Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity

Dietary calcium decreases but short-chain fructo-oligosaccharides increase colonic permeability in rats

An increased intestinal permeability is associated with several diseases. Nutrition can influence gut permeability. Previously, we showed that dietary Ca decreases whereas dietary short-chain fructo-oligosaccharides (scFOS) increase intestinal permeability in rats. However, it is unknown how and where in the gastrointestinal tract Ca and scFOS exert their effects. Rats were fed a Western low-Ca control diet, or a similar diet supplemented with either Ca or scFOS. Lactulose plus mannitol and Cr-EDTA were added to the diets to quantify small and total gastrointestinal permeability, respectively. Additionally, colonic tissue was mounted in Ussing chambers and exposed to faecal water of these rats. Dietary Ca immediately decreased urinary Cr-EDTA excretion by 24 % in Ca-fed rats compared with control rats. Dietary scFOS increased total Cr-EDTA permeability gradually with time, likely reflecting relatively slow gut microbiota adaptations, which finally resulted in a 30 % increase. The lactulose: mannitol ratio was 15 % higher for Ca-fed rats and 16 % lower for scFOS-fed rats compared with control rats. However, no dietary effect was present on individual urinary lactulose and mannitol excretion. The faecal waters did not influence colonic permeability in Ussing chambers. In conclusion, despite effects on the lactulose: mannitol ratio, individual lactulose values did not alter, indicating that diet did not influence small-intestinal permeability. Therefore, both nutrients affect permeability only in the colon: Ca decreases, while scFOS increase colonic permeability. As faecal water did not influence permeability in Ussing chambers, probably modulation of mucins and/or microbiota is important for the in vivo effects of dietary Ca and scFOS

An attempt to define the sodium requirements of lactating dairy cows in a tropical environment

BACKGROUND: Lactating dairy cattle in the tropics may require more sodium (Na) owing to the hot and humid climatic conditions. It is unknown whether the current recommendations on Na for lactating cows can be quantitatively used in tropical countries. This study attempted to define the Na requirement of lactating dairy cows under tropical conditions by measuring Na levels in saliva, milk and faeces. RESULTS: The concentrations of Na and potassium (K) in milk, faeces and serum were not affected by dietary treatments. The amount of Na absorbed by cows fed the basal (low-Na) diet containing 0.4 g Na kg-1 dry matter (DM) was equal to the amount of Na lost in the milk, showing that these animals were fed an Na-deficient ration. This observation was corroborated by salivary Na and K levels, with the cows on the low-Na diet having salivary Na concentrations below 120 mmol L-1 in combination with salivary K concentrations above 20 mmol L-1 (P <0.05). CONCLUSION: Consumption of a daily ration formulated to contain the current Na requirement set by the NRC appears to provide too much Na for lactating cows under tropical conditions. A tentative value of 1.2 g kg-1 DM is proposed as the Na requirement for dairy cows under tropical conditions. Copyright © 2011 Society of Chemical Industr

Ileal Mucosal and Fecal Pancreatitis Associated Protein Levels Reflect Severity of Salmonella Inflection in Rats

Background Microbial infections induce ileal pancreatitis-associated protein/regenerating gene III (PAP/RegIII) mRNA expression. Despite increasing interest, little is known about the PAP/RegIII protein. Therefore, ileal mucosal PAP/RegIII protein expression, localization, and fecal excretion were studied in rats upon Salmonella infection. Results Salmonella infection increased ileal mucosal PAP/RegIII protein levels in enterocytes located at the crypt-villus junction. Increased colonization and translocation of Salmonella was associated with higher ileal mucosal PAP/RegIII levels and secretion of this protein in feces. Conclusions PAP/RegIII protein is increased in enterocytes of the ileal mucosa during Salmonella infection and is associated with infection severity. PAP/RegIII is excreted in feces and might be used as a new and non-invasive infection marke

Мерчандайзинг як партнерська взаємодія виробника та роздробу

У даній статті розглянуто мерчандайзинг як елемент комплексу маркетингових комунікацій, задачі та функції мерчандайзингу для виробника та для роздрібного торговця, їх точки пересічення та розбіжності, висувається припущення про їх взаємодію по цьому питанню, що може збільшити ефект, що очікується від використання методів мерчандайзингу в місцях продажу, як для виробника, так і для магазину.In this article merchandising is considered. Its task and functions for a producer and for a retail dealer, their intersection and divergence. There are also pulled out supposition about their cooperation in this field, what can increase an effect, which is expected from merchandising methods using to both in the places of sale

Oil palm (Elaeis guineensis Jacq.) frond feeding of goats in the humid tropics

Twenty four goats were allocated to three groups (n = 8) and fed either a control diet Without Oil Palm Fronds (CON), a diet incorporated with 25% Oil Palm Fronds (OPFM) or 50% Oil Palm Fronds (OPFH) for 100 days to evaluate their growth rates, carcass characteristics and subcutaneous fatty acid profiles. Animals in all three groups exhibited similar final body weights (p>0.05). The OPFH group showed a significant linear reduction (p<0.05) in dressing percentage, warm carcass weight and back fat thickness and total muscle when compared to the CON group. The total n-3 Polyunsaturated Fatty Acid (PUFA) concentrations in the subcutaneous fat of the OPFH animals were significantly higher (linear, p<0.05) than the CON group. The diet containing 25% of oil palm fronds did not produce any adverse effects on the growth performance and carcass characteristics. This demonstrates an environmental-friendly way of utilizing agricultural waste by products for the small ruminant industry in tropical countries growing oil palm tree

Urinary excretion of advanced glycation end products in dogs and cats

The present study was conducted with privately owned dogs and cats to investigate whether a relationship exists between the dietary AGEs and the urinary excretion of AGEs, as indication of possible effective absorption of those compounds in the intestinal tract of pet carnivores. For this purpose, data were collected from both raw fed and dry processed food (DPF) fed to dogs and cats, through spot urine sampling and questionnaires. Raw pet food (RF, low in AGE diets) was fed as a primary food source to 29 dogs and DPF to 28 dogs. Cats were categorized into 3 groups, which were RF (n = 15), DPF (n = 14) and dry and wet processed pet food (DWF, n = 25). Urinary-free carboxymethyllysine (CML), carboxyethyllysine (CEL) and lysinoalanine (LAL) were analysed using ultrahigh-performance liquid chromatography (UHPLC)—mass spectrometry, and were standardized for variable urine concentration by expressing the AGE concentrations as a ratio to urine creatinine (Ucr) concentration (µg/µmol Ucr). Urinary excretion of CML, CEL and LAL in dogs fed with DPF was 2.03, 2.14 and 3 times higher compared to dogs fed with RF (p <.005). Similar to the dogs, a significant difference in CML:Ucr, CEL:Ucr and LAL:Ucr between the three diet groups was observed in cats (p-overall < 0.005, ANOVA), in which the RF fed group excreted less AGEs than the other groups. Linear regression coefficients and SE of CML:Ucr, CEL:Ucr and LAL:Ucr showed that body weight and neuter status were significantly correlated with CML and CEL excretion, but not to LAL excretion. Our results revealed a significant correlation between dietary AGEs and urinary excretion of free CML, CEL and LAL, and also showed that endogenous formation of these AGEs occurs in both dogs and cats under physiological conditions.</p

Extent of hypoattenuation on CT angiography source images in Basilar Artery occlusion: prognostic value in the Basilar Artery International Cooperation Study

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at &#8805;8 versus &#60;8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0–3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0–2).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS ≥8. Patients with a pc-ASPECTS ≥8 more often had a favorable outcome than patients with a pc-ASPECTS &#60;8 (crude RR, 1.7; 95% CI, 0.98–3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS &#8805;8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8–2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5–0.98) and functional independence (RR, 2.0; 95% CI, 1.1–3.8). In post hoc analysis, pc-ASPECTS dichotomized at &#8805;6 versus &#60;6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2–7.5).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.&lt;/p&gt

Pre-ataxic loss of intrinsic plasticity and motor learning in a mouse model of SCA1

Spinocerebellar ataxias are neurodegenerative diseases, the hallmark symptom of which is the development of ataxia due to cerebellar dysfunction. Purkinje cells, the principal neurons of the cerebellar cortex, are the main cells affected in these disorders, but the sequence of pathological events leading to their dysfunction is poorly understood. Understanding the origins of Purkinje cells dysfunction before it manifests is imperative to interpret the functional and behavioural consequences of cerebellar-related disorders, providing an optimal timeline for therapeutic interventions. Here, we report the cascade of events leading to Purkinje cells dysfunction before the onset of ataxia in a mouse model of spinocerebellar ataxia 1 (SCA1). Spatiotemporal characterization of the ATXN1[82Q] SCA1 mouse model revealed high levels of the mutant ATXN1[82Q] weeks before the onset of ataxia. The expression of the toxic protein first caused a reduction of Purkinje cells intrinsic excitability, which was followed by atrophy of Purkinje cells dendrite arborization and aberrant glutamatergic signalling, finally leading to disruption of Purkinje cells innervation of climbing fibres and loss of intrinsic plasticity of Purkinje cells. Functionally, we found that deficits in eyeblink conditioning, a form of cerebellum-dependent motor learning, precede the onset of ataxia, matching the timeline of climbing fibre degeneration and reduced intrinsic plasticity. Together, our results suggest that abnormal synaptic signalling and intrinsic plasticity during the pre-ataxia stage of spinocerebellar ataxias underlie an aberrant cerebellar circuitry that anticipates the full extent of the disease severity. Furthermore, our work indicates the potential for eyeblink conditioning to be used as a sensitive tool to detect early cerebellar dysfunction as a sign of future disease.</p