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Posterodorsal septal lesions impair performance on both shift and stay working memory tasks.

Two groups of rats were trained preoperatively on either a shift or a stay problem in a T-maze. Training trials consisted of two runs, an "information run" in which a subject was forced to go down one of the two arms of the T-maze, followed immediately by a "choice run" in which the subject could choose either arm. In the shift condition, rats were rewarded with wet mash only for choosing the arm opposite the one they entered on the information run. In the stay condition, rats were rewarded for entering the arm that was entered on the information run. In both conditions, rats ultimately learned to perform with median accuracy of 100%, but the shift group reached this level of performance after fewer trials than the stay group. In a subsequent phase, the delay between information runs and choice runs was increased from 0 to 30, 60, 90, 210 and then decreased back to 0 s. Choice accuracy in both groups declined as the delay increased and returned to 100% at the 0-s delay. Half of the subjects in each condition then received either lesions of the posterodorsal septum-aimed at disconnecting the septum and hippocampus-or control surgery. Postoperative retention deficits resulted from posterodorsal septal lesions in both shift and stay conditions. There was some recovery of performance but no indication of "savings" during postoperative training. These results indicate that deficits in maze performance by rats with septo-hippocampal damage are not restricted to tasks that require alternation of spatial locations. This finding falsifies the notion that maze deficits reflect a spontaneous alternation deficit or changed "spatial strategy," but it supports the hypothesis of a working memory deficit in these animals.

Animals↗

The role of drinking in the suppression of food intake by recent activity.

The standard activity-based anorexia procedure provides rats with access to a running wheel while restricting their access to dry food. This can produce reduced food intake and progressive weight loss. Using this procedure, in the present study (Experiment 1) the authors found changes in drinking patterns both in the period of high activity preceding food access and during the feeding period. Varying the procedure by providing wet mash (Experiment 2) or by prior adaptation to a drinking schedule (Experiment 3) prevented the self-starvation effect. These results indicate the importance of drinking when analyzing the effect of recent activity on food intake.

Animals↗

Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat.

Bilateral 6-hydroxydopamine lesions of the nucleus accumbens septi (NAS) and olfactory tubercle (OT) caused enhanced intake of wet mash in 23-hr-food-deprived rats tested in photocell activity cages during restricted 30-min sessions. This mild hyperphagia was accompanied by a significant hypoactivity in the group with NAS/OT lesions. No hyperphagia was observed during a prolonged 120-min test session or in free-feeding tests conducted in the home cage. Anorexia induced by d-amphetamine (.5 and 1.5 mg/kg) was unaltered by the lesion, although the locomotor stimulant action of the drug was attenuated. A second experiment showed that the NAS/OT lesion also enhanced food intake in the photocell cages during 30-min sessions with dry food pellets but that food-associated drinking was concomitantly reduced. The results are consistent with the hypothesis that the behavioral changes caused by mesolimbic neuron destruction result in part from an inability to switch from one behavioral activity to another.

Anorexia↗

Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.

Hepatocellular carcinoma (HCC) is an increasingly prevalent and deadly disease that is initiated by different etiological factors, such as alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, and other hepatotoxic and hepatocarcinogenic agents. The tumor microenvironment (TME) of HCC is characterized by several different fibroblastic and immune cell types, all of which affect the initiation, progression and metastasis of this malignant cancer. This complex immune TME can be divided into an innate component that includes macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, mucosal-associated invariant T cells, natural killer cells, natural killer T cells, and innate lymphoid cells, as well as an adaptive component that includes CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells. In this review, we discuss the latest findings shedding light on the direct or indirect roles of these immune cells (and fibroblastic-like cells such as hepatic stellate cells) in the pathogenesis of HCC. Henceforth, further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options. In line with this, we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.

Humans↗

Comparative genomics reveals population structure and functional differentiation in Limosilactobacillus fermentum.

Limosilactobacillus fermentum is a widely distributed lactic acid bacterium frequently detected in fermented foods and host-associated microbiota, yet its global genomic diversity and functional variability remain insufficiently characterized. Here, we performed a large-scale comparative genomic analysis of 336 high-quality L. fermentum genomes curated from public databases. Species identity was validated using average nucleotide identity (ANI), and population structure was examined using pairwise ANI comparisons together with Mash-based phylogenetic reconstruction. Clustering at ≥ 99% ANI resolved the dataset into 15 genomic clusters, with four dominant lineages comprising the majority of genomes. Pangenome reconstruction identified 5,853 gene clusters, including 1,325 core genes (22.6%) and a large accessory component dominated by low-frequency genes. Heap's law modeling (λ = 0.19) indicated a weakly open pangenome, suggesting ongoing gene acquisition as additional genomes are sampled. Functional annotation revealed that core genes were primarily associated with essential cellular processes, whereas accessory genes were enriched in carbohydrate metabolism, membrane-associated functions, and defense-related systems. Variation in carbohydrate-active enzymes (CAZymes), transport systems, and stress-response genes was observed across lineages, indicating strain-level functional diversity. Although genomes from human and food sources were broadly distributed across phylogenetic lineages, multivariate analysis showed that gene-content variation was more strongly associated with genomic lineage than with isolation source. These results provide a population genomic framework for understanding genomic diversity and functional potential in L. fermentum.

Phylogeny↗

Application of multistage continuous fermentation for production of fuel alcohol by very-high-gravity fermentation technology.

A fermentation system to test the merging of very-high-gravity (VHG) and multistage continuous culture fermentation (MCCF) technologies was constructed and evaluated for fuel ethanol production. Simulated mashes ranging from 15% to 32% w/v glucose were fermented by Saccharomyces cerevisiae and the dilution rates were adjusted for each glucose concentration to provide an effluent containing less than 0.3% w/v glucose (greater than 99% consumption of glucose). The MCCF can be operated with glucose concentrations up to 32% w/v, which indicates that the system can successfully operate under VHG conditions. With 32% w/v glucose in the medium reservoir, a maximum of 16.73% v/v ethanol was produced in the MCCF. The introduction of VHG fermentation into continuous culture technology allows an improvement in ethanol productivity while producing ethanol continuously. In comparing the viability of yeast by methylene blue and plate count procedures, the results in this work indicate that the methylene blue procedure may overestimate the proportion of dead cells in the population. Ethanol productivity (Yps) increased from the first to the last fermentor in the sequence at all glucose concentrations used. This indicated that ethanol is more effectively produced in later fermentors in the MCCF, and that the notion of a constant Yps is not a valid assumption for use in mathematical modeling of MCCFs.

Biomass↗

Immortalization of neuro-endocrine cells from adrenal tumors arising in SV40 T-transgenic mice.

Pheochromocytomas are adrenal medullary tumors which arise from the transformation of neural crest-derived cells. In the course of studies of mice transgenic for an SV40 T-gene ectopically expressed in the adrenal medulla, we observed the occurrence of large, mainly bilateral tumors in a high proportion of transgenic animals. From these tumors we established immortalized cell lines which grow in vitro at 32 degrees C (the permissive temperature for the tsA58 T-protein encoded by the transgene), but not at 38 C. These cells demonstrate characteristics of both neuronal (160 kd neurofilament) and endocrine (chromogranins) cells. The expression of Mash-1 and ret supports their initial characterization as early bipotential neuro-endocrine progenitors.

Adrenal Gland Neoplasms↗

Activation of the neuregulin-1/ErbB signaling pathway promotes the proliferation of neoplastic Schwann cells in human malignant peripheral nerve sheath tumors.

Patients with neurofibromatosis type 1 develop aggressive Schwann cell neoplasms known as malignant peripheral nerve sheath tumors (MPNSTs). Although tumor suppressor gene mutations play an important role in MPNST pathogenesis, it is likely that dysregulated signaling by as yet unidentified growth factors also contributes to the formation of these sarcomas. To test the hypothesis that neuregulin-1 (NRG-1) growth factors promote mitogenesis in MPNSTs, we examined the expression and action of NRG-1 in human MPNSTs and neurofibromas, the benign precursor lesions from which MPNSTs arise. Multiple alpha and beta transmembrane precursors from the class II and III NRG-1 subfamilies are present in both tumor types. Neoplastic Schwann cells within these neoplasms variably express the erbB kinases mediating NRG-1 responses (erbB2, erbB3 and/or erbB4). Human MPNST cell lines (Mash-1, YST-1, NMS-2 and NMS-2PC cells) similarly coexpress multiple NRG-1 isoforms and erbB receptors. These MPNST lines are NRG-1 responsive and demonstrate constitutive erbB phosphorylation. Treatment with PD168393 and PD158780, two structurally and mechanistically distinct erbB inhibitors, abolishes erbB phosphorylation and reduces DNA synthesis in these lines. These findings suggest that autocrine and/or paracrine NRG-1/erbB signaling promotes neoplastic Schwann cell proliferation and may be an important therapeutic target in neurofibromas and MPNSTs.

Biomarkers↗

Conversion of[U-14C]glucose into carbon dioxide, glycogen, cholesterol and fatty acids in liver slices from embryonic and growing chicks.

Incorporation of [U-(14)C]glucose into carbon dioxide, glycogen, cholesterol and fatty acids and of (3)H(2)O into cholesterol and fatty acids was measured in liver slices from embryos and growing chicks. During the embryonic period, rates of incorporation were low and stable for all pathways. Fatty acid synthesis and glucose oxidation increased promptly when the chicks were fed, reaching plateau levels within 6 days. Cholesterol and glycogen synthesis increased only slightly when the birds were fed. After 5 and 11 days respectively, cholesterol and glycogen synthesis began to increase rapidly. The rate of glucose oxidation in liver slices from 4-week-old chicks was 20-fold greater than in slices of embryonic liver; glycogen, cholesterol and fatty acid synthesis had increased approximately 100-, 300- and 1000-fold respectively. The increase in the metabolism of [U-(14)C]glucose that occurred after hatching was probably due to the change from a high-fat non-carbohydrate diet (yolk) to a high-carbohydrate low-fat diet (mash).

Age Factors↗

SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats.

Intracerebroventricular (i.c.v.) administration of the novel hypothalamic neuropeptide orexin-A stimulates food intake in rats, and delays the onset of behavioural satiety (i.e. the natural transition from feeding to resting). Furthermore, preliminary findings with the selective orexin-1 receptor antagonist, SB-334867, suggest that orexin-A regulation of food intake is mediated via the orexin-1 receptor. At present, however, little is known about either the intrinsic effects of SB-334867 on the normal structure of feeding behaviour, or its effects upon orexin-A-induced behavioural change. In the present study, we have employed a continuous monitoring technique to characterize the effects of SB-334867 (3-30 mg/kg, i.p.) on the microstructure of rat behaviour during a 1-h test with palatable wet mash. Administered alone, SB-334867 (30 mg/kg, but not lower doses) significantly reduced food intake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. Although suggestive of a behaviourally nonselective (i.e. sedative) action, the structure of feeding behaviour was well-preserved at this dose level, with the reduction in behavioural output clearly attributable to an earlier onset of behavioural satiety. As previously reported, orexin-A (10 microg per rat i.c.v.) stimulated food intake, increased grooming and delayed the onset of behavioural satiety. Pretreatment with SB-334867 dose-dependently blocked these effects of orexin-A, with significant antagonism evident at dose levels (3-10 mg/kg) below those required to produce intrinsic behavioural effects under present test conditions. Together, these findings strongly support the view that orexin-A is involved in the regulation of feeding patterns and that this influence is mediated through the orexin-1 receptor.

Animals↗

Effects of meal consistency and ingested fluid volume on the intragastric distribution of a drug model in humans--a magnetic resonance imaging study.

BACKGROUND: Controlled delivery of drugs to the small intestine in relation to emptying of an ingested meal is important in various pathophysiological conditions. We investigated the effects of different food consistencies and the amount of co-ingested liquid on the intragastric distribution of a contrast marker. METHODS: Five healthy subjects received four meals (each 650 kcal: A, mashed potato with 100 mL water; B, rice with 100 mL water; C, hamburger meal with 100 mL water; D, hamburger meal with 300 mL water). A capsule filled with gadolinium tetra-azacyclododecane tetra-acetic acid solution (as contrast marker) was ingested following meal termination, and its intragastric distribution was assessed by magnetic resonance imaging. RESULTS: Initially, marker distribution was confined to the fundus, and subsequently extended along the inner curvature of the stomach. The maximum distribution volume of the marker was lower in meal A than in meal B (P < 0.05). No differences in marker distribution were observed when the hamburger meal was given with 100 or 300 mL water. CONCLUSIONS: The intragastric distribution kinetics of the marker gadolinium tetra-azacyclododecane tetra-acetic acid appeared to depend on meal consistency, but not on the amount of water co-ingested. Three-dimensional magnetic resonance imaging allows detailed analysis of the intragastric distribution of a drug model in relation to meal emptying and intragastric meal distribution.

Adult↗

Nurses' knowledge of current guidelines for infant feeding and weaning.

BACKGROUND: Poor infant feeding practices are common causes of nonorganic failure to thrive and may exacerbate the effects of many chronic conditions. It is important therefore that parents receive correct and consistent feeding advice from health professionals. The aim of this study was to determine whether hospital paediatric nursing staff are familiar with the recommendations of the Department of Health (DOH) Weaning Report (DOH, 1994). METHODS: A total of 127 members of nursing staff (79%) at Derbyshire Children's Hospital were interviewed. Knowledge of recommended practices for the introduction and use of cow's milk, gluten, milk products, mashed foods, vitamin supplements and drinks was assessed. RESULTS: Overall, 42 people (33%) answered all questions correctly. In each clinical area, six outpatient (64%), 19 special care baby unit (61%) and 17 ward (20%) staff provided correct answers to all questions. No significant difference was found between staff at each grade in the number of questions answered correctly. CONCLUSIONS: Knowledge of national infant feeding and weaning guidelines was limited suggesting that DOH recommendations are not widely understood or recognized. Further nutrition education and local dissemination of information is required if nurses are to continue to advise parents on aspects of infant feeding.

Animals↗

Fermentation of liquid coproducts and liquid compound diets: Part 1. Effects on chemical composition during a 6-day storage period.

The effects of a 6-day storage period on changes in dry matter, crude ash, crude protein, true protein, crude fat, starch, soluble starch, sugar and lactose of three liquid coproducts and two liquid compound diets were studied. The three liquid coproducts studied were: liquid wheat starch (LWS), mashed potato steam peel (PSP) and cheese whey (CW), and the two liquid compound diets were: liquid grower diet (LGD) and liquid finisher diet (LFD). The loss of corrected dry matter after a 6-day storage, expressed in relation to the initial content, was 1.9, 6.2, 9.6, 4.6 and 4.2% for LWS, PSP, CW, LGD and LFD, respectively. During storage, the total amount of starch decreased 2.7, 24.0, 28.1 and 33.3% for LWS, PSP, LGD and LFD, respectively. The total amount of lactose decreased 23.5% for CW. The gross energy value of the products did not change remarkably during the 6-day storage period; gross energy losses being less than 3% of the initial gross energy content.

Animal Feed↗

Fermentation of liquid coproducts and liquid compound diets: Part 2. Effects on pH, acid-binding capacity, organic acids and ethanol during a 6-day storage period.

The effects of a 6-day storage period on changes in pH, acid-binding capacity, level of organic acids and ethanol of three liquid coproducts [liquid wheat starch (LWS), mashed potato steam peel (PSP) and cheese whey (CW)] and two liquid compound diets [liquid grower diet (LGD) and liquid finisher diet (LFD)] were studied. All products, except LWS, showed a significant decrease in pH and acid-binding capacity during storage. At the end of the storage period, all products reached a pH of between 3.5 and 3.9. In general, it can be concluded that the lactic acid content, and to a lesser extent the acetic acid content, increased dramatically during storage. In contrast, the ethanol content increased significantly in the liquid compound diets only. The pattern of changes in pH and organic acids during the 6-day storage period was different between the liquid coproducts and the liquid compound diets. At the start of storage, liquid coproducts are already in the 'middle' of the fermentation process, while liquid compound diets need approximately 24-36 h before fermentation begins. Consequently, in practice a different approach to obtain fermented diets is needed for liquid coproducts and liquid compound diets.

Acetic Acid↗

Valorization of rapeseed meal. 4. Effects of iodine, copper and ferrous salt supplementation in growing rats.

Ten groups of 10 growing male rats (65 g) were fed ad libitum either a control diet or rapeseed diets (15 mM glucosinolates/kg DM) supplemented either with l- alone, l- and Cu++ (2 levels), l- + Cu++ and methionine or l- and Fe++ (2 levels) (table 1) for 35 days. When the rapeseed diets were given as powder or as mash, food intake decreased 24 and 32%, respectively; live weight gain was reduced by 36 and 46%, liver weight increased 20 and 33%, thyroïd gland was 3 and 4 times as big, and a 30 and 50% decrease in the T4 plasma level was noted (table 2). l- supplementation did not prevent the deleterious effects of rapeseed meal feeding. l- and Fe++ supplementation had detrimental effects on food intake, live weight gain and kidney weight, but beneficial effects on liver and thyroïd weights and on plasma thyroïd hormone levels. The low level of l- and Cu++ supplementation suppressed the depressive effects of rapeseed meal on food intake and live weight gain and reduced the deleterious effects on kidney, liver and thyroïd weights and on plasma thyroïd hormone levels, whereas the higher level almost suppressed them. The results are discussed considering the likelihood of a bivalent cation effect on glucosinolates.

Animals↗

Effects of Aspergillus fumigatus phytase on phosphorus digestibility, phosphorus excretion, bone strength and performance in pigs.

Phytic-phosphorus has a very low bioavailability for monogastric animals and the non-utilized mineral contributes to the phosphorus (P) pollution problems. Phytases may ameliorate phytic-P antinutritive properties. However, phytases are very sensitive to the pelleting temperature commonly used for compound feed production and thus the challenge to produce a more thermostable phytase is very important. Pure Aspergillus fumigatus phytase (AFP) has the ability to refold into a native-like fully active structure after heat denaturation (20 min at 90 degrees C). The aim of the present work was to evaluate in vitro (in feed) and in vivo in young and in growing-finishing pigs the effects of AFP included in the feed at a level of 500 U/kg. Feed supplementation with AFP resulted in an in vitro phosphorus release of about three times higher than that obtained from the basal diets, irrespective of the pH value used for the determination (5.5 or 7). When the supplemented feed was steam pelleted at about 84 degrees C, the free P obtained after incubation at pH 5.5 represented 53% on an average of that obtained from the corresponding mash diets. The phytic-P-rich diets systematically induced hypophosphataemia, hypercalcaemia and hyperphosphatasaemia. The normal blood levels of P, Ca and alkaline phosphatase were restored by AFP. P apparent digestibility was significantly higher for the AFP diet (52.8 versus 30.8%). The improvement in Ca digestibility was not statistically significant. In all three in vivo experiments, AFP significantly decreased the P concentration in faeces (between 13 and 33%) as well as increased the growth rate and decreased the feed conversion ratio. Bone strength was significantly higher in the growing-fattening pigs fed on the AFP diet.

6-Phytase↗

Regulatory transcription factors controlling function and differentiation of human trophoblast--a review.

In transgenic mice, homozygous mutations of trophoblast-specific transcription factors such as Hand1, Mash-2, I-mfa or GCM1 revealed their key regulatory roles in induction, maintenance or differentiation of distinct placental trophoblast subpopulations in vivo. Descriptive studies have shown that several of these factors are also expressed in the human placenta, suggesting that the molecular mechanisms governing trophoblast differentiation could be similar in mice and men. While an increasing number of putative developmental regulators are being identified in the human placenta, little information is available regarding whether the particular factors play an essential role in trophoblast differentiation processes such as formation of anchoring villi, placental bed invasion or syncytialization. However, expression of abundant trophoblast-specific products such as hormones can be regarded as a hallmark of differentiation, suggesting that the factors controlling their transcription could also be involved in the developmental processes of the placenta. Indeed, studies in different model systems revealed that the human homologues of murine trophoblast-specific transcriptional regulators interact with the promoter regions of typical placental genes such as aromatase P450 (CYP19), chorionic gonadotrophin (CG) or placental lactogen (PL). Additionally, the unique combination of more broadly distributed transcription factors of the Sp or Ap-2 protein family in a particular trophoblast cell type is required to govern mRNA expression in a differentiation-dependent manner. Here, we will summarize our present knowledge on these individual transcription factors that are involved in human trophoblast function and differentiation.

Animals↗

[Systematics of imaging artifacts in MRT caused by metallic vascular implants (stents)].

PURPOSE: Imaging artifacts in magnetic resonance tomography (MRT) caused by metallic vascular implants (stents) were characterized systematically in dependence on the material and the construction of the implants as well as with respect to different measurement protocols and for different static field strength B (0). METHODS: Twelve stents, different in material (stainless steel, nitinol, Co-alloy) and/or construction, were examined at B (0) = 0.2 T and 1.0 T with two 2D gradient echo (GE) sequences (TE = 4 and 10 ms), one 3D GE sequence and one spin echo (SE) sequence. The stents were put into water with Gd-DTPA contrast agent. The dependence on the orientation was analyzed for the 9 possibilities of an orthogonal alignment of the stent axis, the direction of B (0), the slice, the read out, and the phase encoding direction. Special interest was given to the visibility of the stent lumen at forced rf excitation, as well as to the influence of broken struts on the signal obtained. RESULTS: For the examined stents GE technique showed, due to spin dephasing regions a total signal loss ranging up to 8 mm away from the stent mashes. The value depends on the stent material, the stent orientation in the scanner and grows with voxel size, echo time and B (0). In SE technique dephasing artifacts vanish and wrong spatial encoding gets visible, rf shielding is more pronounced. The visibility of the stent lumen ranges from nearly unperturbed down to a complete signal loss. An improvement is possible using enlarged flip angles. Broken struts can not be imaged significantly. DISCUSSION: The MR representation of metallic stents commercially available at the time, especially of nitionol stents, can be optimized with a suitable adaptation of the imaging parameters. However, a profound improvement can only be expected from new stent material and design.

Alloys↗