Strategies for improving fertility in the modern dairy cow

The high producing dairy cow of the 21st century is subfertile during lactation. Our objectives are to characterize physiological periods limiting reproductive performance and to describe integrated management strategies to improve pregnancy rates. Ovarian recrudescence with normal re-occurring estrous cycles and restoration of fertility to first service are associated with a reduced occurrence of periparturient metabolic and reproductive disorders. Marked negative changes in energy balance and reduced immunocompetence influence gonadotropic and metabolic hormones. Induced ovarian inactivity was associated with enhanced uterine involution. Post-partum health and reproductive performance were improved when by-pass lipids enriched in polyunsaturated fatty acids were fed in the pre- and post-partum periods. Pharmaceutical control of follicle, CL, and uterine function with PGF, GnRH and intravaginal progesterone releasing inserts, has permitted development of more optimal timed-insemination programs for first service. Likewise, resynchronization of nonpregnant cows coupled with the use of ultrasound for early pregnancy diagnosis provides the opportunity for a second timed-insemination within 3 days of a nonpregnant diagnosis. Bovine somatotropin (bST) increases embryo development and embryo survival when coupled with a timed-insemination program or cows detected in estrus. Presence of a conceptus alters endometrial expression of genes and proteins in response to bST and nutraceuticals (i.e., unsaturated fatty acids such as eicosapentaenoic and docosahexaenoic acid in by-pass lipids) to improve pregnancy rates. Postovulatory increases in progesterone may enhance pregnancy rates in targeted populations of lactating dairy cows, but timing and magnitude of the progesterone increases are pharmaceutically dependent.     

Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraception

Background  

Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1). Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle.     

Mitochondrial metabolism in hibernation: metabolic suppression, temperature effects, and substrate preferences

We compared liver and skeletal muscle mitochondrial function among activity states to characterize regulated reversible metabolic suppression in the mammalian hibernator Spermophilus tridecemlineatus. At 37 degrees C, succinate oxidation was 70% lower in the liver mitochondria from torpid animals than in those from summer-active animals or in animals arousing from torpor. Respiration was very sensitive to temperature (Q(10) 5.8-9.8), and when measured at 25 degrees or 5 degrees C there was no difference among the three states. Liver mitochondria from summer-active animals oxidized pyruvate and beta -hydroxybutyrate at higher rates than those from torpid animals, and flux through complex 4 of the electron transport chain was about three- and fivefold higher than flux through complexes 2-4 and complexes 1-4, respectively. In the hibernating and arousing animals there was no difference in flux through complexes 2-4 and complex 4, suggesting a downregulation of cytochrome c oxidase in liver mitochondria during the hibernation season. Muscle mitochondrial respiration did not differ between the torpid and summer-active states in any of the parameters measured. The data support a regulated, reversible decrease of liver (but not muscle) mitochondrial oxidative phosphorylation in hibernating ground squirrels.     

PRPs localized to the middle lamellae are required for cortical tissue integrity in Medicago truncatula roots

Key message

A family of repetitive proline-rich proteins interact with acidic pectins and play distinct roles in legume root cell walls affecting cortical and vascular structure.

Abstract

A proline-rich protein (PRP) family, composed of tandemly repeated Pro-Hyp-Val-X-Lys pentapeptide motifs, is found primarily in the Leguminosae. Four distinct size classes within this family are encoded by seven tightly linked genes: MtPRP1, MtPRP2 and MtPRP3, and four nearly identical MtPRP4 genes. Promoter fusions to β-glucuronidase showed strong expression in the stele of hairy roots for all 4 PRP genes tested, with additional expression in the cortex for PRP1, PRP2 and PRP4. All except MtPRP4 are strongly expressed in non-tumorous roots, and secreted and ionically bound to root cell walls. These PRPs are absent from root epidermal cell walls, and PRP accumulation is highly localized within the walls of root cortical and vascular tissues. Within xylem tissue, PRPs are deposited in secondary thickenings where it is spatially exclusive to lignin. In newly differentiating xylem, PRPs are deposited in the regularly spaced paired-pits and pit membranes that hydraulically connect neighboring xylem elements. Hairpin-RNA knock-down constructs reducing PRP expression in Medicago truncatula hairy root tumors disrupted cortical and vascular patterning. Immunoblots showed that the knockdown tumors had potentially compensating increases in the non-targeted PRPs, all of which cross-react with the anti-PRP antibodies. However, PRP3 knockdown differed from knockdown of PRP1 and PRP2 in that it greatly reduced viability of hairy root tumors. We hypothesize that repetitive PRPs interact with acidic pectins to form block-copolymer gels that can play distinct roles in legume root cell walls.

     

Helicobacter pylori downregulates expression of human β‐defensin 1 in the gastric mucosa in a type IV secretion‐dependent fashion

Helicobacter pylori establishes a chronic lifelong infection in the human gastric mucosa, which may lead to peptic ulcer disease or gastric adenocarcinoma. The human beta‐defensins (hβDs) are antimicrobial peptides, hβD1 being constitutively expressed in the human stomach. We hypothesized that H. pylori may persist, in part, by downregulating gastric hβD1 expression. We measured hβD1 and hβD2 expression in vivo in relation to the presence, density and severity of H. pylori infection, investigated differential effects of H. pylori virulence factors, and studied underlying signalling mechanisms in vitro. Significantly lower hβD1 and higher hβD2 mRNA and protein concentrations were present in gastric biopsies from infected patients. Those patients with higher‐level bacterial colonization and inflammation had significantly lower hβD1 expression, but there were no differences in hβD2. H. pylori infection of human gastric epithelial cell lines also downregulated hβD1. Using wild‐type strains and isogenic mutants, we showed that a functionalcag pathogenicity island‐encoded type IV secretion system induced this downregulation. Treatment with chemical inhibitors or siRNA revealed that H. pylori usurped NF‐κB signalling to modulate hβD1 expression. These data indicate that H. pylori downregulates hβD1 expression via NF‐κB signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche.     

Mitochondrial respiration and succinate dehydrogenase are suppressed early during entrance into a hibernation bout,but membrane remodeling is only transient

We examined respiration and lipid composition of liver mitochondria purified from a hibernator (Ictidomys tridecemlineatus) in different stages of a torpor bout. Between interbout euthermia (body temperature, T _b, 37°C) and early entrance (T _b 30°C), state 3 and state 4 respirations, fueled by 6 mM succinate, fell by over 50%. Mitochondrial respiration did not decline any further in the late entrance and torpor stages (T _b 15 and 5°C, respectively). Succinate dehydrogenase (SDH) activity declined in a similar pattern as mitochondrial respiration, and there was a significant positive correlation between state 3 respiration and SDH activity. However, unlike during arousal from torpor, oxaloacetate was not a major factor in inhibition of SDH. Analysis of mitochondrial lipids showed little change in neutral lipids or phospholipid classes, except for a transient decrease in phosphatidylethanolamine content in early entrance. In the transition from interbout euthermia to early entrance, we found transient increases in some saturated phospholipid fatty acids (16:0, 18:0) and decreases in some unsaturates (18:2, 20:4). These changes resulted in transient increases in total saturates and the ratio of saturates to unsaturates, and transient decreases in total unsaturates, total polyunsaturates, total n-6, the ratio of monounsaturates to polyunsaturates, and unsaturation index. None of these changes persisted into late entrance or torpor, nor did they correlate with mitochondrial respiration. We conclude that mitochondrial metabolic suppression during entrance into a torpor bout occurs very early and is likely related to acute regulation of electron transport chain enzymes rather than changes in membrane phospholipid composition.     

On the treatment of airline travelers in mathematical models

The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.     

Evidence for an active-inactive subunit complex in jack bean urease.

The structural subunit molecular weight of jack bean urease has been determined to be 30,400 on the basis of the chemical evidence presented. Each polypeptide chain has been shown to possess four types of sulfhydryl groups. In half of the subunits the sulfhydryl group required for catalytic activity is involved in a disulfide bond. This results in a catalytic subunit of 60,800 molecular weight composed of two polypeptide chains but having only one active site.     

Redox-dependent CO2 reduction activity of CO dehydrogenase from Rhodospirillum rubrum.

Carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum catalyzes both the oxidation of CO and the reduction of CO(2). Studies of the redox dependence of CO(2) reduction by R. rubrum CODH show that (1) CODH is unable to catalyze CO(2) reduction at potentials greater than -300 mV; (2) the maximum activity is observed at potentials less than -480 mV; and (3) the midpoint potential (E(m)) of the transition from minimum to maximum CO(2) reduction activity occurs at approximately -339 mV. These results indicate that the C(red1) state of R. rubrum CODH (E(m) = -110 mV; g(zyx)() = 2.03, 1.88, 1.71) is not competent to reduce CO(2). Nernst analyses suggest that the reduction of CODH from the C(red1) state to the CO(2)-reducing form (C(unc), g(zyx)() = 2.04, 1.93, 1.89; E < approximately -300 mV) of the enzyme is a one-electron process. For the entire redox range, viologens stimulate CO(2) reduction by CODH more than 50-fold, and it is proposed that viologens accelerate the redox equilibration of redox buffers and [Fe(4)S(4)](B) during catalysis.