these cells. Addition of the calcium antagonist, LaCl3 (La3+), produced a gradual increase in [Ca2+]in in large cells but no changes in [Ca2+]in in small cells. Additionally, treatment with increasing concentrations of 4-bromo-A23187 resulted in titratable increases in [Ca2+]in that are greater in large than small cells, suggesting that small cells possess a higher Ca(2+)-buffering capacity than large cells. Progesterone secretion by large cells was significantly inhibited at alkaline pHex. In the presence of PGF2 alpha, progesterone secretion exhibited a distinct pH optimum of 7.0. In contrast, pHex did not affect secretion of progesterone in small cells under any of the conditions tested. TG, CPA, and La3+ all reduced secretion of progesterone in large, but not small, cells. These results demonstrate that ovine large and small luteal cells differ in regulation of [Ca2+]in homeostasis, and that treatments that increase [Ca2+]in decrease progesterone secretion in large cells but have no effect in small cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: I. Alterations in cytosolic-free calcium levels and calcium flux.

The effect of prostaglandin F2 alpha (PGF2 alpha) on cytosolic calcium homeostasis was studied in suspensions of ovine large or small luteal cells from superovulated ewes. In large cells loaded with fura-2 (AM), resting cytosolic-free calcium ([Ca2+]i) was 62 +/- 5 nM (Hanks' medium, pH 7.15), and PGF2 alpha (0.5 microM) induced a rapid transient increase in [Ca2+]i to 152 +/- 6 nM, which then decreased to 97 +/- 6 nM within 3 min and remained at this level for the remainder of the treatment period (10-20 min). PGF2 alpha did not alter intracellular pH (pHi) in cells loaded with snarf-1 (AM) (pHi indicator). The transient nature of the [Ca2+]i increase was due, at least in part, to the ability of PGF2 alpha to stimulate (P less than 0.05) 45Ca2+ efflux. In small cells, resting [Ca2+]i was 57 +/- 5 nM, and no change in [Ca2+]i levels or pHi occurred with the addition of PGF2 alpha. PGF2 alpha also did not affect 45Ca2+ efflux in small cells. Calcium uptake was not significantly altered by PGF2 alpha in large or small cells. Data from kinetic analysis of the calcium transient was best fit to a two-compartment model consisting of a rapidly effluxing compartment and a slowly effluxing compartment. The size and rate constants were 62 +/- 10 nM and 3.6 +/- 1 min-1, respectively, for the rapidly effluxing compartment and 140 +/- 9 nM and 0.02 +/- 0.002 min-1, respectively, for the slowly effluxing compartment. These results provide evidence for a direct effect of PGF2 alpha specifically on the ovine large luteal cell that involves alterations in [Ca2+]i and calcium flux. This effect is likely to be involved in intracellular mediation of the signal for luteal regression.

Outcome study of first-episode psychosis. I: Relapse rates after 1 year.

One-year relapse rates were assessed in a group of 64 patients diagnosed by Research Diagnostic Criteria who were hospitalized for their first psychotic episode. Life-table analysis showed that of the 51 remitted patients, 71.4% of the schizophrenic patients (N = 20), 71.4% of patients with affective disorders (N = 10), and 77.8% of patients diagnosed as having either unspecified functional psychosis or other psychiatric disorder (N = 7) remained in remission at 1-year follow-up. Factors associated with relapse or poor outcome (patients who remained in episode) included no maintenance medication, longer duration of illness, and premorbid asociality.

Aerobic and myocardial demands of lawn mowing in patients with coronary artery disease.

Lawn mowing approximates 4 to 6 METs and may evoke heart rate and systolic blood pressure responses that approach and exceed those attained during maximal exercise testing. The excessive cardiac demands may be deceptively camouflaged by the moderate aerobic requirements and perceived effort.

Feeding daidzein to late pregnant sows influences the estrogen receptor beta and type 1 insulin-like growth factor receptor mRNA expression in newborn piglets.

The present study was undertaken to determine the tissue-specific expression of estrogen receptor beta (ERbeta), and the effects of a daidzein supplement to the diet of pregnant sows on the expression of ERbeta, and type 1 insulin-like growth factor receptor (IGF-1R) genes in newborn piglets by using semi-quantitative RT-PCR. Eight sows received a dietary supplement of daidzein at a dosage of 8 mg per kg feed from day 85 of gestation, and six sows were used as controls. After parturition, 2 male neonatal piglets were selected from each litter for sampling. ERbeta mRNA was detected in intestine, lung, thymus, kidney, pituitary and hypothalamus tissues, but not in heart, adrenal, skeletal muscle, liver or placental tissues. Daidzein treatment significantly increased the birth weight of male piglets and markedly reduced the level of ERbeta mRNA in the hypothalamus, but not in the pituitary. An up-regulation of IGF-1R gene transcription was observed in skeletal muscles of newborn piglets. In addition, the IGF-1R mRNA was found to be most abundant in pituitary and hypothalamus, followed by skeletal muscle, thymus, and liver tissues in decreasing order. Our results demonstrate that (1) ERbeta is expressed in a tissue-specific manner in newborn piglets, (2) daidzein down-regulates ERbeta gene expression in the hypothalamus, possibly indicating central effects of daidzein, and (3) daidzein influences fetal growth associated with higher IGF-IR gene expression in skeletal muscle.

Familial occurrence of tardive dyskinesia.

Tardive dyskinesia remains a poorly understood consequence of neuroleptic treatment for psychiatric illness. To date, there have been no reports in the literature regarding the presence of dyskinetic symptomatology in first degree relatives or other family members. The following two cases reveal the development of abnormal involuntary movement in brothers with similar mental illness and treatment histories, and suggest the importance of examining neuroleptically treated relatives of an affected individual for dyskinesia and may suggest a genetic factor in vulnerability.