Relationships between diet-related changes in the gut microbiome and cognitive flexibility.

Western diets are high in fat and sucrose and can influence behavior and gut microbiota. There is growing evidence that altering the microbiome can influence the brain and behavior. This study was designed to determine whether diet-induced changes in the gut microbiota could contribute to alterations in anxiety, memory or cognitive flexibility. Two-month-old, male C57BL/6 mice were randomly assigned high-fat (42% fat, 43% carbohydrate (CHO), high-sucrose (12% fat, 70% CHO (primarily sucrose) or normal chow (13% kcal fat, 62% CHO) diets. Fecal microbiome analysis, step-down latency, novel object and novel location tasks were performed prior to and 2weeks after diet change. Water maze testing for long- and short-term memory and cognitive flexibility was conducted during weeks 5-6 post-diet change. Some similarities in alterations in the microbiome were seen in both the high-fat and high-sucrose diets (e.g., increased Clostridiales), as compared to the normal diet, but the percentage decreases in Bacteroidales were greater in the high-sucrose diet mice. Lactobacillales was only significantly increased in the high-sucrose diet group and Erysipelotrichales was only significantly affected by the high-fat diet. The high-sucrose diet group was significantly impaired in early development of a spatial bias for long-term memory, short-term memory and reversal training, compared to mice on normal diet. An increased focus on the former platform position was seen in both high-sucrose and high-fat groups during the reversal probe trials. There was no significant effect of diet on step-down, exploration or novel recognitions. Higher percentages of Clostridiales and lower expression of Bacteroidales in high-energy diets were related to the poorer cognitive flexibility in the reversal trials. These results suggest that changes in the microbiome may contribute to cognitive changes associated with eating a Western diet.

Incidence of Guillain-Barré syndrome in Alberta, Canada: an administrative data study.

BACKGROUND: To examine the epidemiology of Guillain-Barré syndrome (GBS) in Alberta between 1994 and 2004 with data derived from hospital administration procedures. METHODS: Data from 3,959,857 individuals (1,956,841 females and 2,003,016 males) aged 1-110 years and residing in Alberta, Canada, were included in the analysis. A Poisson regression analysis was performed to determine the predictors of GBS events. RESULTS: After age and sex standardisation to the 2001 Canadian census population, incidence rates ranged from 0.97 to 2.32 per 100,000 over the course of the 11-year period, with a mean incidence of 1.6 per 100,000. Significant effects of gender, age group and year were found. Males were found to be 1.5 times more likely to acquire GBS than females. Relative to those in their first decade, the risk of acquiring GBS increased with advancing age, whereby the incidence in males peaked in the 7th decade of life and in females in the 8th decade of life. The incidence fluctuated over the 11-year period, with a minimum in 1998 and a maximum in 2004. CONCLUSIONS: The incidence of GBS in Alberta between 1994 and 2004 fluctuated within a narrow range, was similar to that previously reported worldwide, demonstrated a male preponderance and increased in elderly patients.

Environmental benefits and economic costs of manure incorporation on dairy waste application fields.

Model simulations performed representing dairies in a 93000 ha watershed in north central Texas suggest that manure incorporation results in reduced phosphorus (P) losses at relatively small to moderate cost to producers. Simulated manure incorporation with a tandem disk on fields double-cropped with sorghum/winter wheat resulted in up to 33, 45, and 37% reductions in per hectare sediment-bound, soluble, and total P losses in edge-of-field runoff, relative to simulated surface manure applications. The effects of incorporation were evaluated at three different manure application rates. On aggregate across all three manure application rates, significant declines in P losses were obtained with incorporation except for sediment-bound P losses under the N-based manure application rate scenario. We found that the practice of incorporating manure shortly after it has been broadcast on the soil surface could help reduce P losses in such situations where P-based rates alone prove inadequate. The cost the producer incurs when manure is incorporated is on average about 1% of net returns when manure is applied at the N rate and 2-3% when it is applied at alternative P-based rates. In practice the costs could be lower because producers may substitute the manure incorporation operation for a tandem disk operation performed prior to manure application. As more and more dairy producers switch to the use of sorghum and corn silage in dairy rations and consequent on-farm production of these forages, the practice of manure incorporation may help to reduce phosphorus losses resulting from dairy manure applications to fields with these forage crops.

Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death.

After mild ischemic insults, many neurons undergo delayed neuronal death. Aberrant activation of the cell cycle machinery is thought to contribute to apoptosis in various conditions including ischemia. We demonstrate that loss of endogenous cyclin-dependent kinase (Cdk) inhibitor p16(INK4a) is an early and reliable indicator of delayed neuronal death in striatal neurons after mild cerebral ischemia in vivo. Loss of p27(Kip1), another Cdk inhibitor, precedes cell death in neocortical neurons subjected to oxygen-glucose deprivation in vitro. The loss of Cdk inhibitors is followed by upregulation of cyclin D1, activation of Cdk2, and subsequent cytoskeletal disintegration. Most neurons undergo cell death before entering S-phase, albeit a small number ( approximately 1%) do progress to the S-phase before their death. Treatment with Cdk inhibitors significantly reduces cell death in vitro. These results show that alteration of cell cycle regulatory mechanisms is a prelude to delayed neuronal death in focal cerebral ischemia and that pharmacological interventions aimed at neuroprotection may be usefully directed at cell cycle regulatory mechanisms.

A mammalian myocardial cell-free system to study cell cycle reentry in terminally differentiated cardiomyocytes.

Cardiomyocytes withdraw from the cell cycle in the early neonatal period, rendering the adult heart incapable to regenerate after injury. In the present study, we report the establishment of a cell-free system to investigate the control of cell cycle reentry in mammalian ventricular cardiomyocyte nuclei and to specifically address the question of whether nuclei from terminally differentiated cardiomyocytes can be stimulated to reenter S phase when incubated with extracts from S-phase cells. Immobilized cardiomyocyte nuclei were incubated with nuclei and cytoplasmic extract of synchronized H9c2 muscle cells or cardiac nonmyocytes. Ongoing DNA synthesis was monitored by biotin-16-dUTP incorporation as well as proliferating cell nuclear antigen expression and localization. Nuclei and cytoplasmic extract from S-phase H9c2 cells but not from H9c2 myotubes induced DNA synthesis in 92% of neonatal cardiomyocyte nuclei. Coincubation in the presence of cycloheximide indicated that de novo translation is required for the reinduction of S phase. Similar results were obtained with adult cardiomyocyte nuclei. When coincubated with both cytoplasmic extract and nuclei or nuclear extracts of S-phase cells, >70% of adult cardiomyocyte nuclei underwent DNA synthesis. In conclusion, these results demonstrate that postmitotic ventricular myocyte nuclei are responsive to stimuli derived from S-phase cells and can thus bypass the cell cycle block. This cell-free system now makes it feasible to analyze the molecular requirements for the release of the cell cycle block and will help to engineer strategies for regenerative growth in cardiac muscle.

E2F-1 overexpression in cardiomyocytes induces downregulation of p21CIP1 and p27KIP1 and release of active cyclin-dependent kinases in the presence of insulin-like growth factor I.

The heart is a postmitotic organ unable to regenerate after injury. The mechanisms controlling cell cycle arrest in cardiomyocytes are still unknown. Adenoviral delivery of E2F-1 to primary rat cardiomyocytes resulted in an increase in the expression of key cell cycle activators and apoptosis in >90% of the cells. However, insulin-like growth factor I (IGF-I) rescued cardiomyocytes from E2F-1-induced apoptosis. Furthermore, overexpression of E2F-1 in the presence of IGF-I induced the specific downregulation of total p21(CIP1) and p27(KIP1) protein levels and their dissociation from cyclin-dependent kinases (cdks). In contrast, p16(INK4) and p57(KIP2) protein levels and their association with cdks remained unaltered. The dissociation of p21(CIP1) and p27(KIP1) from their cdk complexes correlated well with the activation of cdk2, cdk4, and cdk6 and the release from cell cycle arrest. Under these circumstances, the number of cardiomyocytes in S phase rose from 1.2% to 23%. These results indicate that IGF-I renders cardiomyocytes permissive for cell cycle reentry. Finally, the specific downregulation of p21(CIP1) and p27(KIP1) further suggests their key role in the maintenance of cell cycle arrest in cardiomyocytes.

Phosphate, ammonium, magnesium and iron nutrition of Streptomyces hygroscopicus with respect to rapamycin biosynthesis.

Phosphate, ammonium and magnesium salts interfered with rapamycin production by Streptomyces hygroscopicus at concentrations optimal for growth. These observations point to the existence of phosphorus, magnesium and nitrogen-negative regulation mechanisms for rapamycin biosynthesis. On the other hand, Fe2+ stimulated rapamycin production at concentrations greater than that required for growth.

Human Genome Project and cancer: the ethical implications for clinical practice.

The Human Genome Project has far-reaching implications for the entire spectrum of cancer care. An understanding of fundamental gene biology clarifies the role of genetics in cancer causation. The scientific advances of genetic screening for cancers have also given rise to problems such as employment and insurance discrimination, adverse psychosocial effects, and the ethical dilemma of "to screen or not to screen."

Mosaicism for ring and isopseudodicentric chromosome 13.

A three-month-old female infant with multiple malformations was noted on routine cytogenetic evaluation to have dicentric/ring mosaicism of chromosome 13. Additional cytogenic investigations indicated that the dicentric could be further defined as an isopseudodicentric. Unlike the double chromosome break in the more common ring 13 cases, the mechanism for isopseudodicentric/ring generation is attributed to chromosome and chromatid breaks with subsequent bridging, breaking and fusion. The phenotypic features are those of a combined duplication-deficiency of chromosome 13.

Syndrome of camptodactyly, ankyloses, facial anomalies, and pulmonary hypoplasia (Pena-Shokeir syndrome): obstetric and ultrasound aspects.

Two siblings with Pena-Shokeir syndrome are described. This syndrome consists of polyhydramnios, intrauterine growth retardation, short umbilical cord, perinatal death, facial abnormalities, limb abnormalities including arthrogryposis, and lethal pulmonary hypoplasia. The mode of inheritance is most likely autosomal recessive. Prenatal diagnosis was made in the second pregnancy with ultrasound performed at 26 weeks' gestation. The roles of fetal akinesia and fetal apnea in the production of the various manifestations of the syndrome are detailed, and the possibility of early prenatal diagnosis is considered.

Balanced translocation karyotypes in patients with repetitive abortion. Case study and literature review.

Cytogenetic studies were conducted upon 100 consecutive couples with abortions. Eight balanced carrier translocation karyotypes were discovered (8%): three cases of Robertsonian translocations and five reciprocal translocations. Two structural variant karyotypes and a poly-X mosaic were also found. A review of the literature on repetitive abortion revealed 82 balanced translocations in 1,331 couples, a rate of 6.2%. Cytogenetic studied should be routine for patients with repetitive abortion. In the pooled series, 3.7% of couples with translocation had wastage, including some with normal offspring; 9.2% had malformed offspring; 62% of the carrier couples lacked the malformation history. Seventy-four percent of the translocations were reciprocal; risk rates for imbalanced progeny were undefined for 90% of the carrier couples. Only 11 imbalanced conceptuses were demonstrated cytogenetically in 262 pregnancies of the carrier group.